NZ510464A

NZ510464A - Further pro polypeptides and sequences thereof

Info

Publication number: NZ510464A
Application number: NZ510464A
Authority: NZ
Inventors: Kevin Baker; Audrey Goddard; Austin L Gurney; Victoria Smith; Colin K Watanabe; William I Wood
Original assignee: Genentech Inc
Priority date: 1998-09-01
Filing date: 1999-09-01
Publication date: 2004-05-28
Also published as: CA2339043A1; WO2000012708A2; NZ531664A; WO2000012708A3

Abstract

An isolated nucleic acid has at least 80% sequence identity to a nucleotide sequence that encodes a polypeptide comprising the amino acid sequence shown in Figure 32(SEQ IDNO:54). Preferably the nucleotide sequence is that shown in Figure 31 (SEQ ID NO:53) or that deposited under ATCC 203287. Also described are vectors, host cells and antibodies associated with the nucleic acids and polypeptides. The polypeptide can be used in the manufacture of a pharmaceutical for treating a tumor.

Description

FURTHER PRO POLYPEPTIDES AND SEQUENCES THEREOF FIELD OF THE INVENTION The present invention relates generally to the identification and isolation of novel DNA and to the recombinant production of novel polypeptides.

BACKGROUND OF THE INVENTION Extracellular proteins play important roles in, among other things, the formation, differentiation and maintenance of multicellular organisms. The fate of many individual cells, e.g., proliferation, migration, differentiation, or interaction with other cells, is typically governed by information received from other cells 10 and/or the immediate environment. This information is often transmitted by secreted polypeptides (for instance, mitogenicfactors, survival factors, cytotoxic factors, differentiation factors, neuropeptides, and hormones) which are, in turn, received and interpreted by diverse cell receptors or membrane-bound proteins. These secreted polypeptides or signaling molecules normally pass through the cellular secretory pathway to reach their site of action in the extracellular environment.

Secreted proteins have various industrial applications, including as pharmaceuticals, diagnostics, biosensors and bioreactors. Most protein drugs available at present, such as thrombolytic agents, interferons, interleukins, erythropoietins, colony stimulating factors, and various other cytokines, are secretory proteins. Their receptors, which are membrane proteins, also have potential as therapeutic or diagnostic agents. Efforts are being undertaken by both industry and academia to identify new, native secreted proteins. Many efforts are 20 focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. Examples of screening methods and techniques are described in the literature [see, for example, Klein et al., Proc. Natl. Acad. Sci. 93:7108-7113 (1996); U.S. Patent No. 5,536,637)].

Membrane-bound proteins and receptors can play important roles in, among other things, the formation, differentiation and maintenance of multicellular organisms. The fate of many individual cells, e.g., proliferation, 25 migration, differentiation, or interaction with other cells, is typically governed by information received from other cells and/or the immediate environment. This information is often transmitted by secreted polypeptides (for instance, mitogenic factors, survival factors, cytotoxic factors, differentiation factors, neuropeptides, and hormones) which are, in turn, received and interpreted by diverse cell receptors or membrane-bound proteins. Such membrane-bound proteins and cell receptors include, but are not limited to, cytokine receptors, receptor 30 kinases, receptor phosphatases, receptors involved in cell-cell interactions, and cellular adhesin molecules like selectins and integrins. For instance, transduction of signals that regulate cell growth and differentiation is regulated in part by phosphorylation of various cellular proteins. Protein tyrosine kinases, enzymes that catalyze that process, can also act as growth factor receptors. Examples include fibroblast growth factor receptor and nerve growth factor receptor. 1 Membrane-bound proteins and receptor molecules have various industrial applications, including as pharmaceutical and diagnostic agents. Receptor immunoadhesins, for instance, can be employed as therapeutic agents to block receptor-ligand interactions. The membrane-bound proteins can also be employed for screening of potential peptide or small molecule inhibitors of the relevant receptor/ligand interaction.

Efforts are being undertaken by both industry and academia to identify new, native receptor or 5 membrane-bound proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel receptor or membrane-bound proteins. 1. PRQ1560 The tetraspan family of proteins has grown to include approximately 20 known genes from various 10 species, including drosophila. The tetraspans are also known as the transmembrane 4 (TM4) superfamily and are proposed to have an organizing function in the cell membrane. Their ability to interact with other molecules and function in such diverse activities as cell adhesion, activation and differentiation, point to a role of aggregating large molecular complexes. Skubitz, et al., J. Immunology. 157:3617-3626(1996). The tetraspan group has also emerged as a set of proteins with prominent functions in Schwann cell biology. Mirsky and 15 lessen, Curr. Opin. Neurobiol.. 6(l):89-96 (1996). Tetraspans (also sometimes called tetraspanins) are further described in Maecker, et al., FASEB. 11:428-442 (1997). Thus, members of the tetraspan family are of interest. 2. PRQ444 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins. 20 Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PR0444. 3. PRQ1018 Efforts are being undertaken by both industry and academia to identify new, native transmembrane and receptor proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane polypeptide designated herein as PR01018. 4. PRQ1773 The primary and rate-limiting step in retinoic acid biosynthesis requires the conversion of retinol to retinal. Retinol dehydrogenase proteins are enzymes which function to recognize holo-cellular retinol-binding protein as a substrate, thereby catalyzing the first step of retinoic acid biogenesis from its substrate. Various retinol dehydrogenase genes have been cloned and characterized, wherein the products of these genes are 35 suggested as potentially being useful for the treatment of retinitis pigmentosa, psoriasis, acne and various cancers (Chai et al., J. Biol. Chem. 270:28408-28412 (1995) and Chai et al., Gene 169:219-222 (1996)). Given the obvious importance of the retinol dehydrogenase enzymes, there is significant interest in the identification and 2 characterization of novel polypeptides having homology to a retinol dehydrogenase. We herein describe the identification and characterization of novel polypeptides having homology to a retinol dehydrogenase protein, designated herein as PRO1773 polypeptides.

. PRQ1477 Glycosylation is an important mechanism for modulating the physiochemical and biological properties of proteins in a stage- and tissue-specific manner. One of the important enzymes involved in glycosylation in Saccharomyces cerevisiae is alpha 1,2-mannosidase, an enzyme that catalyzes the conversion of Man9GlcNAc2 to Man8GlcNAc2 during the formation of N-linked oligosaccharides. The Saccharomyces cerevisiae alpha 1,2-mannosidase enzyme of is a member of the Class 1 alpha 1,2-mannosidases that are conserved from yeast to 10 mammals. Given the important roles played by the alpha 1,2-maimosidases and the mannosidases in general in glycosylation and the physiochemical activity regulated by glycosylation, there is significant interest in identifying novel polypeptides having homology to one or more mannosidases. We herein describe the identification and characterization of novei polypeptides having homology to a mannosidase protein, designated herein as PR01477 polypeptides. 6. PRQ1478 Recently, a new subfamily of galactosyltransferase genes that encode type II transmembrane proteins was identified from a mouse genomic library (Hennet et al., (1998) J. Biol. Chem. 272111:58-65). Galactosyl transferases, in general, are all of interest. Beta 1,4-galactosyltransferase is been found in two 20 subcellular compartments where it is believed to perform two distinct function. Evans, et al., loess ays. 17(3):261-268 (1995). Beta 1,4-galactosyltransferase is described as a possible transducing receptor in Dubois and Shur. Adv. Exp. Med. Biol.. 376:105-114 (19951. and further reported on in Shur. Glvcobiologv. 1(6):563-575 (1991). Expression and function of cell surface galactosyltransferase is reported on in Shur, Biochim. Bioohvs. Acta.. 988(3):389-409 (1989). Moreover, the receptor function of galactosyltransferase during 25 mammalian fertilization is described in Shur, Adv. Exp. Biol.. 207:79-93 (1986), and the receptor function during cellular interactions is described in Shur, Mol. Cell Biochem.. 61(2):143-158 (1984). Thus, it is understood that galactosyltransferases and their related proteins axe of interest. 7. PRQ831 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.

Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PR0831. 8. PRQ1113 Protein-proteininteractions include receptor and antigen complexes and signaling mechanisms. As more is known about the structural and functional mechanisms underlying protein-protein interactions, protein-protein 3 interactions can be more easily manipulated to regulate the particular result of the protein-protein interaction. Thus, the underlying mechanisms of protein-protein interactions are of interest to the scientific and medical community.

All proteins containing leucine-rich repeats are thought to be involved in protein-protein interactions. Leucine-rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular 5 locations. The crystal structure of ribonuclease inhibitor protein has revealed that leucine-rich repeats correspond to beta-alpha structural units. These units are arranged so that they form a parallel beta-sheet with one surface exposed to solvent, so that the protein acquires an unusual, nonglubular shape. These two features have been indicated as responsible for the protein-binding functions of proteins containing leucine-rich repeats. See, Kobe and Deisenhofer, Trends Biochem. Sci.. 19(10):415-421 (Oct. 1994).

A study has been reported on leucine-rich proteoglycans which serve as tissue organizers, orienting and ordering collagen fibrils during ontogeny and are involved in pathological processes such as wound healing, tissue repair, and tumor stroma formation. Iozzo, R. V., Crit. Rev. Biochem. Mol. Biol.. 32(2): 141-174 (1997). Others studies implicating leucine rich proteins in wound healing and tissue repair are De La Salle, C., et al.. Vouv. Rev. Fr. Hematol. (Germany), 37(4):215-222(1995), reporting mutations in the leucine rich motif 15 in a complex associated with the Weeding disorder Bernard-Soulier syndrome, Chlemetson, K. J., Thromb. Haemost. (Germany), 74(1): 111-116 (July 1995), reporting that platelets have leucine rich repeats and Ruosiahti, E. I., et al., W09110727-A by La Jolla Cancer Research Foundation reporting that decorin binding to transforming growth factor^ has involvement in a treatment for cancer, wound healing and scarring. Related by function to this group of proteins is the insulin like growth factor (IGF), in that it is useful in wound-healing and 20 associated therapies concerned with re-growth of tissue, such as connective tissue, skin and bone; in promoting body growth in humans and animals; and in stimulating other growth-related processes. The acid labile subunit of IGF (ALS) is also of interest in that it increases the half-life of IGF and is part of the IGF complex in vivo.

Another protein which has been reported to have leucine-rich repeats is the SLIT protein which has been reported to be useful in treating neuro-degenerative diseases such as Alzheimer's disease, nerve damage such 25 as in Parkinson's disease, and for diagnosis of cancer, see, Artavanistsakonas, S. and Rothberg, J. M., W09210518-A1 by Yale University. Of particular interest is LIG-1, a membrane glycoprotein that is expressed specifically in glial cells in the mouse brain, and has leucine rich repeats and immunoglobulin-like domains. Suzuki, et al., J. Biol. Chem. (U.S.), 271(37)-.22522 (1996). Other studies reporting on the biological functions ofproteins having leucine rich repeats include: Tayar, N., etal., Mol. Cell Endocrinol.. (Ireland). 125(l-2):65-30 70(Dec. 1996) (gonadotropin receptor involvement); Miura, Y., etal., Nippon Rinsho (Japan). 54(7): 1784-1789 (July 1996) (apoptosis involvement); Harris, P. C., etal., J. Am. Soc. Nephrol.. 6(4): 1125-1133 (Oct. 1995) (kidney disease involvement). 9. PRQ1194 The nuclear genes PET117 and PET119 are required for the assembly of active cytochrome c oxidase in S. Cerevisiae, and therefore, are of interest. Also of interest are nucleic acids which have sequence identity with these genes. PET genes are further described in McEwen, et al., Curr. Genet.. 23(1):9-14 (1993). 4 . PROlllO The bone marrow plays many important roles in the mammal. One of those roles is to provide a source of various progenitor cells that differentiate into important cells and other components of the blood and immune systems. As such, the function of the myeloid system is of extreme interest.

We herein describe the identification and characterization of novel polypeptides having homology to 5 myeloid upregulated protein, designated herein as PROl 110 polypeptides. 11. PRQ1378 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding 10 sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PRO1378. 12. PRQ1481 Efforts are being undertaken by both industry and academia to identify new, native proteins. Many 15 efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel proteins. We herein describe the identification and characterization of a novel protein designated herein as PRO 1481. 13. PRQ1189 There has been much interest in the identification of receptor proteins on stem cells and progenitor cells which may be involved in triggering proliferation or differentiation. A type II transmembrane protein was identified in proliferating progenitor cells in the outer perichondrial rim of the postnatal mandibular condyle proliferation. The investigators concluded that E25 could be a useful marker for chondro-osteogenic differentiation (Deleersnijder, et al. J. Biol. Chem. 271(321:19475-19482 (1996)). 14. PRQ1415 Efforts are being undertaken by both industry and academia to identify new, native transmembrane and receptor proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and 30 characterization of a novel transmembrane polypeptide designated herein as PR01415.

. FRQ1411 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding 35 sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PR01411. 16. PRQ1295 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PR01295. 17. PRQ1359 Enzymes such as hyaluronidase, sialyltransferase, urokinase-type plasminogenactivator.plasmin, matrix metalloproteinases, and others, play central roles in the catabolism of extracellular matrix molecules. As such, these enzymes and inhibitors thereof, may play roles in metastatic cancer and the treatment thereof. Van 10 Aswegen and du Plessis, Med. Hypotheses. 48(5):443-447 (1997). For the foregoing reason, as well as their diversity in substrate specificity example, sialyltransferases are of particular interest. For example, a peptide of interest is the GalNAc alpha 2, 6-sailytransferase as described in Kurosawa, et al., J. Biol. Chem.. 269(2):1402-1409 (1994). This peptide was constructed to be secreted, and retained its catalytic activity. The expressed enzyme exhibited activity toward asialomucin and asialofetuin, but not other glycoproteins tested. As 15 sialylation is an important function, sialyltransferases such as this one, and peptides related by sequence identity, are of interest. Sialyltransferases are further described in the literature, see for example, Sjoberg, et al, J. Biol. Chem.. 271(13):7450-7459 (1996), Tsuji, J. Biochem.. 120(1): 1-13 (1996) and Harduin-Lepers, et al., Glvcobiologv. 5(8):741-758 (1995). 18. PRQ1190 Kang et al. reported the identification a novel cell surface glycoprotein of the Ig superfamily (J. Cell biol. (1997) 138(0:203-213'). Cell adhesion molecules of the Ig superfamily are implicated in a wide variety of biological processes, including cell migration, growth control, and tumorigenesis. The Kang et al. studies suggest that loss of CDO function may play a role in oncogenesis. Accordingly, the identification of additional 25 CDO-like molecules, and more generally, cell adhesion molecules of the Ig superfamily, is of interest. 19. PRQ1772 Peptidases are enzymatic proteins that function to cleave peptide substrates either in a specific or nonspecific manner. Peptidases are generally involved in a large number of very important biological processes in 30 mammalian and non-mammalian organisms. Numerous different peptidase enzymes from a variety of different mammalian and non-mammalian organisms have been both identified and characterized. The mammalian peptidase enzymes play important roles in many different biological processes including, for example, protein digestion, activation, inactivation, or modulation of peptide hormone activity, and alteration of the physical properties of proteins and enzymes.

In light of the important physiological roles played by peptidase enzymes, efforts are currently being undertaken by both industry and academia to identify new, native peptidase homologs. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for 6 novel transmembrane proteins. Examples of screening methods and techniques are described in the literature [see, for example, Klein etal., Proc. Natl. Acad. Sci.. 93:7108-7113 (1996); U.S. Patent No. 5,536,637)]. We herein describe the identification of novel polypeptides having homology to various peptidase enzymes, designated herein as PRO1772 polypeptides. 20. PRQ1248 Putative protein-2 (PUT-2) is a homolog of the human disease genes L1CAM, G6PD and P55 (Riboldi Tunnicliffeetal., Genome Analysis, submitted). As such, there is interest in identifying novel polypeptides and encoding DNA having homology to the PUT-2 protein. We herein describe the identification and characterization of novel polypeptides having homology to PUT-2 protein, designated herein as PR01248 polypeptides. 21. PRQ1316 Dickkopf (Dkk) is a family of secreted proteins having a high degree of homology in the cysteine-rich domains (i.e., 80-90%). Dkk-1, the first discovered member, of this family has potent head-inducgin activity on the Spemann organizer. Glinka et al., Nature 391 (6665): 357-362 (1988). The Spemann organizer of the 15 amphibian embryo can be subdivided into two discrete activities, namely trunk organizer and head organizer. Dkk-1 has been found to be both sufficient and necessary to cause head induction in Xenopus embryos and is further a potent antagonist of Wnt signaling, suggesting that the Dkk genes encode an entire family of Wnt inhibitors.

Members of the Wnt gene family function in both normal development and differentiation as well as 20 in tumorigenesis. Wnts are encoded by a large gene family whose members have been found in round worms, insects, cartilaginous fish, and vertebrates. Holland et al., Dev. Suppl., 125-133 (1994). Wnt genes encode a family of secreted glycoproteins that modulate cell fate and behavior in embryos through activation of receptor-mediated signaling pathways.

Studies of mutations in Wnt genes have indicated a role for Wnts in growth control and tissue 25 patterning. In Drosophila, wingless (wg) encodes a Wnt-related gene (Rijsewik et al., Cell, 50: 649-657 (1987)) and wg mutations alter the pattern of embryonic ectoderm, neurogenesis, and imaginal disc outgrowth. Morata and Lawerence, Dev. Biol., 56: 227-240 (1977); Baker, Dev. Biol., 125: 96-108 (1988); Klingensmith and Nusse, Dev. Biol., 166: 396-414 (1994). In Caenorhabditis elegans, lin-44 encodes a Wnt homolog which is required for asymmetric cell divisions. Herman and Horvitz, Development, 120:1035-1047(1994). Knock-out 30 mutations in mice have shown Wnts to be essential for brain development (McMahon and Bradley, Cell, 62: 1073-1085 (1990); Thomas and Cappechi, Nature, 346: 847-850 (1990)), and the outgrowth of embryonic primordia for kidney (Stark et al., Nature, 372: 679-683 (1994)), tail bud (Takada et al., Genes Dev., 8: 174-189 (1994)), and limb bud. Parr and McMahon, Nature, 374: 350-353 (1995). Overexpression of Wnts in the mammary gland can result in mammary hyperplasia and tumors, ((McMahon, supra (1992); Nusse and 35 Varmus, H.E., Cell 69: 1073-1087(1992)), and precocious alveolar development. Bradbury etal., Dev. Biol., 170: 553-563 (1995). Moreover, constitutive expression of Wnt-4 in virgin hosts of transplanted mammary epithelium resulted in highly branched tissue, similar to a pregnancy-like growth pattern. Bradbury et al., Dev. 7 Biol. 170: 553-563 (1995).

The Wnt/Wg signal transduction pathway plays an important role in the biological development of the organism and has been implicated in several human cancers. This pathway also includes the tumor suppressor gene, APC. Mutations in the APC gene are associated with the development of sporadic and inherited forms of human colorectal cancer. For example, elevated levels of Wnt-2 have been observed in colorectal cancers. 5 Vider, B-Z. et al., Oncogene 12: 153-158 (1996). 22. FRQ1197 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding 10 sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PR01197. 23. PRQ1293 Immunoglobulins are antibody molecules, the proteins that function both as receptors for antigen on the 15 B-cell membrane and as the secreted products of the plasma cell. Like all antibody molecules, immunoglobulins perform two major functions: they bind specifically to an antigen and they participate in a limited number of biological effector functions. Therefore, new members of the Ig superfamily and fragments thereof are always of interest. Molecules which act as receptors by various viruses and those which act to regulate immune function are of particular interest. Also of particular interest are those molecules which have homology to known Ig 20 family members which act as virus receptors or regulate immune function. Thus, molecules having homology to Ig superfamily members and fragments thereof (i.e., heavy and light chain fragments) are of particular interest.

We herein describe the identification and characterization of novel polypeptides having homology to an immunoglobulin heavy chain variable region protein, designated herein as PR01293 polypeptides. 24. PRQ1380 Efforts are being undertaken by both industry and academia to identify new, native transmembrane and receptor proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and 30 characterization of a novel transmembrane polypeptide designated herein as PR01380.

. PRQ1265 The identification of novel secreted proteins involved in physiological and metabolic pathways is of interest because of their potential use as pharmaceutical agents. Of particular interest is the identification of 35 novel polypeptides that are potentially involved in immune response and inflammation mechanisms. A novel polypeptide has recently been identified that is expressed in mouse B cells in response to IL-4. The gene encoding this polypeptide is referred to as interleukin-four induced gene 1, or "Figl" (Chu et al. Proc. Natl. 8 Acad. Sci (1997) 94(61:2507-25121. 26. PRQ1250 Long chain fatty acid Co A ligase is an enzymatic protein that functions to ligate together long chain fatty acids, a function that plays important roles in a variety of different physiological processes. Given the 5 importance of this enzymatic protein, efforts are currently being undertaken to identify novel long chain fatty acid Co A ligase homologs. We herein describe the identification and characterization of novel polypeptides having homology to long chain fatty acid CoA ligase, designated herein as PR01250 polypeptides. 27. PRQ1475 N-acetylglucosaminyltransferase proteins comprise a family of enzymes that provide for a variety of important biological functions in the mammalian organism. As an example, UDP-N-acetylglucosamine: alpha-3-D-mannoside beat-1,2-N-acetylglucosaminyltransferase I is an enzymatic protein that catalyzes an essential first step in the conversion of high-mannose N-glycans to hybrid and complex N-glycans (Sarkar et al., Proc. Natl. Acad. Sci. USA. 88:234-238 (1991). Given the obvious importance of the N-acetylglucosaminyltransferase 15 enzymes, there is significant interest in the identification and characterization of novel polypeptides having homology to an N-acetylglucosaminyltransferase protein. We herein describe the identification and characterization of novel polypeptides having homology to an N-acetylglucosaminyitransferase protein, designated herein as PRO1475 polypeptides. 28. PRQ1377 Efforts are being undertaken by both industry and academia to identify new, native transmembrane and receptor proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane polypeptide designated herein as PRO1377. 29. PRQ1326 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel 30 secreted protein designated herein as PRO 1326.

. PRQ1249 Efforts are being undertaken by both industry and academia to identify new, native transmembrane and receptor proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to 35 identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane polypeptide designated herein as PR01249. 9 31. PRQ1315 Many important cytokine proteins have been identified and characterized and shown to signal through specific cell surface receptor complexes. For example, the class II cytokine receptor family (CRF2) includes the interferon receptors, the interleukin-10 receptor and the tissue factor CRFB4 (Spencer et al., J. Exp. Med. 187:571-578 (1998) and Kotenko et al., EMBO J. 16:5894-5903 (1997)). Thus, the multitude of biological 5 activities exhibited by the various cytokine proteins is absolutely dependent upon the presence of cytokine receptor proteins on the surface of target cells. There is, therefore, a significant interest in identifying and characterizing novel polypeptides having homology to one or more of the cytokine receptor family. We herein describe the identification and characterization of a novel polypeptide having homology to cytokine receptor family-4 proteins, designated herein as PRO 1315 polypeptides. 32. PRQ1S99 Granzyme M is a natural killer cell serine protease. The human gene is 7.5 kilobases, has an exon-intron structure identical to other serine proteases, and is closely linked to the serine protease gene cluster on chromosome 19pl3.3. (Pilat et al., Genomics. 24:445-450 (1994)). Granzyme M has been found in two human 15 natural killer leukemia cell lines, unstimulated human peripheral blood monocytes and untreated purified CD3-CD56+ large granular lymphocytes. (Smyth et al., J. Immunol.. 151:6195-6205 (1993)). 33. PRQ1430 Reductases form a large class of enzymatic proteins found in a variety of mammalian tissues and play 20 many important roles for the proper functioning of these tissues. They are antioxidant enzymes that catalyze the conversion of reactive oxygen species to water. Abnormal levels or functioning of reductases have been implicated in several diseases and disorders including strokes, heart attacks, oxidative stress, hypertension and the development of both benign and malignant tumors. For example, malignant prostate epithelium may have lowered expression of such antioxidant enzymes [Baker et al., Prostate 32(4):229-233 (1997)]. International 25 patent application no. W09622360-A1 describes a prostate specific reductase that is useful for diagnosing and treating prostate cancer and screening new antagonists. Inhibitors of alpha-reductase have been used in the treatment of benign prostatic hyperplasia (Anderson, Drugs Aging (19961 6(51:388-396). For these reasons, the identification of new members of the reductase family has been of interest for the treatment and diagnosis of cancers and other diseases and disorders. 34. PRQ1374 Prolyl 4-hyroxylase (P4HA) catalyzes the formation of 4-hydroxyproline in collagens. Annunen, et al., J. Biol. Chem., 272(28): 17342-17348 (1997); Helaakoski, et al., PNAS USA, 92(10):4427-4431 (1995); and Hopkinson, et al., Gene, 149(2):391-392 (1994). This enzyme and molecules related thereto are of interest.

. PRQ1311 The tetraspan family of proteins, also referred to as the "transmembrane 4 (TM4) superfamily", are proposed to have an organizing function in the cell membrane. It is believed that they interact with large molecular complexes and function in such diverse activities as cell adhesion, activation and differentiation (see Maecker et al. FASEB (1997111:428-442). Accordingly, the identification of new members of the tetraspan family of proteins is of interest. Efforts are being undertaken by both industry and academia to identify new, native transmembrane proteins. Many efforts are focused on the screening of mammalian recombinant DNA 5 libraries to identify the coding sequences for novel receptor proteins. 36. PRO 1357 Ebnerin is a cell surface protein associated with von Ebner glands in mammals. Efforts are being undertaken by both industry and academia to identify new, native proteins and specifically those which possess 10 sequence homology to cell surface proteins such as ebnerin or other salivary gland-associated proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel receptor proteins. We herein describe the identification of novel polypeptides having significant homology to the von Ebner minor salivary gland-associated protein, designated herein as PRO 1357 polypeptides. 37. PRQ1244 One type of transmembrane protein that has received attention is implantation-associated uterine protein. Deficiencies or abnormalities of this protein may be a cause of miscarriage. Therefore, the identification and characterization of implantation-associated proteins is of interest. 38. PRQ1246 Bone-related sulphatase is an enzymatic protein that has been shown to degrade sulphate groups of proteoglycan sugar chains in bone tissue (Australian Patent Publication No. AU 93/44921-A, March 3, 1994). Because of its specific sulphatase activity, it has been suggested that bone-related sulphatase may find use in the 25 treatment of bone metabolic diseases. As such, there is significant interest in identifying and characterizing novel polypeptides having sequence similarity to bone-related sulphatase. We herein describe the identification and characterization of novel polypeptides having homology to bone-related sulphatase, designated herein as PR01246 polypeptides. 39. PRQ1356 Clostridium perfringens enterotoxin (CPE) is considered to be the virulence factor responsible for causing the symptoms of C. perfringens type A food poisoning and may also be involved in other human and veterinary illnesses (McClane, Toxicon. 34:1335-1343 (1996)). CPE carries out its adverse cellular functions by binding to an approximately 50 kD cell surface receptor protein designated the Clostridium perfringens 35 enterotoxin receptor (CPE-R) to form an approximately 90,000 kD complex on the surface of the cell. cDNAs encoding the CPE-R protein have been identified characterized in both human and mouse (Katahira et al., J. Cell Biol. 136:1239-1247 (1997) and Katahira et al., J. Biol. Chem. 272:26652-26658 (1997)). Since the CPE toxin 11 has been reported to cause a variety of illnesses in mammalian hosts and those illnesses are initiated by binding of the CPE toxin to the CPE-R, there is significant interest in identifying novel CPE-R homologs. We herein describe the identification and characterization of novel polypeptides having homology to the CPE-R, designated herein as PR01356 polypeptides. 40. PRQ1275 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PRO 1275. 41. PRQ1274 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel 15 secreted protein designated herein as PRO1274. 42. PRQ1412 Efforts are being undertaken by both industry and academia to identify new, native transmembrane and receptor proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to 20 identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane polypeptide designated herein as PRO 1412. 43. PRQ1S57 The identification of secretory proteins that play roles in neural development are of interest. Such 25 proteins may fmd use in the understanding of and possible treatment of neurological diseases and disorders. Chordin protein, which has been isolated from Xenopus, is a potent dorsalizing factor that regulates cell-cell interactions in the organizing centers of Xenopus head, trunk and tail development (Sasai et al., (1994) Cell 79(51:779-790: see also Mullins, (1998) Trends Genet. 14/41:127-129: and Kessel etal. (1998)) Trends Genet. 14(51:169-1711. It may be used as a component of culture medium for culturing nerve and muscle cells, and 30 may have use in the treatment of neurodegenerative diseases and neural injury (U.S. Pat. No. 5,679,783). 44. PRQ1286 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding 35 sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PR01286. 12 45. PRQ1294 The extracellular mucous matrix of olfactory neuroepithelium is a highly organized structure in intimate contact with chemosensory cilia that house the olfactory transduction machinery. The major protein component of this extracellular matrix is olfactomedin, a glycoprotein that is expressed in olfactory neuroepithelium and which form intermolecular disulfide bonds so as to produce a polymer (Yokoe et al., Proc. Natl. Acad. Sci. USA 5 90:4655-4659 (1993), Bal et al., Biochemistry 32:1047-1053 (1993) and Snyder et al.. Biochemistry 30:9143-9153 (1991)). It has been suggested that olfactomedin may influence the maintenance, growth or differentiation of chemosensory cilia on the apical dendrites of olfactory neurons. Given this important role, there is significant interest in identifying and characterizing novel polypeptides having homology to olfactomedin. We herein describe the identification and characterization of a novel polypeptide having homology to olfactomedin protein. 10 We herein describe the identification and characterization of novel polypeptides having homology to olfactomedin protein, designated herein as PR01294 polypeptides. 46. PRO 1347 Butyrophilin is a milk glycoprotein that constitutes more than 40% of the total protein associated with 15 the fat globule membrane in mammalian milk. Expression of butyrophilin mRNA has been shown to correlate with the onset of milk fat production toward the end pregnancy and is maintained throughout lactation. Butyrophilin has been identified in bovine, murine and human (see Taylor et al., Biochim. Biophvs. Acta 1306:1-4 (1996), Ishii et al., Riochim. Biophvs. Acta 1245:285-292 (1995), Mather et al., J. Dairy Sci. 76:3832-3850 (1993), Ogg, et al., Mamm. Genome. 7(12):900-905 (1996), Sato, et al., J. Biochem.. 20 117(1): 147-157 (1995) and Banghart et al., J. Biol. Chem. 273:4171-4179 (1998)) and is a type I transmembrane protein that is incorporated into the fat globulin membrane. It has been suggested that butyrophilin may play a role as the principle scaffold for the assembly of a complex with xanthine dehydrogenase/oxidase and other proteins that function in the budding and release of milk-fat globules from the apical surface during lactation (Banghait et al., suoral. Given that butyrophilin plays a role in mammalian milk production, there is substantial 25 interest in identifying novel butyrophilin homologs. 47. PRQ1305 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding 30 sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PR01305. 48. PRQ1273 The lipocalin protein family is a large group of small extracellular proteins. The family demonstrates 35 great diversity at the sequence level; however, most lipocalins share characteristic conserved sequence motifs. Lipocalins are known to be involved in retinol transport, invertebrate cryptic coloration, olfaction and pheromone transport, and prostaglandin synthesis. The lipocalins have also been implicated in the regulation of cell 13 homoeostasis and the modulation of the immune response, and as carrier proteins, to act in the general clearance of endogenous and exogenous compounds. Flower, Biochem. J.. 318(Pt 1): 1-14- (1996); Flower, FEBS Lett.. 354(1):7-11 (1994). Thus, novel members of the lipocalin protein family are of interest. 49. PRQ1302 CD33 is a cell-surface protein that is a member of the sialoadhesin family of proteins that are capable of mediating sialic-acid dependent binding with distinct specificities for both the type of sialic acid and its linkage to subterminal sugars. CD33 is specifically expressed in early myeloid and some monocyte cell lineages and has been shown to be strongly associated with various myeloid tumors including, for example, acute non-lymphocytic leukemia (ANLL). As such, CD33 has been suggested as a potential target for the treatment 10 of cancers associated with high level expression of the protein. One CD33 homolog (designated CD33L) is described in Takei et al., Cvtoeenet. Cell Genet. 78:295-300 (1997). Another study describes the use of CD33 monoclonal antibodies in bone marrow transplantation for acute myeloid leukemia. Robertson, et al., Prog. Clin. Biol. Res.. 389:47-63 (1994).

Moreover, studies have reported that members of the sialoadhesion family contribute to a range of 15 macrophage functions, both under normal conditions as well as during inflammatory reactions. Crocker, et al., Glvcoconi. J., 14(5):601-609 (1997). Moreover, these proteins are associated with diverse biological processes, i.e., hemopoiesis, neuronal development and immunity. Kelm, et al., Glvcoconi. J.. 13(6):913-926 (1996). Thus, novel polypeptides related to CD33 by sequence identity are of interest. 50. PRQ1283 Olfactory reception occurs via the interaction of odorants with the chemosensory cilia of the olfactory receptor cells located in the nasal epithelium. Based upon the diversity of nasal epithelial-associated odorant binding proteins, the mammalian olfactory system is capable of recognizing and discriminating a large number of different odorant molecules. In this regard, numerous different odorant binding proteins and their encoding 25 DNA have recently been identified and characterized (Dear etal., Biochemistry 30:10376-10382 (1991). Pevsner etal., Sdencg241:336-339(1988), Bucketal., Cell 65:175-187 (1991)andBreeretal.. J. Recent. Res. 13:527-540 (1993)). Because study of the mechanisms of odorant detection by the mammalian olfactory system are of interest, there is significant interest in identifying novel odorant binding protein. We herein describe the identification and characterizationof novel polypeptides having homology to odorant binding proteins, designated 30 herein as PR01283 polypeptides. 51. PRQ1279 Proteases are enzymatic proteins which are involved in a large number of very important biological processes in mammalian and non-mammalian organisms. Numerous different protease enzymes from a variety 35 of different mammalian and non-mammalian organisms have been both identified and characterized, including the serine proteases which exhibit specific activity toward various serine-containing proteins. The mammalian protease enzymes play important roles in biological processes such as, for example, protein digestion, activation. 14 inactivation, or modulation of peptide hormone activity, and alteration of the physical properties of proteins and enzymes.

Neuropsin is a novel serine protease whose mRNA is expressed in the central nervous system. Mouse neuropsin has been cloned, and studies have shown that it is involved in the hippocampal plasticity. Neuropsin has also been indicated as associated with extracellular matrix modifications and cell migrations. See, generally, 5 Chen, et al., Neurosci.. 7(2):5088-5097 (1995) and Chen, et al., J. Histochem. Cvtochem.. 46:313-320 (1998).

We herein describe the identification and characterization of novel polypeptides having homology to neuropsin protein, designated herein as PR01279 polypeptides. 52. PRQ1304 The immunophilins are a family of proteins that function as receptors for immunosuppressant drugs, such as cyclosporin A, FK506, and rapamycin. The immunophilins occur in two separate classes, (1) the FK506-binding proteins (FKBPs), which bind to FK506 and rapamycin, and (2) the cyclophilins, which bind to cyclosporin A. With regard to the FK506-binding proteins, it has been reported that the FK506/FKBP complex functions to inhibit the activity of the serine/threonine protein phosphatase 2B (calcineurin), thereby 15 providing immunosuppressant activity (Gold, Mol. Neurobiol. 15:285-306 (1997V). It has also been reported that the FKJBP immunophilins are found in the mammalian nervous system and may be involved in axonal regeneration in the central nervous system through a mechanism that is independent of the process by which immunosuppression is achieved (Gold, supra). Thus, there is substantial interest in identifying novel polypeptides having homology to the FKBP immunophilins.

We herein describe the identification and characterization of novel polypeptides having homology to FK506 binding protein, designated herein as PR01304 polypeptides. 53. PRQ1317 There is considerable interest in the identification of molecules whose expression is increased upon 25 stimulation of leukocyte populations because insights into the structure and function of these molecules may lead to farther understanding of the intracellular and intercellular events that accompany activation. One such molecule, CD97, a cell surface antigen that is rapidly upregulated upon activation on lymphocytes, has recently been the subject of several publications (see Eichler el al. in Tissue Antigens (1997) 50(5);429-438: Aust et al., Cancer Res. (1997) 57(91:1798-18061. Leukocytes strongly positive for CD97 are concentrated at sites of 30 inflammation relative to CD97 expression in normal lymphoid tissue. A soluble subunit of CD97, CD97alpha, has been found in the body fluids from inflamed tissues (Gray et al. J. Immunol. (1996) 157(121:5438-54471. 54. PRQ1303 Proteases are enzymatic proteins which are involved in a large number of very important biological 35 processes in mammalian and non-mammalian organisms. Numerous different protease enzymes from a variety of different mammalian and non-mammalian organisms have been both identified and characterized, including the serine proteases which exhibit specific activity toward various serine-containing proteins. The mammalian protease enzymes play important roles in biological processes such as, for example, protein digestion, activation, inactivation, or modulation of peptide hormone activity, and alteration of the physical properties of proteins and enzymes.

Neuropsin is a novel serine protease whose mRNA is expressed in the central nervous system. Mouse neuropsin has been cloned, and studies have shown that it is involved in the hippocampal plasticity. Neuropsin 5 has also been indicated as associated with extracellular matrix modifications and cell migrations. See, generally, Chen, et al., J. Neurosci.. 7(2):5088-5097 (1995) and Chen, et al., J. Histochem. Cvtochem.. 46:313-320 (1998). Other studies have reported that kindling induces neuropsin mRNA in the mouse brain. Okabe, et al., Brain Res., 728(1): 116-120 (1996). Additionally, a study has reported that generation of reactive oxygen species has an important role in neuropsin transcript in the limbic areas which might be related to the disturbance in 10 avoidance learning. Akita, et al., Brain Res.. 769(l):86-96 (1997). Thus, neuropsins, and related proteins and agents, including agonists and antagonists are of interest. 55. PRQ1306 There is much interest in the identification of proteins that play roles in mammalian disease and 15 disorders which could lead to new methods of treatment. A macrophage polypeptide, daintain/allograft inflammatory factor 1 (daintain/AlFl), has been identified in the pancreas of prediabetic rats, and has been determined to have a direct effect on insulin secretion. When injected intravenously in mice in low doses, daintain/AIFl doses inhibited glucose-stimulated insulin secretion with a concomitant impairment of glucose elimination. At higher doses, daintain/AIFl potentiated glucose-stimulated insulin secretion and enhanced 20 glucose elimination. Thus, it was suggested that daintain/AIFl may have a role in connection with the pathogenesis of insulin-dependent diabetes mellitus (Chen et al. Proc. Natl Acad. Sci. (1997) 94(251:13879-13884). AIF-1 has also been implicated in both rat and human allogenic heart transplant rejection (Utans et al. Transplantation (19961 61(91:1387-1392), and may play a role in macrophage activation and function (Utans et al. J. Clin. Invest. (19951 95(61:2954-29621. 56. PRQ1336 Protein-protein interactions include receptor and antigen complexes and signalingmechanisms. As more is known about the structural and functional mechanisms underlying protein-protein interactions, protein-protein interactions can be more easily manipulated to regulate the particular result of the protein-protein interaction. 30 Thus, the underlying mechanisms of protein-protein interactions are of interest to the scientific and medical community.

Leucine-rich proteins are known to be involved in protein-protein interactions. A study has been reported on leucine-rich proteoglycans which serve as tissue organizers, orienting and ordering collagen fibrils during ontogeny and are involved in pathological processes such as wound healing, tissue repair, and tumor 35 stroma formation. Iozzo, R. V., Crit. Rev. Biochem. Mol. Biol.. 32(2):141-174 (1997). Others studies implicating leucine rich proteins in wound healing and tissue repair are De La Salle, C., et al., Vouv. Rev. Fr. Hematol. (Germany), 37(4):215-222 (1995), reporting mutations in the leucine rich motif in a complex associated 16 with the bleeding disorder Bemard-Soulier syndrome and Chlemetson, K. J., Thromb. Haemost. (Germany), 74(1): 111-116 (July 1995), reporting that platelets have leucine rich repeats.

Another protein of particular interest which has been reported to have leucine-rich repeats is the slit protein which has been reported to be useful in treating neuro-degenerative diseases such as Alzheimer's disease, nerve damage such as in Parkinson's disease, and for diagnosis of cancer, see, Artavanistsakonas, S. and 5 Rothberg, J. M., W09210518-A1 by Yale University. The slit protein has been characterized and reported to be secreted by glial cells and involved in the formation of axonal pathways in Drosophila as well as the mediation of extracellular protein interactions. Wharton and Crews, Mech. Dev.. 40(3): 141-154 91993); Rothberg and Artavanis-Tsakonas, J. Mol. Biol.. 227(2):367-370 (1992); Rothberg, et al., Genes Dev.. 4(12A):2169-2187 (1990); and Rothberg, et al., QelL 55(6): 1047-1059 (1988). 57. PRQ1278 Lysozymes are secretedenzymes that preferentially hydrolyze the [beta]-l ,4 glucosidic linkages between N-acetylmuramic acid and N-acetylgucosamine which occur in the mucopeptide cell wall structure of certain microoganisms. Lysozyme is of widespread distribution in animals and plants. It has been found in mammalian 15 secretions and tissues including saliva, tears, milk, cervical mucus, leucocytes, kidneys, etc. The identification of new members of the lysozyme family of proteins is of interest because of the variety of roles lysozymes play in metabolic function and dysfunction. Abnormal levels of lysozymes have been implicated in various disease states. Lysozymes have been reported to have anti-microbial, analgesic, and antinociceptive properties. Additional characteristics and possible uses of lysozymes are described in U.S. Pat. No. 5,618,712. 58. PRQ1298 Glycosylation can determine the fate of a protein, for example, whether it is secreted or not. Also, glycoproteins play many structural and functional roles, particularly as pan of the cell membrane. Therefore, glycosylation is of interest. Studies have reported on the growth-related coordinate regulation of the early N-25 glycosylation genes in yeast. Kukuruzinska and Lennon, Glvcobiologv. 4(4):437-443 (1994). Moreover, the relationship between protein glycosylation and fatty acylation of glycoproteins was studied in the wild-type and asparagine-linked glycosylation-deficient mutants in yeast. Appukuttan, FEBS Lett.. 255(1):139-142 (1989). The biosynthesis of asparagine-linked oligosaccharides in yeast was also studied using a mutant. Jackson, et al., Glvcobiologv. 3(4):357-364 (1993). Yeast mutants deficient in protein glycosylation have also been reported 30 in Huffacker and Robbins, PNAS. 80(24)-.7466-7470 (1983). 59. PRQ1301 Cytochrome P450 proteins form a large class of monooxygenase enzymes involved in hydroxylation. Hydroxylation reactions are important in the synthesis of cholesterol and steroid hormones. Enzymes of the 35 cytochrome P450 family play an important role in the metabolism endogenous compounds such as arachidonic acid. These enzymes are also important in the metabolism of foreign substances such as the elimination of drugs from the body [see, for example, Peterson, Aliment. Pharmacol. Ther.. 9:1-9 (1995).]. In addition, metabolites 17 generated through the cytochrome P450 pathway may play a role in carcinogenesis, blood pressure regulation and renal function [see, for example, Rahman et al., Am. J. Hvnertens.. 10:356-365 (1997)]. 60. PRQ1268 Efforts are being undertaken by both industry and academia to identify new, native transmembrane and 5 receptor proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmehibrane proteins. We herein describe the identification and characterization of a novel transmembrane polypeptide designated herein as PR01268. 61. PRQ1269 Granulocytes, the most common type of white blood cell, have the ability to mediate immunologic cytotoxicity against tumor cells and microorganisms. Accordingly, there has been interest in identifying various factors that are produced by these cells because of their potential use as pharmaceutical agents. Patent publication no. W09729765-A1, to Selsted, describes the identification of granulocyte peptide A which was isolated from bovine and murine granulocytes. Several uses for this peptide were identified including, a 15 therapeutic use, use as an agricultural agent, use as a preservative for food, and use as a water treatment agent. 62. PRQ1327 Neurexophilin is a protein that was discovered as a neuronal glycoprotein that was copurified with neurexin I alpha during affinity chromatography on immobilized alpha-latrotoxin (Missler et al., J. Neurosci. 20 18:3630-3638 (1998)). Recent data has shown that the mammalian brain contains four genes for neurexophilins the products of which share a common structure composed of five domains: (1) an N-terminal signal peptide, (2) a variable N-terminal domain, (3) a highly conserved central domain that is N-glycosylated, (4) a short linker region and (5) a conserved C-terminal domain that is cysteine-rich (Missler et al., supra). These data further demonstrate that the neurexophilins are proteolytically processed after synthesis and bind to alpha-neurexins. 25 The structure and characteristics of neurexophilins indicate that they may function as neuropeptides that may signal via alpha-neurexins. Therefore, there is significant interest in identifying and characterizing novel polypeptides having homology to the neurexophilins.

We herein describe the identification and characterization of novel polypeptides having homology to neurexophilin protein, designated herein as PR01327 polypeptides. 63. PRQ1382 Cerebellin is a secreted, postsynaptic neuroprotein found throughout the brain. The highest concentrations of this protein have been found in the cerebellum. It has also been detected in the pituitary, spinal cord, and adrenal glands (Satoh et al. J. Endocrinol. (1997) 15491):27-34). The feasibility of using cerebellum 35 as a quantifiable marker for the investigation of the maturation of Purkinje ceils of the cerebellum and to chart neurodevelopment has been reported (see Slemmon et al. Proc. Natl. Acad. Sci (1985) 82(20V.7145-7148>. Significantly decreased levels of cerebellin have been found in human brains obtained in post-mortem studies 18 from patients with spinocerebellar degeneration, olivopontocerebellar atrophy (OPCAQ) and Shy-Drager syndrome, suggesting that cerebellin plays important pathophysiological roles in these cerebellar diseases (Mizuno etal. Brain Res. (19951 686(11:115-118: Mizuno etal. No To Shinkei (19951 47(111:1069-10741. In view of the importance of cerebellin in neurodevelopment and in neurological diseases and disorders, the identification and characterization of members of this protein family is of interest (see also Yiangou et al. JL 5 Neurochem (19891 53(31:886-889 and Muenaini et al. Synapse (19881 2(21:125-1381. 64. PRQ1328 Efforts are being undertaken by both industry and academia to identify new, native transmembrane and receptor proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to 10 identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane polypeptide designated herein as PR01328. 65. PRQ1325 Efforts are being undertaken by both industry and academia to identify new, native transmembrane and 15 receptor proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane polypeptide designated herein as PR01325. 66. PRQ1340 Cadherins are known as the principal mediators of homotypic cellular recognition and play a demonstrated role in the morphogenic direction of tissue development. Cadherins are a diverse family of proteins that have been identified in various tissues including nervous tissue (Suzuki et al., Cell Reeul.. 2:261-270 (1991)). Ksp-cadherinis a kidney-specific member of the cadherin multigene family (Thomson et al., Biol. Chem. 270:17594-17601 (1995)). Cadherins are thought to play an important role in human cancer (Yap, 25 Cancer Invest.. 16:252-261 (1998)). 67. PRQ1339 Carboxypeptidases are of interest. Carboxypeptidase E appears to be involved in the biosynthesis of a wide range of peptide hormones. Fricker, Anna. Rev. Phvsiol.. 50:309-321 (1988). This carboxypeptidase 30 has been associated with obesity. Leiter. J. Endocrinol.. 155(21:211-214(19971. Carboxypeptidase M has been reported as being a marker of macrophage maturation. Krause, et al., Immunol. Rev.. 161:119-127 (1998). Human mast cell carboxypeptidase has been reported to be associated with allergies. Goldstein, et al., Monoar. Allergy. 27:132-145 (1990). Carboxypeptidase A2 has also been reported on. Faming, et al., J. Biol. Chem.. 266(36):24606-24612 (1991). Other carboxypeptidases of particular interest which are known in the art include 35 human pancreatic carboxypeptidase 2, carboxypeptidase al and carboxypeptidase B. Therefore, novel members of the carboxypeptidase family are of interest. 19 68. PRQ1337 Of particular interest is the identification of blood-related proteins which may have potential therapeutic use or may be useful in the diagnosis of blood-related disorders. Thyroxine-binding globulin (TBG) is synthesized by the liver and secreted into the bloodstream. It is the principal thyroid hormone transport protein in human serum (Refetoff et al. Horm. Res. (1996) 45(3-51:128-138). High serum levels of TBG have been 5 found to cause hyperthyroxinaemia (Leahy etal., Postgrad Med. J. (1984) 60(7031:324-327). Accordingly, the identification and characterization of TBG proteins is of interest (see Flink et al. Proc. Natl Acad Sci. USA (1986) 83(201:7708-7712: Bartalena et al. Acta Med. Austriaca. (1988) 15 SuppI 1:12-15). including the identification of abnormal TBG proteins (see Refetoff, Endocr Rev. (19891 10(31:275-2931. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel 10 secreted proteins. Examples of screening methods and techniques are described in the literature [see, for example, Klein et al., Proc. Natl. Acad. Sci.. 93:7108-7113 (1996); U.S. Patent No. 5,536,637)]. 69. PRQ1342 Efforts are being undertaken by both industry and academia to identify new, native transmembrane and 15 receptor proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane polypeptide designated herein as PR01342. 70. PRQ1343 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.

Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PRO1343. 71. PRQ1480 Semaphores are a large family of transmembrane and secreted proteins, many of which are expressed in the nervous system. Members of the semaphorin family include both ligands and receptors. (Eckhardt et al„ Mol. Cell. Neurosci.- 9: 409-419 (1997)). Studies have revealed a role for semaphorins in embryonic motor and central nervous system axon guidance and synapse formation. (Catalano et al-, Mol. Cell. Neurosci.. 11: 30 173-182 (1998); Kitsukawa et al., Neuron. 19: 995-1005 (1997); Yu et al., Neuron. 20: 207-220 (1998)). Semaphorins have been shown to induce neuronal growth cone collapse and alter their pathway in vivo. (Shoji et al., Development. 125: 1275-1283 (1998)). Members of the semaphorin family have been shown to be immunologically active, inducing cytokine production in human monocytes. (Comeau et al., Immunity. 8:473-482 (1998)). Semaphorins may also play a role in cancer. Expression of a mouse semaphorin gene is known 35 to correlate with metastatic ability in mouse tumor cell lines. (Christensen et al., Cancer Res.. 58: 1238-1244 (1998)). 72. PRQ1487 Fringe is a protein which specifically blocks serrate-mediated activation of notch in the dorsal compartment of the Drosophila wing imaginal disc (see Fleming et al., Development. 124(15):2973-81 (1997); Wu et al. Science (1996) 273/5273):355-3581. Fringe protein is also involved in vertebrate development where a thickening of the apical ectodermal ridge essential for limb bud outgrowth involves an interaction between 5 dorsal cells that express radical fringe and those that do not (see Wolpert, L. Philos Trans R Soc Lond B Biol gci 1998) 353(13701:871-875: Kengaku et al. Science (1998) 280(53671:1274-1277: Cohen et al. Nat. Genet. (1997) 16(31:283-288: Johnston et al. Development (1997) 124(111:2245-2254: Laufer et al. Nature (1997) 386(66231:366-373: Rodriguez-Esteban etal. Nature (19971 386(66231:360-366:1. ). Therefore, fringe protein is of interest for both its role in development as well as its ability to regulate serrate, particularly serrate's 10 signaling abilities. Also of interest are novel polypeptides which may have a role in development and/or the regulation of serrate-like molecules. Of particular interest are novel polypeptides having homology to fringe protein. 73. PRQ1418 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.

Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PR01418. 74. PRQ1472 Butyrophilin is a milk glycoprotein that constitutes more than 40% of the total protein associated with the fat globule membrane in mammalian milk. Expression of butyrophilin mRNA has been shown to correlate with the onset of milk fat production toward the end pregnancy and is maintained throughout lactation. Butyrophilin has been identified in bovine, murine and human (see Taylor et al., Biochim. Biophvs. Acta 25 1306:1-4 (1996), Ishii et al., Biochim. Biophvs. Acta 1245:285-292 (1995), Mather et al., J. Dairy Sci. 76:3832-3850 (1993), Ogg, et al., Mamm. Genome. 7(12):900-905 (1996), Sato, et al., J. Biochem.. 117(1): 147-157 (1995) and Banghart et al., J. Biol. Chem. 273:4171-4179 (1998)) and is a type I transmembrane protein that is incorporated into the fat globulin membrane. It has been suggested that butyrophilin may play a role as the principle scaffold for the assembly of a complex with xanthine dehydrogenase/oxidase and other 30 proteins that function in the budding and release of milk-fat globules from the apical surface during lactation (Banghart et al., supral. Given that butyrophilin plays a role in mammalian milk production, there is substantial interest in identifying novel butyrophilin homologs. Members of the butyrophilin family are further described in Tazi-Ahnini, et al., Immunoeenetics. 47(l):55-63 (1997); Davey, et al., Gene. 199(l-2):57-62 (1997); and Mather and Jack, J. Dairy Sci.. 76(12):3832-3850 (1993). 75. PRQ1461 Proteases are enzymatic proteins which are involved in many biological processes in mammalian and 21 non-mammalian organisms including digestion, protein activation and inactivation, modulation of peptide hormone activity, and alteration of the physical properties of proteins and enzymes. Serine proteases comprise a large class of enzymes that exhibit specific activity toward various serine-containing proteins. Trypsin, which is synthesized by the pancreas and secreted to the small intestine, is a well-characterized serine protease that hydrolyzes peptide bonds of ingested proteins. Trypsin-like proteases have been characterized that are cell-5 surface proteins (see Farlev etal. Biochim Biophvs Acta (1993) 1173(3):350-352: and Levtus et al. Biochemistry (1988) 27(3): 1067-1074). It is believed that some of these trypsin-like proteins may be synthesized as a membrane-bound precursor which matures to a soluble and active protease (Yamaoka et al. J. Biol. Chem (1998) 273(19): 11895-11901).

Because of there importance in metabolism and other enzymatic processes, efforts are being undertaken 10 by both industry and academia to identify new, native serine-like proteases. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel receptor proteins. 76. FRQ1410 Efforts are being undertaken by both industry and academia to identify new, native transmembrane and 15 receptor proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane polypeptide designated herein as PR01410. 77. FRQ1568 The tetraspanin (or tetraspan) family of proteins has grown to include approximately twenty known genes from various species. The tetraspanins are four transmembrane domain membrane-bound molecules which include for example, CD81, CD82, CD9, CD63, CD37 and CD53. Many of these proteins have a flair for promiscuous associations with other molecules, including lineage-specific proteins, integrins, and other transpanins. In terms of function, they are involved in diverse processes such as cell activation and proliferation, 25 adhesion and motility, differentiation and cancer. One study has proposed that these functions may all relate to their ability to act as "molecular facilitators", grouping specific cell-surface proteins and thus increasing the formation and stability of functional signaling complexes. Maecker, et al., FASEB, ll(6):428-42 (1997). Another study concludes that they are responsible for changes in cell morphology, cell-ECM adhesion and cell-signaling. Skubitz, et al., J. Immunology. 157:3617-3626 (1996). Thus, new members of this family are of 30 interest. 78. PRQ1570 Proteases are enzymatic proteins which are involved in many biological processes in mammalian and non-mammalian organisms including digestion, protein activation and inactivation, modulation of peptide 35 hormone activity, and alteration of the physical properties of proteins and enzymes. Serine proteases comprise a large class of enzymes that exhibit specific activity toward various serine-containing proteins. Trypsin, which is synthesized by the pancreas and secreted to the small intestine, is a well-characterized serine protease that 22 hydrolyzes peptide bonds of ingested proteins. Trypsin-like proteases have been characterized that are cell-surface proteins (see Farley etal. Biochim Biophvs Acta (19931 1173(31:350-352: andLeytus etal. Biochemistry (1988) 27(31:1067-10741. It is believed that some of these trypsin-like proteins may be synthesized as a membrane-bound precursor which matures to a soluble and active protease (Y amaoka et al. J. Biol. Chem (1998) 273(191:11895-119011.

Of particular interest are human colon carcinoma derived serine proteases SP59, SP60 and SP67 which may be useful to screen for specific inhibitors or modulators to use in treatment of associated disease states and disorders related to these proteins. In Japanese patent J09149790-A, SP60 is reported to be identified, having accession number P W22986 and 233 amino acids. 79. PRQ1317 Members of the semaphorin family of glycoproteins play important roles in the developing nervous system, and more particularly in axonal guidance. Semaphorins have been identified in the human immune system, where they are believed to play functional roles including B-cell signaling (Hall et al. Proc. Natl. Acad. Sci (1996) 93(211:11780-501. A human semaphorin gene, useful in the diagnosis of nervous system an immune 15 disorders, is disclosed in Japanese Pat. No. J10155490-A, published June 16, 1998. The identification of additional members of the semaphorin family if of interest. 80. PRQ1780 Enzymatic proteins that may be implicated in metabolic diseases or disorders are of particular interest. 20 The enzymatic addition of sugars to fat-soiuble chemicals is an important process that increases their solubility in water and aids in their excretion. In mammals, glucuronic acid is the main sugar that is used to prevent the waste products of metabolism and fat-soluble chemicals from reaching toxic levels in the body. The UDP glucuronosyltransferases that carry out this reaction are part of a super family of UDP glycosy ltransferases found in animals, plants and bacteria. In the liver, UDP-glucuronosyltransferase conjugates bilirubin. There are a 25 number of conditions which affect UDP-glucuronosyltransferase activity resulting in unconjugated hyperbilirubinemia. These conditions include genetic disorders such as Crigler-Najjar Syndrome (see Jurgen et al., Biochem. J. (1996) 314:477-483) and Gilbert syndrome, as well as acquired conditions such as Lucey-Driscoll Syndrome. Accordingly, the identification of novel members of the glucuronosyltransferase family is of interest (see Tukey et al., J. Biol. Chem. (19931 268(20): 15260-6; and W09212987-A). 81. PRQ1486 The cerebellum contains a hexadecapeptide, termed cerebellin, that is conserved in sequence from human to chicken. Three independent, overlapping cDNA clones have been isolated from a human cerebellum cDNA library that encode the cerebellin sequence. The longest clone codes for a protein of 193 amino acids 35 generally termed precerebellin, or a cerebellin precursor. This protein has a significant similarity to the globular region of the B chain of human complement component Clq. The region of relatedness extends approximately over 145 amino acids located in the carboxyl terminus of both proteins. Unlike Clq B chain, no collagen-like 23 motifs are present in the araino-terminal regions of precerebellin. It is believed that cerebellin is not liberated from precerebellin by the classical dibasic amino acid protealytic cleavage mechanism seen in many neuropeptide precursors. The cerebellin precursor has been associated with synaptic physiology. Urade, etal., PNAS. USA. 88(3): 1069-1073 (1991). Cerebellin, its precursor, and related molecules, particularly those having sequence identity with cerebellin, are therefore of interest. 82. PRQ1433 Efforts are being undertaken by both industry and academia to identify new, native transmembrane and receptor proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and 10 characterization of a novel transmembrane polypeptide designated herein as PRO 1433. 83. PRQ1490 Enzymatic proteins play important roles in the chemical reactions involved in the digestion of foods, the biosynthesis of macromolecules, the controlled release and utilization of chemical energy, and other processes 15 necessary to sustain life. Acyltransferases are enzymes which acylate moieties. For example, acyl-glycerol-phosphate acyltransferases can act on lysophosphatidic acid as a substrate. The lysophosphatidic acid is converted to phophatidic acid and thus plays a role in forming phosphatidylethanolamine found in membranes. See, Brown, et al., Plant Mol. Biol.. 26(l):211-223 (1994). Moreover, l-acyl-sn-glycerol-3-phosphate acyltransferase (LPAAT) is an enzymatic protein that shows a preference for medium-chain-length fatty acyl-20 coenzyme A substrates. See. Knutson etal.. Plant Phvsiol. 109:999-1006(199511. Thus, acyltransferases play an important role in the biosynthesis of molecules requiring acylation.

We herein describe the identification and characterization of novel polypeptides having homology to a l-acyl-sn-glycerol-3-phosphate acyltransferase protein, designated herein as PR01490 polypeptides. 84. PRQ1482 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PR01482. 85. PRQ1446 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel 35 secreted protein designated herein as PR01446. 24 86. PRQ1S58 Methyltransferase enzymes catalyze the transfer of methyl groups from a donor molecule to an acceptor molecule. Methyltransferase enzymes play extremely important roles in a number of different biological processes including, for example, in the electron transport chain in the plasma membrane in prokaryotes and in the inner mitochondrial membrane in eukaiyotic cells (see, e.g., Barkovich et al., J. Biol. Chem. 272:9182-9188 5 (1997), Dibrov et al., J. Biol. Chem. 272:9175-9181 (1997), Lee et al., J. Bacteriol.. 179:1748-1754 (1997) and Marbois et al., Arch. Biochem. Biophvs. 313:83-88 (1994)). Methyltransferase enzymes have been shown to be essential for the biosynthesis of ubiquinone (coenzyme Q) and menaquinone (vitamin K2), both of which are essential isoprenoid quinone components of the respiratory electron transport chain. Given the obvious importance of the methyltransferase enzymes, there is substantial interest in identifying novel polypeptide 10 homologs of the methyltransferases. We herein describe the identification and characterization of a novel polypeptide having homology to methyltransferase enzymes, designated herein as PR01558 polypeptides. 87. PRQ1604 The identification of novel growth factors is of particular interest because of the roles they play in 15 inducing cellular growth, proliferation and differentiation in both normal states and abnormal states. The identification of growth factors that are over- or under-expressed in abnormal tissues (e.g. tumors) may lead to the development of diagnostic tools and therapeutic agents. Growth factors have been isolated from hepatoma-derived cell lines. Hepatoma-derived growth factors have been isolated from mouse (Japanese Pat. No. J09313185-A, published December 9,1997) and human (Japanese Pat. No. J06343470-A, published December 20 20, 1994) tissues. A hepatoma-derived growth factor, isolated from a human hepatoma-derived cell line, has been found to be ubiquitously expressed in several tumor-derived cell lines, as well as in normal tissues (Nakamura et al., J. Biol. Chem (1994) 269(401:25143-91. The growth factor was determined to be a novel heparin-binding protein that is mitogenic for fibroblasts. 88. PRQ1491 The neuronal cell body is usually round like any other cell. However, these cells have structures, also referred to as "processes", which grow from them to form synaptic connections. Some of these processes carry information away from the cell body; sometimes over very long distances. These long and thin processes are axons. The axon is a thin, static tube. Other processes carry information either towards the cell body, or both 30 towards and away from the cell body. These shorter and usually thicker processes are called dendrites. Both axons and dendrites are called neurites.

During development and the growth stage of neurons, neurites are formed by means of growth cones. A growth cone is the growing tip of a neurite. The growth cone is flattened and highly motile. It is where new material is added and further extension of the axon originates. Controlling where the growth cone crawls controls 35 were the axon will be laid down and thus where it will be present.

The growth cone has several definable parts. The thin, flattened, veil-like processes that stick out and retract from the leading edge are called lamellipodia. The needle-like processes that stick out and retract from the leading edge are called microspikes or filopodia. These are the structures involved in pushing the leading edge of the growth cone forward.

The accurate navigation of growth cones to their appropriate targets requires that they Tecognize and respond to navigational cues in their immediate environment. Some of these cues encourage extension into certain areas whereas others discourage extension into others. Well characterized molecules that encourage neurite 5 outgrowth in vitro include the extracellular matrix molecule laminin and the neuronal cell surface molecule L1/G4/8D9. These molecules which promote neurite extension are generally widely distributed throughout the body. Laminin immunoreactivity is reasonably widespread in the developing central and peripheral nervous systems. Similarly, L1/G4/8D9 is present on a wide variety of neuronal processes in the developing central nervous system, particularly long projecting axons. It is, therefore, unclear whether the known outgrowth 10 promoting molecules play an important role in self-specific choices growth cones make as they decide between possible routes. Instead, their function is believed to provide a generally permissive environment in which growth cones extend and respond to more specific navigational cues.

Among these more specific cues are molecules that inhibit the motility of particular growth cones. Growth cones have been observed to lose their motile morphology and cease advancing (collapse) on contact with 15 other neurites of different types. Territory formation in vitro may mean the manifestation of a process that leads to selective fasciculation in vivo. Some growth cones have been observed to crawl along specific axonal pathways, or stereotype sequences of axonal pathways in developing embryos. Specific motility inhibiting effects could determine which of several alternative pathways a growth cone will extend on. Growth cones would be expected to prefer growing on axons that do not induce them to collapse while shunning those that do. 20 It has been observed that, for example, sympathetic growth cones will be inhibited or collapse when coming in contact with retinal neurites. Likewise, growth cones of retinal neurites will collapse when coming in contact with sympathetic neurites. It is believed that such cell activity is achieved through the presence of receptors which specifically respond to specific growth inhibition cues by the molecules which transmit specific cues pertaining to growth. Cues are believed to be present on cell surfaces, particularly on axon surfaces. 25 When nerve damage occurs, repair is impeded or incapable of occurring due to the failure of neurites to replace damaged axons or dendrites. If an existing neurite is damaged, severed or destroyed, a new neurite is incapable of growing out from the cell body to replace it. The presence of molecules which inhibit neurite growth are believed to be responsible for the difficulty in neurite regeneration. Collapsins are proteins that function to modulate the activity of molecules which modulate growth cone extension. 30 We herein describe the identification and characterization of novel polypeptides having homology to a collapsin protein, designated herein as PRO 1491 polypeptides. 89. PRQ1431 The transduction of intracellular signaling is crucial to cell processing such as differentiation, motility 35 and division. Such signal transduction is believed to occur throughout the cell in the form of complex interactions between proteins. Such protein-protein interactions are often mediated by modular domains within signaling proteins. As a result, signal transduction is now modeled as a system in which molecules act in a 26 combination, and the composition of that combination, determines the signal.

Src homology domains (e.g., SH2 and SH3) are two domains found in regions of sequence similarity of proteins involved in signal transduction. Early work on the oncogenic tyrosine kinase Src identified the SH2 domain. Since then, SH2 and SH3 domains have been found in many diverse proteins, making them among the most common type of structural motif. SH2 and SH3 domains are modular in that they fold independently of 5 the protein that contains them, their secondary structure places N- and C- termini close to one another in space, and they appear at variable locations (anywhere from N- to C-terminal) from one protein ot the next (Cohen et al., Cell 80: 237-348, 1995).

Early studies that mutated the SH2 or SH3 domain showed that these two domains were important for function, but it was not until the cloning of unrelated families of signaling proteins such as RAS-GAP, and the 10 Crk oncogene that the modular nature of these domains was revealed. These latter experiments demonstrated that RAS-GAP and Crk bound tightly to receptor tyrosine kinases upon ligand stimulation. Follow-up studies demonstrated that the mechanism of this binding was through the SH2 domain and that receptor autophosphorylation was required. Such a finding implied that activation of the receptor tyrosine kinase could be viewed as a means of changing the binding aspect of the intracellular domain, and the receptor-SH2 containing 15 protein interaction would initiate the signal transduction cascade.

SH3 domains have a more general function than that which is purported for SH2. SH3 binding proteins have been isolated by screening bacteriophage expression libraries with labeled SH3 domains. The results of these experiments showed that SH3 domains would bind to short proline-rich peptides, in particular the motif PxxP. Based on the level of knowledge present at the time of the preparation of the present patent application, 20 all of the SH3 binding sites identified have the property of being proline rich. Binding of an SH3 domain is independent of covalent modification of the binding site, such as phosphorylation as occurs with the SH2 domain. As a result, SH3-ligand interactions are usually constitutive and not inducible, although exceptions do exist. In general, SH3 domains are less likely to act as signal "switches" than as a means of assembling protein complexes via moderate-affinity interactions. Such moderate affinity interactions also imply that the SH3-mediated 25 interactions will be relatively short in duration and remodeled in response to changes in concentration of binding partners.

The resolution of binding characteristics of SH2 and SH3 domains has led to proposed compounds which would block signal transduction. Peptidomimetic ligands based on the sequence of target proteins for SH2 and SH3 domains may represent new lead compounds for the therapy of proliferative diseases that are dependent 30 upon constitutively activated tyrosine kinases (e.g., BCR/ABL in chronic myelogenous and acute lymphocytic leukemias or HER-2/Neu in breast and ovarian cancer). 90. FRQ1563 Cellular disintegrin and metalloproteinase (ADAMs) are a family of genes with a sequence similar to 35 those of snake venom metalloproteinases and disintegrins. The ADAMTS-1 gene encodes a new type of ADAM protein with respect to possessing the thrombospondin (TSP) type I motifs, the expression of which is associated with the inflammatory process (Kuno et al., J. Biol. Chem. 273:13912-13917 (1998), Kuno et al., Genomics 27 46:466-471 (1997) and Kuno et al., J. Biol. Chem. 272:556-562 (1997)). Expression of the ADAMTS-1 gene is induced in kidney and heart by in vivo administration of lipopolysaccharide, suggesting a ppssible role in the inflammation reaction. In this regard, the ADAMTS-1 protein has been suggested as playing a possible role in various inflammatory processes as well as in the development of cancer cachexia (Kuno et al., 1998, supra). We herein describe the identification and characterization of novel polypeptides having homology to ADAMTS-1 5 protein, designated herein as PR01563 polypeptides. 91. PRQ1565 Chondromodulin proteins are cartilage-generated matrix components that synergisticaily stimulate the growth and differentiation of chondrocytes (Suzuki, Connect. Tissue Res. 35:303-307 (1996)). More 10 specifically, chondromodulin-I functions to inhibit the proliferation of vascular endothelial cells and tube formation, thereby functioning to stimulate cartilage growth and inhibiting replacing cartilage by bone in an early stage. Chondromodulin-II, while not capable of inhibiting vascularization like chondromodulin-1, also functions to stimulate osteoclast differentiation and cartilage growth. As such, these two polypeptides are essential for the regulation of the formation of cartilage and endochondral bone structures. Given the extremely important 15 physiological roles played by the chondromodulin proteins, there is significant interest in identifying and characterizing novel polypeptides having homology to these proteins. We herein describe the identification and characterization of novel polypeptides having homology to cbondromodulin-I protein, designated herein as PR01565 polypeptides. 92. PRQ1571 Clostridium perfringens enterotoxin (CPE) is considered to be the virulence factor responsible for causing the symptoms of C. perfringens type A food poisoning and may also be involved in other human and veterinary illnesses (McClane, Toxicon. 34:1335-1343 (1996)). CPE carries out its adverse cellular functions by binding to an approximately 50 kD cell surface receptor protein designated the Clostridium perfringens 25 enterotoxin receptor (CPE-R) to form an approximately 90,000 kD complex on the surface of the cell. cDNAs encoding the CPE-R protein have been identified characterized in both human and mouse (Katahira et al., J. Cell Biol. 136:1239-1247 (1997) andKatahira etal., J.Biol. Chem. 272:26652-26658(1997)). Since the CPE toxin has been reported to cause a variety of illnesses in mammalian hosts and those illnesses are initiated by binding of the CPE toxin to the CPE-R, there is significant interest in identifying novel CPE-R homologs. We herein 30 describe the identification and characterization of novel polypeptides having homology to the CPE-R, designated herein as PRO 1679 polypeptides. 93. PRQ1572 Clostridium perfringens enterotoxin utilizes two structurally related membrane proteins as functional 35 receptors in vivo. Human and mouse cDNAs showing homology to the Clostridium enterotoxin receptor (CPE-R) gene have previously been cloned as described in Katahira, et al., J. Biol. Chem.. 272(42):26652-8 (1997). They have been classified into two groups, the Vero cell CPE receptor homologues and rat androgen withdrawal 28 apoptosis protein (RVP1). These receptors are thus of interest as are related molecules. Of particular interest is the use of these receptors and related molecules in the identification of modulators of these receptors.

Also of interest are members of the claudin family and molecules related thereto. Claudins are integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. Furuse, et al., J. Cell Biol.. 141(7): 1539-50 (1998). 94. PRQ1573 Clostridium perfringens enterotoxin utilizes two structurally related membrane proteins as functional receptors in vivo. Human and mouse cDNAs showing homology to the Clostridium enterotoxin receptor (CPE-R) gene have previously been cloned as described in Katahira, et al., J. Biol. Chem.. 272(42):26652-8 (1997). 10 They have been classified into two groups, the Vero cell CPE receptor homologues and rat androgen withdrawal apoptosis protein (RVP1). These receptors are thus of interest as are related molecules. Of particular interest is the use of these receptors and related molecules in the identification of modulators of these receptors.

Also of interest is the ventral prostate. 1 protein (RVP.l) which is transcriptionally induced in the regressing rat prostate after castration. This protein is further described in Peacock, et al., Genomics. 15 46(3):443-9 (1997). 95. PRQ1488 Clostridium perfringens enterotoxin utilizes two structurally related membrane proteins as functional receptors in vivo. Human and mouse cDNAs showing homology to the Clostridium enterotoxin receptor 20 (CPE-R) gene have previously been cloned as described in Katahira, et al., J. Biol. Chem.. 272(42):26652-8 (1997), and Katahira, etal., J. Cell Biol.. 136(6): 1239-1247 (1997). They have been classified into two groups, the Vero cell CPE receptor homologues and rat androgen withdrawal apoptosis protein (RVP1). These receptors are thus of interest as are related molecules. Of particular interest is the use of these receptors and related molecules in the identification of modulators of these receptors.

Efforts are being undertaken by both industry and academia to identify new, native receptor proteins.

Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel receptor proteins. 96. PRQ1489 Clostridium perfringens enterotoxin (CPE) is considered to be the virulence factor responsible for causing the symptoms of C. perfringens type A food poisoning and may also be involved in other human and veterinary illnesses (McClane, Toxicon. 34:1335-1343 (1996)). CPE carries out its adverse cellular functions by binding to an approximately 50 kD cell surface receptor protein designated the Clostridium perfringens enterotoxin receptor (CPE-R) to form an approximately 90,000 kD complex on the surface of the cell. cDNAs 35 encodingtheCPE-Rproteinhavebeenidentifiedcharacterizedinbothhumanandmouse(Katahiraetal., J. Cell Biol. 136:1239-1247 (1997) and Katahira etal., J.Biol. Chem. 272:26652-26658(1997)). Since the CPE toxin has been reported to cause a variety of illnesses in mammalian hosts and those illnesses are initiated by binding 29 of the CPE toxin to the CPE-R, there is significant interest in identifying novel CPE-R homologs. We herein describe the identification and characterization of novel polypeptides having homology to the CPE-R, designated herein as PR01489 polypeptides. 97. PRQ1474 Avian egg whites are a rich source of protein inhibitors of proteinases belonging to all four mechanistic classes. Ovomucoid and ovoinhibitor are muitidomain Kazal-type inhibitors with each domain containing an actual or putative reactive site for a serine proteinase. Cystatin is a cysteine proteinase inhibitor, while ovostatin inhibits proteinases of all four mechanistic classes. For a review of these inhibitors, see Saxena and Tayyab, Cell Mol. Life Sci.. 53(1): 13-23 (1997). New members of protein inhibitors of proteinases are of interest, particularly those having sequence identity with known inhibitors such as ovomucoid.

Serine protease inhibitors in general are of interest. Serine proteases such as neuropsin have been indicated as associated with extracellular matrix modifications and cell migrations. See, generally, Chen, et al., Neurosci.. 7(2):5088-5097 (1995) and Chen, et al., J. Histochem. Cvtochem.. 46:313-320 (1998). Another serine protease, the enamel matrix serine proteinase, is associated with the degradation of organic matrix in teeth.

Simmer, et al., J. Dent. Res.. 77(2):377-386 (1998), Overall and Limeback, Biochem J.. 256(3):965-972 (1988), and Moradian-Oldak, Connect. Tissue Res.. 35(1-41:231-238 (1996'). Thus, inhibitors of these proteases are of interest in the case that these mechanisms require control. 98. PRQ1508 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.

Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PRO1508. 99. PRQ1555 Efforts are being undertaken by both industry and academia to identify new, native transmembrane proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane protein designated herein as PRO1555. 100. PRQ1485 Lysozymes are secreted enzymes that preferentially hydrolyze the [beta] -1,4 glucosidic linkages between N-acetylmuramic acid and N-acetylgucosamine which occur in the mucopeptide cell wall structure of certain microoganisms. Lysozyme is of widespread distribution in animals and plants. It has been found in mammalian secretions and tissues including saliva, tears, milk, cervical mucus, leucocytes, kidneys, etc. The identification of new members of the lysozyme family of proteins is of interest because of the variety of roles lysozymes play in metabolic function and dysfunction. Abnormal levels of lysozymes have been implicated in various disease states. Lysozymes have been reported to have anti-microbial, analgesic, and antinociceptive properties. Additional characteristics and possible uses of lysozymes are described in U.S. Pat. No. 5,618,712.

Of particular interest is lysozyme C which has been recruited as a digestive enzyme in the stomachs of creatures needing to retrieve nutrients from microorganisms in fermented food. The history of lysozyme C and related proteins are further described in Qasba and Kumar, Crit. Rev. Biochem. Mol. Biol.. 32(4):255-306 5 (1997); Irwin, EXS, 75:347-361 (1996) 101. PRQ1564 Glycosylation is a common and complex form of post-translational protein modification. Although a large and increasing number of unique structures is known to exist, most arise from a series of common synthetic 10 intermediates and differ at their periphery glycosyltransferases, which recognize both the oligosaccharide acceptor and features of the underlying protein. UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase is an enzymatic protein that initiates O-glycosylation of specific serine and threonine amino acids in proteins by adding N-acetylgalactosamine to the hydroxy group of these amino acids. Since numerous important biological and physiological events are reguited by protein glycosylation, there is 15 significant interest in identifying and characterizing novel polypeptides having homology to the known glycosylation proteins. We herein describe the identification and characterization of novel polypeptides having homology to an N-acetylgalactosaminyltransferase protein, designated herein as PR01564 polypeptides. 102. PRQ17S5 Efforts are being undertaken by both industry and academia to identify new, native transmembrane proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane protein designated herein as PR01755. 103. PRQ1757 Efforts are being undertaken by both industry and academia to identify new, native transmembrane proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane protein designated herein as PR01757. 104. PRQ17S8 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel 35 secreted protein designated herein as PR01758. 31 105. PRQ1575 Protein Disulfide Isomerase (PDI) enhances formation of disulfide bonds in human serum albumin (HSA). Consequently, PDI assists in the formation of the overall structure of human serum albumin. Co-expression of PDI with human serum albumin increases secretion of HSA by reducing the chance of HSA structural instability and destruction by cellular proteases. Co-expression of PDI and HSA improved localization 5 in the endoplasmic reticulum of eukaryotic cells. (Hayano et al., EP-50941-A (1992)). PDI and the beta-subunit of human prolyl 4-hydroxylase have been shown to be products of the same gene. (Pihlajaniemi et al., EMBO L, 6:643-49 (1987)). In addition, copies of the CGHC-containing active site sequences of PDI have been found in an abundant luminal endoplasmic reticulum protein, Erp72. (Mazzarella et al., J. Biol. Chem.. 2:1094-1101 (1990)).

Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel receptor proteins. 106. PRQ1787 Multiple de novo MPZ (P0) point mutations have been identified in a sporadic Dejerine-Sottas (DDS) case. Warner, et al., Hum. Mutat., 10(l):21-4 (1997). DDS is a severe demyelinating peripheral neuropathy with onset in infancy, and has been associated with mutations in either PMP22 or MPZ. Moreover, mutational analysis of the MPZ, PMP22 and Cx32 genes in patients of Spanish ancestry with Charcot-Marie-Tooth disease and hereditary neuropathy with liability to pressure palsies have been reported on. Bort, et al., Hum. Genet., 99(6):746-54 (1997). Myelin glycoprotein P0 has been reported on in a number of other studies as well (Blanquet-Grossard, et al., Clin. Genet., 48(6):281-3 (1995), Hayasaka, et al., Nat. Genet., 5(l):31-4 (1993) and Saavedra, et al., J. Mol. Evol., 29(2):149-56 (1989). Thus, proteins which may belong to the myelin pO family are of interest. 107. PRQ1781 Efforts are being undertaken by both industry and academia to identify new, native transmembrane proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane protein designated herein as PR01781. 108. PRQ1556 Efforts are being undertaken by both industry and academia to identify new, native transmembrane proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane protein designated herein as PR01556. 32 109. PRQ1759 Efforts are being undertaken by both industry and academia to identify new, native transmembrane proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane protein designated herein as PRO 1759. 110. PRQ1760 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel 10 secreted protein designated herein as PR01760. 111. PRQ1561 Phospholipase A2 (PLA2) is a protein which hydrolyzes a 2-acyl ester bond of phospholipids, and examples thereof include cytosolic PLA2 and secretory PLA2 which can be clearly distinguished from each 15 other. It has been known that the cytosolic PLA2 (cPLA2) selectively hydrolyzes phospholipids containing arachidonic acid of which 2-position is esterified. Given these important biological activities, there is significant interest in identifying and characterizing novel plypeptides having homology to phospholipase A2 proteins. We herein describe the identification and characterization of novel polypeptides having homology to human phospholipase A2 protein, designated herein as PR01561 polypeptides. 112. PRQ1567 Colon specific genes (CSGs)and their expression products are described in published international application W09639419. They are useful diagnostic markers for colon cancer and for colon cancer metastasis and can also be used to screen for potential pharmaceutical and diagnostic agents. The identification of new 25 members of the CSG family is of interest. 113. PRQ1693 Insulin-like growth factors have both growth-promoting and insulin-like activities. There are two well characterized plasma IGF-binding proteins in human. The larger protein is an acid-labile protein of 53K which 30 circulates mostly as a 125 to 150 kD complex thought to be composed of IGF-I or IGF-II, the binding protein itself and an acid-labile non-IGF-binding protein with an approximate molecular mass of 100K kD. The smaller protein has an apparent molecular mass of 28K in the non-reduced form and 34K when reduced. These IGF-binding proteins have been shown to play important roles in the physiological activities played by the insulin-like growth factor proteins. As such, there is substantial interest in identifying and characterizing novel polypeptides 35 having homology to the insulin-like growth factor binding proteins. We herein describe the identification and characterization of novel polypeptides having homology to an insulin-like growth factor binding protein, designated herein as PR01693 polypeptides. 33 114. PRQ1784 Efforts are being undertaken by both industry and academia to identify new, native transmembrane proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane protein designated herein as PR01784. 115. PRQ1605 N-acetylglucosaminyltransferase proteins comprise a family of enzymes that provide for a variety of important biological functions in the mammalian organism. As an example, UDP-N-acetylglucosamine: alpha-3-D-mannoside beat-l,2-N-acetyIglucosaminyltransferase I is an enzymatic protein that catalyzes an essential first 10 step in the conversion of high-mannose N-glycans to hybrid and complex N-glycans (Sarkar et al., Proc. Nad. Acad. Sci. USA. 88:234-238 (1991). Given the obvious importance of the N-acetylglucosaminyltransferase enzymes, there is significant interest in the identification and characterization of novel polypeptides having homology to an N-acetylglucosaminyltransferase protein. We herein describe the identification and characterization of novel polypeptides having homology to an N-acetylglucosaminyltransferase protein, 15 designated herein as PRQ1605 polypeptides. 116. PRQ1788 Protein-protein interactions include receptor and antigen complexes and signaling mechanisms. As more is known about the structural and functional mechanisms underlying protein-protein interactions, protein-protein 20 interactions can be more easily manipulated to regulate the particular result of the protein-protein interaction. Thus, the underlying mechanisms of protein-protein interactions are of interest to the scientific and medical community.

Proteins containing leucine-rich repeats are thought to be involved in protein-protein interactions. Leucine-rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular 25 locations. The crystal structure of ribonuclease inhibitor protein has revealed that leucine-rich repeats correspond to beta-alpha structural units. These units are arranged so that they form a parallel beta-sheet with one surface exposed to solvent, so that the protein acquires an unusual, nonglobular shape. These two features have been indicated as responsible for the protein-binding functions of proteins containing leucine-rich repeats. See, Kobe and Deisenhofer, Trends Biochem. Sci.. 19(10):415-421 (Oct. 1994).

A study has been reported on leucine-rich proteoglycans which serve as tissue organizers, orienting and ordering collagen fibrils during ontogeny and are involved in pathological processes such as wound healing, tissue repair, and tumor stroma formation. Iozzo, R. V., Crit. Rev. Biochem. Mol. Biol.. 32(2):141-174 (1997). Others studies implicating leucine rich proteins in wound healing and tissue repair have been reported including De La Salle, C., et al., Vouv. Rev. Fr. Hematol. (Germany), 37(4):215-222 (1995), reporting 35 mutations in the leucine rich motif in a complex associated with the bleeding disorder Bernard-Soulier syndrome; Chlemetson, K. J., Thromb. Haemost. (Germany), 74(1):111-116 (July 1995), reporting that platelets have leucine rich repeats and Ruoslahti, E. I., et al.; and W09110727-A by La Jolla Cancer Research Foundation, 34 reporting that decorin binding to transforming growth factor-a has involvement in a treatment for cancer, wound healing and scarring. Related by function to this group of proteins is the insulin like growth factor (IGF), in that it is useful in wound-healing and associated therapies concerned with re-growth of tissue, such as connective tissue, skin and bone; in promoting body growth in humans and animals; and in stimulating other growth-related processes. The acid labile subunit of IGF (ALS) is also of interest in that it increases the half-life of IGF and 5 is part of the IGF complex in vivo. Ollendorff, V., et al., Cell Growth Differ. 5(2):213-219 (Feb. 1994) identified the GARP gene which encodes a leucine-rich repeat-containing protein that has structural similarities with human GP lb alpha and GP V platelet proteins, and with the Chaoptin, Toll, and Connectin adhesion molecules of Drosophila.

Another protein which has been reported to have leucine-rich repeats is the SLIT protein which has been 10 reported to be useful in treating neurodegenerative diseases such as Alzheimer's disease, nerve damage such as in Parkinson's disease, and for diagnosis of cancer, see, Artavanistsakonas, S. and Rothberg, J. M., W09210518-A1 by Yale University. Of particular interest is LIG-1, a membrane glycoprotein that is expressed specifically in glial cells in the mouse brain, and has leucine rich repeats and immunoglobulin-like domains. Suzuki, et al., J. Biol. Chem. (U.S.), 27I(37):22522 (1996). Other studies reporting on the biological functions 15 of proteins having leucine rich repeats include: Tayar, N., et al., Mol. Cell Endocrinol.. (Ireland), 125(l-2):65-70 (Dec. 1996) (gonadotropin receptor involvement); Miura, Y., et al., Ninpon Rinsho (Japan), 54(7): 1784-1789 (July 1996) (apoptosis involvement); Harris, P. C., et al., J. Am. Soc. Nephrol.. 6(4): 1125-1133 (Oct. 1995) (kidney disease involvement); and Almeida, A., et al., Oncogene 16(23):2997-3002 (June 1998) (malignant glioma involvement). 117. FRQ1801 lnterleukin-10 (IL-10) is a pleiotropic immunosuppressive cytokine that has been implicated as an important regulator of the functions of myeloid and lymphoid cells. It has been demonstrated that IL-10 functions as a potent inhibitor of the activation of the synthesis of various inflammatory cytokines including, for 25 example, IL-1, IL-6, IFN-y and TNF-cc (Gesser et al., Proc. Natl. Acad. Sci. USA 94:14620-14625 (1997)). Moreover, IL-10 has been demonstrated to strongly inhibit several of the accessory activities of macrophages, thereby functioning as a potent suppressor of the effector functions of macrophages, T-cells and NK cells (Kuhn et al., Cell 75:263-274 (1993)). Furthermore, IL-10 has been strongly implicated in the regulation of B-cell, mast cell and thymocyte differentiation.

IL-10 was independently identified in two separate lines of experiments. First, cDNA clones encoding murine IL-10 were identified based upon the expression of cytokine synthesis inhibitory factor (Moore et al., Science 248:1230-1234 (1990)), wherein the human IL-10 counterpart cDNAs were subsequently identified by cross-hybridization with the murine IL-10 cDNA (Viera et al., Proc. Natl. Acad. Sci. USA 88:1172-1176 (1991)). Additionally, IL-10 was independently identified as a B-cell-derived mediator which functioned to co-35 stimulate active thymocytes (Suda et al., Cell Immunol. 129:228 (1990)).

Recently, a novel cytokine polypeptide which is member of the IL-10-related cytokine family has been identified and characterized. This novel secreted cytokine, designated IL-19, is a 177 amino acid polypeptide having a molecular weight of approximately 20.4 kD (see WO 98/08870, published March 5,1998). It has been reported that IL-19 is specifically expressed by activated monocytes, wherein increased and/or decreased levels of IL-19 may be associated with one or more physiological disorders that are associated with increased or decreased levels of cytokine production (see WO 98/08870). Specifically, IL-19 is suggested as being capable of inhibiting the synthesis of inflammatory cytokines by cells of the immune system.

Given the obvious importance of the various cytokine polypeptides and, more specifically, immunosuppressive cytokines such as IL-10 and potentially IL-19, there is significant interest in the identification and characterization of novel cytokine polypeptides having homology to IL-10 and/or IL-19. We herein describe the identification and characterization of novel polypeptides having homology to IL-19, designated herein as PR01801 polypeptides. 118. UCP4 Uncoupling proteins or "UCPs", believed to play a role in the metabolic process, have been reported in the literature. UCPs were first found and described in the brown fat cells of hibernating animals, such as bears. UCPs were believed to help such hiberaators and other cold-weather adapted animals maintain core body 15 temperatures in cold weather by raising their body's resting metabolic rate. Because humans possess relatively small quantities of brown adipose tissue, UCPs were originally thought to play a minor role in human metabolism.

Several different human uncoupling proteins have now been described. [See, generally, Gura, Science, 280:1369-1370 (1998)]. The human uncoupling protein referred to as UCP1 was identified by Nicholls et al. 20 Nicholls et al. showed that the inner membrane of brown fat cell mitochondria was very permeable to proteins, and the investigators traced the observed permeability to aprotein, called UCP1, in the mitochondrial membrane. Nicholls et al. reported that the UCP1, by creating such permeability, reduced the number of ATPs that can be made from a food source, thus raising body metabolic rate and generating heat. [Nicholls et al., Physiol. Rev., 64, 1-64 (1984)].

It was later found that UCP1 is indeed expressed only in brown adipose tissue [Bouillaud et al., Proc.

Natl. Acad. Sci., 82:445-448 (1985); Jacobsson et al., J. Biol. Chem., 260:16250-16254 (1985)]. Genetic mapping studies have shown that the human UCP1 gene is located on chromosome 4. [Cassard et al., J. Cell. Biochem., 43:255-264 (1990)].

Another human UCP, referred to as UCPH or UCP2, has also been described. [Gimeno et al., Diabetes, 30 46:900-906 (1997); Fleury et al., Nat. Genet., 15:269-272 (1997); Boss et al., FEBS Letters, 408:39-42 (1997); see also, Wolf, Nutr. Rev. , 55:178-179(1997)]. Fleury etal. teach that the UCP2 protein has 59% amino acid identity to UCP1, and that UCP2 maps to regions of human chromosome 11 which have been linked to hyperinsulinaemia and obesity. [Fleury et al., supra]. It has also been reported that UCP2 is expressed in a variety of adult tissues, such as brain and muscle and fat cells. [Gimeno et al., supra, and Fleury et al., supra]. 35 A third human UCP, UCP3, was recently described in Boss etal., supra; Vidal-Puig et al., Biochem.

Biophys. Res. Comm., 235:79-82 (1997); Solanes et al., J. Biol. Chem., 272:25433-25436 (1997); and Gong et al., J. Biol. Chem., 272:24129-24132 (1997). [See also Great Britain Patent No. 9716886]. Solanes et al. 36 report that unlike UCP1 and UCP2, UCP3 is expressed preferentially in human skeletal muscle, and that the UCP3 gene maps to human chromosome 11, adjacent to the UCP2 gene. [Solanes et al., supra]. Gong et al. describe that the UCP3 expression can be regulated by known thermogenic stimuli, such as thyroid hormone, beta3-andrenergic agonists and leptin. [Gong et al., supra]. 119. PRQ193 Efforts are being undertaken by both industry and academia to identify new, native transmembrane proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane protein designated herein as PR0193. 120. PRQ1130 Polypeptides such as the human 2-19 protein may function as cytokines. Cytokines are low molecular weight proteins which function to stimulate or inhibit the differentiation, proliferation or function of immune cells. Cytokine proteins often act as intercellular messengers and have multiple physiological effects. Given 15 the physiological importance of immune mechanisms in vivo, efforts are currently being undertaken to identify new, native proteins which are involved in effecting the immune system. We describe herein the identification of a novel polypeptide which has sequence similarity to the human 2-19 protein. 121. FRQ1335 Carbonic anhydrase is an enzymatic protein that which aids carbon dioxide transport and release in the dioxide and water. Thus, the actions of carbonic anhydrase are essential for a variety of important physiological reactions in the mammal. As such, there is significant interest in the identification and characterization of novel polypeptides having homology to carbonic anhydrase. We herein describe the identification and characterization 25 of novel polypeptides having homology to carbonic anhydrase, designated herein as PR01335 polypeptides. 122. PRQ1329 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding 30 sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PR01329. 123. PRQ1550 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins. 35 Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PR01550. 37 SUMMARY OF THE INVENTION In a first aspect, the present invention provides an isolated nucleic acid having at least 80% sequence identity to a nucleotide sequence that encodes a polypeptide comprising the amino acid sequence shown in Figure 32 (SEQ ID NO: 54).

In a further aspect, the present invention provides an isolated nucleic acid which comprises the full-length coding sequence of the DNA deposited under accession number ATCC 203287.

In a yet further aspect, the present invention provides a vector comprising a nucleic acid of any one of the previous aspects.

In a still further aspect, the present invention provides a non-human host cell comprising a vector of the previous aspect.

In another aspect, the present invention provides a process for producing a polypeptide comprising culturing a host cell of the above aspect under conditions suitable for expression of said polypeptide and recovering said polypeptide from the cell culture.

In another aspect, the present invention provides an isolated PRO1295 polypeptide having at least 80% sequence identity to the amino acid sequence shown in Figure 32 (SEQ ID NO: 54).

In another aspect the present invention provides an isolated PRO 1295 polypeptide having at least 80% sequence identity to the amino acid sequence encoded by the nucleotide deposited under ATCC 203287.

In another aspect the present invention provides an isolated polypeptide comprising a polypeptide sequence having at least about 80% amino acid sequence identity to the extracellular domain of a PRO1295 polypeptide of SEQ In another aspect the present invention provides an isolated polypeptide having at least about 80% amino acid sequence identity to a PRO1295 polypeptide of SEQ ID NO: 54 lacking its associated signal peptide.

In another aspect, the present invention provides an isolated nucleic acid encoding a polypeptide of the above aspects.

In another aspect, the present invention provides a chimeric molecule comprising a polypeptide according to any one of the above aspects fused to a heterologous amino acid sequence.

In another aspect, the present invention provides an antibody which specifically binds to a polypeptide ID NO: 54. according to any one of the above aspects.

O-ICE OF M.Z 38 17 KAH 2C34 RECEIVED In another aspect, the present invention provides a pharmaceutical composition comprising a polypeptide of any one of the above aspects and a pharmaceutically acceptable carrier, diluent or excipient.

In another aspect, the present invention provides a use of a polypeptide of any one of the above aspects in the manufacture of a medicament for treating tumor.

The invention relates to the aspects as set out above. Some materials have been divided out of the present application that were previously present and claimed herein and are to be found in New Zealand Patent Specification Nos 531662 to 531668. Not all of the stated aspects and embodiments set out below fall within the scope of the invention as claimed. These divided out materials and other non-claimed materials, are still presented in .the present specification to assist the reader to practice the claimed invention. 2. PRQ444 A cDNA clone (DNA26846-1393) has been identified that encodes a novel secreted polypeptide, designated in the present application as "PR0444," In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0444 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR0444 polypeptide having 15 the sequence of amino acid residues from about 1 or about 17 to about 117, inclusive of Figure 4 (SEQ ID NO:6), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0444 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 656 and about 958, inclusive, of Figure 3 (SEQ ID NO:5). Preferably, hybridization occurs under stringent hybridization 20 and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203406 25 (DNA26846-1397), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203406 (DNA26846-1397).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence 30 identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or about 17 to about 117, inclusive of Figure 4 (SEQ ID NO:6), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 10 nucleotides, more preferably at least about 20 nucleotides, and most preferably at least about 40 nucleotides and 35 produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0444 polypeptide having the sequence of amino acid residues from about 1 or about 17 to about 117, inclusive of Figure 4 (SEQ ID NO:6), or (b) the complement of the DNA molecule of (a), and, if the DNA 40 INT^LLL'uAi PROPERTY office OF N Z 2 4 OCT 2003 RECEIVED molecule has at least about an 80% sequence identity, preferably at least about an 83% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0444 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is 5 complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 16 in the sequence of Figure 4 (SEQ ID NO:6).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 10 preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 17 to about 117, inclusive of Figure 4 (SEQ ID NO:6), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR0444 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 15 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR0444 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR0444 polypeptide, which in one 20 embodiment, includes an amino acid sequence comprising residues 1 or about 17 to 117 of Figure 4 (SEQ ID NO:6).

In another aspect, the invention concerns an isolated PR0444 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 25 sequence of amino acid residues 1 or about 17 to about 117, inclusive of Figure 4 (SEQ ID NO:6).

In a further aspect, the invention concerns an isolated PR0444 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 17 to 117 of Figure 4 (SEQ ID NO:6).

In yet another aspect, the invention concerns an isolated PR0444 polypeptide, comprising the sequence of amino acid residues 1 or about 17 to about 117, inclusive of Figure 4 (SEQ ID NO:6), or a fragment thereof sufficient to provide a binding site for an anti-PR0444 antibody. Preferably, the PR0444 fragment retains a qualitative biological activity of a native PR0444 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 35 molecule under stringent conditions with (a) a DNA molecule encoding a PR0444 polypeptide having the sequence of amino acid residues from about 1 or about 17 to about 117, inclusive of Figure 4 (SEQ ID NO:6), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an J 41 PCT/US99/20U1 sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. 3. FRQ1018 A cDNA clone (DNA56107-1415) has been identified that encodes a novel transmembrane polypeptide, designated in the present application as "PR01018".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01018 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01018 polypeptide having the sequence of amino acid residues from about 1 or about 25 to about 189, inclusive of Figure 6 (SEQ ID NO:8), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR010I8 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 129 or about 201 and about 695, inclusive, of Figure 5 (SEQ ID NO:7). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 20 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203405 (DNA56107-1415) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in 25 ATCC Deposit No. 203405 (DNA56107-1415).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 25 to about 189, inclusive of Figure62 (SEQ ID 30 NO:8), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01018 polypeptide having the sequence of amino acid residues from 1 or about 25 to about 189, inclusive of Figure 6 (SEQ ID NO:8), or (b) the complement of the DNA molecule of (a), and, if 35 the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule. 42 In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01018 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 24 in the sequence of Figure 6 (SEQ ID NO:8). The transmembrane 5 domains have been tentatively identified as extending from about amino acid position 86 to about amino acid position 103 and from about amino acid position 60 to about amino acid position 75 in the PR01018 amino acid sequence (Figure 6, SEQ ID NO:8).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 10 preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 25 to about 189, inclusive of Figure 6 (SEQ ID NO:8), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01018 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 15 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 5 (SEQ ID NO:7).

In another embodiment, the invention provides isolated PR01018 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01018 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 25 to about 189 of Figure 6 (SEQ ID NO:8).

In another aspect, the invention concerns an isolated PRO 1018 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more 25 preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 25 to about 189, inclusive of Figure 6 (SEQ ID NO:8).

In a further aspect, the invention concerns an isolated PR01018 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence 30 of residues 1 or about 25 to about 189, inclusive of Figure 6 (SEQ ID NO:8).

In yet another aspect, the invention concerns an isolated PR01018 polypeptide, comprising the sequence of amino acid residues 1 or about 25 to about 189, inclusive of Figure 6 (SEQ ID NO:8), or a fragment thereof sufficient to provide a binding site for an anti-PR01018 antibody. Preferably, the PR01018 fragment retains a qualitative biological activity of a native PRO 1018 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01018 polypeptide having the sequence of amino acid residues from about 1 or about 25 to about 189, inclusive of Figure 6 (SEQ ID NO:8), 43 or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. 4. PRQ1773 A cDNA clone (DNA56406-1704) has been identified, having homology to nucleic acid encoding a retinol dehydrogenase protein that encodes a novel polypeptide, designated in the present application as "PR01773".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1773 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1773 polypeptide having 15 the sequence of amino acid residues from about 1 or about 18 to about 319, inclusive of Figure 8 (SEQ ID NO: 10), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1773 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 111 or about 162 and about 1067, inclusive, of Figure 7 (SEQ ID NO:9). Preferably, hybridization occurs under 20 stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203478 25 (DNA56406-1704) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203478 (DNA56406-1704).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence 30 identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 18 to about 319, inclusive of Figure 8 (SEQ ID NO: 10), or (b) the complement of the DNA of (a).

In a farther aspect, the invention concerns an isolated nucleic acid molecule having at least 525 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA 35 molecule encoding a PR01773 polypeptide having the sequence of amino acid residues from 1 or about 18 to about 319, inclusive of Figure 8 (SEQ ID NO: 10), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, prefereably at least about an 85% sequence 44 identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01773 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding 5 nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 17 in the sequence of Figure 8 (SEQ ID NO: 10). The transmembrane domain has been tentatively identified as extending from about amino acid position 136 to about amino acid position 152 in the PR01773 amino acid sequence (Figure 8, SEQ ID N0:10).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 10 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 18 to about 319, inclusive of Figure 8 (SEQ ID NO: 10), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO 1773 polypeptide coding sequence that may find IS use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 7 (SEQ ID NO:9).

In another embodiment, the invention provides isolated PRO1773 polypeptide encoded by any of the 20 isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01773 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 18 to about 319 of Figure 8 (SEQ ID NO: 10).

In another aspect, the invention concerns an isolated PR01773 polypeptide, comprising an amino acid 25 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identify to the sequence of amino acid residues 1 or about 18 to about 319, inclusive of Figure 8 (SEQ ID N0:10).

In a further aspect, the invention concerns an isolated PR01773 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 % positives, more preferably at least 30 about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 18 to about 319, inclusive of Figure 8 (SEQ ID NO: 10).

In yet another aspect, the invention concerns an isolated PR01773 polypeptide, comprising the sequence of amino acid residues 1 or about 18 to about 319, inclusive of Figure 8 (SEQ ID NO: 10), or a fragment thereof sufficient to provide a binding site for an anti-PR01773 antibody. Preferably, the PROI773 fragment retains 35 a qualitative biological activity of a native PR01773 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01773 polypeptide having the 45 sequence of amino acid residues from about 1 or about 18 toabout319, inclusive ofFigure 8 (SEQ ID NO: 10), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) 5 recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1773 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01773 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PRO1773 polypeptide by contacting the native PRO1773 polypeptide with a candidate molecule and 10 monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01773 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.

. PRQ1477 A cDNA clone (DNA56529-1647) has been identified, having homology to nucleic acid encoding a mannosidase protein that encodes a novel polypeptide, designated in the present application as "PROMT?".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01477 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 20 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1477 polypeptide having the sequence of amino acid residues from about 1 to about 699, inclusive of Figure 10 (SEQ ID NO: 12), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01477 25 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 23 and about 2119, inclusive, of Figure 9 (SEQ ID NO: 11). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 30 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203293 (DNA56529-1647) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203293 (DNA56529-1647).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence 46 identity to the sequence of amino acid residues 1 to about 699, inclusive of Figure 10 (SEQ ID NO: 12), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 540 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1477 polypeptide having the sequence of amino acid residues from 1 to about 699, 5 inclusive of Figure 10 (SEQ ID NO: 12), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01477 polypeptide, with or without and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domains have been tentatively identified as extending from about amino acid position 21 to about amino acid position 40 and from about amino acid position 84 to about amino acid position 105 in the PRO 1477 amino acid sequence (Figure 10, SEQ ID NO: 12).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to about 699, inclusive of Figure 10 (SEQ ID NO: 12), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO 1477 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 9 (SEQ ID NO: 11).

In another embodiment, the invention provides isolated PRO1477 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01477 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 to about 699 of Figure 10 (SEQ ID NO: 12).

In another aspect, the invention concerns an isolated PR01477 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 699, inclusive of Figure 10 (SEQ ID NO: 12).

In a further aspect, the invention concerns an isolated PR01477 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to about 699, inclusive of Figure 10 (SEQ ID NO: 12). 47 In yet another aspect, the invention concerns an isolated PRO1477 polypeptide, comprising the sequence of amino acid residues 1 to about 699, inclusive of Figure 10 (SEQ ID NO: 12), or a fragment thereof sufficient to provide a binding site for an anti-PR01477 antibody. Preferably, the PR01477 fragment retains a qualitative biological activity of a native PR01477 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 5 molecule under stringent conditions with (a) a DNA molecule encoding a PR01477 polypeptide having the sequence of amino acid residues from about 1 to about 699, inclusive of Figure 10 (SEQ ID NO: 12), or (b) the complement of the DNA molecuie of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising 10 the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01477 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01477 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a 15 native PR01477 polypeptide by contacting the native PR01477 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01477 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier. 6. FRQ1478 A cDNA clone (DN A56531-1648) has been identified that encodes a novel polypeptide having sequence identity with galactosyltransferase and designated in the present application as "PR01478." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01478 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1478 polypeptide having the sequence of amino acid residues from about 1 to about 327, inclusive of Figure 12 (SEQ ID NO: 17), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01478 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 77 and about 1057, inclusive, of Figure 11 (SEQ ID NO: 16). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 35 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203286 48 PCTAJS99/20111 (DNA56531-1648), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203286 (DNA56531-1648).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence 5 identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 327, inclusive of Figure 12 (SEQ ID NO:17), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule 10 under stringent conditions with (a) a DNA molecule encoding a PR01478 polypeptide having the sequence of amino acid residues from about 1 to about 327, inclusive of Figure 12 (SEQ ID NO: 17), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule. 15 In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01478 polypeptide in its soluble form, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domain (type II) has been tentatively identified as extending from about amino acid position 29 through about amino acid position 49 in the PR01478 amino acid sequence (Figure 12, SEQ ID NO: 17). Therefore, a peptide including amino acids 20 50-327, with or without amino acids 1-28, is specifically embodied herein, as well as the nucleic acid encoding such a peptide.

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 25 amino acid sequence of residues 1 to about 327, inclusive of Figure 12 (SEQ ID NO: 17), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01478 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 30 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01478 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO1478 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 327 of Figure 12 (SEQ ID NO: 17). 35 In another aspect, the invention concerns an isolated PR01478 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 49 sequence of amino acid residues 1 to about 327, inclusive of Figure 12 (SEQ ID NO: 17).

In a further aspect, the invention concerns an isolated PRO 1478 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 through 327 of Figure 12 (SEQ ID NO: 17).

In yet another aspect, the invention concerns an isolated PRO1478 polypeptide, comprising the sequence of amino acid residues 1 to about 327, inclusive of Figure 12 (SEQ ID NO: 17), or a fragment thereof sufficient to provide a binding site for an anti-PR01478 antibody. Preferably, the PR01478 fragment retains a qualitative biological activity of a native PR01478 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 10 molecule under stringent conditions with (a) a DNA molecule encoding a PR01478 polypeptide having the sequence of amino acid residues from about 1 to about 327, inclusive of Figure 12 (SEQ ID NO: 17), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising 15 the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1478 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01478 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a 20 native PRO1478 polypeptide, by contacting the native PRO1478 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1478 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier. 7. PRQ831 A cDNA clone (DNA56862-1343) has been identified that encodes a novel secreted polypeptide, designated in the present application as "PR0831".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0831 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR0831 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 73, inclusive of Figure 14 (SEQ ID NO:22), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0831 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 40 or about 85 and about 258, inclusive, of Figure 13 (SEQ ID NO:21). Preferably, hybridization occurs under 50 stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203174 5 (DNA56862-1343) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203174 (DNA56862-1343).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence 10 identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 16 to about 73, inclusive of Figure 14 (SEQ ID NO:22), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucieic acid molecule having at least 470 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA 15 molecule encoding a PR0831 polypeptide having the sequence of amino acid residues from 1 or about 16 to about 73, inclusive of Figure 14 (SEQ ID NO:22), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0831 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 15 in the sequence of Figure 14 (SEQ ID NO:22).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 16 to about 73, inclusive of Figure 14 (SEQ ID NO:22), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR0831 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 13 (SEQ ID NO:21).

In another embodiment, the invention provides isolated PR0831 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR0831 polypeptide, which in 51 certain embodiments, includes an amino acid sequence comprising residues 1 or about 16 to about 73 of Figure 14 (SEQ ID NO:22).

In another aspect, the invention concerns an isolated PR0831 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 5 sequence of amino acid residues 1 or about 16 to about 73, inclusive of Figure 14 (SEQ ID NO:22).

In a further aspect, the invention concerns an isolated PR0831 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 16 to about 73, inclusive of Figure 14 (SEQ ID NO:22).

In yet another aspect, the invention concerns an isolated PR0831 polypeptide, comprising the sequence of amino acid residues 1 or about 16 to about 73, inclusive of Figure 14 (SEQ ID NO:22), or a fragment thereof sufficient to provide a binding site for an anti-PR0831 antibody. Preferably, the PR0831 fragment retains a qualitative biological activity of a native PR0831 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 15 molecule under stringent conditions with (a) a DNA molecule encoding a PR0831 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 73, inclusive of Figure 14 (SEQ ID NO:22), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell 20 comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. 8. PRQ1113 A cDNA clone (DNA57254-1477) has been identified that encodes a novel polypeptide having sequence 25 identity with leucine rich repeat proteins and designated in the present application as "PR01113." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01113 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 30 preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PROl 113 polypeptide having the sequence of amino acid residues from about 1 to about 616, inclusive of Figure 16 (SEQ ID NO:24), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PROl 113 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 214 and 35 about 2061, inclusive, of Figure 15 (SEQ ID NO:23). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 52 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203289 (DNA57254-1477), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC 5 Deposit No. 203289 (DNA57254-1477).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 616, inclusive of Figure 16 (SEQ ID 10 NO:24), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROl 113 polypeptide having the sequence of amino acid residues from about 1 to about 616, inclusive of Figure 16 (SEQ ID NO:24), or (b) the complement 15 of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROl 113 polypeptide in its soluble, i.e. transmembrane domain deleted or inactivated variants, or is 20 complementary to such encoding nucleic acid molecule. The transmembrane domain has been tentatively identified as extending from about amino acid position 13 through about amino acid position 40 in the PROl 113 amino acid sequence (Figure 16, SEQ ID NO:24). Thus, also presented herein is a peptide comprising amino acids 41-616, and optionally 1-12 of SEQ ID NO:24, and the nucleic acids encoding the same.

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 25 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues I to about 616, inclusive of Figure 16 (SEQ ID NO:24), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PROl 113 polypeptide coding sequence that may find 30 use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PROl 113 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PROl 113 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 616 of Figure 16 (SEQ ID NO:24).

In another aspect, the invention concerns an isolated PROl 113 polypeptide, comprising an amino acid 53 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 616, inclusive of Figure 16 (SEQ ID NO:24).

In a further aspect, the invention concerns an isolated PROl 113 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least 5 about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 through 616 of Figure 16 (SEQ ID NO:24).

In yet another aspect, the invention concerns an isolated PROl 113 polypeptide, comprising the sequence of amino acid residues 1 to about 616, inclusive of Figure 16 (SEQ ID NO:24), or a fragment thereof sufficient to provide a binding site for an anti-PROl 113 antibody. Preferably, the PROl 113 fragment retains a qualitative 10 biological activity of a native PROl 113 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROl 113 polypeptide having the sequence of amino acid residues from about 1 to about 616, inclusive of Figure 16 (SEQ ID NO:24), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence 15 identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PROl 113 20 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PROl 113 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PROl 113 polypeptide, by contacting the native PR01113 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PROl 113 polypeptide, 25 or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 9. PROl 194 A cDNA clone (DNA57841-1522) has been identified that encodes a novel secreted polypeptide designated in the present application as "PROl 194." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROl 194 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PROl 194 polypeptide having 35 the sequence of amino acid residues from 1 or about 22 to about 81, inclusive of Figure 18 (SEQ ID NO:29), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PROl 194 54 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 72 and about 251, inclusive, of Figure 17 (SEQ ID NO:28). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 5 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203458 (DNA57841-1522), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203458 (DNA57841-1522).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 22 to about 81, inclusive of Figure 18 (SEQ ID NO:29), or the complement of the DNA of (a).

IS In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROl 194 polypeptide having the sequence of amino acid residues from about 22 to about 81, inclusive of Figure 18 (SEQ ID NO:29), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably 20 at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 25 amino acid sequence of residues 22 to about 81, inclusive of Figure 18 (SEQ ID NO:29), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PROl 194 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 30 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO 1194 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PROl 194 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 22 through 81 of Figure 18 (SEQ ID NO:29). 35 In another aspect, the invention concerns an isolated PROl 194 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 55 sequence of amino acid residues 22 to about 81, inclusive of Figure 18 (SEQ ID NO:29).

In a further aspect, the invention concerns an isolated PROl 194 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 22 through 81 of Figure 18 (SEQ ID NO:29).

In yet another aspect, the invention concerns an isolated PRO 1194 polypeptide, comprising the sequence of amino acid residues 22 to about 81, inclusive of Figure 18 (SEQ ID NO:29), or a fragment thereof sufficient to provide a binding site for an anti-PROl 194 antibody. Preferably, the PROl 194 fragment retains a qualitative biological activity of a native PROl 194 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 10 molecule under stringent conditions with (a) a DNA molecule encoding a PROl 194 polypeptide having the sequence of amino acid residues from about 22 to about 81, inclusive of Figure 18 (SEQ ID NO:29), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising 15 the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PROl 194 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PROl 194 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a 20 native PRO 1194 polypeptide, by contacting the native PRO 1194 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PROl 194 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 10. PROmO A cDNA clone (DNA58727-1474) has been identified, having homology to nucleic acid encoding myeloid upregulated protein that encodes a novel polypeptide, designated in the present application as "PROlllO".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding 30 a PROl 110 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PROl 110 polypeptide having the sequence of amino acid residues from about 1 to about 322, inclusive of Figure 20 (SEQ ID NO:31), or (b) 35 the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PROlllO polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 131 56 and about 1096, inclusive, of Figure 19 (SEQ ID N0:30). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule 5 encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203171 (DNA58727-1474) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203171 (DNA58727-1474).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 10 encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 322, inclusive of Figure 20 (SEQ ID NO:31), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 15 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROl 110 polypeptide having the sequence of amino acid residues from 1 to about 322, inclusive of Figure 20 (SEQ ID NO:31), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) 20 or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROlllO polypeptide,with or without the initiating methionine and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domains have been tentatively identified as extending from about amino acid position 41 to about amino acid 25 position 60, from about amino acid position 66 to about amino acid position 85, from about amino acid position 101 to about amino acid position 120, from about amino acid position 137 to about amino acid position 153, from about amino acid position 171 to about amino acid position 192, from about amino acid position 205 to about amino acid position 226, from about amino acid position 235 to about amino acid position 255, and from about amino acid position 294 to about amino acid position 312 in the PROl 110 amino acid sequence (Figure 30 20, SEQ ID NO-.31).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 322, inclusive of Figure 20 (SEQ ID NO:31), or (b) the complement 35 of the DNA of (a).

Another embodiment is directed to fragments of a PROl 110 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 57 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 19 (SEQ ID N0:30).

In another embodiment, the invention provides isolated PROlllO polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PROlllO polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 to about 322 of Figure 20 (SEQ ID NO:31).

In another aspect, the invention concerns an isolated PROlllO polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more 10 preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 322, inclusive of Figure 20 (SEQ ID NO:31).

In a further aspect, the invention concerns an isolated PRO 1110 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence 15 of residues 1 to about 322, inclusive of Figure 20 (SEQ ID NO:31).

In yet another aspect, the invention concerns an isolated PROl 110 polypeptide, comprising the sequence of amino acid residues 1 to about 322, inclusive of Figure 20 (SEQ ID NO:31), or a fragment thereof sufficient to provide a binding site for an anti-PROl 110 antibody. Preferably, the PROl 110 fragment retains a qualitative biological activity of a native PROlllO polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROlllO polypeptide having the sequence of amino acid residues from about 1 to about 322, inclusive of Figure 20 (SEQ ID NO:31), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence 25 identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PROlllO polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PROl 110 antibody. 30 In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PROlllO polypeptide by contacting the native PROlllO polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PROl 110 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 11. PRQ1378 A cDNA clone (DNA58730-1607) has been identified that encodes a novel secreted polypeptide 58 designated in the present application as "PRO1378".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01378 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 5 preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01378 polypeptide having the sequence of amino acid residues from 1 or about 16 to about 335, inclusive of Figure 22 (SEQ ID NO:33), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1378 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 1365 10 and about 2369, inclusive, of Figure 21 (SEQ ID NO:32). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule 15 encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203221 (DNA58730-1607), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203221 (DNA58730-1607).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 20 encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from 1 or about 16 to about 335, inclusive of Figure 22 (SEQ ID NO:33), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 20 25 nucleotides, preferably at least about 50 nucleotides, and more preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1378 polypeptide having the sequence of amino acid residues from about 16 to about 335, inclusive of Figure 22 (SEQ ID NO:33), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at 30 least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01378 polypeptide, with or without the N-terminal signal sequence, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 35 1 through about amino acid position 15 in the sequence of Figure 22 (SEQ ID NO:33).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 59 preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 16 to about 335, inclusive of Figure 22 (SEQ ID NO:33), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1378 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 5 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01378 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01378 polypeptide, which in one 10 embodiment, includes an amino acid sequence comprising residues 16 to 335 of Figure 22 (SEQ ID NO:33).

In another aspect, the invention concerns an isolated PR01378 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 16 to about 335, inclusive of Figure 22 (SEQ ID NO:33). 15 In a further aspect, the invention concerns an isolated PR01378 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 16 to 335 of Figure 22 (SEQ ID NO:33).

In yet another aspect, the invention concerns an isolated PR01378 polypeptide, comprising the sequence 20 of amino acid residues 16 to about 335, inclusive of Figure 22 (SEQ ID NO:33), or a fragment thereof sufficient to provide a binding site for an anti-PR01378 antibody. Preferably, the PR01378 fragment retains a qualitative biological activity of a native PR01378 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1378 polypeptide having the 25 sequence of amino acid residues from about 16 to about 335, inclusive of Figure 22 (SEQ ID NO:33), or (b) the complement of the DNA molecuie of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the 30 polypeptide from the cell culture. 12. PRQ1481 A cDNA clone (DNA58732-1650) has been identified that encodes a novel polypeptide designated in the present application as "PRO 1481." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1481 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 60 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1481 polypeptide having the sequence of amino acid residues from 1 or about 24 to about 334, inclusive of Figure 24 (SEQ ID NO:41), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1481 5 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 88 and about 1321, inclusive, of Figure 23 (SEQ ID N0:40). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 10 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203290 (DNA58732-1650), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203290 (DNA58732-1650).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 24 to about 334, inclusive of Figure 24 (SEQ ID NO:41), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01481 polypeptide having the sequence of amino acid residues from about 24 to about 334, inclusive of Figure 24 (SEQ ID NO:41), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably 25 at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01481 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted, truncated or inactivated variants, or is complementary to such 30 encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 23 in the sequence of Figure 24 (SEQ ID NO:41). The transmembrane domain has been tentatively identified as extending from about amino acid position 235 through about amino acid position 262 in the PR01481 amino acid sequence (Figure 24, SEQ ID NO:41).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 35 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 24 to about 334, inclusive of Figure 24 (SEQ ID NO:41), or (b) the complement 61 of the DNA of (a).

Another embodiment is directed to fragments of a PR01481 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01481 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO 1481 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 24 through 334 of Figure 24 (SEQ ID NO:41).

In another aspect, the invention concerns an isolated PR01481 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 24 to about 334, inclusive of Figure 24 (SEQ ID NO:41).

In a further aspect, the invention concerns an isolated PRO 1481 polypeptide, comprising an amino acid 15 sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 24 through 334 of Figure 24 (SEQ ID NO:41).

In yet another aspect, the invention concerns an isolated PRO 1481 polypeptide, comprising the sequence of amino acid residues 24 to about 334, inclusive of Figure 24 (SEQ ID NO:41), or a fragment thereof sufficient 20 to provide a binding site for an anti-PR01481 antibody. Preferably, the PR01481 fragment retains a qualitative biological activity of a native PR01481 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01481 polypeptide having the sequence of amino acid residues from about 24 to about 334, inclusive of Figure 24 (SEQ ID NO:41), or (b) 25 the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01481 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01481 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PRO 1481 polypeptide, by contacting the native PRO 1481 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01481 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 62 13. PROl 189 A cDN A clone (DN A58828-1519) has been identified that encodes a novel polypeptidehaving homology to E25 which is designated in the present application as "PROl 189." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1189 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PROl 189 polypeptide having the sequence of amino acid residues from about 1 to about 263, inclusive of Figure 26 (SEQ ID NO:43), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PROl 189 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 79 and about 867, inclusive, of Figure 25 (SEQ ID NO:42). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 15 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203172 (DNA58828-1519), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC 20 Deposit No. 203172 (DNA58828-1519).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 263, inclusive of Figure 26 (SEQ ID 25 NO:43), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROl 189 polypeptide having the sequence of amino acid residues from about 1 to about 263, inclusive of Figure 26 (SEQ ID NO:43), or (b) the complement 30 of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1189 polypeptide with its transmembrane domain deleted or inactivated, or is complementary to such 35 encoding nucleic acid molecule. The transmembrane domain has been tentatively identified as extending from about amino acid position 53 through about amino acid position 75 in the PROl 189 amino acid sequence (Figure 26, SEQ ID NO:43). 63 In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 263, inclusive of Figure 26 (SEQ ID NO:43), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PROl 189 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO 1189 polypeptide encoded by any of the 10 isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PROl 189 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 263 of Figure 26 (SEQ ID NO:43).

In another aspect, the invention concerns an isolated PROl 189 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more 15 preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 263, inclusive of Figure 26 (SEQ ID NO:43).

In a further aspect, the invention concerns an isolated PROl 189 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence 20 of residues 1 to 263 of Figure 26 (SEQ ID NO:43).

In yet another aspect, the invention concerns an isolated PROl 189 polypeptide, comprising the sequence of amino acid residues 1 to about 263, inclusive of Figure 26 (SEQ ID NO:43), or a fragment thereof sufficient to provide a binding site for an anti-PRO 1189 antibody. Preferably, the PRO 1189 fragment retains a qualitative biological activity of a native PRO 1189 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1189 polypeptide having the sequence of amino acid residues from about 1 to about 263, inclusive of Figure 26 (SEQ ID NO:43), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence 30 identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PROl 189 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PROl 189 antibody. 35 In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PRO 1189 polypeptide, by contacting the native PROl 189 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide. 64 In a still further embodiment, the invention concerns a composition comprising a PRO 1189 polypeptide, or an agonist or antagonist as hereinabove defmed, in combination with a pharmaceuticaliy acceptable carrier. 14. PRQ1415 A cDNA clone (DNA58852-1637) has been identified that encodes a novel polypeptide, designated in 5 the present application as "PR01415".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01415 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 10 preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1415 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 283, inclusive of Figure 28 (SEQ ID N0:50), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01415 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 148 15 or about 223 and about 996, inclusive, of Figure 27 (SEQ ID NO:49). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule 20 encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203271 (DNA58852-1637) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203271 (DNA58852-1637).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 25 encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 283, inclusive of Figure 28 (SEQ ID N0:50), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 100 30 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1415 polypeptide having the sequence of amino acid residues from 1 or about 26 to about 283, inclusive of Figure 28 (SEQ ID N0:50), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence 35 identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01415 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and 65 its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 25 in the sequence of Figure 28 (SEQ ID N0:50). The transmembrane domain has been tentatively identified as extending from about amino acid position 94 to about amino acid position 118 in the PR01415 amino acid sequence (Figure 28, SEQ ID N0:50).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 26 to about 283, inclusive of Figure 28 (SEQ ID N0:50), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO 1415 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 27 (SEQ ID NO:49).

In another embodiment, the invention provides isolated PR01415 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01415 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 26 to about 283 of Figure 28 (SEQ ID N0:50).

In another aspect, the invention concerns an isolated PR01415 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 283, inclusive of Figure 28 (SEQ ID N0:50).

In a further aspect, the invention concerns an isolated PR01415 polypeptide, comprising an amino acid 25 sequence scoring at least about 80% positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 26 to about 283, inclusive of Figure 28 (SEQ ID N0:50).

In yet another aspect, the invention concerns an isolated PR01415 polypeptide, comprising the sequence of amino acid residues 1 or about 26 to about 283, inclusive of Figure 28 (SEQ ID N0:50), or a fragment 30 thereof sufficient to provide a binding site for an anti-PR01415 antibody. Preferably, the PR01415 fragment retains a qualitative biological activity of a native PR01415 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1415 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 283, inclusive of Figure 28 (SEQ ID 35 N0:50), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell 66 comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01415 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01415 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a 5 native PR01415 polypeptide by contacting the native PR01415 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO 1415 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier.

IS. PRQ1411 A cDNA clone (DNA59212-1627) has been identified that encodes a novel secreted polypeptide designated in the present application as "PR01411." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01411 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1411 polypeptide having the sequence of amino acid residues from 1 or about 22 to about 440, inclusive of Figure 30 (SEQ ID NO:52), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01411 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 247 and about 1503, inclusive, of Figure 29 (SEQ ID NO:51). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 25 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203245 (DNA59212-1627), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC 30 Deposit No. 203245 (DNA592I2-1627).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 22 to about 440, inclusive of Figure 30 (SEQ ID 35 NO:52), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule 67 PCT/US99/201I1 under stringent conditions with (a) a DNA molecule encoding a PR01411 polypeptide having the sequence of amino acid residues from about 22 to about 440, inclusive of Figure 30 (SEQ ID NO:52), or (b) the complement of the DNA molecule of (a), and, if die DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 22 to about 440, inclusive of Figure 30 (SEQ ID NO:52), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01411 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01411 polypeptide encoded by any of the 15 isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01411 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 22 through 440 of Figure 30 (SEQ ID NO:52).

In another aspect, the invention concerns an isolated PR01411 polypeptide, comprising an amino acid 20 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 22 to about 440, inclusive of Figure 30 (SEQ ID NO:52).

In a further aspect, the invention concerns an isolated PROI411 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least 25 about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 22 through 440 of Figure 30 (SEQ ID NO:52).

In yet another aspect, the invention concerns an isolated PRO 1411 polypeptide, comprising the sequence of amino acid residues 22 to about 440, inclusive of Figure 30 (SEQ ID NO:52), or a fragment thereof sufficient to provide a binding site for an anti-PR01411 antibody. Preferably, the PR01411 fragment retains a qualitative 30 biological activity of a native PR01411 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01411 polypeptide having the sequence of amino acid residues from about 22 to about 440, inclusive of Figure 30 (SEQ ID NO:52), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence 35 identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host ceil comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the 68 polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01411 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01411 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01411 polypeptide, by contacting the native PR01411 polypeptide with a candidate molecule and 5 monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO 1411 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 16. PROI295 A cDNA clone (DNA59218-1559) has been identified that encodes a novel secreted polypeptide designated in the present application as "PRO1295." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1295 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 15 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1295 polypeptide having the sequence of amino acid residues from 1 or about 19 to about 280, inclusive of Figure 32 (SEQ ID NO:54), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01295 20 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 261 and about 1046, inclusive, of Figure 31 (SEQ ID NO:53). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 25 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203287 (DNA59218-1559), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203287 (DNA59218-1559).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 19 to about 280, inclusive of Figure 32 (SEQ ID NO:54), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1295 polypeptide having the sequence of 69 amino acid residues from about 19 to about 280, inclusive of Figure 32 (SEQ ID NO:54), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 5 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with die amino acid sequence of residues 19 to about 280, inclusive of Figure 32 (SEQ ID NO:54), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO 1295 polypeptide coding sequence that may find 10 use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1295 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO1295 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 19 through 280 of Figure 32 (SEQ ID NO:54).

In another aspect, the invention concerns an isolated PRO 1295 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more 20 preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 19 to about 280, inclusive of Figure 32 (SEQ ID NO:54).

In a further aspect, the invention concerns an isolated PR01295 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence 25 of residues 19 through 280 of Figure 32 (SEQ ID NO:54).

In yet another aspect, the invention concerns an isolated PRO1295 polypeptide, comprising the sequence of amino acid residues 19 to about 280, inclusive of Figure 32 (SEQ ID NO:54), or a fragment thereof sufficient to provide a binding site for an anti-PR01295 antibody. Preferably, the PRO1295 fragment retains a qualitative biological activity of a native PRO1295 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1295 polypeptide having the sequence of amino acid residues from about 19 to about 280, inclusive of Figure 32 (SEQ ID NO:54), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence 35 identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. 70 In yet another embodiment, the invention concerns agonists and antagonists of a native PR01295 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01295 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01295 polypeptide, by contacting the native PR01295 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the inventionconeernsacompositioncomprisingaPR01295polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 17. PRQ1359 A cDNA clone (DNA59219-1613) has been identified that encodes a novel polypeptide having sequence 10 identity with sialytransferases and designated in the present application as "PROI359" polypeptides.

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01359 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 15 preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1359 polypeptide having the sequence of amino acid residues from 1 or about 32 to about 299, inclusive of Figure 34 (SEQ ID NO:56), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01359 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 277 and 20 about 1080, inclusive, of Figure 33 (SEQ ID NO:55). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule 25 encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203220 (DNA59219-1613), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203220 (DNA59219-1613).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 30 encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 32 to about 299, inclusive of Figure 34 (SEQ ID NO:56), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 35 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1359 polypeptide having the sequence of amino acid residues from about 32 to about 299, inclusive of Figure 34 (SEQ ID NO:56), or (b) the complement 71 of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01359 polypeptide in its soluble, i.e. transmembrane domain deleted or inactivated variants, or is 5 complementary to such encoding nucleic acid molecule. The transmembrane domain (type II) has been tentatively identified as extending from about amino acid position 9 through about amino acid position 31 in the PR01359 amino acid sequence (Figure 34, SEQ ID NO:56).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 10 preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 32 to about 299, inclusive of Figure 34 (SEQ ID NO:56), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01359 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 15 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01359 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO1359 polypeptide, which in one 20 embodiment, includes an amino acid sequence comprising residues 32 through 299 of Figure 34 (SEQ ID NO:56).

In another aspect, the invention concerns an isolated PR01359 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 25 sequence of amino acid residues 32 to about 299, inclusive of Figure 34 (SEQ ID NO:56).

In a further aspect, the invention concerns an isolated PR01359 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 32 through 299 of Figure 34 (SEQ ID NO:56).

In yet another aspect, the invention concerns an isolated PR01359 polypeptide, comprising the sequence of amino acid residues 32 to about 299, inclusive of Figure 34 (SEQ ID NO:56), or a fragment thereof sufficient to provide a binding site for an anti-PR01359 antibody. Preferably, the PR01359 fragment retains a qualitative biological activity of a native PR01359 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 35 molecule under stringent conditions with (a) a DNA molecule encoding a PRO1359 polypeptide having the sequence of amino acid residues from about 32 to about 299, inclusive of Figure 34 (SEQ ID NO:56), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence 72 identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the ceil culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01359 5 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01359 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01359 polypeptide, by contacting the native PR01359 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO 1359 polypeptide, 10 or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 18. PROl 190 A\:DNA clone (DNA59586-1520) has been identified that encodes a novel polypeptide designated in the present application as "PROl 190", and which has homology to CDO protein.

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROl 190 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identiiy, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PROl 190 polypeptide having 20 the sequence of amino acid residues from about 1 to about 1115, inclusive of Figure 36 (SEQ ID NO:58), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PROl 190 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 340 and about 3684, inclusive, of Figure 35 (SEQ ID NO:58). Preferably, hybridization occurs under stringent 25 hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203288 30 (DNA59586-1520), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203288 (DNA59586-152Q).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence 35 identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 1115, inclusive of Figure 36 (SEQ ID NO:58), or the complement of the DNA of (a). 73 WO 00/12708 PCT/US99/20111 In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROl 190 polypeptide having the sequence of amino acid residues from about 1 to about 1115, inclusive of Figure 36 (SEQIDNO:58), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably 5 at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROl 190 polypeptide, with one or more of its transmembrane domains deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domains have been tentatively 10 identified in the PROl 190 amino acid sequence shown in Figure 36 (SEQ ID NO:58) as extending from about amino acid position 16 to about amino acid position 30 and from about amino acid position 854 to about amino acid position 879.

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 15 preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to about 1115, inclusive of Figure 36 (SEQ ID NO:58), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO 1190 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 20 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

. In another embodiment, the invention provides isolated PROl 190 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove definied.

In a specific aspect, the invention provides isolated native sequence PRO 1190 polypeptide, which in one 25 embodiment, includes an amino acid sequence comprising residues 1 to 1115 of Figure 36 (SEQ ID NO:58).

In another aspect, the invention concerns an isolated PRO 1190 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 1115, inclusive of Figure 36 (SEQ ID NO:58). 30 In a further aspect, the invention concerns an isolated PROl 190 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to 1115 of Figure 36 (SEQ ID NO:58).

In yet another aspect, the invention concerns an isolated PRO 1190 polypeptide, comprising the sequence 35 of amino acid residues 1 to about 1115, inclusive of Figure 36 (SEQ ID NO:58), or a fragment thereof sufficient to provide a binding site for an anti-PROl 190 antibody. Preferably, the PROl 190 fragment retains a qualitative biological activity of a native PROl 190 polypeptide. 74 In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROl 190 polypeptide having the sequence of amino acid residues from about 1 to about 1115, inclusive of Figure 36 (SEQ ID NO:58), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence 5 identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1190 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PROl 190 antibody. 10 In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PROl 190 polypeptide, by contacting the native PROl 190 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PROl 190 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 19. PRQ1772 A cDNA clone (DNA59817-1703) has been identified, having homology to nucleic acid encoding peptidase enzymes, that encodes a novel polypeptide, designated in the present application as "PR01772".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding 20 a PRO1772 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01772 polypeptide having the sequence of amino acid residues from about 1 or about 37 to about 487, inclusive of Figure 38 (SEQ ID 25 NO:63), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01772 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 93 or about 201 and about 1553, inclusive, of Figure 37 (SEQ ID NO:62). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203470 (DNA59817-1703) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the 35 nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203470 (DNA59817-1703).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 75 encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 37 to about 487, inclusive of Figure 38 (SEQ ID NO:63), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 415 5 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1772 polypeptide having the sequence of amino acid residues from 1 or about 37 to about 487, inclusive of Figure 38 (SEQ ID NO:63), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence 10 identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1772 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid 15 position 1 to about amino acid position 36 in the sequence of Figure 38 (SEQ ID NO:63). The transmembrane domain has been tentatively identified as extending from about amino acid position 313 to about amino acid position 331 in the PR01772 amino acid sequence (Figure 38, SEQ ID NO:63).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 20 preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 37 to about 487, inclusive of Figure 38 (SEQ ID NO:63), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO 1772 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 25 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 37 (SEQ ID NO:62).

In another embodiment, the invention provides isolated PRO1772 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01772 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 37 to about 487 of Figure 38 (SEQ ID NO:63).

In another aspect, the invention concerns an isolated PRO1772 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more 35 preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 37 to about 487, inclusive of Figure 38 (SEQ ID NO:63).

In a further aspect, the invention concerns an isolated PR01772 polypeptide, comprising an amino acid 76 sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 37 to about 487, inclusive of Figure 38 (SEQ ID NO:63).

In yet another aspect, the invention concerns an isolated PRO1772 polypeptide, comprising the sequence of amino acid residues 1 or about 37 to about 487, inclusive of Figure 38 (SEQ ID NO.-63), or a fragment 5 thereof sufficient to provide a binding site for an anti-PR01772 antibody. Preferably, the PROI772 fragment retains a qualitative biological activity of a native PR01772 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROI772 polypeptide having the sequence of amino acid residues from about 1 or about 37 to about 487, inclusive of Figure 38 (SEQ ID 10 NO:63), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PROI772 polypeptide. In a particular embodiment, the agonist or antagonist is an anti~PROI772 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01772 polypeptide by contacting the native PR01772 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01772 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier.

. PRQ1248 A cDNA clone (DNA60278-1530) has been identified, having homology to nucleic acid encoding PUT-25 2, that encodes a novel polypeptide, designated in the present application as "PR01248".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01248 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 30 preferably at least about 95 % sequence identity to (a) a DNA molecuie encoding a PRO1248 polypeptide having the sequence of amino acid residues from about 1 or about 21 to about 183, inclusive of Figure 40 (SEQ ID NO:68), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1248 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 122 35 or about 182 and about 670, inclusive, of Figure 39 (SEQ ID NO:67). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 77 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203170 (DNA60278-1530) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in 5 ATCC Deposit No. 203170 (DNA60278-1530).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 21 to about 183, inclusive of Figure 40 (SEQ ID 10 NO:68), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01248 polypeptide having the sequence of amino acid residues from 1 or about 21 to about 183, inclusive of Figure 40 (SEQ ID NO:68), or (b) the complement of the DNA molecule of (a), and, 15 if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01248 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and 20 its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 20 in the sequence of Figure 40 (SEQ ID NO:68). The transmembrane domain has been tentatively identified as extending from about amino acid position 90 to about amino acid position 112 in the PR01248 amino acid sequence (Figure 40, SEQ ID NO:68).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 21 to about 183, inclusive of Figure 40 (SEQ ID NO:68), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01248 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 39 (SEQ ID NO:67).

In another embodiment, the invention provides isolated PRO1248 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01248 polypeptide, which in 78 PCT/US99/20U1 certain embodiments, includes an amino acid sequence comprising residues 1 or about 21 to about 183 of Figure 40 (SEQ ID NO:68).

In another aspect, the invention concerns an isolated PRO 1248 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 5 sequence of amino acid residues 1 or about 21 to about 183, inclusive of Figure 40 (SEQ ID NO:68).

In a further aspect, the invention concerns an isolated PRO1248 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 21 to about 183, inclusive of Figure 40 (SEQ ID NO:68).

In yet another aspect, the invention concerns an isolated PR01248 polypeptide, comprising the sequence of amino acid residues 1 or about 21 to about 183, inclusive of Figure 40 (SEQ ID NO:68), or a fragment thereof sufficient to provide a binding site for an anti-PR01248 antibody. Preferably, the PR01248 fragment retains a qualitative biological activity of a native PR01248 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 15 molecule under stringent conditions with (a) a DNA molecule encoding a PRO1248 polypeptide having the sequence of amino acid residues from about 1 or about 21 to about 183, inclusive of Figure 40 (SEQ ID N0:68), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell 20 comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1248 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01248 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a 25 native PR01248 polypeptide by contacting the native PR01248 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01248 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 21. PRQ1316 A cDNA clone (DNA60608-1577) has been identified, having homology to Dickkopf that encodes a novel polypeptide, designated in the present application as "PR01316." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01316 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01316 polypeptide having 79 the sequence of amino acid residues from 1 or about 26 to about 259, inclusive of Figure 42 (SEQ ID N0:70), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01316 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 281 and about 987, inclusive, of Figure 41 (SEQ ID NO:69). Preferably, hybridization occurs under stringent 5 hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203126 10 (DNA60608-1577), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203126 (DNA60608-1577).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence 15 identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 26 to about 259, inclusive of Figure 42 (SEQ ID N0:70), or the complement of the DNA of (a).

In a further aspect, the invention concern an isolated nucleic acid molecule having at least 15 nucleotides which hybridizes under stringent conditions with (a) a DNA molecule having a identity with a region spanning 20 either from residues 1-454 or from residues 1095-3130 of the Figure 41 (SEQ ID NO:69), or (b) the complement of the DNA molecule of (a). Alternatively, an isolated nucleic acid molecuie having at least 15 nucleotides having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, and most preferably at least about 95% sequence identity to: (a) a DNA molecule having a identity with a region spanning either from residues 1-454 or from residues 1095-3130 of the 25 Figure 41 (SEQ ID NO:69), or (b) the complement of the DNA molecule of (a).

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROD 16 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 30 1 to about amino acid position 25 in the sequence of Figure 42 (SEQ ID N0:70). An N-glycosylation site has been identified at position 52 and a fungal Zn(2)-Cys(6) binuciear cluster has been identified at position 99.

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 35 amino acid sequence of residues 26 to about 259, inclusive ofFigure 42 (SEQ ID N0:70), or (b) the complement of the DNA of (a).

In another embodiment, the invention provides isolated PR01316 polypeptide encoded by any of the 80 isolated nucleic acid sequences herein above defined.

In a specific aspect, the invention provides isolated native sequence PRO 1316 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 26 to 259 of Figure 42 (SEQ ID N0:70).

In another aspect, the invention concerns an isolated PR01316 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more 5 preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 26 to about 259, inclusive of Figure 42 (SEQ ID N0:70).

In a further aspect, the invention concerns an isolated PR01316 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence 10 of residues 26 to 259 of Figure 42 (SEQ ID N0:70).

In yet another aspect, the invention concerns an isolated PRO 1316 polypeptide, comprising the sequence of amino acid residues 26 to about 259, inclusive of Figure 42 (SEQ ID N0:70), or a fragment thereof sufficient to provide a binding site for an anti-PR01316 antibody. Preferably, the PR01316 fragment retains a qualitative biological activity of a native PRO 1316 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01316 polypeptide having the sequence of amino acid residues from about 26 to about 259, inclusive of Figure 42 (SEQ ID N0:70), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence 20 identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01316 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01316 antibody. 25 In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01316 polypeptide, by contacting the native PR01316 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO 1316 polypeptide, or an agonist or antagonist as herein above defined, in combination with a pharmaceuticaliy acceptable carrier. 22. PRQ1197 A cDNA clone (DNA60611-1524) has been identified that encodes a novel secreted polypeptide designated in the present application as "PROl 197." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding 35 a PROl 197 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 81 preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1197 polypeptide having the sequence of amino acid residues from 1 or about 25 to about 363, inclusive of Figure 44 (SEQ ID NO:72), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PROl 197 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 383 and 5 about 1399, inclusive, of Figure 43 (SEQ ID NO:71). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule 10 encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203175 (DNA60611-1524), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203175 (DNA60611-1524).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 15 encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 25 to about 363, inclusive of Figure 44 (SEQ ID NO:72), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 20 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROl 197 polypeptide having the sequence of amino acid residues from about 25 to about 363, inclusive of Figure 44 (SEQ ID NO:72), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably 25 at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 25 to about 363, inclusive of Figure 44 (SEQ ID NO-.72), or (b) the complement 30 of the DNA of (a).

Another embodiment is directed to fragments of a PROl 197 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length. 35 In another embodiment, the invention provides isolated PROl 197 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PROl 197 polypeptide, which in one 82 PCT/US99/20U1 embodiment, includes an amino acid sequence comprising residues 25 through 363 of Figure 44 (SEQ ID NO:72).

In another aspect, the invention concerns an isolated PROl 197 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 5 sequence of amino acid residues 25 to about 363, inclusive of Figure 44 (SEQ ID NO:72).

In a further aspect, the invention concerns an isolated PROl 197 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 25 through 363 of Figure 44 (SEQ ID NO:72).

In yet another aspect, the invention concerns an isolated PROl 197 polypeptide, comprising the sequence of amino acid residues 25 to about 363, inclusive of Figure 44 (SEQ ID NO:72), or a fragment thereof sufficient to provide a binding site for an anti-PROl 197 antibody. Preferably, the PROl 197 fragment retains a qualitative biological activity of a native PROl 197 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 15 molecule under stringent conditions with (a) a DNA molecule encoding a PROl 197 polypeptide having the sequence of amino acid residues from about 25 to about 363, inclusive of Figure 44 (SEQ ID NO:72), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising 20 the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PROl 197 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PROl 197 antibody. 23. PR01293 A cDNA clone (DNA60618-1557) has been identified, having homology to nucleic acid encoding an immunoglobulin heavy chain variable region protein that encodes a novel polypeptide, designated in the present application as "PR01293".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding 30 a PR01293 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1293 polypeptide having the sequence of amino acid residues from about 1 or about 20 to about 341, inclusive of Figure 46 (SEQ ID 35 NO:77), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1293 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 37 83 or about 94 and about 1059, inclusive, of Figure 45 (SEQ ID NO:76). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule 5 encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203292 (DNA60618-1557) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203292 (DNA60618-1557).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 10 encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 20 to about 341, inclusive of Figure 46 (SEQ ID NO:77), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 100 15 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1293 polypeptide having the sequence of amino acid residues from 1 or about 20 to about 341, inclusive of Figure 46 (SEQ ID NO:77), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence 20 identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01293 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid 25 position 1 to about amino acid position 19 in the sequence of Figure 46 (SEQ ID NO:77). The transmembrane domain has been tentatively identified as extending from about amino acid position 237 to about amino acid position 262 in the PR01293 amino acid sequence (Figure 46, SEQ ID NO:77).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 30 preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 20 to about 341, inclusive of Figure 46 (SEQ ID NO:77), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1293 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 35 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 45 (SEQ ID NO:76). 84 In another embodiment, the invention provides isolated PRO 1293 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01293 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 20 to about 341 of Figure 46 (SEQ ID NO:77).

In another aspect, the invention concerns an isolated PRO1293 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 20 to about 341, inclusive of Figure 46 (SEQ ID NO:77).

In a further aspect, the invention concerns an isolated PR01293 polypeptide, comprising an amino acid 10 sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 20 to about 341, inclusive of Figure 46 (SEQ ID NO:77).

In yet another aspect, the invention concerns an isolated PR01293 polypeptide, comprising the sequence of amino acid residues 1 or about 20 to about 341, inclusive of Figure 46 (SEQ ID NO:77), or a fragment 15 thereof sufficient to provide a binding site for an anti-PR01293 antibody. Preferably, the PRO1293 fragment retains a qualitative biological activity of a native PRO1293 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01293 polypeptide having the sequence of amino acid residues from about i or about 20 to about 341, inclusive of Figure 46 (SEQ ID 20 N0.77), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01293 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01293 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PRO 1293 polypeptide by contacting the native PR01293 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1293 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 24. PRQ1380 A cDNA clone (DNA60740-16I5) has been identified that encodes a novel multi-span transmembrane 35 polypeptide designated in the present application as "PR01380".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1380 polypeptide. 85 In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01380 polypeptide having the sequence of amino acid residues from about 1 to about 470, inclusive of Figure 48 (SEQ ID NO:79), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1380 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 36 and about 1460, inclusive, of Figure 47 (SEQ ID NO:78). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 10 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203456 (DNA60740-1615), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC 15 Deposit No. 203456 (DNA60740-1615).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 470, inclusive of Figure 48 (SEQ ID 20 NO:79), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01380 polypeptide having the sequence of amino acid residues from about 1 to about 470, inclusive of Figure 48 (SEQ ID N0:79), or (b) the complement 25 of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01380 polypeptide, and its soluble variants (i.e. one or more transmembrane domains deleted or 30 inactivated), or is complementary to such encoding nucleic acid molecule. Transmembrane domains have been tentatively identified at about the following amino acid positions: 50-74, 105-127,135-153, 163-183,228-252, 305-330, and 448-472 in the PR01380 amino acid sequence (Figure 48, SEQ ID NO:79).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 35 preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 470, inclusive of Figure 48 (SEQ ID NO:79), or (b) the complement of the DNA of (a). 86 Another embodiment is directed to fragments of a PRO1380 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01380 polypeptide encoded by any of the 5 isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO1380 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 470 of Figure 48 {SEQ ID NO:79).

In another aspect, the invention concerns an isolated PR01380 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more 10 preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 470, inclusive of Figure 48 (SEQ ID NO:79).

Ina further aspect, the invention concerns an isolated PR01380 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence 15 of residues 1 to 470 of Figure 48 (SEQ ID NO:79).

In yet another aspect, the invention concerns an isolated PR01380 polypeptide, comprising the sequence of amino acid residues 1 to about 470, inclusive of Figure 48 (SEQ ID NO:79), or a fragment thereof sufficient to provide a binding site for an anti-PR01380 antibody. Preferably, the PR01380 fragment retains a qualitative biological activity of a native PR01380 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1380 polypeptide having the sequence of amino acid residues from about 1 to about 470, inclusive of Figure 48 (SEQ ID NO:79), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence 25 identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

. PRQ1265 AcDNAclone (DNA60764-1533) has been identified that encodes a novel polypeptide having homology to the Figl polypeptide and designated in the present application as "PR01265." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01265 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 35 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01265 polypeptide having the sequence of amino acid residues from 1 or about about 22 to about 567, inclusive of Figure 50 (SEQ ID 87 NO:84), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PROl265 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 142 and about 1779, inclusive, of Figure 49 (SEQ ID NO:83). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203452 (DNA60764-1533), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic 10 acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203452 (DNA60764-1533).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence 15 identity to the sequence of amino acid residues from about 22 to about 567, inclusive of Figure 50 (SEQ ID NO:84), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01265 polypeptide having the sequence of 20 amino acid residues from about 22 to about 567, inclusive of Figure 50 (SEQ ID NO:84), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding 25 a PR01265 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 21 in the sequence of Figure 50 (SEQ ID NO: 84).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 30 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 22 to about 567, inclusive of Figure 50 (SEQ ID NO:84), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01265 polypeptide coding sequence that may find 35 use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length. 88 In another embodiment, the invention provides isolated PRO1265 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01265 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 22 to 567 of Figure 50 (SEQ ID NO:84).

In another aspect, the invention concerns an isolated PR01265 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 22 to about 567, inclusive of Figure 50 (SEQ ID NO:84).

In a further aspect, the invention concerns an isolated PR01265 polypeptide, comprising an amino acid 10 sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 22 to 567 of Figure 50 (SEQ ID NO:84).

In yet another aspect, the invention concerns an isolated PRO1265 polypeptide, comprising the sequence of amino acid residues 22 to about 567, inclusive of Figure 50 (SEQ ID NO:84), or a fragment thereof sufficient 15 to provide a binding site for ananti-PR01265 antibody. Preferably, the PR01265 fragment retains a qualitative biological activity of a native PRO1265 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01265 polypeptide having the sequence of amino acid residues from about 22 to about 567, inclusive of Figure 50 (SEQ ID NO:84), or (b) 20 the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. 26. PRQ1250 A cDNA clone (DNA60775-1532) has been identified, having homology to nucleic acid encoding long chain fatty acid CoA ligase that encodes a novel polypeptide, designated in the present application as "PRO1250".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01250 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01250 polypeptide having 35 the sequence of amino acid residues from about 1 to about 739, inclusive of Figure 52 (SEQ ID N0:86), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1250 89 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 74 and about 2290, inclusive, of Figure 51 (SEQ ID NO:85). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 5 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203173 (DNA60775-1532) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203173 (DNA60775-1532).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 739, inclusive of Figure 52 (SEQ ID NO:86), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1250 polypeptide having the sequence of amino acid residues from 1 to about 739, inclusive of Figure 52 (SEQ ID NO:86), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more 20 preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01250 polypeptide, with or without the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The type II 25 transmembrane domain has been tentatively identified as extending from about amino acid position 61 to about amino acid position 80 in the PRO1250 amino acid sequence (Figure 52, SEQ ID NO: 86).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 30 amino acid sequence of residues 1 to about 739, inclusive of Figure 52 (SEQ ID NO:86), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01250 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 35 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 51 (SEQ ID NO:85).

In another embodiment, the invention provides isolated PR01250 polypeptide encoded by any of the 90 isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01250 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 to about 739 of Figure 52 (SEQ ID N0:86).

In another aspect, the invention concerns an isolated PR01250 polypeptide, comprising an amino acid 5 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 739, inclusive of Figure 52 (SEQ ID NO:86).

In a further aspect, the invention concerns an isolated PRO1250 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least 10 about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to about 739, inclusive of Figure 52 (SEQ ID NO:86).

In yet another aspect, the invention concerns an isolated PRO1250 polypeptide, comprising the sequence of amino acid residues 1 to about 739, inclusive of Figure 52 (SEQ ID NO:86), or a fragment thereof sufficient to provide a binding site for an anti-PR01250 antibody. Preferably, the PR01250 fragment retains a qualitative 15 biological activity of a native PR01250 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (l) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01250 polypeptide having the sequence of amino acid residues from about 1 to about 739, inclusive of Figure 52 (SEQ ID NO:86), or (b) the complement of the DNA molecuie of (a), and if the test DNA molecule has at least about an 80% sequence 20 identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01250 25 polypeptide. In a particular embodiment, the agonist or antagonist is an anli-PRO 1250 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01250 polypeptide by contacting the native PR01250 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1250 polypeptide, 30 or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 27. PRQ1475 A cDNA clone (DNA61185-1646) has been identified, having homology to nucleic acid encoding an N-acety lglucosaminy ltransferase that encodes a novel polypeptide, designated in the present application as 35 "PR01475".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01475 polypeptide. 91 PCT/US99/201U In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecuie encoding a PRO1475 polypeptide having the sequence of amino acid residues from about 1 to about 660, inclusive of Figure 54 (SEQ ID NO:88), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01475 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 130 and about 2109, inclusive, of Figure 53 (SEQ ID NO:87). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 10 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203464 (DNA61185-1646) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in 15 ATCC Deposit No. 203464 (DNA61I85-1646).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 660, inclusive of Figure 54 (SEQ ID NO:88), or (b) 20 the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 180 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01475 polypeptide having the sequence of amino acid residues from 1 to about 660, inclusive of Figure 54 (SEQ ID NO:88), or (b) the complement of the DNA molecule of (a), and, if the DNA 25 molecule has at least about an 80% sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1475 polypeptide, with or without the initiating methionine, and its soluble, i.e., transmembrane domain 30 deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domain has been tentatively identified as extending from about amino acid position 38 to about amino acid position 55 in the PR01475 amino acid sequence (Figure 54, SEQ ID NO:88).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 35 preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 660, inclusive of Figure 54 (SEQ ID NO:88), or (b) the complement of the DNA of (a). 92 PCT/US99/201I1 Another embodiment is directed to fragments of a PRO1475 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 53 (SEQ ID NO:87).

In another embodiment, the invention provides isolated PRO1475 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PRO 1475 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 to about 660 of Figure 54 (SEQ ID NO:88).

In another aspect, the invention concerns an isolated PR01475 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 660, inclusive of Figure 54 (SEQ ID NO:88).

In a further aspect, the invention concerns an isolated PR01475 polypeptide, comprising an amino acid 15 sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to about 660, inclusive of Figure 54 (SEQ ID NO:88).

In yet another aspect, the invention concerns an isolated PR01475 polypeptide, comprising the sequence of amino acid residues 1 to about 660, inclusive of Figure 54 (SEQ ID NO:88), or a fragment thereof sufficient 20 to provide a binding site for an anti-PR01475 antibody. Preferably, the PRO 1475 fragment retains a qualitative biological activity of a native PR01475 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1475 polypeptide having the sequence of amino acid residues from about 1 to about 660, inclusive of Figure 54 (SEQ ID NO:88), or (b) the 25 complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01475 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01475 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01475 polypeptide by contacting the native PR01475 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01475 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 93 28. PROl 377 A cDNA clone (DNA61608-1606) has been identified that encodes a novel multi-span transmembrane polypeptide designated in the present application as "PR01377." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01377 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01377 polypeptide having the sequence of amino acid residues from 1 or about 19 to about 307, inclusive of Figure 56 (SEQ ID NO:95), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1377 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 203 and about 1069, inclusive, of Figure 55 (SEQ ID NO:94). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 15 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203239 (DNA61608-1606), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC 20 Deposit No. 203239 (DNA61608-1606).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 19 to about 307, inclusive of Figure 56 (SEQ ID 25 NO:95), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1377 polypeptide having the sequence of amino acid residues from about 19 to about 307, inclusive of Figure 56 (SEQ ID NO:95), or (b) the complement 30 of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01377 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and 35 one or more of its transmembrane domains deleted or inactivated, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 18 in the sequence of Figure 56 (SEQ ID N0:95). Transmembrane domain 94 has been tentatively identified as extending from about amino acid positions 37-56, 106-122, 211-20, 240-260, and 288-304 in the PR01377 amino acid sequence (Figure 56, SEQ ID NO:95).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 5 amino acid sequence of residues 19 to about 307, inclusive of Figure 56 (SEQ ID NO:95), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01377 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 10 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1377 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01377 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 19 to 307 of Figure 56 (SEQ ID NO:95). 15 In another aspect, the invention concerns an isolated PR01377 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 19 to about 307, inclusive of Figure 56 (SEQ ID NO:95).

In a further aspect, the invention concerns an isolated PR01377 polypeptide, comprising an amino acid 20 sequence scoring at least about 80% positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 19 to 307 of Figure 56 (SEQ ID NO:95).

In yet another aspect, the invention concerns an isolated PRO1377 polypeptide, comprising the sequence of amino acid residues 19 to about 307, inclusive of Figure 56 (SEQ ID NO:95), or a fragment thereof sufficient 25 to provide a binding site for an anti-PR01377 antibody. Preferably, the PR01377 fragment retains a qualitative biological activity of a native PR01377 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01377 polypeptide having the sequence of amino acid residues from about 19 to about 307, inclusive of Figure 56 (SEQ ID N0:95), or (b) 30 the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. 29. PRQ1326 A cDNA clone (DNA62808-I582) has been identified that encodes a novel secreted polypeptide 95 designated in the present application as "PR01326." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1326 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 5 preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01326 polypeptide having the sequence of amino acid residues from 1 or about 30 to about 401, inclusive of Figure 58 (SEQ ID N0:100), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecuie encoding a PR01326 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 199 and 10 about 1314, inclusive, of Figure 57 (SEQ ID NO:99). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule 15 encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203358 (DNA62808-1582), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203358 (DNA62808-1582).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 20 encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 30 to about 401, inclusive of Figure 58 (SEQ ID NO: 100), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 25 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1326 polypeptide having the sequence of amino acid residues from about 30 to about 401, inclusive of Figure 58 (SEQ ID NO: 100), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90 % sequence identity, most 30 preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01326 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 29 in the sequence of Figure 58 (SEQ 35 ID NO: 100).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 96 preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 30 to about 401, inclusive of Figure 58 (SEQ ID N0:100), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1326 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 5 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01326 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01326 polypeptide, which in one 10 embodiment, includes an amino acid sequence comprising residues 30 to 401 of Figure 58 (SEQ ID NO: 100).

In another aspect, the invention concerns an isolated PR01326 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 30 to about 401, inclusive of Figure 58 (SEQ ID N0:100).

IS In a further aspect, the invention concerns an isolated PR01326 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 30 to 401 of Figure 58 (SEQ ID NO: 100).

In yet another aspect, the invention concerns an isolated PR01326polypeptide, comprising the sequence 20 of amino acid residues 30 to about 401, inclusive of Figure 58 (SEQ ID NO: 100), or a fragment thereof sufficient to provide a binding site for an anti-PR01326 antibody. Preferably, the PR01326 fragment retains a qualitative biological activity of a native PR01326 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01326 polypeptide having the 25 sequence of amino acid residues from about 30 to about 401, inclusive of Figure 58 (SEQ ID NO: 100), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the 30 polypeptide from the cell culture.

. PRQ1249 A cDNA clone (DNA62809-1531) has been identified that encodes a novel transmembrane polypeptide, designated in the present application as "PRO1249".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01249 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 97 PCMJS99/20U1 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01249 polypeptide having the sequence of amino acid residues from about 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ ID NO: 102), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01249 5 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 3 or about 51 and about 3269, inclusive, of Figure 59 (SEQ ID NO: 101). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 10 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203237 (DNA62809-1531) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203237 (DNA62809-1531).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ ID NO: 102), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01249 polypeptide having the sequence of amino acid residues from 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ ID NO: 102), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence 25 identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01249 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding 30 nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 16 in the sequence of Figure 60 (SEQ ID N0:102). The transmembrane domains have been tentatively identified as extending from about amino acid position 317 to about amino acid position 341, from about amino acid position 451 to about amino acid position 470, from about amino acid position 481 to about amino acid position 500, from about amino acid position 510 to about amino acid position 35 527, from about amino acid position 538 to about amino acid position 555, from about amino acid position 831 to about amino acid position 850, from about amino acid position 1016 to about amino acid position 1034 and from about amino acid position 1052 to about amino acid position 1070 in the PR01249 amino acid sequence 98 (Figure 60, SEQ ID NO: 102).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ ID NO: 102), or (b) 5 the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01249 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived 10 from the nucleotide sequence shown in Figure 59 (SEQ ID NO: 101).

In another embodiment, the invention provides isolated PRO1249 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01249 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 17to about 1089 of Figure 15 60 (SEQ ID NO: 102).

In another aspect, the invention concerns an isolated PR01249 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ ID NO: 102). 20 In a further aspect, the invention concerns an isolated PR01249 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ ID NO: 102).

In yet another aspect, the invention concerns an isolated PRO1249 polypeptide, comprising the sequence 25 of amino acid residues 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ ID NO: 102), or a fragment thereof sufficient to provide a binding site for an anti-PR01249 antibody. Preferably, the PR01249 fragment retains a qualitative biological activity of a native PR01249 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01249 polypeptide having the 30 sequence of amino acid residues from about 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ ID NO: 102), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) 35 recovering the polypeptide from the cell culture. 99 31. PRQ1315 A cDNA clone (DNA62815-1576) has been identified, having homology to nucleic acid encoding cytokine receptor family-4 proteins that encodes a novel polypeptide, designated in the present application as "PRO 1315".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding 5 a PRODIS polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1315 polypeptide having the sequence of amino acid residues from about 1 or about 29 to about 442, inclusive of Figure 62 (SEQ ID 10 NO: 104), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRODIS polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 121 or about 205 and about 1446, inclusive, of Figure 61 (SEQ ID NO: 103). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203247 (DNA62815-1576) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the 20 nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203247 (DNA62815-1576).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence 25 identity to the sequence of amino acid residues 1 or about 29 to about 442, inclusive of Figure 62 (SEQ ID N0:104), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 500 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRODIS polypeptide having the sequence of amino acid residues from 1 ot about 29 to 30 about 442, inclusive of Figure 62 (SEQ ID NO: 104), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding 35 a PR01315 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid 100 position 1 to about amino acid position 28 in the sequence of Figure 62 (SEQ ID NO: 104). The transmembrane domain has been tentatively identified as extending from about amino acid position 140 to about amino acid position 163 in the PR01315 amino acid sequence (Figure 62, SEQ ID NO: 104).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 5 preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 29 to about 442, inclusive of Figure 62 (SEQ ID NO: 104), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01315 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 10 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 61 (SEQ ID NO: 103).

In another embodiment, the invention provides isolated PROD 15 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01315 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 29 to about 442 of Figure 62 (SEQ ID NO: 104).

In another aspect, the invention concerns an isolated PROD 15 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more 20 preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 29 to about 442, inclusive of Figure 62 (SEQ ID NO: 104).

In a further aspect, the invention concerns an isolated PRO 1315 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence 25 of residues 1 or about 29 to about 442, inclusive of Figure 62 (SEQ ID NO: 104).

In yet another aspect, the invention concerns an isolated PRO 1315 polypeptide, comprising the sequence of amino acid residues 1 or about 29 to about 442, inclusive of Figure 62 (SEQ ID NO: 104), or a fragment thereof sufficient to provide a binding site for an anti-PR01315 antibody. Preferably, the PRO 1315 fragment retains a qualitative biological activity of a native PR01315 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROD 15 polypeptide having the sequence of amino acid residues from about 1 or about 29 to about 442, inclusive of Figure 62 (SEQ ID NO: 104), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 35 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. 101 In yet another embodiment, the invention concerns agonists and antagonists of a native PR01315 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01315 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01315 polypeptide by contacting the native PR01315 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01315 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 32. PRO 1599 A cDNA clone (DNA62845-1684)has been identified that encodes a novel polypeptide having homology 10 to Granzyme M and designated in the present application as "PRO1599." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01599 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 15 preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1599 polypeptide having the sequence of amino acid residues from 1 or about 31 to about 283, inclusive of Figure 64 (SEQ ID NO: 111), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1599 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 159 and 20 about 917, inclusive, of Figure 63 (SEQ ID NO: 110). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule 25 encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203361 (DNA62845-1684), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203361 (DNA62845-1684).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 30 encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 31 to about 283, inclusive of Figure 64 (SEQ ID NO:111), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 35 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01599 polypeptide having the sequence of amino acid residues from about 31 to about 283, inclusive of Figure 64 (SEQ ID NO:111), or (b) the 102 complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01599 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is 5 complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 30 in the sequence of Figure 64 (SEQ ID NO: 111).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 10 preferably at ieast about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 31 to about 283, inclusive of Figure 64 (SEQ ID NO:111), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01599 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 15 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PROI599 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01599 polypeptide, which in one 20 embodiment, includes an amino acid sequence comprising residues 31 to 283 of Figure 64 (SEQ ID NO:111).

In another aspect, the invention concerns an isolated PR01599 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 31 to about 283, inclusive of Figure 64 (SEQ ID NO: 111). 25 In a further aspect, the invention concerns an isolated PRO 1599 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 31 to 283 of Figure 64 (SEQ ID NO:lll).

In yet another aspect, the invention concerns an isolated PR01599 polypeptide, comprising the sequence 30 of amino acid residues 31 to about 283, inclusive of Figure 64 (SEQ ID NO:111), or a fragment thereof sufficient to provide a binding site for an anti-PR01599 antibody. Preferably, the PR01599 fragment retains a qualitative biological activity of a native PRO1599 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01599 polypeptide having the 35 sequence of amino acid residues from about 31 to about 283, inclusive of Figure 64 (SEQ ID NO: 111), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence 103 identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1599 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01599 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01599 polypeptide, by contacting the native PR01599 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01599 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 33. PRQ1430 A cDNA clone (DNA64842-1632) has been identified that encodes a novel polypeptide having homology to reductase proteins, designated in the present application as "PR01430." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding 15 a PR01430 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO1430 polypeptide having the sequence of amino acid residues from 1 or about 18to about 331, inclusive of Figure 66 (SEQ ID NO:116), 20 or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1430 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 33 and about 1074, inclusive, of Figure 65 (SEQ ID NO: 115). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecuie comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203278 (DNA64842-1632), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic 30 acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203278 (DNA64842-1632).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence 35 identity to the sequence of amino acid residues from about 18 to about 331, inclusive of Figure 66 (SEQ ID NO: 116), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 104 nucleotides, and preferably at least about 100 and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01430 polypeptide having the sequence of amino acid residues from about 18 to about 331, inclusive of Figure 66 (SEQ ID NO: 116), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least 5 about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01430 polypeptide, with or without the N-terminal signal sequence, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 17 in the sequence of Figure 66 (SEQ ID NO: 116). 10 In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 18 to about 331, inclusive of Figure 66 (SEQ ID NO:116), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO 1430 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO 1430 polypeptide encoded by any of the 20 isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO 1430 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 18 to 331 of Figure 66 (SEQ ID NO:116).

In another aspect, the invention concerns an isolated PRO 1430 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more 25 preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 18 to about 331, inclusive of Figure 66 (SEQ ID NO:116).

In a further aspect, the invention concerns an isolated PRO 1430 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence 30 of residues 18 to 331 of Figure 66 (SEQ ID NO:116).

In yet another aspect, the invention concerns an isolated PR01430polypeptide, comprising the sequence of amino acid residues 18 to about 331, inclusive of Figure 66 (SEQ ID NO:116), or a fragment thereof sufficient to provide a binding site for an anti-PR01430 antibody. Preferably, the PR01430 fragment retains a qualitative biological activity of a native PRO1430 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01430 polypeptide having the sequence of amino acid residues from about 18 to about 331, inclusive of Figure 66 (SEQ ID NO:116), or (b) 105 PCT7US99/20111 the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1430 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PROl430 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01430 polypeptide, by contacting the native PR01430 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01430polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 34. PRQ1374 A cDNA clone (DNA64849-1604) has been identified that encodes a novel polypeptide having sequence 15 identity with P4HA and designated in the present application as "PR01374." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1374 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 20 preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01374 polypeptide having the sequence of amino acid residues from 1 or about 20 to about 544, inclusive of Figure 68 (SEQ ID NO:118), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01374 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 78 and 25 about 1652, inclusive, of Figure 67 (SEQ ID NO: 117). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule 30 encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203468 (DNA64849-1604), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203468 (DNA64849-1604).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 35 encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 20 to about 544, inclusive of Figure 68 (SEQ ID 106 NO: 118), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1374 polypeptide having the sequence of amino acid residues from about 20 to about 544, inclusive of Figure 68 (SEQ ID NO: 118), or (b) the 5 complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 10 preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 20 to about 544, inclusive of Figure 68 (SEQ ID NO: 118), or (b) the complement of the DNA of (a).

Another embodimem is directed to fragments of a PRO 1374 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 15 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01374 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01374 polypeptide, which in one 20 embodiment, includes an amino acid sequence comprising residues 20 through 544 of Figure 68 (SEQ ID NO: 118).

In another aspect, the invention concerns an isolated PR01374 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 25 sequence of amino acid residues 20 to about 544, inclusive of Figure 68 (SEQ ID NO: 118).

In a further aspect, the invention concerns an isolated PR01374 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 20 through 544 of Figure 68 (SEQ ID NO:l 18).

In yet another aspect, the invention concerns an isolated PR01374 polypeptide, comprising the sequence of amino acid residues 20 to about 544, inclusive of Figure 68 (SEQ ID NO: 118), or a fragment thereof sufficient to provide a binding site for an anti-PR01374 antibody. Preferably, the PR01374 fragment retains a qualitative biological activity of a native PR01374 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 35 molecule under stringent conditions with (a) a DNA molecule encoding a PRO1374 polypeptide having the sequence of amino acid residues from about 20 to about 544, inclusive of Figure 68 (SEQ ID NO:118), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence 107 identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or <b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1374 5 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01374 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01374 polypeptide, by contacting the native PR01374 polypeptide with a candidate molecuie and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO 1374 polypeptide, 10 or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier.

. PRQ1311 A cDNA clone (DNA64863-1573) has been identified that encodes a novel tetraspan polypeptide designated in the present application as "PR01311".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1311 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01311 polypeptide having 20 the sequence of amino acid residues from 1 or about 45 to about 294, inclusive of Figure 70 (SEQ ID NO: 123), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PROD 11 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 327 and about 1076, inclusive, of Figure 69 (SEQ ID NO: 122). Preferably, hybridization occurs under stringent 25 hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203251 30 (DNA64863-1573), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203251 (DNA64863-1573).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence 35 identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 45 to about 294, inclusive of Figure 70 (SEQ ID NO: 123), or the complement of the DNA of (a). 108 In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROI311 polypeptide having the sequence of amino acid residues from about 45 to about 294, inclusive of Figure 70 (SEQ ID NO: 123), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, 5 preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01311 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domains deleted or inactivated variants, or is complementary to such encoding 10 nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 44 in the sequence of Figure 70 (SEQ ID NO: 123). Four transmembrane domains has been tentatively identified as extending from about amino acid 22-42,57-85, 94-116, and 230-257 in the PR01311 amino acid sequence (Figure 70, SEQ ID NO: 123).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 15 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 45 to about 294, inclusive of Figure 70 (SEQ ID NO: 123), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO 1311 polypeptide coding sequence that may find 20 use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO 13II polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO 1311 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 45 to 294 of Figure 70 (SEQ ID NO: 123).

In another aspect, the invention concerns an isolated PR01311 polypeptide, comprising an amino acid sequence having at ieast about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 30 sequence of amino acid residues 45 to about 294, inclusive of Figure 70 (SEQ ID NO: 123).

In a further aspect, the invention concerns an isolated PR01311 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 % positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 45 to 294 of Figure 70 (SEQ ID NO: 123).

In yet another aspect, the invention concerns an isolated PR01311 polypeptide, comprising the sequence of amino acid residues 45 to about 294, inclusive of Figure 70 (SEQ ID NO: 123), or a fragment thereof sufficient to provide a binding site for an anti-PR01311 antibody. Preferably, the PR01311 fragment retains 109 a qualitative biological activity of a native PRO 1311 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01311 polypeptide having the sequence of amino acid residues from about 45 to about 294, inclusive of Figure 70 (SEQ ID NO: 123), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence 5 identity, preferably at least about an 85% sequence identity, more preferably at ieast about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. 36. PRQ1357 A cDNA clone (DNA64881-1602) has been identified, having homology to nucleic acid encoding the von Ebner minor salivary gland protein that encodes a novel polypeptide, designated in the present application as "PRO 1357".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding 15 a PR01357 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01357 polypeptide having the sequence of amino acid residues from about 1 or about 22 to about 484, inclusive of Figure 72 (SEQ ID 20 NO: 128), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01357 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 74 or about 137 and about 1525, inclusive, ofFigure71 (SEQ ID NO: 127). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203240 (DNA64881-1602) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the 30 nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203240 (DNA64881-1602).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence 35 identity to the sequence of amino acid residues 1 or about 22 to about 484, inclusive of Figure 72 (SEQ ID NO: 128), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 40 110 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1357 polypeptide having the sequence of amino acid residues from 1 or about 22 to about 484, inclusive of Figure 72 (SEQ ID NO: 128), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence 5 identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01357 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 21 in the sequence of Figure 72 (SEQ 10 ID NO: 128).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 22 to about 484, inclusive of Figure 72 (SEQ ID NO: 128), or (b) 15 the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01357 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived 20 from the nucleotide sequence shown in Figure 71 (SEQ ID NO:127).

In another embodiment, the invention provides isolated PR01357 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01357 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 22 to about 484 of Figure 25 72 (SEQ ID NO: 128).

In another aspect, the invention concerns an isolated PR01357 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 22 to about 484, inclusive of Figure 72 (SEQ ID NO: 128). 30 In a further aspect, the invention concerns an isolated PR01357 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 22 to about 484, inclusive of Figure 72 (SEQ ID NO: 128).

In yet another aspect, the invention concerns an isolated PR01357 polypeptide, comprising the sequence 35 of amino acid residues 1 or about 22 to about 484, inclusive of Figure 72 (SEQ ID NO: 128), or a fragment thereof sufficient to provide a binding site for an anti-PR01357 antibody. Preferably, the PR01357 fragment retains a qualitative biological activity of a native PR01357 polypeptide.

Ill In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1357 polypeptide having the sequence of amino acid residues from about 1 or about 22 to about 484, inclusive of Figure 72 (SEQ ID NO: 128), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1357 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01357 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01357 polypeptide by contacting the native PR01357 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1357 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 39. PRQ1356 A cDNA clone (DNA64886-1601) has been identified, having homology to nucleic acid encoding Clostridium perfringens enterotoxin receptor, that encodes a novel polypeptide, designated in the present application as "PR01356".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01356 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01356 polypeptide having the sequence of amino acid residues from about 1 or about 25 to about 230, inclusive of Figure 78 (SEQ ID NO: 134), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01356 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 122 or about 194 and about 811, inclusive, of Figure 77 (SEQ ID NO: 133). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 112 (followedby page 117) 2 4 OCT 2003 received at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203241 (DNA64886-1601) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in 5 ATCC Deposit No. 203241 (DNA64886-1601).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 25 to about 230, inclusive of Figure 78 (SEQ ID 10 NO: 134), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 20 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROI356 polypeptide having the sequence of amino acid residues from 1 or about 25 to about 230, inclusive of Figure 78 (SEQ ID NO: 134), or (b) the complement of the DNA molecule of (a), and, 15 if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01356 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and 20 its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 24 in the sequence of Figure 78 (SEQ ID NO: 134). The transmembrane domains have been tentatively identified as extending from about amino acid position 82 to about amino acid position 102, from about amino acid position 117 to about amino acid position 140 and from about amino acid 25 position 163 to about amino acid position 182 in the PR01356 amino acid sequence (Figure 78, SEQ ID NO: 134).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 30 amino acid sequence of residues 1 or about 25 to about 230, inclusive of Figure 78 (SEQ ID NO: 134), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01356 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 35 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 77 (SEQ ID NO: 133).

In another embodiment, the invention provides isolated PRO1356 polypeptide encoded by any of the 117 isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PRO1356 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 25 to about 230 of Figure 78 (SEQ ID NO: 134).

In another aspect, the invention concerns an isolated PR01356 polypeptide, comprising an amino acid 5 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 25 to about 230, inclusive of Figure 78 (SEQ ID NO: 134).

In a further aspect, the invention concerns an isolated PRO1356 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least 10 about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 25 to about 230, inclusive of Figure 78 (SEQ ID NO: 134).

In yet another aspect, the invention concerns an isolated PR01356 polypeptide, comprising the sequence of amino acid residues 1 or about 25 to about 230, inclusive of Figure 78 (SEQ ID NO: 134), or a fragment thereof sufficient to provide a binding site for an anti-PR01356 antibody. Preferably, the PR01356 fragment 15 retains a qualitative biological activity of a native PR01356 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROl356 polypeptide having the sequence of amino acid residues from about 1 or about 25 to about 230, inclusive of Figure 78 (SEQ ID NO:134), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about 20 an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host ceil comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01356 25 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01356 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01356 polypeptide by contacting the native PRO 1356 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01356polypeptide, 30 or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 40. PRQ1275 A cDNA clone (DNA64888-1542) has been identified that encodes a novel secreted polypeptide designated in the present application as "PR01275." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1275 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 118 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO1275 polypeptide having the sequence of amino acid residues from about 26 to about 119, inclusive of Figure 80 (SEQ ID NO: 136), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01275 5 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 112 and about 393, inclusive, of Figure 79 (SEQ ID NO: 135). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 10 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203249 (DNA64888-1542), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203249 (DNA64888-1542).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 26 to about 119, inclusive of Figure 80 (SEQ ID NO: 136), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01275 polypeptide having the sequence of amino acid residues from about 26 to about 119, inclusive of Figure 80 (SEQ ID NO:136), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, 25 preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acid molecuie comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 30 amino acid sequence of residues 26 to about 119, inclusive of Figure 80 (SEQ ID NO: 136), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1275 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 35 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01275 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined. 119 In a specific aspect, the invention provides isolated native sequence PRO1275 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 26 through 119 of Figure 80 (SEQ ID NO: 136).

In another aspect, the invention concerns an isolated PR01275 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more 5 preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 26 to about 119, inclusive of Figure 80 (SEQ ID NO: 136).

In a further aspect, the invention concerns an isolated PRO1275 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence 10 of residues 26 through 119 of Figure 80 (SEQ ID NO: 136).

In yet another aspect, the invention concerns an isolated PRO1275 polypeptide, comprising the sequence of amino acid residues 26 to about 119, inclusive of Figure 80 (SEQ ID NO: 136), or a fragment thereof sufficient to provide a binding site for an anti-PR01275 antibody. Preferably, the PR01275 fragment retains a qualitative biological activity of a native PR01275 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1275 polypeptide having the sequence of amino acid residues from about 26 to about 119, inclusive of Figure 80 (SEQ ID NO: 136), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence 20 identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01275 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01275 antibody. 25 In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01275 polypeptide, by contacting the native PR01275 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01275 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 42. FRQ1412 A cDNA clone (DNA64897-1628) has been identified that encodes a novel transmembrane polypeptide designated in die present application as "PR01412." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01412 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01412 polypeptide having 120 INTELLECTUAL PROPERTY 0FRCF OF N.Z (followed by page 123) 24 OCT 2003 received the sequence of amino acid residues from 1 or about 29 to about 311, inclusive of Figure 84 (SEQ ID NO: 140), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PROM 12 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 226 and about 1074, inclusive, of Figure 83 (SEQ ID NO: 139). Preferably, hybridization occurs under stringent 5 hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203216 10 (DNA64897-1628), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203216 (DNA64897-1628).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence 15 identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 29 to about 311, inclusive of Figure 84 (SEQ ID NO: 140), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule 20 under stringent conditions with (a) a DNA molecuie encoding a PR01412 polypeptide having the sequence of amino acid residues from about 29 to about 311, inclusive of Figure 84 (SEQ ID NO: 140), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule. 25 In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01412 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 28 in the sequence of Figure 84 (SEQ ID NO: 140). The transmembrane 30 domain has been tentatively identified as extending from about amino acid position 190 through about amino acid position 216 in the PR01412 amino acid sequence (Figure 84, SEQ ID N0:140).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 35 amino acid sequence of residues 29 to about 311, inclusive of Figure 84 (SEQ ID N0:140), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO 1412 polypeptide coding sequence that may find 123 use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01412 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

Inaspecific aspect, the invention provides isolated native sequence PR01412 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 29 to 311 of Figure 84 (SEQ ID NO: 140).

In another aspect, the invention concerns an isolated PROM 12 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 10 sequence of amino acid residues 29 to about 311, inclusive of Figure 84 (SEQ ID N0:140).

In a further aspect, the invention concerns an isolated PR01412 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 29 to 311 of Figure 84 (SEQ ID N0:140).

In yet another aspect, the invention concerns an isolated PRO 1412 polypeptide, comprising the sequence of amino acid residues 29 to about 311, inclusive of Figure 84 (SEQ ID NO: 140), or a fragment thereof sufficient to provide a binding site for an anti-PR01412 antibody. Preferably, the PR01412 fragment retains a qualitative biological activity of a native PR01412 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 20 molecule under stringent conditions with (a) a DNA molecule encoding a PR01412 polypeptide having the sequence of amino acid residues from about 29 to about 311, inclusive of Figure 84 (SEQ ID NO: 140), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising 25 the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. 43. PRQ1557 A cDNA clone (DNA64902-1667) has been identified that encodes a novel polypeptide having homology 30 to chordin and designated in the present application as "PR01557".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1557 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 35 preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01557 polypeptide having the sequence of amino acid residues from 1 or about 26 to about 451, inclusive of Figure 86 (SEQ ID NO: 142), or (b) the complement of the DNA molecule of (a). 124 In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01557 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 362 and about 1639, inclusive, of Figure 85 (SEQ ID NO: 141). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 5 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203317 (DNA64902-1667), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC 10 Deposit No. 203317 (DNA64902-1667).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 26 to about 451, inclusive of Figure 86 (SEQ ID 15 NO: 142), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1557 polypeptide having the sequence of amino acid residues from about 26 to about 451, inclusive of Figure 86 (SEQ ID NO: 142), or (b) the 20 complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1557 polypeptide, with or without the N-terminal signal sequence, or is complementary to such encoding 25 nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 25 in the sequence of Figure 86 (SEQ ID NO: 142).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 30 amino acid sequence of residues 26 to about 451, inclusive of Figure 86 (SEQ ID NO:142), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01557 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 35 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01557 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined. 125 In a specific aspect, the invention provides isolated native sequence PRO 1557 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 26 to 451 of Figure 86 (SEQ ID N0:142).

In another aspect, the invention concerns an isolated PR01557 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 5 sequence of amino acid residues 26 to about 451, inclusive of Figure 86 (SEQ ID NO: 142).

In a further aspect, the invention concerns an isolated PR01557 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 26 to 451 of Figure 86 (SEQ ID NO: 142).

In yet another aspect, the invention concerns an isolated PRO1557 polypeptide, comprising the sequence of amino acid residues 26 to about 451, inclusive of Figure 86 (SEQ ID NO:142), or a fragment thereof sufficient to provide a binding site for an anti-PR01557 antibody. Preferably, the PR01557 fragment retains a qualitative biological activity of a native PR01557 polypeptide. molecule under stringent conditions with (a) a DNA molecule encoding a PR01557 polypeptide having the sequence of amino acid residues from about 26 to about 451, inclusive of Figure 86 (SEQ ID NO: 142), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising 20 the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01557 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01557 antibody. native PRO1557 polypeptide by contacting the native PRO1557 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1557 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 46. PRQ1347 A cDNA clone (DNA64950-1590) has been identified that encodes a novel polypeptide having sequence identity with butyrophilin and designated in the present application as "PR01347." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01347 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a 126 (followed by page 131) INTELLECTUAL PROPERTY OFRCE OF N.Z 24 OCT 2003 received preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO1347 polypeptide having the sequence of amino acid residues from 1 or about 18 to about 500, inclusive of Figure 92 (SEQ ID NO: 148), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01347 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 234 and 5 about 1682, inclusive, of Figure 91 (SEQ ID NO: 147). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule 10 encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203224 (DNA64950-1590), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203224 (DNA64950-1590).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 15 encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 18 to about 500, inclusive of Figure 92 (SEQ ID NO: 148), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 20 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1347 polypeptide having the sequence of amino acid residues from about 18 to about 500, inclusive of Figure 92 (SEQ ID NO: 148), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most 25 preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01347 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted (or that terminus truncated) or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as 30 extending from amino acid position 1 through about amino acid position 17 in the sequence of Figure 92 (SEQ ID NO: 148). The transmembrane domain has been tentatively identified as extending from about amino acid position 239 through about amino acid position 255 in the PR01347 amino acid sequence (Figure 92, SEQ ID NO: 148).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 35 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 18 to about 500, inclusive of Figure 92 (SEQ ID NO: 148), or (b) the 131 complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1347 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PROl 347 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01347 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 18 through 500 of Figure 92 (SEQ ID NO: 148).

In another aspect, the invention concerns an isolated PR01347 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 18 to about 500, inclusive of Figure 92 (SEQ ID NO: 148).

In a further aspect, the invention concerns an isolated PR01347 polypeptide, comprising an amino acid 15 sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 18 through 500 of Figure 92 (SEQ ID NO: 148).

In yet another aspect, the invention concerns an isolated PR01347 polypeptide, comprising the sequence of amino acid residues 18 to about 500, inclusive of Figure 92 (SEQ ID NO: 148), or a fragment thereof 20 sufficient to provide a binding site for an anti-PROl347 antibody. Preferably, the PRO1347 fragment retains a qualitative biological activity of a native PRO 1347 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01347 polypeptide having the sequence of amino acid residues from about 18 to about 500, inclusive of Figure 92 (SEQ ID NO: 148), or (b) 25 the complement of the DNA molecuie of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01347 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01347 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PRO1347 polypeptide, by contacting the native PRO1347 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO 1347 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 132 47. PRQ1305 A cDNA clone (DNA64952-1568) has been identified that encodes a novel secreted polypeptide, designated in the present application as "PRO1305".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1305 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01305 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 258, inclusive of Figure 94 (SEQ ID NO: 153), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01305 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 126 or about 201 and about 899, inclusive, of Figure 93 (SEQ ID NO:152). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 15 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203222 (DNA64952-1568) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in 20 ATCC Deposit No. 203222 (DNA64952-1568).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 258, inclusive of Figure 94 (SEQ ID 25 NO: 153), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01305 polypeptide having the sequence of amino acid residues from 1 or about 26 to about 258, inclusive of Figure 94 (SEQ ID NO: 153), or (b) the complement of the DNA molecule of (a), and, 30 if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01305 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is 35 complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position I to about amino acid position 25 in the sequence of Figure 94 (SEQ ID NO: 153). 133 In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 26 to about 258, inclusive of Figure 94 (SEQ ID NO: 153), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO 1305 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 93 (SEQ ID NO: 152).

In another embodiment, the invention provides isolated PRO1305 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01305 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 26 to about 258 of Figure 94 (SEQ ID NO: 153).

In another aspect, the invention concerns an isolated PR01305 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 258, inclusive of Figure 94 (SEQ ID NO: 153).

In a further aspect, the invention concerns an isolated PR01305 polypeptide, comprising an amino acid 20 sequence scoring at least about 80% positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 26 to about 258, inclusive of Figure 94 (SEQ ID NO: 153).

In yet another aspect, the invention concerns an isolated PRO 1305 polypeptide, comprising the sequence of amino acid residues 1 or about 26 to about 258, inclusive of Figure 94 (SEQ ID NO: 153), or a fragment 25 thereof sufficient to provide a binding site for an anti-PR01305 antibody. Preferably, the PR01305 fragment retains a qualitative biological activity of a native PR01305 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01305 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 258, inclusive of Figure 94 (SEQ ID 30 NO: 153), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. 48. PRQ1273 A cDNA clone (DNA65402-1540) has been identified that encodes a novel polypeptide having sequence 134 identity with lipocalins and designated in the present application as "PRO 1273." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROI273 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 5 preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01273 polypeptide having the sequence of amino acid residues from 1 or about 21 to about 163, inclusive of Figure 96 (SEQ ID NO: 158), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01273 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 86 and 10 about 514, inclusive, of Figure 95 (SEQ ID NO: 157). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule 15 encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203252 (DNA65402-1540), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203252 (DNA65402-1540).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 20 encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 21 to about 163, inclusive of Figure 96 (SEQ ID NO: 158), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 25 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01273 polypeptide having the sequence of amino acid residues from about 21 to about 163, inclusive of Figure 96 (SEQ ID NO: 158), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most 30 preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 21 to about 163, inclusive of Figure 96 (SEQ ID NO: 158), or (b) the 35 complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1273 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 135 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1273 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01273 polypeptide, which in one 5 embodiment, includes an amino acid sequence comprising residues 21 through 163 of Figure 96 (SEQ ID NO: 158).

In another aspect, the invention concerns an isolated PR01273 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at.least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 10 sequence of amino acid residues 21 to about 163, inclusive of Figure 96 (SEQ ID NO: 158).

In a further aspect, the invention concerns an isolated PROI273 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 21 through 163 of Figure 96 (SEQ ID NO: 158).

In yet another aspect, the invention concerns an isolated PRO1273 polypeptide, comprising the sequence of amino acid residues 21 to about 163, inclusive of Figure 96 (SEQ ID NO: 158), or a fragment thereof sufficient to provide a binding site for an anti-PR01273 antibody. Preferably, the PR01273 fragment retains a qualitative biological activity of a native PR01273 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 20 molecule under stringent conditions with (a) a DNA molecule encoding a PR01273 polypeptide having the sequence of amino acid residues from about 21 to about 163, inclusive of Figure 96 (SEQ ID NO: 158), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising 25 the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1273 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01273 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a 30 native PR01273 polypeptide, by contacting the native PR01273 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01273 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 49. PRQ1302 A cDNA clone (DNA65403-1565) has been identified that encodes a novel polypeptide having sequence identity with CD33 and designated in the present application as "PRO 1302." 136 In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01302 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01302 polypeptide having 5 the sequence of amino acid residues from 1 or about 16 to about 463, inclusive of Figure 98 (SEQ ID NO: 160), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01302 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 88 and about 1431, inclusive, of Figure 97 (SEQ ID NO: 159). Preferably, hybridization occurs under stringent 10 hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203230 15 (DNA65403-1565), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203230 (DNA65403-1565).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence 20 identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 16 to about 463, inclusive of Figure 98 (SEQ ID NO: 160), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule 25 under stringent conditions with (a) a DNA molecule encoding a PRO1302 polypeptide having the sequence of amino acid residues from about 16 to about 463, inclusive of Figure 98 (SEQ ID NO: 160), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule. 30 In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01302 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted (or truncated form) or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 15 in the sequence of Figure 98 (SEQ ID NO: 160). 35 The transmembrane domain has been tentatively identified as extending from about amino acid position 351 through about amino acid position 370 in the PRO 1302 amino acid sequence (Figure 98, SEQ ID N0:160).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 137 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 16 to about 463, inclusive of Figure 98 (SEQ ID NO: 160), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO 1302 polypeptide coding sequence that may find 5 use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PROI302 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PROl302 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 16 through 463 of Figure 98 (SEQ ID NO: 160).

In another aspect, the invention concerns an isolated PR01302 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more 15 preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 16 to about 463, inclusive of Figure 98 (SEQ ID NO: 160).

In a further aspect, the invention concerns an isolated PR01302 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence 20 of residues 16 through 463 of Figure 98 (SEQ ID NO: 160).

In yet another aspect, the invention concerns an isolated PRO 1302 polypeptide, comprising the sequence of amino acid residues 16 to about 463, inclusive of Figure 98 (SEQ ID NO: 160), or a fragment thereof sufficient to provide a binding site for an anti-PR01302 antibody. Preferably, the PR01302 fragment retains a qualitative biological activity of a native PR01302 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1302 polypeptide having the sequence of amino acid residues from about 16 to about 463, inclusive of Figure 98 (SEQ ID NO: 160), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence 30 identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01302 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01302 antibody. 35 In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01302 polypeptide, by contacting the native PR01302 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide. 138 In a still further embodiment, the invention concerns a composition comprising a PROl 302 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 50. PRQ1283 A cDNA clone (DNA65404-1551) has been identified, having homology to nucleic acid encoding 5 odorant binding protein, that encodes a novel polypeptide, designated in the present application as " PRO1283".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01283 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 10 preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01283 polypeptide having the sequence of amino acid residues from about 1 or about 18 to about 170, inclusive of Figure 100 (SEQ ID NO: 162), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1283 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 45 15 or about 96 and about 554, inclusive, of Figure 99 (SEQ ID NO: 161). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule 20 encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203244 (DNA65404-1551) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203244 (DNA65404-1551).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 25 encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 18 to about 170, inclusive of Figure 100 (SEQ ID NO: 162), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 30 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01283 polypeptide having the sequence of amino acid residues from 1 or about 18 to about 170, inclusive of Figure 100 (SEQ ID NO: 162), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence 35 identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01283 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is 139 complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 17 in the sequence of Figure 100 (SEQ ID NO: 162).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 5 preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 18 to about 170, inclusive of Figure 100 (SEQ ID NO: 162), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01283 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 10 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 99 (SEQ ID NO: 161).

In another embodiment, the invention provides isolated PR01283 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PRO1283 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 18 to about 170 of Figure 100 (SEQ ID NO: 162).

In another aspect, the invention concerns an isolated PRO1283 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more 20 preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 18 to about 170, inclusive of Figure 100 (SEQ ID NO: 162).

In a further aspect, the invention concerns an isolated PR01283 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence 25 of residues 1 or about 18 to about 170, inclusive of Figure 100 (SEQ ID NO: 162).

In yet another aspect, the invention concerns an isolated PRO 1283 polypeptide, comprising the sequence of amino acid residues 1 or about 18 to about 170, inclusive of Figure 100 (SEQ ID NO: 162), or a fragment thereof sufficient to provide a binding site for an anti-PR01283 antibody. Preferably, the PR01283 fragment retains a qualitative biological activity of a native PR01283 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01283 polypeptide having the sequence of amino acid residues from about 1 or about 18 to about 170, inclusive of Figure 100 (SEQ ID NO: 162), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 35 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. 140 In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1283 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01283 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01283 polypeptide by contacting the native PR01283 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01283 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 51. PROl 279 A cDNA clone (DNA65405-1547) has been identified, having homology to nucleic acid encoding 10 neuropsin that encodes a novel polypeptide, designated in the present application as "PR01279".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01279 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 15 preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01279 polypeptide having the sequence of amino acid residues from about 1 or about 19 to about 250, inclusive of Figure 102 (SEQ ID NO: 170), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01279 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 106 20 or about 160 and about 855, inclusive, of Figure 101 (SEQ ID NO: 169). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule 25 encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203476 (DNA65405-1547) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203476 (DNA65405-1547).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 30 encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 19 to about 250, inclusive of Figure 102 (SEQ ID NO: 170), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 100 35 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01279 polypeptide having the sequence of amino acid residues from 1 or about 19 to about 250, inclusive of Figure 102 (SEQ ID NO: 170), or (b) the complement of the DNA molecule of (a), and, 141 if the DNA molecuie has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01279 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is 5 complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 18 in the sequence of Figure 102 (SEQ ID NO: 170).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 10 preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 19 to about 250, inclusive of Figure 102 (SEQ ID NO: 170), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01279 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 15 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 101 (SEQ ID NO: 169).

In another embodiment, the invention provides isolated PRO 1279 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PROI279 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 19 to about 250 of Figure 102 (SEQ ID NO: 170).

In another aspect, the invention concerns an isolated PR01279 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more 25 preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 19 to about 250, inclusive of Figure 102 (SEQ ID NO: 170).

In a further aspect, the invention concerns an isolated PR01279polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence 30 of residues 1 or about 19 to about 250, inclusive of Figure 102 (SEQ ID NO: 170).

In yet another aspect, the invention concerns an isolated PR01279 polypeptide, comprising the sequence of amino acid residues 1 or about 19 to about 250, inclusive of Figure 102 (SEQ ID NO: 170), or a fragment thereof sufficient to provide a binding site for an anti-PR01279 antibody. Preferably, the PRO1279 fragment retains a qualitative biological activity of a native PR01279 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01279 polypeptide having the sequence of amino acid residues from about 1 or about 19 to about 250, inclusive of Figure 102 (SEQ ID 142 NO: 170), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1279 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01279 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01279 polypeptide by contacting the native PR01279 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01279 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier.

S3. PRQ1317 A cDNA clone (DNA65408-1578) has been identified that encodes a novel secreted polypeptide that IS shares homology with human CD97. The novel polypeptide is designated in the present application as "PR01317".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01317 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 20 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01317 polypeptide having the sequence of amino acid residues from 1 or about 19 to about 74, inclusive of Figure 106 (SEQ ID NO: 189), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01317 25 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 60 and about 227, inclusive, of Figure 105 (SEQ ID NO: 188). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 30 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203217 (DNA65408-1578), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203217 (DNA65408-1578). ; , 143 ^followed by page 146) INTELLECTUAL PROPERTY OFRCE OF IM.Z 24 OCT 2003 received In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 19 to about 74, inclusive of Figure 106 (SEQ ID NO: 189), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01317 polypeptide having the sequence of amino acid residues from about 19 to about 74, inclusive of Figure 106 (SEQ ID NO: 189), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, 10 preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01317 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as 15 extending from amino acid position 1 through about amino acid position 18 in the sequence of Figure 106 (SEQ ID NO: 189).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 20 amino acid sequence of residues 19 to about 74, inclusive of Figure 106 (SEQ ID NO: 189), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01317 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 25 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01317 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01317 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 19 to 74 of Figure 106 (SEQ ID NO: 189). 30 In another aspect, the invention concerns an isolated PR01317 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 19 to about 74, inclusive of Figure 106 (SEQ ID NO: 189).

In a further aspect, the invention concerns an isolated PROI317 polypeptide, comprising an amino acid 35 sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 19 to 74 of Figure 106 (SEQ ID NO: 189). 146 In yet another aspect, the invention concerns an isolated PRO 1317 polypeptide, comprising the sequence of amino acid residues 19 to about 74, inclusive of Figure 106 (SEQ ID NO: 189), or a fragment thereof sufficient to provide a binding site for an anti-PR01317 antibody. Preferably, the PR01317 fragment retains a qualitative biological activity of a native PR01317 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 5 molecule under stringent conditions with (a) a DNA molecule encoding a PR01317 polypeptide having the sequence of amino acid residues from about 19 to about 74, inclusive of Figure 106 (SEQ ID NO: 189), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising 10 the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. 55. PRQ1306 o A cDNA clone (DNA65410-1569) has been identified that encodes a novel polypeptide having homology to AIFl/daintain and designated in the present application as "PR01306".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01306 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01306 polypeptide having the sequence of amino acid residues from about 1 to about 150, inclusive of Figure 110 (SEQ ID NO: 196), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01306 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 106 and about 555, inclusive, of Figure 109 (SEQ ID NO: 195). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203231 (DNA65410-1569), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203231 (DNA65410-1569).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 150, inclusive of Figure 110 (SEQ ID NO: 196), or the complement of the DNA of (a). 147 (followed by page 150) INTELLECTUAL PROPERTY OFRCE OF N.Z 2 4 OCT 2003 received In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1306 polypeptide having the sequence of amino acid residues from about 1 to about 150, inclusive of Figure 110 (SEQ ID NO: 196), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, 5 preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 10 amino acid sequence of residues 1 to about 150, inclusive of Figure 110 (SEQ ID NO: 196), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1306 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 15 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01306 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO 1306 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 150 of Figure 110 (SEQ ID NO:196). 20 In another aspect, the invention concerns an isolated PRO 1306 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 150, inclusive of Figure 110 (SEQ ID NO: 196).

In a further aspect, the invention concerns an isolated PRO1306 polypeptide, comprising an amino acid 25 sequence scoring at least about 80% positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to 150 of Figure 110 (SEQ ID NO:196).

In yet another aspect, the invention concerns an isolated PRO1306 polypeptide, comprising the sequence of amino acid residues 1 to about 150, inclusive of Figure 110 (SEQ ID NO: 196), or a fragment thereof 30 sufficient to provide a binding site for an anti-PR01306 antibody. Preferably, the PR01306 fragment retains a qualitative biological activity of a native PR01306 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1306 polypeptide having the sequence of amino acid residues from about 1 to about 150, inclusive of Figure 110 (SEQ ID NO: 196), or (b) 35 the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising 150 the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01306 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01306 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a 5 native PR01306 polypeptide, by contacting the native PR01306 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01306 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 56. PRQ1336 A cDNA clone (DNA65423-1595) has been identified that encodes a novel polypeptide having sequence identity with slit and designated in the present application as "PRO 1336." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01336 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01336 polypeptide having the sequence of amino acid residues from 1 or about 28 to about 1523, inclusive of Figure 112 (SEQ ID NO: 198), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01336 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 164 and about 4651, inclusive, ofFigures lllA-B(SEQIDNO:197). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 25 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203227 (DNA65423-1595), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC 30 Deposit No. 203227 (DNA65423-1595).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 28 to about 1523, inclusive of Figure 112 (SEQ ID 35 NO: 198), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule 151 under stringent conditions with (a) a DNA molecule encoding a PRO 1336 polypeptide having the sequence of amino acid residues from about 28 to about 1523, inclusive of Figure 112 (SEQ ID NO: 198), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 28 to about 1523, inclusive of Figure 112 (SEQ ID NO: 198), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01336 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO 1336 polypeptide encoded by any of the 15 isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO 1336 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 28 through 1523 of Figure 112 (SEQ ID NO:198).

In another aspect, the invention concerns an isolated PR01336 polypeptide, comprising an amino acid 20 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 28 to about 1523, inclusive of Figure 112 (SEQ ID N0:198).

In a further aspect, the invention concerns an isolated PRO1336 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least 25 about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 28 through 1523 of Figure 112 (SEQ ID NO: 198).

In yet another aspect, the invention concerns an isolated PR01336 polypeptide, comprising the sequence of amino acid residues 28 to about 1523, inclusive of Figure 112 (SEQ ID NO: 198), or a fragment thereof sufficient to provide a binding site for an anti-PR01336 antibody. Preferably, the PR01336 fragment retains 30 a qualitative biological activity of a native PR01336 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01336 polypeptide having the sequence of amino acid residues from about 28 to about 1523, inclusive of Figure 112 (SEQ ID NO: 198), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% 35 sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) 152 recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01336 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01336 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01336 polypeptide, by contacting the native PROI336 polypeptide with a candidate molecule and 5 monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO 1336 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 57. PRQ1278 A cDNA clone (DNA66304-1546) has been identified that encodes a novel polypeptidehavinghomology to lysozyme C and designated in the present application as "PR01278." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01278 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 15 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01278 polypeptide having the sequence of amino acid residues from 1 or about 20 to about 148, inclusive of Figure 114 (SEQ ID N0:203), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01278 20 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 198 and about 584, inclusive, of Figure 113 (SEQ ID N0:202). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 25 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203321 (DNA66304-1546), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203321 (DNA66304-1546).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 20 to about 148, inclusive of Figure 114 (SEQ ID N0:203), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01278 polypeptide having the sequence of 153 amino acid residues from about 20 to about 148, inclusive of Figure 114 (SEQ ID N0:203), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding 5 a PR01278 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 19 in the sequence of Figure 114 (SEQ ID N0:203).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 10 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 20 to about 148, inclusive of Figure 114 (SEQ ID N0:203), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO 1278 polypeptide coding sequence that may find 15 use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01278 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO1278 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 20 to 148 of Figure 114 (SEQ ID N0:203).

In another aspect, the invention concerns an isolated PRO1278 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 25 sequence of amino acid residues 20 to about 148, inclusive of Figure 114 (SEQ ID N0:203).

In a further aspect, the invention concerns an isolated PR01278 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 20 to 148 of Figure 114 (SEQ ID N0:203).

In yet another aspect, the invention concerns an isolated PR01278 polypeptide, comprising the sequence of amino acid residues 20 to about 148, inclusive of Figure 114 (SEQ ID N0:203), or a fragment thereof sufficient to provide a binding site for an anti-PR01278 antibody. Preferably, the PR01278 fragment retains a qualitative biological activity of a native PRO1278 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 35 molecule under stringent conditions with (a) a DNA molecuie encoding a PROI278 polypeptide having the sequence of amino acid residues from about 20 to about 148, inclusive of Figure 114 (SEQ ID N0:203), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence 154 identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1278 5 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01278 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PRO 1278 polypeptide, by contacting the native PRO 1278 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO 1278 polypeptide, 10 or an agonist or antagonist as hereinabove defmed, in combination with a pharmaceuticaliy acceptable carrier. 58. PRQ1298 A cDNA clone (DNA66511-1563) has been identified that encodes a novel polypeptide having sequence identity with glycosyltransferases and designated in the present application as "PR01298." 15 In one embodiment, the invention provides an isolated nucleic acid molecuie comprising DNA encoding a PR01298 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01298 polypeptide having 20 the sequence of amino acid residues from 1 or about 16 to about 323, inclusive of Figure 116 (SEQ ID N0:210), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01298 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 139 and about 1062, inclusive, of Figure 115 (SEQ ID N0:209). Preferably, hybridization occurs under stringent 25 hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203228 30 (DNA66511-1563), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203228 (DNA66511-1563).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence 35 identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 16 to about 323, inclusive of Figure 116 (SEQ ID N0:210), or the complement of the DNA of (a). 155 In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1298 polypeptide having the sequence of amino acid residues from about 16 to about 323, inclusive of Figure 116 (SEQ ID N0:210), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, 5 preferably at least about an 85% sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 10 amino acid sequence of residues 16 to about 323, inclusive of Figure 116 (SEQ ID N0:210), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01298 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 15 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01298 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO1298 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 16 through 323 of Figure 116 (SEQ ID 20 N0:210).

In another aspect, the invention concerns an isolated PRO1298 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 16 to about 323, inclusive of Figure 116 (SEQ ID N0:210). 25 In a further aspect, the invention concerns an isolated PRO1298 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 16 through 323 of Figure 116 (SEQ ID N0:210).

In yet another aspect, the invention concerns an isolated PRO1298 polypeptide, comprising the sequence 30 of amino acid residues 16 to about 323, inclusive of Figure 116 (SEQ ID N0:210), or a fragment thereof sufficient to provide a binding site for an anti-PR01298 antibody. Preferably, the PR01298 fragment retains a qualitative biological activity of a native PRO 1298 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01298 polypeptide having the 35 sequence of amino acid residues from about 16 to about 323, inclusive of Figure 116 (SEQ ID N0:210), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence 156 identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. in yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1298 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01298 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01298 polypeptide, by contacting the native PR01298 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO 1298 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 59. PRQ1301 A cDN A clone (DN A66512-1564) has been identified that encodes a novel polypeptide having homology to cytochrome P450 and designated in the present application as "PR01301." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding 15 a PR01301 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01301 polypeptide having the sequence of amino acid residues from 1 or about 19 to about 462, inclusive of Figure 118(SEQIDNO:212), 20 or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1301 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 97 and about 1428, inclusive, of Figure 117 (SEQ ID NO:211). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203218 (DNA66512-1564), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic 30 acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203218 (DNA66512-1564).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence 35 identity to the sequence of amino acid residues from about 19 to about 462, inclusive of Figure 118 (SEQ ID NO:212), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 157 PCMJS99/20I11 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecuie encoding a PRO 1301 polypeptide having the sequence of amino acid residues from about 19 to about 462, inclusive of Figure 118 (SEQ ID N0:212), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most 5 preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1301 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 10 through about amino acid position 18 in the sequence of Figure 118 (SEQ ID NO:212). The transmembrane domain has been tentatively identified as extending from about amino acid position 271 through about amino acid position 290 in the PR01301 amino acid sequence (Figure 118, SEQ ID NO:212).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 15 preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 19 to about 462, inclusive of Figure 118 (SEQ ID NO:212), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO 1301 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 20 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01301 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

Inaspecific aspect, the invention provides isolated native sequence PR01301 polypeptide, which in one 25 embodiment, includes an amino acid sequence comprising residues 19 to 462 of Figure 118 (SEQ ID N0:212).

In another aspect, the invention concerns an isolated PR01301 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 19 to about 462, inclusive of Figure 118 (SEQ ID N0:212). 30 In a further aspect, the invention concerns an isolated PRO 1301 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 19 to 462 of Figure 118 (SEQ ID NO:212).

In yet another aspect, the invention concerns an isolated PR01301 polypeptide, comprising the sequence 35 of amino acid residues 19 to about 462, inclusive of Figure 118 (SEQ ID NO:212), or a fragment thereof sufficient to provide a binding site for an anti-PR01301 antibody. Preferably, the PR01301 fragment retains a qualitative biological activity of a native PR01301 polypeptide. 158 In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01301 polypeptide having the sequence of amino acid residues from about 19 to about 462, inclusive of Figure 118 (SEQ ID NO:212), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence 5 identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. 60. PRQ1268 A cDNA clone (DNA66519-1535) has been identified that encodes a novel transmembrane polypeptide designated in the present application as "PR01268." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1268 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 15 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1268 polypeptide having the sequence of amino acid residues from about 1 to about 140, inclusive of Figure 120 (SEQ ID NO:214), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1268 20 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 89 and about 508, inclusive, of Figure 119 (SEQ ID NO:213). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 25 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203236 (DNA66519-1535), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203236 (DNA66519-1535).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 140, inclusive of Figure 120 (SEQ ID NO:214), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01268 polypeptide having the sequence of 159 WO 00/12708 PCT/US99/20111 amino acid residues from about 1 to about 140, inclusive of Figure 120 (SEQ ID NO:214), or (b) the complement of the DNA molecule of (a), and, if the DNA molecuie has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding 5 a PR01268 polypeptide, with one or more of its soluble, i.e. transmembrane, domains deleted or inactivated, or is complementary to such encoding nucleic acid molecule. Transmembrane domains has been tentatively identified at about amino acids 12-28 (type II), 51-66, and 107-124 in the PRO 1268 amino acid sequence (Figure 120, SEQ ID N0:214).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 10 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 140, inclusive of Figure 120 (SEQ ID NO:214), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1268 polypeptide coding sequence that may find 15 use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01268 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO1268 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 140 of Figure 120 (SEQ ID NO:214).

In another aspect, the invention concerns an isolated PR01268 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 25 sequence of amino acid residues 1 to about 140, inclusive of Figure 120 (SEQ ID NO:214).

In a further aspect, the invention concerns an isolated PRO1268 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to 140 of Figure 120 (SEQ ID NO:214).

In yet another aspect, the invention concerns an isolated PR01268 polypeptide, comprising the sequence of amino acid residues 1 to about 140, inclusive of Figure 120 (SEQ ID NO:214), or a fragment thereof sufficient to provide a binding site for an anti-PR01268 antibody. Preferably, the PRO1268 fragment retains a qualitative biological activity of a native PR01268 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 35 molecule under stringent conditions with (a) a DNA moiecule encoding a PR01268 polypeptide having the sequence of amino acid residues from about 1 to about 140, inclusive of Figure 120 (SEQ ID NO:214), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence 160 identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. 61. PRQ1269 A cDNA clone (DNA66520-1536) has been identified thatencodesa novel polypeptide having homology to granulocyte peptide A and designated in the present application as "PR01269." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1269 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1269 polypeptide having the sequence of amino acid residues from 1 or about 21 to about 196, inclusive of Figure 122 (SEQ ID NO:2I6), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01269 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 86 and about 613, inclusive, of Figure 121 (SEQ ID NO:215). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 20 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203226 (DNA66520-1536), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC 25 Deposit No. 203226 (DNA66520-1536).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 21 to about 196, inclusive of Figure 122 (SEQ ID 30 NO:216), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01269 polypeptide having the sequence of amino acid residues from about 21 to about 196, inclusive of Figure 122 (SEQ ID NO:216), or (b) the 35 complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule. 161 WO 00/12708 PCT/US99/20111 In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01269 polypeptide, with or without the N-teraiinal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 20 in the sequence of Figure 122 (SEQ ID NO:216).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 21 to about 196, inclusive of Figure 122 (SEQ ID NO:21)6, or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1269 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO 1269 polypeptide encoded by any of the 15 isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01269 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 21 to 196 of Figure 122 (SEQ ID NO:216).

In another aspect, the invention concerns an isolated PRO1269 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more 20 preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 21 to about 196, inclusive of Figure 122 (SEQ ID NO:216).

In a further aspect, the invention concerns an isolated PR01269 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence 25 of residues 21 to 196 of Figure 122 (SEQ ID NO:216).

In yet another aspect, the invention concerns an isolated PRO1269 polypeptide, comprising the sequence of amino acid residues 21 to about 196, inclusive of Figure 122 (SEQ ID NO:216), or a fragment thereof sufficient to provide a binding site for an anti-PR01269 antibody. Preferably, the PR01269 fragment retains a qualitative biological activity of a native PRO 1269 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1269 polypeptide having the sequence of amino acid residues from about 21 to about 196, inclusive of Figure 122 (SEQ ID NO:216), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence 35 identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. 162 In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1269 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01269 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01269 polypeptide, by contacting the native PR01269 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1269 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 62. PRQ1327 A cDNA clone (DNA66521-1583) has been identified, having homology to nucleic acid encoding 10 neurexoplilin, that encodes a novel polypeptide, designated in the present application as "PR01327".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01327 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 15 preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1327 polypeptide having the sequence of amino acid residues from about 1 or about 15 to about 252, inclusive of Figure 124 (SEQ ID NO:218), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01327 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 55 20 or about 97 and about 810, inclusive, of Figure 123 (SEQ ID NO:217). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule 25 encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203225 (DNA66521-1583) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203225 (DNA66521-1583).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 30 encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 15 to about 252, inclusive of Figure 124 (SEQ ID NO:218), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 260 35 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01327 polypeptide having the sequence of amino acid residues from 1 or about 15 to about 252, inclusive of Figure 124 (SEQ ID NO:218), or (b) the complement of the DNA molecule of (a), and, 163 WO 00/12708 PCT/US99/20111 if the DNA molecule has at least about an 80% sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01327 polypeptide, with or without the N-teiminal signal sequence and/or the initiating methionine, or is 5 complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 14 in the sequence of Figure 124 (SEQ ID NO:218).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 10 preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 15 to about 252, inclusive of Figure 124 (SEQ ID NO:218), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1327 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 15 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 123 (SEQ ID NO:217).

In another embodiment, the invention provides isolated PR01327 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01327 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 15 to about 252 of Figure 124 (SEQ ID NO:218).

In another aspect, the invention concerns an isolated PR01327 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more 25 preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 15 to about 252, inclusive of Figure 124 (SEQ ID NO:218).

In a further aspect, the invention concerns an isolated PRO1327 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence 30 of residues 1 or about 15 to about 252, inclusive of Figure 124 (SEQ ID NO:218).

In yet another aspect, the invention concerns an isolated PRO1327 polypeptide, comprising the sequence of amino acid residues 1 or about 15 to about 252, inclusive of Figure 124 (SEQ ID NO:218), or a fragment thereof sufficient to provide a binding site for an anti-PR01327 antibody. Preferably, the PR01327 fragment retains a qualitative biological activity of a native PR01327 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01327 polypeptide having the sequence of amino acid residues from about 1 or about 15 to about 252, inclusive of Figure 124 (SEQ ID 164 PCMJS99/201U NO:218), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01327 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01327 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01327 polypeptide by contacting the native PR01327 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO 1327 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 63. PRQ1382 A cDNA clone (DNA66526-1616) has been identified that encodes a novel polypeptide having homology 15 to cerebellin and designated in the present application as "PR01382." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01382 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 20 preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01382 polypeptide having the sequence of amino acid residues from 1 or about 28 to about 201, inclusive of Figure 126 (SEQ ID N0:220), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01382 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 418 and 25 about 939, inclusive, of Figure 125 (SEQ ID NO:219). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecuie comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule 30 encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203246 (DNA66526-1616), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203246 (DNA66526-1616).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 35 encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 28 to about 201, inclusive of Figure 126 (SEQ ID 165 N0:220), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01382 polypeptide having the sequence of amino acid residues from about 28 to about 201, inclusive of Figure 126 (SEQ ID N0:220), or (b) the 5 complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1382 polypeptide, with or without the N-terminal signal sequence, or is complementary to such encoding 10 nucleic acid molecuie. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 27 in the sequence of Figure 126 (SEQ ID N0:220).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 15 amino acid sequence of residues 28 to about 201, inclusive of Figure 126 (SEQ ID N0:220), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01382 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 20 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1382 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO 1382 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 28 to 201 of Figure 126 (SEQ ID N0:220). 25 In another aspect, the invention concerns an isolated PRO 1382 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 28 to about 201, inclusive of Figure 126 (SEQ ID N0:220).

In a further aspect, the invention concerns an isolated PR01382 polypeptide, comprising an amino acid 30 sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 28 to 201 of Figure 126 (SEQ ID N0:220).

In yet another aspect, the invention concerns an isolated PRO1382 polypeptide, comprising the sequence of amino acid residues 28 to about 201, inclusive of Figure 126 (SEQ ID N0:220), or a fragment thereof 35 sufficient to provide a binding site for an anti-PR01382 antibody. Preferably, the PR01382 fragment retains a qualitative biological activity of a native PR01382 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 166 WO 00/12708 PCT/US99/20111 molecule under stringent conditions with (a) a DNA molecule encoding a PR01382 polypeptide having the sequence of amino acid residues from about 28 to about 201, inclusive of Figure 126 (SEQ ID N0.220), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising 5 the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1382 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PRO!382 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a 10 native PR01382 polypeptide, by contacting the native PR01382 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1382 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 64. PRQ1328 A cDNA clone (DNA66658-1584) has been identified that encodes a novel transmembrane polypeptide, designated in the present application as "PRO1328".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01328 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01328 polypeptide having the sequence of amino acid residues from about 1 or about 20 to about 257, inclusive of Figure 128 (SEQ ID NO:225), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01328 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 9 or about 66 and about 779, inclusive, of Figure 127 (SEQ ID NO:224). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 30 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203229 (DNA66658-1584) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in 35 ATCC Deposit No. 203229 (DNA66658-1584).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence 167 identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 20 to about 257, inclusive of Figure 128 (SEQ ID NO:225), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 475 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA 5 molecule encoding a PR01328 polypeptide having the sequence of amino acid residues from 1 or about 20 to about 257, inclusive of Figure 128 (SEQ ID NO:225), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1328 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 19 in the sequence of Figure 128 (SEQ ID NO:225). The transmembrane IS domains have been tentatively identified as extending from about amino acid position 32 to about amino acid position 51, from about amino acid position 119 to about amino acid position 138, from about amino acid position 152 to about amino acid position 169 and from about amino acid position 216 to about amino acid position 235 in the PR01328 amino acid sequence (Figure 128, SEQ ID NO:225).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 20 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 20 to about 257, inclusive of Figure 128 (SEQ ID NO:225), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01328 polypeptide coding sequence that may find 25 use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 127 (SEQ ID NO:224).

In another embodiment, the invention provides isolated PRO1328 polypeptide encoded by any of the 30 isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01328 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 20 to about 257 of Figure 128 (SEQ ID NO:225).

In another aspect, the invention concerns an isolated PR01328 polypeptide, comprising an amino acid 35 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 20 to about 257, inclusive of Figure 128 (SEQ ID NO:225). 168 In a further aspect, the invention concerns an isolated PR01328 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 20 to about 257, inclusive of Figure 128 (SEQ ID NO:225).

In yet another aspect, the invention concerns an isolated PR01328 polypeptide, comprising the sequence 5 of amino acid residues 1 or about 20 to about 257, inclusive of Figure 128 (SEQ ID NO:225), or a fragment thereof sufficient to provide a binding site for an anti-PR01328 antibody. Preferably, the PR01328 fragment retains a qualitative biological activity of a native PR01328 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01328 polypeptide having the 10 sequence of amino acid residues from about 1 or about 20 to about 257, inclusive of Figure 128 (SEQ ID NO:225), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) 15 recovering the polypeptide from the cell culture. 65. PROl 325 A cDNA clone (DNA66659-1593) has been identified that encodes a novel transmembrane polypeptide, designated in the present application as "PR01325".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01325 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1325 polypeptide having 25 the sequence of amino acid residues from about 1 or about 19 to about 832, inclusive of Figure 130 (SEQ ID NO:227), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01325 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 51 or about 105 and about 2546, inclusive, of Figure 129 (SEQ ID NO:226). Preferably, hybridization occurs 30 under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203269 35 (DNA66659-1593) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203269 (DNA66659-1593). 169 In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 19 to about 832, inclusive of Figure 130 (SEQ ID NO:227), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01325 polypeptide having the sequence of amino acid residues from 1 or about 19 to about 832, inclusive of Figure 130 (SEQ ID NO:227), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence 10 identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01325 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding 15 nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 18 in the sequence of Figure 130 (SEQ ID NO:227). The transmembrane domains have been tentatively identified as extending from about amino acid position 292 to about amino acid position 317, from about amino acid position 451 to about amino acid position 470, from about amino acid position 501 to about amino acid position 520, from about amino acid position 607 to about amino acid position 20 627 and from about amino acid position 751 to about amino acid position 770 in the PRO1325 amino acid sequence (Figure 130, SEQ ID NO:227).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 25 amino acid sequence of residues 1 or about 19 to about 832, inclusive of Figure 130 (SEQ ID NO:227), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1325 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 30 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 129 (SEQ ID NO:226).

In another embodiment, the invention provides isolated PRO 1325 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PRO1325 polypeptide, which in 35 certain embodiments, includes an amino acid sequence comprising residues 1 or about 19 to about 832 of Figure 130 (SEQ ID NO:227).

In another aspect, the invention concerns an isolated PRO1325 polypeptide, comprising an amino acid 170 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 19 to about 832, inclusive of Figure 130 (SEQ ID NO:227).

In a further aspect, the invention concerns an isolated PRO1325 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least 5 about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 19 to about 832, inclusive of Figure 130 (SEQ ID NO:227).

In yet another aspect, the invention concerns an isolated PRO 1325 polypeptide, comprising the sequence of amino acid residues 1 or about 19 to about 832, inclusive of Figure 130 (SEQ ID NO:227), or a fragment thereof sufficient to provide a binding site for an anti-PROl325 antibody. Preferably, the PR01325 fragment 10 retains a qualitative biological activity of a native PR01325 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1325 polypeptide having the sequence of amino acid residues from about 1 or about 19 to about 832, inclusive of Figure 130 (SEQ ID NO:227), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about 15 an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. 66. PRQ1340 A cDNA clone (DN A66663-1598) has been identified that encodes a novel polypeptide having homology to Ksp-cadherin and designated in the present application as "PR01340." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01340 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1340 polypeptide having the sequence of amino acid residues from 1 or about 19 to about 807, inclusive of Figure 132 (SEQ ID NO:229), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01340 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 182 and about 2548, inclusive, of Figure 131 (SEQ ID NO:228). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 35 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203268 171 (DNA66663-1598), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203268 (DNA66663-1598).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence 5 identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 19 to about 807, inclusive of Figure 132 (SEQ ID NO:229), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule 10 under stringent conditions with (a) a DNA molecule encoding a PRO1340 polypeptide having the sequence of amino acid residues from about 19 to about 807, inclusive of Figure 132 (SEQ ID NO:229), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule. 15 In a specific aspect, the invention provides an isolated nucleic acid molecuie comprising DNA encoding a PRO1340 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 18 in the sequence of Figure 132 (SEQ ID NO:229). The transmembrane 20 domain has been tentatively identified as extending from about amino acid position 762 to about amino acid position 784 in the PR01340 amino acid sequence (Figure 132, SEQ ID NO:229).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 25 amino acid sequence of residues 19 to about 807, inclusive of Figure 132 (SEQ ID NO:229), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1340 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 30 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01340 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01340 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 19 to 807 of Figure 132 (SEQ ID NO:229). 35 In another aspect, the invention concerns an isolated PR01340 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 172 PCT/US99/201H sequence of amino acid residues 19 to about 807, inclusive of Figure 132 (SEQ ID NO:229).

In a further aspect, the invention concerns an isolated PR01340 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 19 to 807 of Figure 132 (SEQ ID NO:229).

In yet another aspect, the invention concerns an isolated PRO1340 polypeptide, comprising the sequence of amino acid residues 19 to about 807, inclusive of Figure 132 (SEQ ID NO:229), or a fragment thereof sufficient to provide a binding site for an anti-PR01340 antibody. Preferably, the PR01340 fragment retains a qualitative biological activity of a native PRO 1340 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 10 molecule under stringent conditions with (a) a DNA molecule encoding a PRO1340 polypeptide having the sequence of amino acid residues from about 19 to about 807, inclusive of Figure 132 (SEQ ID N0.229), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising 15 the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01340 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01340 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a 20 native PR01340 polypeptide, by contacting the native PR01340 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1340 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 67. PRQ1339 A cDNA clone (DNA66669-1597) has been identified that encodes a novel polypeptide having sequence identity with carboxypepsidases and designated in the present application as "PR01339." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01339 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01339 polypeptide having the sequence of amino acid residues from 1 or about 17 to about 421, inclusive of Figure 134 (SEQ IDN0:234), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01339 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 58 and about 1271, inclusive, of Figure 133 (SEQ ID N0:233). Preferably, hybridization occurs under stringent 173 hybridization and wash conditions.

In a farther aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203272 5 (DNA66669-1597), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203272 (DNA66669-1597).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence 10 identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 17 to about 421, inclusive of Figure 134 (SEQ ID NO:234), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule 15 under stringent conditions with (a) a DNA molecule encoding a PR01339 polypeptide having the sequence of amino acid residues from about 17 to about 421, inclusive of Figure 134 (SEQ ID NO:234), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least abouta 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule. 20 In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 17 to about 421, inclusive of Figure 134 (SEQ ID NO:234), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01339 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01339 polypeptide encoded by any of the 30 isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01339 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 17 through 421 of Figure 134 (SEQ ID NO:234).

In another aspect, the invention concerns an isolated PRO 1339 polypeptide, comprising an amino acid 35 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 17 to about 421, inclusive of Figure 134 (SEQ ID N0:234). 174 PCT/US99/201U In a further aspect, the invention concerns an isolated PRO 1339 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 17 through 421 of Figure 134 (SEQ ID NO:234).

In yet another aspect, the invention concerns an isolated PRO1339 polypeptide, comprising the sequence 5 of amino acid residues 17 to about 421, inclusive of Figure 134 (SEQ ID NO:234), or a fragment thereof sufficient to provide a binding site for an anti-PR01339 antibody. Preferably, the PR01339 fragment retains a qualitative biological activity of a native PR01339 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1339 polypeptide having the 10 sequence of amino acid residues from about 17 to about 421, inclusive of Figure 134 (SEQ ID NO:234), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the 15 polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01339 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01339 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01339 polypeptide, by contacting the native PR01339 polypeptide with a candidate molecule and 20 monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1339 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 68. PRQ1337 A cDNA clone (DNA66672- I586)has been identified that encodes a novel polypeptide having homology to human thyroxine-binding globulin designated in die present application as "PR01337".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1337 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 30 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01337 polypeptide having the sequence of amino acid residues from 1 or about 21 to about 417, inclusive of Figure 136 (SEQ ID NO:236), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PROI337 35 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 120 and about 1310, inclusive, of Figure 135 (SEQ ID NO:235). Preferably, hybridization occurs under stringent hybridization and wash conditions. 175 In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203265 (DNA66672-66672), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic 5 acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203265 (DNA66672-66672).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence 10 identity to the sequence of amino acid residues from about 21 to about 417, inclusive of Figure 136 (SEQ ID NO:236), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1337 polypeptide having the sequence of 15 amino acid residues from about 21 to about 417, inclusive of Figure 136 (SEQ ID NO:236), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecuie.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding 20 a PR01337 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 20 in the sequence of Figure 136 (SEQ ID NO:236).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 25 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 21 to about 417, inclusive of Figure 136 (SEQ ID NO:236), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01337 polypeptide coding sequence that may find 30 use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1337 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01337 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 21 to 417 of Figure 136 (SEQ ID NO:236).

In another aspect, the invention concerns an isolated PRO1337 polypeptide, comprising an amino acid 176 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 21 to about 417, inclusive of Figure 136 (SEQ ID NO:236).

In a further aspect, the invention concerns an isolated PRO 1337 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least 5 about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 21 to 417 of Figure 136 (SEQ ID NO:236).

In yet another aspect, the invention concerns an isolated PRO1337 polypeptide, comprising the sequence of amino acid residues 21 to about 417, inclusive of Figure 136 (SEQ ID NO:236), or a fragment thereof sufficient to provide a binding site for an anti-PR01337 antibody. Preferably, the PRO 1337 fragment retains 10 a qualitative biological activity of a native PR01337 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01337 polypeptide having the sequence of amino acid residues from about 21 to about 417, inclusive of Figure 136 (SEQ ID NO:236), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence 15 identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01337 20 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01337 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01337 polypeptide, by contacting the native PR01337 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01337 polypeptide, 25 or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 69. PRQ1342 A cDNA clone (DNA66674-1599) has been identified that encodes a novel transmembrane polypeptide designated in the present application as "PR01342".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01342 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01342 polypeptide having 35 the sequence of amino acid residues from 1 or about 21 to about 596, inclusive of Figure 138 (SEQ ID NO:243), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01342 177 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 299 and about 2026, inclusive, of Figure 137 (SEQ ID NO:242). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 5 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203281 (DNA66674-1599), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203281 (DNA66674-1599).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 21 to about 596, inclusive of Figure 138 (SEQ ID NO:243), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01342 polypeptide having the sequence of amino acid residues from about 21 to about 596, inclusive of Figure 138 (SEQ ID NO:243), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, 20 preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01342 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble variants (i.e. transmembrane domain deleted or inactivated), or is complementary to such encoding 25 nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 20 in the sequence of Figure 138 (SEQ ID NO:243). The transmembrane domain has been tentatively identified as extending from about amino acid position 510 to about amino acid position 532 in the PR01342 amino acid sequence (Figure 138, SEQ ID NO:243).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 30 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 21 to about 596, inclusive of Figure 138 (SEQ ID NO:243), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1342 polypeptide coding sequence that may find 35 use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length. 178 In another embodiment, the invention provides isolated PRO1342 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO1342 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 21 to 596 of Figure 138 (SEQ ID N0.243).

In another aspect, the invention concerns an isolated PR01342 polypeptide, comprising an amino acid 5 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 21 to about 596, inclusive of Figure 138 (SEQ ID NO:243).

In a further aspect, the invention concerns an isolated PR01342 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least 10 about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 21 to 596 of Figure 138 (SEQ ID N0:243).

In yet another aspect, the invention concerns an isolated PRO1342 polypeptide, comprising the sequence of amino acid residues 21 to about 596, inclusive of Figure 138 (SEQ ID NO:243), or a fragment thereof sufficient to provide a binding site for an anti-PR01342 antibody. Preferably, the PR01342 fragment retains 15 a qualitative biological activity of a native PR01342 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01342 polypeptide having the sequence of amino acid residues from about 21 to about 596, inclusive of Figure 138 (SEQ ID NO:243), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence 20 identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. 70. PRQ1343 A cDNA clone (DNA66675-1587) has been identified that encodes a novel secreted polypeptide, designated in the present application as "PR01343".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01343 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01343 polypeptide having the sequence of ammo acid residues from about 1 or about 26 to about 247, inclusive of Figure 140 (SEQ ID NO:248), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1343 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 71 or about 146 and about 811, inclusive, of Figure 139(SEQIDNO:247). Preferably, hybridization occurs under 179 stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203282 5 (DNA66675-1587) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203282 (DNA66675-1587).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence 10 identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 247, inclusive of Figure 140 (SEQ ID NO:248), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA 15 molecule encoding a PRO 1343 polypeptide having the sequence of amino acid residues from 1 or about 26 to about 247, inclusive of Figure 140 (SEQ ID NO:248), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01343 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 25 in the sequence of Figure 140 (SEQ ID NO:248).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 26 to about 247, inclusive of Figure 140 (SEQ ID NO:248), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO 1343 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 139 (SEQ ID NO:247).

In another embodiment, the invention provides isolated PRO1343 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01343 polypeptide, which in 180 PCT/US99/201U certain embodiments, includes an amino acid sequence comprising residues 1 or about 26 to about 247 of Figure 140 (SEQ ID NO:248).

In another aspect, the invention concerns an isolated PR01343 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 5 sequence of amino acid residues 1 or about 26 to about 247, inclusive of Figure 140 (SEQ ID NO:248).

In a further aspect, the invention concerns an isolated PROI343 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues I or about 26 to about 247, inclusive of Figure 140 (SEQ ID NO:248).

In yet another aspect, the invention concerns an isolated PR01343 polypeptide, comprising the sequence of amino acid residues 1 or about 26 to about 247, inclusive of Figure 140 (SEQ ID NO:248), or a fragment thereof sufficient to provide a binding site for an anti-PR01343 antibody. Preferably, the PR01343 fragment retains a qualitative biological activity of a native PRO1343 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 15 molecule under stringent conditions with (a) a DNA molecule encoding a PR01343 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 247, inclusive of Figure 140 (SEQ ID NO:248), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host 20 cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. 71. PROI48Q A cDNA clone (DNA67962-1649) has been identified that encodes a novel polypeptide having homology 25 to Semaphorin C and designated in the present application as "PRO1480." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01480 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 30 preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1480 polypeptide having the sequence of amino acid residues from about 1 to about 837, inclusive of Figure 142 (SEQ ID NO:253), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01480 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 241 and 35 about 2751, inclusive, of Figure 141 (SEQ ID NO:252). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 181 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203291 (DNA67962-1649), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC 5 Deposit No. 203291 (DNA67962-1649).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 837, inclusive of Figure 142 (SEQ ID 10 NO:253), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01480 polypeptide having the sequence of amino acid residues from about 1 to about 837, inclusive of Figure 142 (SEQ ID NO:253), or (b) the 15 complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01480 polypeptide, its soluble variants, (i.e. transmembrane domains deleted or inactivated) or is 20 complementary to such encoding nucleic acid molecule. Transmembrane domains have been tentatively identified as extending from about amino acid position 23 to about amino acid position 46 (type II) and about amino acid position 718 to about amino acid position 738 in the PR01480 amino acid sequence (Figure 142, SEQ ID NO:253).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 25 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 837, inclusive of Figure 142 (SEQ ID NO:253), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1480 polypeptide coding sequence that may find 30 use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1480 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO 1480 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 837 of Figure 142 (SEQ ID NO:253).

In another aspect, the invention concerns an isolated PRO 1480 polypeptide, comprising an amino acid 182 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 837, inclusive of Figure 142 (SEQ ID NO:253).

In a further aspect, the invention concerns an isolated PR01480 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least 5 about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to 837 of Figure 142 (SEQ ID NO:253).

In yet another aspect, the invention concerns an isolated PRO1480 polypeptide, comprising the sequence of amino acid residues 1 to about 837, inclusive of Figure 142 (SEQ ID NO:253), or a fragment thereof sufficient to provide a binding site for an anti-PR01480 antibody. Preferably, the PR01480 fragment retains 10 a qualitative biological activity of a native PRO1480 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01480 polypeptide having the sequence of amino acid residues from about 1 to about 837, inclusive of Figure 142 (SEQ ID NO:253), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence 15 identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01480 20 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01480 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0148Q polypeptide, by contacting the native PR01480 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1480 polypeptide, 25 or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 72. PRQ1487 A cDNA clone (DNA68836-1656) has been identified that encodes a novel polypeptide having homology to fringe protein and designated in the present application as "PR01487".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1487 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01487 polypeptide having 35 the sequence of amino acid residues from 1 or about 24 to about 802, inclusive of Figure 144 (SEQ ID N0:260), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1487 183 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 558 and about 2894, inclusive, of Figures 143A-B (SEQ ID NO:259). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 5 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203455 (DNA68836-1656), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203455 (DNA68836-1656).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 24 to about 802, inclusive of Figure 144 (SEQ ID N0:260), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1487 polypeptide having the sequence of amino acid residues from about 24 to about 802, inclusive of Figure 144 (SEQ ID N0:260), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, 20 preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecuie.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01487 polypeptide, with or without the N-terminal signal sequence and/or the initiating, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as 25 extending from amino acid position 1 through about amino acid position 23 in the sequence of Figure 144 (SEQ ID N0:260).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 30 amino acid sequence of residues 24 to about 802, inclusive of Figure 144 (SEQ ID N0:260), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1487 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 35 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1487 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined. 184 In a specific aspect, the invention provides isolated native sequence PRO1487 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 24 to 802 of Figure 144 (SEQ ID N0:260).

In another aspect, the invention concerns an isolated PRO 1487 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 5 sequence of amino acid residues 24 to about 802, inclusive of Figure 144 (SEQ ID N0:260).

In a further aspect, the invention concerns an isolated PRO1487 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 24 to 802 of Figure 144 (SEQ ID N0:260).

In yet another aspect, the invention concerns an isolated PRO 1487 polypeptide, comprising the sequence of amino acid residues 24 to about 802, inclusive of Figure 144 (SEQ ID N0:260), or a fragment thereof sufficient to provide a binding site for an anti-PR01487 antibody. Preferably, the PR01487 fragment retains a qualitative biological activity of a native PRO1487 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 15 molecule under stringent conditions with (a) a DNA molecule encoding a PRO1487 polypeptide having the sequence of amino acid residues from about 24 to about 802, inclusive of Figure 144 (SEQ ID N0:260), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising 20 the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01487 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01487 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a 25 native PR01487 polypeptide, by contacting the native PR01487 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01487 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 73. PRQ1418 A cDNA clone (DNA68864-1629) has been identified that encodes a novel secreted polypeptide designated in the present application as "PRO 1418." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01418 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01418 polypeptide having 185 the sequence of amino acid residues from 1 or about 20 to about 350, inclusive of Figure 146 (SEQ ID NO:265), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concents an isolated nucleic acid molecule encoding a PR01418 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 195 and about 1187, inclusive, of Figure 145 (SEQ ID NO:264). Preferably, hybridization occurs under stringent 5 hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203276 10 (DNA68864-1629), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203276 (DNA68864-1629).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence 15 identity, moTe preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 20 to about 350, inclusive of Figure 146 (SEQ ID NO:265), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule 20 under stringent conditions with (a) a DNA molecule encoding a PR01418 polypeptide having the sequence of amino acid residues from about 20 to about 350, inclusive of Figure 146 (SEQ ID NO:265), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule. 25 In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 20 to about 350, inclusive of Figure 146 (SEQ ID NO:265), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01418 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01418 polypeptide encoded by any of the 35 isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01418 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 20 through 350 of Figure 146 (SEQ ID 186 NO:265).

In another aspect, the invention concerns an isolated PR01418 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 83% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 20 to about 350, inclusive of Figure 146 (SEQ ID NO:265).

In a further aspect, the invention concerns an isolated PR01418 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 20 through 350 of Figure 146 (SEQ ID NO:265).

In yet another aspect, the invention concerns an isolated PRO 1418 polypeptide, comprising the sequence 10 of amino acid residues 20 to about 350, inclusive of Figure 146 (SEQ ID NO:265), or a fragment thereof sufficient to provide a binding site for an anti-PR01418 antibody. Preferably, the PR01418 fragment retains a qualitative biological activity of a native PR01418 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01418 polypeptide having the 15 sequence of amino acid residues from about 20 to about 350, inclusive of Figure 146 (SEQ ID NO:265), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identiiy, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the 20 polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01418 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01418 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01418 polypeptide, by contacting the native PRO 1418 polypeptide with a candidate molecule and 25 monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO 1418 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 74. PRQ1472 A cDN A clone (DN A68866-1644) has been identified that encodes a novel polypeptide having sequence identity with butyrophilin and designated in the present application as "PR01472." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1472 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 35 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO1472 polypeptide having the sequence of amino acid residues from 1 or about 18 to about 466, inclusive of Figure 148 (SEQ ID NO:267), 187 or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01472 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 185 and about 1531, inclusive, of Figure 147 {SEQ ID NO:266). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203283 (DNA68866-1644), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic 10 acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203283 (DNA68866-1644).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence 15 identity to the sequence of amino acid residues from about 18 to about 466, inclusive of Figure 148 (SEQ ID NO:267), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01472 polypeptide having the sequence of 20 amino acid residues from about 18 to about 466, inclusive of Figure 148 (SEQ ID NO:267), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding 25 a PR01472 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domains deleted or inactivated variants, or is complementary to such encoding nucleic acid molecuie. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 1-17 in the sequence of Figure 148 (SEQ ID NO:267). The transmembrane domains have been tentatively identified as being from about amino acid position 131 through about amino acid 30 position 150 and from about amino acid position 235 through about amino acid position 259 in the PRO 1472 amino acid sequence (Figure 148, SEQ ID NO:267). It is understood that PR01472 can be manipulated to contain only particular regions given the information herein, e.g. to have only the extracellular or cytoplasmic regions only, or to have the carboxyl end truncated wherein the second transmembrane domain is deleted.

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 35 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 18 to about 466, inclusive of Figure 148 (SEQ ID NO:267), or (b) the 188 PCTAJS99/20111 complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1472 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01472 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO1472 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 18 through 466 of Figure 148 (SEQ ID N0:267).

In another aspect, the invention concerns an isolated PR01472 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 18 to about 466, inclusive of Figure 148 (SEQ ID NO:267).

In a further aspect, the invention concerns an isolated PR01472 polypeptide, comprising an amino acid 15 sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 18 through 466 of Figure 148 (SEQ ID NO:267).

In yet another aspect, the invention concerns an isolated PR01472polypeptide, comprising the sequence of amino acid residues 18 to about 466, inclusive of Figure 148 (SEQ ID NO:267), or a fragment thereof 20 sufficient to provide a binding site for an anti-PR01472 antibody. Preferably, the PRO1472 fragment retains a qualitative biological activity of a native PRO1472 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1472 polypeptide having the sequence of amino acid residues from about 18 to about 466, inclusive of Figure 148 (SEQ ID NO:267), or (b) 25 the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01472 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01472 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01472 polypeptide, by contacting the native PR01472 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01472 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 189 75. PROl 461 A cDNA clone (DNA68871-1638) has been identified that encodes a novel polypeptidehaving homology to serine protease and designated in the present application as "PR01461".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01461 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR0146I polypeptide having the sequence of amino acid residues from about 1 to about 423, inclusive of Figure 150 (SEQ ID NO:269), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01461 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 32 and about 1300, inclusive, of Figure 149 (SEQ ID NO:268). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 15 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203280 (DNA68871-68871), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC 20 Deposit No. 203280 (DNA68871-68871).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 423, inclusive of Figure 150 (SEQ ID 25 NO:269), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01461 polypeptide having the sequence of amino acid residues from about 1 to about 423, inclusive of Figure 150 (SEQ ID NO:269), or (b) the 30 complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01461 polypeptide, with or without the initiating methionine, and its soluble variants (i.e. transmembrane 35 domain deleted or inactivated), or is complementary to such encoding nucleic acid molecule. A type II transmembrane domain has been tentatively identified as extending from about amino acid position 21 to about amino acid position 40 in the PR01461 amino acid sequence (Figure 150, SEQ ID NO:269). 190 In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 423, inclusive of Figure 150 (SEQ ID NO:269), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO 2461 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01461 polypeptide encoded by any of the 10 isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO 1461 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 423 of Figure 150 (SEQ ID NO:269).

In another aspect, the invention concerns an isolated PR01461 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more 15 preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 423, inclusive of Figure 150 (SEQ ID NO:269).

In a further aspect, the invention concerns an isolated PR01461 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence 20 of residues 1 to 423 of Figure 150 (SEQ ID NO:269). in yet another aspect, the invention concerns an isolated PR01461 polypeptide, comprising the sequence of amino acid residues 1 to about 423, inclusive of Figure 150 (SEQ ID NO:269), or a fragment thereof sufficient to provide a binding site for an anti-PR01461 antibody. Preferably, the PR01461 fragment retains a qualitative biological activity of a native PR01461 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01461 polypeptide having the sequence of amino acid residues from about 1 to about 423, inclusive of Figure 150 (SEQ ID NO:269), or (b) the complement of the DNA molecuie of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence 30 identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1461 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01461 antibody. 35 In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01461 polypeptide, by contacting the native PR01461 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide. 191 In a still further embodiment, the invention concerns a composition comprising a PRO 1461 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 76. PRQ1410 A cDNA clone (DNA68874-1622) has been identified that encodes a novel transmembrane polypeptide, 5 designated in the present application as "PR01410".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01410 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 10 preferably at least about 95 % sequence identiiy to (a) a DNA molecule encoding a PR01410 polypeptide having the sequence of amino acid residues from about 1 or about 21 to about 238, inclusive of Figure 152 (SEQ ID NO:271), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1410 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 152 15 orabout212andabout865, inclusive, ofFigure 151 (SEQ ID N0:270). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule 20 encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203277 (DNA68874-1622) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203277 (DNA68874-1622).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 25 encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 21 to about 238, inclusive of Figure 152 (SEQ ID N0:271), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 100 30 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01410 polypeptide having the sequence of amino acid residues from 1 or about 21 to about 238, inclusive of Figure 152 (SEQ ID NO:271), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence 35 identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01410 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and 192 its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 20 in the sequence of Figure 152 (SEQ ID NO:271). The transmembrane domain has been tentatively identified as extending from about amino acid position 194 to about amino acid position 220 in the PROI410 amino acid sequence (Figure 152, SEQ ID NO:271).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 21 to about 238, inclusive of Figure 152 (SEQ ID NO:271), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO 1410 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 151 (SEQ ID N0.270).

In another embodiment, the invention provides isolated PR01410 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01410 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 21 to about 238 of Figure 152 (SEQ ID NO:271).

In another aspect, the invention concerns an isolated PRO 1410 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 21 to about 238, inclusive of Figure 152 (SEQ ID NO:271).

In a further aspect, the invention concerns an isolated PR01410 polypeptide, comprising an amino acid 25 sequence scoring at least about 80% positives, preferably at least about 85 % positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 21 to about 238, inclusive of Figure 152 (SEQ ID N0.271).

In yet another aspect, the invention concerns an isolated PR01410 polypeptide, comprising the sequence of amino acid residues 1 or about 21 to about 238, inclusive of Figure 152 (SEQ ID NO:271), or a fragment 30 thereof sufficient to provide a binding site for an anti-PROI410 antibody. Preferably, the PR01410 fragment retains a qualitative biological activity of a native PR01410 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01410 polypeptide having the sequence of amino acid residues from about 1 or about 21 to about 238, inclusive of Figure 152 (SEQ ID 35 NO:271), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host 193 ceil comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1410 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01410 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a 5 native PR01410 polypeptide by contacting the native PROI410 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO 1410 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 77. PRQ1568 A cDNA clone (DNA68880-1676) has been identified that encodes a novel polypeptide having sequence identity with tetraspanins and designated in the present application as "PR01568." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1568 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1568 polypeptide having the sequence of amino acid residues from 1 or about 34 to about 305, inclusive ofFigure 154 (SEQ ID NO:273), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1568 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 307 and about 1122, inclusive, of Figure 153 (SEQ ID NO:272). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 25 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably al least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203319 (DNA68880-1676), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC 30 Deposit No. 203319 (DNA68880-1676).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 34 to about 305, inclusive of Figure 154 (SEQ ID 35 NO:273), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule 194 under stringent conditions with (a) a DNA molecule encoding a PR01568 polypeptide having the sequence of amino acid residues from about 34 to about 305, inclusive of Figure 154 (SEQ ID NO:273), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

S In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01568 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 33 in the sequence of Figure 154 (SEQ ID NO:273). The transmembrane 10 domains have been tentatively identified as extending from about amino acids 12-35,57-86,94-114 and 226-248 in the PR01568 amino acid sequence (Figure 154, SEQ ID NO:273).

In another aspect, the invention concerns an isolated nucleic acid molecuie comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the 15 amino acid sequence of residues 34 to about 305, inclusive of Figure 154 (SEQ ID NO:273), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO 1568 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 20 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01568 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO1568 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 34 through 305 of Figure 154 (SEQ ID 25 NO:273).

In another aspect, the invention concerns an isolated PRO1568 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 34 to about 305, inclusive of Figure 154 (SEQ ID NO:273). 30 In a further aspect, the invention concerns an isolated PRO1568 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 34 through 305 of Figure 154 (SEQ ID N0.273).

In yet another aspect, the invention concerns an isolated PR01568 polypeptide, comprising the sequence 35 of amino acid residues 34 to about 305, inclusive of Figure 154 (SEQ ID N0:273), or a fragment thereof sufficient to provide a binding site for an anti-PR01568 antibody. Preferably, the PR01568 fragment retains a qualitative biological activity of a native PR01568 polypeptide. 195 In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1568 polypeptide having the sequence of amino acid residues from about 34 to about 305, inclusive of Figure 154 (SEQ ID NO:273), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence 5 identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01568 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01568 antibody. 10 In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01568 polypeptide, by contacting the native PR01568 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01568 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 78. FR01570 A cDNA clone (DNA68885-1678) has been identified that encodes a novel polypeptide having sequence identity with SP60 and designated in the present application as "PR01570." In particular, for the first time, Applicants have identified an additional 199 amino acids on the amino terminal end of the protein previously 20 identified as SP60.

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01570 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 25 preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO1570 polypeptide having the sequence of amino acid residues from about 1 to about 432, inclusive ofFigure 156 (SEQ ID N0:275), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01570 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 210 and 30 about 1505, inclusive, of Figure 155 (SEQ ID NO:274). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule 35 encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203311 (DNA68885-I678), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC 196 Deposit No. 203311 (DNA68885-1678).

In a stili further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 432, inclusive of Figure 156 (SEQ ID 5 NO:275), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01570 polypeptide having the sequence of amino acid residues from about 1 to about 432, inclusive of Figure 156 (SEQ ID NO:275), or (b) the 10 complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule. In a preferred embodiment, the probes provided herein are from the amino terminal end of the peptide identified in Figure 1, defined as amino acids 1-199 of SEQ ID NO:275.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01570 polypeptide, in a form which is secreted and is soluble, i.e. transmembrane domain deleted, truncated or inactivated variants.

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 20 preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 432, inclusive of Figure 156 (SEQ ID NO:275), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO 1570 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 25 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length. Preferably, the probes are from the amino terminal end as provided herein.

In another embodiment, the invention provides isolated PRO1570 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO1570 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 432 of Figure 156 (SEQ ID NO-.275).

In another aspect, the invention concerns an isolated PR01570 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more 35 preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 432, inclusive ofFigure 156 (SEQ ID NO:275).

In a further aspect, the invention concerns an isolated PRO 1570 polypeptide, comprising an amino acid 197 sequence scoring at least about 80% positives, preferably at least about 83% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 through 432 ofFigure 156 (SEQ ID NO:275).

In yet another aspect, the invention concerns an isolated PRO1570 polypeptide, comprising the sequence of amino acid residues 1 to about 432, inclusive of Figure 156 (SEQ ID NO:275), or a fragment thereof 5 sufficient to provide a binding site for an anti-PROl570 antibody. Preferably, the PRO1570 fragment retains a qualitative biological activity of a native PR01570 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01570 polypeptide having the sequence of amino acid residues from about 1 to about 432, inclusive of Figure 156 (SEQ ID NO:275), or (b) 10 the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 83% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01570 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01570 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01570 polypeptide, by contacting the native PR01570 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1570 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 79. PROl 317 A cDNA clone (DNA71166-1685) has been identified that encodes a novel polypeptide having homology 25 to semaphorin B and designated in the present application as "PR01317".

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 30 preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01317 polypeptide having the sequence of amino acid residues from 1 or about 31 to about 761, inclusive of Figure 158 (SEQ ID NO:277), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01317 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 195 and 35 about 2387, inclusive, of Figure 157 (SEQ ID NO:276). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 198 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203355 (DNA71166-1685), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC 5 Deposit No. 203355 (DNA71166-1685).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 31 to about 761, inclusive of Figure 158 (SEQ ID 10 NO:277), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01317 polypeptide having the sequence of amino acid residues from about 31 to about 761, inclusive of Figure 158 (SEQ ID NO:277), or (b) the 15 complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01317 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and 20 its soluble variants (i.e. transmembrane domains deleted or inactivated), or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 30 in the sequence of Figure 158 (SEQ ID NO:277). Transmembrane domains have been tentatively identified as extending from about amino acid positions 13-31,136-156,222-247, 474-490, and 685-704 in the PR01317 amino acid sequence (Figure 158, SEQ ID NO:277). 25 In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 31 to about 761, inclusive of Figure 158 (SEQ ID NO:277), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01317 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01317 polypeptide encoded by any of the 35 isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO 1317 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 31 to 761 of Figure 158 (SEQ ID NO:277). 199 In another aspect, the invention concerns an isolated PRO 1317 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 31 to about 761, inclusive of Figure 158 (SEQ ID NO:277).

In a further aspect, the invention concerns an isolated PR01317 polypeptide, comprising an amino acid 5 sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 31 to 761 ofFigure 158 (SEQ ID NO:277).

In yet another aspect, the invention concerns an isolated PR01317 polypeptide, comprising the sequence of amino acid residues 31 to about 761, inclusive of Figure 158 (SEQ ID NO:277), or a fragment thereof 10 sufficient to provide a binding site for an anti-PR01317 antibody. Preferably, the PR01317 fragment retains a qualitative biological activity of a native PR01317 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01317 polypeptide having the sequence of amino acid residues from about 31 to about 761, inclusive of Figure 158 (SEQ ID N0:277), or (b) 15 the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01317 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01317 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01317 polypeptide, by contacting the native PR01317 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01317 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 80. PRQ1780 A cDN A clone (DN A71169-1709) has been identified that encodes a novel polypeptide having homology 30 to glucuronosyltransferase and designated in the present application as "PRO1780".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01780 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 3 5 preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1780 polypeptide having the sequence of amino acid residues from 1 or about 20 to about 523, inclusive ofFigure 160 (SEQ ID NO-.282), or (b) the complement of the DNA molecule of (a). 200 In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1780 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 125 and about 1636, inclusive, of Figure 159 (SEQ ID N0.281). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 5 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203467 (DNA71169-1709), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC 10 Deposit No. 203467 (DNA71169-1709).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 20 to about 523, inclusive of Figure 160 (SEQ ID 15 NO:282), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1780 polypeptide having the sequence of amino acid residues from about 20 to about 523, inclusive of Figure 160 (SEQ ID NO:282), or (b) the complement of the 20 DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01780 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and 25 its soluble variants (i.e. transmembrane domain deleted or inactivated), or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 19 in the sequence of Figure 160 (SEQ ID NO:282). The transmembrane domain has been tentatively identified as extending from about amino acid position 483 to about amino acid position 504 in the PR01780 amino acid sequence (Figure 160, SEQ ID NO:282).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 20 to about 523, inclusive of Figure 160 (SEQ ID NO:282), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01780 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 201 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01780 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01780 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 20 to 523 ofFigure 160 (SEQ ID NO:282).

In another aspect, the invention concerns an isolated PRO 1780 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 20 to about 523, inclusive ofFigure 160 (SEQ ID NO:282).

In a further aspect, the invention concerns an isolated PRO 1780 polypeptide, comprising an amino acid 10 sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 20 to 523 of Figure 160 (SEQ ID NO:282).

In yet another aspect, the invention concerns an isolated PRO1780 polypeptide, comprising the sequence of amino acid residues 20 to about 523, inclusive of Figure 160 (SEQ ID NO:282), or a fragment thereof 15 sufficient to provide a binding site for an anti-PR01780 antibody. Preferably, the PR01780 fragment retains a qualitative biological activity of a native PR01780 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1780 polypeptide having the sequence of amino acid residues from about 20 to about 523, inclusive of Figure 160 (SEQ ID NO:282), or (b) 20 the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecuie under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01780 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01780 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PROI780 polypeptide, by contacting the native PR01780 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1780 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 81. PRQ1486 A cDNA clone (DNA71180-1655) has been identified that encodes a novel polypeptide having sequence 35 identity with cerebellin, particularly precerebellin, and designated in the present application as "PR01486." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01486 polypeptide. 202 PCT/US99/201H In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01486 polypeptide having the sequence of amino acid residues from 1 or about 33 to about 205, inclusive ofFigure 162 (SEQ ID NO:287), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01486 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 568 and about 1086, inclusive, of Figure 161 (SEQ ID NO:286). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 10 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203403 (DNA71180-1655), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC 15 Deposit No. 203403 (DNA71180-1655).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 33 to about 205, inclusive of Figure 162 (SEQ ID 20 N0:287), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01486 polypeptide having the sequence of amino acid residues from about 33 to about 205, inclusive of Figure 162 (SEQ ID NO:287), or (b) the 25 complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 30 preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 33 to about 205, inclusive of Figure 162 (SEQ ID NO:287), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO I486 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 35 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01486 polypeptide encoded by any of the 203 isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01486 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 33 through 205 of Figure 162 (SEQ ID NO:287).

In another aspect, the invention concerns an isolated PRO 1486 polypeptide, comprising an amino acid 5 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 33 to about 205, inclusive of Figure 162 (SEQ ID NO:287).

In a further aspect, the invention concerns an isolated PRO1486 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least 10 about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 33 through 205 of Figure 162 (SEQ ID NO:287).

In yet another aspect, the invention concerns an isolated PRO 1486 polypeptide, comprising the sequence of amino acid residues 33 to about 205, inclusive of Figure 162 (SEQ ID NO:287), or a fragment thereof sufficient to provide a binding site for an anti-PR01486 antibody. Preferably, the PR01486 fragment retains 15 a qualitative biological activity of a native PR01486 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1486 polypeptide having the sequence of amino acid residues from about 33 to about 205, inclusive ofFigure 162 (SEQ ID NO:287), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence 20 identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1486 25 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01486 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01486 polypeptide, by contacting the native PR01486 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1486 polypeptide, 30 or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 82. PRQ1433 A cDNA clone (DNA71184-1634) has been identified that encodes a novel transmembrane polypeptide, designated in the present application as "PR01433".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01433 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 204 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1433 polypeptide having the sequence of amino acid residues from about 1 to about 388, inclusive of Figure 164 (SEQ ID NO:292), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1433 5 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 185 and about 1348, inclusive, of Figure 163 (SEQ ID NO:291). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 10 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203266 (DNA71184-1634) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203266 (DNA7I184-1634).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 388, inclusive of Figure 164 (SEQ ID NO:292), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 250 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01433 polypeptide having the sequence of amino acid residues from 1 to about 388, inclusive of Figure 164 (SEQ ID NO:292), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more 25 preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01433 polypeptide, with or without the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane 30 domain has been tentatively identified as extending from about amino acid position 76 to about amino acid position 97 in the PR01433 amino acid sequence (Figure 164, SEQ ID NO:292).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 35 amino acid sequence of residues 1 to about 388, inclusive of Figure 164 (SEQ ID NO:292), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01433 polypeptide coding sequence that may find 205 use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 163 (SEQ ID NO:291).

In another embodiment, the invention provides isolated PR01433 polypeptide encoded by any of the 5 isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01433 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 to about 388 of Figure 164 (SEQ ID NO:292).

In another aspect, the invention concerns an isolated PR01433 polypeptide, comprising an amino acid 10 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 388, inclusive of Figure 164 (SEQ ID NO:292).

In a further aspect, the invention concerns an isolated PR01433 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least 15 about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 388, inclusive of Figure 164 (SEQ ID NO:292).

In yet another aspect, the invention concents an isolated PR01433 polypeptide, comprising the sequence of amino acid residues 1 to about 388, inclusive of Figure 164 (SEQ ID NO:292), or a fragment thereof sufficient to provide a binding site for an anti-PR01433 antibody. Preferably, the PR01433 fragment retains 20 a qualitative biological activity of a native PR01433 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01433 polypeptide having the sequence of amino acid residues from about 1 to about 388, inclusive of Figure 164 (SEQ ID NO:292), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence 25 identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01433 30 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01433 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01433 polypeptide by contacting the native PR01433 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1433 polypeptide, 35 or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 206 83. PRQ1490 A cDNA clone (DNA71213-1659) has been identified, having homology to nucleic acid encoding a 1-acyl-sn-glycerol-3-phosphate acyltransferase protein that encodes a novel polypeptide, designated in the present application as "PR01490".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding 5 a PRO1490 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01490 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 368, inclusive of Figure 166 (SEQ ID 10 NO:297), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1490 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 272 or about 347 and about 1375, inclusive, of Figure 165 (SEQ ID NO:296). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203401 (DNA71213-1659) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the 20 nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203401 (DNA71213-1659).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence 25 identity to the sequence of amino acid residues 1 or about 26 to about 368, inclusive of Figure 166 (SEQ ID NO:297), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 285 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01490 polypeptide having the sequence of amino acid residues from 1 or about 26 to 30 about 368, inclusive of Figure 166 (SEQ ID NO:297), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding 35 a PR01490 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid 207 position 1 to about amino acid position 25 in the sequence ofFigure 166 (SEQ ID NO:297). The transmembrane domains have been tentatively identified as extending from about amino acid position 307 to about amino acid position 323 and from about amino acid position 335 to about amino acid position 352 in the PRO1490 amino acid sequence (Figure 166, SEQ ID NO:297).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 5 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 26 to about 368, inclusive of Figure 166 (SEQ ID NO:297), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1490 polypeptide coding sequence that may find 10 use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 165 (SEQ ID NO:296).

In another embodiment, the invention provides isolated PR01490 polypeptide encoded by any of the 15 isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01490 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 26 to about 368 ofFigure 166 (SEQ ID NO:297).

In another aspect, the invention concerns an isolated PRO1490 polypeptide, comprising an amino acid 20 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 368, inclusive of Figure 166 (SEQ ID NO:297).

In a further aspect, the invention concerns an isolated PRO1490 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least 25 about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 26 to about 368, inclusive of Figure 166 (SEQ ID NO:297).

In yet another aspect, the invention concerns an isolated PR01490 polypeptide, comprising the sequence of amino acid residues 1 or about 26 to about 368, inclusive of Figure 166 (SEQ ID NO:297), or a fragment thereof sufficient to provide a binding site for an anti-PR01490 antibody. Preferably, the PR01490 fragment 30 retains a qualitative biological activity of a native PR01490 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01490 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 368, inclusive of Figure 166 (SEQ ID NO:297), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about 35 an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) 208 recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1490 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01490 antibody.

In a further embodiment, the invendon concerns a method of identifying agonists or antagonists of a native PR01490 polypeptide by contacting the native PR01490 polypeptide with a candidate molecule and 5 monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO 1490 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 84. PROl 482 A cDNA clone (DNA71234-1651) has been identified that encodes a novel secreted polypeptide, designated in the present application as "PRO1482".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1482 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 15 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01482 polypeptide having the sequence of amino acid residues from about 1 or about 29 to about 143, inclusive of Figure 168 (SEQ ID N0:302), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1482 20 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 33 orabout 117 and about 461, inclusive, ofFigure 167(SEQIDNO:301). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 25 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203402 (DNA71234-1651) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203402 (DNA71234-1651).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 29 to about 143, inclusive of Figure 168 (SEQ ID N0:302), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 260 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1482 polypeptide having the sequence of amino acid residues from 1 or about 29 to 209 about 143, inclusive ofFigure 168 (SEQ ID N0:302), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding 5 a PR01482 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 28 in the sequence of Figure 168 (SEQ ID N0:302).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 10 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 29 to about 143, inclusive of Figure 168 (SEQ ID N0:302), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01482polypeptide coding sequence that may find 15 use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 167 (SEQ ID N0:301).

In another embodiment, the invention provides isolated PR01482 polypeptide encoded by any of the 20 isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01482 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 29 to about 143 of Figure 168 (SEQ ID N0:302).

In another aspect, the invention concerns an isolated PR01482 polypeptide, comprising an amino acid 25 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 29 to about 143, inclusive of Figure 168 (SEQ ID N0:302).

In a further aspect, the invention concerns an isolated PRO 1482 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least 30 about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 29 to about 143, inclusive of Figure 168 (SEQ ID N0:302).

In yet another aspect, the invention concerns an isolated PR01482 polypeptide, comprising the sequence of amino acid residues 1 or about 29 to about 143, inclusive of Figure 168 (SEQ ID N0:302), or a fragment thereof sufficient to provide a binding site for an anti-PR01482 antibody. Preferably, the PR01482 fragment 35 retains a qualitative biological activity of a native PR01482 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01482 polypeptide having the 210 sequence of amino acid residues from about 1 or about 29 to about 143, inclusive of Figure 168 (SEQ ID N0:302), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) 5 recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01482 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01482 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01482 polypeptide by contacting the native PR01482 polypeptide with a candidate molecule and 10 monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01482 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a phanoaceutically acceptable carrier. 85. PRQ1446 A cDNA clone (DNA71277-1636) has been identified that encodes a novel secreted polypeptide designated in the present application as "PR01446." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1446 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 20 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01446 polypeptide having the sequence of amino acid residues from 1 or about 16 to about 109, inclusive ofFigure 170(SEQIDNO:304), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1446 25 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 197 and about 478, inclusive, of Figure 169 (SEQ ID N0:303). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 30 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203285 (DNA71277-1636), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203285 (DNA7I277-1636).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence 211 identity to the sequence of amino acid residues from about 16 to about 109, inclusive of Figure 170 (SEQ ID N0:304), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1446 polypeptide having the sequence of 5 amino acid residues from about 16 to about 109, inclusive of Figure 170 (SEQ ID N0:304), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 10 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 16 to about 109, inclusive of Figure 170 (SEQ ID N0:304), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01446 polypeptide coding sequence that may find 15 use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1446 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01446polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 16 through 109 of Figure 170 (SEQ ID N0:304).

In another aspect, the invention concerns an isolated PR01446 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more 25 preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 16 to about 109, inclusive of Figure 170 (SEQ ID N0.304).

In a further aspect, the invention concerns an isolated PR01446 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence 30 of residues 16 through 109 of Figure 170 (SEQ ID N0:304).

In yet another aspect, the invention concerns an isolated PR01446polypeptide, comprising the sequence of amino acid residues 16 to about 109, inclusive of Figure 170 (SEQ ID N0.304), or a fragment thereof sufficient to provide a binding site for an anti-PR01446 antibody. Preferably, the PR01446 fragment retains a qualitative biological activity of a native PR01446 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01446 polypeptide having the sequence of amino acid residues from about 16 to about 109, inclusive ofFigure 170 (SEQ ID N0:304), or (b) 212 PCTAJS99/20111 the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01446 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01446 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01446 polypeptide, by contacting the native PR01446 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO 1446 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 86. PRQ1S58 A cDNA clone (DNA71282-1668) has been identified, having homology to nucleic acid encoding 15 methyltransferase enzymes that encodes a novel polypeptide, designated in the present application as "PR01558".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01558 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 20 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identiiy to (a) a DNA molecule encoding a PR01558 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 262, inclusive of Figure 172 (SEQ ID N0:306), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1558 25 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 84 or about 159 and about 869, inclusive, ofFigure 171 (SEQ ID N0:305). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 30 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203312 (DNA71282-1668) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203312 (DNA7I282-1668).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence 213 identiiy to the sequence of amino acid residues 1 or about 26 to about 262, inclusive of Figure 172 (SEQ ID N0:306), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR015S8 polypeptide having the sequence of amino acid residues from 1 or about 26 to 5 about 262, inclusive of Figure 172 (SEQ ID N0:306), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding 10 a PR01558 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 25 in the sequence ofFigure 172 (SEQ ID N0:306). The transmembrane domains have been tentatively identified as extending from about amino acid position 8 to about amino acid 15 position 30 and from about amino acid position 109 to about amino acid position 130 in the PR01558 amino acid sequence (Figure 172, SEQ ID N0:306).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 20 amino acid sequence of residues 1 or about 26 to about 262, inclusive of Figure 172 (SEQ ID N0:306), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01558 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 25 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 171 (SEQ ID N0:305).

In another embodiment, the invention provides isolated PR01558 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PRO1558 polypeptide, which in 30 certain embodiments, includes an amino acid sequence comprising residues 1 or about 26 to about 262 of Figure 172 (SEQ ID N0:306 In another aspect, the invention concerns an isolated PR01558 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 35 sequence of amino acid residues 1 or about 26 to about 262, inclusive of Figure 17(SEQ ID N0:306 In a further aspect, the invention concerns an isolated PR01558 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least 214 about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 26 to about 262, inclusive of Figure 17(SEQ ID N0:306 In yet another aspect, the invention concerns an isolated PR01558 polypeptide, comprising the sequence of amino acid residues 1 or about 26 to about 262, inclusive of Figure 172 (SEQ ID N0:306), or a fragment thereof sufficient to provide a binding site for an anti-PR01558 antibody. Preferably, the PR01558 fragment 5 retains a qualitative biological activity of a native PR01S58 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1558 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 262, inclusive of Figure 172 (SEQ ID N0.306), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about 10 an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1558 15 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01558 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01558 polypeptide by contacting the native PR01558 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01558 polypeptide, 20 or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 87. PROl 604 A cDNA clone (DNA71286-1687)has been identified that encodes a novel polypeptide having homology to hepatoma-derived growth factor (HDGF) designated in the present application as "PRO1604". 25 In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01604 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO1604 polypeptide having 30 the sequence of amino acid residues from 1 or about 14 to about 671, inclusive of Figure 174 (SEQ ID NO :308), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1604 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 104 and about 2077, inclusive, of Figure 173 (SEQ ID N0:307). Preferably, hybridization occurs under stringent 35 hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 215 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203357 (DNA71286-1687), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203357 (DNA71286-1687).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 14 to about 671, inclusive of Figure 174 (SEQ ID N0:308), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1604 polypeptide having the sequence of amino acid residues from about 14 to about 671, inclusive of Figure 174 (SEQ ID N0:308), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, 15 preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1604 polypeptide, with or without the N-terminal signal sequence, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 20 1 through about amino acid position 13 in the sequence of Figure 174 (SEQ ID N0:308).

In another aspect, the invention concents an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 14 to about 671, inclusive of Figure 174 (SEQ ID N0:308), or (b) the 25 complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01604 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length. 30 In another embodiment, the invention provides isolated PRO1604 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01604polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 14 to 671 of Figure 174 (SEQ ID N0:308).

In another aspect, the invention concerns an isolated PR01604 polypeptide, comprising an amino acid 35 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 14 to about 671, inclusive of Figure 174 (SEQ ID N0:308). 216 In a further aspect, the invention concerns an isolated PR01604 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 14 to 671 of Figure 174 (SEQ ID NO:308).

In yet another aspect, the invention concerns an isolated PR01604 polypeptide, comprising the sequence 5 of amino acid residues 14 to about 671, inclusive of Figure 174 (SEQ ID N0:308), or a fragment thereof sufficient to provide a binding site for an anti-PRQI604 antibody. Preferably, the PR01604 fragment retains a qualitative biological activity of a native PR01604 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1604 polypeptide having the 10 sequence of amino acid residues from about 14 to about 671, inclusive of Figure 174 (SEQ ID N0:308), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the 15 polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PROl 604 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PROl604 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01604 polypeptide, by contacting the native PR01604 polypeptide with a candidate molecule and 20 monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1604 polypeptide, or an agonist or antagonist as hereinabove defmed, in combination with a pharmaceuticaliy acceptable carrier. 88. PRQ1491 A cDNA clone (DNA71883-1660) has been identified, having homology to nucleic acid encoding a collapsin protein, that encodes a novel polypeptide, designated in the present application as "PR01491".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01491 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 30 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01491 polypeptide having the sequence of amino acid residues from about 1 or about 37 to about 777, inclusive of Figure 176 (SEQ ID N0.310), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01491 35 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 107 or about 215 and about 2437, inclusive, of Figure 175 (SEQ ID N0:309). Preferably, hybridization occurs under stringent hybridization and wash conditions. 217 In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203475 (DNA71883-1660) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the 5 nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203475 (DNA71883-1660).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence 10 identity to the sequence of amino acid residues 1 or about 37 to about 777, inclusive of Figure 176 (SEQ ID N0:310), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 1,670 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01491 polypeptide having the sequence of amino acid residues from 1 or about 37 to 15 about 777, inclusive of Figure 176 (SEQ ID N0:310), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding 20 a PR01491 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 36 in the sequence ofFigure 176 (SEQ ID N0:310).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 25 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 37 to about 777, inclusive of Figure 176 (SEQ ID N0:310), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01491 polypeptide coding sequence that may find 30 use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 175 (SEQ ID N0:309).

In another embodiment, the invention provides isolated PR01491 polypeptide encoded by any of the 35 isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01491 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 37 to about 777 of Figure 218 176 (SEQ ID N0:310).

In another aspect, the invention concerns an isolated PR01491 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 37 to about 777, inclusive of Figure 176 (SEQ ID N0r310).

In a further aspect, the invention concerns an isolated PR01491 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 37 to about 777, inclusive of Figure 176 (SEQ ID N0:310).

In yet another aspect, the invention concerns an isolated PRO 1491 polypeptide, comprising the sequence 10 of amino acid residues 1 or about 37 to about 777, inclusive of Figure 176 (SEQ ID N0:310), or a fragment thereof sufficient to provide a binding site for an anti-PR01491 antibody. Preferably, the PROI491 fragment retains a qualitative biological activity of a native PRO 1491 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01491 polypeptide having the 15 sequence of amino acid residues from about 1 or about 37 to about 777, inclusive of Figure 176 (SEQ ID N0:310), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) 20 recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1491 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PROI491 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PRO 1491 polypeptide by contacting the native PRO 1491 polypeptide with a candidate molecule and 25 monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01491 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 89. PRQ1431 A cDNA clone (DNA73401-1633) has been identified having a domain with homology to SH3 that encodes a novel polypeptide, which has been designated in the present application as "PR0143P.

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01431 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 35 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1431 polypeptide having the sequence of amino acid residues from about 1 to about 370, inclusive of Figure 178 (SEQ ID NO:315) or 219 PCT/US99/201I1 (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1431 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between residues 1 to about 133S and about 1560 to about 3934, inclusive, of Figure 177 (SEQ ID NO:314). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns (a) an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203273 (DNA73401-1633) or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic 10 acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203273 (DNA73401-1633).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence 15 identity to the sequence of amino acid residues from about 1 to about 370, inclusive, of Figure 178 (SEQ ID NO:315), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 15 nucleotides that is produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01431 polypeptide having the sequence of amino acid residues from about 1 to about 20 370, inclusive, of Figure 178 (SEQ ID NO:315), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 25 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 370, inclusive, of Figure 178 (SEQ ID NO-.315), inclusive, ofFigure 178 (SEQ ID NO:315).

In another embodiment, the invention provides isolated PR01431 polypeptide encoded by any of the 30 isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01431 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 370, inclusive, of Figure 178 (SEQ ID NO-.315).

In another aspect, the invention concerns an isolated PR01431 polypeptide, comprising an amino acid 35 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 370, inclusive, of Figure 178 (SEQ ID NO:315). 220 In a further aspect, the invention concerns an isolated PRO 1431 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to 370 ofFigure 178 (SEQ ID NO:315).

In yet another aspect, the invention concerns an isolated PR01431 or PR01432 polypeptide, comprising 5 the sequence of amino acid residues 1 to about 370, inclusive, or Figure 178 (SEQ ID N0.315), inclusive, of Figure 178 (SEQ ID N0:315), or a fragment thereof sufficient to provide a binding site for an anti-PR01431 antibody. Preferably, the PR0I431 fragment retains a qualitative biological activity of a native PR01431 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 10 molecule under stringent conditions with (a) a DNA molecule encoding a PR01431 polypeptide having the sequence of amino acid residues from about 1 to about 370, inclusive, of Figure 178 (SEQ ID N0:315), inclusive, of Figure 178 (SEQ ID N0:315), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at ieast about a 95% sequence identity 15 to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1431 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01431 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a 20 native PR01431 polypeptide, by contacting the native PR01431 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01431 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 90. PRQ1563 A cDNA clone (DNA73492-1671) has been identified, having homology to nucleic acid encoding ADAMTS-1 that encodes a novel polypeptide, designated in the present application as "PR01563".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01563 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO1563 polypeptide having the sequence of amino acid residues from about 1 or about 49 to about 837, inclusive of Figure 180 (SEQ ID NO:317), or (b) the complement of the DNA molecule of (a). in another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01563 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 419 or about 563 and about 2929, inclusive, of Figures 179A-B (SEQ ID NO:316). Preferably, hybridization occurs 221 under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203324 5 (DNA73492-1671) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203324 (DNA73492-1671).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence 10 identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 49 to about 837, inclusive of Figure 180 (SEQ ID N0.-317), or (b) the complement of the DNA of (a).

In a farther aspect, the invention concerns an isolated nucleic acid molecule having at least 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA 15 molecule encoding a PR01563 polypeptide having the sequence of amino acid residues from 1 or about 49 to about 837, inclusive of Figure 180 (SEQ ID N0:317), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1563 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 48 in the sequence of Figure 180 (SEQ ID NO:317).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 49 to about 837, inclusive of Figure 180 (SEQ ID NO:3I7), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1563 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figures 179 A-B (SEQ ID N0.316).

In another embodiment, the invention provides isolated PR01563 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01563 polypeptide, which in 222 certain embodiments, includes an amino acid sequence comprising residues 1 or about 49 to about 837 of Figure 180 (SEQ ID NO:317).

In another aspect, the invention concerns an isolated PR01563 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 5 sequence of amino acid residues 1 or about 49 to about 837, inclusive of Figure 180 (SEQ ID N0:3I7).

In a further aspect, the invention concerns an isolated PRO1563 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 49 to about 837, inclusive of Figure 180 (SEQ ID N0:317).

In yet another aspect, the invention concerns an isolated PRO1563 polypeptide, comprising the sequence of amino acid residues 1 or about 49 to about 837, inclusive of Figure 180 (SEQ ID NO:317), or a fragment thereof sufficient to provide a binding site for an anti-PR01563 antibody. Preferably, the PR01563 fragment retains a qualitative biological activity of a native PR01563 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 15 molecule under stringent conditions with (a) a DNA molecule encoding a PR01563 polypeptide having the sequence of amino acid residues from about 1 or about 49 to about 837, inclusive of Figure 180 (SEQ ID NO:317), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host 20 cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01563 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01563 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a 25 native PR01563 polypeptide by contacting the native PR01563 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1563 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 91. PROl 565 A cDNA clone (DNA73727-1673) has been identified, having homology to nucleic acid encoding a chondromodulin protein that encodes a novel polypeptide, designated in the present application as "PR01565".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1565 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01565 polypeptide having 223 the sequence of amino acid residues from about 1 or about 41 to about 317, inclusive of Figure 182 (SEQ ID NO:322), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01565 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 59 or about 179 and about 1009, inclusive, of Figure 181 (SEQ ID NO:321). Preferably, hybridization occurs 5 under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203459 10 (DNA73727-1673) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203459 (DNA73727-1673).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence 15 identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 41 to about 317, inclusive of Figure 182 (SEQ ID NO:322), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 410 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA 20 molecule encoding a PRO1565 polypeptide having the sequence of amino acid residues from 1 or about 41 to about 317, inclusive ofFigure 182 (SEQ ID NO:322), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01565 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 40 in the sequence ofFigure 182 (SEQ ID N0.322). The transmembrane 30 domain has been tentatively identified as extending from about amino acid position 25 to about amino acid position 47 in the PR01565 amino acid sequence (Figure 182, SEQ ID NO:322).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 35 amino acid sequence of residues 1 or about 41 to about 317, inclusive of Figure 182 (SEQ ID NO:322), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01565 polypeptide coding sequence that may find 224 PCT/US99/20I11 use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 181 (SEQ ID NO:321).

In another embodiment, the invention provides isolated PRO1565 polypeptide encoded by any of the 5 isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PRO1565 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 41 to about 317 ofFigure 182 (SEQ ID NO:322).

In another aspect, the invention concerns an isolated PROI565 polypeptide, comprising an amino acid 10 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 41 to about 317, inclusive of Figure 182 (SEQ ID NO:322).

In a further aspect, the invention concerns an isolated PR01565 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least 15 about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 41 to about 317, inclusive of Figure 182 (SEQ ID N0:322).

In yet another aspect, the invention concerns an isolated PR01565 polypeptide, comprising the sequence of amino acid residues 1 or about 41 to about 317, inclusive ofFigure 182 (SEQ ID NO:322), or a fragment thereof sufficient to provide a binding site for an anti-PR01565 antibody. Preferably, the PR01565 fragment 20 retains a qualitative biological activity of a native PRO1565 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01565 polypeptide having the sequence of amino acid residues from about 1 or about 41 to about 317, inclusive of Figure 182 (SEQ ID NO:322), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about 25 an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01565 30 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01565 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01565 polypeptide by contacting the native PR01565 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01565 polypeptide, 35 or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 225 92. PRQ1571 A cDNA clone (DNA73730-1679) has been identified, having homology to nucleic acid encoding the Clostridium perfringens enterotoxin receptor (CPE-R) that encodes a novel polypeptide, designated in the present application as "PR01571".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding 5 a PR01571 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1571 polypeptide having the sequence of amino acid residues from about 1 or about 22 to about 239, inclusive of Figure 184 (SEQ ID 10 NO:324), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1571 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 90 or about 153 and about 806, inclusive, ofFigure 183 (SEQ ID NO:323). Preferably, hybridization occurs under stringent hybridization and wash conditions.

IS In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203320 (DNA73730-1679) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the 20 nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203320 (DNA73730-1679).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence 25 identity to the sequence of amino acid residues I or about 22 to about 239, inclusive of Figure 184 (SEQ ID NO:324), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 910 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01571 polypeptide having the sequence of amino acid residues from 1 or about 22 to 30 about 239, inclusive of Figure 184 (SEQ ID NO:324), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding 35 a PR01571 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid 226 position 1 to about amino acid position 21 in the sequence of Figure 184 (SEQ IDNO:324). The transmembrane domains have been tentatively identified as extending from about amino acid position 82 to about amino acid position 103, from about amino acid position 1 IS to about amino acid position 141 and from about amino acid position 160 to about amino acid position 182 in the PR01571 amino acid sequence (Figure 184, SEQ ID NO:324).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 22 to about 239, inclusive of Figure 184 (SEQ ID NO:324), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01571 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 183 (SEQ ID N0.323).

In another embodiment, the invention provides isolated PRO 1571 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01571 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 22 to about 239 of Figure 184 (SEQ ID N0:324).

In another aspect, the invention concerns an isolated PR01571 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 22 to about 239, inclusive of Figure 184 (SEQ ID N0.324).

In a further aspect, the invention concerns an isolated PR01571 polypeptide, comprising an amino acid 25 sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 22 to about 239, inclusive of Figure 184 (SEQ ID NO:324).

In yet another aspect, the invention concerns an isolated PRO 1571 polypeptide, comprising the sequence of amino acid residues 1 or about 22 to about 239, inclusive of Figure 184 (SEQ ID NO:324), or a fragment 30 thereof sufficient to provide a binding site for an anti-PR01571 antibody. Preferably, the PR01571 fragment retains a qualitative biological activity of a native PRO 1571 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01571 polypeptide having the sequence of amino acid residues from about 1 or about 22 to about 239, inclusive of Figure 184 (SEQ ID 35 N0:324), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host 227 cell comprising Che test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01S71 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01571 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a 5 native PR01571 polypeptide by contacting the native PR01571 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO 1571 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 93. PRQ1572 A cDNA clone (DNA73734-1680) has been identified that encodes a novel polypeptide having sequence identity with CPE-R and designated in the present application as "PR01572." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01572 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1572 polypeptide having the sequence of amino acid residues from 1 or about 24 to about 261, inclusive of Figure 186 (SEQ ID NO:326), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1572 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 159 and about 872, inclusive, of Figure 185 (SEQ ID NO:325). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 25 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203363 (DNA73734-1680), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC 30 Deposit No. 203363 (DNA73734-1680).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 24 to about 261, inclusive of Figure 186 (SEQ ID 35 NO:326), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule 228 under stringent conditions with (a) a DNA molecule encoding a PR01572 polypeptide having the sequence of amino acid residues from about 24 to about 261, inclusive of Figure 186 (SEQ ID NO:326), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01572 polypeptide, with or without the N-tenninal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 23 in the sequence of Figure 186 (SEQ ID NO:326). The transmembrane 10 domains have been tentatively identified as approximately at about 81-100,121-141 and 173-194 in the PR01572 amino acid sequence (Figure 186, SEQ ID NO:326).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 15 amino acid sequence of residues 24 to about 261, inclusive of Figure 186 (SEQ ID NO:326), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01572 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 20 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01572 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01572 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 24 through 261 of Figure 186 (SEQ ID 25 NO-.326).

In another aspect, the invention concerns an isolated PR01572 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 24 to about 261, inclusive of Figure 186 (SEQ ID NO:326). 30 In a further aspect, the invention concerns an isolated PR01572 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 24 through 261 of Figure 186 (SEQ ID N0:326).

In yet another aspect, the invention concerns an isolated PR01572 polypeptide, comprising the sequence 35 of amino acid residues 24 to about 261, inclusive of Figure 186 (SEQ ID NO:326), or a fragment thereof sufficient to provide a binding site for an anti-PR01572 antibody. Preferably, the PR01572 fragment retains a qualitative biological activity of a native PR01572 polypeptide. 229 In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01572 polypeptide having the sequence of amino acid residues from about 24 to about 261, inclusive of Figure 186 (SEQ ID NO:326), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence 5 identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01572 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01572 antibody. 10 In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01572 polypeptide, by contacting the native PR01572 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1572 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 94. PRQ1S73 A cDNA clone (DNA73735-1681) has been identified that encodes a novel polypeptide having sequence identity with CPE-R and designated in the present application as "PR01573".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding 20 a PRO1573 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01573 polypeptide having the sequence of amino acid residues from 1 or about 18 to about 225, inclusive of Figure 188 (SEQ ID N0.328), 25 or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1573 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 148 and about 771, inclusive, of Figure 187 (SEQ ID N0.327). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203356 (DNA73735-1681), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic 35 acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203356 (DNA73735-1681).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 230 encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 18 to about 225, inclusive of Figure 188 (SEQ ID NO:328), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 5 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1573 polypeptide having the sequence of amino acid residues from about 18 to about 225, inclusive of Figure 188 (SEQ ID NO:328), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most 10 preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01573 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 15 1 through about amino acid position 17 in the sequence of Figure 188 (SEQ ID NO:328). The transmembrane domains have been tentatively identified as at approximately 82-101, 118-145 and 164-188 in the PR01573 amino acid sequence (Figure 188, SEQ ID NO:328).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 20 preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 18 to about 225, inclusive of Figure 188 (SEQ ID NO:328), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01573 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 25 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01573 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO1573 polypeptide, which in one 30 embodiment, includes an amino acid sequence comprising residues 18 through 225 of Figure 188 (SEQ ID N0:328).

In another aspect, the invention concerns an isolated PRO 1573 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 35 sequence of amino acid residues 18 to about 225, inclusive of Figure 188 (SEQ ID NO:328).

In a further aspect, the invention concerns an isolated PRO 1573 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least 231 about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 18 through 225 of Figure 188 (SEQ ID NO:328).

In yet another aspect, the invention concerns an isolated PRO 1573 polypeptide, comprising the sequence of amino acid residues 18 to about 225, inclusive of Figure 188 (SEQ ID NO:328), or a fragment thereof sufficient to provide a binding site for an anti-PR01573 antibody. Preferably, the PR01573 fragment retains 5 a qualitative biological activity of a native PR01573 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01573 polypeptide having the sequence of amino acid residues from about 18 to about 225, inclusive of Figure 188 (SEQ ID NO:328), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence 10 identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01573 15 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01573 antibody.

In a farther embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01573 polypeptide, by contacting the native PR01573 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1573 polypeptide, 20 or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 95. PRQ1488 A cDNA clone (DN A73736-1657)has been identified that encodes a novel polypeptide having homology to Clostridium perfringens enterotoxin receptor (CPE-R), designated in the present application as "PR01488". 25 In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01488 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1488 polypeptide having 30 the sequence of amino acid residues from about 1 to about 220, inclusive of Figure 190 (SEQ ID N0:330), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01488 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 6 and about 665, inclusive, of Figure 189 (SEQ ID NO:329). Preferably, hybridization occurs under stringent 35 hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 232 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203466 (DNA73736-1657), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203466 (DNA73736-1657).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 220, inclusive of Figure 190 (SEQ ID N0:330), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1488 polypeptide having the sequence of amino acid residues from about 1 to about 220, inclusive of Figure 190 (SEQ ID N0:330), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, 15 preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01488 polypeptide, with or without the initiating methionine, and its soluble variants (i.e. transmembrane domains deleted or inactivated), or is complementary to such encoding nucleic acid molecule. Transmembrane 20 domains has been tentatively identified as being located at about amino acid positions 8-30, 82-102, 121-140, and 166-186 in the PR01488 amino acid sequence (Figure 190, SEQ ID N0.330).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 25 amino acid sequence of residues 1 to about 220, inclusive of Figure 190 (SEQ ID N0:330), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO 1488 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to aboui 50 30 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1488 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

Ina specific aspect, the invention provides isolated native sequence PR01488 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues I to 220 of Figure 190 (SEQ ID N0:330). 35 In another aspect, the invention concerns an isolated PRO1488 polypeptide, comprising an amino acid sequence having al least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 233 sequence of amino acid residues 1 to about 220, inclusive of Figure 190 (SEQ ID N0:330).

In a further aspect, the invention concerns an isolated PR01488 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to 220 ofFigure 190 (SEQ ID N0:330).

In yet another aspect, the invention concerns an isolated PR01488 polypeptide, comprising the sequence of amino acid residues 1 to about 220, inclusive of Figure 190 (SEQ ID N0:330), or a fragment thereof sufficient to provide a binding site for an anti-PR01488 antibody. Preferably, the PR01488 fragment retains a qualitative biological activity of a native PRO1488 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 10 molecule under stringent conditions with (a) a DNA molecule encoding a PR01488 polypeptide having the sequence of amino acid residues from about 1 to about 220, inclusive of Figure 190 (SEQ ID N0:330), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising 15 the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1488 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01488 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a 20 native PR01488 polypeptide, by contacting the native PR01488 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1488 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 96. PROl 489 A cDNA clone (DNA73737-1658) has been identified, having homology to nucleic acid encoding the Clostridium perfringens enterotoxin receptor (CPE-R) that encodes a novel polypeptide, designated in the present application as "PR01489".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DN A encoding 30 a PR01489 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01489 polypeptide having the sequence of amino acid residues from about 1 to about 173, inclusive of Figure 192 (SEQ ID N0:332), or 35 (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1489 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 264 234 and about 782, inclusive, ofFigure 191 (SEQ ID N0.331). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule 5 encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203412 (DNA73737-1658) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203412 (DNA73737-1658).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 10 encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 173, inclusive of Figure 192 (SEQ ID NO:332), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 25 15 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1489 polypeptide having the sequence of amino acid residues from 1 to about 173, inclusive of Figure 192 (SEQ ID NO:332), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) 20 or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01489 polypeptide, with or without the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domains have been tentatively identified as extending from about amino acid position 31 to about amino acid 25 position 51, from about amino acid position 71 to about amino acid position 90 and from about amino acid position 112 to about amino acid position 133 in the PR01489 amino acid sequence (Figure 192, SEQ ID NO:332).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 30 preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 173, inclusive of Figure 192 (SEQ ID NO:332), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01489 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 35 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 191 (SEQ ID NO:331). 235 PCT/US99/20T11 In another embodiment, the invention provides isolated PR01489 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01489 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 to about 173 ofFigure 192 (SEQ ID NO:332).

In another aspect, the invention concerns an isolated PRO 1489 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 173, inclusive ofFigure 192 (SEQ ID NO:332).

In a further aspect, the invention concerns an isolated PR01489 polypeptide, comprising an amino acid 10 sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to about 173, inclusive ofFigure 192 (SEQ ID NO:332).

In yet another aspect, the invention concerns an isolated PR01489 polypeptide, comprising the sequence of amino acid residues 1 to about 173, inclusive of Figure 192 (SEQ ID NO:332), or a fragment thereof 15 sufficient to provide a binding site for an anti-PR01489 antibody. Preferably, the PR01489 fragment retains a qualitative biological activity of a native PRO1489 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01489 polypeptide having the sequence of amino acid residues from about 1 to about 173, inclusive of Figure 192 (SEQ ID NO:332), or (b) 20 the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identiiy, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1489 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01489 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01489 polypeptide by contacting the native PR01489 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1489 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 97. PRQ1474 A cDNA clone (DNA73739-1645) has been identified that encodes a novel polypeptide having sequence 35 identity with ovomucoid and designated in the present application as "PRO1474." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01474 polypeptide. 236 In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1474 polypeptide having the sequence of amino acid residues from 1 or about 20 to about 85, inclusive ofFigure 194 (SEQ ID NO:334), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01474 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 102 and about 299, inclusive, of Figure 193 (SEQ ID NO:333). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 10 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203270 (DNA73739-1645), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC 15 Deposit No. 203270 (DNA73739-1645).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 20 to about 85, inclusive of Figure 194 (SEQ ID 20 NO:334), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1474 polypeptide having the sequence of amino acid residues from about 20 to about 85, inclusive of Figure 194 (SEQ ID NO:334), or (b) the 25 complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 30 preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 20 to about 85, inclusive of Figure 194 (SEQ ID NO:334), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1474 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 35 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01474 polypeptide encoded by any of the 237 isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01474 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 20 through 85 of Figure 194 (SEQ ID N0:334).

In another aspect, the invention concerns an isolated PR01474 polypeptide, comprising an amino acid 5 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 20 to about 85, inclusive of Figure 194 (SEQ ID N0:334).

In a further aspect, the invention concerns an isolated PRO1474 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least 10 about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 20 through 85 of Figure 194 (SEQ ID NO:334).

In yet another aspect, the invention concerns an isolated PRO1474 polypeptide, comprising the sequence of amino acid residues 20 to about 85, inclusive of Figure 194 (SEQ ID NO:334), or a fragment thereof sufficient to provide a binding site for an anti-PR01474 antibody. Preferably, the PR01474 fragment retains 15 a qualitative biological activity of a native PRO1474 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecuie encoding a PR01474 polypeptide having the sequence of amino acid residues from about 20 to about 85, inclusive of Figure 194 (SEQ ID NO:334), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence 20 identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01474 25 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01474 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PRO1474 polypeptide, by contacting the native PRO1474 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01474 polypeptide, 30 or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 98. PRQ1508 A cDNA clone (DNA73742-1662) has been identified that encodes a novel secreted polypeptide and designated in the present application as "PR01508." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01508 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 238 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO1508 polypeptide having the sequence of amino acid residues from 1 or about 31 to about 148, inclusive of Figure 196 (SEQ ID NO:336), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01508 5 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 160 and about 513, inclusive, of Figure 195 (SEQ ID NO:335). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 10 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203316 (DNA73742-1662), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203316 (DNA73742-1662).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 31 to about 148, inclusive of Figure 196 (SEQ ID NO:336), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01508 polypeptide having the sequence of amino acid residues from about 31 to about 148, inclusive of Figure 196 (SEQ ID NO:336), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, 25 preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01508 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as 30 extending from amino acid position 1 through about amino acid position 30 in the sequence of Figure 196 (SEQ ID N0:336).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 35 amino acid sequence of residues 31 to about 148, inclusive of Figure 196 (SEQ ID NO:336), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01508 polypeptide coding sequence that may find 239 use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO 1508 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01508 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 31 to 148 of Figure 196 (SEQ ID NO:336).

In another aspect, the invention concerns an isolated PR01508 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 10 sequence of amino acid residues 31 to about 148, inclusive of Figure 196 (SEQ ID NO:336).

In a further aspect, the invention concerns an isolated PRO1508 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 31 to 148 ofFigure 196 (SEQ ID NO:336).

In yet another aspect, the invention concerns an isolated PRO1508 polypeptide, comprising the sequence of amino acid residues 31 to about 148, inclusive of Figure 196 (SEQ ID NO:336), or a fragment thereof sufficient to provide a binding site for an anti-PR01508 antibody. Preferably, the PRO1508 fragment retains a qualitative biological activity of a native PR01508 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 20 molecule under stringent conditions with (a) a DNA molecule encoding a PRO1508 polypeptide having the sequence of amino acid residues from about 31 to about 148, inclusive of Figure 196 (SEQ ID NO:336), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising 25 the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. 99. PRQ1555 A cDNA clone (DNA73744-1665) has been identified that encodes a novel transmembrane polypeptide 30 designated in the present application as "PR01555".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01555 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 35 preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1555 polypeptide having the sequence of amino acid residues from 1 or about 32 to about 246, inclusive ofFigure 198 (SEQ ID N0:338), or (b) the complement of the DNA molecule of (a). 240 In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1555 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 83 and about 827, inclusive, of Figure 197 (SEQ ID NO:337). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 5 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203322 (DNA73744-1665), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC 10 Deposit No. 203322 (DNA73744-1665).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 32 to about 246, inclusive of Figure 198 (SEQ ID 15 NO:338), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecuie having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1555 polypeptide having the sequence of amino acid residues from about 32 to about 246, inclusive of Figure 198 (SEQ ID NO:338), or (b) the 20 complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01555 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and 25 its soluble variants (i.e. transmembrane domains deleted or inactivated), or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 31 in the sequence of Figure 198 (SEQ ID NO:338). Two transmembrane domains have been tentatively identified as extending from about amino acid position 1 to about aminn acid position 32, and from about amino acid position 195 through about amino acid position 217, in the PRO 1555 30 amino acid sequence (Figure 198, SEQ ID NO:338).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 32 to about 246, inclusive of Figure 198 (SEQ ID NO:338), or (b) the 35 complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01555 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 241 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PROI555 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PROI555 polypeptide, which in one 5 embodiment, includes an amino acid sequence comprising residues 32 to 246 ofFigure 198 (SEQ ID NO:338).

In another aspect, the invention concerns an isolated PR01555 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 32 to about 246, inclusive ofFigure 198 (SEQ ID NO:338). 10 In a further aspect, the invention concerns an isolated PRO 1555 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 32 to 246 of Figure 198 (SEQ ID NO:338).

In yet another aspect, the invention concerns an isolated PR01555 polypeptide, comprising the sequence 15 of amino acid residues 32 to about 246, inclusive of Figure 198 (SEQ ID NO:338), or a fragment thereof sufficient to provide a binding site for an anti-PR01555 antibody. Preferably, the PR01555 fragment "-tains a qualitative biological activity of a native PRO1555 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1555 polypeptide having the 20 sequence of amino acid residues from about 32 to about 246, inclusive of Figure 198 (SEQ ID NO:338), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the 25 polypeptide from the cell culture. 100. PRO 1485 A cDN A clone (DNA73746-1654) has been identified that encodes a novel polypeptide having sequence identity with lysozyme, and more particularly, lysozyme C precursor, and designated in the present application 30 as "PR01485." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01485 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 35 preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01485 polypeptide having the sequence of amino acid residues from 1 or about 19 to about 148, inclusive ofFigure 200 (SEQ ID N0:340), or (b) the complement of the DNA molecule of (a). 242 In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1485 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 205 and about 594, inclusive, of Figure 199 (SEQ ID NO:339). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having S at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203411 (DNA73746-1654), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC 10 Deposit No. 203411 (DNA73746-1654).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 19 to about 148, inclusive ofFigure 200 (SEQ ID 15 N0:340), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecuie under stringent conditions with (a) a DNA molecule encoding a PRO1485 polypeptide having the sequence of amino acid residues from about 19 to about 148, inclusive of Figure 200 (SEQ ID N0:340), or (b) the 20 complement of die DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 25 preferably at least about 90% positives, most preferably at least about 95% positives when compared with die amino acid sequence of residues 19 to about 148, inclusive of Figure 200 (SEQ ID N0:340), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01485 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 30 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01485 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO1485 polypeptide, which in one 35 embodiment, includes an amino acid sequence comprising residues 19 through 148 of Figure 200 (SEQ ID N0:340).

In another aspect, the invention concerns an isolated PRO1485 polypeptide, comprising an amino acid 243 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 19 to about 148, inclusive of Figure 200 (SEQ ID N0:340).

In a further aspect, the invention concerns an isolated PR01485 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least 5 about 90 % positives, most preferabty at least about 95 % positives when compared with the amino acid sequence of residues 19 through 148 of Figure 200 (SEQ ID NO:340).

In yet another aspect, the invention concerns an isolated PR01485 polypeptide, comprising the sequence of amino acid residues 19 to about 148, inclusive of Figure 200 (SEQ ID N0:340), or a fragment thereof sufficient to provide a binding she for an anti-PR01485 antibody. Preferably, the PR01485 fragment retains 10 a qualitative biological activity of a native PR01485 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01485 polypeptide having the sequence of amino acid residues from about 19 to about 148, inclusive of Figure 200 (SEQ ID N0:340), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence 15 identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecuie under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01485 20 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01485 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01485 polypeptide, by contacting the native PR01485 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1485 polypeptide, 25 or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 101. PROl 564 A cDNA clone (DNA73760-1672) has been identified, having homology to nucleic acid encoding an N-acetylgalactosaminyltransferase protein that encodes a novel polypeptide, designated in the present application 30 as "PRO1564".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1564 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 35 preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01564 polypeptide having the sequence of amino acid residues from about 1 or about 29 to about 639, inclusive of Figure 202 (SEQ ID NO:347), or (b) the complement of the DNA molecule of (a). 244 la another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01564 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 462 or about 546 and about 2378, inclusive, of Figure 201 (SEQ ID NO:346). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 5 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203314 (DNA73760-1672) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, die nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in 10 ATCC Deposit No. 203314 (DNA73760-1672).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 29 to about 639, inclusive of Figure 202 (SEQ ID 15 NO:347), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01564 polypeptide having the sequence of amino acid residues from 1 or about 29 to about 639, inclusive of Figure 202 (SEQ ID NO:347), or (b) the complement of the DNA molecule of (a), and, 20 if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01564 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and 25 its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid positionl toaboutaminoacidposition28inthesequenceofFigure202(SEQIDNO:347). The transmembrane domain has been tentatively identified as extending from about amino acid position 11 to about amino acid position 36 in the PR01564 amino acid sequence (Figure 202, SEQ ID NO:347).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 29 to about 639, inclusive of Figure 202 (SEQ ID NO:347), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1564 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 245 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 201 (SEQ ID NO:346).

In another embodiment, the invention provides isolated PR01S64 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PRO1564 polypeptide, which in 5 certain embodiments, includes an amino acid sequence comprising residues 1 or about 29 to about 639 of Figure 202 (SEQ ID NO:347).

In another aspect, the invention concerns an isolated PR01564 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 10 sequence of amino acid residues 1 or about 29 to about 639, inclusive of Figure 202 (SEQ ID N0:347).

In a further aspect, the invention concerns an isolated PR01564 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 29 to about 639, inclusive of Figure 202 (SEQ ID NO:347).

In yet another aspect, the invention concerns an isolated PR01564 polypeptide, comprising the sequence of amino acid residues 1 or about 29 to about 639, inclusive of Figure 202 (SEQ ID NO:347), or a fragment thereof sufficient to provide a binding site for an anti-PROl564 antibody. Preferably, the PR01564 fragment retains a qualitative biological activity of a native PR01564 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 20 molecule under stringent conditions with (a) a DNA molecule encoding a PR01564 polypeptide having the sequence of amino acid residues from about 1 or about 29 to about 639, inclusive of Figure 202 (SEQ ID NO:347), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host 25 cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01564 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01564 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a 30 native PR01564 polypeptide by contacting the native PR01564 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1564 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 102. PRQ1755 A cDNA clone (DNA76396-1698) has been identified that encodes a novel transmembrane polypeptide designated in the present application as "PR01755". 246 In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01755 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO1755 polypeptide having 5 the sequence of amino acid residues from 1 or about 32 to about 276, inclusive ofFigure 204 (SEQ ID NO:352), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1755 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 151 and about 885, inclusive, of Figure 203 (SEQ ID NO:351). Preferably, hybridization occurs under stringent 10 hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203471 15 (DNA76396-1698), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203471 (DNA76396-1698).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence 20 identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 32 to about 276, inclusive of Figure 204 (SEQ ID NO:352), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule 25 under stringent conditions with (a) a DNA molecule encoding a PR01755 polypeptide having the sequence of amino acid residues from about 32 to about 276, inclusive of Figure 204 (SEQ ID NO:352), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule. 30 In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01755 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble variants (i.e. transmembrane domain deleted or inactivated), or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 31 in the sequence of Figure 204 (SEQ ID NO:352). The transmembrane 35 domain has been tentatively identified as extending from about amino acid position 178 to about amino acid position 198 in the PR01755 amino acid sequence (Figure 204, SEQ ID NO:352).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 247 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 32 to about 276, inclusive of Figure 204 (SEQ ID NO:352), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01755 polypeptide coding sequence that may find 5 use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO 1755 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO1755 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 32 to 276 of Figure 204 (SEQ ID NO:352).

In another aspect, the invention concerns an isolated PR01755 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 15 sequence of amino acid residues 32 to about 276, inclusive of Figure 204 (SEQ ID NO:352).

In a further aspect, the invention concerns an isolated PR01755 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 32 to 276 of Figure 204 (SEQ ID NO:352).

In yet another aspect, the invention concerns an isolated PR01755 polypeptide, comprising the sequence of amino acid residues 32 to about 276, inclusive of Figure 204 (SEQ ID NO:352), or a fragment thereof sufficient to provide a binding site for an anti-PR01755 antibody. Preferably, the PR01755 fragment retains a qualitative biological activity of a native PRO1755 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 25 molecule under stringent conditions with (a) a DNA molecule encoding a PR01755 polypeptide having the sequence of amino acid residues from about 32 to about 276, inclusive of Figure 204 (SEQ ID NO:352), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising 30 the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1755 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01755 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a 35 native PR01755 polypeptide, by contacting the native PR01755 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1755 polypeptide, 248 or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 103. PRQ1757 A cDNA clone (DNA76398-1699) has been identified that encodes a novel transmembrane polypeptide, designated in the present application as "PRO1757".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01757 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PROI757 polypeptide having 10 the sequence of amino acid residues from about 1 or about 20 to about 121, inclusive of Figure 206 (SEQ ID NO:354), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01757 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 59 or about 116 and about 121, inclusive, ofFigure 205 (SEQIDNO:353). Preferably, hybridization occurs under 15 stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identiiy to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203474 20 (DNA76398-1699) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203474 (DNA76398-1699).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence 25 identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 20 to about 121, inclusive of Figure 206 (SEQ ID NO:354), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 125 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA 30 molecule encoding a PRO1757 polypeptide having the sequence of amino acid residues from 1 or about 20 to about 121, inclusive of Figure 206 (SEQ ID NO:354), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecuie comprising DNA encoding a PR01757 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding 249 nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 19 in the sequence ofFigure 206 (SEQ ID NO:354). The transmembrane domain has been tentatively identified as extending from about amino acid position 91 to about amino acid position 110 in the PR01757 amino acid sequence (Figure 206, SEQ ID NO:354).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 5 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 20 to about 121, inclusive of Figure 206 (SEQ ID NO:354), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01757 polypeptide coding sequence that may find 10 use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 205 (SEQ ID NO:353).

In another embodiment, the invention provides isolated PR01757 polypeptide encoded by any of the 15 isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01757 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 20 to about 121 ofFigure 206 (SEQ ID NO:354).

In another aspect, the invention concerns an isolated PR01757 polypeptide, comprising an amino acid 20 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 20 to about 121, inclusive of Figure 206 (SEQ ID NO:354).

In a further aspect, the invention concerns an isolated PR01757 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least 25 about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 20 to about 121, inclusive of Figure 206 (SEQ ID NO:354).

In yet another aspect, the invention concerns an isolated PRO1757 polypeptide, comprising the sequence of amino acid residues 1 or about 20 to about 121, inclusive of Figure 206 (SEQ ID NO:354), or a fragment thereof sufficient to provide a binding site for an anti-PR01757 antibody. Preferably, the PR01757 fragment 30 retains a qualitative biological activity of a native PR01757 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01757 polypeptide having the sequence of amino acid residues from about 1 or about 20 to about 121, inclusive of Figure 206 (SEQ ID N0:354), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about 35 an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) 250 recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01757 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01757 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01757 polypeptide by contacting the native PR01757 polypeptide with a candidate molecule and 5 monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01757 polypeptide, or an agonist or antagonist as hereinabove defmed, in combination with a pharmaceuticaliy acceptable carrier. 104. PRQ1758 A cDNA clone (DNA76399-1700) has been identified that encodes a novel secreted polypeptide designated in the present application as "PR01758".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01758 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 15 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1758 polypeptide having the sequence of amino acid residues from 1 or about 16 to about 157, inclusive ofFigure 208 (SEQ ID NO:356), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01758 20 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 123 and about 548, inclusive, of Figure 207 (SEQ ID NO:355). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 25 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203472 (DNA76399-1700), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203472 (DNA76399-1700).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 16 to about 157, inclusive of Figure 208 (SEQ ID NO:356), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01758 polypeptide having the sequence of 251 PCT/US99/20I11 amino acid residues from about 16 to about 157, inclusive of Figure 208 (SEQ ID N0:356), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding 5 a PRO 1758 polypeptide, with or without the N-terminal signal sequence, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 15 in the sequence of Figure 208 (SEQ ID NO:356).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more 10 preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 16 to about 157, inclusive of Figure 208 (SEQ ID NO:356), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1758 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, 15 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01758 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01758 polypeptide, which in one 20 embodiment, includes an amino acid sequence comprising residues 16 to 157 ofFigure 208 (SEQ ID NO:356).

In another aspect, the invention concerns an isolated PR01758 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 16 to about 157, inclusive of Figure 208 (SEQ ID NO:356). 25 In a further aspect, the invention concerns an isolated PR01758 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 16 to 157 of Figure 208 (SEQ ID NO:356).

In yet another aspect, the invention concerns an isolated PR01758 polypeptide, comprising the sequence 30 of amino acid residues 16 to about 157, inclusive of Figure 208 (SEQ ID NO:356), or a fragment thereof sufficient to provide a binding site for an anti-PROI758 antibody. Preferably, the PR01758 fragment retains a qualitative biological activity of a native PR01758 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01758 polypeptide having the 35 sequence of amino acid residues from about 16 to about 157, inclusive of Figure 208 (SEQ ID N0:356), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence 252 identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. 105. FRQ1S7S A cDNA clone (DNA76401-1683) has been identified that encodes a novel polypeptide having homology to protein disulfide isomerase and designated in the present application as "PRO 1575." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01575 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 10 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01575 polypeptide having the sequence of amino acid residues from 1 or about 21 to about 273, inclusive ofFigure 210 (SEQIDNO:358), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1575 IS polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 82 and about 840, inclusive, of Figure 209 (SEQ ID NO:357). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 20 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203360 (DNA76401-1683), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203360 (DNA76401-1683).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 21 to about 273, inclusive of Figure 210 (SEQ ID NO:358), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01575 polypeptide having the sequence of amino acid residues from about 21 to about 273, inclusive of Figure 210 (SEQ ID NO:358), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, 35 preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding 253 a PR01575 polypeptide, its soluble variants, (i.e. transmembrane domain and/or signal peptide deleted or inactivated) or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 20 in the sequence of Figure 210 (SEQ ID N0:358). The transmembrane domain has been tentatively identified as extending from about amino acid position 143 to about amino acid position 162 in the PR0157S amino acid sequence (Figure 5 210, SEQ ID NO:358).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 21 to about 273, inclusive of Figure 210 (SEQ ID NO:358), or (b) the 10 complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO 1575 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length. 15 In another embodiment, the invention provides isolated PR01575 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01575 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 21 to 273 ofFigure 210 (SEQ ID NO:358).

In another aspect, the invention concerns an isolated PR01575 polypeptide, comprising an amino acid 20 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 21 to about 273, inclusive of Figure 210 (SEQ ID N0:358).

In a further aspect, the invention concerns an isolated PR01575 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least 25 about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 21 to 273 ofFigure 210 (SEQ ID NO:358).

In yet another aspect, the invention concerns an isolated PRO1575 polypeptide, comprising the sequence of amino acid residues 21 to about 273, inclusive of Figure 210 (SEQ ID NO:358), or a fragment thereof sufficient to provide a binding site for an anti-PR01575 antibody. Preferably, the PR01575 fragment retains 30 a qualitative biological activity of a native PRO1575 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1575 polypeptide having the sequence of amino acid residues from about 21 to about 273, inclusive of Figure 210 (SEQ ID NO:358), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence 35 identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the 254 polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1575 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01575 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01575 polypeptide, by contacting the native PR01575 polypeptide with a candidate molecule and 5 monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01575 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 106. PRO 1787 A cDN A clone (DN A76510-2504) has been identified that encodes a novel polypeptide having sequence identity with myelin pO and designated in the present application as "PRO1787." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01787 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 15 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01787 polypeptide having the sequence of amino acid residues from 1 or about 38 to about 269, inclusive ofFigure 212 (SEQ ID NO:364), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1787 20 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 274 and about 969, inclusive, of Figure 211 (SEQ ID NO:363). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 25 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203477 (DNA76510-2504), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203477 (DNA76510-2504).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 38 to about 269, inclusive of Figure 212 (SEQ ID NO:364), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1787 polypeptide having the sequence of 255 amino acid residues from about 38 to about 269, inclusive of Figure 212 (SEQ ID NO:364), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding 5 a PR01787 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 37 in the sequence of Figure 212 (SEQ ID NO:364). The transmembrane domain has been tentatively identified as extending from about amino acid position 161 through about amino acid 10 position 183 in the PR01787 amino acid sequence (Figure 212, SEQ ID NO:364).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 38 to about 269, inclusive of Figure 212 (SEQ ID NO:364), or (b) the 15 complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01787 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length. 20 In another embodiment, the invention provides isolated PRO1787 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01787 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 38 through 269 of Figure 212 (SEQ ID N0:364).

In another aspect, the invention concerns an isolated PR01787 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 38 to about 269, inclusive of Figure 212 (SEQ ID NO:364).

In a further aspect, the invention concerns an isolated PR01787 polypeptide, comprising an amino acid 30 sequence scoring at least about 80% positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 38 through 269 of Figure 212 (SEQ ID NO:364).

In yet another aspect, the invention concerns an isolated PRO1787 polypeptide, comprising the sequence of amino acid residues 38 to about 269, inclusive of Figure 212 (SEQ ID NO:364), or a fragment thereof 35 sufficient to provide a binding site for an anti-PR01787 antibody. Preferably, the PR01787 fragment retains a qualitative biological activity of a native PR01787 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 256 molecule under stringent conditions with (a) a DNA molecule encoding a PRO1787 polypeptide having the sequence of amino acid residues from about 38 to about 269, inclusive of Figure 212 (SEQ ID NO:364), or (b) the complement of the DNA molecuie of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising 5 the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1787 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01787 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a 10 native PR01787 polypeptide, by contacting the native PR01787 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01787 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 107. PRQ1781 A cDNA clone (DNA76522-2500) has been identified that encodes a novel transmembrane polypeptide designated in the present application as "PRO 1781".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01781 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01781 polypeptide having the sequence of amino acid residues from 1 or about 20 to about 373, inclusive of Figure 214 (SEQ ID NO:366), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01781 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 78 and about 1139, inclusive, ofFigure 213 (SEQ ID NO:365). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 30 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203469 (DNA76522-2500), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC 35 Deposit No. 203469 (DNA76522-2500).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence 257 identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 20 to about 373, inclusive of Figure 214 (SEQ ID NO:366), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule baving at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule 5 under stringent conditions with (a) a DNA molecule encoding a PR01781 polypeptide having the sequence of amino acid residues from about 20 to about 373, inclusive of Figure 214 (SEQ ID NO:36), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule. 10 In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01781 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble variants (i.e. transmembrane domain deleted or inactivated), or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 19 in the sequence of Figure 214 (SEQ ID NO:366). The transmembrane 15 domain has been tentatively identified as extending from about amino acid position 39 to about amino acid position 60 in the PR01781 amino acid sequence (Figure 214, SEQ ID NO:366).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 20 amino acid sequence of residues 20 to about 373, inclusive of Figure 214 (SEQ ID NO:366), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO 1781 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 25 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01781 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01781 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 20 to 373 ofFigure 214 (SEQ ID NO:366). 30 In another aspect, the invention concerns an isolated PR01781 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 20 to about 373, inclusive of Figure 214 (SEQ ID NO:366).

In a further aspect, the invention concerns an isolated PR01781 polypeptide, comprising an amino acid 35 sequence scoring at least about 80% positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 20 to 373 of Figure 214 (SEQ ID N0:366). 258 In yet another aspect, the invention concerns an isolated PRO 1781 polypeptide, comprising the sequence of amino acid residues 20 to about 373, inclusive of Figure 214 (SEQ ID NO:366), or a fragment thereof sufficient to provide a binding site for an anti-PROI781 antibody. Preferably, the PROI781 fragment retains a qualitative biological activity of a native PR01781 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 5 molecule under stringent conditions with (a) a DNA molecule encoding a PR01781 polypeptide having the sequence of amino acid residues from about 20 to about 373, inclusive of Figure 214 (SEQ ID NO:366), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising 10 the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. 108. PRQ1556 A cDNA clone (DNA76529-1666) has been identified that encodes a novel transmembrane polypeptide 15 designated in the present application as "PRO 1556".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01556 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 20 preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01556 polypeptide having the sequence of amino acid residues from 1 or about 25 to about 269, inclusive ofFigure 216 (SEQ ID N0:372), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1556 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 160 and 25 about 891, inclusive, of Figure 215 (SEQ ID NO:371). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule 30 encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203315 (DNA76529-1666), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203315 (DNA76529-1666).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 35 encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 25 to about 269, inclusive of Figure 216 (SEQ ID 259 NO:372), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1556 polypeptide having the sequence of amino acid residues from about 25 to about 269, inclusive of Figure 216 (SEQ ID NO:372), or (b) the 5 complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01556 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and 10 its soluble variants (i.e. transmembrane domains deleted or inactivated), or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 24 in the sequence of Figure 216 (SEQ ID N0:372). Two transmembrane domains have been tentatively identified as extending from about amino acid position 11 to about amino acid position 25 and from about amino acid position 226 to about amino acid position 243 in the PR01556 amino acid 15 sequence (Figure 216, SEQ ID NO:372).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 25 to about 269, inclusive of Figure 216 (SEQ ID NO:372), or (b) the 20 complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01556 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length. 25 In another embodiment, the invention provides isolated PR01556 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01556 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 25 to 269 ofFigure 216 (SEQ ID NO:372).

In another aspect, the invention concerns an isolated PR01556 polypeptide, comprising an amino acid 30 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 25 to about 269, inclusive of Figure 216 (SEQ ID NO:372).

In a further aspect, the invention concerns an isolated PR01556 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least 35 about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 25 to 269 of Figure 216 (SEQ ID NO:372).

In yet another aspect, the invention concerns an isolated PR01556 polypeptide, comprising the sequence 260 PCT/U S99/20111 of amino acid residues 25 to about 269, inclusive of Figure 216 (SEQ ID NO:372), or a fragment thereof sufficient to provide a binding site for an anti-PR01556 antibody. Preferably, the PR01556 fragment retains a qualitative biological activity of a native PRO1556 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01556 polypeptide having the 5 sequence of amino acid residues from about 25 to about 269, inclusive of Figure 216 (SEQ ID NO:372), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the 10 polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1556 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01556 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01556 polypeptide, by contacting the native PR01556 polypeptide with a candidate molecule and 15 monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1556 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 109. PRQ1759 A cDNA clone (DNA76531-1701) has been identified that encodes a novel polypeptide having multiple transmembrane domains, designated in the present application as "PR01759." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1759 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 25 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01759 polypeptide having the sequence of amino acid residues from 1 or about 19 to about 450, inclusive ofFigure 218 (SEQ ID NO:374), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01759 30 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 179 and about 1474, inclusive, of Figure 217 (SEQ ID NO:373). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 35 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203465 (DNA76531-1701), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic 261 acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203465 (DNA76531-1701).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence 5 identity to the sequence of amino acid residues from about 19 to about 450, inclusive of Figure 218 (SEQ ID NO:374), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1759 polypeptide having the sequence of 10 amino acid residues from about 19 to about 450, inclusive of Figure 218 (SEQ ID NO:374), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding 15 a PR01759 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domains deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 18 in the sequence of Figure 218 (SEQ ID N0:374). The transmembrane domains have been tentatively identified as being at about amino acids 1-19 (possibly a signal peptide), 41-55, 20 75-94,127-143,191-213, 249-270,278-299,314-330, 343-359,379-394, and 410-430 in the PR01759 amino acid sequence (Figure 218, SEQ ID NO:374).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 25 amino acid sequence of residues 19 to about 450, inclusive of Figure 218 (SEQ ID NO:374), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01759 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 30 nucleotides in length, and most preferably frotn about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO 1759 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO1759 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 19 through 450 of Figure 218 (SEQ ID 35 NO:374).

In another aspect, the invention concerns an isolated PR01759 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more 262 preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 19 to about 450, inclusive of Figure 218 (SEQ ID NO:374).

In a further aspect, the invention concerns an isolated PR01759 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence 5 of residues 19 through 450 of Figure 218 (SEQ ID NO:374).

In yet another aspect, the invention concerns an isolated PR01759polypeptide, comprising the sequence of amino acid residues 19 to about 450, inclusive of Figure 218 (SEQ ID NO:374), or a fragment thereof sufficient to provide a binding site for an anti-PR01759 antibody. Preferably, the PR01759 fragment retains a qualitative biological activity of a native PR01759 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01759 polypeptide having the sequence of amino acid residues from about 19 to about 450, inclusive of Figure 218 (SEQ ID NO:374), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence 15 identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01759 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01759 antibody. 20 In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01759 polypeptide, by contacting the native PR01759 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1759 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 110. PROl 760 A cDNA clone (DNA76532-1702) has been identified that encodes a novel secreted polypeptide, designated in the present application as "PR01760." In one embodiment, the invention provides an isolated nucleic acid molecuie comprising DNA encoding 30 a PR01760 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1760 polypeptide having the sequence of amino acid residues from 1 or about 21 to about 188, inclusive ofFigure 220 (SEQ ID NO:376), 35 or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01760 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 120 and 263 about 623, inclusive, of Figure 219 (SEQ ID NO:375). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule 5 encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203473 (DNA76532-1702), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203473 (DNA76532-1702).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 10 encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 21 to about 188, inclusive of Figure 220 (SEQ ID NO:376), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 15 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1760 polypeptide having the sequence of amino acid residues from about 21 to about 188, inclusive of Figure 220 (SEQ ID NO:376), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most 20 preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 21 to about 188, inclusive of Figure 220 (SEQ ID NO:376), or (b) the 25 complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1760 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length. 30 In another embodiment, the invention provides isolated PR01760 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01760 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 21 through 188 of Figure 220 (SEQ ID NO:376).

In another aspect, the invention concerns an isolated PR01760 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 264 sequence of amino acid residues 21 to about 188, inclusive of Figure 220 (SEQ ID NO:376).

In a further aspect, the invention concerns an isolated PR01760 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 21 through 188 of Figure 220 (SEQ ID NO:376).

In yet another aspect, theinventionconcernsanisolatedPR01760polypeptide, comprising the sequence of amino acid residues 21 to about 188, inclusive of Figure 220 (SEQ ID NO:376), or a fragment thereof sufficient to provide a binding site for an anti-PROI760 antibody. Preferably, the PR01760 fragment retains a qualitative biological activity of a native PR01760 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 10 molecule under stringent conditions with (a) a DNA molecule encoding a PRO1760 polypeptide having the sequence of amino acid residues from about 21 to about 188, inclusive ofFigure 220 (SEQ ID NO:376), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising 15 the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01760 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01760 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a 20 native PR01760 polypeptide, by contacting the native PR01760 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PROl760polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 112. PRQ1567 A cDN A clone (DNA76541-1675) has been identified that encodes a novel polypeptidehaving homology to the expression product of the colon specific gene, CSG6, and is designated in the present application as "PR01567".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding 30 a PR01567 polypeptide. 265 (followed by page 268) INTELLECTUAL PROPERTY OFFICE OF N Z 2 4 OCT 2003 Received In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01567 polypeptide having the sequence of amino acid residues from 1 or about 23 to about 178, inclusive ofFigure 224 (SEQ ID NO:383), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1567 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 175 and about 642, inclusive, of Figure 223 (SEQ ID NO:382). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 10 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203409 (DNA76541-1675), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC 15 Deposit No. 203409 (DNA76541-1675).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 23 to about 178, inclusive of Figure 224 (SEQ ID 20 NO:383), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01567 polypeptide having the sequence of amino acid residues from about 23 to about 178, inclusive of Figure 224 (SEQ ID NO:383), or (b) the 25 complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01567 polypeptide, with or without the N-terminal signal sequence, or is complementary to such encoding 30 nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 22 in the sequence of Figure 224 (SEQ ID NO:383).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 35 amino acid sequence of residues 23 to about 178, inclusive of Figure 224 (SEQ ID NO:383), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1567 polypeptide coding sequence that may fmd 268 use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01567 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defmed.

In a specific aspect, the invention provides isolated native sequence PROIS67 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 23 to 178 ofFigure 224 (SEQ ID NO:383).

In another aspect, the invention concerns an isolated PR01567 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 10 sequence of amino acid residues 23 to about 178, inclusive of Figure 224 (SEQ ID NO:383).

In a further aspect, the invention concerns an isolated PRO1567 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 23 to 178 of Figure 224 (SEQ ID NO:383).

In yet another aspect, the invention concerns an isolated PRO1567 polypeptide, comprising the sequence of amino acid residues 23 to about 178, inclusive of Figure 224 (SEQ ID NO:383), or a fragment thereof sufficient to provide a binding site for an anti-PR01567 antibody. Preferably, the PR01567 fragment retains a qualitative biological activity of a native PR01567 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 20 molecule under stringent conditions with (a) a DNA molecule encoding a PR01567 polypeptide having the sequence of amino acid residues from about 23 to about 178, inclusive of Figure 224 (SEQ ID N0:383), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising 25 the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01567 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01567 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a 30 native PR01567 polypeptide, by contacting the native PR01567 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR0I567 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 113. PRO 1693 A cDNA clone (DNA77301-1708) has been identified, having homology to nucleic acid encoding an insulin-like growth factor binding protein that encodes a novel polypeptide, designated in the present application 269 as "PR01693".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01693 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 5 preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1693 polypeptide having the sequence of amino acid residues from about 1 or about 34 to about 513, inclusive of Figure 226 (SEQ ID NO:385), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01693 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 508 10 or about 607 and about 2046, inclusive, of Figure 225 (SEQ ID NO:384). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule 15 encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203407 (DNA77301-1708) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203407 (DNA77301-1708).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 20 encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 34 to about 513, inclusive of Figure 226 (SEQ ID NO:385), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 175 25 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01693 polypeptide having the sequence of amino acid residues from 1 or about 34 to about 513, inclusive of Figure 226 (SEQ ID NO-.385), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence 30 identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01693 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid 35 position 1 to about amino acid position 33 in the sequence of Figure 226 (SEQ ID NO:385). The transmembrane domain has been tentatively identified as extending from about amino acid position 420 to about amino acid position 442 in the PR01693 amino acid sequence (Figure 226, SEQ ID NO:385). 270 In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 34 to about 513, inclusive of Figure 226 (SEQ ID NO:385), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1693 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 225 (SEQ ID NO:384).

In another embodiment, the invention provides isolated PR01693 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01693 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 34 to about 513 ofFigure 226 (SEQ ID NO:385).

In another aspect, the invention concerns an isolated PR01693 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 34 to about 513, inclusive of Figure 226 (SEQ ID NO:385).

In a further aspect, the invention concerns an isolated PR01693 polypeptide, comprising an amino acid 20 sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 34 to about 513, inclusive of Figure 226 (SEQ ID NO:385).

In yet another aspect, the invention concerns an isolated PR01693 polypeptide, comprising the sequence of amino acid residues 1 or about 34 to about 513, inclusive of Figure 226 (SEQ ID NO:385), or a fragment 25 thereof sufficient to provide a binding site for an anti-PR01693 antibody. Preferably, the PR01693 fragment retains a qualitative biological activity of a native PR01693 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01693 polypeptide having the sequence of amino acid residues from about 1 or about 34 to about 513, inclusive of Figure 226 (SEQ ID 30 NO:385), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01693 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01693 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a 271 native PRO1693 polypeptide by contacting the native PRO1693 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1693 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 114. PRQ1784 A cDNA clone (DNA77303-2502) has been identified that encodes a novel transmembrane polypeptide designated in the present application as "PR01784." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01784 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1784 polypeptide having the sequence of amino acid residues from 1 or about 30 to about 146, inclusive ofFigure 228 (SEQ ID N0:390), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01784 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 155 and about 505, inclusive, of Figure 227 (SEQ ID NO:389). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 20 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203479 (DNA77303-2502), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC 25 Deposit No. 203479 (DNA77303-2502).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 30 to about 146, inclusive of Figure 228 (SEQ ID 30 N0:390), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecuie having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01784 polypeptide having the sequence of amino acid residues from about 30 to about 146, inclusive of Figure 228 (SEQ ID N0:390), or (b) the 35 complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule. 272 In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01784 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its-soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 29 in the sequence of Figure 228 (SEQ ID N0:390). The transmembrane 5 domain has been tentatively identified as extending from about amino acid position 52 through about amino acid position 70 in the PR01784 amino acid sequence (Figure 228, SEQ ID N0:390).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 10 amino acid sequence of residues 30 to about 146, inclusive of Figure 228 (SEQ ID N0:390), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO 1784 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 15 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01784 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PROl784 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 30 through 146 of Figure 228 (SEQ ID 20 N0:390).

In another aspect, the invention concerns an isolated PRO1784 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 30 to about 146, inclusive of Figure 228 (SEQ ID N0:390). 25 In a further aspect, the invention concerns an isolated PR01784 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 30 through 146 of Figure 228 (SEQ ID N0:390).

In yet another aspect, the invention concerns an isolated PRO1784 polypeptide, comprising the sequence 30 of amino acid residues 30 to about 146, inclusive of Figure 228 (SEQ ID N0:390), or a fragment thereof sufficient to provide a binding site for an anti-PR01784 antibody. Preferably, the PRO1784 fragment retains a qualitative biological activity of a native PR01784 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1784 polypeptide having the 35 sequence of amino acid residues from about 30 to about 146, inclusive of Figure 228 (SEQ ID N0:390), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence 273 PCTAJS99/20111 identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO 1784 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01784 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01784 polypeptide, by contacting the native PR01784 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01784 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 115. PRQ1605 A cDNA clone (DNA77648-1688) has been identified, having homology to nucleic acid encoding a glycosyltransferase protein that encodes a novel polypeptide, designated in the present application as "PR01605".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01605 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01605 polypeptide having 20 the sequence of amino acid residues from about 1 or about 27 to about 140, inclusive of Figure 230 (SEQ ID NO:395), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO 1605 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 425 or about 503 and about 844, inclusive, ofFigure 229 (SEQ ID NO:394). Preferably, hybridization occurs under 25 stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit 203408 30 (DNA77648-1688) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, die nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203408 (DNA77648-1688).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence 35 identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 27 to about 140, inclusive of Figure 230 (SEQ ID NO:395), or (b) the complement of the DNA of (a). 274 In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 380 nucleotides and produced by hybridizing a test DNA molecuie under stringent conditions with (a) a DNA molecule encoding a PR01605 polypeptide having the sequence of amino acid residues from 1 or about 27 to about 140, inclusive ofFigure 230 (SEQ ID NO:395), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence 5 identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01605 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as 10 extending from about amino acid position 1 to about amino acid position 26 in the sequence of Figure 230 (SEQ ID NO:395).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 15 amino acid sequence of residues 1 or about 27 to about 140, inclusive of Figure 230 (SEQ ID NO:395), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1605 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 20 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 229 (SEQ ID NO:394).

In another embodiment, the invention provides isolated PRO1605 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01605 polypeptide, which in 25 certain embodiments, includes an amino acid sequence comprising residues 1 or about 27 to about 140 of Figure 230 (SEQ ID NO:395).

In another aspect, the invention concerns an isolated PRO1605 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 30 sequence of amino acid residues 1 or about 27 to about 140, inclusive of Figure 230 (SEQ ID NO:395).

In a further aspect, the invention concerns an isolated PR01605 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 27 to about 140, inclusive of Figure 230 (SEQ ID NO:395).

In yet another aspect, the invention concerns an isolated PR01605 polypeptide, comprising the sequence of amino acid residues 1 or about 27 to about 140, inclusive of Figure 230 (SEQ ID NO:395), or a fragment thereof sufficient to provide a binding site for an anti-PR01605 antibody. Preferably, the PR01605 fragment 275 retains a qualitative biological activity of a native PRO1605 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1605 polypeptide having the sequence of amino acid residues from about 1 or about 27 to about 140, inclusive of Figure 230 (SEQ ID NO:395), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about 5 an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concents agonists and antagonists of a native PR01605 10 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01605 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PRO1605 polypeptide by contacting the native PRO1605 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO 1605 polypeptide, 15 or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 116. PRQ1788 A cDN A clone (DN A77652-2505) has been identified that encodes a novel polypeptide having homology to leucine-rich repeat proteins and designated in the present application as "PR01788." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01788 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01788 polypeptide having 25 the sequence of amino acid residues from 1 or about 17 to about 353, inclusive ofFigure 232 (SEQ ID NO:397), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01788 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 112 and about 1122, inclusive, of Figure 231 (SEQ ID NO:396). Preferably, hybridization occurs under stringent 30 hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203480 35 (DNA77652-2505), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203480 (DNA77652-2505). 276 In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 17 to about 353, inclusive of Figure 232 (SEQ ID NO:397), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1788 polypeptide having the sequence of amino acid residues from about 17 to about 353, inclusive of Figure 232 (SEQ ID NO:397), or (b) the complement of the DNA molecule of (a), and, if the DNA molecuie has at least about an 80% sequence identity, 10 preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01788 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding 15 nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 16 in the sequence of Figure 232 (SEQ ID NO:397). Transmembrane domains have been tentatively identified as extending from about amino acid position 215 through about amino acid position 232 and about amino acid position 287 through about amino acid position 304 in the PRO 1788 amino acid sequence (Figure 232, SEQ ID NO:397).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 17 to about 353, inclusive of Figure 232 (SEQ ID NO:397), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01788 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01788 polypeptide encoded by any of the 30 isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO 1788 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 17 to 353 of Figure 232 (SEQ ID NO-.397).

In another aspect, the invention concerns an isolated PR01788 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at Least about 85% sequence identity, more 35 preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 17 to about 353, inclusive of Figure 232 (SEQ ID NO:397).

In a further aspect, the invention concerns an isolated PRO1788 polypeptide, comprising an amino acid 277 sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 17 to 353 of Figure 232 (SEQ ID NO:397).

In yet another aspect, the invention concerns an isolated PRO1788 polypeptide, comprising the sequence of amino acid residues 17 to about 353, inclusive of Figure 232 (SEQ ID NO:397), or a fragment thereof 5 sufficient to provide a binding site for an anti-PR01788 antibody. Preferably, the PR01788 fragment retains a qualitative biological activity of a native PR01788 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1788 polypeptide having the sequence of amino acid residues from about 17 to about 353, inclusive of Figure 232 (SEQ ID N0:397), or (b) 10 the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01788 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01788 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01788 polypeptide, by contacting the native PR01788 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1788 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 117. PRQ1801 A cDNA clone (DNA83500-2506) has been identified, having homology to nucleic acid encoding IL-19 25 polypeptide, that encodes a novel polypeptide, designated in the present application as "PR01801".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding aPR01801 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most 30 preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1801 polypeptide having the sequence of amino acid residues from about 1 or about 43 to about 261, inclusive of Figure 234 (SEQ ID N0:402), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01801 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 109 35 or about 235 and about 891, inclusive, of Figure 233 (SEQ ID N0:401). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 278 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203391 (DNA83500-2506) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in 5 ATCC Deposit No. 203391 (DNA83500-2506).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 43 to about 261, inclusive of Figure 234 (SEQ ID 10 N0:402), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 30 nucleotides, usually at least about 50 nucleotides, more usually at least about 100 nucleotides and generally at least about 150 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01801 polypeptide having the sequence of amino acid residues from 1 or 15 about 43 to about 261, inclusive of Figure 234 (SEQ ID N0:402), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding 20 a PRO 1801 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 42 in the sequence ofFigure 234 (SEQ ID N0:402).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 25 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 43 to about 261, inclusive of Figure 234 (SEQ ID N0:402), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01801 polypeptide coding sequence that may find 30 use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 233 (SEQ ID N0:401).

In another embodiment, the invention provides isolated PRO 1801 polypeptide encoded by any of the 35 isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PROl 801 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 43 to about 261 ofFigure 279 234 (SEQ ID N0:402).

In another aspect, the invention concerns an isolated PRO 1801 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 43 to about 261, inclusive of Figure 234 (SEQ ID NO:4Q2).

In a further aspect, the invention concerns an isolated PR01801 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 43 to about 261, inclusive of Figure 234 (SEQ ID N0:402).

In yet another aspect, the invention concerns an isolated PR01801 polypeptide, comprising the sequence 10 of amino acid residues 1 or about 43 to about 261, inclusive of Figure 234 (SEQ ID NO:402), or a fragment thereof sufficient to provide a binding site for an anti-PROl801 antibody. Preferably, the PROl801 fragment retains a qualitative biological activity of a native PR01801 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01801 polypeptide having the 15 sequence of amino acid residues from about 1 or about 43 to about 261, inclusive of Figure 234 (SEQ ID N0:402), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) 20 recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PR01801 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01801 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PRO 1801 polypeptide by contacting the native PRO 1801 polypeptide with a candidate molecule and 25 monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR01801 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier.

Another embodiment of the present invention is directed to a method of inhibiting the production of an inflammatory cytokine by a cell capable of producing that inflammatory cytokine, wherein the method comprises 30 the step of contacting the cell with a PR01801 polypeptide, wherein the production of the inflammatory cytokine is inhibited. The ceil may be, for example, a T-cell, an NK cell or a macrophage and the inflammatory cytokine whose production is inhibited may be, for example, IL-1, IL-6, IFN-y or TNF-a.

A further embodiment of the present invention is directed to a method for the treatment of an individual in need of immunosuppression, wherein the method comprises the step of administering to the individual an 35 immunosuppressive amount of a PR01801 polypeptide. The individual in need of immunosuppression may suffer from an autoimmune disease, such as rheumatoid arthritis, myasthenia gravis, insulin-dependent diabetes mellitus, systemic lupus erythematosus, thyroiditis or colitis, or from septic shock, endotoxic shock or any other 280 type of disorder where immunosuppression is desired. The individual may also be one who has received or is to receive a tissue transplant, where the method serves to inhibit rejection of the tissue transplant.

Other embodiments will become evident upon a reading of the present specification. 118. UCP4 A cDNA clone (DNA77568-1626) has been identified, having certain homologies to some known human uncoupling proteins, that encodes a novel polypeptide, designated in the present application as "UCP4." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a UCP4 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 10 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a UCP4 polypeptide having the sequence of amino acid residues from about 1 to about 323, inclusive of Figure 236 (SEQ ID N0:406), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a UCP4 polypeptide 15 comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 40 and about 1011 inclusive, of Figure 235 (SEQ ID N0:405). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least 20 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203134, or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203134. In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding 25 a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 323, inclusive of Figure 236 (SEQ ID N0:406), or the complement of the DNA of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA 30 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 323, inclusive of Figure 236 (SEQ ID N0:406), or (b) the complement of the DNA of (a).

Further embodiments of the invention are directed to fragments of the UCP4 coding sequence, which 35 are sufficiently long to be used as hybridization probes. Preferably, such fragments contain at least about 20 to about 80 consecutive bases included in the sequence of Figure 235 (SEQ ID N0:405). Optionally, such fragments include the N-terminus or the C-terminus of the sequence of Figure 236 (SEQ ID N0:406). 281 In another embodiment, the invention provides isolated UCP4 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence UCP4 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 323 of Figure 236 (SEQ ID N0:406).

In another aspect, the invention concerns an isolated UCP4 polypeptide, comprising an amino acid 5 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 323, inclusive of Figure 236 (SEQ ID N0:406).

In a further aspect, the invention concerns an isolated UCP4 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least 10 about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to 323 of Figure 236 (SEQ ID N0:406).

In yet another aspect, the invention concerns an isolated UCP4 polypeptide, comprising the sequence of amino acid residues 1 to about 323, inclusive of Figure 236 (SEQ ID N0:406), or a fragment thereof sufficient to, for instance, provide a binding site for an anti-UCP4 antibody. Preferably, the UCP4 fragment 15 retains at least one biological activity of a native UCP4 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a UCP4 polypeptide having the sequence of amino acid residues from about 1 to about 323, inclusive of Figure 236 (SEQ ID N0:406), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence 20 identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of the native UCP4 25 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-UCP4 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native UCP4 polypeptide, by contacting the native UCP4 polypeptide with a candidate molecule and monitoring the desired activity. The invention also provides therapeutic methods and diagnostic methods using UCP4.

In a still further embodiment, the invention concerns a composition comprising a UCP4 polypeptide, 30 or an agonist or antagonist as hereinabove defined, in combination with a carrier. 119. FRQ193 A cDNA clone (DNA23322-1393) has been identified that encodes a novel multi-transmembrane polypeptide, designated in the present application as "PR0193." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0193 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 282 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR0193 polypeptide having the sequence of amino acid residues from about 1 to about 158, inclusive of Figure 238 (SEQ ID N0:410), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0193 5 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 138 and about 611, inclusive, of Figure 237 (SEQ ID N0:409). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about. 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 10 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203400 (DNA23322-1393), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203400 (DNA23322-1393).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 158, inclusive of Figure 238 (SEQ ID N0:410), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0193 polypeptide having the sequence of amino acid residues from about 1 to about 158, inclusive of Figure 238 (SEQ ID N0:410), or (b) the complement of the DNA molecuie of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% 25 sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule. in a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0193 polypeptide in its soluble form, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domain has been tentatively 30 identified as extending from about amino acid positions 23-42,60-80,97-117 and 128-148 in the PR0193 amino acid sequence (Figure 238, SEQ ID N0:410).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 35 amino acid sequence of residues 1 to about 158, inclusive of Figure 238 (SEQ ID N0:410), or (b) the complement of the DNA of (a).

In another embodiment, the invention provides isolated PRO 193 polypeptide encoded by any of the 283 isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO 193 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 158 of Figure 238 (SEQ ID N0:410).

In another aspect, the invention concerns an isolated PR0193 polypeptide, comprising an amino acid 5 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 158, inclusive of Figure 238 (SEQ ID N0:410).

In a further aspect, the invention concerns an isolated PRO 193 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least 10 about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 through 158 of Figure 238 (SEQ ID N0:410).

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0193 polypeptide having the sequence of amino acid residues from about 1 to about 158, inclusive of Figure 238 (SEQ ID N0:410), or (b) 15 the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of die polypeptide, and (iii) recovering the polypeptide from tbe cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of the a native PR0193 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0193 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0193 polypeptide, by contacting the native PR0193 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PR0193 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 121. PRQ1335 A cDNA clone (DNA62812-1594) has been identified, having homology to nucleic acid encoding carbonic anhydrase that encodes a novel polypeptide, designated in the present application as "PRO1335*.

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1335 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01335 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 337, inclusive of Figure 242 (SEQ ID NO:423), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01335 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 271 or about 316 and about 1281, inclusive, of Figure 241 (SEQ ID NO:422). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 10 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203248 (DNA62812-1594) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in 15 ATCC Deposit No. 203248 (DNA62812-1594).

In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 16 to about 337, inclusive of Figure 242 (SEQ ID 20 NO:423), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 180 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01335 polypeptide having the sequence of amino acid residues from 1 or about 16 to about 337, inclusive of Figure 242 (SEQ ID NO:423), or (b) the complement of the DNA molecule of (a), and, 25 if the DNA molecuie has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01335 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and 30 its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 15 in the sequence of Figure 242 (SEQ ID NO:423). The transmembrane domain has been tentatively identified as extending from about amino acid position 291 to about amino acid position 310 in the PR01335 amino acid sequence (Figure 242, SEQ ID NO:423).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 287 amino acid sequence of residues 1 or about 16 to about 337, inclusive of Figure 242 (SEQ ID NO:423), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01335 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 5 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 241 (SEQ ID NO:422).

In another embodiment, the invention provides isolated PR01335 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequence PR01335 polypeptide, which in 10 certain embodiments, includes an amino acid sequence comprising residues 1 or about 16 to about 337 ofFigure 242 (SEQ ID NO:423).

In another aspect, the invention concerns an isolated PR01335 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the IS sequence of amino acid residues 1 or about 16 to about 337, inclusive of Figure 242 (SEQ ID NO:423).

In a further aspect, the invention concerns an isolated PR01335 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 16 to about 337, inclusive of Figure 242 (SEQ ID NO:423).

In yet another aspect, the invention concerns an isolated PROI335 polypeptide, comprising the sequence of amino acid residues 1 or about 16 to about 337, inclusive of Figure 242 (SEQ ID NO:423), or a fragment thereof sufficient to provide a binding site for an anti-PR01335 antibody. Preferably, the PR01335 fragment retains a qualitative biological activity of a native PR01335 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA 25 molecule under stringent conditions with (a) a DNA molecule encoding a PR01335 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 337, inclusive of Figure 242 (SEQ ID NO:423), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host 30 cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.

In yet anotber embodiment, the invention concerns agonists and antagonists of a native PR01335 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PRO!335 antibody.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a 35 native PR01335 polypeptide by contacting the native PR01335 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a composition comprising a PRO1335 polypeptide, 288 or an agonist or antagonist as hereinabove defined, in combination with a pharmaceuticaliy acceptable carrier. 122. PROl 329 A cDNA clone (DNA66660-1585) has been identified that encodes a novel polypeptide designated in the present application as "PR01329." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01329 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PROI329 polypeptide having 10 the sequence of amino acid residues from 1 or about 17 to about 209, inclusive ofFigure 244 (SEQ ID N0.429), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01329 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 138 and about 716, inclusive, of Figure 243 (SEQ ID NO:428). Preferably, hybridization occurs under stringent 15 hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203279 20 (DNA66660-1585), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203279 (DNA66660-1585).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence 25 identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 17 to about 209, inclusive of Figure 244 (SEQ ID NO:429), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule 30 under stringent conditions with (a) a DNA molecule encoding a PRO1329 polypeptide having the sequence of amino acid residues from about 17 to about 209, inclusive of Figure 244 (SEQ ID NO:429), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule. 35 In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01329 polypeptide, with or without the N-tenninal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as 289 extending from amino acid position 1 through about amino acid position 16 in the sequence ofFigure 244 (SEQ ID NO:429).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the 5 amino acid sequence of residues 17 to about 209, inclusive of Figure 244 (SEQ ID NO:429), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO 1329 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 10 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01329 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PRO1329 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 17 to 209 ofFigure 244 (SEQ ID NO:429). 15 In another aspect, the invention concerns an isolated PR01329 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 17 to about 209, inclusive of Figure 244 (SEQ ID N0:429).

In a further aspect, the invention concerns an isolated PR01329 polypeptide, comprising an amino acid 20 sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 17 to 209 of Figure 244 (SEQ ID N0:429).

In yet another aspect, the invention concerns an isolated PRO1329 polypeptide, comprising the sequence of amino acid residues 17 to about 209, inclusive of Figure 244 (SEQ ID NO:429), or a fragment thereof 25 sufficient to provide a binding site for an anti-PR01329 antibody. Preferably, the PR01329 fragment retains a qualitative biological activity of a native PR01329 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01329 polypeptide having the sequence of amino acid residues from about 17 to about 209, inclusive of Figure 244 (SEQ ID N0:429), or (b) 30 the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. 123. PRQ1550 A cDNA clone (DNA76393-1664) has been identified that encodes a novel secreted polypeptide and 290 designated in the present application as "PR01550." In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01550 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01550 polypeptide having the sequence of amino acid residues from 1 or about 31 to about 243, inclusive ofFigure 246 (SEQ ID NO:232), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01550 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 228 and about 866, inclusive, of Figure 245 (SEQ ID NO:231). Preferably, hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203323 (DNA76393-1664), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC 1 Deposit No. 203323 (DNA76393-1664).

In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 31 to about 243, inclusive of Figure 246 (SEQ ID NO:232), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01550 polypeptide having the sequence of amino acid residues from about 31 to about 243, inclusive of Figure 246 (SEQ ID NO:232), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1550 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 30 in the sequence of Figure 246 (SEQ ID NO:232).

In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 31 to about 243, inclusive of Figure 246 (SEQ ID NO:232), or (b) the complement of the DNA of (a).

Another embodiment is directed to fragments of a PR01550 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PR01550 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.

In a specific aspect, the invention provides isolated native sequence PR01550 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 31 to 243 of Figure 246 (SEQ ID NO:232).

In another aspect, the invention concerns an isolated PRO1550 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 31 to about 243, inclusive of Figure 246 (SEQ ID NO:232).

In a further aspect, the invention concerns an isolated PR01550 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 31 to 243 ofFigure 246 (SEQ ID NO:232).

In yet another aspect, the invention concerns an isolated PRO 1550 polypeptide, comprising the sequence of amino acid residues 31 to about 243, inclusive of Figure 246 (SEQ ID NO:232), or a fragment thereof sufficient to provide a binding site for an anti-PR01550 antibody. Preferably, the PR01550 fragment retains a qualitative biological activity of a native PRO 1550 polypeptide.

In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1550 polypeptide having the sequence of amino acid residues from about 31 to about 243, inclusive of Figure 246 (SEQ ID NO:232), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture. 124. Additional Embodiments In other embodiments of the present invention, the invention provides vectors comprising DNA encoding any of the herein described polypeptides. Host cell comprising any such vector are also provided. By way of example, the host cells may be CHO cells, E. coli, or yeast. A process for producing any of the herein described polypeptides is further provided and comprises culturing host cells under conditions suitable for expression of the desired polypeptide and recovering the desired polypeptide from the cell culture.

In other embodiments, the invention provides chimeric moleculescomprising any of the herein described polypeptides fused to a heterologous polypeptide or amino acid sequence. Example of such chimeric molecules comprise any of the herein described polypeptides fused to an epitope tag sequence or a Fc region of an immunoglobulin.

In another embodiment, the invention provides an antibody which specifically binds to any of the above 5 or below described polypeptides. Optionally, the antibody is a monoclonal antibody, humanized antibody, antibody fragment or single-chain antibody.

In yet other embodiments, the invention provides oligonucleotide probes useful for isolating genomic and cDNA nucleotide sequences, wherein those probes may be derived from any of the above or below described nucleotide sequences.

In other embodiments, the invention provides an isolated nucleic acid molecule comprising a nucleotide sequence that encodes a PRO polypeptide.

In one aspect, the isolated nucleic acid molecule comprises a nucleotide sequence having at least about 80% sequence identity, preferably at least about 81% sequence identity, more preferably at least about 82% sequence identity, yet more preferably at least about 83% sequence identity, yet more preferably at least about 15 84% sequence identity, yet more preferably at least about 85% sequence identity, yet more preferably at least about 86% sequence identity, yet more preferably at least about 87% sequence identity, yet more preferably at least about 88% sequence identiiy, yet more preferably at least about 89% sequence identity, yet more preferably at least about 90% sequence identity, yet more preferably at least about 91% sequence identity, yet more preferably at least about 92% sequence identity, yet more preferably at least about 93% sequence identity, yet 20 more preferably at least about 94 % sequence identity, yet more preferably at least about 95 % sequence identity, yet more preferably at least about 96% sequence identity, yet more preferably at least about 97% sequence identity, yet more preferably at least about 98% sequence identity and yet more preferably at least about 99% sequence identity to (a) a DNA molecule encoding a PRO polypeptide having a full-length amino acid sequence as disclosed herein, an amino acid sequence lacking the signal peptide as disclosed herein or an extracellular 25 domain of a transmembrane protein, with or without the signal peptide, as disclosed herein, or (b) the complement of the DNA molecule of (a).

In other aspects, the isolated nucleic acid molecule comprises a nucleotide sequence having at least about 80% sequence identity, preferably at least about 81% sequence identity, more preferably at least about 82% sequence identity, yet more preferably at least about 83% sequence identity, yet more preferably at least about 30 84% sequence identity, yet more preferably at least about 85% sequence identity, yet more preferably at least about 86% sequence identity, yet more preferably at least about 87% sequence identity, yet more preferably at least about 88 % sequence identity, yet more preferably at least about 89 % sequence identity, yet more preferably at least about 90% sequence identity, yet more preferably at least about 91 % sequence identity, yet more preferably at least about 92% sequence identity, yet more preferably at least about 93% sequence identity, yet 35 more preferably at least about 94% sequence identity, yet more preferably at least about 95 % sequence identity, yet more preferably at least about 96% sequence identity, yet more preferably at least about 97% sequence identity, yet more preferably at least about 98% sequence identity and yet more preferably at least about 99% 293 sequence identity to (a) a DNA molecule comprising the coding sequence of a full-length PRO polypeptide cDNA as disclosed herein, the coding sequence of a PRO polypeptide lacking the signal peptide as disclosed herein or the coding sequence of an extracellular domain of a transmembrane PRO polypeptide, with or without the signal peptide, as disclosed herein, or (b) the complement of the DNA molecule of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising a nucleotide 5 sequence having at least about 80% sequence identity, preferably at least about 81% sequence identity, more preferably at least about 82% sequence identity, yet more preferably at least about 83% sequence identity, yet more preferably at least about 84 % sequence identity, yet more preferably at least about 85 % sequence identity, yet more preferably at least about 86% sequence identity, yet more preferably at least about 87% sequence identity, yet more preferably at least about 88% sequence identity, yet more preferably at least about 89% 10 sequence identity, yet more preferably at least about 90% sequence identity, yet more preferably at least about 91 % sequence identity, yet more preferably at least about 92% sequence identity, yet more preferably at least about 93% sequence identity, yet more preferably at least about 94% sequence identity, yet more preferably at least about 95 % sequence identity, yet more preferably at least about 96% sequence identity, yet more preferably at least about 97% sequence identity, yet more preferably at least about 98% sequence identity and yet more 15 preferably at least about 99% sequence identity to (a) a DNA molecule that encodes the same mature polypeptide encoded by any of the human protein cDNAs deposited with the ATCC as disclosed herein, or (b) the complement of the DNA molecule of (a).

Another aspect the invention provides an isolated nucleic acid molecule comprising a nucleotide sequence encoding a PRO polypeptide which is either transmembrane domain-deleted or transmembrane domain-20 inactivated, or is complementary to such encoding nucleotide sequence, wherein the transmembrane domain(s) of such polypeptide are disclosed herein. Therefore, soluble extracellular domains of the herein described PRO polypeptides are contemplated.

Another embodiment is directed to fragments of a PRO polypeptide coding sequence that may find use as, for example, hybridization probes or for encoding fragments of a PRO polypeptide that may optionally 25 encode a polypeptide comprising a binding site for an anti-PRO antibody. Such nucleic acid fragments are usually at least about 20 nucleotides in length, preferably at least about 30 nucleotides in length, more preferably at least about 40 nucleotides in length, yet more preferably at least about 50 nucleotides in length, yet more preferably at least about 60 nucleotides in length, yet more preferably at least about 70 nucleotides in length, yet more preferably at least about 80 nucleotides in length, yet more preferably at least about 90 nucleotides in 30 length, yet more preferably at least about 100 nucleotides in length, yet more preferably at least about 110 nucleotides in length, yet more preferably at least about 120 nucleotides in length, yet more preferably at least about 130 nucleotides in length, yet more preferably at least about 140 nucleotides in length, yet more preferably at least about 150 nucleotides in length, yet more preferably at least about 160 nucleotides in length, yet more preferably at least about 170 nucleotides in length, yet more preferably at least about 180 nucleotides in length, 35 yet more preferably at least about 190 nucleotides in length, yet more preferably at least about 200 nucleotides in length, yet more preferably at least about 250 nucleotides in length, yet more preferably at least about 300 nucleotides in length, yet more preferably at least about 350 nucleotides in length, yet more preferably at least 294 about 400 nucleotides in length, yet more preferably at least about 450 nucleotides in length, yet more preferably at least about 500 nucleotides in length, yet more preferably at least about 600 nucleotides in length, yet more preferably at least about 700 nucleotides in length, yet more preferably at least about 800 nucleotides in length, yet more preferably at least about 900 nucleotides in length and yet more preferably at least about 1000 nucleotides in length, wherein in this context the term "about" means the referenced nucleotide sequence length 5 plus or minus 10% of that referenced length. It is noted that novel fragments of a PRO polypeptide-encoding nucleotide sequence may be determined in a routine manner by aligning the PRO polypeptide-encoding nucleotide sequence with other known nucleotide sequences using any of a number of well known sequence alignment programs and determining which PRO polypeptide-encoding nucleotide sequence fragments) are novel. All of such PRO polypeptide-encoding nucleotide sequences are contemplated herein. Also contemplated are the PRO 10 polypeptide fragments encoded by these nucleotide molecule fragments, preferably those PRO polypeptide fragments that comprise a binding site for an anti-PRO antibody.

In another embodiment, the invention provides isolated PRO polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a certain aspect, the invention concerns an isolated PRO polypeptide, comprising an amino acid 15 sequence having at least about 80% sequence identity, preferably at least about 81% sequence identity, more preferably at least about 82% sequence identity, yet more preferably at least about 83% sequence identity, yet more preferably at least about 84% sequence identity, yet more preferably at least about 85% sequence identity, yet more preferably at least about 86% sequence identity, yet more preferably at least about 87% sequence identity, yet more preferably at least about 88% sequence identity, yet more preferably at least about 89% 20 sequence identity, yet more preferably at least about 90% sequence identity, yet more preferably at least about 91% sequence identity, yet more preferably at least about 92% sequence identity, yet more preferably at least about 93% sequence identity, yet more preferably at least about 94% sequence identity, yet more preferably at least about 95 % sequence identity, yet more preferably at least about 96% sequence identity, yet more preferably at least about 97% sequence identity, yet more preferably at least about 98% sequence identity and yet more 25 preferably at least about 99% sequence identity to a PRO polypeptide having a full-length amino acid sequence as disclosed herein, an amino acid sequence lacking the signal peptide as disclosed herein or an extracellular domain of a transmembrane protein, with or without the signal peptide, as disclosed herein.

In a further aspect, the invention concerns an isolated PRO polypeptide comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 81 % sequence identity, more 30 preferably at least about 82% sequence identity, yet more preferably at least about 83% sequence identity, yet more preferably at least about 84% sequence identity, yet more preferably at least about 85% sequence identity, yet more preferably at least about 86% sequence identity, yet more preferably at least about 87% sequence identity, yet more preferably at least about 88% sequence identity, yet more preferably at least about 89% sequence identity, yet more preferably at least about 90% sequence identity, yet more preferably at least about 35 91 % sequence identity, yet more preferably at least about 92% sequence identity, yet more preferably at least about 93 % sequence identity, yet more preferably at least about 94% sequence identity, yet more preferably at least about 95 % sequence identity, yet more preferably at least about 96 % sequence identity, yet more preferably 295 at least about 97% sequence identity, yet more preferably at least about 98% sequence identity and yet more preferably at least about 99% sequence identity to an amino acid sequence encoded by any of the human protein cDNAs deposited with the ATCC as disclosed herein.

In a further aspect, the invention concerns an isolated PRO polypeptide comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 81 % positives, more preferably at least 5 about 82% positives, yet more preferably at least about 83 % positives, yet more preferably at least about 84% positives, yet more preferably at least about 85 % positives, yet more preferably at least about 86% positives, yet more preferably at least about 87% positives, yet more preferably at least about 88% positives, yet more preferably at least about 89% positives, yet more preferably at least about 90% positives, yet more preferably at least about 91 % positives, yet more preferably at least about 92 % positives, yet more preferably at least about 10 93% positives, yet more preferably at least about 94% positives, yet more preferably at least about 95% positives, yet more preferably at least about 96% positives, yet more preferably at least about 97% positives, yet more preferably at least about 98% positives and yet more preferably at least about 99% positives when compared with the amino acid sequence of a PRO polypeptide having a full-length amino acid sequence as disclosed herein, an amino acid sequence lacking the signal peptide as disclosed herein or an extracellular domain 15 of a transmembrane protein, with or without the signal peptide, as disclosed herein.

In a specific aspect, the invention provides an isolated PRO polypeptide without the N-terminal signal sequence and/or the initiating methionine and is encoded by a nucleotide sequence that encodes such an amino acid sequence as hereinbefore described. Processes for producing the same are also herein described, wherein those processes comprise culturing a host cell comprising a vector which comprises the appropriate encoding 20 nucleic acid molecule under conditions suitable for expression of the PRO polypeptide and recovering the PRO polypeptide from the cell culture.

Another aspect the invention provides an isolated PRO polypeptide which is either transmembrane domain-deleted or transmembrane domain-inactivated. Processes for producing the same are also herein described, wherein those processes comprise culturing a host cell comprising a vector which comprises the 25 appropriate encoding nucleic acid molecule under conditions suitable for expression of the PRO polypeptide and recovering the PRO polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO polypeptide as defined herein. In a particular embodiment, the agonist or antagonist is an anti-PRO antibody or a small molecule.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists to a PRO polypeptide which comprise contacting the PRO polypeptide with a candidate molecule and monitoring a biological activity mediated by said PRO polypeptide. Preferably, the PRO polypeptide is a native PRO polypeptide.

In a still further embodiment, the invention concerns a composition of matter comprising a PRO 35 polypeptide, or an agonist or antagonist of a PRO polypeptide as herein described, or an anti-PRO antibody, in combination with a carrier. Optionally, the carrier is a pharmaceuticaliy acceptable carrier.

Another embodiment of the present invention is directed to the use of a PRO polypeptide, or an agonist 296 or antagonist thereof as hereinbefore described, or an anti-PRO antibody, for the preparation of a medicament useful in the treatment of a condition which is responsive to the PRO polypeptide, an agonist or antagonist thereof or an anti-PRO antibody.

BRIEF DESCRIPTION OF THE DRAWINGS 5 Figure 1 shows a nucleotide sequence (SEQ ID NO:3) of anative sequence PR01560 (UNQ767) cDNA, wherein SEQ ID NO:3 is a clone designated herein as "DNA19902-1669". The start and stop codons are shown in bold and underlined fcmt.

Figure 2 shows the amino acid sequence (SEQ ID NO:4) derived from the coding sequence of SEQ ID NO:3 shown in Figure 1.

Figure 3 shows a nucleotide sequence (SEQ ID NO:5) of a native sequence PR0444 (UNQ328) cDNA, wherein SEQ ID NO:5 is a clone designated herein as "DNA26846-1397". The start and stop codons are shown in bold and underlined font.

Figure 4 shows the amino acid sequence (SEQ ID NO:6) derived from the coding sequence of SEQ ID NO:5 shown in Figure 3.

Figure 5 shows a nucleotide sequence (SEQ ID NO:7) of anative sequence PRO 1018 (UNQ501) cDNA, wherein SEQ ID NO:7 is a clone designated herein as "DNA56107-1415". The start and stop codons are shown in bold and underlined font.

Figure 6 shows the amino acid sequence (SEQ ID NO:8) derived from the coding sequence of SEQ ID NO:7 shown in Figure 5.

Figure 7 shows a nucleotide sequence (SEQ ID NO:9) of a native sequence PR01773 (UNQ835) cDNA, wherein SEQ ID NO:9 is a clone designated herein as "DNA56406-1704". The start and stop codons are shown in bold and underlined font.

Figure 8 shows the amino acid sequence (SEQ ID NO: 10) derived from the coding sequence of SEQ ID NO:9 shown in Figure 7.

Figure 9 shows a nucleotide sequence (SEQ ID NO: 11) of a native sequence PR01477 (UNQ747) cDNA, wherein SEQ ID NO:ll is a clone designated herein as "DNA56529-1647". The start and stop codons are shown in bold and underlined font.

Figure 10 shows the amino acid sequence (SEQ ID NO: 12) derived from the coding sequence of SEQ ID NO: 11 shown in Figure 9.

Figure 11 shows a nucleotide sequence (SEQ ID NO: 16) of a native sequence PR01478 (UNQ748) cDNA, wherein SEQ ID NO:16 is a clone designated herein as "DNA56531-1648". The start and stop codons are shown in bold and underlined font.

Figure 12 shows the amino acid sequence (SEQ ID NO: 17) derived from the coding sequence of SEQ ID NO:16 shown in Figure 11.

Figure 13 shows a nucleotide sequence (SEQ ID NO:21) of a native sequence PR0831 (UNQ471) cDNA, wherein SEQ ID NO:21 is a clone designated herein as "DNA56862-1343". The start and stop codons are shown in bold and underlined font. 297 Figure 14 shows the amino acid sequence (SEQ ID NO:22) derived from the coding sequence of SEQ ID NO:21 shown in Figure 13.

Figure 15 shows a nucleotide sequence (SEQ ID NO:23) of a native sequence PROl 113 (UNQ556) cDNA, wherein SEQ ID NO:23 is a clone designated herein as "DNA57254-1477". The start and stop codons axe shown in bold and underlined font.

Figure 16 shows the amino acid sequence (SEQ ID NO:24) derived from the coding sequence of SEQ ID NO:23 shown in Figure 15.

Figure 17 shows a nucleotide sequence (SEQ ID NO:28) of a native sequence PROl 194 (UNQ607) cDNA, wherein SEQ ID NO:28 is a clone designated herein as "DNA57841-1522". The start and stop codons are shown in bold and underlined font.

Figure 18 shows the amino acid sequence (SEQ ID NO:29) derived from the coding sequence of SEQ ID NO:28 shown in Figure 17.

Figure 19 shows a nucleotide sequence (SEQ ID N0:30) of a native sequence PROlllO (UNQ553) cDNA, wherein SEQ ID N0:30 is a clone designated herein as "DNA58727-1474". The start and stop codons are shown in bold and underlined font.

Figure 20 shows the amino acid sequence (SEQ ID NO:31) derived from the coding sequence of SEQ ID N0:30 shown in Figure 19.

Figure 21 shows a nucleotide sequence (SEQ ID NO:32) of a native sequence PR01378 (UNQ715) cDNA, wherein SEQ ID NO:32 is a clone designated herein as "DNA58730-1607". The start and stop codons are shown in bold and underlined font.

Figure 22 shows the amino acid sequence (SEQ ID NO:33) derived from the coding sequence of SEQ ID NO:32 shown in Figure 21.

Figure 23 shows a nucleotide sequence (SEQ ID N0:40) of a native sequence PR01481 (UNQ750) cDNA, wherein SEQ ID N0:40 is a clone designated herein as "DNA58732-1650". The start and stop codons are shown in bold and underlined font.

Figure 24 shows the amino acid sequence (SEQ ID NO:41) derived from the coding sequence of SEQ ID N0:40 shown in Figure 23.

Figure 25 shows a nucleotide sequence (SEQ ID N0:42) of a native sequence PROl 189 (UNQ603) cDNA, wherein SEQ ID NO:42 is a clone designated herein as "DNA58828-1519". The start and stop codons are shown in bold and underlined font.

Figure 26 shows the amino acid sequence (SEQ ID NO:43) derived from the coding sequence of SEQ ID NO:42 shown in Figure 25.

Figure 27 shows a nucleotide sequence (SEQ ID NO:49) of a native sequence PR01415 (UNQ731) cDNA, wherein SEQ ID N0:49 is a clone designated herein as "DNA58852-1637". The start and stop codons are shown in bold and underlined font.

Figure 28 shows the amino acid sequence (SEQ ID N0:50) derived from the coding sequence of SEQ ID N0:49 shown in Figure 27. 298 Figure 29 shows a nucleotide sequence (SEQ ID NO:51) of a native sequence PR01411 (UNQ729) cDNA, wherein SEQ ID NO:5I is a clone designated herein as "DNA59212-I627". The start and stop codons are shown in bold and underlined font.

Figure 30 shows the amino acid sequence (SEQ ID NO:52) derived from the coding sequence of SEQ ID NO:5I shown in Figure 29.

Figure 31 shows a nucleotide sequence (SEQ ID NO:53) of a native sequence PRO1295 (UNQ664) cDNA, wherein SEQ ID NO:53 is a clone designated herein as "DNA59218-1559". The start and stop codons are shown in bold and underlined font.

Figure 32 shows the amino acid sequence (SEQ ID NO:54) derived from the coding sequence of SEQ ID NO:53 shown in Figure 31.

Figure 33 shows a nucleotide sequence (SEQ ID NO:55) of a native sequence PR01359 (UNQ708) cDNA, wherein SEQ ID N0:55 is a clone designated herein as "DNA59219-1613". The start and stop codons are shown in bold and underlined font.

Figure 34 shows the amino acid sequence (SEQ ID NO:56) derived from the coding sequence of SEQ ID NO:55 shown in Figure 33.

Figure 35 shows a nucleotide sequence (SEQ ID NO:57) of a native sequence PROl 190 (UNQ604) cDNA, wherein SEQ ID NO:57 is a clone designated herein as "DNA59586-1520". The start and stop codons are shown in bold and underlined font.

Figure 36 shows the amino acid sequence (SEQ ID NO:58) derived from the coding sequence of SEQ ID NO:57 shown in Figure 35.

Figure 37 shows a nucleotide sequence (SEQ ID NO:62) of a native sequence PR01772 (UNQ834) cDNA, wherein SEQ ID NO:62 is a clone designated herein as "DNA59817-1703". The start and stop codons are shown in bold and underlined font.

Figure 38 shows the amino acid sequence (SEQ ID NO:63) derived from the coding sequence of SEQ ID NO:62 shown in Figure 37.

Figure 39 shows a nucleotide sequence (SEQ ID NO:67) of a native sequence PR01248 (UNQ631) cDNA, wherein SEQ ID N0:67 is a clone designated herein as "DNA60278-1530". The start and stop codons are shown in bold and underlined font.

Figure 40 shows the amino acid sequence (SEQ ID NO :68) derived from the coding sequence of SEQ ID NO:67 shown in Figure 39.

Figure 41 shows a nucleotide sequence (SEQ ID NO:69) of a native sequence PR01316 (UNQ682) cDNA, wherein SEQ ID NO:69 is a clone designated herein as "DNA60608-1577". The start and stop codons are shown in bold and underlined font.

Figure 42 shows the amino acid sequence (SEQ ID N0:70) derived from the coding sequence of SEQ ID NO:69 shown in Figure 41.

Figure 43 shows a nucleotide sequence (SEQ ID NO:71) of a native sequence PROl 197 (UNQ610) cDNA, wherein SEQ ID NO:71 is a clone designated herein as "DNA60611-1524". The start and stop codons are shown in bold and underlined font. 299 PCT/US99/201H Figure 44 shows the amino acid sequence (SEQ ID NO:72) derived from the coding sequence of SEQ ID NO:71 shown in Figure 43.

Figure 45 shows a nucleotide sequence (SEQ ID NO:76) of a native sequence PR01293 (UNQ662) cDNA, wherein SEQ ID NO:76 is a clone designated herein as "DNA60618-1557". The start and stop codons are shown in bold and underlined font.

Figure 46 shows the amino acid sequence (SEQ ID NO:77) derived from the coding sequence of SEQ ID NO:76 shown in Figure 45.

Figure 47 shows a nucleotide sequence (SEQ ID NO:78) of a native sequence PR01380 (UNQ717) cDNA, wherein SEQ ID NO:78 is a clone designated herein as "DNA60740-1615". The start and stop codons are shown in bold and underlined font.

Figure 48 shows the amino acid sequence (SEQ ID NO:79) derived from the coding sequence of SEQ ID NO:78 shown in Figure 47.

Figure 49 shows a nucleotide sequence (SEQ ID NO:83) of a native sequence PRO1265 (UNQ636) cDNA, wherein SEQ ID NO:83 is a clone designated herein as "DNA60764-1533". The start and stop codons are shown in bold and underlined font.

Figure 50 shows the amino acid sequence (SEQ ID NO:84) derived from the coding sequence of SEQ ID NO:83 shown in Figure 49.

Figure 51 shows a nucleotide sequence (SEQ ID NO:85) of a native sequence PRO 1250 (UNQ633) cDNA, wherein SEQ ID NO:85 is a clone designated herein as "DNA60775-1532". The start and stop codons are shown in bold and underlined font.

Figure 52 shows the amino acid sequence (SEQ ID NO:86) derived from the coding sequence of SEQ ID NO:85 shown in Figure 51.

Figure 53 shows a nucleotide sequence (SEQ ID NO:87) of a native sequence PRO1475 (UNQ746) cDNA, wherein SEQ ID NO:87 is a clone designated herein as "DNA61185-1646". The start and stop codons are shown in bold and underlined font.

Figure 54 shows the amino acid sequence (SEQ ID NO:88) derived from the coding sequence of SEQ ID NO:87 shown in Figure 53.

Figure 55 shows a nucleotide sequence (SEQ ID NO:94) of a native sequence PR01377 (UNQ714) cDNA, wherein SEQ ID NO:94 is a clone designated herein as "DNA61608-1606". The start and stop codons are shown in bold and underlined font.

Figure 56 shows the amino acid sequence (SEQ ID NO:95) derived from the coding sequence of SEQ ID NO:94 shown in Figure 55.

Figure 57 shows a nucleotide sequence (SEQ ID NO:99) of a native sequence PR01326 (UNQ686) cDNA, wherein SEQ ID NO:99 is a clone designated herein as "DNA62808-1582". The start and stop codons are shown in bold and underlined font.

Figure 58 shows the amino acid sequence (SEQ ID NO: 100) derived from the coding sequence of SEQ ID NO:99 shown in Figure 57. 300 Figure 59 shows a nucleotide sequence (SEQ ID NO: 101) of a native sequence PR01249 (UNQ632) cDNA, wherein SEQ IDNO.lOl is a clone designated herein as "DNA62809-1531". The start and stop codons are shown in bold and underlined font.

Figure 60 shows the amino acid sequence (SEQ ID NO: 102) derived from the coding sequence of SEQ ID NO.IOO shown in Figure 59.

Figure 61 shows a nucleotide sequence (SEQ ID NO: 103) of a native sequence PR01315 (UNQ681) cDNA, wherein SEQ ID NO: 103 is a clone designated herein as "DNA62815-1578". The start and stop codons are shown in bold and underlined font.

Figure 62 shows the amino acid sequence (SEQ ID NO: 104) derived from the coding sequence of SEQ ID NO: 103 shown in Figure 61.

Figure 63 shows a nucleotide sequence (SEQ ID NO:l 10) of a native sequence PR01549 (UNQ782) cDNA, wherein SEQ ID NO:l 10 is a clone designated herein as "DNA62845-1684". The start and stop codons are shown in bold and underlined font.

Figure 64 shows the amino acid sequence (SEQ ID NO: 111) derived from the coding sequence of SEQ ID NO:l 10 shown in Figure 63.

Figure 65 shows a nucleotide sequence (SEQ ID NO: 115) of a native sequence PR01430 (UNQ736) cDNA, wherein SEQ ID NO: 115 is a clone designated herein as "DNA64842-1632". The start and stop codons are shown in bold and underlined font.

Figure 66 shows the amino acid sequence (SEQ ID NO: 116) derived from the coding sequence of SEQ ID NO: 115 shown in Figure 65.

Figure 67 shows a nucleotide sequence (SEQ ID NO: 117) of a native sequence PR01374 (UNQ711) cDNA, wherein SEQ ID NO: 117 is a clone designated herein as "DNA64849-1604". The start and stop codons are shown in bold and underlined font.

Figure 68 shows the amino acid sequence (SEQ ID NO: 118) derived from the coding sequence of SEQ ID NO: 117 shown in Figure 67.

Figure 69 shows a nucleotide sequence (SEQ ID NO: 122) of a native sequence PRO 1311 (UNQ677) cDNA, wherein SEQ ID NO: 122 is a clone designated herein as "DNA64863-1573". The start and stop codons are shown in bold and underlined font.

Figure 70 shows the amino acid sequence (SEQ ID NO: 123) derived from the coding sequence of SEQ ID NO: 122 shown in Figure 69.

Figure 71 shows a nucleotide sequence (SEQ ID NO: 127) of a native sequence PRO 1357 (UNQ706) cDNA, wherein SEQ ID NO: 127 is a clone designated herein as "DNA64881-1602". The start and stop codons are shown in bold and underlined font.

Figure 72 shows the amino acid sequence (SEQ ID NO: 128) derived from the coding sequence of SEQ ID NO: 127 shown in Figure 71.

Figure 73 shows a nucleotide sequence (SEQ ID NO: 129) of a native sequence PR01244 (UNQ628) cDNA, wherein SEQ ID NO: 129 is a clone designated herein as "DNA64883-1526". The start and stop codons are shown in bold and underlined font. 301 Figure 74 shows the amino acid sequence (SEQ ID NO: 130) derived from the coding sequence of SEQ ID NO: 129 shown in Figure 73.

Figure 75 shows a nucleotide sequence (SEQ ID NO: 131) of a native sequence PRO1246 (UNQ630) cDNA, wherein SEQ ID NO: 131 is a clone designated herein as "DNA64885-1529". The start and stop codons are shown in bold and underlined font.

Figure 76 shows the amino acid sequence (SEQ ID NO: 132) derived from the coding sequence of SEQ ID NO:131 shown in Figure 75.

Figure 77 shows a nucleotide sequence (SEQ ID NO: 133) of a native sequence PRO 1356 (UNQ705) cDNA, wherein SEQ ID NO: 133 is a clone designated herein as "DNA64886-1601". The start and stop codons are shown in bold and underlined font.

Figure 78 shows the amino acid sequence (SEQ ID NO: 134) derived from the coding sequence of SEQ ID NO: 133 shown in Figure 77.

Figure 79 shows a nucleotide sequence (SEQ ID NO: 135) of a native sequence PR01275 (UNQ645) cDNA, wherein SEQ ID NO: 135 is a clone designated herein as "DNA64888-1542". The start and stop codons are shown in bold and underlined font.

Figure 80 shows the amino acid sequence (SEQ ID NO: 136) derived from the coding sequence of SEQ ID NO: 135 shown in Figure 79.

Figure 81 shows a nucleotide sequence (SEQ ID NO: 137) of a native sequence PR01274 (UNQ644) cDNA, wherein SEQ ID NO: 137 is a clone designated herein as "DNA64889-1542". The start and stop codons are shown in bold and underlined font.

Figure 82 shows the amino acid sequence (SEQ ID NO: 138) derived from the coding sequence of SEQ ID NO: 137 shown in Figure 81.

Figure 83 shows a nucleotide sequence (SEQ ID NO: 139) of a native sequence PR01412 (UNQ730) cDNA, wherein SEQ ID NO:139 is a clone designated herein as "DNA64897-1628". The start and stop codons are shown in bold and underlined font.

Figure 84 shows the amino acid sequence (SEQ ID NO: 140) derived from the coding sequence of SEQ ID NO: 139 shown in Figure 83.

Figure 85 shows a nucleotide sequence (SEQ ID NO: 141) of a native sequence PR01557 (UNQ765) cDNA, wherein SEQ ID NO: 141 is a clone designated herein as "DNA64902-1667". The start and stop codons are shown in bold and underlined font.

Figure 86 shows the amino acid sequence (SEQ ID NO: 142) derived from the coding sequence of SEQ ID NO: 141 shown in Figure 85.

Figure 87 shows a nucleotide sequence (SEQ ID NO: 143) of a native sequence PRO 1286 (UNQ655) cDN A, wherein SEQ ID NO: 143 is a clone designated herein as "DNA64903-1553". The start and stop codons are shown in bold and underlined font.

Figure 88 shows the amino acid sequence (SEQ ID NO: 144) derived from the coding sequence of SEQ ID NO: 143 shown in Figure 87. 302 Figure 89 shows a nucleotide sequence (SEQ ID NO: 145) of a native sequence PR01294 (UNQ663) cDNA, wherein SEQ ID NO: 145 is a clone designated herein as "DNA64905-1558". The start and stop codons are shown in bold and underlined font.

Figure 90 shows the amino acid sequence (SEQ ID NO: 146) derived from the coding sequence of SEQ ID NO: 145 shown in Figure 89.

Figure 91 shows a nucleotide sequence (SEQ ID NO: 147) of a native sequence PR01347 (UNQ702) cDNA, wherein SEQ ID NO: 147 is a clone designated herein as "DNA64950-1590". The start and stop codons are shown in bold and underlined font.

Figure 92 shows the amino acid sequence (SEQ ID NO: 148) derived from the coding sequence of SEQ ID NO: 147 shown in Figure 91.

Figure 93 shows a nucleotide sequence (SEQ ID NO: 152) of a native sequence PR01305 (UNQ671) cDNA, wherein SEQ ID NO: 152 is a clone designated herein as "DNA64952-1568". The start and stop codons are shown in bold and underlined font.

Figure 94 shows the amino acid sequence (SEQ ID NO: 153) derived from the coding sequence of SEQ ID NO: 152 shown in Figure 93.

Figure 95 shows a nucleotide sequence (SEQ ID NO: 157) of a native sequence PRO1273 (UNQ643) cDNA, wherein SEQ ID NO: 157 is a clone designated herein as "DNA65402-1540". The start and stop codons are shown in bold and underlined font.

Figure 96 shows the amino acid sequence (SEQ ID NO: 158) derived from the coding sequence of SEQ ID NO: 157 shown in Figure 95.

Figure 97 shows a nucleotide sequence (SEQ ID NO: 159) of a native sequence PR01302 (UNQ668) cDNA, wherein SEQ ID NO: 159 is a clone designated herein as "DNA65403-1565". The start and stop codons are shown in bold and underlined font.

Figure 98 shows the amino acid sequence (SEQ ID NO: 160) derived from the coding sequence of SEQ ID NO: 159 shown in Figure 97.

Figure 99 shows a nucleotide sequence (SEQ ID NO: 161) of a native sequence PR01283 (UNQ653) cDNA, wherein SEQ ID NO: 161 is a clone designated herein as "DNA65404-1551". The start and stop codons are shown in bold and underlined font.

Figure 100 shows the amino acid sequence (SEQ ID NO: 162) derived from the coding sequence of SEQ ID NO: 161 shown in Figure 99.

Figure 101 shows a nucleotide sequence (SEQ ID NO: 169) of a native sequence PR01279 (UNQ649) cDNA, wherein SEQ ID NO: 169 is a clone designated herein as "DNA65405-1547". The start and stop codons are shown in bold and underlined font.

Figure 102 shows the amino acid sequence (SEQ ID NO: 170) derived from the coding sequence of SEQ ID NO: 169 shown in Figure 101.

Figure 103 shows a nucleotide sequence (SEQ ID NO: 179) of a native sequence PR01304 (UNQ670) cDNA, wherein SEQ ID NO: 179 is a clone designated herein as "DNA65406-1567". The start and stop codons are shown in bold and underlined font. 303 Figure 104 shows the amino acid sequence (SEQ ID NO: 180) derived from the coding sequence of SEQ ID NO: 179 shown in Figure 103.

Figure 105 shows a nucleotide sequence (SEQ ID NO: 188) of a native sequence PRO 1317 (UNQ683) cDNA, wherein SEQ ID NO: 188 is a clone designated herein as "DNA65408-1578". The start and stop codons are shown in bold and underlined font.

Figure 106 shows the amino acid sequence (SEQ ID NO: 189) derived from the coding sequence of SEQ ID NO:188 shown in Figure 105.

Figure 107 shows a nucleotide sequence (SEQ ID NO: 193) of a native sequence PR01303 (UNQ669) cDNA, wherein SEQ ID NO: 193 is a clone designated herein as "DNA65409-1566". The start and stop codons are shown in bold and underlined font.

Figure 108showstheaminoacidsequence(SEQIDNO:194)derivedfromthecodingsequenceofSEQ ID NO:193 shown in Figure 107.

Figure 109 shows a nucleotide sequence (SEQ ID NO-.195) of a native sequence PR013Q6 (UNQ672) cDNA, wherein SEQ ID NO: 195 is a clone designated herein as "DNA65410-1569". The start and stop codons are shown in bold and underlined font.

Figure 110 shows the amino acid sequence (SEQ ID NO: 196) derived from the coding sequence of SEQ ID NO: 195 shown in Figure 109.

Figures 111A-B show a nucleotide sequence (SEQ ID NO: 197) of a native sequence PR01336 (UNQ691) cDNA, wherein SEQ ID NO: 197 is a clone designated herein as "DNA65423-1595". The start and stop codons are shown in bold and underlined font.

Figure 112 shows the amino acid sequence (SEQ ID NO: 198) derived from the coding sequence of SEQ ID NO: 198 shown in Figures 111A-B.

Figure 113 shows a nucleotide sequence (SEQ ID N0:202) of a native sequence PR01278 (UNQ648) cDNA, wherein SEQ ID N0:202 is a clone designated herein as "DNA66304-1546". The start and stop codons are shown in bold and underlined font.

Figure 114 shows the amino acid sequence (SEQ ID N0:203) derived from the coding sequence of SEQ ID N0:202 shown in Figure 113.

Figure 115 shows a nucleotide sequence (SEQ ID N0:209) of anative sequence PRO1298 (UNQ666) cDN A, wherein SEQ ID N0:209 is a clone designated herein as "DN A66511-1563". The start and stop codons are shown in bold and underlined font.

Figure 116 shows the amino acid sequence (SEQ ID N0:210) derived from the coding sequence of SEQ ID N0:209 shown in Figure 115.

Figure 117 shows a nucleotide sequence (SEQ ID NO:211) of a native sequence PROI301 (UNQ667) cDNA, wherein SEQ ID NO:211 is a clone designated herein as "DNA66512-1564". The start and stop codons are shown in bold and underlined font.

Figure 118 shows the amino acid sequence (SEQ ID NO:212) derived from the coding sequence of SEQ ID NO:211 shown in Figure 117. 304 Figure 119 shows a nucleotide sequence (SEQ ID NO:213) of a native sequence PR01268 (UNQ638) cDNA, wherein SEQ ID NO:213 is a clone designated herein as "DNA66519-1535". The start and stop codons are shown in bold and underlined font.

Figure 120 shows the amino acid sequence (SEQ ID NO:214) derived from the coding sequence of SEQ ID NO:213 shown in Figure 119.

Figure 121 shows a nucleotide sequence (SEQ ID NO:215) of a native sequence PR01269 (UNQ639) cDNA, wherein SEQ ID NO:215 is a clone designated herein as "DNA66520-1536". The start and stop codons are shown in bold and underlined font.

Figure 122 shows the amino acid sequence (SEQ ID NO:216) derived from the coding sequence of SEQ ID NO:215 shown in Figure 121.

Figure 123 shows a nucleotide sequence (SEQ ID NO:217) of a native sequence PR01327 (UNQ687) cDNA, wherein SEQ ID NO:217 is a clone designated herein as "DNA66521-1583". The start and stop codons are shown in bold and underlined font.

Figure 124 shows the amino acid sequence (SEQ ID NO:218) derived from the coding sequence of SEQ ID NO:217 shown in Figure 123.

Figure 125 shows a nucleotide sequence (SEQ ID NO:219) of a native sequence PR01382 (UNQ718) cDNA, wherein SEQ ID NO:219 is a clone designated herein as "DNA66526-1616". The start and stop codons are shown in bold and underlined font.

Figure 126 shows the amino acid sequence (SEQ ID N0:220) derived from the coding sequence of SEQ ID NO:219 shown in Figure 125.

Figure 127 shows a nucleotide sequence (SEQ ID NO:224) of a native sequence PR01328 (UNQ688) cDNA, wherein SEQ ID NO:224 is a clone designated herein as "DNA66658-1584". The start and stop codons are shown in bold and underlined font.

Figure 128 shows the amino acid sequence (SEQ ID NO:225) derived from the coding sequence of SEQ ID NO:224 shown in Figure 127.

Figure 129 shows a nucleotide sequence (SEQ ID NO:226) of a native sequence PR01325 (UNQ685) cDNA, wherein SEQ ID NO;226 is a clone designated herein as "DNA66659-1593". The start and stop codons are shown in bold and underlined font.

Figure 130 shows the amino acid sequence (SEQ ID NO:227) derived from the coding sequence of SEQ ID NO:226 shown in Figure 129.

Figure 131 shows a nucleotide sequence (SEQ ID N0.228) of a native sequence PR01340 (UNQ695) cDNA, wherein SEQ ID NO:228 is a clone designated herein as "DNA66663-1598". The start and stop codons are shown in bold and underlined font.

Figure 132 shows the amino acid sequence (SEQ ID N0.229) derived from the coding sequence of SEQ ID NO:228 shown in Figure 131.

Figure 133 shows a nucleotide sequence (SEQ ID NO:233) of a native sequence PR01339 (UNQ694) cDNA, wherein SEQ ID NO:233 is a clone designated herein as "DNA66669-1597". The start and stop codons are shown in bold and underlined font. 305 Figure 134 shows the amino acid sequence (SEQ ID NO:234) derived from the coding sequence of SEQ ID NO:233 shown in Figure 133.

Figure 135 shows a nucleotide sequence (SEQ ID NO:235) of a native sequence PR01337 (UNQ692) cDNA, wherein SEQ ID NO:235 is a clone designated herein as "DNA66672-1586". The start and stop codons are shown in bold and underlined font.

Figure 136 shows the amino acid sequence (SEQ ID NO :236) derived from the coding sequence of SEQ ID NO:235 shown in Figure 135.

Figure 137 shows a nucleotide sequence (SEQ ID NO:242) of a native sequence PR01342 (UNQ697) cDNA, wherein SEQ ID NO:242 is a clone designated herein as "DNA66674-1599". The start and stop codons , are shown in bold and underlined font.

Figure 138 shows the amino acid sequence (SEQ ID NO:243) derived from the coding sequence of SEQ ID NO:242 shown in Figure 137.

Figure 139 shows a nucleotide sequence (SEQ ID NO:247) of a native sequence PR01343 (UNQ698) cDNA, wherein SEQ ID NO:247 is a clone designated herein as "DN A66675-1587". The start and stop codons are shown in bold and underlined font.

Figure 140 shows the amino acid sequence (SEQ ID NO:248) derived from the coding sequence of SEQ ID NO:247 shown in Figure 139.

Figure 141 shows a nucleotide sequence (SEQ ID NO:252) of a native sequence PRO1480 (UNQ749) cDNA, wherein SEQ ID NO:252 is a clone designated herein as "DNA67962-1649". The start and stop codons are shown in bold and underlined font.

Figure 142 shows the amino acid sequence (SEQ ID NO:253) derived from the coding sequence of SEQ ID NO:252 shown in Figure 141.

Figures 143A-B show a nucleotide sequence (SEQ ID NO:259) of a native sequence PR01487 (UNQ756) cDNA, wherein SEQ ID NO:259 is a clone designated herein as "DNA68836-1656". The start and stop codons are shown in bold and underlined font.

Figure 144 shows the amino acid sequence (SEQ ID N0:260) derived from the coding sequence of SEQ ID NO:259 shown in Figures 143A-B.

Figure 145 shows a nucleotide sequence (SEQ ID NO:264) of anative sequence PR01418 (UNQ732) cDNA, wherein SEQ ID NO:264 is a clone designated herein as "DNA68864-1629". The start and stop codons are shown in bold and underlined font.

Figure 146 shows the amino acid sequence (SEQ ID NO-.265) derived from the coding sequence of SEQ ID NO:264 shown in Figure 145.

Figure 147 shows a nucleotide sequence (SEQ ID NO:266) of a native sequence PRO1472 (UNQ744) cDNA, wherein SEQ ID NO:266 is a clone designated herein as "DNA68866-1644". The start and stop codons are shown in bold and underlined font.

Figure 148 shows the amino acid sequence (SEQ ID NO:267) derived from the coding sequence of SEQ ID NO:266 shown in Figure 147. 306 Figure 149 shows a nucleotide sequence (SEQ ID NO:268) of a native sequence PR01461 (UNQ742) cDNA, wherein SEQ ID NO:268 is a clone designated herein as "DNA68871 -1638". The start and stop codons are shown in bold and underlined font.

Figure 150 shows the amino acid sequence (SEQ ID NO:269) derived from the coding sequence of SEQ ID NO:268 shown in Figure 149.

Figure 151 shows a nucleotide sequence (SEQ ID N0:270) of a native sequence PR01410 (UNQ728) cDNA, wherein SEQ ID N0:270 is a clone designated herein as "DNA68874-1622". The start and stop codons are shown in bold and underlined font.

Figure 152 shows the amino acid sequence (SEQ ID NO:271) derived from the coding sequence of SEQ ID N0:270 shown in Figure 151.

Figure 153 shows a nucleotide sequence (SEQ ID NO:272) of a native sequence PR01568 (UNQ774) cDNA, wherein SEQ ID NO:272 is a clone designated herein as "DNA68880-1676". The start and stop codons are shown in bold and underlined font.

Figure 154 shows the amino acid sequence (SEQ ID NO:273) derived from the coding sequence of SEQ ID NO:272 shown in Figure 153.

Figure 155 shows a nucleotide sequence (SEQ ID NO:274) of a native sequence PRO1570 (UNQ776) cDNA, wherein SEQ ID NO:274 is a clone designated herein as "DNA68885-1678". The start and stop codons are shown in bold and underlined font.

Figure 156 shows the amino acid sequence (SEQ ID NO:275) derived from the coding sequence of SEQ ID NO:274 shown in Figure 155.

Figure 157 shows a nucleotide sequence (SEQ ID NO:276) of a native sequence PR01317 (UNQ783) cDNA, wherein SEQ ID NO:276 is a clone designated herein as "DNA71166-1685". The start and stop codons are shown in bold and underlined font.

Figure 158 shows the amino acid sequence (SEQ ID NO:277) derived from the coding sequence of SEQ ID NO:276 shown in Figure 157.

Figure 159 shows a nucleotide sequence (SEQ ID NO:281) of a native sequence PR01780 (UNQ842) cDNA, wherein SEQ ID N0:281 is a clone designated herein as "DNA71169-I709". The start and stop codons are shown in bold and underlined font.

Figure 160 shows the amino acid sequence (SEQ ID NO:282) derived from the coding sequence of SEQ ID NO:281 shown in Figure 159.

Figure 161 shows a nucleotide sequence (SEQ ID NO:286) of a native sequence PR01486 (UNQ755) cDNA, wherein SEQ ID NO:286 is a clone designated herein as "DNA71180-1655". The start and stop codons are shown in bold and underlined font.

Figure 162 shows the amino acid sequence (SEQ ID NO:287) derived from the coding sequence of SEQ ID NO:286 shown in Figure 161.

Figure 163 shows a nucleotide sequence (SEQ ID NO:291) of a native sequence PR01433 (UNQ738) cDNA, wherein SEQ ID NO:291 is a clone designated herein as "DNA71184-1634". The start and stop codons are shown in bold and underlined font. 307 Figure 164 shows the amino acid sequence (SEQ ID NO:292) derived from the coding sequence of SEQ ID NO:29I shown in Figure 163.

Figure 165 shows a nucleotide sequence (SEQ ID NO:296) of a native sequence PR01490 (UNQ759) cDNA, wherein SEQ ID NO:296 is a clone designated herein as "DNA71213-1659". The start and stop codons are shown in bold and underlined font.

Figure 166 shows the amino acid sequence (SEQ ID NO:297) derived from the coding sequence of SEQ ID NO:296 shown in Figure 165.

Figure 167 shows a nucleotide sequence (SEQ ID N0:301) of a native sequence PR01482 (UNQ751) cDNA, wherein SEQ ID N0:301 is a clone designated herein as "DNA71234-1651". The start and stop codons are shown in bold and underlined font.

Figure 168 shows the amino acid sequence (SEQ ID N0:302) derived from the coding sequence of SEQ ID N0:301 shown in Figure 167.

Figure 169 shows a nucleotide sequence (SEQ ID N0:303) of a native sequence PR01446 (UNQ740) cDNA, wherein SEQ IDNO:303 is a clone designated herein as "DNA71277-1636". The start and stop codons are shown in bold and underlined font.

Figure 170 shows the amino acid sequence (SEQ ID N0:304) derived from the coding sequence of SEQ ID N0:303 shown in Figure 169.

Figure 171 shows a nucleotide sequence (SEQ ID N0:305) of a native sequence PR01558 (UNQ766) cDNA, wherein SEQ ID N0:305 is a clone designated herein as "DNA71282-1668". The start and stop codons are shown in bold and underlined font.

Figure 172 shows the amino acid sequence (SEQ ID N0:306) derived from the coding sequence of SEQ ID N0:305 shown in Figure 171.

Figure 173 shows a nucleotide sequence (SEQ ID N0:307) of a native sequence PR01604 (UNQ785) cDNA, wherein SEQ ID N0:307 is a clone designated herein as "DNA71286-1687". The start and stop codons are shown in bold and underlined font.

Figure 174 shows the amino acid sequence (SEQ ID N0:308) derived from the coding sequence of SEQ ID N0:307 shown in Figure 173.

Figure 175 shows a nucleotide sequence (SEQ ID N0:309) of a native sequence PR01491 (UNQ760) cDNA, wherein SEQ ID N0:309 is a clone designated herein as "DNA71883-1660". The start and stop codons are shown in bold and underlined font.

Figure 176 shows the amino acid sequence (SEQ ID NO:310) derived from the coding sequence of SEQ ID N0:309 shown in Figure 175.

Figure 177 shows a nucleotide sequence (SEQ ID NO:314) of a native sequence PR01431 (UNQ737) cDNA, wherein SEQ ID NO:314 is a clone designated herein as "DNA73401-1633". The start and stop codons are shown in bold and underlined font.

Figure 178 shows the amino acid sequence (SEQ ID NO:315) derived from the coding sequence of SEQ ID NO:314 shown in Figure 177. 308 Figures 179A-B show a nucleotide sequence (SEQ ID NO:316) of a native sequence PR01563 (UNQ769) cDNA, wherein SEQ ID NO:316 is a clone designated herein as "DNA73492-1671". The start and stop codons are shown in bold and underlined font.

Figure 180 shows the amino acid sequence (SEQ ID NO:317) derived from the coding sequence of SEQ ID N0.316 shown in Figures 179A-B.

Figure 181 shows a nucleotide sequence (SEQ ID NO:321) of a native sequence PR01565 (UNQ771) cDNA, wherein SEQ ID NO:32I is a clone designated herein as "DNA73727-1673". The start and stop codons are shown in bold and underlined font.

Figure 182 shows the amino acid sequence (SEQ ID NO:322) derived from the coding sequence of SEQ ID NO:321 shown in Figure 181.

Figure 183 shows a nucleotide sequence (SEQ ID NO:323) of a native sequence PR01571 (UNQ777) cDNA, wherein SEQ ID NO:323 is a clone designated herein as "DNA73730-1679". The start and stop codons are shown in bold and underlined font.

Figure 184 shows the amino acid sequence (SEQ ID NO:324) derived from the coding sequence of SEQ ID NO:323 shown in Figure 183.

Figure 185 shows a nucleotide sequence (SEQ ID NO:325) of a native sequence PR01572 (UNQ778) cDNA, wherein SEQ ID NO:325 is a clone designated herein as "DNA73734-1680". The start and stop codons are shown in bold and underlined font.

Figure 186 shows the amino acid sequence (SEQ ID NO:326) derived from the coding sequence of SEQ ID NO:325 shown in Figure 185.

Figure 187 shows a nucleotide sequence (SEQ ID NO:327) of a native sequence PR01573 (UNQ779) cDNA, wherein SEQ ID NO:327 is a clone designated herein as "DN A73735-1681". The start and stop codons are shown in bold and underlined font.

Figure 188 shows the amino acid sequence (SEQ ID NO:328) derived from the coding sequence of SEQ ID NO:327 shown in Figure 187.

Figure 189 shows a nucleotide sequence (SEQ ID NO:329) of a native sequence PR01488 (UNQ757) cDNA, wherein SEQ ID NO:329 is a clone designated herein as "DNA73736-1657". The start and stop codons are shown in bold and underlined font.

Figure 190 shows the amino acid sequence (SEQ ID N0:330) derived from the coding sequence of SEQ ID NO:329 shown in Figure 189.

Figure 191 shows a nucleotide sequence (SEQ ID NO:331) of a native sequence PR01489 (UNQ758) cDNA, wherein SEQ ID NO:331 is a clone designated herein as "DNA73737-1658". The start and stop codons are shown in bold and underlined font.

Figure 192 shows the amino acid sequence (SEQ ID NO:332) derived from the coding sequence of SEQ ID NO:331 shown in Figure 191.

Figure 193 shows a nucleotide sequence (SEQ ID NO:333) of a native sequence PR01474 (UNQ745) cDNA, wherein SEQ ID NO:333 is a clone designated herein as "DNA73739-1645". The start and stop codons are shown in bold and underlined font. 309 Figure 194 shows the amino acid sequence (SEQ ID NO:334) derived from the coding sequence of SEQ ID NO:333 shown in Figure 193.

Figure 195 shows a nucleotide sequence (SEQ ID NO:335) of a native sequence PRO1508 (UNQ761) cDNA, wherein SEQ ID NO:335 is a clone designated herein as "DNA73742-1662". The start and stop codons are shown in bold and underlined font.

Figure 196 shows the amino acid sequence (SEQ ID NO:336) derived from the coding sequence of SEQ ID NO:335 shown in Figure 195.

Figure 197 shows a nucleotide sequence (SEQ ID NO:337) of a native sequence PR01555 (UNQ763) cDNA, wherein SEQ ID NO:337 is a clone designated herein as "DNA73744-1665". The start and stop codons are shown in bold and underlined font.

Figure 198 shows the amino acid sequence (SEQ ID NO:338) derived from the coding sequence of SEQ ID NO:337 shown in Figure 197.

Figure 199 shows a nucleotide sequence (SEQ ID NO:339) of a native sequence PR01485 (UNQ754) cDNA, wherein SEQ ID NO:339 is a clone designated herein as "DNA73746-1654". The start and stop codons are shown in bold and underlined font.

Figure 200 shows the amino acid sequence (SEQ ID N0:340) derived from the coding sequence of SEQ ID NO:339 shown in Figure 199.

Figure 201 shows a nucleotide sequence (SEQ ID NO:346) of a native sequence PR01564 (UNQ770) cDNA, wherein SEQ ID NO:346 is a clone designated herein as "DNA73760-1672". The start and stop codons are shown in bold and underlined font.

Figure 202 shows the amino acid sequence (SEQ ID NO:347) derived from the coding sequence of SEQ ID NO:346 shown in Figure 201.

Figure 203 shows a nucleotide sequence (SEQ ID NO:351) of a native sequence PRO1755 (UNQ828) cDNA, wherein SEQ ID NO:351 is a clone designated herein as "DNA76396-1698". The start and stop codons are shown in bold and underlined font.

Figure 204 shows die amino acid sequence (SEQ ID NO:352) derived from the coding sequence of SEQ ID NO:351 shown in Figure 203.

Figure 205 shows a nucleotide sequence (SEQ ID NO:353) of a native sequence PR01757 (UNQ830) cDNA, wherein SEQ ID N0:353 is a clone designated herein as "DNA76398-1699". The start and stop codons axe shown in bold and underlined font.

Figure 206 shows the amino acid sequence (SEQ ID NO:354) derived from the coding sequence of SEQ ID NO:353 shown in Figure 205.

Figure 207 shows a nucleotide sequence (SEQ ID NO:355) of a native sequence PR01758 (UNQ831) cDNA, wherein SEQ ID NO:355 is aclone designated herein as "DNA76399-1700". The start and stop codons are shown in bold and underlined font.

Figure 208 shows the amino acid sequence (SEQ ID NO:356) derived from the coding sequence of SEQ ID NO-.355 shown in Figure 207. 310 Figure 209 shows a nucleotide sequence (SEQ ID NO:357) of a native sequence PR01575 (TJNQ781) cDNA, wherein SEQ ID NO:357 is a clone designated herein as "DNA76401-1683". The start and stop codons are shown in bold and underlined font.

Figure 210 shows the amino acid sequence (SEQ ID NO:358) derived from the coding sequence of SEQ ID NO:357 shown in Figure 209.

Figure 211 shows a nucleotide sequence (SEQ ID NO:363) of a native sequence PR01787 (UNQ849) cDNA, wherein SEQ ID NO:363 is a clone designated herein as "DNA76510-2504". The start and stop codons are shown in bold and underlined font.

Figure 212 shows the amino acid sequence (SEQ ID NO:364) derived from the coding sequence of SEQ ID NO:363 shown in Figure 211.

Figure 213 shows a nucleotide sequence (SEQ ID NO:365) of a native sequence PR01781 (UNQ843) cDNA, wherein SEQ ID N0:365 is a clone designated herein as "DNA76522-2500". The start and stop codons are shown in bold and underlined font.

Figure 214 shows the amino acid sequence (SEQ ID NO:366) derived from the coding sequence of SEQ ID NO:365 shown in Figure 213.

Figure 215 shows a nucleotide sequence (SEQ ID NO:371) of a native sequence PR01556 (UNQ764) cDNA, wherein SEQ ID N0:371 is a clone designated herein as "DNA76529-1666". The start and stop codons are shown in bold and underlined font.

Figure 216 shows the amino acid sequence (SEQ ID NO.-372) derived from the coding sequence of SEQ ID NO:371 shown in Figure 215.

Figure 217 shows a nucleotide sequence (SEQ ID NO:373) of a native sequence PR01759 (UNQ832) cDNA, wherein SEQ IDNO:373 is a clone designated herein as "DNA76531-1701". The start and stop codons are shown in bold and underlined font.

Figure 218 shows the amino acid sequence (SEQ ID NO:374) derived from the coding sequence of SEQ ID NO:373 shown in Figure 217.

Figure 219 shows a nucleotide sequence (SEQ ID NO:375) of a native sequence PR01760 (UNQ833) cDNA, wherein SEQ ID NO:375 is a clone designated herein as "DNA76532-1702". The start and stop codons are shown in bold and underlined font.

Figure 220 shows the amino acid sequence (SEQ ID NO:376) derived from the coding sequence of SEQ ID NO:375 shown in Figure 219.

Figure 221 shows a nucleotide sequence (SEQ ID NO:377) of a native sequence PR01561 (UNQ768) cDNA, wherein SEQ ID NO:377 is a clone designated herein as "DNA76538-1670". The start and stop codons are shown in bold and underlined font.

Figure 222 shows the amino acid sequence (SEQ ID NO:378) derived from the coding sequence of SEQ ID NO:377 shown in Figure 221.

Figure 223 shows a nucleotide sequence (SEQ ID NO:382) of a native sequence PR01567 (UNQ773) cDNA, wherein SEQ ID N0:382 is a clone designated herein as "DNA76541-1675". The start and stop codons are shown in bold and underlined font. 311 Figure 224 shows the amino acid sequence (SEQ ID NO:383) derived from the coding sequence of SEQ ID NO:382 shown in Figure 223.

Figure 225 shows a nucleotide sequence (SEQ ID NO:384) of a native sequence PRO 1693 (UNQ803) cDNA, wherein SEQ ID NO:384 is a clone designated herein as "DNA77301-1693". The start and stop codons are shown in bold and underlined font.

Figure 226 shows the amino acid sequence (SEQ ID NO:385) derived from the coding sequence of SEQ ID NO:384 shown in Figure 225.

Figure 227 shows a nucleotide sequence (SEQ ID NO:389) of a native sequence PR01784 (UNQ846) cDNA, wherein SEQ ID NO:389 is a clone designated herein as "DNA77303-2502". The start and stop codons are shown in bold and underlined font.

Figure 228 shows the amino acid sequence (SEQ ID N0:390) derived from the coding sequence of SEQ ID NO:389 shown in Figure 227.

Figure 229 shows a nucleotide sequence (SEQ ID NO:394) of a native sequence PRO 1605 (UNQ786) cDNA, wherein SEQ ID NO:394 is a clone designated herein as "DNA77648-1688". The start and stop codons are shown in bold and underlined font.

Figure 230 shows the amino acid sequence (SEQ ID NO:395) derived from the coding sequence of SEQ ID NO:394 shown in Figure 229.

Figure 231 shows a nucleotide sequence (SEQ ID NO:396) of a native sequence PR01788 (UNQ850) cDNA, wherein SEQ ID NO:396 is a clone designated herein as "DNA77652-2505". The start and stop codons are shown in bold and underlined font.

Figure 232 shows the amino acid sequence (SEQ ID NO:397) derived from the coding sequence of SEQ ID NO:396 shown in Figure 231.

Figure 233 shows a nucleotide sequence (SEQ ID N0:401) of a native sequence PR01801 (UNQ852) cDNA, wherein SEQ ID N0:401 is a clone designated herein as "DNA83500-2506". The start and stop codons are shown in bold and underlined font.

Figure 234 shows the amino acid sequence (SEQ ID N0:402) derived from the coding sequence of SEQ ID N0:401 shown in Figure 233.

Figure 235 shows a nucleotide sequence (SEQ ID N0:405) of a native sequence UCP4 cDNA, wherein SEQ ID N0:405 is a clone designated herein as "DNA77568-1626". The start and stop codons are shown in bold and underlined font.

Figure 236 shows the amino acid sequence (SEQ ID NO :406) derived from the coding sequence of SEQ ID N0:405 shown in Figure 235.

Figure 237 shows a nucleotide sequence (SEQ ID N0:409) of a native sequence PR0193 cDNA, wherein SEQ ID N0:409 is a clone designated herein as "DNA23322-1393". The start and stop codons are shown in bold and underlined font.

Figure 238 shows the amino acid sequence (SEQ ID N0:410) derived from the coding sequence of SEQ ID N0:409 shown in Figure 237. 312 Figure 239 shows a nucleotide sequence (SEQ ID NO:414) of a native sequence PROl 130 cDNA, wherein SEQ ID NO:414 is a done designated herein as "DNA59814-1486". The start and stop codons are shown in bold and underlined font.

Figure 240 shows the amino acid sequence (SEQ ID NO:415) derived from the coding sequence of SEQ ID NO:414 shown in Figure 239.

Figure 241 shows a nucleotide sequence (SEQ ID NO:422) of a native sequence PR01335 cDNA, wherein SEQ ID NO:422 is a clone designated herein as "DNA62812-1594". The start and stop codons are shown in bold and underlined font.

Figure 242 shows the amino acid sequence (SEQ ID NO:423) derived from the coding sequence of SEQ ID NO:422 shown in Figure 241.

Figure 243 shows a nucleotide sequence (SEQ ID NO:428) of a native sequence PR01329 cDNA, wherein SEQ ID NO:428 is a clone designated herein as "DNA66660-1585". The start and stop codons are shown in bold and underlined font.

Figure 244 shows the amino acid sequence (SEQ ID NO:429) derived from the coding sequence of SEQ ID NO:428 shown in Figure 243.

Figure 245 shows a nucleotide sequence (SEQ ID NO:231) of a native sequence PR01550 cDNA, wherein SEQ ID NO:231 is a clone designated herein as "DNA76393-1664". The start and stop codons are shown in bold and underlined font.

Figure 246 shows the amino acid sequence (SEQ ID NO:232) derived from the coding sequence of SEQ ID NO:231 shown in Figure 245.

Figures 247A-D show hypothetical exemplifications for using the below described method to determine % amino acid sequence identity (Figures 247A-B) and % nucleic acid sequence identity (Figures 247C-D) using the ALIGN-2 sequence comparison computer program, wherein "PRO" represents the amino acid sequence of a hypothetical PEACH polypeptide of interest, "Comparison Protein" represents the amino acid sequence of a polypeptide against which the "PRO" polypeptide of interest is being compared, "PRO-DNA" represents a hypothetical PEACH-encoding nucleic acid sequence of interest, "Comparison DNA" represents the nucleotide sequence of a nucleic acid molecule against which the "PRO-DNA" nucleic acid molecule of interest is being compared, "X, "Y" and "Z" each represent different hypothetical amino acid residues and "N", "L" and "V" each represent different hypothetical nucleotides.

Figures 248A-Q provide the complete source code for the ALIGN-2 sequence comparison computer program. This source code may be routinely compiled for use on a UNIX operating system to provide the ALIGN-2 sequence comparison computer program.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS I. Definitions The terms "PRO polypeptide" and "PRO" or "UCP"as used herein and when immediately followed by a numerical designation refer to various polypeptides, wherein the complete designation (i.e., PRO/number) refers to specific polypeptide sequences as described herein. The terms "PRO/number polypeptide" and 313 f OFRCE OF i\|.z 24 OCT 2003 received "PRO/number" wherein the term "number" is provided as an actual numerical designation as used herein encompass native sequence polypeptides and polypeptide variants (which are further defined herein). The PRO polypeptides described herein may be isolated from a variety of sources, such as from human tissue types or from another source, or prepared by recombinant or synthetic methods.

A "native sequence PRO polypeptide" or "UCP" comprises a polypeptide having the same amino acid 5 sequence as the corresponding PRO polypeptide derived from nature. Such native sequence PRO polypeptides can be isolated from nature or can be produced by recombinant or synthetic means. The term "native sequence PRO polypeptide" specifically encompasses naturally-occurring truncated or secreted forms of the specific PRO polypeptide (e.g., an extracellular domain sequence), naturally-occurring variant forms (e.g., alternatively spliced forms) and naturally-occurring allelic variants of the polypeptide. In various embodiments of the 10 invention, native sequence PRO polypeptides are mature or full-length native sequence polypeptides comprising the full-length amino acids sequences shown in the accompanying figures. Start and stop codons are shown in bold font and underlined in the figures. However, while the PRO polypeptide disclosed in the accompanying figures are shown to begin with methionine residues designated herein as amino acid position I in the figures, it is conceivable and possible that other methionine residues located either upstream or downstream from the IS amino acid position 1 in the figures may be employed as the starting amino acid residue for the PRO polypeptides.

The PRO polypeptide "extracellular domain" or "ECD" refers to a form of the PRO polypeptide which is essentially free of the transmembrane and cytoplasmic domains. Ordinarily, a PRO polypeptide ECD will have less than 1 % of such transmembrane and/or cytoplasmic domains and preferably, will have less than 0.5% of 20 such domains. It will be understood that any transmembrane domains identified for the PRO polypeptides of the present invention are identified pursuant to criteria routinely employed in the art for identifying that type of hydrophobic domain. The exact boundaries of a transmembrane domain may vary but most likely by no more than about 5 amino acids at either end of the domain as initially identified herein. Optionally, therefore, an extracellular domain of a PRO polypeptide may contain from about 5 or fewer amino acids on either side of the 25 transmembrane domain/extracellular domain boundary as identified in the Examples or specification and such polypeptides, with or without the associated signal peptide, and nucleic acid encoding them, are comtempiated by the present invention.

The approximate location of the "signal peptides" of the various PRO polypeptides disclosed herein are shown in the accompanying figures. It is noted, however, that the C-terminal boundary of a signal peptide may 30 vary, but most likely by no more than about 5 amino acids on either side of the signal peptide C-terminal boundary as initially identified herein, wherein the C-terminal boundary of the signal peptide may be identified pursuant to criteria routinely employed in the art for identifying that type of amino acid sequence element (e.g., Nielsen et al., Prot. Eng. 10:1-6 (1997) and von Heinje et al., Nucl. Acids. Res. 14:4683-4690 (1986)). Moreover, it is also recognized that, in some cases, cleavage of a signal sequence from a secreted polypeptide 35 is not entirely uniform, resulting in more than one secreted species. These mature polypeptides, where the signal peptide is cleaved within no more than about 5 amino acids on either side of the C-terminal boundary of the signal peptide as identified herein, and the polynucleotides encoding them, are contemplated by the present 314 invention.

"PRO polypeptide variant" means an active PRO polypeptide as defined above or below having at least about 80% amino acid sequence identity with a full-length native sequence PRO polypeptide sequence as disclosed herein, a PRO polypeptide sequence lacking the signal peptide as disclosed herein, an extracellular domain of a PRO polypeptide, with or without the signal peptide, as disclosed herein or any other fragment of 5 a full-length PRO polypeptide sequence as disclosed herein. Such PRO polypeptide variants include, for instance, PRO polypeptides wherein one or more amino acid residues are added, or deleted, at the N- or C-terminus of the full-length native amino acid sequence. Ordinarily, a PRO polypeptide variant will have at least about 80% amino acid sequence identity, preferably at least about 81 % amino acid sequence identity, more preferably at least about 82% amino acid sequence identity, more preferably at least about 83% amino acid 10 sequence identity, more preferably at least about 84% amino acid sequence identity, more preferably at least about 85 % amino acid sequence identity, more preferably at least about 86% amino acid sequence identity, more preferably at least about 87% amino acid sequence identity, more preferably at least about 88% amino acid sequence identity, more preferably at least about 89% amino acid sequence identity, more preferably at least about 90% amino acid sequence identity, more preferably at least about 91 % amino acid sequence identity, more IS preferably at least about 92% amino acid sequence identity, more preferably at least about 93% amino acid sequence identity, more preferably at least about 94% amino acid sequence identity, more preferably at least about 95% amino acid sequence identity, more preferably at least about 96% amino acid sequence identity, more preferably at least about 97% amino acid sequence identity, more preferably at least about 98% amino acid sequence identity and most preferably at least about 99% amino acid sequence identity with a full-length native 20 sequence PRO polypeptide sequence as disclosed herein, a PRO polypeptide sequence lacking the signal peptide as disclosed herein, an extracellular domain of a PRO polypeptide, with or without the signal peptide, as disclosed herein or any other fragment of a full-length PRO polypeptide sequence as disclosed herein. Ordinarily, PRO variant polypeptides are at least about 10 amino acids in length, often at least about 20 amino acids in length, more often at least about 30 amino acids in length, more often at least about 40 amino acids in 25 length, more often at least about 50 amino acids in length, more often at least about 60 amino acids in length, more often at least about 70 amino acids in length, more often at least about 80 amino acids in length, more often at least about 90 amino acids in length, more often at least about 100 amino acids in length, more often at least about 150 amino acids in length, more often at least about 200 amino acids in length, more often at least about 300 amino acids in length, or more.

"Percent (%) amino acid sequence identity" with respect to the PRO polypeptide sequences identified herein is defined as the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the specific PRO polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid 35 sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed 315 PCTAJS99/20111 to achieve maximal alignment over the full length of the sequences being compared. For purposes herein, however, % amino acid sequence identity values are generated using the WU-BLAST-2 computer program (Altschul et al., Methods in Enzvmologv 266:460-480 (1996)). Most of the WU-BLAST-2 search parameters are set to the default values. Those not set to default values, i.e., the adjustable parameters, are set with the following values: overlap span = 1, overlap fraction = 0.125, word threshold (T) = 11, and scoring matrix 5 = BLOSUM62. For purposes herein, a % amino acid sequence identity value is determined by dividing (a) the number of matching identical amino acid residues between the amino acid sequence of the PRO polypeptide of interest having a sequence derived from the native PRO polypeptide and the comparison amino acid sequence of interest (i.e., the sequence against which the PRO polypeptide of interest is being compared which may be a PRO variant polypeptide) as determined by WU-BLAST-2 by (b) die total number of amino acid residues of 10 the PRO polypeptide of interest. For example, in the statement "a polypeptide comprising an the amino acid sequence A which has or having at least 80% amino acid sequence identity to the amino acid sequence B", the amino acid sequence A is the comparison amino acid sequence of interest and the amino acid sequence B is the amino acid sequence of the PRO polypeptide of interest.

Unless specifically stated otherwise, all % amino acid sequence identity values used herein are obtained 15 as described in the immediately preceding paragraph using the WU-BLAST-2 computer program. However, % amino acid sequence identity values may also be obtained as described below by using the sequence comparison computer program ALIGN-2, wherein the complete source code for the ALIGN-2 program is provided in Figures 248A-Q. The ALIGN-2 sequence comparison computer program was authored by Genentecb, Inc. and the source code shown in Figures 248A-Q has been filed with user documentation in the 20 U.S. Copyright Office, Washington D.C., 20559, where it is registered under U.S. Copyright Registration No. TXU510087. The ALIGN-2 program is publicly available through Genentech, Inc., South San Francisco, California or may be compiled from the source code provided in Figures 248A-Q. The ALIGN-2 program should be compiled for use on a UNIX operating system, preferably digital UNIX V4.0D. All sequence comparison parameters are set by the ALIGN-2 program and do not vary.

In situations where ALIGN-2 is employed for amino acid sequence comparisons, the % amino acid sequence identity of a given amino acid sequence A to, with, or against a given amino acid sequence B (which can alternatively be phrased as a given amino acid sequence A that has or comprises a certain % amino acid sequence identity to, with, or against a given amino acid sequence B) is calculated as follows: 100 times the fraction X/Y where X is the number of amino acid residues scored as identical matches by the sequence alignment program ALIGN-2 in that program's alignment of A and B, and where Y is the total number of amino acid residues in B. It will be appreciated that where the length of amino acid sequence A is not equal to the length of amino acid 35 sequence B, the % amino acid sequence identity of A to B will not equal the % amino acid sequence identity of B to A. As examples of % amino acid sequence identity calculations using this method, Figures 247A-B demonstrate how to calculate the % amino acid sequence identity of the amino acid sequence designated 316 "Comparison Protein" to the amino acid sequence designated "PRO".

Percent amino acid sequence identity may also be determined using the sequence comparison program NCBI-BLAST2 (Altschul et al., Nucleic Acids Res. 25:3389-3402 (1997)). The NCBI-BLAST2 sequence comparison program may be downloaded from http://www.ncbi.nlm.nih.gov. NCBI-BLAST2 uses several search parameters, wherein all of those search parameters are set to default values including, for example, 5 unmask = yes, strand = all, expected occurrences = 10, minimum low complexity length = 15/5, multi-pass e-value — 0.01, constant for multi-pass = 25, dropoff for final gapped alignment = 25 and scoring matrix = BLOSUM62.

In situations where NCBI-BLAST2 is employed for amino acid sequence comparisons, the % amino acid sequence identity of a given amino acid sequence A to, with, or against a given amino acid sequence B 10 (which can alternatively be phrased as a given amino acid sequence A that has or comprises a certain % amino acid sequence identity to, with, or against a given amino acid sequence B) is calculated as follows: 100 times the fraction X/Y where X is the number of amino acid residues scored as identical matches by the sequence alignment program NCBI-BLAST2 in that program's alignment of A and B, and where Y is the total number of amino acid residues in B. It will be appreciated that where the length of amino acid sequence A is not equal to the length of amino acid sequence B, the % amino acid sequence identity of A to B will not equal the % amino acid sequence identity of B to A.

"PRO variant polynucleotide" or "PRO variant nucleic acid sequence" means a nucleic acid molecule which encodes an active PRO polypeptide as defined below and which has at least about 80% nucleic acid sequence identity with a nucleotide acid sequence encoding a full-length native sequence PRO polypeptide sequence as disclosed herein, a full-length native sequence PRO polypeptide sequence lacking the signal peptide as disclosed herein, an extracellular domain of a PRO polypeptide, with or without the signal peptide, as 25 disclosed herein or any other fragment of a full-length PRO polypeptide sequence as disclosed herein. Ordinarily, a PRO variant polynucleotide will have at least about 80% nucleic acid sequence identity, more preferably at least about 81% nucleic acid sequence identity, more preferably at least about 82% nucleic acid sequence identity, more preferably at least about 83% nucleic acid sequence identity, more preferably at least about 84% nucleic acid sequence identity, more preferably at least about 85% nucleic acid sequence identity, 30 more preferably at least about 86% nucleic acid sequence identity, more preferably at least about 87% nucleic acid sequence identity, more preferably at least about 88% nucleic acid sequence identity, more preferably at least about 89% nucleic acid sequence identity, more preferably at least about 90% nucleic acid sequence identity, more preferably at least about 91% nucleic acid sequence identity, more preferably at least about 92% nucleic acid sequence identity, more preferably at least about 93% nucleic acid sequence identity, more 35 preferably at least about 94% nucleic acid sequence identity, more preferably at least about 95% nucleic acid sequence identity, more preferably at least about 96% nucleic acid sequence identity, more preferably at least about 97% nucleic acid sequence identity, more preferably at least about 98% nucleic acid sequence identity and 317 yet more preferably at least about 99% nucleic acid sequence identity with the nucleic acid sequence encoding a full-length native sequence PRO polypeptide sequence as disclosed herein, a full-length native sequence PRO polypeptide sequence lacking the signal peptide as disclosed herein, an extracellular domain of a PRO polypeptide, with or without the signal sequence, as disclosed herein or any other fragment of a full-length PRO polypeptide sequence as disclosed herein. Variants do not encompass the native nucleotide sequence.

Ordinarily, PRO variant polynucleotides are at least about 30 nucleotides in length, often at least about 60 nucleotides in length, more often at least about 90 nucleotides in length, more often at least about 120 nucleotides in length, more often at least about 150 nucleotides in length, more often at least about 180 nucleotides in length, more often at least about 210 nucleotides in length, more often at least about 240 nucleotides in length, more often at least about 270 nucleotides in length, more often at least about 300 10 nucleotides in length, more often at least about 450 nucleotides in length, more often at least about 600 nucleotides in length, more often at least about 900 nucleotides in length, or more.

"Percent (%) nucleic acid sequence identity" with respect to PRO-encoding nucleic acid sequences identified herein is defined as the percentage of nucleotides in a candidate sequence that are identical with the nucleotides in the PRO nucleic acid sequence of interest, after aligning the sequences and introducing gaps, if 15 necessary, to achieve the maximum percent sequence identity. Alignment for purposes of determining percent nucleic acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. For purposes herein, however, % nucleic acid sequence identity values are generated using the WU-BLAST-2 computer program (Altschul et al., Methods in Enzvmology 266:460-480 (1996)). Most of the WU-20 BLAST-2 search parameters are set to the default values. Those not set to default values, i.e., the adjustable parameters, are set with the following values: overlap span = 1, overlap fraction = 0.125, word threshold (T) = 11, and scoring matrix = BLOSUM62. For purposes herein, a % nucleic acid sequence identity value is determined by dividing (a) the number of matching identical nucleotides between the nucleic acid sequence of the PRO polypeptide-encoding nucleic acid molecule of interest having a sequence derived from the native 25 sequence PRO polypeptide-encoding nucleic acid and the comparison nucleic acid molecule of interest (i.e., the sequence against which the PRO polypeptide-encoding nucleic acid molecule of interest is being compared which may be a variant PRO polynucleotide) as determined by WU-BLAST-2 by (b) the total number of nucleotides of the PRO polypeptide-encoding nucleic acid molecule of interest. For example, in the statement "an isolated nucleic acid molecuie comprising a nucleic acid sequence A which has or having at least 80% nucleic acid 30 sequence identity to the nucleic acid sequence B", the nucleic acid sequence A is the comparison nucleic acid molecule of interest and the nucleic acid sequence B is the nucleic acid sequence of the PRO polypeptide-encoding nucleic acid molecuie of interest.

Unless specifically stated otherwise, all % nucleic acid sequence identity values used herein are obtained as described in the immediately preceding paragraph using the WU-BLAST-2 computer program. However, 35 % nucleic acid sequence identity values may also be obtained as described below by using the sequence comparison computer program ALIGN-2, wherein the complete source code for the ALIGN-2 program is provided in Figures 248A-Q. The ALIGN-2 sequence comparison computer program was authored by 318 Genentech, Inc. and the source code shown in Figures 248A-Q has been filed with user documentation in the U.S. Copyright Office, Washington D.C., 20559, where it is registered under U.S. Copyright Registration No. TXU510087. The ALIGN-2 program is publicly available through Genentech, Inc., South San Francisco, California or may be compiled from the source code provided in Figures 248A-Q. The ALIGN-2 program should be compiled for use on a UNIX operating system, preferably digital UNIX V4.0D. All sequence comparison parameters are set by the ALIGN-2 program and do not vary.

In situations where ALIGN-2 is employed for nucleic acid sequence comparisons, the % nucleic acid sequence identity of a given nucleic acid sequence C to, with, or against a given nucleic acid sequence D (which can alternatively be phrased as a given nucleic acid sequence C that has or comprises a certain % nucleic acid sequence identity to, with, or against a given nucleic acid sequence D) is calculated as follows: 100 times the fraction W/Z where W is the number of nucleotides scored as identical matches by the sequence alignment program ALIGN-2 in that program's alignment of C and D, and where Z is the total number of nucleotides in D. It will be 15 appreciated that where the length of nucleic acid sequence C is not equal to the length of nucleic acid sequence D, the % nucleic acid sequence identity of C to D will not equal the % nucleic acid sequence identity of D to C. As examples of % nucleic acid sequence identity calculations, Figures 247C-D demonstrate how to calculate the % nucleic acid sequence identity of the nucleic acid sequence designated "Comparison DNA" to the nucleic acid sequence designated "PRO-DNA".

Percent nucleic acid sequence identity may also be determined using the sequence comparison program NCBI-BLAST2 (Altschul et al., Nucleic Acids Res. 25:3389-3402 (1997)). The NCBI-BLAST2 sequence comparison program may be downloaded from http://www.ncbi.nlm.nih.gov. NCBI-BLAST2 uses several search parameters, wherein all of those search parameters are set to default values including, for example, unmask = yes, strand = all, expected occurrences = 10, minimum low complexity length = 15/5, multi-pass 25 e-value = 0.01, constant for multi-pass = 25, dropoff for final gapped alignment = 25 and scoring matrix = BLOSUM62.

In situations where NCBI-BLAST2 is employed for sequence comparisons, the % nucleic acid sequence identity of a given nucleic acid sequence C to, with, or against a given nucleic acid sequence D (which can alternatively be phrased as a given nucleic acid sequence C that has or comprises a certain % nucleic acid 30 sequence identity to, with, or against a given nucleic acid sequence D) is calculated as follows: 100 times the fraction W/Z where W is the number of nucleotides scored as identical matches by the sequence alignment program NCBI-35 BLAST2 in that program's alignment of C and D, and where Z is the total number of nucleotides in D. It will be appreciated that where the length of nucleic acid sequence C is not equal to the length of nucleic acid sequence D, the % nucleic acid sequence identity of C to D will not equal the % nucleic acid sequence identity of D to 319 C.

In other embodiments, PRO variant polynucleotides are nucleic acid molecules that encode an active PRO polypeptide and which are capable of hybridizing, preferably under stringent hybridization and wash conditions, to nucleotide sequences encoding a full-length PRO polypeptide as disclosed herein. PRO variant polypeptides may be those that are encoded by a PRO variant polynucleotide.

Hie term "positives", in the context of sequence comparison performed as described above, includes residues in the sequences compared that are not identical but have similar properties (e.g. as a result of conservative substitutions, see Table 1 below). For purposes herein, the % value of positives is determined by dividing (a) the number of amino acid residues scoring a positive value between the PRO polypeptide amino acid sequence of interest having a sequence derived from the native PRO polypeptide sequence and the comparison 10 amino acid sequence of interest (i.e., the amino acid sequence against which the PRO polypeptide sequence is being compared) as determined in the BLOSUM62 matrix of WU-BLAST-2 by (b) the total number of amino acid residues of the PRO polypeptide of interest.

Unless specifically stated otherwise, the % value of positives is calculated as described in the immediately preceding paragraph. However, in the context of the amino acid sequence identity comparisons IS performed as described for ALIGN-2 and NCBI-BLAST2 above, includes amino acid residues in the sequences compared that are not only identical, but also those that have similar properties. Amino acid residues that score a positive value to an amino acid residue of interest are those that are either identical to the amino acid residue of interest or are a preferred substitution (as defined in Table 1 below) of the amino acid residue of interest.

For amino acid sequence comparisons using ALIGN-2 or NCBI-BLAST2, the % value of positives of 20 a given amino acid sequence A to, with, or against a given amino acid sequence B (which can alternatively be phrased as a given amino acid sequence A that has or comprises a certain % positives to, with, or against a given amino acid sequence B) is calculated as follows: 100 times the fraction X/Y where X is the number of amino acid residues scoring a positive value as defined above by the sequence alignment program ALIGN-2 or NCBI-BLAST2 in that program's alignment of A and B, and where Y is the total number of amino acid residues in B. It will be appreciated that where the length of amino acid sequence A is not equal to the length of amino acid sequence B, the % positives of A to B will not equal the % positives 30 of B to A.

"Isolated," when used to describe the various polypeptides disclosed herein, means polypeptide that has been identified and separated and/or recovered from a component of its natural environment. Contaminant components of its natural environment are materials that would typically interfere with diagnostic or therapeutic uses for the polypeptide, and may include enzymes, hormones, and other proteinaceous or non-proteinaceous 35 solutes. In preferred embodiments, the polypeptide will be purified (1) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, or (2) to homogeneity by SDS-PAGE under non-reducing or reducing conditions using Coomassie blue or, preferably, 320 silver stain. Isolated polypeptide includes polypeptide in situ within recombinant cells, since at least one component of the PRO polypeptide natural environment will not be present. Ordinarily, however, isolated polypeptide will be prepared by at least one purification step.

An "isolated" PRO polypeptide-encoding nucleic acid is a nucleic acid molecule that is identified and separated from at least one contaminant nucleic acid molecuie with which it is ordinarily associated in the natural 5 source of the PRO polypeptide nucleic acid. An isolated PRO polypeptide nucleic acid molecule is other than in the form or setting in which it is found in nature. Isolated PRO polypeptide nucleic acid molecules therefore are distinguished from the specific PRO polypeptide nucleic acid molecule as it exists in natural cells. However, an isolated PRO polypeptide nucleic acid molecule includes PRO polypeptide nucleic acid molecules contained in cells that ordinarily express the PRO polypeptide where, for example, the nucleic acid molecule is in a 10 chromosomal location different from that of natural cells.

The term "control sequences" refers to DNA sequences necessary for the expression of an operably linked coding sequence in a particular host organism. The control sequences that are suitable for prokaryotes, for example, include a promoter, optionally an operator sequence, and a ribosome binding site. Eukaryotic ceils are known to utilize promoters, polyadenylation signals, and enhancers.

Nucleic acid is "operably linked" when it is placed into a functional relationship with another nucleic acid sequence. For example, DNA for a presequence or secretory leader is operably linked to DNA for a polypeptide if it is expressed as a preprotein that participates in the secretion of the polypeptide; a promoter or enhancer is operably linked to a coding sequence if it affects the transcription of the sequence; or a ribosome binding site is operably linked to a coding sequence if it is positioned so as to facilitate translation. Generally, 20 "operably linked" means that the DNA sequences being linked are contiguous, and, in the case of a secretory ieader, contiguous and in reading phase. However, enhancers do not have to be contiguous. Linking is accomplished by ligation at convenient restriction sites. If such sites do not exist, the synthetic oligonucleotide adaptors or linkers are used in accordance with conventional practice.

The term "antibody" is used in the broadest sense and specifically covers, for example, single anti-PRO 25 monoclonal antibodies (including agonist, antagonist, and neutralizing antibodies), anti-PRO antibody compositions with poiyepitopic specificity, single chain anti-PRO antibodies, and fragments of anti-PRO antibodies (see below). The term "monoclonal antibody" as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally-occurring mutations that may be present in minor amounts. 30 "Stringency" of hybridization reactions is readily determinable by one of ordinary skill in the art, and generally is an empirical calculation dependent upon probe length, washing temperature, and salt concentration. In general, longer probes require higher temperatures for proper annealing, while shorter probes need lower temperatures. Hybridization generally depends on the ability of denatured DNA to reanneal when complementary strands are present in an environment below their melting temperature. The higher the degree 35 of desired homology between the probe and hybridizable sequence, the higher the relative temperature which can be used. As a result, it follows that higher relative temperatures would tend to make the reaction conditions more stringent, while lower temperatures less so. For additional details and explanation of stringency of 321 hybridization reactions, see Ausubel et al., Current Protocols in Molecular Biology. Wiley Interscience Publishers, (1995).

"Stringent conditions" or "high stringency conditions", as defined herein, may be identified by those that: (1) employ low ionic strength and high temperature for washing, for example 0.015 M sodium chloride/0.0015 M sodium citrate/0.1% sodium dodecyl sulfate at 50°C; (2) employ during hybridization a S denaturing agent, such as formamide, for example, 50% (v/v) formamide with 0.1% bovine serum albumin/0.1 % Ficoll/0.1 % polyvinylpyrrolidone/50mMsodium phosphate buffer at pH 6.5 with 750 mM sodium chloride, 75 mM sodium citrate at 42°C; or (3) employ 50% formamide, 5 x SSC (0.75 M NaCl, 0.075 M sodium citrate), 50 mM sodium phosphate (pH 6.8), 0.1% sodium pyrophosphate, 5 x Denhardt's solution, sonicated salmon sperm DNA (50 pg/ml), 0.1 % SDS, and 10% dextran sulfate at 42°C, with washes at 42°C 10 in0.2xSSC (sodium chloride/sodium citrate) and 50% formamide at 55 °C, followedby a high-stringency wash consisting of 0.1 x SSC containing EDTA at 55 °C.

"Moderately stringent conditions" may be identified as described by Sambrook et al., Molecular Cloning: A Laboratory Manual. New York: Cold Spring Harbor Press, 1989, and include the use of washing solution and hybridization conditions (e.g., temperature, ionic strength and %SDS) less stringent that those 15 described above. An example of moderately stringent conditions is overnight incubation at 37°C in a solution comprising: 20% formamide, 5 x SSC (150 mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5 x Denhardt's solution, 10% dextran sulfate, and 20 mg/ml denatured sheared salmon sperm DNA, followed by washing the filters in 1 x SSC at about 37-50°C. The skilled artisan will recognize how to adjust the temperature, ionic strength, etc. as necessary to accommodate factors such as probe length and the like. 20 The term "epitope tagged" when used herein refers to a chimeric polypeptide comprising a PRO polypeptide fused to a "tag polypeptide". The tag polypeptide has enough residues to provide an epitope against which an antibody can be made, yet is short enough such that it does not interfere with activity of the polypeptide to which it is fused. The tag polypeptide preferably also is fairly unique so that the antibody does not substantially cross-react with other epitopes. Suitable tag polypeptides generally have at least six amino acid 25 residues and usually between about 8 and 50 amino acid residues (preferably, between about 10 and 20 amino acid residues).

As used herein, the term "immunoadhesin" designates antibody-like molecules which combine the binding specificity of a heterologous protein (an "adhesin") with the effector functions of immunoglobulin constant domains. Structurally, the immunoadhesins comprise a fusion of an amino acid sequence with the 30 desired binding specificity which is other than the antigen recognition and binding site of an antibody (i.e., is "heterologous"), and an immunoglobulin constant domain sequence. The adhesin part of an immunoadhesin molecule typically is a contiguous amino acid sequence comprising at least the binding site of a receptor or a ligand. The immunoglobulin constant domain sequence in the immunoadhesin may be obtained from any immunoglobulin, such as IgG-1, IgG-2, IgG-3, or IgG-4 subtypes, IgA (including IgA-1 and IgA-2), IgE, IgD 35 or IgM.

"Active" or "activity" for the purposes herein refers to form(s) of a PRO polypeptide which retain a biological and/or an immunological activity of native or naturally-occurring PRO, wherein "biological" activity 322 refers to a biological function (either inhibitory or stimulatory) caused by a native or naturally-occurring PRO other than the ability to induce the production of an antibody against an antigenic epitope possessed by a native or naturally-occurring PRO and an "immunological" activity refers to the ability to induce the production of an antibody against an antigenic epitope possessed by a native or naturally-occurring PRO.

The term "antagonist" is used in the broadest sense, and includes any molecule that partially or fully 5 blocks, inhibits, or neutralizes a biological activity of a native PRO polypeptide disclosed herein. In a similar manner, the term "agonist" is used in the broadest sense and includes any molecule that mimics a biological activity of a native PRO polypeptide disclosed herein. Suitable agonist ot antagonist molecules specifically include agonist or antagonist antibodies or antibody fragments, fragments or amino acid sequence variants of native PRO polypeptides, peptides, antisense oligonucleotides, small organic molecules, etc. Methods for 10 identifying agonists or antagonists of a PRO polypeptide may comprise contacting a PRO polypeptide with a candidate agonist or antagonist molecule and measuring a detectable change in one or more biological activities normally associated with the PRO polypeptide.

"Treatment" refers to both therapeutic treatment and prophylactic or preventative measures, wherein the object is to prevent or slow down (lessen) the targeted pathologic condition or disorder. Those in need of 15 treatment include those already with the disorder as well as those prone to have the disorder or those in whom the disorder is to be prevented.

"Chronic" administration refers to administration of the agent(s) in a continuous mode as opposed to an acute mode, so as to maintain the initial therapeutic effect (activity) for an extended period of time. "Intermittent" administration is treatment that is not consecutively done without interruption, but rather is cyclic 20 in nature.

"Mammal" for purposes of treatment refers to any animal classified as a mammal, including humans, domestic and farm animals, and zoo, sports, or pet animals, such as dogs, cats, cattle, horses, sheep, pigs, goats, rabbits, etc. Preferably, the mammal is human.

Administration "in combination with" one or more further therapeutic agents includes simultaneous 25 (concurrent) and consecutive administration in any order.

"Carriers" as used herein include pharmaceuticaliy acceptable carriers, excipients, or stabilizers which are nontoxic to the cell or mammal being exposed thereto at the dosages and concentrations employed. Often the physiologically acceptable carrier is an aqueous pH buffered solution. Examples of physiologically acceptable carriers include buffers such as phosphate, citrate, and other organic acids; antioxidants including 30 ascorbic acid; low molecular weight (less than about 10 residues) polypeptide; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, arginine or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugar alcohols such as mannitol or sorbitol; salt-forming counterfoils such as sodium; and/or nonionic surfactants such as TWEEN™, polyethylene glycol (PEG), 35 and PLURONICS™.

"Antibody fragments" comprise a portion of an intact antibody, preferably the antigen binding or variable region of the intact antibody. Examples of antibody fragments include Fab, Fab", F(ab') 2, and Fv 323 fragments; diabodies; linear antibodies (Zapata et al., Protein Eng. 8(10): 1057-1062 [1995]); single-chain antibody molecules; and multispecific antibodies formed from antibody fragments.

Papain digestion of antibodies produces two identical antigen-binding fragments, called "Fab" fragments, each with a single antigen-binding site, and a residual "Fc" fragment, a designation reflecting the ability to crystallize readily. Pepsin treatment yields an F(ab')2 fragment that has two antigen-combining sites 5 and is still capable of cross-linking antigen.

"Fv" is the minimum antibody fragment which contains a complete antigen-recognition and -binding site. This region consists of a dimer of one heavy- and one light-chain variable domain in tight, non-covalent association. It is in this configuration that the three CDRs of each variable domain interact to define an antigen-binding site on the surface of the VH-VL dimer. Collectively, the six CDRs confer antigen-binding specificity 10 to the antibody. However, even a single variable domain (or half of an Fv comprising only three CDRs specific for an antigen) has the ability to recognize and bind antigen, although at a lower affinity than the entire binding site.

The Fab fragment also contains the constant domain of the light chain and the first constant domain (CHI) of the heavy chain. Fab fragments differ from Fab* fragments by the addition of a few residues at the 15 carboxy terminus of the heavy chain CHI domain including one or more cysteines from die antibody hinge region. Fab'-SH is the designation herein for Fab' in which the cysteine residue(s) of the constant domains bear a free thiol group. F(ab')2 antibody fragments originally were produced as pairs of Fab' fragments which have hinge cysteines between them. Other chemical couplings of antibody fragments are also known.

The "light chains" of antibodies (immunoglobulins) from any vertebrate species can be assigned to one 20 of two clearly distinct types, called kappa and lambda, based on the amino acid sequences of their constant domains.

Depending on the amino acid sequence of the constant domain of their heavy chains, immunoglobulins can be assigned to different classes. There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgGl, IgG2, IgG3, IgG4, IgA, 25 and IgA2.

"Single-chain Fv" or "sFv" antibody fragments comprise the VH and VL domains of antibody, wherein these domains are present in a single polypeptide chain. Preferably, the Fv polypeptide further comprises a polypeptide linker between the VH and VL domains which enables the sFv to form the desired structure for antigen binding. For a review of sFv, see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol. 113, 30 Rosenburg and Moore eds., Springer-Verlag, New York, pp. 269-315 (1994).

The term "diabodies" refers to small antibody fragments with two antigen-binding sites, which fragments comprise a heavy-chain variable domain (VH) connected to a light-chain variable domain (VL) in the same polypeptide chain (VH - VL). By using a linker that is too short to allow pairing between the two domains on the same chain, the domains are forced to pair with the complementary domains of another chain and create 35 two antigen-binding sites. Diabodies are described more fully in, for example, EP 404,097; WO 93/11161; and Holiinger et al., Proc. Nad. Acad. Sci. USA. 90:6444-6448 (1993).

An "isolated" antibody is one which has been identified and separated and/or recovered from a 324 component of its natural environment. Contaminant components of its natural environment are materials which would interfere with diagnostic or therapeutic uses for the antibody, and may include enzymes, hormones, and other proteinaceous or nonproteinaceous solutes. In preferred embodiments, the antibody will be purified (1) to greater than 95 % by weight of antibody as determined by the Lowry method, and most preferably more than 99% by weight, (2) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid 5 sequence by use of a spuming cup sequenator, or (3) to homogeneity by SDS-PAGE under reducing or nonreducing conditions using Coomassie blue or, preferably, silver stain. Isolated antibody includes the antibody in situ within recombinant cells since at least one component of the antibody's natural environment will not be present. Ordinarily, however, isolated antibody will be prepared by at least one purification step.

The word "label" when used herein refers to a detectable compound or composition which is conjugated 10 directly or indirectly to the antibody so as to generate a "labeled" antibody. The label may be detectable by itself (e.g. radioisotope labels or fluorescent labels) or, in the case of an enzymatic label, may catalyze chemical alteration of a substrate compound or composition which is detectable.

By "solid phase" is meant a non-aqueous matrix to which the antibody of the present invention can adhere. Examples of solid phases encompassed herein include those formed partially or entirely of glass (e.g., 15 controlled pore glass), polysaccharides (e.g., agarose), polyacrylamides, polystyrene, polyvinyl alcohol and silicones. In certain embodiments, depending on the context, the solid phase can comprise the well of an assay plate; in others it is a purification column (e.g., an affinity chromatography column). This term also includes a discontinuous solid phase of discrete particles, such as those described in U.S. Patent No. 4,275,149.

A "liposome" is a small vesicle composed of various types of lipids, phospholipids and/or surfactant 20 which is useful for delivery of a drug (such as a PRO polypeptide or antibody thereto) to a mammal. The components of the liposome are commonly arranged in a bilayer formation, similar to the lipid arrangement of biological membranes.

A "small molecule" is defined herein to have a molecular weight below about 500 Daltons.

II. Compositions and Methods of the Invention The present invention provides newly identified and isolated nucleotidesequencesencoding polypeptides referred to in the present application as PRO polypeptides. In particular, cDNAs encoding various PRO polypeptides have been identified and isolated, as disclosed in further detail in the Examples below. It is noted that proteins produced in separate expression rounds may be given different PRO numbers but the UNQ number 30 is unique for any given DNA and the encoded protein, and will not be changed. However, for sake of simplicity, in the present specification the protein encoded by the full length native nucleic acid molecules disclosed herein as well as all further native homologues and variants included in the foregoing definition of PRO, will be referred to as "PRO/number", regardless of their origin or mode of preparation.

As disclosed in the Examples below, various cDNA clones have been deposited with the ATCC. The 35 actual nucleotide sequences of those clones can readily be determined by the skilled artisan by sequencing of the deposited clone using routine methods in the art. The predicted amino acid sequence can be determined from the nucleotide sequence using routine skill. For the PRO polypeptides and encoding nucleic acids described 325 herein, Applicants have identified what is believed to be the reading frame best identifiable with the sequence information available at the time.

A. Full-Leneth PRO Polypeptides 1. PRQ1560 Using the WU-BLAST2 sequence alignment computer program, the full-length native sequence PR01560 (shown in Figure 2 and SEQ ID NO:4) has certain amino acid sequence identity with Tspan-6, identified after the discovery of the present invention herein. Accordingly, it is presently believed that PR01560 disclosed in the present application is a newly identified member of the tetraspan family. 2. PRQ444 The DNA26846-I397 clone was isolated from a human fetal lung library using a trapping technique which selects for nucleotide sequences encoding secreted proteins. Thus, the DNA26846-1397 clone encodes a secreted factor. As far as is known, the DNA26846-1397 sequence encodes a novel factor designated herein as PR0444. Using the WU-BLAST2 sequence alignment computer program, no significant sequence identity 15 with known proteins was revealed. 3. PRQ1018 The DNA56107-1415 clone was isolated from a human ovary tumor tissue library using a trapping technique which selects for nucleotide sequences encoding secreted proteins. As far as is known, the 20 DNA56107-1415 sequence encodes a novel factor designated herein as PR01018; using the WU-BLAST2 sequence alignment computer program, no significant sequence identities to any known proteins were revealed. 4. PRQ1773 Using the WU-BLAST2 sequence alignment computer program, it has been found that a portion of the 25 full-length native sequence PRO1773 (shown in Figure 8 and SEQ ID NO: 10) has certain amino acid sequence identity with a portion of the retinol dehydrogenase type II protein of rattus norvegicus (ROH2_RAT). Accordingly, it is presently believed that PR01773 disclosed in the present application is a newly identified member of the retinol dehydrogenase protein family and may possess activity typical of that protein family. 5. PRQ1477 Using the WU-BLAST2 sequence alignment computer program, it has been found that a full-length native sequence PR01477 (shown in Figure 10 and SEQ ID NO: 12) has certain amino acid sequence identity with the mannosyl-oiigosaccharide 1,2-alpha-mannosidase protein (A54408). Accordingly, it is presently believed that PRO1477 disclosed in the present application is a newly identified member of the mannosidase 35 protein family and may possess activity typical of the mannosidase protein family. 326 6. PRQ1478 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01478 (shown in Figure 12 and SEQ ID NO: 17) has certain amino acid sequence identity with galactosyltransferases. Accordingly, it is presently believed that PR01478 disclosed in the present application is a newly identified member of the galactosyltransferase family and may possess at least one shared mechanism 5 with other members of this family. 7. PRQ831 The DNA56862-1343 clone was isolated from a human uterus library using a trapping technique which selects for nucleotide sequences encoding secreted proteins. Thus, the DNA56862-1343 clone does encode a 10 secreted factor. As far as is known, the DNAS6862-1343 sequence encodes a novel factor designated herein as PR0831; using the WU-BLAST2 sequence alignment computer program, no sequence identities to any known proteins were revealed. 8- PRQ1113 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PROl 113 (shown in Figure 16 and SEQ ID N0:24) has certain amino acid sequence identity with LIG-1 and SLIT. Accordingly, it is presently believed that PROH13 disclosed in the present application is a newly identified member of the leucine rich repeat family and may possess protein-protein interaction activity as is typical of this family. 9. PROl 194 As far as is known, the DNA57841-1522 sequence encodes a novel factor designated herein as PROl 194; using WU-BLAST2 sequence alignment computer programs, limited sequence identities to known proteins were revealed.

. PROlllO Using the WU-BLAST2 sequence alignment computer program, it has been found that a full-length native sequence PROlllO (shown in Figure 20 and SEQ ID NO:31) has certain amino acid sequence identity with the murine myeloid upregulated protein. Accordingly, it is presently believed that PROl 110 disclosed in 30 the present application is a newly identified member of the myeloid upregulated protein family and may possess activity typical of that family.

U. PRQ1378 The DNA58730-1607 clone was isolated from a bone marrow library using a trapping technique which 35 selects for nucleotide sequences encoding secreted proteins. Thus, the DN A58730-1607 clone encodes a secreted factor. As far as is known, the DNA58730-1607 sequence encodes a novel factor designated herein as PR01378. WU-BLAST2 sequence alignment computer programs revealed some sequence identities between 327 the amino acid sequence of PR01378 with known proteins. However, they were determined to not be significant. 12. PRO 1481 As far as is known, the DNA58732-1650 sequence encodes a novel factor designated herein as 5 PR01481. Using WU-BLAST2 sequence alignment computer programs, only some sequence identities to known proteins were revealed. 13. PROl 189 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native 10 sequence PROl 189 (shown in Figure 26 and SEQ ID NO:43) has certain amino acid sequence identity with die amino acid sequence of an E2S protein designated "MUSE25A_1" in the Dayhoff database. Accordingly, it is presently believed that PROl 189 disclosed in the present application is a newly identified member of the E2S protein family and may possess activity or properties typical of that family. 14. PRQ1415 The DNA58852-1637 clone was isolated from a diseased human prostate tissue library using a trapping technique which selects for nucleotide sequences encoding secreted proteins. As far as is known, the DNA58852-1637 sequence encodes a novel factor designated herein as PR01415; using the WU-BLAST2 sequence alignment computer program, no significant sequence identities to any known proteins were revealed.

. PRQ1411 As far as is known, the DNA59212-1627 sequence encodes a novel factor designated herein as PRO 1411. However, using WU-BLAST2 sequence alignment computer programs, some sequence identities to known proteins were revealed. 16. PRQ1295 As far as is known, the DNA59218-1559 sequence encodes a novel factor designated herein as PR01295. Using WU-BLAST2sequence alignment computer programs, only some sequence identities to known proteins were revealed. 17. PRQ13S9 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR013S9 (shown in Figure 34 and SEQ ID NO:56) has certain amino acid sequence identity with N-acetylgalactosamine alpha-2, 6-sialyltransferase. Accordingly, it is presently believed that PR01359 disclosed 35 in the present application is a newly identified member of the sialyltransferase family and may possess transferase activity typical of this family. 328 18. PROl 190 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PROl 190 (shown in Figure 36 and SEQ ID NO:58) has certain amino acid sequence identity with both rat and human CDO. Accordingly, it is presently believed that PROl 190 disclosed in the present application is a newly identified member of the CDO family and may possess cell adhesion activity typical of the CDO 5 family. 19. PRQ1772 Using the WU-BLAST2 sequence alignment computer program, it has been found that a portion of the full-length native sequence PRO1772 (shown in Figure 38 and SEQ ID NO:63) has certain amino acid sequence 10 identity with a human microsomal dipeptidase protein (P R13857). Accordingly, it is presently believed that PRO1772 disclosed in the present application is a newly identified member of the peptidase protein family and may possess activity typical of that protein family.

. PRQ1248 Using the WU-BLAST2 sequence alignment computer program, it has been found that a full-length native sequence PR01248 (shown in Figure 40 and SEQ ID NO:68) has amino acid sequence identity with the PUT-2 protein (AF026198_5). Accordingly, it is presently believed that PR01248 disclosed in the present application is a newly PUT-2 homolog and may possess activity typical of the PUT-2 protein. 21. PRQ1316 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01316 (shown in Figure 42 and SEQ ID N0:70) has certain amino acid sequence identity with murine dickkopf. Accordingly, it is presently believed that PR01316 disclosed in the present application is a newly identified member of the dickkopf family and may possess the ability to cause head induction from the 25 Spemann organizer and/or Wnt antagonism. 22. PROl 197 As far as is known, the DNA60611-1524 sequence encodes a novel factor designated herein as PROl 197. Using WU-BLAST2 sequence alignment computer programs, only some sequence identities to known 30 proteins were revealed as further described in the examples. 23. PRQ1293 Using the WU-BLAST2 sequence alignment computer program, it has been found that a full-length native sequence PR01293 (shown in Figure 46 and SEQ ID NO:77) has certain amino acid sequence identity 35 with the human Ig heavy chain V region protein (HSVCD541). Accordingly, it is presently believed that PRO 1293 disclosed in the present application is a newly identified member of the Ig superfamily of proteins and fragments thereof and may possess activity typical of that family. 329 24. PRO 1380 The DNA60740-1615 clone was isolated from a human retina library. As far as is known, the DNA60740-1615 sequence encodes a novel multi-span transmembrane polypeptide designated herein as PR01380. Using WU-BLAST2 sequence alignment computer programs, some sequence identity with known proteins were revealed.

. PRQ1265 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PRO1265 (shown in Figure 50 and SEQ ID NO:84) has certain amino acid sequence identity with the Figl polypeptide designated "MMU70429 1" in the Dayhoff database (version 35.45 SwissProt 35). 10 Accordingly, it is presently believed that PR01265 disclosed in the present application is a newly identified member of the FIG1 family and may possess activity typical of the FIG1 polypeptide, including activation by interleukin-4. 26. PRQ1250 Using the WU-BLAST2 sequence alignment computer program, it has been found that a full-length native sequence PR01250 (shown in Figure 52 and SEQ ID NO:86) has certain amino acid sequence identity with the human long chain fatty acid CoA ligase protein (LCFB HUMAN). Accordingly, it is presently believed that PR01250 disclosed in the present application is a newly identified long chain fatty acid CoA ligase homolog that may have activity typical of long chain fatty acis CoA ligase. 27. PRQ1475 Using the WU-BLAST2 sequence alignment computer program, it has been found that a full-length native sequence PR01475 (shown in Figure 54 and SEQ ID NO:88) has certain amino acid sequence identity with a portion of the mouse alpha-3-D-mannoside beat-l,2-N-acetylglucosaminyltransferase I protein. 25 Accordingly, it is presently believed that PRO1475 disclosed in the present application is a newly identified member of the N-acetylglucosaminyltransferase protein family and may possess activity typical of that protein family. 28. PRQ1377 As described herein, WU-BLAST2 sequence alignment computer programs were used to determine the sequence identity of the PR01377 amino acid sequence with the amino acid sequences of known proteins. While some sequence identities were revealed, they were determined to not be significant. Accordingly, as far as is known, the DNA61608 sequence encodes a novel transmembrane protein designated herein as PROI377. 29. PRQ1326 The DNA62808-1582 clone is believed to encode a secreted factor. As far as is known, the DNA62808-1582 sequence encodes a novel factor designated herein as PR01326; using WU-BLAST2 sequence alignment 330 computer programs, sequence identities to known proteins were revealed but determined not to be significant.

. FRQ1249 The DNA62809-1531 clone was isolated from a human colon tumor tissue library using a trapping technique which selects for nucleotide sequences encoding secreted proteins. As far as is known, the DNA62809-5 1531 sequence encodes a novel factor designated herein as PR01249; using the WU-BLAST2 sequence alignment computer program, no sequence identities to any known proteins were revealed. 31. PRQ1315 Using the WU-BLAST2 sequence alignment computer program, it has been found that a full-length 10 native sequence PRO 1315 (shown in Figure 62 and SEQ ID N0:104) has certain amino acid sequence identity with the class II cytokine receptor 4 protein of mus musculus (MMU53696 1). Accordingly, it is presendy believed that PR01315 disclosed in the present application is a newly identified member of the cytokine reeptor protein family and may possess activity typical of that family. 32. FRQ1599 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01599 (shown in Figure 64 and SEQ ID NO:111) has certain amino acid sequence identity with Dayhoff sequence "CFAD_PIG". Accordingly, it is presently believed that PR01599 disclosed in the present application is a newly identified member of the Granzyme M family and may possess activity or properties 20 typical of the Granzyme M family. 33. PRQ1430 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PRO1430 (shown in Figure 66 and SEQ ID NO: 116) has certain amino acid sequence identity prostate 25 specific reductase (designated "P_W03198" in the Dayhoff database). Accordingly, it is presently believed that PR01430 disclosed in the present application is a newly identified member of the reductase family and may possess activity typical of members of the reductase family. 34. PRQ1374 As far as is known, the DNA64849-1604 sequence encodes a novel factor designated herein as PR01374; using WU-BLAST2 sequence alignment computer programs, some sequence identities to known proteins such as the human alpha subunit of P4HA were revealed. Therefore, it is believed that PR01374 is related to P4HA and may share one or more mechanisms. 35. PRQ1311 The DNA64863-1573 clone was isolated from human aortic endothelial cells and is believed to encode a novel transmembrane polypeptide designated herein as PR01311. Using WU-BLAST2 sequence alignment 331 computer programs, some sequence identities with known proteins were revealed, but were determined to not be significant. 36, PRQ13S7 Using the WU-BLAST2 sequence alignment computer program, it has been found that a full-length 5 native sequence PR01357 (shown in Figure 72 and SEQ ID NO: 128) has certain amino acid sequence identity with the von Ebner minor salivary gland protein of mus musculus (MMU46068 1). Accordingly, it is presently believed that PR013S7 disclosed in the present application is a newly identified von Ebner minor salivary gland protein homolog. 37. FRQ1244 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01244 (shown in Figure 74 and SEQ ID NO: 130) has certain amino acid sequence identity with a known implantation-associated protein designated "AF008554 1" on the Dayhoff database (version 35.45 SwissProt 35). Accordingly, it is presently believed that PR01244 disclosed in the present application is a newly IS identified member of the implantation-associated protein family and may possess attachment activity typical of that protein family. 38. PROl 246 Using the WU-BLAST2 sequence alignment computer program, it has been found that a full-length 20 native sequence PR01246 (shown in Figure 76 and SEQ ID N0:132) has certain amino acid sequence identity with the murine bone-related sulphatase-like precursor protein (P_R51355). Accordingly, it is presently believed that PRO1246 disclosed in the present application is a newly identified bone-related sulphatase homolog and may possess activity typical of bone-related sulfatase. 39. PROl 356 Using the WU-BLAST2 sequence alignment computer program, it has been found that a full-length native sequence PR01356 (shown in Figure 78 and SEQ ID NO: 134) has certain amino acid sequence identity with the CPE-receptor protein of mus musculus (AB000713_1). Accordingly, it is presently believed that PRO 1356 disclosed in the present application is a newly identified member of the CPE receptor family and may 30 possess activity typical of that family. 40. PRQ1275 As far as is known, the DNA64888-1542 sequence encodes a novel factor designated herein as PR01275. Using WU-BLAST2 sequence alignment computer programs, some sequence identities to known 35 proteins were revealed. 332 41. PRQ1274 As far as is known, the DNA64889-1S41 sequence encodes a novel factor designated herein as PR01274. Using WU-BLAST2 sequence alignment computer programs, some sequence identities to known proteins were revealed. 42. PRQ1412 The DNA64897-1628 clone is believed to be a secreted factor. As far as is known, the DNA64897-1628 sequence encodes a novel factor designated herein as PRO 1412; using WU-BLAST2 sequence alignment computer programs, sequence identities to known proteins were revealed but determined not to be significant. 43. PRQ1557 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01SS7 (shown in Figure 86; SEQ ID NO: 142) has certain amino acid sequence identity chordin protein designated AF034606 1 in the Dayhoff database. Accordingly, it is presently believed that PR01557 disclosed in the present application is a newly identified member of the chordin family and may possess activity 15 typical of the chordin family. 44. PRQ1286 The DNA64903-1553 clone identified using techniques which selects for nucleotide sequences encoding secreted proteins. As far as is known, the DNA64903 sequence encodes a novel secreted factor designated herein 20 as PRO1286. Using WU-BLAST2 sequence alignment computer programs, some sequence identities to known proteins were revealed; however, it was determined that they were not significant. 45. PRQ1294 Using the WU-BLAST2 sequence alignment computer program, it has been found that a full-length 25 native sequence PRO1294 (shown in Figure 90 and SEQ ID NO: 146) has certain amino acid sequence identity with the neuronal olfactomedin-related ER localized protein of the rat (173636). Accordingly, it is presently believed that PROI294 disclosed in the present application is a newly identified olfactomedin homolog and may possess activity typical of that protein. 46. PRQ1347 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PRO 1347 (shown in Figure 92 and SEQ ID NO: 148) has certain amino acid sequence identity with butyrophilin. Moreover, there is a transmembrane domain approximately in the middle of the sequence as is typical of butyrophilins. Accordingly, it is presently believed that PR01347 disclosed in the present application 35 is a newly identified member of the butyrophilin family and may play a role in the budding and release of milk-fat glubules during lactation. 333 47. PRQ1305 The DNA64952-1568 clone was isolated from a human fetal kidney library using a trapping technique which selects for nucleotide sequences encoding secreted proteins. Thus, the DNA54952-1568 clone does encode a secreted factor. As far as is known, the DNA64952-1568 sequence encodes a novel factor designated herein as PR01305; using the WU-BLAST2 sequence alignment computer program, no sequence identities to 5 any known proteins were revealed. 48. PRQ1273 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PRO1273 (shown in Figure 96 and SEQ ID NO: 158) has certain amino acid sequence identity with a 10 lipocalin precursor. Moreover, Figure 96 shows that PR01273 has a motif conserved in lipocalins. Accordingly, it is presently believed that PR01273 disclosed in the present application is a newly identified member of the lipocalin family and shares at least one mechanism with lipocalins. 49. PRQ1302 IS Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01302 (shown in Figure 98 and SEQ ID NO: 160) has certain amino acid sequence identity with CD33L1 and CD33L2. Accordingly, it is presently believed that PR01302 disclosed in the present application is a newly identified member of the siaioadhesin family and possesses characteristics typical of this family. Specifically, PR01302 may be involved in cancer, inflammation, hemopoisis, neuronal development and/or 20 immunity. 50. PRQ1283 Using the WU-BLAST2 sequence alignment computer program, it has been found that a full-length native sequence PRO1283 (shown in Figure 100 and SEQ ID NO: 162) has certain amino acid sequence identity 25 with the rat odorant binding protein homolog OBP-II precursor (A40464). Accordingly, it is presently believed that PRO1283 disclosed in the present application is a newly odorant binding protein and may possess activity typical of the odorant binding proteins. 51. PRQ1279 Using the WU-BLAST2 sequence alignment computer program, it has been found that a full-length native sequence PRO 1279 (shown in Figure 102 and SEQ ID NO: 170) has certain amino acid sequence identity with the mouse neuropsin protein (156559). Accordingly, it is presently believed that PRO1279 disclosed in the present application is a newly identified neuropsin homolog and may possess activity typical of the neuropsin protein. 52. PRO1304 Using the WU-BLAST2 sequence alignment computer program, it has been found that a full-length 334 native sequence PR01304 (shown in Figure 104 and SEQ ID NO: 180) has certain amino acid sequence identity with the FK-506 binding protein of mus musculus (AF040252 1). Accordingly, it is presently believed that PR01304 disclosed in the present application is a newly identified member of the FK506 binding protein family and may possess activity typical of that family.

S3. FRQ1317 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01317 (shown in Figure 106 and SEQ ID NO: 189) has certain amino acid sequence identity with human CD97 protein. Accordingly, it is presently believed that PR01317 disclosed in the present application is a leukocyte antigen that may be involved in leukocyte activation. 54. PRQ1303 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01303 (shown in Figure 108 and SEQ ID NO: 194) has certain amino acid sequence identity with neuropsin. Accordingly, it is presently believed that PR01303 disclosed in the present application is a newly IS identified member of the serine protease family and may possess catabolic activity typical of this family. 55. PROl 306 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01306 (shown in Figure 110 and SEQ ID NO: 196) has certain amino acid sequence identity with 20 Dayhoff sequence no. AIF1HUMAN. Accordingly, it is presently believed that PR01306 disclosed in the present application is a newly identified member of the AIFl/daintain family and may possess activity and properties typical of AIFl/daintain. 56. PROl 336 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01336 (shown in Figure 112 and SEQ ID NO: 198) has certain amino acid sequence identity with slit. Accordingly, it is presently believed that PRO1336 disclosed in the present application is a newly identified member of the EGF-repeat family and may possess protein interaction mediation activity. 57. PRQ1278 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PRO1278 (shown in Figure 114 and SEQ ID N0:203) has certain amino acid sequence identity lysozyme c -1 precursor designated "LYC1ANAPL" in the Dayhoff database. Accordingly, it is presently believed that PR01278 disclosed in the present application is a newly identified member of the lysozyme family 35 and may possess hydrolytic and other activity typical of the lysozyme family. 335 58. PRQ1298 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PRO1298 (shown in Figure 116 and SEQ ID N0.210) has certain amino acid sequence identity with glycosyltransferase alg2. Accordingly, it is presently believed that PR01298 disclosed in the present application is a newly identified member of the glycosyltransferase family and may share at least one mechanism with 5 members of this family. 59. PRQ1301 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01301 (shown in Figure 118 and SEQ ID NO:212) has consistent amino acid sequence identity with 10 cytochrome P4S0 proteins. Accordingly, it is presently believed that PR01301 disclosed in the present application is a newly identified member of the cytochrome P450 family and may possess monooxygenase activity typical of the cytochrome P450 family. 60. PRQ1268 As far as is known, the DNA66519-1535 sequence encodes a novel transmembrane polypeptide factor designated herein as PR01268. Using WU-BLAST2 sequence alignment computer programs, sequence identity to a known protein was revealed, but determined to not be significant. 61. PRQ1269 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01269 (shown in Figure 122 and SEQ ID NO:216) has certain amino acid sequence identity a bovine granulocyte peptide A precursor, designated "P_W23722" on the Dayhoff database (version 35.45 SwissProt 35). Accordingly, it is presently believed that PRO1269 disclosed in the present application is a newly identified member of the granulocyte A peptide family and may possess microbial activity typical of that family 25 of peptides. 62. PRQ1327 Using the WU-BLAST2 sequence alignment computer program, it has been found that a full-length native sequence PROI327 (shown in Figure 124 and SEQ ID NO:218) has certain amino acid sequence identity 30 with the rat neurexophilin-1 protein (NPH1RAT). Accordingly, it is presently believed that PR01327 disclosed in the present application is a newly identified member of the neurexophilin protein family and may possess activity typical of that protein family. 63. PRQ1382 Using WU-BLAST2 sequence alignment computer programs, it has been found that a lull-length native sequence PR01382 (shown in Figure 126 and SEQ ID N0:220) has certain amino acid sequence identity with the amino acid sequence of a known cerebellin-like glycoprotein designated "CERLRAT" in the Dayhoff 336 database. Accordingly, it is presently believed that PR01382 disclosed in the present application is a newly identified member of the cerebellin family of neuropeptides and may possess activity and properties typical of cerebellin. 64. PRQ1328 The DNA66658-1584 clone was isolated from a human diseased prostate tissue library using a trapping technique which selects for nucleotide sequences encoding proteins. As far as is known, the DNA66658-1584 sequence encodes a novel factor designated herein as PR01328; using the WU-BLAST2 sequence alignment computer program, no significant sequence identities to any known proteins were revealed. 65. PROl 325 The DNA66659-1593 clone was isolated from a human thymus tissue library using a trapping technique which selects for nucleotide sequences encoding proteins. As far as is known, the DNA66659-1593 sequence encodes a novel factor designated herein as PR01325; using the WU-BLAST2 sequence alignment computer program, no sequence identities to any known proteins were revealed. 66. PRQ1340 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01340 (shown in Figure 132 and SEQ ID NO:229) has certain amino acid sequence identity with Dayhoff sequence no. 146536. Accordingly, it is presently believed that PROl340 disclosed in the present 20 application is a newly identified member of the cadherin family and may possess activity and properties typical of the cadherin family. 67. PRQ1339 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native 25 sequence PR01339 (shown in Figure 134 and SEQ ID NO:234) has certain amino acid sequence identity with human pancreatic carboxypeptidase and carboxypeptidase al. Accordingly, it is presently believed that PRO1339 disclosed in the present application is a newly identified member of the carboxypeptidase family and possesses caboxypeptidase activity. 68. PRQ1337 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01337 (shown in Figure 136 and SEQ ID NO:236) has certain amino acid sequence identity with a human TBG identified as "THBG_HUMAN" in the Dayhoff database. Accordingly, it is presently believed that PR01337 disclosed in the present application is a newly identified member of the TBG family and may 35 possess thyroid hormone transport capability and have other 337 69. PROl 342 The DNA66674-1599 clone was isolated from human esophageal tissue. As described in further detail below, using WU-BLAST2 sequence alignment computer programs, some sequence identities to known proteins were revealed. The DNA66674-1599 clone appears to encode for a novel transmembrane polypeptide. 70. PRQ1343 The DNA6667S-1587 clone was isolated from a human smooth muscle cell tissue library using a trapping technique which selects for nucleotide sequences encoding secreted proteins. Thus, the DNA66675-1587 clone does encode a secreted factor. As far as is known, the DNA66675-1587 sequence encodes a novel factor designated herein as PR01343; using the WU-BLAST2 sequence alignment computer program, no 10 significant sequence identities to any known proteins were revealed. 71. PRQ1480 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01480 (shown in Figure 142 and SEQ ID NO:253) has certain amino acid sequence identity with 15 Dayhoff sequence no. 148746. Accordingly, it is presently believed that PR01480 disclosed in the present application is a newly identified member of the Semaphorin C family 72. PRQ1487 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native 20 sequence PR01487 (Figure 144; SEQ ID N0:260) has certain amino acid sequence identity with a radical fringe protein designated GGU82088 1 on the Dayhoff database. Accordingly, it is presently believed that PR01487 disclosed in the present application is a newly identified member of the hinge family and may possess activity typical of the fringe family. 73. PRQ1418 As far as is known, the DNA68864-1629 sequence encodes a novel factor designated herein as PR01418. Using WU-BLAST2 sequence alignment computer programs, sequence identities to known proteins were minimal. 74. PRQ1472 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01472 (shown in Figure 148 and SEQ ID NO:267) has certain amino acid sequence identity with butyrophilin. Accordingly, it is presently believed that PR01472 disclosed in the present application is a newly identified member of the butyrophilin family and may possess involvement in lactation. 75. PRQ1461 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native 338 sequence PR01461 (shown in Figure ISO and SEQ ID NO:269) has certain amino acid sequence identity the trypsin-like enzyme identified as "P_R89435" on the Dayhoff database. Accordingly, it is presently believed that PR01461 disclosed in the present application is a newly identified member of the serine protease family and may possess serine protease activity, and more particularly, may possess enzymatic activity typical of other trypsin-like enzymes. Homology was also found to exist between the PR01461 amino acid sequence and other 5 trypsin-like enzymes and serine proteases in the Dayhoff database. 76. PRQ1410 The DNA68874-1622 clone was isolated from a human brain meningioma tissue library using a trapping technique which selects for nucleotide sequences encoding proteins. As far as is known, the DNA68874-1622 10 sequence encodes a novel factor designated herein as PR01410; using the WU-BLAST2 sequence alignment computer program, no sequence identities to any known proteins were revealed. 77. PRQ1S68 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native 15 sequence PR01568 (shown in Figure 154 and SEQ ID NO:273) has certain amino acid sequence identity to tetraspan 5 and tetraspan 4. Accordingly, it is presently believed that PR01568 disclosed in the present application is a newly identified member of the tetraspanin family and may possess molecular facilitator activity typical of this family. 78. PROl 570 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01570 (shown in Figure 156 and SEQ ID NO:275) has certain amino acid sequence identity with SP60; however, for the first time, the first 199 amino acids (or amino terminal end) of that protein are identified and presented herein. Accordingly, it is presently believed that PR01570 disclosed in the present application 25 is a newly identified member of the serine protease family and is involved in carcinoma. 79. PRQ1317 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01317 (shown in Figure 158 and SEQ ID NO:277) has certain amino acid sequence identity with 30 a known semaphorin B protein, designated "148745" on the Dayhoff database. Accordingly, it is presently believed that PR01317 disclosed in the present application is a newly identified member of the semaphorin glycoprotein family and may possess activity or properties typical of semaphorins. 80. PRQ1780 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01780 (shown in Figure 160 and SEQ ID NO:282) has certain amino acid sequence identity with a known glucuronosyltransferase designated "UDA2 RAB1T" in the Dayhoff database. Accordingly, it is 339 presently believed that PRO 1780 disclosed in the present application is a newly identified member of the gluciironosyltransferase family and may possess enzymatic activity and other properties typical of the glucuronosyltransferase family. 81. PRQ1486 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01486 (shown in Figure 162 and SEQ ID NO:287) has certain amino acid sequence identity with cerebellin I precursor. Accordingly, it is presently believed that PRO1486 disclosed in the present application is a newly identified member of the cerebellin family and shares at least one mechanism with cerebellin. 82. PRQ1433 The DNA71184-1634 clone was isolated from a human adrenal gland tissue library using a trapping technique which selects for nucleotide sequences encoding proteins. As far as is known, the DNA71184-1634 sequence encodes a novel factor designated herein as PR01433; using the WU-BLAST2 sequence alignment computer program, no sequence identities to any known proteins were revealed. 83. PROl 490 Using the WU-BLAST2 sequence alignment computer program, it has been found that a portion of the full-length native sequence PR01490 (shown in Figure 166 and SEQ ID NO-.297) has certain amino acid sequence identity with a portion of the l-acyl-sn-glycerol-3-phosphate acyltransferase protein (S60478). 20 Accordingly, it is presently believed that PR01490 disclosed in the present application is a newly identified member of the acyltransferase protein family and may possess activity typical of l-acyl-sn-glycerol-3-phosphate acyltransferase proteins. 84. PRQ1482 The DNA71234-1651 clone was isolated from a human adrenal gland library using a trapping technique which selects for nucleotide sequences encoding secreted proteins. Thus, the DNA71234-1651 clone does encode a secreted factor. As far as is known, the DNA71234-1651 sequence encodes a novel factor designated herein as PR01482; using the WU-BLAST2 sequence alignment computer program, no sequence identities to any known proteins were revealed. 85. PROl 446 As far as is known, the DNA71277-1636 sequence encodes a novel factor designated herein as PRO1446. Using WU-BLAST2 sequence alignment computer programs, minimal sequence identities to known proteins were revealed. 86. PRQ1558 Using the WU-BLAST2 sequence alignment computer program, it has been found that a full-length 340 native sequence PRO 1558 (shown in Figure 172 and SEQ ID N0:306) has significant amino acid sequence identity with a methyltransferase protein (CAMTEUCGU). Accordingly, it is presently believed that PR01558 disclosed in the present application is a newly identified member of the methyltransferase protein family and may possess activity typical of that protein family. 87. PRQ16Q4 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01604 (shown in Figure 174 and SEQ ID N0:308) has certain amino acid sequence identity with the mouse liver cancer-originated cell growth factor designated PW37483 on the Dayhoff database. Accordingly, it is presently believed that PR01604 disclosed in the present application is a newly identified 10 member of the HDGF family and may possess growth factor activity typical of other HDGFs. 88. PRQ149I Using the WU-BLAST2 sequence alignment computer program, it has been found that a portion of the full-length native sequence PRO 1491 (shown in Figure 176 and SEQ ID N0:310) has certain amino acid 15 sequence identity with a portion of the collapsin-2 protein of Gallus gallus (GGU28240 1). Accordingly, it is presently believed that PR01491 disclosed in the present application is a newly identified member of the collapsin protein family and may possess activity typical of that protein family. 89. PRQ1431 It has been found that the full-length native sequence PRO 1431 [shown in Figure 178(SEQIDNO:315) has significant sequence identity with the SID domain containing protein SHI7HUMAN. Accordingly, it is presently believed that PR01431 disclosed in the present application is a newly identified member of proteins having an SH3 domains and may possess signal transduction properties. 90. PROl 563 Using the WU-BLAST2 sequence alignment computer program, it has been found that a portion of a full-length native sequence PR01563 (shown in Figure 180 and SEQ ID N0:317) has certain amino acid sequence identity with aportion of the mouse ADAMTS-1 protein (AB001735 1). Accordingly, it is presently believed that PR0I563 disclosed in the present application is a newly identified member of the ADAM protein 30 family and may possess activity typical of that protein family. 91. PRQ1S6S Using the WU-BLAST2 sequence alignment computer program, it has been found that a portion of the full-length native sequence PRO 1565 (shown in Figure 182 and SEQ ID N0-.322) has certain amino acid 35 sequence identity with a portion of the chondromodulin-I protein of rattus norvegicus (AF051425_1). Accordingly, it is presently believed that PR01565 disclosed in the present application is a newly identified member of the chondromodulin protein family and may possess activity typical of that protein family. 341 92. PRQ1571 Using the WU-BLAST2 sequence alignment computer program, it has been found that a portion of die full-length native sequence PR01571 (shown in Figure 184 and SEQ ID NO:324) has certain amino acid sequence identity with a portion of the human Clostridium perfringens enterotoxin receptor protein (AB000712_1). Accordingly, it is presently believed that PR01S71 disclosed in the present application is a 5 newly identified CPE-R homolog and may possess activity typical of the CPE-R protein. 93. PRQ1S72 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01S72 (shown in Figure 186 and SEQ ID NO:326) has certain amino acid sequence identity with 10 CPE-R. Accordingly, it is presently believed that PR01572 disclosed in the present application is related to CPE-R and may possess at least one shared mechanism. 94. PRQ1573 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native 15 sequence PR01S73 (shown in Figure 188 and SEQ ID NO:328) has certain amino acid sequence identity with CPE-R. Accordingly, it is presently believed that PR01573 disclosed in the present application is related to CPE-R and may possesses at least one shared mechanism. 95. PROl 488 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PRO1488 (Figure 190; SEQ ID N0:330) has certain amino acid sequence identity with a known CPE-R designated "AB0007I2_1" on the Dayhoff database. Accordingly, it is presently believed that PR01488 disclosed in the present application is a newly identified member of the CPE-R family and may possess binding activity typical of the CPE-R family. 96. FRQ1489 Using the WU-BLAST2 sequence alignment computer program, it has been found that a portion of the full-length native sequence PR01489 (shown in Figure 192 and SEQ ID NO:332) has certain amino acid sequence identity with the Clostridium perfringens enterotoxin receptor of Cercopithecus aethiops (D88492 1).

Accordingly, it is presently believed that PR01489 disclosed in the present application is a newly identified Clostridium perfringens enterotoxin receptor homolog and may possess activity typical of the Clostridium perfringens enterotoxin receptor protein. 97. PRQ1474 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01474 (shown in Figure 194 and SEQ ID NO:334) has certain amino acid sequence identity with ovomucoid. Accordingly, it is presendy believed that PRO1474 disclosed in the present application is a newly 342 identified member of the kazal serine protease inhibitor family and may possess serine protease inhibitory activity typical of this family. 98. PROl 508 The DNA73742-1508 clone was isolated from a human diseased cartilage tissue library. As far as is S known, the DNA73742-1508 sequence encodes a novel factor designated herein as PRO1508; although, using WU-BLAST2 sequence alignment computer programs, some sequence identities to known proteins were revealed. 99. PROl 555 The DNA73744-1665 clone was isolated from a human tissue library. As far as is known, the DNA73744 sequence encodes a novel transmembrane protein designated herein as PRO1555. Using WU-BLAST2 sequence alignment computer programs, some sequence identities to known proteins were revealed. 100. PROl 485 IS Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01485 (shown in Figure 200 and SEQ ID N0:340) has certain amino acid sequence identity with lysozyme C precursor peptide. Accordingly, it is presently believed that PR01485 disclosed in the present application is a newly identified member of the lysozyme family and shares at least one like mechanism. 101. PRQ1564 Using the WU-BLAST2 sequence alignment computer program, it has been found that a portion of a full-length native sequence PR01564 (shown in Figure 202 and SEQ ID N0:347) has certain amino acid sequence identity with a portion of a mouse polypeptide GalNAc transferase T4 protein (MMU73819_1). Accordingly, it is presently believed that PRO1564 disclosed in the present application is a newly identified 25 member of the N-acetylgalactosaminyltransferase protein family and may possess activity typical of that protein family. 102. FRQ1755 As far as is known, the DNA76396-1698 sequence encodes a novel transmembrane protein designated 30 herein as PR01755. Although, some sequence identities to known proteins was revealed using WU-BLAST2 sequence alignment computer programs. 103. PROl 757 The DNA76398-1699 clone was isolated from a human testicular tissue library using a trapping 35 technique which selects for nucleotide sequences encoding proteins. As far as is known, the DNA76398-1699 sequence encodes a novel factor designated herein as PR01757; using the WU-BLAST2 sequence alignment computer program, no significant sequence identities to any known proteins were revealed. 343 104. PRQ17S8 The DNA76399-1700 clone was isolated from a library derived from human thymus tissue obtained from a fetus that died at 17 weeks' gestation from anencephalus. It is believed that the DNA76399-1700 clone encodes a novel secreted factor, designated herein as PR01758. Using WU-BLAST2 sequence alignment computer programs, significant sequence identity was revealed between the amino acid sequences of PRO 1758 5 and Dayhoff sequence No. AC005328_2. 105. PRQ1575 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01S7S (shown in Figure 210 and SEQ ID NO:358) has certain amino acid sequence identity with 10 Dayhoff sequence no. A12005_l. Accordingly, it is presently believed that PROI575 disclosed in the present application is a newly identified member of the protein disulfide isomerase family and may possess activity and properties typical of the disulfide isomerase family. 106. PRQ1787 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01787 (shown in Figure 212 and SEQ ID NO:364) has certain amino acid sequence identity with various species of myelin pO. Accordingly, it is presently believed that PR01787 disclosed in the present application is a newly identified member of the myelin pO protein family and may share at least one similar mechanism. It is believed that modulators of PRO1787 may be used to treat myelin pO associated disorders, such 20 as neuropathy, hereditary tooth disease, etc. 107. PRQ1781 Using WU-BLAST2 sequence alignment computer programs, some sequence identities were found between the PR01781 amino acid sequence (SEQ ID NO:366) and the amino acid sequences of known proteins, 25 but were not found to be significant. Accordingly, as far as is known, the DNA76522-2500 sequence encodes a novel protein. 108. PROl 556 The DNA76529-1666 clone was isolated from a human breast tumor tissue library. As far as is known, 30 the DNA76S29-1666 sequence encodes a novel transmembrane protein designated herein as PR01S56. Using WU-BLAST2 sequence alignment computer programs, some sequence identities to known proteins were revealed. 109. PRQ17S9 As far as is known, the DNA76531-1701 sequence encodes a novel factor designated herein as PR017S9; using WU-BLAST2 sequence alignment computer programs, limited sequence identities to known proteins were revealed. 344 110. PRQ1760 As far as is known, the DNA76532-1702 sequence encodes a novel factor designated herein as PR01760; using WU-BLAST2 sequence alignment computer programs, limited sequence identities to known proteins were revealed. 111. PROl 561 Using the WU-BLAST2 sequence alignment computer program, it has been found that a portion of a full-length native sequence PRO 1561 (shown in Figure 222 and SEQ ID NO:378) has certain amino acid sequence identity with a portion of the human phospholipase A2 protein (P_R63053). Accordingly, it is presently believed that PR01561 disclosed in the present application is a newly identified member of the 10 phospholipase A2 protein family and may possess activity typical of that protein family. 112. PRQ1S67 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01567 (Figure 224; SEQ ID NO:383) has certain amino acid sequence identity with human colon 15 specific gene CSG6 polypeptide, identified as P W06549 on the Dayhoff database. Accordingly, it is presently believed that PR01567 disclosed in the present application is a newly identified CSG expression product, and may possess properties typical of such proteins. 113. PRQ1693 Using the WU-BLAST2 sequence alignment computer program, it has been found that a portion of the full-length native sequence PR01693 (shown in Figure 226 and SEQ ID NO:385) has certain amino acid sequence identity with a portion of a mouse insulin-like growth factor binding protein (ALS_MOUSE). Accordingly, it is presently believed that PR01693 disclosed in the present application is a newly identified member of the insulin-like growth factor binding protein family and may possess activity typical of that protein 25 family. 114. PROl 784 As far as is known, die DNA77303-2502 sequence encodes a novel factor designated herein as PR01784; using WU-BLAST2 sequence alignment computer programs, some sequence identities to known 30 proteins were revealed. 115. PRQ1605 Using the WU-BLAST2 sequence alignment computer program, it has been found that a portion of the full-length native sequence PR01605 (shown in Figure 230 and SEQ ID NO:395) has certain amino acid 35 sequence identity with a portion of the human alpha-l,3-mannosylglycoprotein beta-1,6-n-acetyltransferase protein (GNT5_HUMAN). Accordingly, it is presently believed that PR01605 disclosed in the present application is a newly identified member of the glycosyltransferase protein family and may possess activity 345 typical of that protein family. 116. PRQ1788 Using WU-BLAST2 sequence alignment computer programs, it has been found that a full-length native sequence PR01788 (shown in Figure 232 and SEQ ID NO-.397) has certain amino acid sequence identity with 5 Dayhoff sequence " GARP_HUMAN", a leucine-rich repeat-containing protein encoded by a gene localized in the llql4 chromosomal region. Accordingly, it is presently believed that PR01788 disclosed in the present application is a newly identified member of the leucine-rich repeat-containing family and may possess activity or properties typical of the leucine-rich repeat-containing family. 117. PRQ1801 Using the WU-BLAST2 sequence alignment computer program, it has been found that a portion of the full-length native sequence PR01801 (shown in Figure 234 and SEQ ID N0:402) has certain amino acid sequence identity with a portion of the IL-19 protein (P W37935). Accordingly, it is presently believed that PR01801 disclosed in the present application is a newly identified member of the IL-10-related cytokine family 15 and may possess activity typical of that cytokine family. 118. UCP4 Using the Megalign DNASTAR computer program (and algorithms and parameters in this software set by the manufacturer) (Oxford Molecular Group, Inc.), it has been found that a full-length native sequence UCP4 20 (shown in Figure 236 and SEQ ID N0:406) has certain amino acid sequence identity with UCP3, UCP2 and UCP1. Accordingly, it is presently believed that UCP4 disclosed in the present application is a newly identified member of the human uncoupling protein family and may possess activity(s) and/or property(s) typical of that protein family, such as the ability to enhance or supress metabolic rate by affecting mitochondrial membrane potential. 119. PRQ193 The present inventionprovides newly identified and isolated nucleotide sequences encoding polypeptides referred to in die present application as PR0193. In particular, Applicants have identified and isolated cDNA encoding a PR0193 polypeptide, as disclosed in further detail in the Examples below. The PR0193-encoding 30 clone was isolated from a human retina library. 120. PROl 130 Using the WU-BLAST2 sequence alignment computer program, it has been found that a full-length native sequence PROl 130 (shown in Figure 240 and SEQ ID NO-.415) has amino acid sequence identity with 35 the human2-19 protein. Accordingly, it is presently believed that PROl 130 disclosed in the present application is a newly identified 2-19 protein homolog. 346 121. PROl 335 Using the WU-BLAST2 sequence alignment computer program, it has been found that a full-length native sequence PR01335 (shown in Figure 242 and SEQ ID NO-.423) has certain amino acid sequence identity with the human carbonic anhydrase precursor protein (AF037335 1). Accordingly, it is presently believed that PRO1335 disclosed in the present application is a newly identified member of the carbonic anhydrase protein 5 family and may possess activity typical of that family. 122. PRQ1329 The DNA66660-1585 clone is believed to encode a secreted factor. As far as is known, the DNA66660-1585 sequence encodes a novel factor designated herein as PR01329; using WU-BLAST2 sequence alignment 10 computer programs, sequence identities to known proteins were revealed but determined not to be significant. 123. PROl 550 The DNA76393-1664 clone was isolated from a subtracted human breast tumor tissue library. As far as is known, the DNA76393-1664 sequence encodes a novel factor designated herein as PR01550; using WU-15 BLAST2 sequence alignment computer programs, sequence identities to known proteins were revealed but determined not to be significant.

B. PRO Variants In addition to the full-length native sequence PRO polypeptides described herein, it is contemplated that 20 PRO variants can be prepared. PRO variants can be prepared by introducing appropriate nucleotide changes into the PRO DNA, and/or by synthesis of the desired PRO polypeptide. Those skilled in the art will appreciate that amino acid changes may alter post-translational processes of the PRO, such as changing the number or position of glycosylation sites or altering the membrane anchoring characteristics.

Variations in the native full-length sequence PRO or in various domains of the PRO described herein, 25 can be made, for example, using any of the techniques and guidelines for conservative and non-conservative mutations set forth, for instance, in U.S. Patent No. 5,364,934. Variations may be a substitution, deletion or insertion of one or more codons encoding the PRO that results in a change in the amino acid sequence of the PRO as compared with the native sequence PRO. Optionally the variation is by substitution of at least one amino acid with any other amino acid in one or more of the domains of the PRO. Guidance in determining which 30 amino acid residue may be inserted, substituted or deleted without adversely affecting the desired activity may be found by comparing the sequence of the PRO with that of homologous known protein molecules and minimizing the number of amino acid sequence changes made in regions of high homology. Amino acid substitutions can be the result of replacing one amino acid with another amino acid having similar structural and/or chemical properties, such as the replacement of a leucine with a serine, i.e., conservative amino acid 35 replacements. Insertions or deletions may optionally be in the range of about 1 to 5 amino acids. The variation allowed may be determined by systematically making insertions, deletions or substitutions of amino acids in the sequence and testing the resulting variants for activity exhibited by the full-length or mature native sequence. 347 WO 00/12708 PCT/US99/20111 PRO polypeptide fragments are provided herein. Such fragments may be truncated at the N-terminus or C-terminus, or may lack internal residues, for example, when compared with a full length native protein. Certain fragments lack amino acid residues that are not essential for a desired biological activity of the PRO polypeptide.

PRO fragments may be prepared by any of a number of conventional techniques. Desired peptide 5 fragments may be chemically synthesized. An alternative approach involves generating PRO fragments by enzymatic digestion, e.g., by treating the protein with an enzyme known to cleave proteins at sites defined by particular amino acid residues, or by digesting the DNA with suitable restriction enzymes and isolating the desired fragment. Yet another suitable technique involves isolating and amplifying a DNA fragment encoding a desired polypeptide fragment, by polymerase chain reaction (PCR). Oligonucleotides that define the desired 10 termini of the DNA fragment are employed at the 5* and 3' primers in die PCR. Preferably, PRO polypeptide fragments share at least one biological and/or immunological activity with the native PRO polypeptide disclosed herein.

In particular embodiments, conservative substitutions of interest are shown in Table 1 under the heading of preferred substitutions. If such substitutions result in a change in biological activity, then more substantial IS changes, denominated exemplary substitutions in Table 1, or as further described below in reference to amino acid classes, are introduced and the products screened. 348 Table 1 Original Exemplary Preferred Residue Substitutions Substitutions Ala (A) val; ieu; ile val Arg (R) lys; gin; asn lys Asn(N) gin; his; lys; arg gin Asp (D) glu glu Cys (C) ser ser Gln(Q) asn asn Glu (E) asp asp Gly (G) pro; ala ala His (H) asn; gin; lys; arg arg De (D leu; val; met; ala; phe; norleucine leu Leu (L) norleucine; ile; val; met; ala; phe ile Lys (K) arg; gin; asn arg Met (M) leu; phe; ile leu Phe (F) leu; val; ile; ala; tyr leu Pro (P) ala ala Ser (S) thr thr Thr (T) ser ser Trp (W) tyr; phe tyr TyrOO trp; phe; thr; ser phe Val (V) ile; leu; met; phe; ala; norleucine leu Substantial modifications in functionor immunologicalidentity of the PRO polypeptide are accomplished 30 by selecting substitutions that differ significantly in their effect on maintaining (a) the structure of the polypeptide backbone in the area of the substitution, for example, as a sheet or helical conformation, (b) the charge or hydrophobicity of the molecule at the target site, or (c) the bulk of the side chain. Naturally occurring residues are divided into groups based on common side-chain properties: (1) hydrophobic: norleucine, met, ala, val, leu, ile; (2) neutral hydrophiiic: cys, ser, thr; (3) acidic: asp, glu; (4) basic: asn, gin, his, lys, arg; (5) residues that influence chain orientation: gly, pro; and (6) aromatic: trp, tyr, phe. 40 Non-conservative substitutions will entail exchanging a member of one of these classes for another class.

Such substituted residues also may be introduced into the conservative substitution sites or, more preferably, into the remaining (non-conserved) sites.

The variations can be made using methods known in the art such as oiigonucleotide-mediated (site-directed) mutagenesis, alanine scanning, and PCR mutagenesis. Site-directed mutagenesis [Carter etal., Nucl. 45 Acids Res.. 13:4331 (1986); Zoller et al., Nucl. Acids Res.. 10:6487 (1987)], cassene mutagenesis [Wells et al., Gene. 24:315 (1985)], restriction selection mutagenesis [Wells et al., Philos. Trans. R. Soc. London Ser A. 317:415 (1986)] or other known techniques can be performed on the cloned DNA to produce the PRO variant 349 DNA.

Scanning amino acid analysis can also be employed to identify one or more amino acids along a contiguous sequence. Among the preferred scanning amino acids are relatively small, neutral amino acids. Such amino acids include alanine, glycine, serine, and cysteine. Alanine is typically a preferred scanning amino acid among this group because it eliminates the side-chain beyond the beta-carbon and is less likely to alter the main-5 chain conformation of the variant [Cunningham and Wells, Science. 244: 1081-1085 (1989)]. Alanine is also typically preferred because it is the most common amino acid. Further, it is frequently found in both buried and exposed positions [Creighton, The Proteins. (W.H. Freeman & Co., N.Y.); Chothia, J. Mot. Biol.. 150:1 (1976)]. If alanine substitution does not yield adequate amounts of variant, an isoteric amino acid can be used.

C. Modifications of PRO Covalent modifications of PRO are included within the scope of this invention. One type of covalent modification includes reacting targeted amino acid residues of a PRO polypeptide with an organic derivatizing agent that is capable of reacting with selected side chains or the N- or C- terminal residues of the PRO. Derivatization with bifunctional agents is useful, for instance, for crosslinking PRO to a water-insoluble support 15 matrix or surface for use in the method fm- purifying anti-PRO antibodies, and vice-versa. Commonly used crosslinking agents include, e.g., l,l-bis(diazoacetyl)-2-phenylethane, glutaraldehyde, N-hydroxysuccinimide esters, for example, esters with 4-azidosaiicylic acid, homobifunctional imidoesters, including disuccinimidyl esters such as 3,3'-dithiobis(succinimidylpropionate), bifunctional maleimides such as bis-N-maleimido-1,8-octane and agents such as methyl-3-[(p-azidophenyl)dithio]propioimidate.

Other modifications include deamidation of glutaminyi and asparaginyl residues to the corresponding glutamyl and aspartyl residues, respectively, hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of seryl or threonyl residues, methylation of the a-amino groups of lysine, arginine, and histidine side chains [T.E. Creighton, Proteins: Structure and Molecular Properties. W.H. Freeman & Co., San Francisco, pp. 79-86 (1983)], acetylation of the N-terminal amine, and amidation of any C-terminal carboxyl group. 25 Another type of covalent modification of the PRO polypeptide included within the scope of this invention comprises altering the native glycosylation pattern of the polypeptide. "Altering the native glycosylation pattern" is intended for purposes herein to mean deleting one or more carbohydrate moieties found in native sequence PRO (either by removing the underlying glycosylation site or by deleting the glycosylation by chemical and/or enzymatic means), and/or adding one or more glycosylation sites that are not present in the 30 native sequence PRO. In addition, the phrase includes qualitative changes in the glycosylation of the native proteins, involving a change in the nature and proportions of the various carbohydrate moieties present.

Addition of glycosylation sites to the PRO polypeptide may be accomplished by altering the amino acid sequence. The alteration may be made, for example, by the addition of, or substitution by, one or more serine or threonine residues to the native sequence PRO (for O-linked glycosylation sites). The PRO amino acid 35 sequence may optionally be altered through changes at the DNA level, particularly by mutating the DNA encoding the PRO polypeptide at preselected bases such that codons are generated that will translate into the desired amino acids. 350 Another means of increasing the number of carbohydrate moieties on the PRO polypeptide is by chemical or enzymatic coupling of glycosides to the polypeptide. Such methods are described in the art, e.g., in WO 87/05330 published 11 September 1987, and in Aplin and Wriston, CRC Crit. Rev. Biochem.. pp. 259-306 (1981).

Removal of carbohydrate moieties present on the PRO polypeptide may be accomplished chemically 5 or enzymatically or by mutational substitution of codons encoding for amino acid residues that serve as targets for glycosylation. Chemical deglycosylation techniques are known in the art and described, for instance, by Hakimuddin, et al., Arch. Biochem. Biophvs.. 259:52 (1987) and by Edge et al., Anal. Biochem.. 118:131 (1981). Enzymatic cleavage of carbohydrate moieties on polypeptides can be achieved by the use of a variety of endo- and exo-glycosidases as described by Thotakura et al., Meth. F.nzvmol 138:350 (1987). 10 Another type of covalent modification of PRO comprises linking the PRO polypeptide to one of a variety of nonproteinaceous polymers, e.g., polyethylene glycol (PEG), polypropylene glycol, or polyoxyalkylenes, in themannersetforthinU.S. Patent Nos. 4,640,835; 4,496,689; 4,301,144; 4,670,417; 4,791,192 or4,179,337.

The PRO of the present invention may also be modified in a way to form a chimeric molecule comprising PRO fused to another, heterologous polypeptide or amino acid sequence.

In one embodiment, such a chimeric molecule comprises a fusion of the PRO with a tag polypeptide which provides an epitope to which an anti-tag antibody can selectively bind. The epitope tag is generally placed at the amino- or carboxyl- terminus of the PRO. The presence of such epitope-tagged forms of the PRO can be detected using an antibody against the tag polypeptide. Also, provision of the epitope tag enables the PRO to be readily purified by affinity purification using an anti-tag antibody or another type of affinity matrix that binds 20 to the epitope tag. Various tag polypeptides and their respective antibodies are well known in the an. Examples include poly-histidine (poly-his) or poly-histidine-glycine (poly-his-gly) tags; the flu HA tag polypeptide and its antibody 12CA5 [Field et al., Mol. Cell. Biol.. &2159-2165 (1988)]; the c-myc tag and the 8F9, 3C7, 6E10, G4, B7 and 9E10 antibodies thereto [Evan et al., Molecular and Cellular Biology. 5,:3610-3616 (1985)]; and the Herpes Simplex virus glycoprotein D (gD) tag and its antibody [Paborsky et al., Protein Engineering. 3(6):547-25 553 (1990)]. Other tag polypeptides include the Flag-peptide [Hopp et al., BioTechnologv. 1204-1210 (1988)]; the KT3 epitope peptide [Martin et al., Science. 255:192-194 (1992)]; an a-tubulin epitope peptide [Skinner et al., J. Biol. Chem.. 266:15163-15166 (1991)]; and the T7 gene 10 protein peptide tag [Lutz-Freyermuth et al., Proc. Natl. Acad. Sci. USA. 82:6393-6397 (1990)].

In an alternative embodiment, the chimeric molecule may comprise a fusion of the PRO with an 30 immunoglobulin or a particular region of an immunoglobulin. For a bivalent form of the chimeric molecule (also referred to as an "immunoadhesin"), such a fusion could be to the Fc region of an IgG molecuie. The Ig fusions preferably include the substitution of a soluble (transmembrane domain deleted or inactivated) form of a PRO polypeptide in place of at least one variable region within an Ig molecule. In a particularly preferred embodiment, the immunoglobulin fusion includes the hinge, CH2 and CH3, or the hinge, CHI, CH2 and CH3 35 regions of an IgGl molecule. For the production of immunoglobulin fusions see also US Patent No. 5,428,130 issued June 27, 1995. 351 D. Preparation of PRO The description below relates primarily to production of PRO by culturing cells transformed or transfected with a vector containing PRO nucleic acid. It is, of course, contemplated that alternative methods, which are well known in the art, may be employed to prepare PRO. For instance, the PRO sequence, or portions thereof, may be produced by direct peptide synthesis using solid-phase techniques [see, e.g., Stewart 5 etal.. Solid-Phase Peptide Synthesis. W.H. Freeman Co.. San Francisco. CAn969t: Merrifield. J. Am. Chem. Soc.. 85:2149-2154 <1963)3- In vitro protein synthesis may be performed using manual techniques or by automation. Automated synthesis may be accomplished, for instance, using an Applied Biosystems Peptide Synthesizer (Foster City, CA) using manufacturer's instructions. Various portions of the PRO may be chemically synthesized separately and combined using chemical or enzymatic methods to produce the full-length 10 PRO. 1. Isolation of DNA Encoding PRO DNA encoding PRO may be obtained from a cDNA library prepared from tissue believed to possess the PRO mRNA and to express it at a detectable level. Accordingly, human PRO DNA can be conveniently IS obtained from a cDNA library prepared from human tissue, such as described in the Examples. The PRO-encoding gene may also be obtained from a genomic library or by known synthetic procedures (e.g., automated nucleic acid synthesis).

Libraries can be screened with probes (such as antibodies to the PRO or oligonucleotides of at least about 20-80 bases) designed to identify the gene of interest or the protein encoded by it. Screening the cDNA 20 or genomic library with the selected probe may be conducted using standard procedures, such as described in Sambrook et al., Molecular Cloning: A Laboratory Mannal rNew York: Cold Spring Harbor Laboratory Press, 1989). An alternative means to isolate the gene encoding PRO is to use PCR methodology [Sambrook et al., sunra: Dieffenbach et al., PCR Primer: A Laboratory Manual (Cold Spring Harbor Laboratory Press, 1995)].

The Examples below describe techniques for screening a cDNA library. The oligonucleotide sequences 25 selected as probes should be of sufficient length and sufficiently unambiguous that false positives are minimized. The oligonucleotide is preferably labeled such that it can be detected upon hybridization to DNA in the library being screened. Methods of labeling are well known in the art, and include the use of radiolabels like 32P-labeled ATP, biotinylation or enzyme labeling. Hybridization conditions, including moderate stringency and high stringency, are provided in Sambrook et al., supra.

Sequences identified in such library screening methods can be compared and aligned to other known sequences deposited and available in public databases such as GenBank or other private sequence databases. Sequence identity (at either the amino acid or nucleotide level) within defined regions of the molecule or across the full-length sequence can be determined using methods known in the art and as described herein.

Nucleic acid having protein coding sequence may be obtained by screening selected cDNA or genomic 35 libraries using the deduced amino acid sequence disclosed herein for the first time, and, if necessary, using conventional primer extension procedures as described in Sambrook et al., supra, to detect precursors and processing intermediates of mRNA that may not have been reverse-transcribed into cDNA. 352 2. Selection and Transformation of Host Cells Host cells are transfected or transformed with expression or cloning vectors described herein for PRO production and cultured in conventional nutrient media modified as appropriate for inducing promoters, selecting transformants, or amplifying the genes encoding the desired sequences. The culture conditions, such as media, temperature, pH and the like, can be selected by the skilled artisan without undue experimentation. In general, principles, protocols, and practical techniques for maximizing the productivity of cell cultures can be found in Mammalian Cell Biotechnology: a Practical Approach. M. Butler, ed. (IRL Press, 1991) and Sambrook et al., Methods of eukaryotic cell transfection and prokaryotic cell transformation are known to the ordinarily skilled artisan, for example, CaCl2, CaP04, liposome-mediated and electroporation. Depending on the host cell 10 used, transformation is performed using standard techniques appropriate to such cells. The calcium treatment employing calcium chloride, as described in Sambrook et al., supra, or electroporation is generally used for prokaryotes. Infection with Agrobacterium tumefaciens is used for transformation of certain plant cells, as described by Shaw etal., Gene, 23:315 (1983) and WO 89/05859 published 29 June 1989. For mammalian cells without such cell walls, the calcium phosphate precipitation method of Graham and van der Eb, Virology. 15 52:456-457 (1978) can be employed. General aspects of mammalian cell host system transfections have been described in U.S. Patent No. 4,399,216. Transformations into yeast are typically carried out according to the method of Van Solingen etal., J. Bact.. 130:946 (1977) and Hsiao etal., Proc. Natl. Acad. Sci. (USA). 76:3829 (1979). However, other methods for introducing DNA into cells, such as by nuclear microinjection, electroporation, bacterial protoplast fusion with intact cells, or polycations, e.g., polybrene, polyoraithine, may 20 also be used. For various techniques for transforming mammalian cells, see Keown et al., Methods in Enzvmologv. 185:527-537 (1990) and Mansour et al., Nature. 336:348-352 (1988).

Suitable host cells for cloning or expressing the DNA in the vectors herein include prokaryote, yeast, or higher eukaryote cells. Suitable prokaryotes include but are not limited to eubacteria, such as Gram-negative or Gram-positive organisms, for example, Enterobacteriaceae such as E. coli. Various E. coli strains are 25 publicly available, such as E. coli K12 strain MM294 (ATCC 31,446); E. coli X1776 (ATCC 31,537); E. coli strain W31I0 (ATCC 27,325) and K5 772 (ATCC 53,635). Other suitable prokaryotic host cells include Enterobacteriaceae such as Escherichia, e.g., E. coli, Enterobacter, Erwinia, Klebsiella, Proteus, Salmonella, e.g., Salmonella typhimurium, Serratia, e.g., Serratia marcescans, and Shigella, as well as Bacilli such as B. subtUis and B. licheniformis (e.g., B. licheniformis 41P disclosed in DD 266,710 published 12 April 1989), 30 Pseudomonas such as P. aeruginosa, and Streptomyces. These examples are illustrative rather than limiting. Strain W3110 is one particularly preferred host or parent host because it is a common host strain for recombinant DNA product fermentations. Preferably, the host cell secretes minimal amounts of proteolytic enzymes. For example, strain W3110 may be modified to effect a genetic mutation in the genes encoding proteins endogenous to the host, with examples of such hosts including E. coli W3110 strain 1A2, which has the complete genotype 35 tonA ; E. coli W3110 strain 9E4, which has the complete genotype tonA ptr3; E. coli W3110 strain 27C7 (ATCC 55,244), which has the complete genotype tonA ptr3 phoA E15 (argF-lac)169 degP ompTkarf; E. coli W3110 strain 37D6, which has the complete genotype tonA ptr3 phoA E15 (argF-lac)169 degP ompT rbs7 353 ilvG kaif; E. coli W3I10 strain 40B4, which is strain 37D6 with a non-kanamycin resistant degP deletion mutation; and an E. coli strain having mutant periplasmic protease disclosed in U.S. Patent No. 4,946,783 issued 7 August 1990. Alternatively, in vitro methods of cloning, e.g., PCR or other nucleic acid polymerase reactions, are suitable.

In addition to prokaryotes, eukaryotic microbes such as filamentous fungi or yeast are suitable cloning 5 or expression hosts for PRO-encoding vectors. Saccharomyces cerevisiae is a commonly used lower eukaryotic host microorganism. Others include Schizosaccharomycespombe (Beach and Nurse, Nature. 290: 140 [1981]; EP 139,383 published 2 May 1985); Kluyveromyces hosts (U.S. Patent No. 4,943,529; Fleer et al., Bio/Technology. 9:968-975 (1991)) such as, e.g., 2ST. lactis (MW98-8C, CBS683, CBS4574; Louvencourtetal., J. Bacterid.. 737 [1983]), K. fragilis (ATCC 12,424), K. bulgaricus (ATCC 16,045), K. wickeramii (ATCC 10 24,178), K. waltii (ATCC 56,500), K. drosophilarum (ATCC 36,906; Van den Berg et al., Bio/Technology. 8:135 (1990)), K. thermotolerans, and K. marxianus; yarrowia (EP 402,226); Pichia pastoris (EP 183,070; Sreekrishna et al., J. Basic Microbiol.. 28:265-278 [1988]); Candida; Trichoderma reesia (EP 244,234); Neurospora crassa (Case et al., Proc. Natl. Acad. Sci. USA. 76:5259-5263 [1979]); Schwanniomyces such as Schwanniomyces occidental^ (EP 394,538 published 31 October 1990); and iilamentous fungi such as, e.g., 15 Neurospora, Pemcillium, Tolypocladium (WO 91/00357 published 10 January 1991), and Aspergillus hosts such as A. nidulans (Ballance et al., Biochem. Biophvs. Res. Commun.. 112:284-289 [1983]; Tilburnet al., Gene. 26:205-221 [1983]; Yelton et al., Proc. Natl. Acad. Sci. USA. 81: 1470-1474 [1984]) and A. niger (Kelly and Hynes, EMBO J.. 4:475-479 [1985]). Methylotropic yeasts are suitable herein and include, but are not limited to, yeast capable of growth on methanol selected from the genera consisting of Hansenula, Candida, Kloeckera, 20 Pichia, Saccharomyces, Torulopsis, and Rhodotorula. A list of specific species that are exemplary of this class of yeasts may be found in C. Anthony, The Biochemistry of Methvlotronhs. 269 (1982).

Suitable host cells for the expression of glycosylated PRO are derived from multicellular organisms. Examples of invertebrate cells include insect cells such as Drosophila S2 and Spodoptera Sf9, as well as plant cells. Examples of useful mammalian host cell lines include Chinese hamster ovary (CHO) and COS cells. 25 More specific examples include monkey kidney CV1 line transformed by SV40 (COS-7, ATCC CRL 1651); human embryonic kidney line (293 or 293 cells subcloned for growth in suspension culture, Graham et al., J._ Gen Virol.. 36:59 (1977)); Chinese hamster ovary cells/-DHFR (CHO, Urlaub and Chasin, Proc. Natl. Acad. Sci. USA. 77:4216 (1980)); mouse Sertoli cells (TM4, Mather, Biol. Reprod.. 23:243-251 (1980)); human lung cells (W138, ATCC CCL 75); human liver cells (Hep G2, HB 8065); and mouse mammary tumor (MMT 30 060562, ATCC CCL51). The selection of the appropriate host cell is deemed to be within the skill in the art. 3. Selection and Use of a Replicable Vector The nucleic acid (e.g., cDNA or genomic DNA) encoding PRO may be inserted into a replicable vector for cloning (amplification of the DNA) or for expression. Various vectors are publicly available. The vector 35 may, for example, be in the form of a plasmid, cosmid, viral panicle, or phage. The appropriate nucleic acid sequence may be insened into the vector by a variety of procedures. In general, DNA is inserted into an appropriate restriction endonuclease site(s) using techniques known in the an. Vector components generally 354 include, but are not limited to, one or more of a signal sequence, an origin of replication, one or more marker genes, an enhancer element, a promoter, and a transcription termination sequence. Construction of suitable vectors containing one or more of these components employs standard ligation techniques which are known to the skilled artisan.

The PRO may be produced recombinantly not only directly, but also as a fusion polypeptide with a 5 heterologous polypeptide, which may be a signal sequence or other polypeptide having a specific cleavage site at the N-terminus of the mature protein or polypeptide. In general, the signal sequence may be a component of the vector, or it may be a part of the PRO-encoding DNA that is inserted into the vector. The signal sequence may be a prokaryotic signal sequence selected, for example, from the group of the alkaline phosphatase, penicillinase, lpp, or heat-stable enterotoxin II leaders. For yeast secretion the signal sequence may be, e.g., 10 the yeast invertase leader, alpha factor leader (including Saccharomyces and Kluyveromyces a-factor leaders, the latter described in U.S. Patent No. 5,010,182), or acid phosphatase leader, the C. albicans glucoamylase leader (EP 362,179 published 4 April 1990), or the signal described in WO 90/13646 published 15 November 1990. In mammalian cell expression, mammalian signal sequences may be used to direct secretion of the protein, such as signal sequences from secreted polypeptides of the same or related species, as well as viral 15 secretory leaders.

Both expression and cloning vectors contain a nucleic acid sequence that enables the vector to replicate in one or more selected host cells. Such sequences are well known for a variety of bacteria, yeast, and viruses. The origin of replication from the plasmid pBR322 is suitable for most Gram-negative bacteria, the 2/t plasmid origin is suitable for yeast, and various viral origins (SV40, polyoma, adenovirus, VSV or BPV) are useful for 20 cloning vectors in mammalian cells.

Expression and cloning vectors will typically contain a selection gene, also termed a selectable marker. Typical selection genes encode proteins that (a) confer resistance to antibiotics or other toxins, e.g., ampicillin, neomycin, methotrexate, or tetracycline, (b) complement auxotrophic deficiencies, or (c) supply critical nutrients not available from complex media, e.g., the gene encoding D-alanine racemase for Bacilli. 25 An example of suitable selectable markers for mammalian cells are those that enable the identification of cells competent to take up the PRO-encoding nucleic acid, such as DHFR or thymidine kinase. An appropriate host cell when wild-type DHFR is employed is the CHO cell line deficient in DHFR activity, prepared and propagated as described by Urlaub etal., Proc. Natl. Acad. Sci. USA. 77:4216 (1980). A suitable selection gene for use in yeast is the trpl gene present in the yeast plasmid YRp7 [Stinchcomb et al., Nature. 30 282:39 (1979); Kingsman et al., Gene. 7:141 (1979); Tschemper et al., Gene. 10:157 (1980)]. The trpl gene provides a selection marker for a mutant strain of yeast lacking the ability to grow in tryptophan, for example, ATCC No. 44076 or PEP4-1 [Jones, Genetics. 85:12 (1977)].

Expression and cloning vectors usually contain a promoter operably linked to the PRO-encoding nucleic acid sequence to direct mRNA synthesis. Promoters recognized by a variety of potential host cells are well 35 known. Promoters suitable for use with prokaryotic hosts include the p-lactamase and lactose promoter systems [Chang et al., Nature. 275:615 (1978); Goeddel et al., Nature. 281:544 (1979)], alkaline phosphatase, a tryptophan (trp) promoter system [Goeddel, Nucleic Acids Res.. 8:4057 (1980); EP 36,776], and hybrid 355 promoters such as the tac promoter [deBoer et al., Proc. Natl. Acad. Sci. USA. 80:21-25 (1983)]. Promoters for use in bacterial systems also will contain a Shine-Daigarno (S.D.) sequence operably linked to the DNA encoding PRO.

Examples of suitable promoting sequences for use with yeast hosts include the promoters for 3-phosphoglycerate kinase [Hitzeman et al., J. Biol. Chem.. 255:2073 (1980)] or other glycolytic enzymes [Hess 5 et al., J. Adv. Enzvme Res.. 7:149 (1968); Holland, Biochemistry. 17:4900 (1978)], such as enolase, glyceraldehyde-3-phosphate dehydrogenase, hexokinase, pyruvate decarboxylase,phosphofructokinase, glucose-6-phosphate isomerase, 3-phosphoglycerate mutase, pyruvate kinase, triosephosphateisomerase,phosphoglucose isomerase, and glucokinase.

Other yeast promoters, which are inducible promoters having the additional advantage of transcription 10 controlled by growth conditions, are the promoter regions for alcohol dehydrogenase 2, isocytochrome C, acid phosphatase, degradative enzymes associated with nitrogen metabolism, metallothionein, glyceraIdehyde-3-phosphate dehydrogenase, and enzymes responsible for maltose and galactose utilisation Suitable vectors and promoters for use in yeast expression are further described in EP 73,657.

PRO transcription from vectors in mammalian host cells is controlled, for example, by promoters 15 obtained from the genomes of viruses such as polyoma virus, fowlpox virus (UK 2,211,504 published 5 July 1989), adenovirus (such as Adenovirus 2), bovine papilloma virus, avian sarcoma virus, cytomegalovirus, a retrovirus, hepatitis-B virus and Simian Virus 40 (SV40), from heterologous mammalian promoters, e.g., the actin promoter or an immunoglobulin promoter, and from heat-shock promoters, provided such promoters are compatible with the host cell systems.

Transcription of a DNA encoding the PRO by higher eukaryotes may be increased by inserting an enhancer sequence into the vector. Enhancers are cis-acting elements of DNA, usually about from 10 to 300 bp, that act on a promoter to increase its transcription. Many enhancer sequences are now known from mammalian genes (globin, elastase, albumin, a-fetoprotein, and insulin). Typically, however, one will use an enhancer from a eukaryotic cell virus. Examples include the SV40 enhancer on the late side of the replication 25 origin (bp 100-270), the cytomegalovirus early promoter enhancer, the polyoma enhancer on the late side of the replication origin, and adenovirus enhancers. The enhancer may be spliced into the vector at a position 5' or 3' to the PRO coding sequence, but is preferably located at a site 5' from the promoter.

Expression vectors used in eukaryotic host cells (yeast, fungi, insect, plant, animal, human, or nucleated cells from other multicellular organisms) will also contain sequences necessary for the termination of 30 transcription and for stabilizing the mRNA. Such sequences are commonly available from the 5' and, occasionally 3', untranslated regions of eukaryotic or viral DNAs or cDNAs. These regions contain nucleotide segments transcribed as polyadenylated fragments in the untranslated portion of the mRNA encoding PRO.

Still other methods, vectors, and host cells suitable for adaptation to the synthesis of PRO in recombinant vertebrate cell culture are described in Gething et al., Nature. 293:620-625 (1981); Mantei et al., 35 Nature. 281:40-46 (1979); EP 117,060; and EP 117,058. 356 4. Detecting Gene Amplification/Expression Gene amplification and/or expression may be measured in a sample directly, for example, by conventional Southern blotting, Northern blotting to quantitate the transcription of mRNA [Thomas, Proc. Natl. Acad. Sci. USA. 77:5201-5205 (1980)], dot blotting (DNA analysis), or in situ hybridization, using an appropriately labeled probe, based on the sequences provided herein. Alternatively, antibodies may be employed 5 that can recognize specific duplexes, including DNA duplexes, RNA duplexes, and DNA-RNA hybrid duplexes or DNA-protein duplexes. The antibodies in turn may be labeled and the assay may be carried out where the duplex is bound to a surface, so that upon the formation of duplex on the surface, the presence of antibody bound to the duplex can be detected.

Gene expression, alternatively, may be measured by immunological methods, such as 10 immunohistochemical staining of cells or tissue sections and assay of cell culture or body fluids, to quantitate directly the expression of gene product. Antibodies useful for immunohistochemical staining and/or assay of sample fluids may be either monoclonal or polyclonal, and may be prepared in any mammal. Conveniently, the antibodies may be prepared against a native sequence PRO polypeptide or against a synthetic peptide based on the DNA sequences provided herein or against exogenous sequence fused to PRO DNA and encoding a specific 15 antibody epitope.

. Purification of Polypeptide Forms of PRO may be recovered from culture medium or from host cell Iysates. If membrane-bound, it can be released from the membrane using a suitable detergent solution (e.g. Triton-X 100) or by enzymatic 20 cleavage. Cells employed in expression of PRO can be disrupted by various physical or chemical means, such as freeze-thaw cycling, sonication, mechanical disruption, or cell lysing agents.

It may be desired to purify PRO from recombinant cell proteins or polypeptides. The following procedures are exemplary of suitable purification procedures: by fractionation on an ion-exchange column; ethanol precipitation; reverse phase HPLC; chromatography on silica or on a cation-exchange resin such as 25 DEAE; cbromatofocusing; SDS-PAGE; ammonium sulfate precipitation; gel filtration using, for example, Sephadex G-75; protein A Sepharose columns to remove contaminants such as IgG; and metal chelating columns to bind epitope-tagged forms of the PRO. Various methods of protein purification may be employed and such methods are known in the art and described for example in Deutscher, Methods in Enzvmologv. 182 (1990); Scopes, Protein Purification: Principles and Practice. Springer-Verlag, New York (1982). The purification 30 step(s) selected will depend, for example, on the nature of the production process used and the particular PRO produced.

E. Uses for PRO Nucleotide sequences (or their complement) encoding PRO have various applications in the art of 35 molecular biology, including uses as hybridization probes, in chromosome and gene mapping and in the generation of anti-sense RNA and DNA. PRO nucleic acid will also be useful for the preparation of PRO polypeptides by the recombinant techniques described herein. 357 The full-length native sequence PRO gene, or portions thereof, may be used as hybridization probes for a cDNA library to isolate the full-length PRO cDNA or to isolate still other cDNAs (for instance, those encoding naturally-occurring variants of PRO or PRO from other species) which have a desired sequence identity to the native PRO sequence disclosed herein. Optionally, the length of the probes will be about 20 to about SO bases. The hybridization probes may be derived from at least partially novel regions of the full length native 5 nucleotide sequence wherein those regions may be determined without undue experimentation or from genomic sequences including promoters, enhancer elements and introns of native sequence PRO. By way of example, a screening method will comprise isolating the coding region of the PRO gene using the known DNA sequence to synthesize a selected probe of about 40 bases. Hybridization probes may be labeled by a variety of labels, including radionucleotides such as nP or 35S, or enzymatic labels such as alkaline phosphatase coupled to the 10 probe via avidin/biotin coupling systems. Labeled probes having a sequence complementary to that of the PRO gene of the present invention can be used to screen libraries of human cDNA, genomic DNA or mRNA to determine which members of such libraries the probe hybridizes to. Hybridization techniques are described in further detail in the Examples below.

Any EST sequences disclosed in the present application may similarly be employed as probes, using 15 the methods disclosed herein.

Other useful fragments of the PRO nucleic acids include antisense or sense oligonucleotides comprising a singe-stranded nucleic acid sequence (either RNA or DNA) capable of binding to target PRO mRNA (sense) or PRO DNA (antisense) sequences. Antisense or sense oligonucleotides, according to the present invention, comprise a fragment of the coding region of PRO DNA. Such a fragment generally comprises at least about 14 20 nucleotides, preferably from about 14 to 30 nucleotides. The ability to derive an antisense or a sense oligonucleotide, based upon a cDNA sequence encoding a given protein is described in, for example, Stein and Cohen (Cancer Res. 48:2659. 1988) and van der Krol et al. (BioTechnioues 6:958. 1988).

Binding of antisense or sense oligonucleotides to target nucleic acid sequences results in the formation of duplexes that block transcription or translation of the target sequence by one of several means, including 25 enhanced degradation of the duplexes, premature termination of transcription or translation, or by other means. The antisense oligonucleotides thus may be used to block expression of PRO proteins. Antisense or sense oligonucleotides further comprise oligonucleotides having modified sugar-phosphodiester backbones (or other sugar linkages, such as those described in WO 91/06629) and wherein such sugar linkages are resistant to endogenous nucleases. Such oligonucleotides with resistant sugar linkages are stable in vivo (i.e„ capable of 30 resisting enzymatic degradation) but retain sequence specificity to be able to bind to target nucleotide sequences.

Other examples of sense or antisense oligonucleotides include those oligonucleotides which are covalently linked to organic moieties, such as those described in WO 90/10048, and other moieties that increases affinity of the oligonucleotide for a target nucleic acid sequence, such as poly-(L-lysine). Further still, intercalating agents, such as ellipticine, and alkylating agents or metal complexes may be attached to sense or 35 antisense oligonucleotides to modify binding specificities of the antisense or sense oligonucleotide for the target nucleotide sequence.

Antisense or sense oligonucleotides may be introduced into a cell containing the target nucleic acid 358 sequence by any gene transfer method, including, for example, CaP04-mediated DNA transfection, electroporation, or by using gene transfer vectors such as Epstein-Barr virus. In a preferred procedure, an antisense or sense oligonucleotide is inserted into a suitable retroviral vector. A cell containing the target nucleic acid sequence is contacted with the recombinant retroviral vector, either in vivo or ex vivo. Suitable retroviral vectors include, but are not limited to, those derived from the murine retrovirus M-MuLV, N2 (a retrovirus 5 derived from M-MuLV), or the double copy vectors designated DCT5A, DCT5B and DCT5C (see WO 90/13641).

Sense or antisense oligonucleotides also may be introduced into a cell containing die target nucleotide sequence by formation of a conjugate with a ligand binding molecule, as described in WO 91/04753. Suitable ligand binding molecules include, but are not limited to, cell surface receptors, growth factors, other cytokines, 10 or other ligands that bind to cell surface receptors. Preferably, conjugation of the ligand binding molecule does not substantially interfere with the ability of the ligand binding molecule to bind to its corresponding molecule or receptor, or block entry of the sense or antisense oligonucleotide or its conjugated version into the cell.

Alternatively, a sense or an antisense oligonucleotide may be introduced into a cell containing the target nucleic acid sequence by formation of an oligonucleotide-lipid complex, as described in WO 90/10448. The 15 sense or antisense oligonucleotide-lipid complex is preferably dissociated within the cell by an endogenous lipase.

The probes may also be employed in PCR techniques to generate a pool of sequences for identification of closely related PRO coding sequences.

Nucleotide sequences encoding a PRO can also be used to construct hybridization probes for mapping the gene which encodes that PRO and for the genetic analysis of individuals with genetic disorders. The 20 nucleotide sequences provided herein may be mapped to a chromosome and specific regions of a chromosome using known techniques, such as in situ hybridization, linkage analysis against known chromosomal markers, and hybridization screening with libraries.

When the coding sequences for PRO encode a protein which binds to another protein (example, where the PRO is a receptor), the PRO can be used in assays to identify the other proteins or molecules involved in the 25 binding interaction. By such methods, inhibitors of the receptor/ligand binding interaction can be identified. Proteins involved in such binding interactions can also be used to screen for peptide or small molecule inhibitors or agonists of the binding interaction. Also, the receptor PRO can be used to isolate correlative ligand(s). Screening assays can be designed to find lead compounds that mimic the biological activity of a native PRO or a receptor for PRO. Such screening assays will include assays amenable to high-throughput screening of 30 chemical libraries, making them particularly suitable for identifying small molecule drug candidates. Small molecules contemplated include synthetic organic or inorganic compounds. The assays can be performed in a variety of formats, including protein-protein binding assays, biochemical screening assays, immunoassays and cell based assays, which are well characterized in the art.

Nucleic acids which encode PRO or its modified forms can also be used to generate either transgenic 35 animals or "knock out" animals which, in turn, are useful in the development and screening of therapeutically useful reagents. A transgenic animal (e.g., a mouse or rat) is an animal having cells that contain a transgene, which transgene was introduced into the animal or an ancestor of the animal at a prenatal, e.g., an embryonic 359 stage. A transgene is a DNA which is integrated into the genome of a cell from which a transgenic animal develops. In one embodiment, cDNA encoding PRO can be used to clone genomic DNA encoding PRO in accordance with established techniques and the genomic sequences used to generate transgenic animals that contain cells which express DNA encoding PRO. Methods for generating transgenic animals, particularly animals such as mice or rats, have become conventional in the art and are described, for example, in U.S. Patent 5 Nos. 4,736,866 and 4,870,009. Typically, particular cells would be targeted for PRO transgene incorporation with tissue-specific enhancers. Transgenic animals that include a copy of a transgene encoding PRO introduced into the germ line of the animal at an embryonic stage can be used to examine the effect of increased expression of DNA encoding PRO. Such animals can be used as tester animals for reagents thought to confer protection from, for example, pathological conditions associated with its overexpression. In accordance with this facet of 10 the invention, an animal is treated with the reagent and a reduced incidence of the pathological condition, compared to untreated animals bearing the transgene, would indicate a potential therapeutic intervention for the pathological condition.

Alternatively, non-human homologues of PRO can be used to construct a PRO "knock out" animal which has a defective or altered gene encoding PRO as a result of homologous recombination between the 15 endogenous gene encoding PRO and altered genomic DNA encoding PRO introduced into an embryonic stem cell of the animal. For example, cDNA encoding PRO can be used to clone genomic DNA encoding PRO in accordance with established techniques. A portion of the genomic DNA encoding PRO can be deleted or replaced with another gene, such as a gene encoding a selectable marker which can be used to monitor integration. Typically, several kilobases of unaltered flanking DNA (both at the 5" and 3' ends) are included 20 in the vector [see e.g., Thomas and Capecchi, Cell. 51:503 (1987) for a description of homologous recombination vectors]. The vector is introduced into an embryonic stem cell line (e.g., by electroporation) and cells in which the introduced DNA has homologously recombined with the endogenous DNA are selected [see e.g., Li et al., Cell. 69:915 (1992)]. The selected cells are then injected into a blastocyst of an animal (e.g., a mouse or rat) to form aggregation chimeras [see e.g., Bradley, in Terutocarcinomas and Embryonic Stem 25 Cells: A Practical Approach, E. J. Robertson, ed. (IRL, Oxford, 1987), pp. 113-152], A chimeric embryo can then be implanted into a suitable pseudopregnant female foster animal and the embryo brought to term to create a "knock out" animal. Progeny harboring the homologously recombined DNA in their germ cells can be identified by standard techniques and used to breed animals in which all cells of the animal contain the homologously recombined DNA. Knockout animals can be characterized for instance, for their ability to defend 30 against certain pathological conditions and for their development of pathological conditions due to absence of the PRO polypeptide.

Nucleic acid encoding the PRO polypeptides may also be used in gene therapy. In gene therapy applications, genes are introduced into cells in order to achieve in vivo synthesis of a therapeutically effective genetic product, for example for replacement of a defective gene. "Gene therapy" includes both conventional 35 gene therapy where a lasting effect is achieved by a single treatment, and the administration of gene therapeutic agents, which involves the one time or repeated administration of a therapeutically effective DNA or mRNA. Antisense RNAs and DNAs can be used as therapeutic agents for blocking the expression of certain genes in 360 vivo. It has already been shown that short antisense oligonucleotides can be imported into cells where they act as inhibitors, despite their low intracellular concentrations caused by their restricted uptake by the cell membrane. (Zameenik et al.. Proc. Natl. Acad. Sci. USA 83:4143-4146 [1986]). The oligonucleotides can be modified to enhance their uptake, e.g. by substituting their negatively charged phosphodiester groups by uncharged groups.

There are a variety of techniques available for introducing nucleic acids into viable cells. The techniques vary depending upon whether the nucleic acid is transferred into cultured cells in vitro, or in vivo in the cells of the intended host. Techniques suitable for the transfer of nucleic acid into mammalian cells in vitro include the use of liposomes, electroporation, microinjection, cell fusion, DEAE-dextran, the calcium phosphate precipitation method, etc. The currently preferred in vivo gene transfer techniques include transfection with viral 10 (typically retroviral) vectors and viral coat protein-liposome mediated transfection (Dzau et al., Trends in Biotechnology 11. 205-210 [1993]). In some situations it is desirable to provide the nucleic acid source with an agent that targets the target ceils, such as an antibody specific for a cell surface membrane protein or the target cell, a ligand for a receptor on the target cell, etc. Where liposomes are employed, proteins which bind to a cell surface membrane protein associated with endocytosis may be used for targeting and/or to facilitate IS uptake, e.g. capsid proteins or fragments thereof tropic for a particular cell type, antibodies for proteins which undergo internalization in cycling, proteins that target intracellular localization and enhance intracellular half-life. The technique of receptor-mediated endocytosis is described, for example, by Wu et al., J. Biol. Chem. 262, 4429-4432 (1987); and Wagner et al., Proc. Natl. Acad. Sci. USA 87, 3410-3414 (1990). For review of gene marking and gene therapy protocols see Anderson et al., Science 256. 808-813 (1992). 20 The PRO polypeptides described herein may also be employed as molecular weight markers for protein electrophoresis purposes and the isolated nucleic acid sequences may be used for recombinantly expressing those markers.

The nucleic acid molecules encoding the PRO polypeptides or fragments thereof described herein are useful for chromosome identification. In this regard, there exists an ongoing need to identify new chromosome 25 markers, since relatively few chromosome marking reagents, based upon actual sequence data are presently available. Each PRO nucleic acid molecule of the present invention can be used as a chromosome marker.

The PRO polypeptides and nucleic acid molecules of the present invention may also be used for tissue typing, wherein the PRO polypeptides of the present invention may be differentially expressed in one tissue as compared to another. PRO nucleic acid molecules will find use for generating probes for PCR, Northern 30 analysis, Southern analysis and Western analysis.

The PRO polypeptides described herein may also be employed as therapeutic agents. The PRO polypeptides of the present invention can be formulated according to known methods to prepare pharmaceuticaliy useful compositions, whereby the PRO product hereof is combined in admixture with a pharmaceuticaliy acceptable carrier vehicle. Therapeutic formulations are prepared for storage by mixing the active ingredient 35 having the desired degree of purity with optional physiologically acceptable carriers, excipients or stabilizers rRmningtrin's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980)), in the form of lyophilized formulations or aqueous solutions. Acceptable carriers, excipients or stabilizers are nontoxic to recipients at the 361 dosages and concentrations employed, and include buffers such as phosphate, citrate and other organic acids; antioxidants including ascorbic acid; low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone, amino acids such as glycine, glutamine, asparagine, arginine or lysine; monosaccharides, disaccharides and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugar alcohols such as 5 mannitol or sorbitol; salt-forming counterions such as sodium; and/or nonionic surfactants such as TWEEN™, PLURONICS™ or PEG.

The formulations to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes, prior to or following lyophilization and reconstitution.

Therapeutic compositions herein generally are placed into a container having a sterile access port, for 10 example, an intravenous solution bag or vial having a stopper pierceable by a hypodermic injection needle.

The route of administration is in accord with known methods, e.g. injection or infusion by intravenous, intraperitoneal, intracerebral, intramuscular, intraocular, intraarterial or intralesional routes, topical administration, or by sustained release systems.

Dosages and desired drug concentrations of pharmaceutical compositions of the present invention may 15 vary depending on the particular use envisioned. The determination of the appropriate dosage or route of administration is well within the skill of an ordinary physician. Animal experiments provide reliable guidance for the determination of effective doses for human therapy. Interspecies scaling of effective doses can be performed following the principles laid down by Mordenti, J. and Chappell, W. "The use of interspecies scaling in toxicokinetics" In Toxicokinetics and New Drug Development, Yacobi et al., Eds., Pergamon Press, New 20 York 1989, pp. 42-96.

When in vivo administration of a PRO polypeptide or agonist or antagonist thereof is employed, normal dosage amounts may vary from about 10 ng/kg to up to 100 mg/kg of mammal body weight or more per day, preferably about 1 pg/kg/day to 10 mg/kg/day, depending upon the route of administration. Guidance as to particular dosages and methods of delivery is provided in the literature; see, for example, U.S. Pat. Nos. 25 4,657,760; 5,206,344; or 5,225,212. It is anticipated that different formulations will be effective for different treatment compounds and different disorders, that administration targeting one organ or tissue, for example, may necessitate delivery in a manner different from that to another organ or tissue.

Where sustained-release administration of a PRO polypeptide is desired in a formulation with release characteristics suitable for the treatment of any disease or disorder requiring administration of the PRO 30 polypeptide, microencapsulation of the PRO polypeptide is contemplated. Microencapsulation of recombinant proteins for sustained release has been successfully performed with human growth hormone (rhGH), interferon-(rhlFN- ), interleukin-2, and MN rgpl20. Johnson et al., Nat. Med.. 2:795-799 (1996); Yasuda, Biomed. Ther.. 27:1221-1223 (1993); Hora et al., Bio/Technology. 8:755-758 (1990); Cleland, "Design and Production of Single Immunization Vaccines Using Polylactide Polyglycolide Microsphere Systems," in Vaccine Design: 35 The Subunit and Adjuvant Approach. Powell and Newman, eds, (Plenum Press: New York, 1995), pp. 439-462; WO 97/03692, WO 96/40072, WO 96/07399; and U.S. Pat. No. 5,654,010.

The sustained-release formulations of these proteins were developed using poly-lactic-coglycolic acid 362 PCT/US99/20U1 (PLGA) polymer due to its biocompatibility and wide range of biodegradable properties. The degradation products of PLGA, lactic and glycolic acids, can be cleared quickly within the human body. Moreover, the degradability of this polymer can be adjusted from months to years depending on its molecular weight and composition. Lewis, "Controlled release of bioactive agents from lactide/glycolide polymer," in: M. Chasm and R. Langer (Eds.), Biodegradable Polymers as Drug Delivery Systems (Marcel Dekker: New York, 1990), pp. 5 1-41.

This invention encompasses methods of screening compounds to identify those that mimic the PRO polypeptide (agonists) or prevent the effect of the PRO polypeptide (antagonists). Screening assays for antagonist drug candidates are designed to identify compounds that bind or complex with the PRO polypeptides encoded by the genes identified herein, or otherwise interfere with tbe interaction of the encoded polypeptides 10 with other cellular proteins. Such screening assays will include assays amenable to high-throughput screening of chemical libraries, making them particularly suitable for identifying small molecule drug candidates.

The assays can be performed in a variety of formats, including protein-protein binding assays, biochemical screening assays, immunoassays, and cell-based assays, which are well characterized in the art.

All assays for antagonists are common in that they call for contacting the drug candidate with a PRO IS polypeptide encoded by a nucleic acid identified herein under conditions and for a time sufficient to allow these two components to interact.

In binding assays, the interaction is binding and the complex formed can be isolated or detected in the reaction mixture. In a particular embodiment, the PRO polypeptide encoded by the gene identified herein or the drug candidate is immobilized on a solid phase, e.g., on a microtiter plate, by covalent or non-covalent 20 attachments. Non-covalent attachment generally is accomplished by coating the solid surface with a solution of the PRO polypeptide and drying. Alternatively, an immobilized antibody, e.g., a monoclonal antibody, specific for the PRO polypeptide to be immobilized can be used to anchor it to a solid surface. The assay is performed by adding the non-immobilized component, which may be labeled by a detectable label, to the immobilized component, e.g., the coated surface containing the anchored component. When the reaction is complete, the 25 non-reacted components are removed, e.g., by washing, and complexes anchored on the solid surface are detected. When the originally non-immobilized component carries a detectable label, the detection of label immobilized on the surface indicates that completing occurred. Where the originally non-immobilized component does not carry a label, complexing can be detected, for example, by using a labeled antibody specifically binding the immobilized complex.

If the candidate compound interacts with but does not bind to a particular PRO polypeptide encoded by a gene identified herein, its interaction with that polypeptide can be assayed by methods well known for detecting protein-protein interactions. Such assays include traditional approaches, such as, e.g., cross-linking, co-immunoprecipitation, and co-purification through gradients or chromatographic columns. In addition, protein-protein interactions can be monitored by using a yeast-based genetic system described by Fields and co-workers 35 (Fields and Song, Nature (London). 340:245-246 (1989); Cfaien et al., Proc. Natl. Acad. Sci. USA. 88:9578-9582 (1991)) as disclosed by Cbevray and Nathans, Proc. Natl. Acad. Sci. USA. 89:5789-5793 (19911. Many transcriptional activators, such as yeast GAL4, consist of two physically discrete modular domains, one acting 363 as the DNA-binding domain, the other one functioning as the transcription-activation domain. The yeast expression system described in the foregoing publications (generally referred to as the "two-hybrid system") takes advantage of this property, and employs two hybrid proteins, one in which the target protein is fused to the DNA-binding domain of GAL4, and another, in which candidate activating proteins are fused to the activation domain. The expression of a GALl-tocZ reporter gene under control of a GAL4-activated promoter 5 depends on reconstitution of GAL4 activity via protein-protein interaction. Colonies containing interacting polypeptides are detected with a chromogenic substrate for p-galactosidase. A complete kit (MATCHMAKER™) for identifying protein-protein interactions between two specific proteins using the two-hybrid technique is commercially available from Clontech. This system can also be extended to map protein domains involved in specific protein interactions as well as to pinpoint amino acid residues that are crucial for 10 these interactions.

Compounds that interfere with die interaction of a gene encoding a PRO polypeptide identified herein and other intra- or extracellular components can be tested as follows: usually a reaction mixture is prepared containing the product of the gene and the intra- or extracellular component under conditions and for a time allowing for the interaction and binding of the two products. To test the ability of a candidate compound to 15 inhibit binding, the reaction is run in the absence and in the presence of the test compound. In addition, a placebo may be added to a third reaction mixture, to serve as positive control. The binding (complex formation) between the test compound and the intra- or extracellular component present in the mixture is monitored as described hereinabove. The formation of a complex in the control reactions) but not in the reaction mixture containing the test compound indicates that the test compound interferes with the interaction of the test compound 20 and its reaction partner.

To assay for antagonists, the PRO polypeptide may be added to a cell along with the compound to be screened for a particular activity and the ability of the compound to inhibit the activity of interest in the presence of the PRO polypeptide indicates that the compound is an antagonist to the PRO polypeptide. Alternatively, antagonists may be detected by combining the PRO polypeptide and a potential antagonist with membrane-bound 25 PRO polypeptide receptors or recombinant receptors under appropriate conditions for a competitive inhibition assay. The PRO polypeptide can be labeled, such as by radioactivity, such that the number of PRO polypeptide molecules bound to the receptor can be used to determine the effectiveness of the potential antagonist. The gene encoding the receptor can be identified by numerous methods known to those of skill in the art, for example, ligand panning and FACS sorting. Coligan et al., Current Protocols in Immnn 1(2): Chapter 5 (1991). 30 Preferably, expression cloning is employed wherein polyadenylated RNA is prepared from a cell responsive to the PRO polypeptide and a cDNA library created from this RNA is divided into pools and used to transfect COS cells or other cells that are not responsive to the PRO polypeptide. Transfected cells that are grown on glass slides are exposed to labeled PRO polypeptide. The PRO polypeptide can be labeled by a variety of means including iodination or inclusion of a recognition site for a site-specific protein kinase. Following fixation and 35 incubation, the slides are subjected to autoradiographic analysis. Positive pools are identified and sub-pools are prepared and re-transfected using an interactive sub-pooling and re-screening process, eventually yielding a single clone that encodes the putative receptor. 364 - As an alternative approach for receptor identification, labeled PRO polypeptide can be photoaffinity-linked with cell membrane or extract preparations that express the receptor molecule. Cross-linked material is resolved by PAGE and exposed to X-ray film. The labeled complex containing the receptor can be excised, resolved into peptide fragments, and subjected to protein micro-sequencing. The amino acid sequence obtained from micro- sequencing would be used to design a set of degenerate oligonucleotide probes to screen a cDNA 5 library to identify the gene encoding the putative receptor.

In another assay for antagonists, mammalian cells or a membrane preparation expressing the receptor would be incubated with labeled PRO polypeptide in the presence of the candidate compound. The ability of the compound to enhance or block this interaction could then be measured.

More specific examples of potential antagonists include an oligonucleotide that binds to the fusions of 10 immunoglobulin with PRO polypeptide, and, in particular, antibodies including, without limitation, poly- and monoclonal antibodies and antibody fragments, single-chain antibodies, anti-idiotypic antibodies, and chimeric or humanized versions of such antibodies or fragments, as well as human antibodies and antibody fragments. Alternatively, a potential antagonist may be a closely related protein, for example, a mutated form of the PRO polypeptide that recognizes the receptor but imparts no effect, thereby competitively inhibiting the action of the 15 PRO polypeptide.

Another potential PRO polypeptide antagonist is an antisense RNA or DNA construct prepared using antisense technology, where, e.g., an antisense RNA or DNA molecule acts to block directly the translation of mRNA by hybridizing to targeted mRNA and preventing protein translation. Antisense technology can be used to control gene expression through triple-helix formation or antisense DNA or RNA, both of which methods are 20 based on binding of a polynucleotide to DNA or RNA. For example, the 5' coding portion of the polynucleotide sequence, which encodes the mature PRO polypeptides herein, is used to design an antisense RNA oligonucleotide of from about 10 to 40 base pairs in length. A DNA oligonucleotide is designed to be complementary to a region of the gene involved in transcription (triple helix - see Lee et al., Nucl. Acids Res.. 6:3073 (1979); Cooney et al., Science. 241: 456 (1988); Dervan et al., Science. 251:1360 (1991)), thereby 25 preventing transcription and the production of the PRO polypeptide. The antisense RNA oligonucleotide hybridizes to the mRNA in vivo and blocks translation of the mRNA molecule into the PRO polypeptide (antisense - Okano, Neurochem.. 56:560 (1991); Oligodeoxvnucleotides as Antisense Inhibitors of Gene Expression (CRC Press: Boca Raton, FL, 1988). The oligonucleotides described above can also be delivered to cells such that the antisense RNA or DNA may be expressed in vivo to inhibit production of the PRO 30 polypeptide. When antisense DNA is used, oligodeoxyribonucieotides derived from the translation-initiation site, e.g., between about -10 and +10 positions of the target gene nucleotide sequence, are preferred.

Potential antagonists include small molecules that bind to the active site, the receptor binding site, or growth factor or other relevant binding site of the PRO polypeptide, thereby blocking the normal biological activity of the PRO polypeptide. Examples of small molecules include, but are not limited to, small peptides 35 or peptide-like molecules, preferably soluble peptides, and synthetic non-peptidyl organic or inorganic compounds.

Ribozymes are enzymatic RNA molecules capable of catalyzing the specific cleavage of RNA. 365 Ribozymes act by sequence-specific hybridization to the complementary target RNA, followed by endonucleolytic cleavage. Specific ribozyme cleavage sites within a potential RNA target can be identified by known techniques. For further details see, e.g., Rossi, Current Biology. 4:469-471 (1994), and PCT publication No. WO 97/33551 (published September 18, 1997).

Nucleic acid molecules in triple-helix formation used to inhibit transcription should be single-stranded 5 and composed of deoxynucleotides. The base composition of these oligonucleotides is designed such that it promotes triple-helix formation via Hoogsteen base-pairing rules, which generally require sizeable stretches of purines or pyrimidines on one strand of a duplex. For further details see, e.g., PCT publication No. WO 97/33551, supra.

These small molecules can be identified by any one or more of the screening assays discussed 10 hereinabove and/or by any other screening techniques well known for those skilled in the art.

F. Anti-PRO Antibodies The present invention further provides anti-PRO antibodies. Exemplary antibodies include polyclonal, monoclonal, humanized, bispecific, and heteroconjugate antibodies. 1. Polyclonal Antibodies The anti-PRO antibodies may comprise polyclonal antibodies. Methods of preparing polyclonal antibodies are known to die skilled artisan. Polyclonal antibodies can be raised in a mammal, for example, by one or more injections of an immunizing agent and, if desired, an adjuvant. Typically, the immunizing agent 20 and/or adjuvant will be injected in the mammal by multiple subcutaneous or intraperitoneal injections. The immunizing agent may include the PRO polypeptide or a fusion protein thereof. It may be useful to conjugate the immunizing agent to a protein known to be immunogenic in the mammal being immunized. Examples of such immunogenic proteins include but are not limited to keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin, and soybean trypsin inhibitor. Examples of adjuvants which may be employed include Freund's 25 complete adjuvant and MPL-TDM adjuvant (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate). The immunization protocol may be selected by one skilled in the art without undue experimentation. 2. Monoclonal Antibodies The anti-PRO antibodies may, alternatively, be monoclonal antibodies. Monoclonal antibodies may be 30 prepared using hybridoma methods, such as those described by Kohler and Milstein, Nature. 256:495 (1975). In a hybridoma method, a mouse, hamster, or other appropriate host animal, is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent. Alternatively, the lymphocytes may be immunized in vitro.

The immunizing agent will typically include the PRO polypeptide or a fusion protein thereof. 35 Generally, either peripheral blood lymphocytes ("PBLs") are used if cells of human origin are desired, orspleen cells or lymph node cells are used if non-human mammalian sources are desired. The lymphocytes are then fused with an immortalized cell line using a suitable fusing agent, such as polyethylene glycol, to form a 366 hybridoma cell [Goding, Monoclonal Antibodies: Principles and Practice. Academic Press, (1986) pp. 59-103]. Immortalized cell lines are usually transformed mammalian ceils, particularly myeloma cells of rodent, bovine and human origin. Usually, rat or mouse myeloma cell lines are employed. The hybridoma cells may be cultured in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, immortalized cells. For example, if the parental cells lack the enzyme hypoxanthine S guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine ("HAT medium"), which substances prevent the growth of HGPRT-deficient cells.

Preferred immortalized cell lines are those that fuse efficiently, support stable high level expression of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium. More 10 preferred immortalized cell lines are murine myeloma lines, which can be obtained, for instance, from the Salk Institute Cell Distribution Center, San Diego, California and the American Type Culture Collection, Manassas, Virginia. Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production ofhuman monoclonal antibodies [Kozbor, J. Immunol.. 133:3001 (1984): Brodeur etal.. Monoclonal Antibody Production Techniques and Applications. Marcel Dekker, Inc., New York, (1987) pp. 51-63]. 15 Hie culture medium in which the hybridoma cells are cultured can then be assayed for the presence of monoclonal antibodies directed against PRO. Preferably, the binding specificity of monoclonal antibodies produced by the hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immunoabsorbent assay (EL1SA). Such techniques and assays are known in the art. The binding affinity of the monoclonal antibody can, for example, be determined by the 20 Scatchard analysis of Munson and Pollard, Anal Rinchnm 107:220 (1980).

After the desired hybridoma cells are identified, the clones may be subcloned by limiting dilution procedures and grown by standard methods [Goding, supra!. Suitable culture media for this purpose include, for example, Dulbecco'sModifiedEaglelsMediumandRPMI-1640 medium. Alternatively, the hybridoma cells may be grown in vivo as ascites in a mammal.

The monoclonal antibodies secreted by the subclones may be isolated or purified from the culture medium or ascites fluid by conventional immunoglobulin purification procedures such as, for example, protein A-Sepharose, hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography.

The monoclonal antibodies may also be made by recombinant DNA methods, such as those described in U.S.Patent No. 4,816,567. DNA encoding the monoclonal antibodies of the invention can be readily isolated 30 and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of murine antibodies). The hybridoma cells of the invention serve as a preferred source of such DNA. Once isolated, tbe DNA may be placed into expression vectors, which are then transfected into host cells such as simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal 35 antibodies in the recombinant host cells. The DNA also may be modified, for example, by substituting the coding sequence for human heavy and light chain constant domains in place of the homologous murine sequences [U.S. Patent No. 4,816,567; Morrison et al., suoral or by covalently joining to the immunoglobulin coding 367 sequence all or part of tbe coding sequence for a non-immunoglobulin polypeptide. Such a non-immunoglobulin polypeptide can be substituted for the constant domains of an antibody of the invention, or can be substituted for the variable domains of one antigen-combining site of an antibody of the invention to create a chimeric bivalent antibody.

The antibodies may be monovalent antibodies. Methods for preparing monovalent antibodies are well 5 known in the art. For example, one method involves recombinant expression of immunoglobulin light chain and modified heavy chain. The heavy chain is truncated generally at any point in the Fc region so as to prevent heavy chain crosslinking. Alternatively, the relevant cysteine residues are substituted with another amino acid residue or are deleted so as to prevent crosslinking.

In vitro methods are also suitable for preparing monovalent antibodies. Digestion of antibodies to 10 produce fragments thereof, particularly, Fab fragments, can be accomplished using routine techniques known in the art. 3. Human and Humanized Antibodies The anti-PRO antibodies of the invention may further comprise humanized antibodies or human 15 antibodies. Humanized forms of non-human (e.g., murine) antibodies are chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab', F(ab')2 or other antigen-binding subsequences of antibodies) which contain minimal sequence derived from non-human immunoglobulin. Humanized antibodies include human immunoglobulins (recipient antibody) in which residues from a complementary determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human 20 species (donor antibody) such as mouse, rat or rabbit having the desired specificity, affinity and capacity. In some instances, Fv framework residues of the human immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies may also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR 25 regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin [Jones etal.. Nature. 321:522-525 (1986): Riechmannetal.. Nature. 332:323-329(1988): andPresta. Curr. Op. Struct. Biol- 2:593-596 (1992)].

Methods for humanizing non-human antibodies are well known in the art. Generally, a humanized antibody has one or more amino acid residues introduced into it from a source which is non-human. These non-human amino acid residues are often referred to as "import" residues, which are typically taken from an "import" variable domain. Humanization can be essentially performed following the method of Winter and co-workers [Jones et al., Nature. 321:522-525 (1986); Riechmann et al., Nature. 332:323-327 (1988); Verhoeyen et al., 35 Science. 23g: 1534-1536 (1988)], by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. Accordingly, such "humanized" antibodies are chimeric antibodies (U.S. Patent No. 4,816,567), wherein substantially less than an intact human variable domain has been substituted by the 368 corresponding sequence from a non-human species. In practice, humanized antibodies are typically human antibodies in which some CDR residues and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies.

Human antibodies can also be produced using various techniques known in the art, including phage display libraries [Hoogenboom and Winter, J. Mol. Biol.. 227:381 (1991); Marks etal., J. Mol. Biol.. 222:581 5 (1991)]. The techniques of Cole et al. and Boerner et al. are also available for the preparation of human monoclonal antibodies (Cole et al., Monoclonal Antibodies and Cancer Therapy. Alan R. Liss, p. 77 (1985) and Boerner et al., J. Immunol.. 147(11:86-95 (1991)]. Similarly, human antibodies can be made by introducing of human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed, 10 which closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and antibody repertoire. This approach is described, for example, in U.S. Patent Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016, and in the following scientific publications: Marks et al., Bio/Technology 10.779-783 (19921: Lonberg etal.. Nature 368 856-859(1994): Morrison, Nature 368.812-13 (1994); Fishwild et al.. Nature Biotechnology 14, 845-51 (1996); Neuberger, Nature Biotechnology 14. 826 15 (1996); Lonberg and Huszar, Intern. Rev. Immunol. 12 65-93 (1995). 4. Bispecific Antibodies Bispecific antibodies are monoclonal, preferably human or humanized, antibodies that have binding specificities for at least two different antigens. In the present case, one of the binding specificities is for the 20 PRO, the other one is for any other antigen, and preferably for a cell-surface protein or receptor or receptor subunit.

Methods for making bispecific antibodies are known in the art. Traditionally, the recombinant production of bispecific antibodies is based on the co-expression of two immunoglobulin heavy-chain/light-chain pairs, where the two heavy chains have different specificities [Milstein and Cuello, Nature. 305:537-539 (1983)]. 25 Because of the random assortment of immunoglobulin heavy and light chains, these hybridomas (quadromas) produce a potential mixture of ten different antibody molecules, of which only one has the correct bispecific structure. The purification of die correct molecule is usually accomplished by affinity chromatography steps. Similar procedures are disclosed in WO 93/08829, published 13 May 1993, and in Traunecker et al., EMBO L., 10:3655-3659 (1991).

Antibody variable domains with the desired binding specificities (antibody-antigen combining sites) can be fused to immunoglobulin constant domain sequences. The fusion preferably is with an immunoglobulin heavy-chain constant domain, comprising at least pan of the lunge, CH2, and CH3 regions. It is preferred to have the first heavy-chain constant region (CHI) containing the site necessary for light-chain binding present in at least one of the fusions. DNAs encoding the immunoglobulin heavy-chain fusions and, if desired, the 35 immunoglobulin light chain, are inserted into separate expression vectors, and are co-transfected into a suitable host organism. For further details of generating bispecific antibodies see, for example, Suresh etal., Methods in Enzvmotogv. 121:210 (1986). 369 PCTAJS99/20111 According to another approach described in WO 96/27011, the interface between a pair of antibody molecules can be engineered to maximize the percentage of heterodimers which are recovered from recombinant cell culture. The preferred interface comprises at least a part of the CH3 region of an antibody constant domain. In this method, one or more small amino acid side chains from the interface of the first antibody molecule are replaced with larger side chains (e.g. tyrosine or tryptophan). Compensatory "cavities" of identical or similar 5 size to the large side chain(s) are created on the interface of the second antibody molecule by replacing large amino acid side chains with smaller ones (e.g. alanine or threonine). This provides a mechanism for increasing the yield of the heterodimer over other unwanted end-products such as homodimers.

Bispecific antibodies can be prepared as full length antibodies or antibody fragments (e.g. F(ab')2 bispecific antibodies). Techniques for generating bispecific antibodies from antibody fragments have been 10 described in the literature. For example, bispecific antibodies can be prepared can be prepared using chemical linkage. Braman etal.. Science 229:81 (1985) describe a procedure wherein intact antibodies are proteolytically cleaved to generate F(ab')j fragments. These fragments are reduced in the presence of the dithiol complexing agent sodium arsenite to stabilize vicinal dithiols and prevent intermolecular disulfide formation. The Fab' fragments generated are then convened to thionitrobenzoate (TNB) derivatives. One of the Fab'-TNB 15 derivatives is then reconverted to the Fab'-thiol by reduction with mercaptoethylamine and is mixed with an equimolar amount of the other Fab'-TNB derivative to form the bispecific antibody. The bispecific antibodies produced can be used as agents for the selective immobilization of enzymes.

Fab' fragments may be directly recovered from E. coli and chemically coupled to form bispecific antibodies. Shalaby et al., J. Exp. Med. 175:217-225 (1992) describe the production of a fully humanized 20 bispecific antibody F(ab')2 molecule. Each Fab' fragment was separately secreted from E. coli and subjected to directed chemical coupling in vitro to form the bispecific antibody. The bispecific antibody thus formed was able to bind to cells overexpressing the ErbB2 receptor and normal human T cells, as well as trigger the lytic activity of human cytotoxic lymphocytes against human breast tumor targets.

Various technique for making and isolating bispecific antibody fragments directly from recombinant cell 25 culture have also been described. For example, bispecific antibodies have been produced using leucine zippers. Kostelny et al., J. Tmwiimnl. 148(5): 1547-1553 (1992). The leucine zipper peptides from the Fos and Jun proteins were linked to the Fab' portions of two different antibodies by gene fusion. The antibody homodimers were reduced at the hinge region to form monomers and then re-oxidized to form the antibody heterodimers. This method can also be utilized for the production of antibody homodimers. The "diabody" technology 30 described by Hollinger et al., Proc. Natl. Acad. Sci. USA 90:6444-6448 (1993) has provided an alternative mechanism for making bispecific antibody fragments. The fragments comprise a heavy-chain variable domain (VH) connected to a light-chain variable domain (VJ by a linker which is too shon to allow pairing between the two domains on the same chain. Accordingly, the VH and VL domains of one fragment are forced to pair with the complementary VL and VH domains of another fragment, thereby forming two antigen-binding sites. Another 35 strategy for making bispecific antibody fragments by the use of single-chain Fv (sFv) dimers has also been reponed. See, Gruber et al., J. Immunol. 152:5368 (1994).

Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. 370 Ttitt et al., J. Immunol. 147:60 (1991).

Exemplary bispecific antibodies may bind to two different epitopes on a given PRO polypeptide herein. Alternatively, an anti-PRO polypeptide arm may be combined with an arm which binds to a triggering molecule on a leukocyte such as a T-cell receptor molecule (e.g. CD2, CD3, CD28, or B7), or Fc receptors for IgG (FcyR), such as FcyRI (CD64), FcyRII (CD32) and FcyRIII (CD16) so as to focus cellular defense mechanisms S to the cell expressing the particular PRO polypeptide. Bispecific antibodies may also be used to localize cytotoxic agents to cells which express a particular PRO polypeptide. These antibodies possess a PRO-binding arm and an arm which binds a cytotoxic agent or a radionuclide chelator, such as EOTUBE, DPTA, DOT A, or TETA. Another bispecific antibody of interest binds the PRO polypeptide and further binds tissue factor (TF).

. Heteroconiueate Antibodies Heteroconjugate antibodies are also within the scope of the present invention. Heteroconjugate antibodies are composed of two covalently joined antibodies. Such antibodies have, for example, been proposed to target immune system cells to unwanted cells [U.S. Patent No. 4,676,980], and for treatment of HIV infection 15 [WO 91/00360; WO 92/200373; EP 03089]. It is contemplated that the antibodies may be prepared in vitro using known methods in synthetic protein chemistry, including those involving crosslinking agents. For example, immunotoxins may be constructed using a disulfide exchange reaction or by forming a thioether bond. Examples of suitable reagents for this purpose include iminothiolate and methyl-4-mercaptobutyrimidate and those disclosed, for example, in U.S. Patent No. 4,676,980. 6. Effector Function Engineering It may be desirable to modify the antibody of the invention with respect to effector function, so as to enhance, e.g., the effectiveness of the antibody in treating cancer. For example, cysteine residue(s) may be introduced into the Fc region, thereby allowing interchain disulfide bond formation in this region. The 25 homodimeric antibody thus generated may have improved internalization capability and/or increased complement-mediated cell killing and antibody-dependent cellular cytotoxicity (ADCC). See Caron et al., L Exp Med.. 176:1191-1195 (1992) and Shopes. I. Immunol- 148:2918-2922 (1992). Homodimeric antibodies with enhanced anti-tumor activity may also be prepared using heterobifunctional cross-linkers as described in Wolff etal. Cancer Research. 53:2560-2565(1993). Alternatively, an antibody can be engineered that has dual 30 Fc regions and may thereby have enhanced complement lysis and ADCC capabilities. See Stevenson etal.. Anti-Cancer Drue Design. 3: 219-230 (1989). 7. Immunoconiugates The invention also pertains to immunoconjugates comprising an antibody conjugated to a cytotoxic agent 35 such as a chemotherapeutic agent, toxin (e.g., an enzymatically active toxin of bacterial, iungal, plant, or animal origin, or fragments thereof), or a radioactive isotope (i.e., a radioconjugate).

Chemotherapeutic agents useful in the generation of such immunoconjugates have been described above. 371 Enzymatically active toxins and fragments thereof that can be used include diphtheria A chain, nonbinding active fragments of diphtheria toxin, exotoxin A chain (from Pseudomonas aeruginosa), ricin A chain, abrin A chain, modeccin A chain, alpha-sarcin, Aleurites fordii proteins, dianthin proteins, Phytolaca americana proteins (PAPI, PAPII, and PAP-S), momordica charantia inhibitor, curcin, crotin, sapaonaria officinalis inhibitor, gelonin, mitogellin, restrictocin, phenomycin, enomycin, and the tricothecenes. A variety of radionuclides are 5 available for the production of radioconjugated antibodies. Examples include 2l2Bi, U1I, 13lIn, S0Y, and IMRe.

Conjugates of the antibody and cytotoxic agent are made using a variety of bifunctional protein-coupling agents such as N-succinimidyl-3-(2-pyridyldithiol) propionate (SPDP), iminothiolane (IT), bifunctional derivatives of imidoesters (such as dimethyl adipimidate HCL), active esters (such as disuccinimidyl suberate), aldehydes (such as glutareldehyde), bis-azido compounds (such as bis (p-azidobenzoyl) hexanediamine), bis-10 diazonium derivatives (such as bis-(p-diazoniumbenzoyl)-ethylenediamine), diisocyanates (such as tolyene 2,6-diisocyanate),andbis-activefiuorinecoinpounds(suchas l,5-difluoro-2,4-dinitrobenzene). For example, a ricin immunotoxin can be prepared as described in Vitetta et al., Science. 238: 1098 (1987). Carbon-14-labeled 1-isothiocyanatobenzyl-3-methyldiethylene triaminepentaacetic acid (MX-DTPA) is an exemplary chelating agent for conjugation of radionucleotide to the antibody. See W094/11026.

IS In another embodiment, the antibody may be conjugated to a "receptor" (such streptavidin) for utilization in tumor pretargeting wherein the antibody-receptor conjugate is administered to the patient, followed by removal of unbound conjugate from the circulation using a clearing agent and then administration of a "ligand" (e.g., avidin) that is conjugated to a cytotoxic agent (e.g., a radionucleotide). 8. ItrnnnnnlfTxrawnec The antibodies disclosed herein may also be formulated as immunoliposomes. Liposomes containing the antibody are prepared by methods known in the art, such as described in Epstein et al., Proc. Natl. Acad. Sci. USA. §2: 3688 (1985); Hwang et al., Proc. Nad Acad. Sci. USA. 77: 4030 (1980); and U.S. Pat. Nos. 4,485,045 and 4,544,545. Liposomes with enhanced circulation time are disclosed in U.S. Patent No. 25 5,013,556.

Particularly useful liposomes can be generated by tbe reverse-phase evaporation method with a lipid composition comprising phosphatidylcholine,cholesterol, and PEG-derivatized phosphatidylethanolamine (PEG-PE). Liposomes are extruded through filters of defined pore size to yield liposomes with the desired diameter. Fab' fragments of the antibody of the present invention can be conjugated to the liposomes as described in Martin 30 et al.. J. Biol. Chem.. 257: 286-288 (1982) via a disulfide-interchange reaction. A chemotherapeutic agent (such as Doxorubicin) is optionally contained within the liposome. SeeGabizon etal.. J. National Cancer Inst.. §1(19): 1484 (1989). 9. Pharmaceutical Compositions of Antibodies 35 Antibodies specifically binding a PRO polypeptide identified herein, as well as other molecules identified by the screening assays disclosed hereinbefore, can be administered for the treatment of various disorders in the form of pharmaceutical compositions. 372 If tbe PRO polypeptide is intracellular and whole antibodies are used as inhibitors, internalizing antibodies are preferred. However, lipofections or liposomes can also be used to deliver the antibody, or an antibody fragment, into cells. Where antibody fragments are used, the smallest inhibitory fragment that specifically binds to the binding domain of the target protein is preferred. For example, based upon the variable-region sequences of an antibody, peptide molecules can be designed that retain the ability to bind the target 5 protein sequence. Such peptides can be synthesized chemically and/or produced by recombinant DNA technology. See, e.g., Marasco etal., Proc. Natl. Acad. Sci. USA. §Q; 7889-7893 (1993). Thefornniabon herein may also contain more than one active compound as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect each other. Alternatively, or in addition, the composition may comprise an agent that enhances its function, such as, for example, a cytotoxic 10 agent, cytokine, chemotherapeutic agent, or growth-inhibitory agent. Such molecules are suitably present in combination in amounts that are effective for the purpose intended.

The active ingredients may also be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxymethylcellulose or gelatin-microcapsules and poly-(methylraethacylate) microcapsules, respectively, in colloidal drug delivery systems (for example, IS liposomes, albumin microspheres, microemulsions, nano-particles, and nanocapsules) or in macroemulsians. Such techniques are disclosed in Remington's Pharmaceutical Sciences, supra.

The formulations to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes.

Sustained-release preparations may be prepared. Suitable examples of sustained-release preparations 20 include semipermeable matrices of solid hydrophobic polymers containing the antibody, which matrices are in the form of shaped articles, e.g., films, or microcapsules. Examples of sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methacrylate), or poly(vinyialcohol)), polylactides (U.S. Pat. No. 3,773,919), copolymers of L-glutamic acid and y ethyl-L-glutamate, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycoiic acid copolymers such as the LUPRON DEPOT ™ (injectable 25 microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D-(-)-3-hydroxybutyric acid. While polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid enable release of molecules for over 100 days, certain hydrogels release proteins for shorter time periods. When encapsulated antibodies remain in the body for a long time, they may denature or aggregate as a result of exposure to moisture at 37°C, resulting in a loss of biological activity and possible changes in immunogenicity. Rational strategies 30 can be devised for stabilization depending on the mechanism involved. For example, if the aggregation mechanism is discovered to be intermolecuiar S-S bond formation through thio-disulflde interchange, stabilization may be achieved by modifying sulfhydiyl residues, lyophilizing from acidic solutions, controlling moisture content, using appropriate additives, and developing specific polymer matrix compositions.

G. Uses for anti-PRO Antibodies The anti-PRO antibodies of the invention have various utilities. For example, anti-PRO antibodies may be used in diagnostic assays for PRO, e.g., detecting its expression in specific cells, tissues, or serum. Various 373 diagnostic assay techniques known in the an may be used, such as competitive binding assays, direct or indirect sandwich assays and immunoprecipitation assays conducted in either heterogeneous or homogeneous phases [Zola, Monoclonal Antibodies: A Manual of Techniques CRC Press, Inc. (1987) pp. 147-158]. The antibodies used in the diagnostic assays can be labeled with a detectable moiety. The detectable moiety should be capable of producing, either directly or indirectly, a detectable signal. For example, the detectable moiety may be a 5 radioisotope, such as 3H, UC, KP, ^S, or mI, a fluorescent or chemiluminescent compound, such as fluorescein isothiocyanate, rhodamine, or luciferin, or an enzyme, such as alkaline phosphatase, beta-galactosidase or horseradish peroxidase. Any method known in the an for conjugating the antibody to the detectable moiety may be employed, including those methods described by Hunter et al., Nature. 144:945 (1962); David et al., Biochemistry. 13:1014(1974): Pain etal.. J. Immunol. Meth.. 40:219 (1981): and Nveren. J. Histochem. and 10 Cvtochem.. 30:407 (1982).

Anti-PRO antibodies also are useful for the affinity purification of PRO from recombinant cell culture or natural sources. In this process, the antibodies against PRO are immobilized on a suitable support, such a Sephadex resin or filter paper, using methods well known in the an. The immobilized antibody then is contacted with a sample containing the PRO to be purified, and thereafter the suppon is washed with a suitable solvent that IS will remove substantially all the material in the sample except the PRO, which is bound to the immobilized antibody. Finally, the suppon is washed with another suitable solvent that will release the PRO from the antibody.

The following examples are offered for illustrative purposes only, and are not intended to limit the scope of the present invention in any way.

All patent and literature references cited in the present specification are hereby incorporated by reference in their entirety.

EXAMPLES Commercially available reagents referred to in the examples were used according to manufacturer's 25 instructions unless otherwise indicated. The source of those cells identified in the following examples, and throughout the specification, by ATCC accession numbers is the American Type Culture Collection, Manassas, VA.

EXAMPLE 1: Extracellular Domain Homology Screening to Identify Novel Polypeptides and cDNA F.nrnriinp 30 Therefor The extracellular domain (ECD) sequences (including the secretion signal sequence, if any) from about 950 known secreted proteins from the Swiss-Prot public database were used to search EST databases. The EST databases included public databases (e.g., Dayhoff, GenBank), and proprietary databases (e.g. LIFESEQ™, Incyte Pharmaceuticals, Palo Alto, CA). The search was performed using the computer program BLAST or 35 BLAST-2 (Altschul et al., Methods in Enzvmologv 266:460-480 (1996)) as a comparison of the ECD protein sequences to a 6 frame translation of the EST sequences. Those comparisons with a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into consensus DNA 374 sequences with tbe program "phrap" (Phil Green, University of Washington, Seattle, WA).

Using this extracellular domain homology screen, consensus DNA sequences were assembled relative to the other identified EST sequences using phrap. In addition, the consensus DNA sequences obtained were often (but not always) extended using repeated cycles of BLAST or BLAST-2 and phrap to extend the consensus sequence as far as possible using the sources of EST sequences discussed above.

Based upon the consensus sequences obtained as described above, oligonucleotides were then synthesized and used to identify by PCR a cDNA library that contained the sequence of interest and for use as probes to isolate a clone of the full-length coding sequence for a PRO polypeptide. Forward and reverse PCR primers generally range from 20 to 30 nucleotides and are often designed to give a PCR product of about 100-1000 bp in length. The probe sequences are typically 40-55 bp in length. In some cases, additional 10 oligonucleotides are synthesized when the consensus sequence is greater than about 1-1.5kbp. In order to screen several libraries for a full-length clone, DNA from the libraries was screened by PCR amplification, as per Ausubel et al., Current Protocols in Molecular Biology, with the PCR primer pair. A positive library was then used to isolate clones encoding the gene of interest using the probe oligonucleotide and one of the primer pairs. The cDNA libraries used to isolate the cDNA clones were constructed by standard methods using 15 commercially available reagents such as those from Invitrogen, San Diego, CA. The cDNA was primed with oligo dT containing a NotI site, linked with blunt to Sail hemikinased adaptors, cleaved with NotI, sized appropriately by gel electrophoresis, and cloned in a defined orientation into a suitable cloning vector (such as pRKB or pRKD; pRK5B is a precursor of pRK5D that does not contain the Sfil site; see, Holmes etal., Science. 253:1278-1280 (1991)) in die unique Xhol and NotI sites.

EXAMPLE 2: Isolation of cDNA clones bv Amylase Screening 1. Preparation of oligo dT primed cDNA library mRNA was isolated from a human tissue of interest using reagents and protocols from Invitrogen, San Diego, CA (Fast Track 2). This RNA was used to generate an oligo dT primed cDNA library in the vector 25 pRK5D using reagents and protocols from Life Technologies, Gaithersburg, MD (Super Script Plasmid System). In this procedure, the double stranded cDNA was sized to greater than 1000 bp and the Sall/NotI linkered cDNA was cloned into XhoI/NotI cleaved vector. pRKSD is a cloning vector that has an sp6 transcription initiation site followed by an Sfil restriction enzyme site preceding the XhoI/NotI cDNA cloning sites. 2. Preparation of random primed cDNA library A secondary cDNA library was generated in order to preferentially represent the 5' ends of the primary cDNA clones. Sp6 RNA was generated from the primary library (described above), and this RNA was used to generate a random primed cDNA library in the vector pSST-AMY.O using reagents and protocols from Life Technologies (Super Script Plasmid System, referenced above). In this procedure the double stranded cDNA 35 was sized to 500-1000 bp, linkered with blunt to NotI adaptors, cleaved with Sfil, and cloned into Sfil/NotI cleaved vector. pSST-AMY.O is a cloning vector that has a yeast alcohol dehydrogenase promoter preceding the cDNA cloning sites and the mouse amylase sequence (the mature sequence without the secretion signal) 375 followed by the yeast alcohol dehydrogenase terminator, after the cloning sites. Thus, cDNAs cloned into this vector that are fused in frame with amylase sequence will lead to the secretion of amylase from appropriately transfected yeast colonies. 3. Transformation and Detection 5 DNA from the library described in paragraph 2 above was chilled on ice to which was added electrocompetent DH10B bacteria (Life Technologies, 20 ml). The bacteria and vector mixture was then electroporated as recommended by the manufacturer. Subsequently, SOC media (Life Technologies, 1 ml) was added and the mixture was incubated at 37DC for 30 minutes. The transformants were then plated onto 20 standard ISO mm LB plates containing ampicillin and incubated for 16 hours (37°C). Positive colonies were 10 scraped off the plates and the DNA was isolated from the bacterial pellet using standard protocols, e.g. CsCl-gradient. The purified DNA was then carried on to the yeast protocols below.

The yeast methods were divided into three categories: (1) Transformation of yeast with the plasmid/cDNA combined vector; (2) Detection and isolation of yeast clones secreting amylase; and (3) PCR amplification of the insert directly from the yeast colony and purification of the DNA for sequencing and further IS analysis.

The yeast strain used was HD56-5A (ATCC-90785). This strain has the following genotype: MAT alpha, ura3-52, leu2-3, leu2-112, his3-ll, his3-15, MAL+, SUC+, GAL+. Preferably, yeast mutants can be employed that have deficient post-translatkmal pathways. Such mutants may have translocation deficient alleles in sec71, sec72, sec62, with truncated sec7l being most preferred. Alternatively, antagonists (including 20 antisense nucleotides and/or ligands) which interfere with the normal operation of these genes, other proteins implicated in this post translation pathway (e.g., SEC61p, SEC72p, SEC62p, SEC63p, TDJlp or SSAlp-4p) or the complex formation of these proteins may also be preferably employed in combination with the amylase-expressing yeast.

Transformation was performed based on the protocol outlined by Gietz et al., Nucl. Acid. Res.. 2Q: 1425 25 (1992). Transformed cells were then inoculated from agar into YEPD complex media broth (100 ml) and grown overnight at 30°C. The YEPD broth was prepared as described in Kaiser et al., Methods in Yeast Genetics. Cold Spring Harbor Press, Cold Spring Harbor, NY, p. 207 (1994). The overnight culture was then diluted to about 2 x 10s cells/ml (approx. 00600=0.1) into fresh YEPD broth (500 ml) and regrown to 1 x 107 cells/ml (approx. 00400=0.4-0.5).

The cells were then harvested and prepared for transformation by transfer into GS3 rotor bottles in a Sorval GS3 rotor at 5,000 rpm for 5 minutes, the supernatant discarded, and then resuspended into sterile water, and centrifuged again in 50 ml falcon tubes at 3,500 rpm in a Beckman GS-6KR centrifuge. The supernatant was discarded and the cells were subsequently washed with LiAc/TE (10 ml, 10 mM Tris-HCl, 1 mM EDTA pH 7.5, 100 mM Li2OOCCH3), and resuspended into LiAc/TE (2.5 ml).

Transformation took place by mixing the prepared cells (100 pi) with freshly denatured single stranded salmon testes DNA (Lofstrand Labs, Gaithersburg, MD) and transfonning DNA (1 jug, vol. < 10 pi) in microfuge tubes. The mixture was mixed briefly by vortexing, then 40% PEG/TE (600 pi, 40% polyethylene 376 glycol-4000, 10 mM Tris-HCl, 1 mM EDTA, 100 mM Li2OOCCH3, pH 7.5) was added. This mixture was gently mixed and incubated at 30°C while agitating for 30 minutes. The cells were then heat shocked at 42°C for 15 minutes, and the reaction vessel centrifuged in a microfuge at 12,000 rpm for 5-10 seconds, decanted and resuspended into TE (500 pi, 10 mM Tris-HCl, 1 mM EDTA pH 7.5) followed by recentrifugation. The cells were then diluted into TE (1 ml) and aliquots (200 pi) were spread onto the selective media previously prepared 5 in 150 mm growth plates (VWR).

Alternatively, instead of multiple small reactions, the transformation was performed using a single, large scale reaction, wherein reagent amounts were scaled up accordingly.

The selective media used was a synthetic complete dextrose agar lacking uracil (SCD-Ura) prepared as described in Kaiser et al., Methods in Yeast Genetics. Cold Spring Harbor Press, Cold Spring Harbor, NY, p. 10 208-210 (1994). Transformants were grown at 30°C for 2-3 days.

The detection of colonies secreting amylase was performed by including red starch in the selective growth media. Starch was coupled to the red dye (Reactive Red-120, Sigma) as per the procedure described by Biely etal., Anal. Biochem.. 172:176-179 (19881. The coupled starch was incorporated into the SCD-Ura agar plates at a final concentration of 0.15 % (w/v), and was buffered with potassium phosphate to a pH of 7.0 (50-15 100 mM final concentration).

The positive colonies were picked and streaked across fresh selective media (onto 150 mm plates) in order to obtain well isolated and identifiable single colonies. Well isolated single colonies positive for amylase secretion were detected by direct incorporation of red starch into buffered SCD-Ura agar. Positive colonies were determined by iheir ability to break down starch resulting in a clear halo around the positive colony visualized 20 directly. 4. Isolation of DNA bv PCR Amplification When a positive colony was isolated, a portion of it was picked by a toothpick and diluted into sterile water (30 pi) in a 96 well plate. At this time, the positive colonies were either frozen and stored for subsequent 25 analysis or immediately amplified. An aliquot of cells (5 pi) was used as a template for tbe PCR reaction in a 25 pi volume containing: 0.5 pi Klentaq (Clontech, Palo Alto, CA); 4.0 pi 10 mM dNTP's (Perkin Elmer-Cetus); 2.5 pi Kentaq buffer (Clontech); 0.25 pi forward oligo 1; 0.25 pi reverse oligo 2; 12.5 pi distilled water. The sequence of the forward oligonucleotide 1 was: ' -TGTAAAACGACGGCC AGTT AAAT AG ACCTGC A ATT ATT A ATCT-3' (SEQ ID NO: 1) 30 The sequence of reverse oligonucleotide 2 was: ' -CAGGAAAC AGCTATGACCACCTGC AC ACCTGC A A ATCC ATT -3' (SEQ ID NO:2) PCR was then performed as follows: a.

Denature 92°C, minutes b. 3 cycles of: Denature Anneal Extend 92 °C, 59"C, 72 °C, seconds 30 seconds 60 seconds 40 c. 3 cycles of: Denature Anneal 92°C, 57°C, seconds 30 seconds 377 Extend 72°C, 60 seconds d. 25 cycles of: Denature 92°C, 30 seconds Anneal 55 °C, 30 seconds Extend 72 °C, 60 seconds e. Hold 4°C The underlined regions of the oligonucleotides annealed to the ADH promoter region and the amylase region, respectively, and amplified a 307 bp region from vector pSST-AMY.O when no insert was present.

Typically, the first 18 nucleotides of the 5' end of these oligonucleotides contained annealing sites for the sequencing primers. Thus, the total product of the PCR reaction from an empty vector was 343 bp. However, signal sequence-fused cDNA resulted in considerably longer nucleotide sequences.

Following the PCR, an aliquot of the reaction (5 pi) was examined by agarose gel electrophoresis in a 1 % agarose gel using a Tris-Borate-EDTA (TBE) buffering system as described by Sambrook et al., supra.

Clones resulting in a single strong PCR product larger than 400 bp were further analyzed by DNA sequencing after purification with a 96 Qiaquick PCR clean-up column (Qiagen Inc., Chalsworth, CA).

EXAMPLE 3: Isolation of cDNA Clones UsinP Siynal Algorithm Analysis Various polypeptide-encoding nucleic acid sequences were identified by applying a proprietary signal 20 sequence finding algorithm developed by Genentech, Inc. (South San Francisco, CA) upon ESTs as well as clustered and assembled EST fragments from public (e.g., GenBank) and/or private (LIFESEQ®, Incyte Pharmaceuticals, Inc., Palo Alto, CA) databases. The signal sequence algorithm computes a secretion signal score based on the character of the DNA nucleotides surrounding the first and optionally the second methionine codon(s) (ATG) at the 5' -end of the sequence or sequence fragment under consideration. The nucleotides 25 following the first ATG must code for at least 35 unambiguous amino acids without any stop codons. If the first ATG has the required amino acids, the second is not examined. If neither meets the requirement, the candidate sequence is not scored. In order to determine whether the EST sequence contains an authentic signal sequence, the DNA and corresponding amino acid sequences surrounding the ATG codon are scored using a set of seven sensors (evaluation parameters) known to be associated with secretion signals. Use of this algorithm resulted 30 in the identification of numerous polypeptide-encoding nucleic acid sequences.

EXAMPLE 4: Isolation of cDNA clones Encoding Human PROI56Q A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is designated herein as DNA17409. Based on the DNA17409 35 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01560.

DNA sequencing of the isolated clones isolated as described above gave the full-length DNA sequence for DNA19902-1669 [Figure 1, SEQ ID NO:3]; and the derived protein sequence for PR01560. 40 The entire coding sequence of DNA19902-1669 is included in Figure 1 (SEQ ID NO:3). Clone 378 DNA19902-1669 contains a single open reading frame with an apparent translations! initiation site at nucleotide positions 41-43, and an apparent stop codon at nucleotide positions 776-778. The predicted polypeptide precursor is 245 amino acids long. The approximate locations of the signal peptide, transmembrane domains, N-glycosylation sites, N-myristoylation sites, tyrosine kinase phosphorylation sites, and membrane lipoprotein lipid attachment sites are also indicated in Figure 2. Clone DNA19902-1669 has been deposited with the ATCC 5 and is assigned ATCC deposit no. 203454. The full-length PR01560 protein shown in Figure 2 has an estimated molecular weight of about 27,563 daltons and a pi of about 8.36.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 2 (SEQ ID NO:4), revealed sequence identity between the PR01560 amino acid sequence and the following Dayhoff sequences: AF053453_1, AF053454_1, 10 A15 HUMAN, AF054840_1, CD63_HUMAN, AF065389_1, AFQ54838_1, AF089749J, P_R27525, and PR86834.

FXAMPI.F. 5: Isolation of cDNA clones Encoding Human PRQ444 A cDNA sequence isolated in the amylase screen described in Example 2 above was designated IS DNA13121. Based upon this sequence, probes were generated and used to screen a human fetal lung library (LIB25) prepared as described in paragraph 1 of Example 2 above. The cloning vector was pRK5B (pRK5B is a precursor of pRKSD that does not contain the Sfil site; see, Holmes et al., Science. 253:1278-1280 (1991)), and the cDNA size cut was less than 2800 bp.

A full length clone was identified that contained a single open reading frame with an apparent 20 translational initiation site at nucleotide positions 608-610 and ending at the stop codon found at nucleotide positions 959-961 (Figure 3, SEQ ID NO:5). The predicted polypeptide precursor is 117 amino acids long, has a calculated molecular weight of approximately 12,692 daltons and an estimated pi of approximately 7.50. Analysis of the full-length PR0444 sequence shown in Figure 4 (SEQ ID NO:6) evidences the presence of a signal peptide at amino acid 1 to about amino acid 16. An analysis of the Dayhoff database (version 35.45 25 SwissProt 35) evidenced homology between the PR0444 amino acid sequence and the following Dayhoff sequences: CEF44D12_8, P_R88452, YNE1_CAEEL, A47312, AF009957_1, and A06133_l. Clone DNA26846-1397 was deposited with the ATCC on October 27,1998 and is assigned ATCC deposit no. 203406.

EXAMPLE 6: Isolation of cDNA clones Encoding Human PRQ1018 30 A cDNA clone (DNA56107-1415) encoding a native human PR01018 polypeptide was identified by a yeast screen, in a human ovary tumor cDNA library that preferentially represents the 5' ends of the primary cDNA clones. The yeast screen employed identified a single EST clone designated herein as DNA41000. The DNA41000 sequence was then compared to various EST databases including public EST databases (e.g., GenBank), and a proprietary EST database (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, CA) to identify 35 homologous EST sequences. The comparison was performed using the computer program BLAST or BLAST2 f Altschul et al.. Methods in Enzvmologv. 266:460-480(1996)]. Those comparisons resulting in a BLAST score of 70 (or in some cases, 90) or greater that did not encode known proteins were clustered and assembled into 379 a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). This consensus sequence is herein designated DNA44449. Oligonucleotide primers based upon the DNA44449 sequence were then synthesized and employed to screen a human ovary tumor cDNA library which resulted in the identification of the DNA56107-1415 clone shown in Figure S.

The full-length DNA56107-1415 clone shown in Figure 5 contains a single open reading frame with 5 an apparent translational initiation site at nucleotide positions 129-131 and ending at the stop codon at nucleotide positions 696-698 (Figure 5). The predicted polypeptide precursor is 189 amino acids long (Figure 6). Analysis of the full-length PR01018 sequence shown in Figure 6 (SEQ ID NO:8) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 24, transmembrane domains from about amino acid 86 to about amino acid 103 and from about amino acid 60 to about amino acid 75 and an amino acid sequence 10 block having homology to G-protein coupled receptor proteins from about amino acid 44 to about amino acid 84. Clone DNA56107-1415 has been deposited with ATCC on October 27,1998 and is assigned ATCC deposit no. 203405.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 6 (SEQ ID NO:8), evidenced significant 15 homology between the PRO 1018 amino acid sequence and the following Dayhoff sequences: CEB0399_4, S59764, YHDT HAE1N and AE000675_3.

EXAMPLE 7: Isolation of cDNA clnnm: F.nrnriinn Human PRQ1773 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described 20 in Example 1 above. This consensus sequence is herein designated DNA49797. Based upon an observed homology between the DNA49797 consensus sequence and an EST sequence contained within Incyte EST clone no. 509434, Incyte EST clone no. 509434 was purchased and its insert obtained and sequenced. That sequence is herein shown in Figure 7 and is designated DNA56406-1704.

The entire nucleotide sequence of DNA56406-1704 is shown in Figure 7 (SEQ ID NO:9). Clone 25 DNA56406-1704 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 111-113 and ending at the stop codon at nucleotide positions 1068-1070 (Figure 7). The predicted polypeptide precursor is 319 amino acids long (Figure 8). The full-length PR01773 protein shown in Figure 8 has an estimated molecular weight of about 35,227 daltons and a pi of about 8.97. Analysis of the full-length PRO1773 sequence shown in Figure 8 (SEQ ID NO: 10) evidences the presence of the following: a signal peptide 30 from about amino acid 1 to about amino acid 17, a transmembrane domain from about amino acid 136 to about amino acid 152, potential N-glycosylation sites from about amino acid 161 to about amino acid 164, from about amino acid 187 to about amino acid 190 and from about amino acid 253 to about amino acid 256, a glycosaminoglycan attachment site from about amino acid 39 to about amino acid 42 and potential N-myristolation sites from about amino acid 36 to about amino acid 41, from about amino acid 42 to about amino 35 acid 47, from about amino acid 108 to about amino acid 113, from about amino acid 166 to about amino acid 171, from about amino acid 198 to about amino acid 203 and from about amino acid 207 to about amino acid 212. Clone DNA56406-1704 has been deposited with ATCC on November 17, 1998 and is assigned ATCC 380 deposit no. 203478.

An analysis of the Dayhoff database (version 3S.4S SwissProt 33), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 8 (SEQ ID NO: 10), evidenced significant homology between the PR01773 amino acid sequence and the following Dayhoff sequences: ROH2RAT, ROH3RAT, AF030513_1 ,ROHl_RAT, AF056194_1, AF057034_1, P_W18337, P_W18328, BDH_HUMAN 5 and BDH_RAT.

EXAMPJUF.g; Isolation of cDNA clones Encoding Human PRO 1477 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is herein designated DNA52641. Based on the DNA52641 10 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR0240.

PCR primers (forward and reverse) were synthesized: forward PCR primer 5 '-CGCCAGAAGGGCGTGATTGACGTC-3' (SEQ ID NO: 13) reverse PCR primer 51 -CCATCCTTCTTCCC AG AC AGGCCG-3' (SEQIDNO:14) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA5264I sequence which had the following nucleotide sequence hybridization probe '-GAAGCCTGTGTCCAGGTCCTTCAGTGAGTGGTTTGGCCTCGGTC-3' (SEQ ID NO:15) 20 In order to screen several libraries for a source of a full-length clone, DNA from die libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR0240 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from human fetal liver tissue.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for 25 PR01477 (designated herein as DNA56529-1647 [Figure 9, SEQ ID NO: 11]; and the derived protein sequence for PRO1477.

The entire nucleotide sequence of DNA56529-1647 is shown in Figure 9 (SEQ ID NO:ll). Clone DNA56529-1647 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 23-25 and ending at the stop codon at nucleotide positions 2120-2122 (Figure 9). The predicted 30 polypeptide precursor is 699 amino acids long (Figure 10). The full-length PR0240 protein shown in Figure 10 has an estimated molecular weight of about 79,553 daltons and a pi of about 7.83. Analysis of die full-length PR01477 sequence shown in Figure 10 (SEQ ID NO: 12) evidences the presence of the following: transmembrane domains from about amino acid 21 to about amino acid 40 and from about amino acid 84 to about amino acid 105. Clone DNA56529-1647 has been deposited with ATCC on September 29,1998 and is assigned 35 ATCC deposit no. 203293.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 10 (SEQ ID NO:12), evidenced significant 381 homology between the PR01477 amino acid sequence and the following Dayhoff sequences: CELT03G111, CEZC410_4, A54408, SSMAN9MAN_1, GEN12643, GEN12642, AF027156_1, P_W46900, SPAC23A1_4 and DMC86E4_5.

EXAMPLE 9: Isolation of cDNA clones F.ncoding Human PRQ1478 5 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is designated herein "DNA52719". Based on the DNA52719 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PRO1478.

PCR primers (forward and reverse) were synthesized: forward PCR nrimer 5'GCGAACGCTTCGAGGAGTCCTGG3' (SEQ ID NO: 18); and reverse PCR nrimer 5' GCAGTGCGGG AAGCC AC AT GGTAC3' (SEQ ID NO:19).

Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensusDNA52719 sequence which had the following nucleotide sequence: hybridization probe 5'CTTCCTGAGCAGGAAGAAGATCCGGCACCACATCTACGTGCTCAAC3'(SEO ID N0:20).

In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01478 gene using the probe oligonucleotide and one of the PCR primers. RNA 20 for construction of the cDNA libraries was isolated from human fetal kidney tissue.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PR01478 and the derived protein sequence for PR01478.

The entire coding sequence of PR01478 is included in Figure 11 (SEQ BDNO;16). Clone DNA56531-1648 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 25 77-79 and an apparent stop codon at nucleotide positions 1058-1060 of SEQ ID NO: 16. The predicted polypeptide precursor is 327 amino acids long. The type II transmembrane sequence is believed to be at about amino acids 29-49 of SEQ ID NO:17, and an N-glycosylation site is believed to be at about amino acids 154-157 of SEQ ID NO: 17. Clone DNA56531-1648 has been deposited with ATCC and is assigned ATCC deposit no. 203286. The full-length PR01478 protein shown in Figure 12 has an estimated molecular weight of about 30 37,406 daltons and a pi of about 9.3.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 12 (SEQ ID NO:17), revealed sequence identity between the PR01478 amino acid sequence and the following Dayhoff sequences: YNJ4_CAEEL, P R55706, A38781_l, NALS MOUSE, HUMHGTJ, AF048687_1, CEW02B12_11, Y09F_MYCTU, FOJO_DROME, 35 and G01936. 382 EXAMPLE 10: Isolation of cDNA clones Encoding Human PRQ831 DNA56862-1343 was identified by applying the proprietary signal sequence finding algorithm described in Example 3 above. Use of the above described signal sequence algorithm allowed identification of an EST cluster sequence from the Incyte database, designated Incyte cluster sequence no. 2SS07. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST 5 databases (e.g., GenBank) and a proprietary EST DNA database (Lifeseq®, Incyte Pharmaceuticals, Palo Alto, CA) to identiiy existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al.. Methods in Enzvmologv 266:460-480 (19%)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington). 10 The consensus sequence obtained therefrom is herein designated as DNA55714.

In light of the sequence homology between the DNA55714 sequence and an EST sequence contained within the Merck EST clone no. AA09944S, the Merck EST clone no. AA09944S was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 13 and is herein designated as DNA56862-1343.

IS Clone DNAS6862-1343 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 40-42 and ending at the stop codon at nucleotide positions 259-261 (Figure 13). The predicted polypeptide precursor is 73 amino acids long (Figure 14). The full-length PR0831 protein shown in Figure 14 has an estimated molecular weight of about 7,879 daltons and a pi of about 7.21. Analysis of the full-length PR0831 sequence shown in Figure 14 (SEQ ID NO:22) evidences the presence of the following: a signal 20 peptide from about amino acid 1 to about amino acid 15 and an amino acid sequence block having homology to growth factor and cytokine receptor family proteins from about amino acid 3 to about amino acid 18. Clone DNA56862-1343 has been deposited with ATCC on September 1, 1998 and is assigned ATCC deposit no. 203174.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence 25 alignment analysis of the full-length sequence shown in Figure 14 (SEQ ID NO:22), evidenced significant homology between the PR0831 amino acid sequence and the following Dayhoff sequences: P_W30724, HUMPPA_1,AF022238_1,4HHB_C,P_R39727,P_R39728, TRYT_MERUN, GPR5HUMAN, AB010266_3 and HSBCL3S2_1.

EXAMPLE 11: Isolation of cDNA clones Encoding Human PROl 113 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is designated herein "DNA34025". Based on the DNA34025 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for 35 PROl 113.

PCR primers (forward and reverse) were synthesized: forward PCR primer 5'GAGGACTCACCAATCTGGTTCGGC3' (SEQ ID NO:25); and 383 reverse PCR primer 5'AACTGGAAAGGAAGGCTGTCTCCC3' (SEQ ID NO:26).

Additionally, a synthetic oligonucleotide hybridization probe was constructed from die consensus DNA34025 sequence which had the following nucleotide sequence: hybridization probe 5 "GTAAAGGAGAAGAACATCACGGTACGGGATACCAGGTGTGTTTATCCTAA3' (SEQ ID NO:27).

In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PROl 113 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from human fetal kidney.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for 10 PR01113 (designated herein as DNA57254-1477 [Figure 15, SEQIDNO:23]; and the derived protein sequence for PROl 113.

The entire coding sequence of PROl 113 is shown in Figure IS (SEQ ID NO:23). Clone DNA57254-1477 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 214-216, and an apparent stop codon at nucleotide positions 2062-2064 of SEQ ID N0.23. The predicted IS polypeptide precursor is 616 amino acids long. The transmembrane domain (type II) is believed to be at about amino acids 13-40 of SEQ ID NO:24. The N-giycosylation sites and N-myristoylation sites are indicated in Figure 16. Clone DNA57254-1477 has been deposited with the ATCC and is assigned ATCC deposit no. 203289. The full-length PROl 113 protein shown in Figure 16 has an estimated molecular weight of about 68,243 daltons and a pi of about 8.66.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 16 (SEQ ID NO:24), revealed sequence identity between the PROl 113 amino acid sequence and the following Dayhoff sequences (data incorporated herein): D86983 1, A58532, SLIT_DROME, AB007865_1, AC004142_1, CELT21D128, AB003184J, DMU42767_1, MUSLRRPJ and GPCR LYMST.

EXAMPLE 12: Isolation of cDNA clones Encoding Human PRO 1194 Use of tbe signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the Incyte database. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary 30 EST DNA database (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. One or more of the ESTs was derived from a human pineal gland library. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, 35 University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated DNA56S11.

In light of the sequence homology between the DNA56511 sequence and an EST contained within the 384 Merck EST AA069568, the clone 382736 which includes this EST was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 17 and is herein designated as DNA57841-1522.

The full length clone shown in Figure 17 contained a single open reading frame with an apparent translational initiation site at nucleotide positions 9-11 and ending at the stop codon found at nucleotide positions 5 252-254 (Figure 17; SEQ ID NO:28). The predicted polypeptide precursor (Figure 18, SEQ ID NO:29) is 81 amino acids long. The signal peptide is at about amino acids 1-21 of SEQ ID NO:29. PROl 194 has a calculated molecular weight of approximately 9,223 daltons and an estimated pi of approximately 10.47. Clone DNA57841-1522 was deposited with the ATCC on November 3, 1998 and is assigned ATCC deposit no. 203458.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 18 (SEQ ID NO:29), revealed sequence identity between the PROl 194 amino acid sequence and the following Dayhoff sequences: PT17_YEAST, RR2CHLVU, CEK12F21, S22452, S76705, AF031898_7, A4_DROME, AF038931_1, E49905, and GSPLAERHY.

EXAMPT.F. W Isolation of cDNA clones Encoding Human PROl 110 A cDNA clone (DNA58727-1474) encoding a native human PROlllO polypeptide was identified by a yeast screen, in a human fetal kidney cDNA library that preferentially represents the 5' ends of the primary cDNA clones. The yeast screen employed identified a single EST clone designated herein as DNA45566. The 20 DNA45566 sequence was then compared to various EST databases including public EST databases (e.g., GenBank), and a proprietary EST database (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, CA) to identify homologous EST sequences. The comparison was performed using the computer program BLAST or BLAST2 f Altschul et al.. Methods in Enzvmologv. 266:460-480 (1996)]. Those comparisons resulting in a BLAST score of 70 (or in some cases, 90) or greater that did not encode known proteins were clustered and assembled into 25 a consensus DNA sequence with the program "phrap'' (Phil Green, University of Washington, Seattle, Washington). This consensus sequence is herein designated DNA46965. Oligonucleotide primers based upcm the DNA46965 sequence were then synthesized and employed to screen a human SK-Lu-1 adenocarcinoma cDNA library (LIB247) which resulted in the identification of the DNA58727-1474 clone shown in Figure 19.

The full-length DNA58727-1474 clone shown in Figure 19 contains a single open reading frame with 30 an apparent translational initiation site at nucleotide positions 131-133 and ending at the stop codon at nucleotide positions 1097-1099 (Figure 19). The predicted polypeptide precursor is 322 amino acids long (Figure 20). The full-length PROl 110 protein shown in Figure 20 has an estimated molecular weight of about 35,274 daltons and a pi of about 8.57. Analysis of the full-length PROlllO sequence shown in Figure 20 (SEQ ID NO:31) evidences the presence of the following: transmembrane domains from about amino acid 41 to about amino acid 35 60, from about amino acid 66 to about amino acid 85, from about amino acid 101 to about amino acid 120, from about amino acid 137 to about amino acid 153, from about amino acid 171 to about amino acid 192, from about amino acid 205 to about amino acid 226, from about amino acid 235 to about amino acid 255 and from about 385 WO 00/12708 PCT/US99/20111 amino acid 294 to about amino acid 312, a potential N-glycosylation site from about amino acid 6 to about amino acid 69, and a glycosaminoglycan attachment site from about amino acid 18 to about amino acid 21. Clone DNA58727-1474 has been deposited with ATCC on September 1, 1998 and is assigned ATCC deposit no. 203171.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence 5 alignment analysis of the full-length sequence shown in Figure 20 (SEQ ID NO:31), evidenced significant homology between the PROl 110 amino acid sequence and the following Dayhoff sequences: MMMYELUPR_1, PR99799, MAL_HUMAN, P_P80929, RNMALGENEJ, S68406, PLLP RAT, MMMALPROT 1,138891 and S55622.

EXAMPLE 14: Isolation of cDNA clones Encoding Human PRQ1378 An initial DNA sequence referred to herein as DNA51941 was identified using a yeast screen, in a human bone marrow cDNA library that preferentially represents the 5' ends of the primary cDNA clones. Based on the DNA51941 sequence, the following oligonucleotides were synthesized for use as probes to isolate a clone of the full-length coding sequence for PR01377 from a bone marrow cDNA library: 15 T G T C C T T T G T C C C A G A C T T C T G T C C (SEQ ID NO:34), CTGGATGCTAATGTGTCCAGTAAATGATCCCCTTATCCCGTCGCGATGCT (SEQ ID NO:35); TTCCACTCAATGAGGTGAGCCACTC ( SEQ ID NO:36); GGCGAGCCCTAACTATCCAGGAG (SEQ ID NO:37); GGAGATCGCTGCGCTGGCCAGGTCCTCCCTGCATGGTAT (SEQ ID NO:38); and CTGCTGCAAAGCGAGCCTCTTG (SEQ ID NO:39).

The full length DNA58730-1607 clone shown in Figure 21 contained a single open reading frame with an apparent translational initiation site at nucleotide positions 1365 to 1367 and ending at the stop codon found at nucleotide positions 2370 to 2372 (Figure 21; SEQ ID NO:32). The predicted polypeptide precursor (Figure 22, SEQ ID NO:33) is 335 amino acids long, with a signal peptide sequence at about amino acids 1-15. PR01378 has a calculated molecular weight of approximately 36,108 daltons and an estimated pi of 25 approximately 4.51.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 22 (SEQ ID NO:33), revealed some homology between the PR01378 amino acid sequence and the following Dayhoff sequences: ICAL RABIT, SP2 HUMAN, SHPSPRBB_1, SP23_HUMAN, P_W08158, and P_W08150.

Clone DNA58730-1607 was deposited with the ATCC on September 15,1998, and is assigned ATCC deposit no. 203221.

EXAMPLE 15: Isolation of cDNA clones Encoding Hnman PRQ1481 An initial DNA sequence, referred to herein as DNA53254, was identified using a yeast screen, in a 35 human fetal kidney cDNA library that preferentially represents the 5' ends of the primary cDNA clones. Based on the DNA53254 sequence, oligonucleotides were synthesized for use as probes (or primers) to isolate a clone of the full-length coding sequence for PR01481 from a human fetal kidney cDNA library. 386 The Ml length DNA58732-1650 done shown in Figure 23 contained a single open reading frame with an apparent translational initiation site at nucleotide positions 320-322 and ending at die stop codon found at nucleotide positions 1322-1324 (Figure 23; SEQ ID N0:40). The predicted polypeptide precursor (Figure 24, SEQ ID NO:41) is 334 amino acids long. The signal peptide is at about amino adds 1-23, and a transmembrane domain is at about amino acids 235-262 of SEQ ID NO:41. The N-glycosylation sites are indicated in Figure 24. PR01481 has a calculated molecular weight of approximately 36,294 daltons and an estimated pi of approximately 4.98. Clone DNA58732-1650 has been deposited with the ATCC and is assigned ATCC deposit no. 203290.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the Ml-length sequence shown in Figure 24 (SEQ ID NO:41), revealed sequence identity between the PR01481 amino acid sequence and the following Dayhoff sequences (data incorporated herein): YN23YEAST, S67770, H36857, YLU2_PICAN, GEN12881, CVY15035_28, YM96_YEAST, ESC1SCHPO, CELZK783 1 and S59310.

EXAMPLE 16: Isolation of cDNA clones Encoding Human PRO 1189 A cDNA sequence isolated in the amylase screen described in Example 2 above is herein designated DNA41784. The DNA41784 sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and proprietary EST DNA databases (LIFESEQTM, Incyte Pharmaceuticals, Palo Alto, CA; and Genentech, South San Francisco, CA) to identify existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into consensus DNA sequences with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated DNA45499.

Based on the DNA45499 sequence, oligonucleotide probes were generated and used to screen a human bone marrow library prepared as described in paragraph 1 of Example 2 above. The cloning vector was pRK5B (pRK5B is a precursor of pRK5D that does not contain the Sfil site; see, Holmes et al., Science. 253:1278-1280 (1991)), and the cDNA size cut was less than 2800 bp.

PCR primers (forward and reverse) were synthesized: forward PCR primer (45499.fl) 5' -G A A AGAC ACG AC AC AGC AGCTTGC-3' (SEQ ID NO:44) forward PCR primer (45499.f2) 5'-GGGAACTGCTATCTGATGCC-3' (SEQ ID NO:45) forward PCR primer (45499.Q) 5'-CAGGATCTCCTCTTGCAGTCTGCAGC-3' (SEQ ID NO:46) reverse PCR nrimer (45499.rl) 5' CTTCTCG A ACC AC AT A AGTTTG AGGC AG-3' (SEQ ID NO: 47) reverse PCR primer (45499. r2) 5' -CACGATTCCCTCCACAGCAACTGGG-3' (SEQ ID NO:48).

Additionally, a synthetic oligonucleotide hybridization probe was constructed from the DNA45499 sequence which had the following nucleotide sequence: hybridization probe (45499.pl) ' -CGCCTT ACCGCGCAGCCCG AAG ATTC ACT ATGGTG A A AATCGCCTTC A AT-3' (SEQ ID N0:230). 387 INTELLECTUAL PROPERTY OFRCE OF i\|.Z 2 h OCT 2003 received In order to screen several libraries for a source of a full-length clone, DNA from tbe libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PROl 189 gene using the probe oligonucleotide and one of the PCR primers.

A full length clone was identified that contained a single open reading frame with an apparent translational initiation site at nucleotide positions 79-81, and a stop signal at nucleotide positions 868-870 5 (Figure 25; SEQ ID NO:42). The predicted polypeptide precursor is 263 amino acids long has a calculated molecular weight of approximately 29,741 daltons and an estimated pi of approximately 5.74. Additional features include a type II transmembrane domain at about amino acids 53-75 and a potential N-glycosylation site at about amino acids 166-169.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence 10 alignment analysis of the full-length sequence shown in Figure 26 (SEQ ID NO:43), evidenced significant homology between the PROl 189 amino acid sequence and Dayhoff sequences MUSE25A1 and HS696H22_1. Additionally, some homology was revealed between the PROl 189 amino acid sequence and the following Dayhoff sequences: AF017985J, CBRG01D9_2,179662, and CHPDRBAG_1.

Clone DNA58828-1519 has been deposited with ATCC and is assigned ATCC deposit no. 203172.

EXAMPLE 17: Isolation of cDNA clones Encoding Human PRQ141S Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the Incyte database, designated Incyte EST cluster sequence no. 150918. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST 20 databases (e.g., GenBank) and a proprietary EST DNA database (Lifeseq®, Incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, 25 Seattle, Washington). The consensus sequence obtained therefrom is herein designated DNA55720.

In light of the sequence homology between the DNA55720 sequence and an EST sequence contained within the Incyte EST cloneno. 4081476, the Incyte EST clone no. 4081476 was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 27 and is herein designated as DNA58852-1637.

Clone DNA58852-1637 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 148-150 and ending at the stop codon at nucleotide positions 997-999 (Figure 27). The predicted polypeptide precursor is 283 amino acids long (Figure 28). The full-length PR01415 protein shown in Figure 28 has an estimated molecular weight of about 29,191 daltons and a pi of about 4.52. Analysis of the full-length PRO 1415 sequence shown in Figure 28 (SEQ ID N0:50) evidences the presence of the 35 following: a signal peptide from about amino acid 1 to about amino acid 25, a transmembrane domain from about amino acid 94 to about amino acid 118 and potential N-myristolation sites from about amino acid 18 to about amino acid 23, from about amino acid 40 to about amino acid 45, from about amino acid 46 to about amino acid 388 SI, from about amino acid 145 to about amino acid 150, from about amino acid 192 to about amino acid 197, from about amino acid 193 to about amino acid 198, from about amino acid 211 to about amino acid 216, from about amino acid 238 to about amino acid 243 and from about amino acid 242 to about amino acid 247. Clone DNA58852-1637 has been deposited with ATCC on September 22, 1998 and is assigned ATCC deposit no. 203271.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 28 (SEQ ID N0:50), evidenced significant homology between the PR01415 amino acid sequence and the following Dayhoff sequences: HSU66616_1, P_W24017, A38219, CD30JHUMAN, HSU78971_1, P_W22214, NFM_HUMAN, ADH 1_ASPFL, PAU93274 5 and CENB MOUSE.

EXAMPLE 18: Isolation of cDNA clones Encoding Hnman PROI411 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from an Incyte database. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary 15 EST DNA database (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. One or more of the ESTs were derived from a thryroid tissue library. The homology search was performed using the computer program BLAST or BLAST2 (Altsbul etal., Methods in Enzvmologv 266:460-480(19961). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, 20 University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated DNA56013.

In light of the sequence homology between die DNA560I3 sequence and an EST sequence contained within the Incyte EST 1444225, the clone including this EST was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 29 and is herein designated as DNA59212-25 1627.

The full length clone shown in Figure 29 contained a single open reading frame with an apparent translational initiation site at nucleotide positions 184-186 and ending at the stop codon found at nucleotide positions 1504-1506 (Figure 29; SEQ ID NO:51). The predicted polypeptide precursor (Figure 30, SEQ ID NO:52) is 440 amino acids long. The signal peptide is at about amino acids 1-21, and the cell attachment site 30 is at about amino acids 301-303 of SEQ ID NO:52. PRO 1411 has a calculated molecular weight of approximately 42,208 daltons and an estimated pi of approximately 6.36. Clone DNA59212-1627 was deposited with the ATCC on September 9, 1998 and is assigned ATCC deposit no. 203245.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 30 (SEQ ID NO:52), revealed sequence identity 35 between the PRO 1411 amino acid sequence and the following Dayhoff sequences (data from database incorporated herein): MTV023_19, P_R05307, P_W26348, P_P82962, AF000949_1, EBN1JEBV, P_R95107, GRP2_PHAVU, P_R81318, andS74439_l. 389 EXAMPLE 19: Isolation of cDNA clones Encoding Human PRQ1295 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the Incyte database. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. One 5 or more of the ESTs was derived from a thymus tissue library. The homology search was performed using die computer program BLAST or BLAST2 (Altshul et al., Methods in Fn?vmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein 10 designated DNAS6262.

In light of the sequence homology between the DNAS6262 sequence and an EST contained within the Incyte EST 3743334, the clone including this EST was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 31 and is herein designated as DNA59218-1559.

The full length clone shown in Figure 31 contained a single open reading frame with an apparent translational initiation site at nucleotide positions 207-209 and ending at the stop codon found at nucleotide positions 1047-1049 (Figure 31; SEQ ID NO:53). The predicted polypeptide precursor (Figure 32, SEQ ID NO:54) is 280 amino acids long. The signal peptide is at about amino acids 1-18 of SEQ ID NO:54. A targeting signal and N-glycosylation site are also indicated in Figure 54. PR01295 has a calculated molecular 20 weight of approximately 30,163 daltons and an estimated pi of approximately 6.87. Clone DNA59218-1559 was deposited with the ATCC on September 29, 1998 and is assigned ATCC deposit no. 203287.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 32 (SEQ ID NO:54), revealed sequence identity between the PRO1295 amino acid sequence and the following Dayhoff sequences (data incorporated herein): 25 AB011099_l, ILVE_MYCTU, ATTECR_2, AF010496_27, P_R15346, S37191, PER_DROMS, L2MU_ADECC and P_W34238.

EXAMPLE 20: Isolation of cDNA clon^ Encoding Human PRQ1359 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST 30 cluster sequence from an Incyte database. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. One or more of the ESTs was derived from a sigmoid colon tissue library. The homology search was performed using the computer program BLAST or BLAST2 (Altshul etal., Methods in Enzvmologv 266:460-480 (1996^. 35 Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein 390 designated DNAS6263.

In light of the sequence homology between the DNA56263 sequence and the Incyte EST 1931418, the clone including this EST was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 33 and is herein designated as DNA59219-16I3.

The full length clone shown in Figure 33 contained a single open reading frame with an apparent 5 translational initiation site at nucleotide positions 184-186 and ending at the stop codon found at nucleotide positions 1081-1083 (Figure 33; SEQ ID NO:55). The predicted polypeptide precursor (Figure 34, SEQ ID NO:56) is 299 amino acids long. The transmembrane domain is at about amino acids 9-31 of SEQ ID NO:56. N-gylcosylation sites are at about amino acids 64-67 and 115-118ofSEQIDNO:56. PR01359 has a calculated molecular weight of approximately 34,291 daltons and an estimated pi of approximately 9.87. Clone 10 DNA59219-1613 was deposited with the ATCC on September 15, 1998 and is assigned ATCC deposit no. 203220.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 34 (SEQ ID NO:56), revealed sequence identity between the PR01359 amino acid sequence and the following Dayhoff sequences (data incorporated herein): 15 GEM14384, P_R78622, A23699_l, P_R65244, A54898, AF059321_1, RNU55938_1, BTRNAST6_1, P_R75I99 and P_R63216.

EXAMPLE 21: Isolation of cDNA clones Encoding Human PROl 190 The method described in Example 1 above allowed the identification of a single Merck/Washington 20 University EST sequence, EST no. AA339802, which is designated herein as "DNA53943". Based on the DNA53943 sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PROl 190.

PCR primers (forward and reverse) were synthesized: forward PCR primer: (53943.fl) GGGAAACACAGCAGTCATTGCCTGC (SEQ ID NO:59) reverse PCR primer: (53943.rl) GCACACGTAGCCTGTCGCTGGAGC (SEQ ID N0:60) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the DNA53943 sequence which had the following nucleotide sequence: hybridization probe: (53943.pl) CACCCCAAAGCCCAGGTCCGGTACAGCGTCAAACAAGAGTGG(SEQ 30 ID NO:61) In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PROl 190 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from human bone marrow. 35 DNA sequencing of tbe clones isolated as described above gave the full-length DNA sequence for PROl 190 (designated herein as DNA59586-1520 [Figure 35, SEQ ID NO:57]; and the derived protein sequence for PROl 190. 391 The entire coding sequence of PR01190 is shown in Figure 35 (SEQ ID NO:57). Clone DNA59586-1520 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 340-342 and an apparent stop codon at nucleotide positions 3685-3687. The predicted polypeptide precursor is 1115 amino acids long. The full-length PROl 190 protein shown in Figure 36 has an estimated molecular weight of about 121,188 daltons and a pi of about 7.07. Other features of the PR01190 protein include: two 5 transmembrane domains at amino acids 16-30 and 854-879; a cytochrome P450 cystein heme-iron ligand signature at amino acids 1051-1060; an N-6 adenine-specific DNA methylases signature at amino acids 1045-1051; and potential N-glycosylation sites at amino acids 65-68,76-79,98-101,189-192,275-278,518-521,726-729, and 760-763. Clone DNA59586-1520 was deposited with the ATCC on September 29, 1998, and is assigned ATCC deposit no. 203288.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 36 (SEQ ID NO:58), revealed homology between the PR01190 amino acid sequence and the following Dayhoff sequences: AF004840_1, AF004841 1, AF026465_1, HSU72391_1, P_R13144, AX01_HUMAN, GEN13349, 158164, D87212_l, A53449, and D86983 1, and KIAA0230.

EXAMPLE 22: Isolation of cDNA clones Encoding Human PRQ1772 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is herein designated DNA45120. Based on the DNA45120 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained 20 the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PRO1772.

PCR primers (forward and reverse) were synthesized: forward PCR primer (45120.fn 5'-CCTTCACCTGCAGTACACCATGGGC-3' (SEQIDNO:64) reverse PCR primer (45120.rn 5 '-GTCACACACAGCTCTGGCAGCTGAG-3' (SEQ ID NO:65) 25 Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA45120 sequence which had the following nucleotide sequence hybridation probe (4512Q,pl) '-CCAAGTTCAGACACCACATGTACACCAACGTCAGCGGATTGACAAGC-3' (SEQ ID NO:66) RNA for construction of the cDNA libraries was isolated from human bone marrow tissue. 30 DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PRO1772 (designated herein as DNA59817-1703 [Figure 37, SEQ ID NO:62]; and the derived protein sequence for PRO1772.

The entire nucleotide sequence of DNA59817-1703 is shown in Figure 37 (SEQ ID NO:62). Clone DNA59817-1703 contains a single open reading frame with an apparent translational initiation site at nucleotide 35 positions 93-95 and ending at the stop codon at nucleotide positions 1554-1556 (Figure 37). The predicted polypeptide precursor is 487 amino acids long (Figure 38). The full-length PR01772 protein shown in Figure 38 has an estimated molecular weight of about 53,569 daltons and a pi of about 7.68. Analysis of the full-length 392 PR01772 sequence shown in Figure 38 (SEQ ID NO:63) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 36, a transmembrane domain from about amino acid 313 to about amino acid 331, potential N-glycosylation sites from about amino acid 119 to about amino acid 122, from about amino acid 184 to about amino acid 187, from about amino acid 243 to about amino acid 246 and from about amino acid 333 to about amino acid 336, potential N-myristolation sites from about amino acid 41 5 to about amino acid 46, from about amino acid 59 to about amino acid 64, from about amino acid 73 to about amino acid 78, from about amino acid 133 to about amino acid 138, from about amino acid 182 to about amino acid 187, from about amino acid 194 to about amino acid 199, from about amino acid 324 to about amino acid 329, from about amino acid 354 to about amino acid 359, from about amino acid 357 to about amino acid 362, from about amino acid 394 to about amino acid 399, from about amino acid 427 to about amino acid 432 and 10 from about amino acid 472 to about amino acid 477 and a prokaryotic membrane lipoprotein lipid attachment site from about amino acid 136 to about amino acid 146. Clone DNA59817-1703 has been deposited withATCC on November 17, 1998 and is assigned ATCC deposit no. 203470.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 38 (SEQ ID NO:63), evidenced significant IS homology between the PR01772 amino acid sequence and the following Dayhoff sequences: P R30823, MDP1_PIG, MDP1HUMAN, P_R13857, P_R53920, MDPl_MOUSE, P_R30822, JC4222, CELF52C6_2 and MYV027 13.

EXAMPLE 23: Isolation of cDNA clones Encoding Human PRQ1248 20 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the Incyte database, designated Incyte EST cluster sequence no. 7494. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database (Lifeseq®, Incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. The homology search was performed using the computer program BLAST 25 or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated DNA56056.

In light of the sequence homology between the DNA56056 sequence and an EST contained within the 30 Merck EST clone no. AA404441, the Merck EST clone no. AA404441 was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 39 and is herein designated as DNA60278-1530.

Clone DNA60278-1530 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 122-124 and ending at the stop codon at nucleotide positions 671-673 (Figure 39). 35 The predicted polypeptide precursor is 183 amino acids long (Figure 40). The full-length PR01248 protein shown in Figure 40 has an estimated molecular weight of about 20,574 daltons and a pi of about 6.60. Analysis of the full-length PR01248 sequence shown in Figure 40 (SEQ ID NO:68) evidences the presence of the 393 PCT/US99/20I11 following: a signal peptide from abom amino acid 1 to about amino acid 20, a transmembrane domain from about amino acid 90 to about amino acid 112 and potential N-glycosylation sites from about amino acid 21 to about amino acid 24, from about amino acid 38 to about amino acid 41 and from about amino acid 47 to about amino acid 50. Clone DNA60278-1530 has been deposited with ATCC on September 1, 1998 and is assigned ATCC deposit no. 203170.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 40 (SEQ ID NO:68), evidenced significant homology between the PR01248 amino acid sequence and the following Dayhoff sequences: AF026198_5, CELR12C12 5, PN0563, S64541J, PN0564, P R44881 and XLU78189_1.

EXAMPLE 24: Isolation of cDNA clones Encoding Human PRQ1316 The extracellular domain (ECD) which includes the signal sequence, if any, of publicly available databases known to contain secreted sequences were used to search various publicly available EST (Expressed Sequenced Tag) databases (GenBank, Merck/Wash. U). The search was performed using the computer program BLAST or BLAST2 [Altschul et al., Methods in Enzymology 266:460-480 (1996)] as a comparison of the ECD 15 protein sequences to a 6 frame translation of the EST sequences. Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not did not encode known proteins were clustered and assembled into consensus DNA sequences with the program "phrap" (Phil Green, University of Washington, Seattle, WA).

The above search resulted in the identification of the EST, designated W55979 which showed homology with the secreted protein Dkk-1. The clone corresponding to EST W55979 (clone NbHH19W) was purchased 20 firom Merck/Washington University and the cDNA insert was obtained and sequenced in its entirety.

The nucleic acid sequence corresponding to the full length PR01316 (designated DNA60608-1577) encoded by the purchased clone, is shown in Figure 41 (SEQ ID NO:69). DNA60608-1577 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 211-213, and a stop codon at nucleotide positions 988-990 (Figure 42; SEQ ID N0:70). The predicted polypeptide precursor is 259 amino 25 acids long. Additional regions of significant interest include the nucleotide residues encoding the signal peptide (211-283), an N-glycosylation site (364-366), and the Zn(2)-Cys(6) binuclear cluster domain (505-655). Clone DNA60608-1577 has been deposited with ATCC and is assigned ATCC deposit no. 203126. The full-length PR01316 protein shown in Figure 42 has an estimated molecular weight of about 28,447 daltons and a pi of about 9.48.

Based on a BLAST and FastA sequence alignment analysis (using the ALIGN computer program) of the full-length sequence, PR01316 shows significant amino acid sequence identity to the dickkopf family of proteins. Additionally, DNA60608 has shown homology to AF030433_1, LFE4_CHICK, COL RABIT, YQI6_CAEEL, ITB6_HUMAN, CONO_LYMST, S41033, D63483_l, D86864_l and AB001978_1.

EXAMPLE 25: Isolation of cDNA clones Encoding Human PROl 197 An initial DNA sequence, referred to herein as DNA56267, was identified using a yeast screen, in a human SK-Lu-1 adenocarcinoma cDNA library that preferentially represents the 5' ends of the primary cDNA 394 clones. ONAS6267 was used to synthesize oligonucleotides for use as probes to isolate a clone of the full-length coding sequence for PROl 197 from a human breast carcinoma cDNA library.

SEQ ID NO:73: 5'AATTC ATGGCAAAT ATTTCCCTTCCC3' (forward); SEQ ID NO:74: 5'TGGTAAACTGGCCCAAACTCGG3' (reverse); and SEQ ID NO:75:5 'TTAAAGTCATCCGTCCTTGGCTCAGGATTTGGAGAGCTTGCACCACCAAA3' (probe).

The full length DNA60611-1524 clone shown in Figure 43 contained a single open reading frame with an apparent translational initiation site at nucleotide positions 311-313 and ending at the stop codon found at nucleotide positions 1400-1402 (Figure 43; SEQ ID NO:71). The predicted polypeptide precursor (Figure 44, SEQ ID NO:72) is 363 amino acids long. The signal peptide is at about amino acids 1-24 of SEQ ID NO:72. 10 PROl 197 has a calculated molecular weight of approximately 38,825 daltons and an estimated pi of approximately 9.88. Clone DNA60611-1524 has been deposited with ATCC and is assigned ATCC deposit no. 203175.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 44 (SEQ ID NO:72), revealed sequence identity 15 between the PROl 197 amino acid sequence and the following Dayhoff sequences (information from database incorporated herein): Y144_HUMAN, 147141 (a gastric mucin, mucins are described in Ann. NY Acad. Sci.. 140(2):804-834 (1967), AMYH_YEAST, CELK06A9_3, CELZK783_1, HKR1YEAST, AB003521_1, D8789S_1, S61993 and YM96_YEAST.

EXAMPLE 26: Isolation of cDNA clones Encoding Human PRQ1293 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the Incyte database, designated Incyte EST cluster sequence no. 115204. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database (Lifeseq®, Incyte Pharmaceuticals, Palo Alto, 25 CA) to identify existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated DNA56522. 30 In light of the sequence homology between the DNA56522 sequence and an EST contained within the Incyte EST clone no. 2966119, the Incyte EST clone no. 2966119 was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 45 and is herein designated as DNA60618-1557.

Clone DNA60618-1557 contains a single open reading frame with an apparent translational initiation 35 site at nucleotide positions 37-39 and ending at the stop codon at nucleotide positions 1060-1062 (Figure 45). The predicted polypeptide precursor is 341 amino acids long (Figure 46). The full-length PR01293 protein shown in Figure 46 has an estimated molecular weight of about 38,070 daltons and a pi of about 6.88. Analysis 395 of the full-length PR01293 sequence shown in Figure 46 (SEQ ID NO:77) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 19, a transmembrane domain from about amino acid 237 to about amino acid 262, a potential N-glycosylation site from about amino acid 205 to about amino acid 208, a cell attachment sequence from about amino acid 151 to about amino acid 152 and an amino acid sequence block having homology to coproporphyrinogen III oxidase proteins from about amino acid 115 5 to about amino acid 140. Clone DNA60618-1557 has been deposited with ATCC on September 29, 1998 and is assigned ATCC deposit no. 203292.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 46 (SEQ ID NO:77), evidenced significant homology between the PR01293 amino acid sequence and the following Dayhoff sequences: HSVCD54_1, 10 A33HUMAN, AF009220_1, HSU82279_1, AF004230_1, P_R13272, AF004231_1, AF043644_1, S44125 and HSIGGHC85_1.

EXAMPT.F. 37: Isolation of cDNA clones Encoding Human PRO 1380 A cDNA sequence isolated in the amylase screen described in Example 2 above is herein designated IS DNA45776. Based on the DNA45776 sequence, oligonucleotide probes were generated and used to screen a human retina library prepared as described in paragraph 1 of Example 2 above. The cloning vector was pRK5B (pRK5B is a precursor of pRK5D that does not contain tbe Sfil site; see. Holmes et al., Science. 253:1278-1280 (1991)), and the cDNA size cut was less than 2800 bp.

PCR primers (forward and reverse) were synthesized: forward PCR nrimer (45776.fn 5'-TTTTGCGGTCACCATTGTCTGC-3' (SEQ ID N0:80) and reverse PCR nrimer (45776.rD 5'-CGTAGGTGACACAGAAGCCCAGG-3' (SEQ ID NO:81). Additionally, a synthetic oligonucleotide hybridization probe was constructed from the DNA45776 sequence which had the following nucleotide sequence: hybridization probe (45776.pd 25 5'-TACGGCATGACCGGCTCCTTTCCTATGAGGAACTCCCAGGCACTGATAT-3' (SEQ ID NO:82).

In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01380 gene using the probe oligonucleotide and one of the PCR primers.

A full length clone was identified that contained a single open reading frame with an apparent 30 translational initiation site at nucleotide positions 36-38, and a stop signal at nucleotide positions 1461-1463 (Figure 47; SEQ ID NO:78). The predicted polypeptide precursor is 470 amino acids long has a calculated molecular weight of approximately 51,715 daltons and an estimated pi of approximately 7.86. Additional features include transmembrane domains at about amino acids 50-74,105-127,135-153,163-183,228-252,305-330, and 448-472; potential N-glycosylation sites at about amino acids 14-17 and 84-87; and a dihydrofoiate 35 reductase signature at about amino acids 60-68.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 48 (SEQ ID NO .79), evidenced homology 396 between the PR01380 amino acid sequence and the following Dayhoff sequences: HSU81375 1, CEZK809_6, CEK02E11_1, AF034102 1, JC4196, CEF36H2_2, P_R92315, YAC2YEAST, F1707_13,andCEF44D12_3.

Clone DNA60740-1615 was deposited with the ATCC on November 3,1998, and is assigned ATCC deposit no. 203456.

EXAMPI.F- 28: Isolation of cDNA clones Encoding Hnman PRO 1265 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the LIFESEQ® database, designated EST Cluster No. 86995. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, CA) to 10 identify existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). One or more of the ESTs used in the assembly was derived from acDNA library prepared 15 from RNA isolated from inflamed human adenoid tissue. The consensus sequence obtained therefrom is herein designated DNA55717.

In light of the sequence homology between the DNA55717 sequence and an EST sequence contained within Incyte EST no. 20965, EST clone no. 20965 was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 49 and is herein designated as DNA60764. 20 The Ml length clone shown in Figure 49 contained a single open reading frame with an apparent translational initiation site at nucleotide positions 79-81 and ending at the stop codon found at nucleotide positions 1780-1782 (Figure 49; SEQ ID NO:83). The predicted polypeptide precursor (Figure 50, SEQ ID NO:84) is 567 amino acids long. PR01265 has a calculated molecular weight of approximately 62,881 daltons and an estimated pi of approximately 8.97. Additional features include a signal peptide sequence at about amino acids 25 1-21; potential N-glycosylation sites at about amino acids 54-57, 134-137,220-223, and 559-562; and a region having amino acid sequence identify with D-amino acid oxidase proteins at about amino acids 61-80.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 50 (SEQ ID NO:84), revealed significant sequence identity between the PR01265 amino acid sequence and Dayhoff sequence no. MMU70429_1. 30 Sequence homology was also found to exist between the full-length sequence shown in Figure 50 (SEQ ID NO:84) and the following additional Dayhoff sequences: BC542A_1, E69899, S76290, MTV014_14, AOFB_HUMAN, ZMJ002204_1, S45812_l, DBRNAPD_1, and CRTl_SOYBN.

Clone DNA60764-1533 was deposited with the ATCC on November 10,1998, and is assigned ATCC deposit no. 203452.

EXAMPLE 29: Isolation of cDNA clones Encoding Human PRQ1250 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST 397 cluster sequence from the Incyte database, designated Incyte EST cluster sequence no. S6523. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database (Lifeseq®, Incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a 5 BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated DNAS6103.

In light of the sequence homology between the DNA56103 sequence and an EST sequence contained within the Incyte EST clone no. 3371784, the Incyte EST clone no. 3371784 was purchased and the cDNA insert 10 was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 51 and is herein designated as DNA60775-1532.

Clone DNA60775-1532 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 74-76 and ending at the stop codon at nucleotide positions 2291-2293 (Figure 51). The predicted polypeptide precursor is 739 amino acids long (Figure 52). The full-length PR01250 protein 15 shown in Figure 52 has an estimated molecular weight of about 82,263 daltons and a pi of about 7.55. Analysis of the full-length PR01250 sequence shown in Figure 52 (SEQ ID NO:86) evidences the presence of the following: a type II transmembrane domain from about amino acid 61 to about amino acid 80, a putative AMP-binding domain signature sequence from about amino acid 314 to about amino acid 325, and potential N-glycosylation sites from about amino acid 102 to about amino acid 105, from about amino acid 588 to about 20 amino acid 591 and from about amino acid 619 to about amino acid 622. Clone DNA60775-1532 has been deposited with ATCC on September 1, 1998 and is assigned ATCC deposit no. 203173.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 52 (SEQ ID NO:86), evidenced significant homology between the PRO1250 amino acid sequence and die following Dayhoff sequences: LCFB HUMAN, 25 S56508_l, BNAMPBP2_1, BNACS7_1, CELT08BI_6, CELC46F4_2, AF008206_6, CELR07C3_11, LMU70253_2 and AF008206_7.

EXAMPLE 30: Isolation of cDNA clones Encoding Human PRQ1475 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described 30 in Example 1 above. This consensus sequence is herein designated DNA45639. Based on the DNA45639 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01475.

PCR primers (forward and reverse) were synthesized: forward PCR primer (45639.fl) 51 -GATGGCAAAACGTGTGTTTGACACG-3' (SEQIDNO:89) forward PCR primer (45639.f2) 5'-CCTCAACCAGGCCACGGGCCAC-3' (SEQIDNO:90) reverse PCR primer (45639.rl) 5'-CCCAGGCAGAGATGCAGTACAGGC-3' (SEQ ID NO:91) 398 reverse PCR primer (4S639.r2~i 5-CCTCCAGTAGGTGGATGGATTGGCTC-3' {SEQ ID NO:92) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA45639 sequence which had the following nucleotide sequence hybridization probe f45639.pl) 51 -CTCACCTCATGAGGATGAGGCCATGGTGCTATTCCTCAACATGGTAG-3' (SEQ ID NO:93) 5 In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01475 gene using die probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from human fetal brain tissue.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for 10 PR01475 (designated herein as DNA61185-1646 [Figure 53, SEQ ID NO:87]; and the derived protein sequence for PRO1475.

The entire nucleotide sequence of DNA61185-1646 is shown in Figure 53 (SEQ ID NO:87). Clone DNA61185-1646 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 130-132 and ending at the stop codon at nucleotide positions 2110-2112 (Figure 53). The predicted 15 polypeptide precursor is 660 amino acids long (Figure 54). The full-length PR01475 protein shown in Figure 54 has an estimated molecular weight of about 75,220 daltons and a pi of about 6.76. Analysis of die full-length PRO1475 sequence shown in Figure 54 (SEQ ID NO:88) evidences the presence of the following: a transmembrane domain from about amino acid 38 to about amino acid 55 and a homologous region to mouse GNTl from about amino acid 229 to about amino acid 660. Clone DNA61185-1646 has been deposited with 20 ATCC on November 17, 1998 and is assigned ATCC deposit no. 203464.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 54 (SEQ ID NO:88), evidenced significant homology between the PR01475 amino acid sequence and the following Dayhoff sequences: GNT1MOUSE, CGU65792_1, CGU65791_1, P_R24781, CELF48E3_1, G786_HUMAN, P_W06547, GNT1_CAEEL, 25 219 HUMAN and EF07_MOUSE.

EXAMPLE 31: Isolation of cDNA clones Encoding Human PRQ1377 An initial DNA sequence, referred to herein as DNA46892, was identified using a yeast screen, in a human umbilical vein endothelial cell cDNA library that preferentially represents the 5' ends of the primary 30 cDNA clones. Based on the DNA46892 sequence, the following oligonucleotides were synthesized for use as probes to isolate a clone of the full-length coding sequence for PR01377 from a human fetal kidney cDNA libraiy: GTTGTGGGTGAATAAAGGAGGGCAG (SEQ ID NO:96), CTGTGCTCATGTTCATGGACAACTG (SEQ ID NO:97), and GGATGATTTCATCTCCATTAGCCTGCTGTCTCTGGCTATGTTGGTGGGAT(SEQ ID NO:98).

The full length DNA61608-1606 clone shown in Figure 55 contained a single open reading frame with an apparent translational initiation site at nucleotide positions 149-151 and ending at the stop codon found at nucleotide positions 1070-1072 (Figure 55; SEQ ID NO:94). The predicted polypeptide precursor (Figure 56, 399 SEQ ID NO:95) is 307 amino acids long. PR01377 has a calculated molecular weight of approximately 32,231 daltons and an estimated pi of approximately 6.62. Additional features include: a signal peptide at about amino acids 1-18; potential N-glycosylation sites at about amino acids 29-32 and 241-244, and transmembrane domains at about amino acids 37-56, 106-122, 211-230, 240-260, and 288-304.

An analysis of the Dayhoff database (version 3S.4S SwissProt 35), using a WU-BLAST2 sequence 5 alignment analysis of the full-length sequence shown in Figure 56 (SEQ ID NO:95), revealed some homology between the PR01377 amino acid sequence and the following Dayhoff sequences: CET01D3 6, CET28F34, CEF26D10_3, S66962, ATX2_YEAST, CEHI3N06_8, S49959, YIC3_YEAST, G02273, and P_W35557.

Clone DNA61608-1606 has been deposited with ATCC and is assigned ATCC deposit no. 203239.

EXAMPLE 32: Isolation of cDNA clones Encoding Human PRQ1326 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from tbe LIFESEQ8 database, designated Incyte Cluster No. 59366, also referred herein as "DNA10295". This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database 15 (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). One or more of the ESTs was derived from RNA 20 isolated from tumor tissue removed from the penis of a male with squamous ceil carcinoma. The consensus sequence obtained therefrom is herein designated DNA56257.

In light of the sequence homology between the DNA56257 sequence and an EST sequence contained within Incyte EST no. 1450878, the EST clone 1450878 was purchased and the cDNA insert was obtained and sequenced in its entirely. The sequence of this cDNA insert is shown in Figure 57 and is herein designated as 25 "DNA62808-1582".

The full length clone shown in Figure 57 contained a single open reading frame with an apparent translational initiation site at nucleotide positions 112 to 114 and ending at the stop codon found at nucleotide positions 1315 to 1317 (Figure 57; SEQ ID NO:99). The predicted polypeptide precursor (Figure 58, SEQ ID N0:100) is 401 amino acids long. Other features of the PR01326 protein include: a signal sequence at about 30 amino acids 1-29; a ribosomal protein S3Ae homologous region at about amino acids 129-166; and potential N-glycosylation sites at about amino acids 109-112,144-147 and 398-401. PR01326 has a calculated molecular weight of approximately 45,333 daltons and an estimated pi of approximately 4.95. Clone DNA62808-1582 was deposited with the ATCC on October 20, 1998 and is assigned ATCC deposit no. 203358.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence 35 alignment analysis of the full-length sequence shown in Figure 58 (SEQ ID NO: 100), revealed some homology between the PR01326 amino acid sequence and the following Dayhoff sequences: AC004013 1, HROMHCEMB J ,CEF47A4_2, A45592, MYSPJHUMAN.NFU43192_l ,ONGMBWMZ_l, CELC25A11_2, 400 CELC25A11_1, and A42184.

EXAMPLE 33: Isolation of cDNA clones Encoding Human PRO 1249 Use of die signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the Incyte database, designated Incyte EST cluster no. 122605. This EST cluster sequence 5 was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database (Lifeseq®, Incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and 10 assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated DNA56060.

In light of the sequence homology between the DNA56060 sequence and an EST sequence contained within the Incyte EST clone no. 2630770, the Incyte EST clone no. 2630770 was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 59 and is herein designated 15 as DNA62809-1531.

Clone DNA62809-1531 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 3-5 and ending at the stop codon at nucleotide positions 3270-3272 (Figure 59). The predicted polypeptide precursor is 1089 amino acids long (Figure 60). The full-length PR01249 protein shown in Figure 60 has an estimated molecular weight of about 118,699 daltons and a pi of about 8.49. Analysis of 20 the full-length PR01249 sequence shown in Figure 60 (SEQ ID NO: 102) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 16, transmembrane domains from about amino acid position 317 to about amino acid position 341, from about amino acid position 451 to about amino acid position 470, from about amino acid position 481 to about amino acid position 500, from about amino acid position 510 to about amino acid position 527, from about amino acid position 538 to about amino acid position 25 555, from about amino acid position 831 to about amino acid position 850, from about amino acid position 1016 to about amino acid position 1034 and from about amino acid position 1052 to about amino acid position 1070, a leucine zipper pattern sequence from about amino acid 843 to about amino acid 864 and potential N-glycosyiations sites from about amino acid 37 to about amino acid 40 and from about amino acid 268 to about amino acid 271. Clone DNA62809-1531 has been deposited with ATCC on September 9,1998 and is assigned 30 ATCC deposit no. 203237.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 60 (SEQ ID NO: 102), evidenced significant homology between the PR01249 amino acid sequence and the following Dayhoff sequences: AC004472_3, AB004539J7, S64782, S62432, YJG2YEAST, CELC27A12_8, YKQ5 YEAST, AB009505_3, SPBC24E9_8 35 and AF060218 4. 401 EXAMPLE 34: Isolation of cDNA clones Encoding Human PRQ1315 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is herein designated DNA35925. Based on the DNA35925 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for 5 PR01315.

PCR primers (forward and reverse) were synthesized: forward PCR primer (35925.fn 5'-CGCTGCTGCTGTTGCTCCTGG-3' (SEQ ID N0:105) forward PCR primer (35925.f2) 5'-CAGTGTGCCAGGACTTTG-3' (SEQ ID NO: 106) forward PCR primer (35925.f31 5' -AGTCGCAGGCAGCGTTGG-3' (SEQ ID NO: 107) reverse PCR primer (35925.rn 5'-CTCCTCCGAGTCTGTGTGCTCCTGC-3' (SEQ ID NO: 108) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA35925 sequence which had the following nucleotide sequence hvhridiration nrobe (35925.pi) '-GGACGGGCAGTTCCCTGTGTCTCTGGTGGTTTGCCTAAACCTGCAAACATC-3' (SEQ ID NO: 109) 15 In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer par identified above. A positive library was then used to isolate clones encoding the PR01315 gene using the probe oligonucleotide and one of die PCR primers. RNA for construction of the cDNA libraries was isolated from human retina tissue.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for 20 PR01315 (designated herein as DNA62815-1576 [Figure 61, SEQ ID NO: 103]; and the derived protein sequence for PR01315.

The entire nucleotide sequence of DNA62815-I576 is shown in Figure 61 (SEQ ID NO: 103). Clone DNA62815-1576 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 121-123 and ending at the stop codon at nucleotide positions 1447-1449 (Figure 61). The predicted 25 polypeptide precursor is 442 amino acids long (Figure 62). The full-length PR01315 protein shown in Figure 62 has an estimated molecular weight of about 49,932 daltons and a pi of about 4.55. Analysis of the full-length PR01315 sequence shown in Figure 62 (SEQ ID NO: 104) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 28, a transmembrane domain from about amino acid 140 to about amino acid 163 and potential N-glycosylation sites from about amino acid 71 to about amino acid 74, 30 from about amino acid 80 to about amino acid 83, from about amino acid 89 to about amino acid 92, from about amino acid 204 to about amino acid 207 and from about amino acid 423 to about amino acid 426. Clone DNA62815-1576 has been deposited with ATCC on September 9, 1998 and is assigned ATCC deposit no. 203247.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence 35 alignment analysis of the full-length sequence shown in Figure 62 (SEQ ID NO: 104), evidenced significant homology between the PR01315 amino acid sequence and the following Dayhoff sequences: MMU53696_1, NVY08571_2, B64560, STMSLPE_1, P_R80508, P_W19258, A55817, GEN14043, AE000768_7 and 402 PCT/US99/201H RNMUC ASGP5_lpSMC.

FX A MPT.F 3S- Isolation of cDNA clones Encoding Human PRQ1599 Incyte EST no. 1491360 was identified as a sequence of interest using the techniques described in Example 1 above having a BLAST score of 70 or greater that does not encode a known protein. The nucleotide 5 sequence of EST no. 1491360 and its complementary sequence is designated herein "DNA37192". Based on the DNA37192 sequence, oligonucleotides were synthesized: I) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01599.

PCR primers (forward and reverse) were synthesized: forward PCR primer: GACGTCTGCAACAGCTCCTGGAAG (37192.fl; SEQ ID NO:112) reverse PCR primer: CGAGAAGGAAACGAGGCCGTGAG (37192.rl; SEQ ID NO:113) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA37192 sequence which had the following nucleotide sequence: hybridization probe: TGACACTTACCATGCTCTGCACCCGCAGTGGGGACAGCCACAGA (SEQ ID 15 NO: 114).

In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01S99 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from human fetal liver tissue. 20 DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PR01S99 (designated herein as DNA6284S-1684 [Figure 63, SEQ ID N0:110]; and the derived protein sequence for PR01599.

TheentirecodingsequenceofPR01599isshowninFigure63(SEQIDNO:HO). Clone DNA62845-1684 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 25 69-71 and an apparent stop codon at nucleotide positions 918-920. The predicted polypeptide precursor is 283 amino acids long. The full-length PR01S99 protein shown in Figure 64 has an estimated molecular weight of about 30,350 daltons and a pi of about 9.66. Additional features of PRO1599 include: a signal peptide at about amino acids 1-30; potential N-glycosylation sites at about amino acids 129-132 and 189-192; a potential cAMP and cGMP-dependent protein kinase phosphorylation site at about amino acids 263-266; potential N-30 myristoylation sites at about amino acids 28-33,55-60,174-179, and236-241; a potential amidation site at about amino acids 144-147; and a serine protease, trypsin family, histidine active site at about amino acids 70-75.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 64 (SEQ ID NO:111), revealed significant homology between the PR01599 amino acid sequence and the following Dayhoff sequence: CFADPIG. 35 Homology was also found between the PR01599 amino acids sequence and the following additional Dayhoff sequences. CFADJHUMAN; PR05421; PR55757; PR05772; GRAMHUMAN; MUSLMETJ; P_P80335; P_R55758; A42048_l; and P_W05383. 403 Clone DNA6284S-1684 was deposited with the ATCC on October 20, 1998 and is assigned ATCC deposit no. 203361.

EXAMPLE 36: Isolation of cDNA clones Encoding Human PRQ1430 A DNA sequence designated herein as DNA49433 was obtained as described in Example 1 above.

Merck EST no. T49469, which was identified as being an EST of interest from the assembly, was purchased and the cDNA insert was obtained and sequenced in entirety.

DNA sequencing of the clone as described above gave the full-length DNA sequence for PR01430, which is designated herein as "DNA64842-1632" (SEQ ID NO:115), and the derived protein sequence for PRO1430 (SEQ ID NO: 116). Clone DNA64842-1632 contains a single open reading frame with an apparent 10 translational initiation site at nucleotide positions 82-84, and an apparent stop codon at nucleotide positions 1075-1077. The full-length PRO1430 protein shown in Figure 66 has an estimated molecular weight of about 35,932 daltons and a pi of about 8.45. The predicted polypeptide precursor is 331 amino acids long. Additional features include a signal peptide at about amino acids 1-17; a potential N-glycosylation site at about amino acids 171-174, and regions of homology with short chain alcohol dehydrogenase family proteins at about amino acids 29-51, 15 116-126, 180-217, and 222-230.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 66 (SEQ ID NO: 116), revealed significant homology between the PR01430 amino acid sequence and Dayhoff sequence no. P_W03198. Homology was also found between the PR01430 amino acid sequence and the following Dayhoff sequences: MTV030_10, 20 MTV037_2, A40116_l, S42651, CEC15H11_6, SPCC736_13, SCU43704_1, S19842, OXIR_STRAT, and OXIRSTRLI.

Clone DNA64842-1632 has been deposited with ATCC and is assigned ATCC deposit no. 203278.

EXAMPLE 37: Isolation of cDNA clones Encoding Hitman PRQ1374 25 A consensus DNA sequence encoding PR01374 was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is designated herein "DNA47357". Based on the DN A47357 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01374.

PCR primers (forward and reverse) were synthesized: forward PCR primer 5' CGGGACAGGAGACCCAGAAAGGG3' (SEQ ID NO:I19) and; reverse PCR primer 5'GGCCAAGTGATCCAAGGCATCTTC3' (SEQ ID N0:120).

Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA47357 sequence which had the following nucleotide sequence: hvbridizationprobe 5'CTGCGGGACCTGACTAGATTCTACGACAAGGTACTTTCTTTGCATGGGG5' (SEQ ID NO: 121).

In order to screen several libraries for a source of a full-length clone, DNA from the libraries was 404 PCT/US99/20I11 screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PRO1374 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from a human adenocarcinoma cell line.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PR01374 and the derived protein sequence for PR01374.

The entire coding sequence of PR01374 is shown in Figure 67 (SEQ ID NO: 117). Clone DNA64849- 1604 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 20-22 and an apparent stop codon at nucleotide positions 1653-1655 of SEQ ID NO: 117. The predicted polypeptide precursor is 544 amino acids long. The approximate locations of die signal peptide, N-glycosylation sites, leucine zipper patterns, and ribonucleotide reductase small subunit signature are indicated in Figure 68. 10 Clone DNA64849-1604 has been deposited with the ATCC and is assigned ATCC deposit no. 203468. The full-length PR01374 protein shown in Figure 68 has an estimated molecular weight of about 61,126 daltons and a pi of about 6.4.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 68 (SEQ ID NO: 118), revealed sequence identity 15 between the PR01374 amino acid sequence and the following Dayhoff sequences: CEF35G2_4, P_W37046, S44204, CET28D61, CET20B3_6, CELC14E23, CUAL_CHICK, ATM7J2_3, S74997andHIVH5994R8_l.

EXAMPLE 38: Isolation of cDNA clones Encoding Human PRQ1311 A cDNA sequence isolated in the amylase screen described in Example 2 above is herein designated 20 DNA37721. The DNA37721 sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and proprietary EST DNA databases (LIFESEQ™, Incyte Pharmaceuticals, Palo Alto, CA; Genentech, South San Franscisco, CA) to identify existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul etal., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or 25 in some cases 90) or greater that did not encode known proteins were clustered and assembled into consensus DNA sequences with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated "DNA48616". Based on the DNA48616 sequence, oligonucleotide probes were generated and used to screen a human aortic endothelial cell library prepared as described in paragraph 1 of Example 2 above. The cloning vector was pRK5B (pRKSB is a precursor of pRK5D 30 that does not contain the Sfil site; see, Holmes et al., Science. 253:1278-1280 (1991)), and the cDNA size cut was less than 2800 bp.

PCR primers (forward and reverse) were synthesized: forward PCR primer f48616.fl1 5'-ATCATCTATTCCACCGTGTTCTGGC-3' (SEQ ID NO: 124) reverse PCR primer (48616.rU 5' -G AC AG AGTGCTCC ATG ATG ATGTCC-3' (SEQ ID NO: 125) 35 Additionally, a synthetic oligonucleotide hybridization probe was constructed from the DNA48616 sequence which had the following nucleotide sequence: hybridization probe (48616.pl> 405 '-CCTGTCTGTGGGCATCTATGCAGAGGTTGAGCGGCAGAAATATAAAACCC-3' (SEQ ID NO:126) In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01311 gene using the probe oligonucleotide and one of the PCR primers.

A full length clone was identified that contained a single open reading frame with an apparent 5 translational initiation site at nucleotide positions 195-197, and a stop signal at nucleotide positions 1077-1079 (Figure 69; SEQ ID NO: 122). The predicted polypeptide precursor is 294 amino acids long has a calculated molecular weight of approximately 33,211 daltons and an estimated pi of approximately 5.35 Additional features include: a signal sequence at about amino acids 1-44; possible transmembrane domains at about amino acids 22-42, 57-85, 94-116, and 230-257; potential N-glycosylation sites at about amino acids 118-121, 1899-192, and 10 230-233; potential tyrosine kinase phosphorylation sites at about amino acids 3-11 and 129-136; potential N-myristoylation sites at about amino acids 80-85, 109-114, 180-185, 218-223, 248-253, 276-281, 285-290, and 287-292; and a cell attachment sequence at about amino acids 3-5.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 70 (SEQ ID NO: 123), evidenced some homology 15 between the PR01311 amino acid sequence and the following Dayhoff sequences: AF065389 1, AF053455 1, CD63 HUMAN, A15_HUMAN, AF043906_1, C151_HUMAN, AF053453_1, AF054838_1, P_R91446, and CD82_HUM AN.

Clone DNA64863-1573 was deposited with the ATCC on September 9, 1998, and is assigned ATCC deposit no. 203251.

EXAMPLE 39: Isolation of cDNA clones Encoding Human PRQ1357 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the Incyte database, designated Incyte EST cluster sequence no. 69537. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST 25 databases (e.g., GenBank) and a proprietary EST DNA database (Lifeseq®, Incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al.. Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, 30 Seattle, Washington). The consensus sequence obtained therefrom is herein designated DNA56034.

In light of the sequence homology between the DNA56034 sequence and an EST sequence contained within the incyte EST clone no. 936239, the Incyte EST clone no. 936239 was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 71 and is herein designated as DNA64881-16G2.

Clone DNA64881-1602 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 74-76 and ending at the stop codon at nucleotide positions 1526-1528 (Figure 71). The predicted polypeptide precursor is 484 amino acids long (Figure 72). The full-length PR01357 protein 406 shown in Figure 72 has an estimated molecular weight of about 52,468 daitons and a pi of about 7.14. Analysis of the full-length PR01357 sequence shown in Figure 72 (SEQ ID NO: 128) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 21, potential N-glycosylation sites from about amino acid 48 to about amino acid 51, from about amino acid 264 to about amino acid 267 and from about amino acid 401 to about amino acid 404, a glycosaminoglycan attachment site from about amino acid 412 to 5 about amino acid 415 and an amino acid sequence block having homology to the LBP/BPI/CETP family of proteins from about amino acid 407 to about amino acid 457. Clone DNA64881-1602 has been deposited with ATCC on September 9, 1998 and is assigned ATCC deposit no. 203240.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 72 (SEQ ID NO: 128), evidenced significant 10 homology between the PRO1357 amino acid sequence and the following Dayhoff sequences: MMU46068_1, S17447, MMU1_1, BPI RABIT, P_W16808, P_R21844, PSP_MOUSE, HSLBPEX1J and BTU79413_1.

EXAMPLE 40: Isolation of cDNA clones Encoding Human PRQ1244 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST IS cluster sequence from the LIFESEQ* database, designated cluster no. 7874. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA databases (LIFESEQ9, Incyte Pharmaceuticals, Palo Alto, CA; Genentech, South San Francisco, CA) to identify existing homologies. One or more of the ESTs was derived from a library constructed from tissue of the corpus cavernosum. The homology search was performed using 20 the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated "DNA56011".

In light of the sequence homology between the DNA56011 sequence and an EST sequence contained within Incyte EST No. 3202349, the EST clone no. 3202349 was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 73 (SEQ ID NO: 129) and is herein designated "DNA64883-1526".

The full length clone shown in Figure 73 contained a single open reading frame with an apparent 30 translational initiation site at nucleotide positions 9-11 and ending at the stop codon found at nucleotide positions 1014-1016 (Figure 73; SEQ ID NO:129). The predicted polypeptide precursor (Figure 74, SEQ ID N0:130) is 335 amino acids long. PR01244 has a calculated molecular weight of approximately 38,037 daltons and an estimated pi of approximately 9.87. Other features include a signal peptide at about amino acids 1-29; transmembrane domains at about amino acids 183-205, 217-237, 271-287, and 301-321; potential N-35 glycosylation sites at about amino acids 71-74, and 215-218; and a cell attachment sequence at about amino acids 150-152.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence 407 alignment analysis of the full-length sequence shown in Figure 74 (SEQ ID NO: 130), revealed homology between the PR01244 amino acid sequence and the following Dayhoff sequences: AF008554_1, P 485334, G02297, HUMN33S111,HUMN33S10_1,Y013_CAEEL,GEN 13255, S49758.E70107, and ERP5_MEDSA.

Clone DNA64883-1526 was deposited with the ATCC on September 9, 1998, and is assigned ATCC deposit no. 203253.

EXAMPLE 41: Isolation of cDNA clones Encoding Human PRQ1246 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the Incyte database, designated Incyte EST cluster sequence no. 56853. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST 10 databases (e.g., GenBank) and a proprietary EST DNA database (Lifeseq®, Incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al.. Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, 15 Seattle, Washington). The consensus sequence obtained therefrom is herein designated DNA56021.

In light of the sequence homology between the DNA56021 sequence and an EST sequence contained within the Incyte EST clone no. 2481345, the Incyte EST clone no. 2481345 was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 75 and is herein designated as DNA64885-1529.

Clone DNA64885-1529 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 119-121 and ending at the stop codon at nucleotide positions 1727-1729 (Figure 75). The predicted polypeptide precursor is 536 amino acids long (Figure 76). The full-length PRO1246 protein shown in Figure 76 has an estimated molecular weight of about 61,450 daltons and a pi of about 9.17. Analysis of the hill-length PRO1246 sequence shown in Figure 76 (SEQ ID NO: 132) evidences the presence of the 25 following: a signal peptide from about amino acid 1 to about amino acid 15, potential N-glycosylation sites from about amino acid 108 to about amino acid 111, from about amino acid 166 to about amino acid 169, from about amino acid 193 to about amino acid 196, from about amino acid 262 to about amino acid 265, from about amino acid 375 to about amino acid 378, from about amino acid 413 to about amino acid 416 and from about amino acid 498 to about amino acid 501 and amino acid sequence blocks having homology to sulfatase proteins from 30 about amino acid 286 to about amino acid 315, from about amino acid 359 to about amino acid 369 and from about amino acid 78 to about amino acid 97. Clone DNA64885-1529 has been deposited with ATCC on November 3, 1998 and is assigned ATCC deposit no. 203457.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 76 (SEQ ID NO: 132), evidenced significant 35 homology between the PR01246 amino acid sequence and the following Dayhoff sequences: PR51355, CELK09C41, BCU44852_1, IDS_HUMAN, G65169, E64903, ARSA HUMAN, GL6SJHUMAN, HSARSF 1 and GEN12648. 408 EXAMPLE 42: Isolation of cDNA clones Encoding Human PRO 1356 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the Incyte database, designated Incyte EST cluster sequence no. 44725. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database (Lifeseq®, Incyte Pharmaceuticals, Palo Alto, 5 CA) to identify existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated DNA56023. 10 In light of the sequence homology between the DNA56023 sequence and an EST sequence contained within the Incyte EST clone no. 4071746, the Incyte EST clone no. 4071746 was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 77 and is herein designated as DNA64886-1601.

Clone DNA64886-1601 contains a single open reading frame with an apparent translational initiation 15 site at nucleotide positions 122-124 and ending at the stop codon at nucleotide positions 812-814 (Figure 77). The predicted polypeptide precursor is 230 amino acids long (Figure 78). The full-length PR01356 protein shown in Figure 78 has an estimated molecular weight of about 24,549 daltons and apl of about 8.56. Analysis of the full-length PR01356 sequence shown in Figure 78 (SEQ ID NO: 134) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 24, transmembrane domains from about 20 amino acid 82 to about amino acid 102, from about amino acid 117 to about amino acid 140 and from about amino acid 163 to about amino acid 182, a potential N-glycosylation site from about amino acid 190 to about amino acid 193 and an amino acid sequence block having homology to the PMP-22/EMP/MP20 family of proteins from about amino acid 46 to about amino acid 59. Clone DNA64886-1601 has been deposited with ATCC on September 9, 1998 and is assigned ATCC deposit no. 203241.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 78 (SEQ ID NO: 134), evidenced significant homology between the PR01356 amino acid sequence and the following Dayhoff sequences: AB00014 1, AB000712_1, A39484, AF000959_1, AF035814_1,HSU89916_1,MMU19582_1,P_R30059,HUAC004125_1 and PM22_RAT.

EXAMPLE 43: Isolation of cDNA clones Encoding Human PRQ1275 A novel secreted molecuie, designated herein as DNA57700, was used to BLAST against Incyte's (LIFESEQ*, Incyte Pharmaceuticals, Palo Alto, CA) proprietary database and Genbank's public database. Positive clones were identified and used to generate assembly files by seqext program. The search was 35 performed using the computer program BLAST or BLAST2 [Altschul et al., Methods in Enzvmologv. 266:460-480 (1996)] as a comparison of the ECD protein sequences to a 6 frame translation of the EST sequences. Those comparisons resulting in a BLAST score of 70 (or in some cases, 90) or greater that did not encode known 409 proteins were clustered and assembled into consensus DNA sequences with the program "phrap" (Phil Green, University of Washington, Seattle, Washington).

A consensus DNA sequence was assembled relative to other GST sequences using repeated cycles of BLAST and phrap. This consensus sequence is designated herein "DNA59572".

Based on the DNAS9S72 consensus sequence and its relation to sequences identified in the assembly, 5 one of the clones (Incyte clone 2026581) including one of the sequences in the assembly was purchased and sequenced. Incyte clone 2026581 came from a library constructed of RNA from epidermal breast keratinocytes.

The entire coding sequence of PRO1275 is shown in Figure 79 (SEQ ID NO: 135). Clone DNA64888-1542 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 37-39 and an apparent stop codon at nucleotide positions 394-396 of SEQ ID NO:135. The predicted 10 polypeptide precursor is 119 amino acids long. The signal peptide is at about amino acids 1-25 of SEQ ID NO: 136. Clone DNA64888-1542 has been deposited with ATCC and is assigned ATCC deposit no. 203249. The full-length PR01275 protein shown in Figure 79 has an estimated molecular weight of about 13,248 daltons and a pi of about 7.78.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence 15 alignment analysis of the full-length sequence shown in Figure 80 (SEQ ID NO: 136), revealed sequence identity between the PRO1275 amino acid sequence and the following Dayhoff sequences (information from database incorporated herein): B48151 (Mst98Cb), D86424 1 (high-sulfur keratin protein), P R79964 (connective tissue growth factor), CHRD RAT (chordin), MT DREPO (metallothionein), PL05 PLETR (plectoxins), P R25156 (Ig antigen), S73732_l (VLDP), AF025440_1 (OIP4) and P_R32757 (IGF-II).

EXAMPLE 44: Isolation of cDNA clones Encoding Human PRQ1274 A novel secreted molecule, designated herein as DNA57700, was used to blast against Incyte's (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, CA) proprietary database and Genbank's public database. Positive clones were identified and used to generate assembly files by seqext program. The search was 25 performed using the computer program BLAST or BLAST2 [Altschul et al., Methods in Enzvmologv. 266:460-480 (1996)] as a comparison of the ECD protein sequences to a 6 frame translation of the EST sequences. Those comparisons resulting in a BLAST score of 70 (or in some cases, 90) or greater that did not encode known proteins were clustered and assembled into consensus DNA sequences with the program "phrap" (Phil Green, University of Washington, Seattle, Washington).

A consensus DNA sequence was assembled relative to other EST sequences using repeated cycles of BLAST and phrap. This consensus sequence is designated herein "DNA59573".

Based on the DNA59573 consensus sequence and its relation to sequences identified in the assembly, one of the clones (Incyte clone 2623992) including one of the sequences in the assembly was purchased and sequenced. Incyte clone 2623992 came from a library constructed of RNA from epidermal breast keratinocytes. 35 TheentirecodingsequenceofPR01274isshowninFigure81(SEQIDNO:137). CloneDNA64889- 1541 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 24-26, and an apparent stop codon at nucleotide positions 354-356 of SEQ ID NO; 137. The predicted 410 polypeptide precursor is 110 amino acids long. The signal peptide is at about 1-24 of SEQ ID NO: 138. Conserved regions in the insulin family of proteins and an N-glycosylation site are indicated in Figure 82. Clone DNA64889-1541 has been deposited with ATCC and is assigned ATCC deposit no. 203250. The full-length PR01274 protein shown in Figure 82 has an estimated molecular weight of about 12,363 daltons and a pi of about 8.31.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 82 (SEQ ID NO: 138), revealed sequence identity between the PRO1274 amino acid sequence and the following Dayhoff sequences (information from database incorporated herein): CEW05B29, AF016922_1 (insulin-like growth factor 1), B48151, A53640, BTIGF2REC1 (insulin-like growth factor 2), HSNF1GEN12_1, TXA3_RADMA (neurotoxin 3), 10 CXMl_CONGE, P P61301, TXA4 RADMA (neurotoxin 4).

EXAMPLE 45: Isolation of cDNA clones Encoding Human PRQ1412 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the LIFESEQ* database, designated Incyte Cluster No. 101368 , also referred herein as IS "DNA10643". This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not 20 encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). One or more of the ESTs was derived from RNA isolated from fibroblasts of the prostate stroma removed from a male fetus. The consensus sequence obtained therefrom is herein designated "DNA58754".

In light of the sequence homology between the DNA58754 sequence and an EST sequence contained 25 within EST no. 3597385, the EST clone 3597385 was purchased and the cDNA insert was obtained and sequenced in its entirety. The sequence of this cDNA insert is shown in Figure 83 and is herein designated as "DNA64897-1628".

The full length clone shown in Figure 83 contained a single open reading frame with an apparent translational initiation site at nucleotide positions 142 to 144 and ending at the stop codon found at nucleotide 30 positions 1075 to 1077 (Figure 83; SEQ ID NO: 139). The predicted polypeptide precursor (Figure 84, SEQ ID NO: 140) is 311 amino acids long. Other features of the PRO 1412 protein include: a signal sequence at about amino acids 1-28; a transmembrane domain at about amino acids 190-216; potential N-glycosylation sites at about amino acids 49-52, 91-94, 108-111, 128-131, 135-138 and 190-193; a tyrosine kinase phosphoiylation site at about amino acids 62-69; and a lysosome-associated membrane glycoprotein duplicated domain at about 35 amino acids 183-224. PR01412 has a calculated molecular weight of approximately 33,908 daltons and as estimated pi of approximately 6.87. Clone DNA64897-1628 was deposited with the ATCC on September 15, 1998, and is assigned ATCC deposit no. 203216. 411 An analysis of the Dayhoff database (version 3S.4S SwissProt 33), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 84 (SEQ ID NO: 140), revealed some homology between the PR01412 amino acid sequence and the following Dayhoff sequences: 150116, AF035963_1, NCA2 RAT, 161783, P_W07682, MMHCI35G15 3, S21461, MMIGL2_1, ONHIGMV9A_l and MMU70448_1.

EXAMPLE 46: Isolation of cDNA clones F.nqvling Human PRO 1557 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST sequence from the Genentech database, designated "DNA58763. This EST sequence was then compared to a variety of expressed sequence tag (EST) databases, which included the EST databases listed above, to identify 10 existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained from the assembly is herein designated "DNA58763". IS In light of the sequence homology between the DNA58763 sequence and an EST sequence contained within the EST no.2267403, EST no. 2267403 was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 85 and is herein designated as DNA64902-1667.

The full length clone shown in Figure 85 contained a single open reading frame with an apparent translational initiation site at nucleotide positions 287 to 289 and ending at the stop codon found at nucleotide 20 positions 1640 to 1642 (Figure 85; SEQ ID NO: 141). The predicted polypeptide precursor (Figure 86, SEQ ID NO:142) is 451 amino acids long. PR01557 has a calculated molecular weight of approximately 49,675 daltons and an estimated pi of approximately 7.15. Additional features include: a signal sequence at about amino acids 1-25; a potential N-glycosylation site at about amino acids 114-117; a potential cAMP and cGMP-dependent protein kinase phosphorylation site at about amino acids 388-41; potential N-myristoylation sites at 2S about amino acids 54-49,66-71,146-151, and 367-372; potential amidation sites at about amino acids 36-39 and 205-208; and an ATP/GTP-binding site motif A (P-loop) at about amino acids 151-258.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), """g a WU-BLAST2 sequence alignment analysis of tbe full-length sequence shown in Figure 86 (SEQ ID NO: 142), revealed significant homology between the PR01557 amino acid sequence and Dayhoff sequence AF034606 1. Homology was also 30 found between the PR01557 amino acid sequence and the following Dayhoff sequences: P_W31559, AF031230_1, SOG DROME, CAll_MOUSE, P_R41320, CHRD RAT, P W40288, NEL_CHICK, and HSMUC5B_1.

Clone DNA64902-1667 was deposited with the ATCC on October 6, 1998, and is assigned ATCC deposit no. 203317.

F.XAMPLE 47: Isolation of cDNA clones Encoding Human PRQ1286 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST 412 cluster sequence from the LIFESEQ* database, designated EST Cluster No. 86809. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, CA) to identiiy existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Fnrvmnlnpv 266:460-480 (1996)). Those comparisons resulting in a 5 BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). ESTs in the assembly included those identified from tumors, cell lines, or diseased tissue. One or more of the ESTs was obtained from a cDNA library constructed from RNA isolated from diseased colon tissue. The consensus sequence obtained therefrom is herein designated DNA58822.

In light of the sequence homology between the DNA58822 sequence and an EST sequence contained within EST no. 169S434, EST clone no. 1695434 was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 87 and is herein designated DNA64903-1553 (SEQ ID NO: 143).

The full length clone shown in Figure 87 contained a single open reading frame with an apparent 15 translational initiation site at nucleotide positions 93-95 and ending at the stop codon found at nucleotide positions 372-374 (Figure 87; SEQ ID NO:143). The predicted polypeptide precursor (Figure 88, SEQ ID NO:144) is 93 amino acids long, with a signal sequence at about amino acids 1-18. PR01286 has a calculated molecular weight of approximately 10, 111 daltons and an estimated pi of approximately 9.70.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence 20 alignment analysis of the full-length sequence shown in Figure 88 (SEQ ID NO: 144), revealed some homology between the PR01286 amino acid sequence and the following Dayhoff sequences: SR5CARATH, CELC17H12_11, MCPD ENTAE, JQ2283, INVO_LEMCA, P_R07309, ADEVBCAGN_4, AF020947_1, CELT23H21, and MDH STRAR.

Clone DNA64903-1553 was deposited with the ATCC on September 15,1998 and is assigned ATCC 25 deposit no. 203223.

EXAMPLE 48: Isolation of cDNA clones Encoding Human PR01294 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the Incyte database, designated Incyte EST cluster sequence no. 10559. This EST cluster 30 sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, C A) to identiiy existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and 35 assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated DNA57203.

In light of the sequence homology between the DNA57203 sequence and an EST sequence contained 413 PCT/US99/20I11 within the Incyte EST clone no. 3037763, the Incyte EST clone no. 3037763 was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 89 and is herein designated as DNA64905-1558.

Clone DNA64905-1558 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 110-112 and ending at the stop codon at nucleotide positions 1328-1330 (Figure 89).

The predicted polypeptide precursor is 406 amino acids long (Figure 90). The full-length PR01294 protein shown in Figure 90 has an estimated molecular weight of about 46,038 daltons and a pi of about 6.50. Analysis of the full-length PR01294 sequence shown in Figure 90 (SEQ ID NO: 146) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 21 and potential N-glycosylation sites from about amino acid 177 to about amino acid 180 and fiom about amino acid 248 to about amino acid 251. 10 Clone DNA64905-1558 has been deposited with ATCC on September 15, 1998 and is assigned ATCC deposit no. 203233.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 90 (SEQ ID NO: 146), evidenced significant homology between the PR01294 amino acid sequence and the following Dayhoff sequences: 173636, 15 AF028740_1, AB006686S3_1, P_R98225, RNU78105_1, CELC48E7_4, CEF11C3J, SCP1_MESAU, TPM3HUMAN and CELK05B2_3.

EXAMPLE 49: Isolation of cDNA clones Encoding Human PRQ1347 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described 20 in Example 1 above. This consensus sequence is designated herein "DNA47373". Based on the DNA47373 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01347.

PCR primers (forward and reverse) were synthesized: forward PCR nrimer 5'GCGTGGTCCACCTCTACAGGGACG3' (SEQ ID NO: 149); and reverse PCR primer 5'GGAACTGACCCAGTGCTGACACC3' (SEQ ID N0:150).

Additionally, a synthetic oligonucleotide hybridization probe was constructed fiom the consensus DNA47373 sequence which had the following nucleotide sequence: hybridization probe 5'GCAGATGCCACAGTATCAAGGCAGGACAAAACTGGTGAAGGATTC3' (SEQ ID 30 NO: 151).

In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01347 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from human small intestine. 35 DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PR01347 and tbe derived protein sequence for PR01347.

The entire coding sequence of PR01347 is shown in Figure 91 (SEQ ID NO: 147). Clone DNA64950- 414 within the Incyte EST clone no. 3037763, the Incyte EST clone no. 3037763 was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 89 and is herein designated as DNA64905-1558.

The predicted polypeptide precursor is 406 amino acids long (Figure 90). The full-length PR01294 protein shown in Figure 90 has an estimated molecular weight of about 46,038 daltons and a pi of about 6.50. Analysis of the full-length PR01294 sequence shown in Figure 90 (SEQ ID NO:146) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 21 and potential N-glycosylation sites from about amino acid 177 to about amino acid 180 and from about amino acid 248 to about amino acid 251. 10 Clone DNA64905-1558 has been deposited with ATCC on September 15, 1998 and is assigned ATCC deposit no. 203233.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 90 (SEQ ID NO: 146), evidenced significant homology between the PR01294 amino acid sequence and the following Dayhoff sequences: 173636, 15 AF028740_1, AB006686S3J, P_R98225, RNU78105_1, CELC48E7_4, CEF11C3J, SCP1_MESAU, TPM3_HUMAN and CELK05B2_3.

PCR primers (forward and reverse) were synthesized: forward PCR primer 5'GCGTGGTCCACCTCTACAGGGACG3' (SEQ ID NO:149); and reverse PCR primer 5'GGAACTGACCCAGTGCTGACACC3' (SEQ ID NO: 150).

Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA47373 sequence which had the following nucleotide sequence: hybridization probe 5'GCAGATGCCACAGTATCAAGGCAGGACAAA ACTGGTGAAGGATTC3' (SEQ ID 30 NO: 151).

In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01347 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from human small intestine. 35 DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PR01347 and the derived protein sequence for PR01347.

The entire coding sequence of PR01347 is shown in Figure 91 (SEQ ID NO: 147). Clone DNA64950- 414 1590 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 183-185, and an apparent stop codon at nucleotide positions 1683-1685 of SEQ ID NO: 147. The predicted polypeptide precursor is 500 amino acids long. The signal peptide is at about amino acids 1-17 and the transmembrane domain is at about 239-255 of SEQ ID NO: 148. Clone DNA64950-1590 has been deposited with ATCC and is assigned ATCC deposit no. 203224. The full-length PR01347 protein shown in Figure 92 5 has an estimated molecular weight of about 56,748 daltons and a pi of about 8.5.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 92 (SEQ ID NO: 148), revealed sequence identity between the PR01347 amino acid sequence and the following Dayhoff sequences (data incorporated herein): BUTY HUMAN, AF033107_1, HSU90142_1, HSU90144_1, HSB73_1, HS111M5_2, R052_HUMAN, 10 AF018080_1, HSAJ03147 4, and MOG_MOUSE.

EXAMPLE 50: Isolation of cDNA clones Encoding Hnman PRQ1305 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is herein designated DNA38103. Based on the DNA38103 15 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01305.

PCR primers (forward and reverse) were synthesized: forward PCR nrimer (381Q3.fn 5'-AACTGCTCTGTGGTTGGAAGCCTG-3' (SEQ ID NO: 154) 20 reverse PCR primer (381Q3.rtt 5'-CAGTCACATGGCTGACAGACCCAC-3' (SEQ ID NO: 155) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA38103 sequence which had the following nucleotide sequence hybridization probe (381Q3.pn 5AGGTTATCAGGGGCTTCACTGTGAAACCTGCAAAGAGG-3' (SEQ ID NO:156) 25 In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01305 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from human fetal kidney tissue.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for 30 PR01305 (designated herein as DNA64952-1568 [Figure 93, SEQ ID NO:152]; and the derived protein sequence for PR01305.

The entire nucleotide sequence of DNA64952-1568 is shown in Figure 93 (SEQ ID NO: 152). Clone DNA64952-1568 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 126-128 and ending at the stop codon at nucleotide positions 900-902 (Figure 93). The predicted 35 polypeptide precursor is 258 amino acids long (Figure 94). The full-length PR01305 protein shown in Figure 94 has an estimated molecular weight of about 25,716 daltons and a pi of about 8.13. Analysis of the full-length PR01305 sequence shown in Figure 94 (SEQ ID NO-.153) evidences the presence of the following: a signal 415 PCT7US99/201H peptide from about amino acid 1 to about amino acid 25, potential N-glycosylation sites from about amino acid 30 to about amino acid 33, from about amino acid 172 to about amino acid 175, from about amino acid 195 to about amino acid 198, from about amino acid 208 to about amino acid 211 and from about amino acid 235 to about amino acid 238 and an EGF-like domain cysteine pattern signature sequence from about amino acid 214 to about amino acid 225. Clone DNA64952-1568 has been deposited with ATCC on September 15, 1998 and 5 is assigned ATCC deposit no. 203222.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 94 (SEQ ID NO: 153), evidenced significant homology between the PR01305 amino acid sequence and the following Dayhoff sequences: CET22A3_7, LMA2_MOUSE,AFQ55580_1,AF016903_1,LMB2_MOUSE,P_R71730,LMB3_MOUSE,LMG1_HUMAN, 10 LMG1DROME and LMA5_MOUSE. As such, the PR01305 polypeptide does show homology to laminin and may be a laminin homolog.

EXAMPLE 51: Isolation of cDNA clones Encoding Human PRQ1273 An expressed sequence tag (EST) DNA database (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, CA) IS was searched and an EST was identified. This sequence was blasted against public databases and Incyte's database. The search was performed using the computer program BLAST or BLAST2 [Altschul et al., Methods in Enzvmologv. 266:460-480 (1996)] as a comparison of the extracellular domain (ECD) protein sequences to a 6 frame translation of the EST sequences. Those comparisons resulting in a BLAST score of 70 (or in some cases, 90) or greater that did not encode known proteins were clustered and assembled into consensus DNA 20 sequences with the program "phrap'' (Phil Green, University of Washington, Seattle, Washington).

A consensus DNA sequence was assembled relative to other EST sequences using repeated cycles of BLAST and phrap. This consensus sequence is designated herein "DNA60747". Based on the DNA60747 consensus sequence and its relation to a sequence within the assembly of aligned sequences, Incyte clone 3541105 was purchased and sequenced in full. This Incyte clone came from a library constructed of RNA 25 isolated from seminal vesicle tissue.

The entire coding sequence of PR01273 is shown in Figure 95 (SEQ ID NO:157). Clone DNA65402-1540 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 26-28 and an apparent stop codon at nucleotide positions 515-517 of SEQ ID NO:157. The predicted polypeptide precursor is 163 amino acids long. The signal peptide is at about amino acids 1-20 and the 30 conserved region in lipocalins is at about amino acids 25-36 of SEQ ID NO: 158. Clone DNA65402-1540 has been deposited with ATCC and is assigned ATCC deposit no. 203252. The full-length PRO1273 protein shown in Figure 96 has an estimated molecular weight of about 18,045 daltons and a pi of about 4.87.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 96 (SEQ ID NO: 158), revealed sequence identity 35 between the PR01273 amino acid sequence and the following Dayhoff sequences (information from database incorporated herein): PGHD FELCA (prostaglandin^ d-isomerase precursor), S57748 (prostaglandin D synthetase precursor), LIPO_BUFMA (lipocalin precursor), S52354, QSP_CHICK, ECP191, LACB CAPHI, 416 OLFARANPI, D87752_l, and LACB_BOVIN.

EXAMPLE 52: Isolation of cDNA clones Encoding Human PRQ13Q2 A consensus DNA sequence encoding PR01302 was assembled relative to other EST sequences using repeated cycles of phrap as described in Example 1 above. This consensus sequence is designated herein 5 "DNA28742". Based on the DNA28742 consensus sequence, the assembly from which the consensus sequence was derived and other information and discoveries provided herein, the Incyte clone 3344926 (from a diseased spleen tissue library) was purchased and sequenced in full. Sequencing provided the full-length DNA sequence for PR01302 and the derived protein sequence for PR01302.

The entire coding sequence of PR01302 is shown in Figure 97 (SEQ ID NO: 159). Clone DNA65403-10 1565 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 43-45 and an apparent stop codon at nucleotide positions 1432-1435 of SEQ ID NO:159. The predicted polypeptide precursor is 463 amino acids long. The signal peptide is at about amino acids 1-15 and the transmembrane sequence is at about amino acids 351-370 of SEQ ID NO: 160. Clone DN A65403-1565 has been deposited with the ATCC and is assigned ATCC deposit no. 203230. The full-length PR01302 protein shown 15 in Figure 98 has an estimated molecular weight of about 50,082 daltons and a pi of about 7.3.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 98 (SEQ ID NO: 160), revealed sequence identity -between the PR01302 amino acid sequence and the following Dayhoff sequences (data incorporated herein): D86358_l, D86359_l, S71403_l, MAGJHUMAN, JH0593, MMSIAL2 _1, C22A_HUMAN, PGBMHUMAN, 20 PGBM HUMAN, LACH DROME, and KMLS HUMAN.

EXAMPLE 53: Isolation of cDNA clones Encoding Human PRQ1283 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is herein designated DNA28753. Based on the DNA28753 25 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01283.

PCR primers (forward and reverse) were synthesized: forward PCR primer (28753.fn 5'-GGAGATGAAGACCCTGTTCCTG-3' (SEQ ID NO: 163) 30 forward PCR primer (28753.fill 5'-GGAGATGAAGACCCTGTTCCTGGGTG-3' (SEQ ID NO: 164) reverse PCR primer (28753.rl) 5'-GTCCTCCGGAAAGTCCTTATC-3' (SEQ ID NO: 165) reverse PCR primer (28753.rllt 5'-GCCTAGTGTTCGGGAACGCAGCTTC-3' (SEQ ID NO: 166) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA28753 sequence which had the following nucleotide sequence 35 hybridization probe (28753.pl) '-CAGGGACCTGGTACGTGAAGGCCATGGTGGTCGATAAGGACTTTCCGGAG-3' (SEQ ID NO:167) hybridization probe (28753.plD 417 '-CTGTCCTTCACCCTGGAGGAGGAGGATATCACAGGGACCTGGTAC-3' (SEQ ID NO: 168) In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PRO1283 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from human breast tumor tissue.

DNA sequencing of die clones isolated as described above gave the full-length DNA sequence for PR01283 (designated herein as DNA65404-I551 [Figure 99, SEQ ID NO: 161]; and the derived protein sequence for PRO1283.

The entire nucleotide sequence of DNA65404-1551 is shown in Figure 99 (SEQ ID NO: 161). Clone DNA65404-1551 contains a single open reading frame with an apparent translational initiation site at nucleotide 10 positions 45-47 and ending at the stop codon at nucleotide positions 555-557 (Figure 99). The predicted polypeptide precursor is 170 amino acids long (Figure 100). The full-length PROI283 protein shown in Figure 100 has an estimated molecular weight of about 19,457 daltons and a pi of about 9.10. Analysis of the full-length PR01283 sequence shown in Figure 100 (SEQ ID NO: 162) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 17. Clone DNA65404-1551 has been deposited with 15 ATCC on September 9, 1998 and is assigned ATCC deposit no. 203244 An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the frill-length sequence shown in Figure 100 (SEQ ID NO: 162), evidenced significant homology between the PR01283 amino acid sequence and the following Dayhoff sequences: A40464, VEGP_HUMAN, ALL1_CANFA, LALP_TRIVU, S51803, XELPDS_1, LIPO BUFMA, S52354, 20 QSP_CHICK and ERBPRAT.

EXAMPLE 54: Isolation of cDNA clones Encoding Human PRQ1279 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is herein designated DNA30856. Based on the DNA30856 25 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PRO1279.

PCR primers (forward and reverse) were synthesized: forward PCR primer (3Q856.fl1 5'-GGCTGCGGGACTGGAAGTCATCGGG-3' (SEQ ID NO:171) 30 forward PCR nrimer (30856.fin 5 -CTCCAGGCCATGAGGATTCTGCAG-3' (SEQ ID NO:172) forward PCR primer (30856. f!2> 5' -CCTCTGGTCTGTAACCAG-3' (SEQ ID NO: 173) reverse PCR primer (3Q856.rn 5' -TCTGTGATGTTGCCGGGGTAGGCG-3' (SEQ ID NO:174) reverse PCR primer (3Q856.rin 5'-CGTGTAGACACCAGGCTTTCGGGTG-3' (SEQ ID NO:175) reverse PCR primer (3Q856.rl2^ 5 '-CCCTTGATGATCCTGGTC-3' (SEQ ID NO: 176) 35 Additionally, synthetic oligonucleotide hybridization probes were constructed from the consensus DNA30856 sequence which had the following nucleotide sequences hybridization probe (30856.pD 418 '-AGGCCATGAGGATTCTGCAGTTAATCCTGCTTGCTCTGGCAACAGGGCTT-3' (SEQ ID NO: 177) hybridization probe (30856.pl H '-GAGAGACCAGGATCATCAAGGGGTTCGAGTGCAAGCCTCACTC-3' (SEQ ID NO-.178) In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to 5 isolate clones encoding the PR01279 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from human lung tumor tissue.

DNA sequencing of die clones isolated as described above gave the full-length DNA sequence for PR01279 (designated herein as DNA65405-1547 [Figure 101, SEQ ID NO:169]; and the derived protein sequence for PR01279.

The entire nucleotide sequence of DNA65405-1547 is shown in Figure 101 (SEQ ID NO: 169). Clone DNA65405-1547 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 106-108 and ending at the stop codon at nucleotide positions 856-858 (Figure 101). The predicted polypeptide precursor is 250 amino acids long (Figure 102). The full-length PR01279 protein shown in Figure 102 has an estimated molecular weight of about 27,466 daltons and a pi of about 8.87. Analysis of the full-15 length PR01279 sequence shown in Figure 102 (SEQ ID N0:170) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 18, a serine protease, trypsin family, histidine active site from about amino acid 58 to about amino acid 63, potential N-glycosylation sites firom about amino acid 99 to about amino acid 102, from about amino acid 165 to about amino acid 168, from about amino acid 181 to about amino acid 184 and from about amino acid 210 to about amino acid 213, a glycosaminogiycan attachment 20 site from about amino acid 145 to about amino acid 148, amino acid sequence blocks present in kringle domain proteins from about amino acid 197 to about amino acid 209 and from about amino acid 47 to about amino acid 64, amino acid sequence blocks having homology to serine protease, trypsin family, histidine proteins from about amino acid 199 to about amino acid 209, from about amino acid 47 to about amino acid 63 and from about amino acid 220 to about amino acid 243 and amino acid sequence blocks having homology to apple domain proteins 25 from about amino acid 222 to about amino acid 249 and from about amino acid 189 to about amino acid 222. Clone DNA65405-1547 has been deposited with ATCC on November 17, 1998 and is assigned ATCC deposit no. 203476.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 102 (SEQ ID NO: 170), evidenced significant 30 homology between the PR01279 amino acid sequence and the following Dayhoff sequences: 156559, S55066, KLK7 RAT, KLK1RAT, KLKB RAT, KLK3_MOUSE, KLK8_RAT, AF013988_1, D78203J and HSU62801_1.

Additionally, DNA65405-1547 was obtained by purchasing the Incyte EST clone no. 2723646 and sequencing the insert of that clone, thereby giving the DNA65405-1547 sequence shown in Figure 101 (SEQ ID 35 NO-.169). 419 EXAMPLE 55: Isolation of cDNA clones Encoding Human PRQ1304 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is herein designated DNA35745. Based on the DNA35745 consensus sequence, oligonucleotides were synthesized: 1) to identiiy by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for 5 PR01304.

PCR primers (forward and reverse) were synthesized: forward PCR nrimer (35745.fn 5'-GTGTTCTGCTGGAGCCGATGCC-3' (SEQ ID NO: 181) forward PCR nrimer f35745.5'-GACATGGACAATGACAGG-3' (SEQ ID NO: 182) forward PCR nrimer (3574S.f3^ 5'-CCTTTCAGGATGTAGGAG-3' (SEQ ID NO: 183) forward PCR primer (35745,f41 5,-GATGTCTGCCACCCCAAG-3• (SEQ ID NO: 184) reverse PCR primer (3S745.rl1 5'-GCATCCTGATATGACTTGTCACGTGGC-3' (SEQ ID NO:185) reverse PCR primer (35745.r2'> 5'-TACAAGAGGGAAGAGGAGTTGCAC-3' (SEQ ID NO:186) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA35745 sequence which had the following nucleotide sequence 15 hybridization probe (35745.pit ' -GCCC ATTATGACGGCTACCTGGCTAAAGACGGCTCGAAATTCTACTGC AGCC-3(SEQ ID NO: 187) In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01304 gene using the probe oligonucleotide and one of the PCR primers. RNA 20 for construction of the cDNA libraries was isolated from human ovary tissue.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PRO1304 (designated herein as DNA65406-1567 [Figure 103, SEQ ID NO: 179]; and the derived protein sequence for PR01304.

The entire nucleotide sequence of DNA65406-1567 is shown in Figure 103 (SEQ ID NO: 179). Clone 25 DNA65406-1567 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 23-25 and ending at the stop codon at nucleotide positions 689-691 (Figure 103). The predicted polypeptide precursor is 222 amino acids long (Figure 104). The full-length PR01304 protein shown in Figure 104 has an estimated molecular weight of about 25,794 daltons and a pi of about 6.24. Analysis of the full-length PR01304 sequence shown in Figure 104 (SEQ ID NO: 180) evidences the presence of the following: an 30 endoplasmic reticulum targeting sequence from about amino acid 219 to about amino acid 222, a potential N-glycosylation site from about amino acid 45 to about amino acid 48, FKBP-type peptidyl-prolyl cis-trans isomerase homology blocks from about amino acid 87 to about amino acid 123 and from about amino acid 129 to about amino acid 142 and EF-hand calcium binding domain protein homology blocks from about amino acid 202 to about amino acid 214 and from about amino acid 195 to about amino acid 214. Clone DNA65406-1567 35 has been deposited with ATCC on September 15, 1998 and is assigned ATCC deposit no. 203219.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 104 (SEQ ID NO: 180), evidenced significant 420 homology between the PR01304 amino acid sequence and the following Dayhoff sequences: AF040252_1, PR28980, S71238, CELC05C8J, VFU52045_1, S75144, FKB3_BOVIN, CELC50F2_6, CELB0511_12and P_R41781.

The DNA65406-1567 sequence was also obtained by isolating and sequencing the insert of Incyte EST clone no. 2813577.

EXAMPLE 56: Isolation of cDNA clones F.nr-nriing Human PRQ1317 Using the technique described in Example 1 above, Incyte EST no. 33598 was identified as a sequence of interest having a BLAST score of 70 or greater that did not encode a known protein. The sequence of Incyte EST no. 33598 is designated herein as "DNA36958". Based on the DNA36958 sequence, oligonucleotides can 10 be synthesized: 1) to identiiy by PCR a cDNA library that contains the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01317.

The following are suitable PCR primers (forward and reverse) that can be synthesized based on the DNA36958 sequence: forward PCR primer: AGGGACCATTGCTTCTTCCAGGCC (36958.fl; SEQ ID N0:190) reverse PCR primer: CGTTACATGTCTCCAAGGGGAATG (36958.rl; SEQ ID NO:191) Additionally, a synthetic oligonucleotide hybridization probe can be constructed from the consensus DNA36958 sequence having the following nucleotide sequence: hybridization probe: CCTGTGCTAAGTGCCCCCCAAATGCTTCCTGTGTCAATAACACTCACTGC (36958.pl; SEQ ID NO: 192) In order to screen several libraries for a source of a full-length clone, DNA from the libraries is screened by PCR amplification with the PCR primer pair identified above. A positive library is then used to isolate clones encoding the PR01317 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries can be isolated from tissue containing the sequence of interest, for example from peripheral blood, particularly blood taken from a patient having a high leukocyte count (e.g 25 hypereosinophilia).

The full-length DNA sequence for PR01317, designated herein as DNA65408-1578 (Figure 105; SEQ ID NO:188) was obtained by purchasing Incyte EST no. 335958, obtaining the cDNA insert, and sequencing it in its entirety. Incyte clone no. 335958 originated from a library constructed using RNA isolated from peripheral blood cells apheresed from a male patient afflicted with hypereosinophilia. 30 The entire coding sequence of PR01317 is shown in Figure 105 (SEQ ID NO: 188). Clone DNA65408- 1578 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 6-8 and an apparent stop codon at nucleotide positions 228-230. The predicted polypeptide precursor is 74 amino acids long. The full-length PR01317 protein shown in Figure 106 has an estimated molecular weight of about 7,831 daltons and a pi of about 9.08. Additional features include: a signal peptide at about amino acids 35 1-18, potential N-glycosylation sites at about amino acids 34-37 and 39-42, and a microbodies C-terminal targeting signal at amino acids 72-74.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence 421 WO 00/12708 PCT/US99/20111 alignment analysis of the full-length sequence shown in Figure 106 (SEQ ID NO: 189), revealed significant homology between the PR01317 amino acid sequence and the Dayhoff sequence designated CD97_HUMAN. Additionally, some homology was found between the PR01317 amino acid sequence and the following Dayhoff sequences: GEN12618, CELZK783_1, G156_PARPR, GIAVSPEJ, AF040387_1, S78059, 150617, XLSEKll, and NEL2 RAT.

Clone DNA65408-1578 was deposited with the ATCC on September 15, 1998, and is assigned ATCC deposit no. 203217.

EXAMPLE 57: Isolation of cDNA clones Encoding Hnman PRQ1303 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described 10 in Example 1 above. This consensus sequence is designated herein "DNA47347". Based on the DNA47347 consensus sequence and its homology to an Incyte EST within the assembly from which DNA47347 was derived, Incyte clone 1430305 (from an ileum tissue library) was purchased and sequenced in full. The sequence encoding PR01303 was thereby identified.

The entire coding sequence of PR01303 is shown in Figure 107 (SEQ ID NO: 193). Clone DNA65409-15 1566 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 121-123 and an apparent stop codon at nucleotide positions 865-867. Tbe predicted polypeptide precursor is 248 amino acids long. The signal peptide is at about amino acids 1-17 of SEQ ID NO: 194. The locations of N-glycosylation sites, active and conserved regions and domains are further indicated in Figure 194. Clone DNA6S409-1566 has been deposited with ATCC and is assigned ATCC deposit no. 203232. The full-length 20 PRO1303 protein shown in Figure 108 has an estimated molecular weight of about 26,734 daltons and a pi of about 7.9.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 108 (SEQ ID NO: 194), revealed sequence identity between the PR01303 amino acid sequence and the following Dayhoff sequences (data incorporated herein): 25 AB009849 1, PW08475, AF024605_1, A42048 1, TRY3_RAT, MMAE00066414, TRY1RAT, MMAE000663 4, MMAE000665_2, and MMAE00066412.

EXAMPLE 58: Isolation of cDNA clones Encoding Human PRO 1306 Using the method described in Example 1 above, Incyte EST No. 2449282, also referred to herein as 30 DNA5918, was identified as a sequence of interest having a BLAST score of 70 or greater that did not encode a known protein. From the DNA5918 sequence, a consensus sequence was assembled using BLAST and the program "phrap" (Phil Green, University of Washington, Seattle, Washington). This consensus sequence is designated herein as "DNA47399". Based on the DNA47399 consensus sequence, oligonucleotides can be synthesized: 1) to identify by PCR a cDNA library that contains die sequence of interest, and 2) for use as 35 probes to isolate a clone of the full-length coding sequence for PR01306.

The entire coding sequence of PR01306 shown in Figure 109 (SEQ ID NO: 195), was obtained by purchasing Incyte EST no. 2449282, obtaining the cDNA insert and sequencing it in its entirety. Clone 422 DNA65410-1569 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 106-108 and an apparent stop codon at nucleotide positions 556-558. The predicted polypeptide precursor is 150 amino acids long. The full-length PR01306 protein shown in Figure 110 has an estimated molecular weight of about 17,068 daltons, a pi of about 7.29, and a potential N-glycosylation site at about amino acids 131-134.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 110 (SEQ ID NO: 196), revealed significant homology between the PR01306 amino acid sequence and Dayhoff sequence AIF1JHUMAN. Homology was also shown between the PR01306 amino acid sequence and the following Dayhoff sequences: JC4902, BAR1JRAT, AF020281_1, HSU95213_1, TCH3ARATH, LEY14765J, CATR_NAEGR, S35185, and 10 AF065247_1.

Clone DNA65410-1569, was deposited with the ATCC on September 15, 1998 and is assigned ATCC deposit no. 203231.

EXAMPLE 59: Isolation of cDNA clones Encoding Human PRQ1336 15 An EST sequence was identified and entered into a proprietary Genentech database. The EST was blasted against various EST databases. The EST databases included public EST databases (e.g., GenBank), and a proprietary EST database (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, CA), and proprietary ESTs from Genentech. The search was performed using the computer program BLAST or BLAST2 [Altschul et al., Methods in Enzvmologv. 266:460-480 (1996)) as a comparison of the ECD protein sequences to a 6 frame 20 translation of the EST sequences. Those comparisons resulting in a BLAST score of 70 (or in some cases, 90) or greater that did not encode known proteins were clustered and assembled into consensus DNA sequences with the program "phrap" (Phil Green, University of Washington, Seattle, Washington).

A consensus DNA sequence encoding PRO1336 was assembled relative to other aligned EST sequences (forming an assembly) using phrap. This consensus sequence is designated herein "DNA43319". Based on the 25 DNA43319 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PRO1336.

PCR primers (forward and reverse) were synthesized: forward PCR primer 51ATGGAG ATTCCTGCC A ACTTGCCG3' (SEQ ID N0:199); and 30 reverse PCR nrimer 5 'TTGTTGGCATTGAGGAGGAGCAGC3'. (SEQ ID N0:200).

Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA43319 sequence which had the following nucleotide sequence: hybridization probe 5 'GAGGGCATCGTCGAAATACGCCTAGAACAGAACTCCATCAAAGCCATCCC3' (SEQ ID N0:201).

In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01336 gene using the probe oligonucleotide and one of the PCR primers. RNA 423 for construction of the cDNA libraries was isolated from human fetal lung tissue.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PRO1336 (designated herein as DNA65423-1595 [Figures 111A-B, SEQ ID NO: 198]; and the derived protein sequence for PR01336.

The entire coding sequence of PR01336 is shown in Figures 111A-B (SEQ ID NO:198). Clone 5 DNA65423-1595 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 83-85 and an apparent stop codon at nucleotide positions 4652-4654 of SEQ ID NO: 198. The predicted polypeptide precursor is 1523 amino acids long. The approximate locations of the signal peptide (amino acids 1-27), aspartic acid and asparagine hydroxylation sites, EGF-like domain cystein pattern signature regions, a leucine zipper pattern region, a region conserved in immunoglobulins and major histocompatibility complexes, 10 and N-glycosyiation sites are indicated in Figure 112. Clone DNA65423-1595 has been deposited with the ATCC and is assigned ATCC deposit no. 203227. The full-length PR01336 protein shown in Figure 112 has an estimated molecular weight of about 167,715 daltons and a pi of about 8.06.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 112 (SEQ ID NO: 198), revealed sequence identity 15 between the PRO1336 amino acid sequence and the following Dayhoff sequences (data incorporated herein): SLTTDROME, CEF40E10_1, LCU58977J, AF029779J, FBP1_STRPU, NOTC_XENLA, AC004663_1, XELXDEL l, P_W05835 and HSU77720_1.

KX A MPT -F. fin- Isolation of cDNA clones Encoding Human PRO 1278 20 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is designated herein uConsen5230". In addition, the Consen5230 consensus sequence was extended using repeated cycles of BLAST and phrap to extend the consensus sequence as far as possible using the sources of EST sequences discussed above. The extended consensus sequence is designated herein as "DNA44801". Based on the DNA44801 consensus sequence, oligonucleotides were 25 synthesized: 1) to identiiy by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01278.

PCR primers (forward and reverse) were synthesized: forward PCR primers: GCAGGCTTTGAGGATGAAGGCTGC (44801.fl; SEQ ID N0:204) and CTCATTGGCTGCCTGGTCACAGGC (44801.f2; SEQ ID N0:205) reverse PCR primers: CCAGTCGGACAGGTCTCTCCCCTC (44801.rl; SEQ ID N0:206) and TCAGTGACCAAGGCTGAGCAGGCG (44801.r2; SEQIDN0:2Q7) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA44801 sequence which had the following nucleotide sequence: hybridization probe: CTACACTCGTTGCAAACTGGCAAAAATATTCTCGAGGGCTGGCCTGQ44801 .pi; 35 SEQ ID N0:208) In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to 424 isolate clones encoding the PROI278 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from human testis.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PR01278 (designated herein as DNA66304-1546 [Figure 113, SEQ ID N0.202]; and the derived protein sequence for PRO1278.

TheentirecodingsequenceofPR01278isshowninFigure 113(SEQIDN0:2Q2). Clone DNA66304- 1546 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 141-143 and an apparent stop codon at nucleotide positions 585-587. The predicted polypeptide precursor is 148 amino acids long. The full-length PRO1278 protein shown in Figure 114 has an estimated molecular weight of about 16,623 daltons and a pi of about 8.47. Additional features include a signal peptide sequence at about 10 amino acids 1-19; a potential N-glycosylation site at about amino acids 58-61; an alpha-lactalbumin/lysozyme C signature at about amino acids 94-112; and homolgy with alpha-lactalbumin/lysozyme C at about amino acids 35-59, 67-59 and 112-133.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 114 (SEQ ID N0:203), revealed significant 15 homology between the PROI278 amino acid sequence and the following Dayhoff sequences; LYC1ANAPL, LYC3_ANAPL, and LYC_HUMAN.

Clone DNA66304-1546 was deposited with the ATCC on October 6, 1998, and is assigned ATCC deposit no. 203321.

EXAMPLE 61: Isolation of cDNA clones Encoding Human PRO 1298 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from an Incyte database. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. One 25 or more of the ESTs was derived from a diseased prostate tissue libraiy. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein 30 designated DNA56389.

In light of the sequence homology between the DNA56389 sequence and an EST sequence contained within an Incyte EST within the assembly from with the consensus sequence was derived, Incyte clone 3355717 was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 115 and is herein designated as DNA66511-1563.

The full length clone shown in Figure 115 contained a single open reading frame with an apparent translational initiation site at nucleotide positions 94-96 and ending at the stop codon found at nucleotide positions 1063-1065 (Figure 115; SEQ ID N0:209). The predicted polypeptide precursor (Figure 116, SEQ ID N0:210) 425 is 323 amino acids long. The signal peptide is at about amino acids 1-15 of SEQ ID N0:210. PR01298 has a calculated molecular weight of approximately 37,017 daltons and an estimated pi of approximately 8.83. Clone DNA66511-1563 was deposited with the ATCC on September 15, 1998 and is assigned ATCC deposit no. 203228.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence 5 alignment analysis of the full-length sequence shown in Figure 116 (SEQIDNO:210), revealed sequence identity between the PR01298 amino acid sequence and the following Dayhoff sequences (data incorporated herein): ALG2_YEAST, CAPM_STAAU, C69098, C69255, SUS2 MAIZE, A69143, S74778, AB009527J3, AF050103_2 and BBA224769_1.

EXAMPLE 62: Isolation of cDNA clones Encoding Human PRQ1301 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the LIFESEQ® database, designated Incyte Cluster No. 93492, also referred herein as "DNA10591". This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database 15 (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). One or more of the ESTs was derived from a 20 cDNA library constructed from RNA isolated from lung tissue removed from a male with adenocarcinoma. The consensus sequence obtained therefrom is herein designated "DNA57725".

In light of the sequence homology between the DNA57725 sequence and an EST sequence contained within the EST no. 3395984, the EST clone 3395984 was purchased and the cDNA insert was obtained and sequenced in its entirety. The sequence of this cDNA insert is shown in Figure 117 and is herein designated as 25 "DNA66512-1564".

The full length clone shown in Figure 117 contained a single open reading frame with an apparent translational initiation site at nucleotide positions 43 to 45 and ending at the stop codon found at nucleotide positions 1429 to 1431 (Figure 117; SEQIDNO:211). The predicted polypeptide precursor (Figure 118, SEQ ID NO:212) is 462 amino acids long. Other features of the PR01301 protein include: a signal sequence at about 30 amino acids 1-18; a transmembrane domain at about amino acids 271-290; a cytochrome P450 homologous region at about amino acids 134-462; and potential N-glycosylation sites at about amino acids 94-97,217-220, and 246-249. PR01301 has a calculated molecular weight of approximately 52,432 daltons and an estimated pi of approximately 6.14. Clone DNA66512-1564 was deposited with the ATCC on September 15, 1998 and is assigned ATCC deposit no. 203218.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 118 (SEQ ID NO:212), revealed some homology between the PR01301 amino acid sequence and the following Dayhoff sequences: PSU29243_1, A69975, 426 ATAC00448418, D78607_l, CEB0331_1, HUMCYTI1IA_], AF014800_1, CELT13C5_4, CELC45H4_14, and CEC54E10J.

EXAMPT .F. 61: Isolation of cDNA clones Encoding Human PRQ1268 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST 5 cluster sequence from the LIFESEQ* database, designated EST No. 8879. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ*, Incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. The homology search was performed Miing the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score 10 of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Piil Green, University of Washington, Seattle, Washington). One or more of the ESTs was derived from a cI>NA library constructed from human brain tumor tissue taken from a cerebral meninges lesion. The consensus sequence obtained therefrom is herein designated DNA56258.

In light of the sequence homology between the DNA56258 sequence and an EST sequence contained within the Incyte EST no. 2944341, EST clone no. 2944541 vas purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 119 and is herein designated as "DNA66519-1535".

Tbe full length clone shown in Figure 119 contained a single open reading frame with an apparent 20 translational initiation site at nucleotide positions 89 to 91 and ending at the stop codon found at nucleotide positions 509 to 511 (Figure 119; SEQ ID NO:213). The predicted polypeptide precursor (Figure 120, SEQ ID NO:214) is 140 amino acids long. PRO 1268 has a calculated molecular weight of approximately 15,503 daltons and an estimated pi of approximately 6.44. Additional features include a type II transmembrane domain at about amino acids 12-28; type I transmembrane domains at a.bout amino acids 51-66 and 107-124; a potential 25 N-glycosylation site at about amino acids 79-82, and a region having homology with G-protein coupbled receptors at about amino acids 59-99.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 120 (SEQ ID NO:214), revealed some homology between the PR01268 amino acid sequence and Dayhoff sequence no. CEF39B2 9. However, the percent 30 sequence identity was determined to not be significant.

Clone DNA66519-1535 was deposited with the ATCC on September 15, 1998 and is assigned ATCC deposit no. 203236.

EXAMPLE 64: Isolation of cDNA clones Encoding Human PRO 1269 35 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the LIFESEQ® database, designated EST Cluster No. 101920. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases 427 (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®, incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enrvmology 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, 5 Seattle, Washington). The consensus sequence obtained therefrom is herein designated DNA56509.

In light of the sequence homology between the DNA56509 sequence and an EST sequence contained within the EST no. 103157, EST clone no.103157 was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 121 and is herein designated as DNA66520-1536.

The full length clone shown in Figure 121 contained a single open reading frame with an apparent translational initiation site at nucleotide positions 26-29 and ending at ihe stop codon found at nucleotide positions 614-616 (Figure 121; SEQ ID NO:215). The predicted polypeptide precursor (Figure 122, SEQ ID NO:216) is 196 amino acids long, with a signal peptide located at about amino acids 1-20. There is a potential N-glycosyiation site at about amino acids 112-115. PR01269 has a calculated molecular weight of approximately 15 21,731 daltons and an estimated pi of approximately 8.97.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 122 (SEQ ID NO:216), revealed significant homology between the PR01269 amino acid sequence and the amino acid sequence of Dayhoff sequence no. P_W23722. In addition, sequence homology was found between the PR01269 amino acid sequences and the 20 amino acid sequences of the following Dayhoff sequences: MMTAG7_1, MTV026 16, NAAA BPT3, S75616J, and NCP_PIG.

Clone DNA66520-1536 was deposited with the ATCC on September 15,1998, and is assigned ATCC deposit no. 203226.

EXAMPLE 65: Isolation of cDNA clones Encoding Human PRQ1327 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the Incyte database, designated Incyte EST cluster sequence no. 173410. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, 30 CA) to identify existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated DNA56520. 35 In light of the sequence homology between the DNA56S20 sequence and an EST sequence contained within the Incyte EST clone no. 3451760, the Incyte EST clone no. 3451760 was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 123 and is herein designated 428 as DNA66521-1583.

Clone DNA66521-1583 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 55-57 and ending at the stop codon at nucleotide positions 811-813 (Figure 123). The predicted polypeptide precursor is 252 amino acids long (Figure 124). The full-length PR01327 protein shown in Figure 124 has an estimated molecular weight of about 28,127 daltons and a pi of about 8.91. Analysis of 5 the full-length PR01327 sequence shown in Figure 124 (SEQ ID NO:218) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 14, potential N-glycosylation sites from about amino acid 62 to about amino acid 65, from about amino acid 127 to about amino acid 130, from about amino acid 137 to about amino acid 140 and from about amino acid 143 to about amino acid 146 and a 2-oxo acid dehydrogenase acyltransferase homology block from about amino acid 61 to about amino acid 71. Clone 10 DNA66521-1583 has been deposited with ATCC on September 15, 1998 and is assigned ATCC deposit no. 203225.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 124 (SEQ ID NO:218), evidenced significant homology between the PR01327 amino acid sequence and the following Dayhoff sequences: NPH1_RAT, 15 NPH2_MOUSE, OTU_DROME, D40750, BB61RABIT, P_R23873, P_W09643, CAGHMGPA_1, HUMPRP11_1 and S670958J.

EXAMPLE 66: Isolation of cDNA clones Encoding Human PRQ1382 Using the method described in Example 1 above, Incyte EST no. 2719 was identified as a sequence of 20 interest having a BLAST score of 70 or greater that does not encode a known protein. The nucleotide sequence of EST no. 2719 is designated herein "DNA42842". Based on the DNA42842 sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01382.

PCR primers (forward and reverse) were synthesized: forward PCR primer ACGGCTCACCATGGGCTCCG (42842.fl; SEQ ID NO:221) reverse PCR primer AGGAAGAGGAGCCCTTGGAGTCCG (42842.rl; SEQ ED NO:222) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA42842 sequence which had the following nucleotide sequence: hybridization probe CGTGCTGGAGGGCAAGTGTCTGGTGGTGTGCGACTCGAAC (42842.pl; SEQ ID 30 NO:223).

In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01382 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from a human breast carcinoma. 35 DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PR01382 (designated herein as DNA66526-1616 [Figure 125, SEQ ID NO:219]; and the derived protein sequence for PR01382. 429 The entire coding sequence of PR01382 is shown in Figure 125 (SEQ ID NO:219). Clone DNA66526-1616 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 337-339 and an apparent stop codon at nucleotide positions 940-942. The predicted polypeptide precursor is 201 amino acids long. The full-length PR01382 protein shown in Figure 126 has an estimated molecular weight of about 21,808 daltons and a pi of about 9.04. Additional features include a signal peptide at about amino acids 5 1-27; potential N-glycosylation sites at about amino acids 29-32 and 88-91; and regions of homology with Clq proteins at about amino acids 92-126, 159-178, and 191-200.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 126 (SEQ ID N0:220), revealed significant homology between the PR01382 amino acid sequence Dayhoff sequence no. CERL RAT. Homology was also 10 revealed between the PR01382 amino acid sequence and the following Dayhoff sequences: CERB HUMAN, S76975_l, A41752, HUMC1QB2_1, A57131, CA1A_HUMAN, ACR3_MOUSE, and COLELEPMA.

Clone DNA66526-1616 has been deposited with ATCC and is assigned ATCC deposit no. 203246.

EXAMPLE 67: Isolation of cDNA clones Encoding Human PRO 132ft IS Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the Incyte database, designated Incyte EST cluster sequence no. 40671. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database (Lifeseq®, Incyte Pharmaceuticals, Palo Alto, CA) to identiiy existing homologies. The homology search was performed using the computer program BLAST 20 or BLAST2 (Altshul et al.. Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated DNA56749.

In light of the sequence homology between the DNA56749. sequence and an ESt sequence contained 25 within the Incyte EST clone no. 4111192, the Incyte EST clone no. 4111192 was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 127 and is herein designated as DNA66658-1584.

Clone DNA66658-1584 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 9-11 and ending at the stop codon at nucleotide positions 780-782 (Figure 127). The 30 predicted polypeptide precursor is 257 amino acids long (Figure 128). The full-length PROI328 protein shown in Figure 128 has an estimated molecular weight of about 28,472 daltons and a pi of about 9.33. Analysis of the full-length PR01328 sequence shown in Figure 128 (SEQ ID NO:225) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 19, transmembrane domains from about amino acid 32 to about amino acid 51, from about amino acid 119 to about amino acid 138, from about amino 35 acid 152 to about amino acid 169 and from about amino acid 216 to about amino acid 235, a glycosaminoglycan attachment site from about amino acid 120 to about amino acid 123 and sodrum/rmerotransmitter symporter family protein homology block from about amino acid 31 to about amino acid 65. Clone DNA66658-1584 has 430 been deposited with ATCC on September 15, 1998 and is assigned ATCC deposit no. 203229.

An analysis of tbe Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 128 (SEQ ID NO:225), evidenced significant homology between the PR01328 amino acid sequence and the following Dayhoff sequences: CEVF36H2L 2, TIP2_TOBAC, AB009466 16, ATU39485_1, P_R60153, P_R77082, S73351, C69392, LEU95008_1 and 5 E64667.

EXAMPLE 68: Isolation of cDNA clones Encoding Human PRQ1325 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the Incyte database, designated Incyte EST cluster sequence no. 139524. This EST cluster 10 sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database (Lifeseq®, Incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and 15 assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated DNA56115.

In light of the sequence homology between the DNA56115 sequence and an EST sequence contained within the Incyte EST clone no. 3744079, the Incyte EST clone no. 3744079 was purchased and the cDN A insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 129 and is herein designated 20 as DNA66659-1593.

Clone DNA66659-1593 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 51-53 and ending at the stop codon at nucleotide positions 2547-2549 (Figure 129). The predicted polypeptide precursor is 832 amino acids long (Figure 130). The full-length PR01325 protein shown in Figure 130 has an estimated molecular weight of about 94,454 daltons and a pi of about 6.94. Analysis 25 of the full-length PR01325 sequence shown in Figure 130 (SEQ ID NO:227) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 18, transmembrane domains from about amino acid 292 to about amino acid 317, from about amino acid 451 to about amino acid 470, from about amino acid 501 to about amino acid 520, from about amino acid 607 to about amino acid 627 from about amino acid 751 to about amino acid 770, a leucine zipper pattern sequence from about amino acid 497 to about amino acid 30 518 and potential N-glycosylation sites from about amino acid 27 to about amino acid 30, from about amino acid 54 to about amino acid 57, from about amino acid 60 to about amino acid 63, from about amino acid position 123 to about amino acid position 126, from about amino acid position 141 to about amino acid position 144, from about amino acid position 165 to about amino acid position 168, from about amino acid position 364 to about amino acid position 367, from about amino acid position 476 to about amino acid position 479, from about 35 amino acid position 496 to about amino acid position 499, from about amino acid position 572 to about amino acid position 575, from about amino acid position 603 to about amino acid position 606 and from about amino acid position 699 to about amino acid position 702. Clone DNA66659-1593 has been deposited with ATCC on 431 September 22,1998 and is assigned ATCC deposit no. 203269.

An analysis of die Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 130 (SEQ ID NO:227), evidenced significant homology between the PRO1325 amino acid sequence and the following Dayhoff sequences: CELR04E51, CELZK721 5, CELC30E1_5, CELC30E1_6, CELC30E12, CEY37H2C_1, CELC30E17, CELT07H8_7 and E64006.

EXAMPLE 69: Isolation of cDNA clones Encoding Human PRQ1340 Using the method set forth in Example 1 above, Incyte EST no. 878906 was identified as a sequence of interest having a BLAST score of 70 or greater that does not encode a known protein. The nucleotide sequence of EST no. 878906 is designated herein "DNA42809", Based on the DNA42809 sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01340.

PCR primers (forward and reverse) were synthesized: forward PCR primer TCCAGGTGGACCCCACTTCAGG (42809.fl; SEQ ID N0:430) reverse PCR nrimer GGGAGGCTTATAGGCCCAATCTGG (42809.rl; SEQ ID NO:431) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the DNA42809 sequence which had the following nucleotide sequence: hybridization nrobe GGCTTCAGCAGCACGTGTGAAGTCGAAGTCGCAGTCACAGATATCAATGA (42809.pl; SEQ ID NO:432) In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01340 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from human fetal kidney tissue.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PR01340 (designated herein as DNA66663-1598 [Figure 131, SEQ ID NO:228]; and the derived protein sequence for PR01340.

The entire coding sequence of PR01340 is shown in Figure 131 (SEQ ID NO:228). Clone DNA66663-1598 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 128-130 and an apparent stop codon at nucleotide positions 2549-2551. The predicted polypeptide precursor is 807 amino acids long. The full-length PR01340 protein shown in Figure 132 has an estimated molecular weight of about 87,614 daltons and a pi of about 4.83. Additional features include: a signal peptide at about amino acids 1-18; a transmembrane domain at about amino acids 762-784; a cell attachment sequence at about amino acids 492-494; potential N-glycosylation sites at about amino acids 517-520, 602-605 and 700-703; and cadherin extracellular repeat domains at about amino acids 307-351, 324-348, 67-103, 97-141 and 114-138.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 132 (SEQ ID NO:229), revealed significant homology between the PR01340 amino acid sequence and Dayhoff sequence no. 146536. Homology was also 432 intellectual property ofrce of m2 24 OCT 2003 received revealed between the PR01340 amino acid sequence and the following Dayhoff sequences: S55396, RATPDRPT_1, CADD_CHICK, CADl_CHICK, CADB CHICK, 150180, CAD4_CHICK, G02878, and DSC1MOUSE.

Clone DNA66663-1598 has been deposited with ATCC and is assigned ATCC deposit no. 203268.

EXAMPLE 70: Isolation of cDNA clones Encoding Human PRQ1339 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is designated herein "DNA40652". Within the consensus sequence assembly was Incyte EST 2479394. Based on the consensus sequence and other discoveries and information provided herein, the clone including Incyte EST 2479394 was purchased and sequenced in full. 10 Sequencing provided the nucleic acid sequence shown in Figure 133 which includes the sequence encoding PR01339.

Clone DNA66669-1597 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 9-11 and an apparent stop codon at nucleotide positions 1272-1274 of SEQ ID NO:233. The predicted polypeptide precursor is 421 amino acids long. The signal peptide is at about amino 15 acids 1-16 of SEQ ID NO:234. The region conserved in zinc carboxypeptidases and the N-glycosylation site are indcated in Figure 134. Clone DNA66669-1597 has been deposited with the ATCC and is assigned ATCC deposit no. 203272. The full-length PR01339 protein shown in Figure 134 has an estimated molecular weight of about 47,351 daltons and a pi of about 6.61.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence 20 alignment analysis of the full-length sequence shown in Figure 134 (SEQ ID NO:234), revealed sequence identity between the PRO1339 amino acid sequence and the following Dayhoff sequences (data incorporated herein): PJW01505, CBP1JHUMAN, HSA224866_1, P_R90293, YHT2_YEAST, CEF02D8_4, CEW01A8_6, P_W36815, HSU83411_1 and CBPNHUMAN.

EXAMPLE 71: Isolation of cDNA clones Encoding Human PRQ1337 Using the method described in Example 1 above, a single Incyte EST was identified (EST No. 1747546) and also referred to herein as "DNA4417". To assemble a consensus sequence, repeated cycles of BLAST and phrap were used to extend the DNA4417 sequence as far as possible using the sources of EST sequences discussed above. The consensus sequence is designated herein as "DNA45669". Based on the DNA45669 30 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01337.

PCR primers (forward and reverse) were synthesized: forward PCR primers: CAACCATGCAAGGACAGGGCAGG (45669.fl; SEQ ID NO:237) and 35 CTTTGCTGTTGGCCTCTGTGCTCCCAACCATGCAAGGACAGGGCAGG (45669.rl; SEQ ID NO:238); reverse PCR primers: TGACTCGGGGTCTCCAAAACCAGC (45669.rl; SEQ ID NO:239) and GGTATAGGCGGAAGGCAAAGTCGG (45669.r2; SEQ ID N0:240); 433 Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA45669 sequence which had the following nucleotide sequence: hvbridizationnrobe: GGC ATCTT ACCTTT ATGG AGT ACTCTTTGCTGTTGGCCTCTGTGCTCCr45669.pl: SEQ ID NO:241).

In order to screen several libraries for a source of a full-length clone, DNA from the libraries was 5 screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01337 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from human tissue.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PR01337 (designated herein as DNA66672-1586 [Figure 135, SEQ ID NO:235]; and the derived protein 10 sequence for PRO 1337.

TheentirecodingsequenceofPR01337isshowninFigure 135(SEQIDN0:235). CloneDNA66672-1586 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 60-62 and an apparent stop codon at nucleotide positions 1311-1313. The predicted polypeptide precursor is 417 amino acids long. The full-length PR01337 protein shown in Figure 136 has an estimated molecular weight of 15 about 46,493 daltons and a pi of about 9.79.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 136 (SEQ ID N0:236) revealed significant homology between the PR01337 amino acid sequence and the Dayhoff sequence THBG_HUMAN. Homology was also found between the PR01337 amino acid sequence and the following Dayhoff sequences: 20 KAINHUMAN, HSACT1_1, IPSP_HUMAN, G02081, HAMHPP_1, CPI6_RAT,S31507, AB000547_1, and KBP_MOUSE.

Clone DNA66672-1586 was deposited with the ATCC on September 22, 1998, and is assigned ATCC deposit no. 203265.

EXAMPLE 72: Isolation of cDNA clones Fnnnriing Human PRO 1342 A cDNA sequence isolated in the amylase screen described in Example 2 above is herein designated DNA43203. The DNA43203 sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and proprietary EST DNA databases (LIFESEQTM, Incyte Pharmaceuticals, Palo Alto, CA; Genentech, South San Francisco, CA) to identify 30 existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al.. Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into consensus DNA sequences with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is designated herein as "DNA48360". 35 Based on the DNA48360 sequence, oligonucleotide probes were generated and used to screen a human esophageal tissue library prepared as described in paragraph 1 of Example 2 above. The cloning vector was pRK5B (pRK5B is a precursor of pRK5D that does not contain the Sfil site; see, Holmes et al., Science. 434 253:1278-1280 (1991)), and tbe cDNA size cut was less than 2800 bp.

PCR primers (forward and reverse) were synthesized: forward PCR nrimer: 5'-GAAGCACCAGCCTTTATCTCTTCACC-3' (48360.fl; SEQ ID NO:244) reverse PCR primer: 5'- GTCAGAGTTGGTGGCTGTGCTAGC-3' (48360.rl; SEQ ID NO:245) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the DNA48360 sequence 5 which had the following nucleotide sequence: hybridization probe: 'GGACCCAGGCATCTTGCTTTCCAGCCACAAAGAGACAGATGAAGATGC-3 (48360.pl; SEQ ID NO:246) In order to screen several libraries for a source of a full-length clone, DNA from the libraries was 10 screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01342 gene using the probe oligonucleotide and one of the PCR primers.

A full length clone was identified that contained a single open reading frame with an apparent translational initiation site at nucleotide positions 239-241, and a stop signal at nucleotide positions 2027-2029 (Figure 137; SEQ ID NO:242). The predicted polypeptide precursor is 596 amino acids long has a calculated 15 molecular weight of approximately 57,173 daltons and an estimated pi of approximately 4.82. Additional features include: signal sequence at about amino acids 1-20; a transmembrane domain at about aminn acids 510-532; a potential N-glycosylation site at about amino acids 25-28; a glycosaminoglycan attachment site at about amino acids 325-328; and bacterial ice-nucieation protein octamer repeats at about amino acids 284-337,404-457,254-307, 359-412, 194-247, 239-292, 299-352, 134-187, 314-367, and 164-217.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 138 (SEQ ID NO:243), evidenced some homology between the PR01342 amino acid sequence and the following Dayhoff sequences: CELZC178 2, LMSAP2GN_1, D88734_, AMYH_YEAST, MMDSPPGJ, VGLXHSVEB, S52714, CELF59A6_5, CELK06A9 3, and YM96 YEAST.

Clone DNA66674-1599 was deposited with the ATCC on September 22,1998, and is assigned ATCC deposit no. 203281.

EXAMPLE 73: Isolation of cDNA clones Encoding Human PRQ1343 A cDNA sequence isolated in the amylase screen described in Example 2 above was found, by the WU-30 BLAST2 sequence alignment computer program, to have no significant sequence identity to any known human encoding nucleic acid. This cDNA sequence is herein designated DNA48921. Probes were generated from the sequence of the DNA48921 molecule and used to screen a human smooth muscle cell tissue library prepared as described in paragraph 1 above. The cloning vector was pRK5B (pRK5B is a precursor of pRK5D that does not contain the Sfil site; see, Holmes et al., Science. 253:1278-1280 (1991)), and the cDNA size cut was less 35 than 2800 bp.

The oligonucleotide probes employed were as follows: forward PCR primer (48921.fl) 5'-CAATATGCATCTTGCACGTCTGG-3' (SEQ ID NO:249) 435 reverse PCR primer (48921.rl) 5,-AAGCTTCTCTGCTTCCTTTCCTGC-3, (SEQ ID N0:250) hybridization probe (48921 .p I) ' -TGACCCCATTGAGAAGGTC ATTG AAGGGATCAACCGAGGGCTG-3' (SEQ ID N0.251) A full length clone was identified that contained a single open reading frame with an apparent translational initiation site at nucleotide positions 71-73 and a stop signal at nucleotide positions 812-814 (Figure 5 139, SEQ ID NO:247). The predicted polypeptide precursor is 247 amino acids long, has a calculated molecular weight of approximately 25,335 daltons and an estimated pi of approximately 7.0. Analysis of the full-length PR01343 sequence shown in Figure 140 (SEQ ID NO:248) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 25 and a homologous region to circumsporozoite repeats from about amino acid 35 to about amino acid 225: Clone DNA66675-1587 has been deposited with ATCC on 10 September 22, 1998 and is assigned ATCC deposit no. 203282.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 140 (SEQ ID NO:248), evidenced significant homology between the PR01343 amino acid sequence and the following Dayhoff sequences: CSP_PLACC, CEF25H82, U88974_40, BNAMRNAA_1, BOBOPC3_l, S58135, AF061832_1, BHU52040_1, 15 HUMPROFILEl and MTV023J4.

Additionally, an Incyte EST clone (Incyte EST clone no. 4701148) having homology to the DNA48921 sequence was obtained and the insert sequenced, thereby giving rise to the DNA66675-1587 sequence shown in Figure 139.

EXAMPLE 74: Isolation of cDNA clones Encoding Human PRQ1480 Using the methods described in Example 1 above, Incyte EST Nos. 550415 and 1628847 were identified as sequences of interest having BLAST scores of 70 or greater that did not encode known proteins. These sequences were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). This consensus sequence is designated herein as "DNA1395". 25 In addition, the "DNA 1395" consensus sequence was extended using repeated cycles of BLAST and phrap to extend the consensus sequence as far as possible using the sources of EST sequences discussed above. The extended consensus sequence is designated herein as "DNA40642". Based on the DNA40642 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01480. 30 PCR primers (forward and reverse) were synthesized: forward PCR primer: AGCCCGTGCAGAATCTGCTCCTGG (40642.fl; SEQ ID N0.254) reverse PCR primers: TGAAGCCAGGGCAGCGTCCTCTGG (40642.rl; SEQ ID NO:255); GTACAGGCTGCAGTTGGC (40642.r2; SEQ ID N0:256) Additionally, synthetic oligonucleotide hybridization probes were constructed from the consensus 35 DNA40642 sequence which had the following nucleotide sequence: hvbridizationprobes: AGAAGCCATGTGAGCAAGTCCAGTTCCAGCCCAACACAGTG(40642.pl; SEQ ID NO-.257); GAGCTGCAGATCTTCTCATCGGGACAGCCCGTGCAGAATCTGCTC (40642.p2; SEQ ID 436 NO:258).

In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01480 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from human fetal kidney tissue.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PRO1480, designated herein as DNA67962-1649 [Figure 141, SEQ ID NO.-252]; and the derived protein sequence for PR01480.

The entire coding sequence of PRO1480 is shown in Figure 141 (SEQIDNO-.252). Clone DNA67962-1649 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 10 241-243 and an apparent stop codon at nucleotide positions 27S2-27S4. The predicted polypeptide precursor is 837 amino acids long. The full-length PRO1480 protein shown in Figure 142 has an estimated molecular weight of about 92,750 daltons and a pi of about 7.04. Additional features include: transmembrane domains at about amino acids 23-46 (type II) and 718-738; potential N-glycosylation sites at about amino acids 69-72,96-99, 165-168, 410-413, 525-528, and 630-633; and a leucine zipper pattern at about amino acids 12-33. 15 An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 142 (SEQ ID NO:253), revealed significant homology between the PR01480amino acid sequence and Dayhoff sequence 148746. Homology was also shown between the PR01480 amino acid sequence and the following Dayhoff sequences: S66498; P_W17658; MMU69535_1; HSU60800_1; 148745; A49069; 148747; GGU28240_1; and AF022946_1. 20 Clone DNA67962-1649 has been deposited with ATCC and is assigned ATCC deposit no. 203291.

EXAMPLE 75: Isolation of cDNA clones Encoding Human PRQ1487 A single Merck EST, HSC2ID011, referred herein as "DNA8208", was identified as an EST of interest having a BLAST score of 70 or greater that did not encode a known protein as described in Example 1 above. 25 The DNA8208 sequence was extended using repeated cycles of BLAST and the program "phrap" (Phil Green, University of Washington, Seattle, Washington) to extend the sequence as far as possible using the sources of EST sequences discussed above. The resulting consensus sequence is designated herein as "DNA68836". Based on the DNA68836 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding 30 sequence for PR01487.

PCR primers (forward and reverse) were synthesized: forward PCR primer: GTGCCACTACGGGGTGTGGACGAC (54209.fl; SEQ ID NO:261) and reverse PCR primer TCCCATTTCTTCCGTGGTGCCCAG (54209.rl; SEQ ID NO:262) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus 35 DNA68836 sequence which had the following nucleotide sequence: hybridization probe CCAGAAGAAGTCCTTCATGATGCTCAAGTACATGCACGACCACTAC (54209.pl; SEQ ID NO:263) 437 In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01487 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated human fetal kidney tissue.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for 5 PRO1487 (designated herein as DNA68836-1656 (Figures 143A-B; SEQ ID NO:259) and the derived protein sequence for PR01487 (Figure 144; SEQ ID N0:260).

The entire coding sequence of PR01487 is shown in Figures I43A-B (SEQ ID NO:259). Clone DNA68836-1656 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 489-491 and an apparent stop codon at nucleotide positions 289S-2897. The predicted polypeptide 10 precursor is 802 amino acids long The full-length PR01487 protein shown in Figure 144 has an estimated molecular weight of about 91,812 daltons and a pi of about 9.S2. Additional features include a signal peptide at about amino acids 1-23; potential N-glycosylation sites at about amino acids 189-192, 623-626, and 796-799; and a cell attachment sequence at about amino acids 62-64.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence 15 alignment analysis of the full-length sequence shown in Figure 144 (SEQ ID N0:260), revealed significant homology between the PR01487 amino acid sequence and the following Dayhoff sequences: CET24D1_1, S44860, CELC02H61, CEC38H2_3, CELC17A2_5, CET09E11_10, CEE03H4_3, CELT22B113, GGU82088_1, and CEF56H6_1.

Clone DNA68836-1656 was deposited with the ATCC on November 3,1998, and is assigned ATCC 20 deposit no. 203455.

EXAMPLE 76: Isolation of cDNA clones Encoding Human PRQ1418 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from an Incyte database. This EST cluster sequence was then compared to a variety of 25 expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ9, Incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. One or more of the ESTs was derived from a placenta tissue library. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known 30 proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated DNA58845.

In light of the sequence homology between the DNA58845 sequence and an EST included in Incyte clone 1306026, that clone was purchased and the cDNA insert was obtained and sequenced. The sequence of 35 this cDNA insert is shown in Figure 145 and is herein designated as DNA68864-1629.

The full length clone shown in Figure 145 contained a single open reading frame with an apparent translational initiation site at nucleotide positions 138-140 and ending at the stop codon found at nucleotide 438 positions 1188-1190 (Figure 145; SEQ ID NO:264). The predicted polypeptide precursor (Figure 146, SEQ ID NO:265) is 350 amino acids long with a signal peptide at about amino acids 1-19 of SEQ ID NO:265. PR01418 has a calculated molecular weight of approximately 39,003 daltons and an estimated pi of approximately 5.59. Clone DNA68864-1629 was deposited with the ATCC on September 22, 1998 and is assigned ATCC deposit no. 203276.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 146 (SEQ ID NO:265), revealed sequence identity between the PR01418 amino acid sequence and the following Dayhoff sequences (data incorporated herein): AGA1_HAEIN (immunoglobulin al protease precursor), P_W03740, CELT23E7_1, SSN6_YEAST, MMPININ_1, AB00993 1, P_R52601, S22624, A10377_l and MUA1_XENLA.

EXAMPLE 77: Isolation of cDNA clones Encoding Human PRQ1472 An Incyte sequence was identified and put in a computer to determine whether it had homology with other proteins in databases. The EST databases included public EST databases (e.g., GenBank), and the proprietary EST database (LIFESEQ*, Incyte Pharmaceuticals, Palo Alto, CA). The search was performed 15 using the computer program BLAST or BLAST2 [Altschul etal., Methods in Enzvmologv. 266:460-480 (1996)1 as a comparison of the ECD protein sequences to a 6 frame translation of the EST sequences. Those comparisons resulting in a BLAST score of 70 (or in some cases, 90) or greater that did not encode known proteins were clustered and assembled into consensus DNA sequences with the program "phrap" (Phil Green, University of Washington, Seattle, Washington).

A consensus DNA sequence encoding PRO1472 was assembled relative to other EST sequences using phrap. This consensus sequence is designated herein "DNA62824". Based on the DNA62824 consensus sequence and other discoveries and information provided herein, the Incyte clone including EST 1579843 (from a duodenal tissue library) found in the assembly was purchased and sequenced in full.

Sequencing provided the entire coding sequence of PRO1472 as shown in Figure 147 (SEQ ID 25 NO:266). Clone DNA68866-1644 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 134-136 and an apparent stop codon at nucleotide positions 1532-1534 of SEQ ID NO:266. The predicted polypeptide precursor is 466 amino acids long. As indicated in Figure 148, the signal peptide is at about amino acid positions 1-17 and the transmembrane domains are at about positions 131-150 and 235-259 of SEQ ID NO:267. Clone DNA68866-1644 has been deposited with ATCC and is assigned ATCC 30 deposit no. 203283. The full-length PR01472 protein shown in Figure 148 has an estimated molecular weight of about 52,279 daltons and a pi of about 6.16.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 148 (SEQ ID NO:267), revealed sequence identity between the PRO 1472 amino acid sequence and the following Dayhoff sequences (data incorporated herein): 35 BUTTHUMAN, HS45P21_1, HS45P21_3, HS45P21_5, HS45P21_4, HSU90142_1, HSU90546_1, AF033107 1, MMHC135G15 7andHSB73 1. 439 PCT/US99/201I1 EXAMPLE 78: Isolation of cDNA clones Encoding Human PRQ1461 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from die LIFESEQ* database, designated Incyte EST Cluster No. 139103, and also referred to herein as "DNA10747". The DNA10747 sequence was then compared to a variety of EST databases which included public EST databases (e.g., GenBank) and the LIFESEQ* database, to identify existing homologies.

The homology search was performed using the computer program BLAST or BLAST2 (Altshul etal., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). One or more of the ESTs used in the assembly was derived from a library constructed from pancreatic tumor tissue. The consensus 10 sequence obtained therefrom is herein designated "DNA59553".

In ligbt of the sequence homology between the DNAS9S53 sequence and an EST sequence contained within Incyte EST no. 2944541, the EST clone was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 149 and is herein designated as DNA68871-1638.

The full length clone shown in Figure 149 contained a single open reading frame with an apparent 15 translational initiation site at nucleotide positions 32-34 and ending at the stop codon found at nucleotide positions 1301-1303 (Figure 149; SEQ ID NO:268). The predicted polypeptide precursor (Figure 150, SEQ ID NO:269) is 423 amino acids long. PR01461 has a calculated molecular weight of approximately 47,696 daltons and an estimated pi of approximately 8.96. Additional features include: a type II transmembrane domain at about amino acids 21-40; an ATP/GTP-binding site motif A (P-loop) at about amino acids 359-366; a trypsin family histidine 20 active site at about amino acids 228-233; potential N-myristoylation sites at about aminn acids 179-184,213-218, 317-322, and 360-365; and potential N-glycosylation sites at about amino acids 75-78, 166-169 and 223-226.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 150 (SEQ ID NO:269), revealed significant homology between the PR0146I amino acid sequence Dayhoff sequence no. P R89435. Homology was also 25 found to exist between the PRO 1461 amino acid sequence and the following additional Dayhoff sequences: AB002134_1, P_R89430, P_W22987, HEPS_MOUSE, ENTKHUMAN, P_W22986, KAL_MOUSE, ACRO_PIG, p_R57283, and TRY7_ANOGA.

Clone DNA68871-68871 was deposited with the ATCC on September 22,1998, and is assigned ATCC deposit no.203280.

FX A MPT,F. 79: Isolation of cDNA clones Encoding Human PRQ1410 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the Incyte database, designated Incyte EST cluster sequence no. 98502. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST 35 databases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ*, Incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a 440 BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Gteen, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated DNA56451.

In light of the sequence homology between the DNA56451 sequence and an EST sequence contained within the Incyte EST clone no. 1257046, the Incyte EST clone 125046 was purchased and the cDNA insert was 5 obtained and sequenced. The sequence of this cDNA insert is shown in Figure 151 and is herein designated as DN A68874-1622.

Clone DNA68874-1622 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 152-154 and ending at the stop codon at nucleotide positions 866-868 (Figure 151). The predicted polypeptide precursor is 238 amino acids long (Figure 152). The full-length PR01410 protein 10 shown in Figure 152 has an estimated molecular weight of about 25,262 daltons and a pi of about 6.44. Analysis of the full-length PR01410 sequence shown in Figure 152 (SEQ ID NO:27i) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 20, a transmembrane domain from about amino acid 194 to about amino acid 220 and a potential N-glycosylation site from about amino acid 132 to about amino acid 135. Clone DNA68874-1622 has been deposited with ATCC on September 22,1998 and is assigned 15 ATCC deposit no. 203277 An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 152 (SEQ ID NO.271), evidenced significant homology between the PR01410 amino acid sequence and die following Dayhoff sequences: 148652, PR76466, HSMHC3W36A_2, EPB4_HUMAN, P_R14256, EPA8_MOUSE, P_R77285, P_W13569, AF000560_1, and 20 ASF1_HELAN.

EXAMPLE 80: Isolation of cDNA clones Encoding Human PRQ1568 A consensus DNA sequence was assembled relative to other EST sequences using phrap to form an assembly as described in Example 1 above. The consensus sequence is designated herein "DNA54208". Based 25 on the DNA54208 consensus sequence, the assembly and other information and discoveries provided herein, a clone including an EST in the assembly was ordered and sequenced. The EST is Incyte 3089490. Sequencing in full gave the sequence shown in Figure 153.

The entire coding sequence of PR01568 is included in Figure 153 (SEQ ID NO:272). Clone DNA68880-1676 contains a single open reading frame with an apparent translational initiation site at nucleotide 30 positions 208-210 and an apparent stop codon at nucleotide positions 1123-1125 of SEQ ID NO:272. The predicted polypeptide precursor is 305 amino acids long. The' signal peptide, transmembrane regions, N-myristoylation and amidation sites axe also indicated in Figure 154. Clone DNA68880-1676 has been deposited with the ATCC and is assigned ATCC deposit no. 203319. The full-length PR01568 protein shown in Figure 154 has an estimated molecular weight of about 35,383 daltons and a pi of about 5.99. 35 An analysis of the Dayhoff database (version 35.45 SwissProt 3S), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 154 (SEQ ID NO:273), revealed sequence identity between the PRO1568 amino acid sequence and the following Dayhoff sequences (incorporated herein): 441 AF089749_1, AF054841_1, NAG2_HUMAN, CD63_HUMAN, CD82_HUMAN, P_W05732, P R86834, A15HUMAN, P W27333 and CD37HUMAN.

EXAMPLE 81: Isolation of cDNA clones Encoding Human PRO 1570 A consensus DNA sequence encoding PR01570 was assembled relative to other EST sequences using 5 phrap as described in Example 1 above to form an assemby. This consensus sequence is designated herein as "DNA65415". Based on the DNA65415 consensus sequence and other discoveries and information provided herein, the clone including Incyte EST 3232285 (from a uterine/colon cancer tissue library) was purchased and sequenced in full which gave SEQ ID NO:274.

The entire coding sequence of PR01570 is included in Figure 155 (SEQ ID NO:274). Clone 10 DNA68885-1678 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 210-212 and an apparent stop codon at nucleotide positions 1506-1508 of SEQ ID NO:274. The predicted polypeptide precursor is 432 amino acids long. Figure 275 shows a number of motifs. Clone DNA68885-1678 has been deposited with the ATCC and is assigned ATCC deposit no. 203311. The full-length PR01570 protein shown in Figure 156 has an estimated molecular weight of about 47,644 daltons and a pi of 15 about 5.18.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 156 (SEQ ID NO:275), revealed sequence identity between the PR01570 amino acid sequence and the following Dayhoff sequences (incorporated herein): P_W22986, TMS2_HUMAN, HEPS_HUMAN, P_R89435, AB002134_1, KAL_MOUSE, ACRO_HUMAN, 20 GEN12917, AF045649_1, and P_W34285.

EXAMPLE 82: Isolation of cDNA clones Encoding Human PRQ1317 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is designated herein "Consen8865". In addition, the Consen8865 25 consensus sequence was extended using repeated cycles of BLAST and phrap to extend the consensus sequence as far as possible using the sources of EST sequences discussed above. The extended consensus sequence is designated herein as HDNA63334". Based on the DNA63334 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA Library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01317.

PCR primers (forward and reverse) were synthesized: forward PCR primer: CTGCTGGTGAAATCTGGCGTGGAG (63334.fl; SEQ ID NO:278); and reverse PCR primer: GTCTGGTCCTGGCTGTCCACCCAG (63334.rl; SEQ ID NO:279).

Additionally, a synthetic oligonucleotide hybridization probe was constructed from tbe consensus DNA63334 sequence which had the following nucleotide sequence: hvbridizationprobe: CATCTTGTCATGTACCTGGGAACCACCACAGGGTCGCTCCACAAG(63334.pl; SEQ ID N0:280).

In order to screen several libraries for a source of a full-length clone, DNA from the libraries was 442 PCT/US99/201II screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01317 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from human hippocampal tissue.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PR01317 (designated herein as DNA71166-1685 [Figure 157, SEQ ID NO:276J; and the derived protein 5 sequence for PR01317.

The entire coding sequence of PRO 1317 is shown in Figure 157 (SEQ ID NO:276). Clone DNA71166-1685 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 105-107 and an apparent stop codon at nucleotide positions 2388-2390. The predicted polypeptide precursor is 761 amino acids long and has an estimated molecular weight of about 83,574 daltons and a pi of about 6.78. 10 An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 158 (SEQ ID NO:277), revealed significant homology between the PR01317 amino acid sequence and Dayhoff sequence no. 148745. Homology was also revealed between the PR01317 amino acid sequence the following Dayhoff sequences: 148746, GEN13418, P_W58540, P 217657, MUSC1J, P_471380, U73167_5, HSU33920_1, and GG828240_1. 15 Clone DNA71166-1685 was deposited with the ATCC on October 20, 1998, and is assigned ATCC deposit no. 203355.

EXAMPLE 83: Isolation of cDNA clones Encoding Human PRQ1780 The DNA63837.init sequence was obtained as described in Example 1 above and was extended using 20 repeated cycles of BLAST and the program "phrap" (Phil Green, University of Washington, Seattle) to extend the consensus sequence as far as possible using the sources of EST sequences discussed above. The extended consensus sequence is designated herein as "DNA63837". Based on the DNA63837 consensus sequence, oligonucleotides were synthesized: 1) to identiiy by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01780. 25 PCR primers (forward and reverse) were synthesized: forward PCR primer: TGCCTTTGCTCACCTACCCCAAGG (63837.fl; SEQ ID NO:283) reverse PCR primer: TCAGGCTGGTCTCCAAAGAGAGGG (63837.rl; SEQ ID NO:284) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA63837 sequence which had the following nucleotide sequence: hybridization probe: CCCAAAGATGTCCACCTGGCTGCAAATGTGAAAATTGTGGACTGG (63837.pl; SEQ ID NO:285) In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01780 gene using the probe oligonucleotide and one of the PCR primers. RNA 35 for construction of the cDNA libraries was isolated from a human fetal kidney.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PR01780 (designated herein as DNA71169-1709 [Figure 159, SEQ ID NO:281]; and the derived protein 443 sequence for PR01780.

The entire coding sequence of PR01780 is shown in Figure 159 (SEQ ID NO:281). Clone DNA71169-1709 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 68-70 and an apparent stop codon at nucleotide positions 1637-1639. The predicted polypeptide precursor is 523 amino acids long. The full-length PR01780 protein shown in Figure 160 has an estimated molecular weight of 5 about 59,581 daltons and a pi of about 8.68. Additional features include a signal peptide sequence at about amino acids 1 • 19; a transmembrane domain at about amino acids 483-504; tyrosine phosphorylation sites at about amino acids 68-74 and 425-433; N-myristoylation sites at about amino acids 16-21,301-206,370-375, and 494-499; and a leucine zipper pattern at about amino acids 493-514.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence 10 alignment analysis of the full-length sequence shown in Figure 160 (SEQ ID NO:282), revealed significant homology between the PR01780 amino acid sequence and the following Dayhoff sequences: UDA2RABIT, CGTHUMAN, UD11_HUMAN, P_R26153, UDB1JRAT, HSU59209_1, AB010872_1, UDB5_MOUSE, UDB8_HUMAN, and UD14JHUMAN.

Clone DNA71169-1709 was deposited with the ATCC on November 17,1998, and is assigned ATCC 15 deposit no. 203467.

EXAMPLE 84: Isolation of cDNA clones Encoding Human PRQ1486 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is designated herein "DNA48897". Based on the DNA48897 20 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01486.

PCR primers (forward and reverse) were synthesized: forward PCR primer 5' AGGCAGCCACCAGCTCTGTGCTAC3' (SEQ ID NO:288); and 25 reverse PCR primer 5'CAGAGAGGGAAGATGAGGAAGCCAGAG3* (SEQ ID NO:289).

Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA48897 sequence which had the following nucleotide sequence: hybridization probe 5'CTGTGCTACTGCCCTTGGACCCTGGGGACCGAGTGTCTCTGC3' (SEQ ID N0:290).

In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01486 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from a human adenocarcinoma cell line.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for 35 PROI486 and the derived protein sequence for PR01486.

The entire coding sequence of PR01486 is included in Figure 161 (SEQ ID NO:286). Clone DNA71180-1655 contains a single open reading frame with an apparent translational initiation site at nucleotide 444 positions 472-474 and an apparent stop codon at nucleotide positions 1087-1089 of SEQ ID NO:286. The predicted polypeptide precursor is 205 amino acids long. The signal peptide is at about amino acids 1-32 of SEQ ID NO:287. Regions similar to those of Clq and an N-glycosylationi site are located as indicated in Figure 162. Clone DNA71180-1655 has been deposited with the ATCC and is assigned ATCC deposit no. 203403. The full-length PR01486protein shown in Figure 162 has an estimated molecular weight of about21,521 daltons 5 and a pi of about 7.07.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 162 (SEQ ID NO:287), revealed sequence identity between the PR01486 amino acid sequence and the following Dayhoff sequences: CERB_HUMAN, CERLJRAT, GEN11893, P_R22263, CA18_HUMAN, C1QCHUMAN, AF054891_1, A57131, 10 HUMClQb2_l, ACR3MOUSE.

EXAMPLE 85: Isolation of cDNA clones Encoding Human PRQ1433 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is herein designated DNA45230. Based on the DNA45230 15 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01433.

PCR primers (forward and reverse) were synthesized: forward PCR primer f45230.fl) 5,-GCTGACCTGGTTCCCATCTACTCC-3, (SEQ ID NO:293) 20 reverse PCR primer (45230.rl) 5' -CCCACAGACACCCATGACACTTCC-3' (SEQ ID NO:294) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA45230 sequence which had the following nucleotide sequence hybridization probe (4S230.pl) '-AAGAATGAATTGTACAAAGCAGGTGATCTTCGAGGAGGGCTCCTGGGGCC-3' (SEQ ID NO-.295) 25 In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01433 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from human adrenal gland tissue.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for 30 PR01433 (designated herein as DNA71184-1634 [Figure 163, SEQ ID NO:291]; and the derived protein sequence for PRO1433.

The entire nucleotide sequence of DNA71184-1634 is shown in Figure 163 (SEQ ID NO:291). Clone DNA71184-1634 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 185-187 and ending at the stop codon at nucleotide positions 1349-1351 (Figure 163). The predicted 35 polypeptide precursor is 388 amino acids long (Figure 164). The full-length PRO1433 protein shown in Figure 164 has an estimated molecular weight of about 43,831 daltons and a pi of about 9.64. Analysis of the full-length PR01433 sequence shown in Figure 164 (SEQ ID NO:292) evidences the presence of the following: a 445 transmembrane domain from about amino acid 76 to about amino acid 97, potential N-glycosylation sites from about amino acid 60 to about amino acid 63, from about amino acid 173 to about amino acid 176 and from about amino acid 228 to about amino acid 231 and potential N-myristolation sites from about amino acid 10 to about amino acid IS, from about amino acid 41 to about amino acid 46, from about amino acid 84 to about amino acid 89, from about amino acid 120 to about amino acid 123, from about amino acid 169 to about amino acid 174, 5 from about amino acid 229 to about amino acid 234, from about amino acid 240 to about amino acid 245, from about amino acid 318 to about amino acid 323 and from about amino acid 378 to about amino acid 383. Clone DNA71184-1634 has been deposited with ATCC on September 22, 1998 and is assigned ATCC deposit no. 203266.

An analysis of the Dayhoff database (version 33.45 SwissProt 35), using a WU-BLAST2 sequence 10 alignment analysis of the full-length sequence shown in Figure 164 (SEQ ID NO:292), evidenced significant homology between the PR01433 amino acid sequence and the following Dayhoff sequences: CELW01A114, CEF59A14, S67138, MTV050 3, S75135 and S12411.

EXAMPLE 86: Isolation of cDNA clones Encoding Human PRQ1490 IS A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is herein designated DNA67006. Based on tbe DNA67006 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01490.

PCR primers (forward and reverse) were synthesized: forward PCR primer f67006.fn 5'-CTTCCTCTGTGGGTGGACCATGTG-3' (SEQ ID NO:298) reverse PCR primer (67006.rn 5' -GCCACCTCCATGCTAACGCGG-3' (SEQ ID NO:299) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA67006 sequence which had the following nucleotide sequence 25 hybridization probe (67006.dP '-CCAAGGTCCTCGCTAAGAAGGAGCTGCTCTACGTGCCCCTCATCG-3' (SEQ ID N0:300) In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PRO1490 gene using the probe oligonucleotide and one of the PCR primers. RNA 30 for construction of the cDNA libraries was isolated from human adrenal gland tissue.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PR01490 (designated herein as DNA71213-1659 [Figure 165, SEQ ID NO:296]; and the derived protein sequence for PR01490.

The entire nucleotide sequence of DNA71213-1659 is shown in Figure 165 (SEQ ID NO:296). Clone 35 DNA71213-1659 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 272-274 and ending at the stop codon at nucleotide positions 1376-1378 (Figure 165). The predicted polypeptide precursor is 368 amino acids long (Figure 166). The full-length PR01490 protein shown in Figure 446 WO 00/12708 PCT/US99/20111 166 has an estimated molecular weight of about 42,550 daltons and a pi of about 9.11. Analysis of the full-length PR01490 sequence shown in Figure 166 (SEQ ID NO:297) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 25, transmembrane domains from about amino acid 307 to about amino acid 323 and from about amino acid 335 to about amino acid 352 and tyrosine kinase phosphorylation sites from about amino acid 160 to about amino acid 168 and from about amino acid 161 to 5 about amino acid 168. Clone DNA71213-1659 has been deposited with ATCC on October 27, 1998 and is assigned ATCC deposit no. 203401.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 166 (SEQ ID NO:297), evidenced significant homology between the PRO1490 amino acid sequence and the following Dayhoff sequences: A52744_l, S60478, 10 P_R99249, P_R59712, YBP2YEAST, S54641, CELT05H4_15, CELF28B3_1, CELZK40J and YIHG_ECOLI.

EXAMPLE 87: Isolation of cDNA clones Encoding Human PRO 1482 A cDNA clone (DNA71234-1651) encoding a native human PR01482 polypeptide was identified by 15 a yeast screen, in a human adrenal gland cDNA library that preferentially represents the 5' ends of the primary cDNA clones.

The full-length DNA71234-1651 clone shown in Figure 167 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 33-35 and ending at the stop codon at nucleotide positions 462-464 (Figure 167). The predicted polypeptide precursor is 143 amino acids long (Figure 168). The 20 full-length PR01482 protein shown in Figure 168 has an estimated molecular weight of about 15,624 daltons and a pi of about 9.58. Analysis of the full-length PR01482 sequence shown in Figure 168 (SEQ ID N0:302) evidences the presence of the following: a signal peptide from about mim acid 1 to about amino acid 28. Clone DNA71234-1651 has been deposited with ATCC on October 27, 1998 and is assigned ATCC deposit no. 203402.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 168 (SEQ ID N0:302), evidenced significant homology between the PR01482 amino acid sequence and the following Dayhoff sequences: A18267_3.

FYAKfpT F SS- Isolation of cDNA clones Encoding Human PRQ1446 30 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from tbe Incyte database. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. One or more of the ESTs was derived from a pancreatic islet cell library. The homology search was performed using 35 the computer program BLAST or BLAST2 (Altshul etal., Methods in Enzvmologv 266:460-480 (1996Y). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, 447 University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated DNAS6514.

In light of the sequence homology between the DNA56514 sequence and an EST sequence contained within the Incyte EST 2380344, the clone including this EST was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 169 and is herein designated as 5 DNA71277-I636.

The full length clone shown in Figure 169 contained a single open reading frame with an apparent translational initiation site at nucleotide positions 152-154 and ending at the stop codon found at nucleotide positions 479-481 (Figure 169; SEQ ID N0:303). The predicted polypeptide precursor (Figure 170, SEQ ID N0:304) is 109 amino acids long with a signal peptide at about amino acids 1-15 of SEQ ID N0:304. PR01446 10 has a calculated molecular weight of approximately 11,822 daltons and an estimated pi of approximately 8.63. Clone DNA71277-1636 was deposited with the ATCC on September 22, 1998 and is assigned ATCC deposit no. 203285.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 170 (SEQ ID N0:304), revealed sequence identity 15 between the PR01446 amino acid sequence and the following Dayhoff sequences (data incorporated herein); P53_CANFA, P53_FELCA,LRP1_HSV1F, OSU57338 1, S75842, P_P93722, AF002189_1, B70408, S54309 andS53365. The first in this list is further described in Kraegel, et al., Cancer Lett.. 92(2): 181-186 (1995).

EXAMPLE ?9: Isolation of cDNA clones Encoding Human PRQ1558 20 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the Incyte database, designated Incyte EST cluster sequence no. 86390. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ*, Incyte Pharmaceuticals, Palo Alto, C A) to identify existing homologies. The homology search was performed using the computer program BLAST 25 or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated DNA58842.

In light of the sequence homology between the DNA58842 sequence and an EST sequence contained 30 within the Incyte EST clone no. 3746964, the Incyte EST clone no. 3746964 was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 171 and is herein designated as DNA71282-1668.

Clone DNA71282-1668 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 84-86 and ending at the stop codon at nucleotide positions 870-872 (Figure 171). The 35 predicted polypeptide precursor is 262 amino acids long (Figure 172). Hie full-length PR01558 protein shown in Figure 172 has an estimated molecular weight of about 28,809 daltons and a pi of about 8.80. Analysis of the full-length PRO 1558 sequence shown in Figure 172 (SEQ ID N0:306) evidences the presence of the 448 WO 00/12708 PCT/US99/20111 following: a signal peptide from about amino acid 1 to about amino acid 25, transmembrane domains from about amino acid 8 to about amino acid 30 and from about amino acid 109 to about amino acid 130, a potential N-glycosylation site from about amino acid 190 to about amino acid 193, a tyrosine kinase phosphorylation site from about amino acid 238 to about amino acid 246, potential N-myristolatkm sites from about amino acid 22 to about amino acid 27, from about amino acid 28 to about amino acid 33, from about amino acid 110 to about 5 amino acid 115, from about amino acid 205 to about amino acid 210 and from about amino acid 255 to about amino acid 260 and amidation sites from about amino acid 31 to about amino acid 34 and from about amino acid 39 to about amino acid 42. Clone DNA71282-1668 has been deposited with ATCC on October 6, 1998 and is assigned ATCC deposit no. 203312.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence 10 alignment analysis of the full-length sequence shown in Figure 172 (SEQ ID N0:306), evidenced significant homology between the PRO1558 amino acid sequence and the following Dayhoff sequences: AF075724_2, MXU24657J, CAMT_EUCGU, MSU20736_1, P_R29515, B70431, JC4004, CEY32B12A_3, CELF53B3_2 and PJR13543.

EXAMPLE 90: Isolation of cDNA clones Encoding Human PRO 1604 An expressed sequence tag (EST) DNA database (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, CA) was searched. Incyte EST No. 3550440 was identified as having homology to HDGF. EST No. 3550440 was then compared to various EST databases including public EST databases (e.g. GenBank), and the LIFESEQ® database, to identify homologous EST sequences. The search was performed using the computer program 20 BLAST or BLAST2 [Altschul et al., Methods in Enzvmologv. 266:460-480 (1996)]. Those comparisons resulting in a BLAST score of 70 (or in some cases, 90) or greater that did not encode known proteins were clustered and assembled into consensus DNA sequences with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). This consensus sequence is designated herein "DNA67237".

In light of the sequence homology between the DNA67237 sequence and EST no. 3367060 from the 25 LIFESEQ® database, the clone containing Incyte EST No. 3367060 was purchased and the cDNA insert was obtained and sequenced to obtain the entire coding sequence of PR01604 which is shown in Figure 173 (SEQ ID N0:307).

Clone DNA71286-1687 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 65-67 and an apparent stop codon at nucleotide positions 2078-2080. The predicted 30 polypeptide precursor is 671 amino acids long. The full-length PR01604 protein shown in Figure 174 has an estimated molecular weight of about 74,317 daltons and a pi of about 7.62. Additional features include a signal peptide at about amino acids 1-13; potential cAMP- and cGMP-dependent protein kinase phosphorylation sites at about amino acids 156-159,171-174, and 451-454; potential N-myristoylation sites at about amino acids 46-51, 365-370, and 367-372; and a cell attachment sequence at about amino acids 661-663. 35 An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 174 (SEQ ID N0:308), revealed significant homology between the PR01604 amino acid sequence and Dayhoff sequence no. P W37483. Homology was 449 also shown between the PR01604 amino acid sequence and the following additional Dayhoff sequences: AF063020J, PR66727, P_W37482, JC5661, CEC25A1_11, CEU33058_1, 138073, MST2JDROHY, and HSATRX36_1.

Clone JDNA71286-1687 was deposited with the ATCC on October 20, 1998, and is assigned ATCC deposit no. 203357.

EXAMPLE 91: Isolation of cDNA clones Encoding Human PRQ1491 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is herein designated DNA67202. Based on the DNA67202 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained 10 the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01491.

PCR primers (forward and reverse) were synthesized: forward PCR primer (67202.fn 5'-CAACGCAGCCGTGATAAACAAGTGG-3' (SEQ ID NO:311) reverse PCR primer (672Q2.rl) 5'-GCTTGGACATGTACCAGGCCGTGG-3' (SEQ ID NO:312) 15 Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA67202 sequence which had the following nucleotide sequence hybridization probe (67202.pn '-GGCCAGACTGATTTGCTCAATTCCTGGAAGTGATGGGGCAGATAC-3' (SEQ ID NO:313) RNA for construction of the cDNA libraries was isolated from human aortic endothelial cell tissue. 20 DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PR01491 (designated herein as DNA71883-1660 [Figure 175, SEQ ID N0:309]; and the derived protein sequence for PRO 1491.

The entire nucleotide sequence of DNA71883-1660 is shown in Figure 175 (SEQ ID N0:309). Clone DNA71883-1660 contains a single open reading frame with an apparent translational initiation site at nucleotide 25 positions 107-109 and ending at the stop codon at nucleotide positions 2438-2440 (Figure 175). The predicted polypeptide precursor is 777 amino acids long (Figure 176). The full-length PR01491 protein shown in Figure 176 has an estimated molecular weight of about 89,651 daltons and a pi of about 7.97. Analysis of the full-length PR01491 sequence shown in Figure 176 (SEQ ID N0:310) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 36, potential N-glycosylation sites from about amino 30 acid 139 to about amino acid 142, from about amino acid 607 to about amino acid 610 and from about amino acid 724 to about amino acid 727, a tyrosine kinase phosphorylation site from about amino acid 571 to about amino acid 576 and a gram-positive cocci surface protein anchoring hexapeptide sequence from about amino acid 32 to about amino acid 37. Clone DNA71883-1660 has been deposited with ATCC on November 17,1998 and is assigned ATCC deposit no. 203475.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 176 (SEQ ID N0:310), evidenced significant homology between the PR01491 amino acid sequence and the following Dayhoff sequences: GGU28240_1, 450 MUSC1_1, D49423, MMSEMH_1, AB002329_1, AF022947 1, HSU33920_1, HUMLUCA191, G01856and AF022946J.

EXAMPLE 92: Isolation of cDNA clones F.nr.ndine Human PRO 1431 An expressed sequence tag (EST) DNA database (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, C A) S was searched and an EST (isolated from adult brain stem tissue) was identified (1370141, DNA66505) which showed homology to SH3. RNA for construction of cDNA libraries was isolated from human bone marrow. Afull length cDNA conresponding to the isolated EST was isolated using an in vitro cloning technique (DNA73401-1633) in pRK5.

The cDNA libraries used to isolate the cDNA clones encoding human PR01431 were constructed by 10 standard methods using commercially available reagents such as those from Invitrogen, San Diego, CA. The cDNA was primed with oligo dT containing a NotI site, linked with blunt to Sail hemikinased adaptors, cleaved with NotI, sized appropriately by gel electrophoresis, and cloned in a defmed orientation into a suitable cloning vector (such as pRKB or pRKD; pRKSB is a precursor of pRKSD that does not contain the Sfil site; see, Holmes et al., Science, 253:1278-1280 (1991)) in the unique Xhol and NotI.

IS A cDNA clone was sequenced in entirety. The entire nucleotide sequence of DNA73401-1633 (SEQ ID N0:314) is shown in Figure 177. Clone DNA73401-1633 contains a single open reading frame with an apparent translational initiation site at about nucleotide positions 630-632 and a stop codon at about nucleotide positions 1740-1742. The predicted polypeptide precursor encoded by DNA734Q1-1633 is 370 amino acids long. Clone DNA73401 (designated as DNA73402-1633) has been deposited with ATCC and is assigned ATCC 20 deposit no. 203273.

Based sequence alignment analysis (using the ALIGN computer program) of the full-length sequence, PRO 1431 shows significant amino acid sequence identity to SH17_HUMAN, an SH3 containing protein known as SH3P17. Additional significant identity score were found with D89164_l, AF0321I8_1, EXLP_TOBAC, YHR4 YEAST, S46992, RATP130CAS_2, AF043259_1, RATP130CAS_1 and MYSC_ACACA.

EXAMPLE 93: Isolation of cDNA clones Encoding Human PRQ1S63 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is herein designated DNA67191. Based on the DNA67191 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained 30 the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01563.

PCR primers (forward and reverse) were synthesized: forward PCR primer (67191 .f 11 5,-CCCTGAAGCTGCCAGATGGCTCC-3, (SEQ ID N0:318) reverse PCR primer (67191 .rH 5'-CTGTGCTCTTCGGTGCAGCCAGTC-3' (SEQ ID NO:3I9) 35 Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA67191 sequence which had the following nucleotide sequence hybridization probe (67191 ,pD 451 '-CCACAGATGTGGTACTGCCTGGGGCAGTCAGCTTGCGCTACAG-3' (SEQ ID N0:320) In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with tbe PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01563 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from human bone marrow tissue.

DNA sequencing of the clones isolated as described above gave tbe full-length DNA sequence for PR01563 (designated herein as DNA73492-1671 [Figures 179A-B, SEQ ID N0:316]; and the derived protein sequence for PR01563.

The entire nucleotide sequence of DNA73492-1671 is shown in Figures 179A-B (SEQ ID NO:316). Clone DNA73492-1671 contains a single open reading frame with an apparent translational initiation site at 10 nucleotide positions 419-421 and ending at the stop codon at nucleotide positions 2930-2932 (Figures 179A-B). The predicted polypeptide precursor is 837 amino acids long (Figure 180). The full-length PR01S63 protein shown in Figure 180 has an estimated molecular weight of about 90,167 daltons and a pi of about 8.39. Analysis of the full-length PR01563 sequence shown in Figure 180 (SEQ ID NO:317) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 48, a potential N-glycosylation site from 15 about amino acid 68 to about amino acid 71, glycosaminoglycan attachment sites from about amino acid 188 to about amino acid 191 and from about amino acid 772 to about amino acid 775, a cAMP- and cGMP-dependent protein kinase phosphorylation site from about amino acid 182 to about amino acid 185, a tyrosine kinase phosphorylation site from about amino acid 730 to about amino acid 736, potential N-myristolation sites from about amino acid 5 to about amino acid 10, from about amino acid 19 to about amino acid 24, from about amino 20 acid 121 to about amino acid 126, from about amino acid 125 to about amino acid 130, from about amino acid 130 to about amino acid 135, from about amino acid 147 to about amino acid 152, from about amino acid 167 to about amino acid 172, from about amino acid 168 to about amino acid 173, from about amino acid 174 to about amino acid 179, from about amino acid 323 to about amino acid 328, from about amino acid 352 to about amino acid 357, from about amino acid 539 to about amino acid 544, from about amino acid 555 to about amino 25 acid 560, from about amino acid 577 to about amino acid 582, from about amino acid 679 to about amino acid 684, from about amino acid 682 to about amino acid 687, and from about amino acid 763 to about amino acid 768, amidation sites from about amino acid 560 to about amino acid 563 and from about amino acid 834 to about amino acid 837, leucine zipper pattern sequences from about amino acid 17 to about amino acid 38 and from about amino acid 24 to about amino acid 45 and a neutral zinc metallopeptidase, zinc-binding region signature 30 sequence from about amino acid 358 to about amino acid 367. Clone DNA73492-1671 has been deposited with ATCC on October 6, 1998 and is assigned ATCC deposit no. 203324.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 180 (SEQ ID NO:317), evidenced significant homology between the PR01563 amino acid sequence and the following Dayhoff sequences: AB014588_1, 35 D67076_1, AB001735_1, P_W47028, AB002364J, P_W47029, GEN13695, P_R40823, AF005665J and DISA TRIGA. 452 EXAMPLE 94: Isolation of cDNA clones Encoding Human PRO 1565 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is herein designated DNA67183. Based on an observed homology between the DNA67183 consensus sequence and an EST sequence contained within Incyte EST clone no. 2510320, Incyte EST clone no. 2510320 was purchased and its insert was obtained and sequenced. That 5 insert sequence is shown in Figure 181 and is herein designated DNA73727-1673 (SEQ ID NO:321).

The entire nucleotide sequence of DNA73727-1673 is shown in Figure 181 (SEQ ID NO:321). Clone DNA73727-1673 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 59-61 and ending at die stop codon at nucleotide positions 1010-1012 (Figure 181). The predicted polypeptide precursor is 317 amino acids long (Figure 182). The full-length PR01565 protein shown in Figure 10 182 has an estimated molecular weight of about 37,130 daltons and a pi of about 5.18. Analysis of the full-length PRO1565 sequence shown in Figure 182 (SEQ ID NO:322) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 40, a potential type II transmembrane domain from about amino acid 25 to about amino acid 47, potential N-glycosylation sites from about amino acid 94 to about amino acid 97 and from about amino acid 180 to about amino acid 183, glycosaminoglycan attachment sites from 15 about amino acid 92 to about amino acid 95, from about amino acid 70 to about amino acid 73, from about amino acid 85 to about amino acid 88, from about amino acid 133 to about amino acid 136, from about amino acid 148 to about amino acid 151, from about amino acid 192 to about amino acid 195 and from about amino acid 239 to about amino acid 242, potential N-myristolation sites from about amino acid 33 to about amino acid 38, from about amino acid 95 to about amino acid 100, from about amino acid 116 to about amino acid 121, 20 from about amino acid 215 to about amino acid 220 and from about amino acid 272 to about amino acid 277, a microbodies C-terminal targeting signal sequence from about amino acid 315 to about amino acid 317 and a cytochrome C family heme-binding site signature sequence from about amino acid 9 to about amino acid 14. Clone DNA73727-1673 has been deposited with ATCC on November 3, 1998 and is assigned ATCC deposit no. 203459.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 182 (SEQ ID NO:322), evidenced significant homology between the PR01565 amino acid sequence and the following Dayhoff sequences: AF051425 1, P_R65490, P_R65488, GRPE STAAU, RNU31330_1, ACCD_BRANA, D50558J, HUMAMYAB3_1, PJW34452 and P_P50629.

EXAMPLE 95: Isolation of cDNA clones Encoding Human PRQ1571 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is herein designated DNA69559. Based on homology observed between the DNA69559 consensus sequence and an EST sequence contained within the Incyte EST clone no. 35 3140760, Incyte EST clone no. 3140760 was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 183 and is herein designated as DNA73730-1679.

Clone DNA73730-1679 contains a single open reading frame with an apparent translational initiation 453 site at nucleotide positions 90-92 and ending at the stop codon at nucleotide positions 807-809 (Figure 183). The predicted polypeptide precursor is 239 amino acids long (Figure 184). The full-length PR01S71 protein shown in Figure 184 has an estimated molecular weight of about 25,699 daltons and a pi of about 8.99. Analysis of the full-length PR01571 sequence shown in Figure 184 (SEQ ID NO:324) evidences the presence of die following: a signal peptide from about amino acid 1 to about amino acid 21 and transmembrane domains from 5 about amino acid 82 to about amino acid 103, from about amino acid 115 to about amino acid 141 and from about amino acid 160 to about amino acid 182. Clone DNA73730-1679 has been deposited with ATCC on October 6, 1998 and is assigned ATCC deposit no. 203320.

An analysis of die Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 184 (SEQ ID NO.-324), evidenced significant 10 homology between the PR0157I amino acid sequence and the following Dayhoff sequences: AF072128_1, AB000712_1, AB000714_1, AF007189_1, AF000959_1, AF068863_1, P_W15288, PM22_HUMAN, PR30056 and LSU46824_1.

EXAMPLE 96: Isolation of cDNA clones Encoding Human PRQ1572 IS Using the method described in Example 1 above, a consensus sequence was obtained. Hie consensus sequence is designated herein "DNA69560". Based on the DNA69560 consensus sequence and other information provided herein, a clone including another EST (Incyte DNA3051424) from the assembly was purchased and sequenced.

The entire coding sequence of PR01573 is included in Figure 185 (SEQ ID NO:325). Clone 20 DNA73734-1680 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 90-92 and an apparent stop codon at nucleotide positions 873-875. The predicted polypeptide precursor is 261 amino acids long. The signal peptide is at about amino acids 1-23 and the transmembrane domains are. at about amino acids 81-100, 121-141, and 173-194 of SEQ ID NO-.326. One or more of the transmembrane domains can be deleted or inactivated. The locations of a N-glycosylation site, N-myristoylation sites, a tyrosine 25 kinase phosphorylation site and a prokaryotic membrane lipoprotein lipid attachment site are indicated in Figure 186. Clone DNA73734-1680 has been deposited with the ATCC and is assigned ATCC deposit no. 203363. The full-length PR01572 protein shown in Figure 186 has an estimated molecular weight of about 27,856 daltons and a pi of about 8.5.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence 30 alignment analysis of the Ml-length sequence shown in Figure 186 (SEQ ID NO:326), revealed sequence identity between the PR01572 amino acid sequence and the following Dayhoff sequences (incorporated herein): AF072127_1, HSU89916_1, AB000713_1, AB000714_1, AB0007I2_1, AF000959_1, AF072128J, AF068863_1, P_W29881, andP_W58869.

EXAMPLE 97: Isolation of cDNA clones Encoding Human PRQ1573 EST 3628990 was identified in an Incyte Database, (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, CA) and extended in a comparison to other sequences in databases to form an assembly. The alignment search 454 was performed using the computer program BLAST or BLAST2 [Altschul et al., Methods in Enzvmologv. 266:460-480 (1996)] as a comparison of the ECD protein sequences to a 6 frame translation of the EST sequences. Those comparisons resulting in a BLAST score of 70 (or in some cases, 90) or greater that did not encode known proteins were clustered and assembled into consensus DNA sequences with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence is designated herein 5 "DNA69561".

Based on the DNA69561 consensus sequence and other information provided herein, a clone including another EST (Incyte DNA3752657) from the assembly was purchased and sequenced. This clone came from a breast tumor tissue library.

The entire coding sequence of PR01573 is included in Figure 187 (SEQ ID NO:327). Clone 10 DNA73735-1681 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 97-99 and an apparent stop codon at nucleotide positions 772-774. The predicted polypeptide precursor is 225 amino acids long. The signal peptide is at about amino acids 1-17 and the transmembrane domains are at about amino acids 82-101, 118-145, and 164-188 of SEQ ID NO:328. One or more of the transmembrane domains can be deleted or inactivated. A phosphorylation site, amidation site, and N-myristoylation sites are 15 shown in Figure 188. Clone DNA73735-1681 has been deposited with ATCC and is assigned ATCC deposit no. 203356. The full-length PR01573 protein shown in Figure 188 has an estimated molecular weight of about 24,845 daltons and a pi of about 9.07.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 188 (SEQ ID NO:328), revealed sequence identity 20 between the PRO1573 amino acid sequence and the following Dayhoff sequences (incorporated herein): AF007189_1, AB0007I41, AB000713_1, AB000712_1, A39484, AF000959_1, AF072127_, AF072128J, AF068863_1 and AF077739_1.

EXAMPLE 98: Isolation of cDNA clones Encoding Human PRO 1488 25 An expressed sequence tag (EST) DNA database (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, CA) was searched and EST No. 3639112H1 was identified as having homology to CPE-R. EST No. 3639112H1 is designated herein as "DNA69562". EST clone 3639112H1, which was derived from a lung tissue library of a 20-week old fetus who died from Patau's syndrome, was purchased and the cDNA insert was obtained and sequenced in its entirety. The entire nucleotide sequence of PR01488 is shown in Figure 189 (SEQ ID 30 N0:329), and is designated herein as DNA73736-1657. DNA73736-1657 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 6-8 and a stop codon at nucleotide positions 666-668 (Figure 189; SEQ ID NO:329). The predicted polypeptide precursor is 220 amino acids long.

The full-length PR01488 protein shown in Figure 190 has an estimated molecular weight of about 23,292 daltons and a pi of about 8.43. Four transmembrane domains have been identified as being located at 35 about amino acid positions 8-30, 82-102, 121-140, and 166-186.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 190 (SEQ ID N0:330), revealed significant 455 homology between the PRO1488 amino acid sequence and Dayhoff sequence AB000712 1. Homology was also found between the PR01488 amino acid sequence and the following additional Dayhoff sequences: AB000714_1, AF007189J, AF000959 1, P_W63697, MMU82758_1, AF072127_1, AF072128_1. HSU89916_1, AF068863 1, CEAF000418_1, and AF077739_1.

Clone DNA73736-1657 was deposited with the ATCC on November 17, 1998, and is assigned ATCC 5 deposit no. 203466.

EXAMPLE 99: Isolation of cDNA clones Encoding Human PRQ1489 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is herein designated DNA69563. Based upon an observed 10 sequence similarity between the DNA69S63 consensus sequence and an EST sequence contained within the Incyte EST clone no. 3376608, Incyte EST clone no. 3376608 was purchased and its insert obtained and sequenced. That insert is herein designated DNA73737-1658.

The entire nucleotide sequence of DNA73737-1658 is shown in Figure 191 (SEQ ID NO:331). Clone DNA73737-16S8 contains a single open reading frame with an apparent translational initiation site at nucleotide 15 positions 264-266 and ending at the stop codon at nucleotide positions 783-78S (Figure 191). The predicted polypeptide precursor is 173 amino acids long (Figure 192). The full-length PR01489 protein shown in Figure 192 has an estimated molecular weight of about 18,938 daltons and a pi of about 9.99. Analysis of the full-length PRO1489 sequence shown in Figure 192 (SEQ ID NO:332) evidences the presence of the following: transmembrane domains from about amino acid 31 to about amino acid 51, from about amino acid 71 to about 20 amino acid 90 and from about amino acid 112 to about amino acid 133 and a potential N-glycosylation site from about amino acid 161 to about amino acid 164. Clone DNA73737-1658 has been deposited with ATCC on October 27, 1998 and is assigned ATCC deposit no. 203412.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 192 (SEQ ID NO:332), evidenced significant 25 homology between the PRO 1489 amino acid sequence and the following Dayhoff sequences: AF007189 1, AB000712_1, AF000959_1, MMU82758_1, AF035814J, AF072127_1, AF072128_1, HSU89916_1, AF068863_1 and PPU50051 1.

EXAMPLE 100: Isolation of cDNA clones Encoding Human PRQ1474 30 An expressed sequence tag (EST) DNA database (LIFESEQ*, Incyte Pharmaceuticals, Palo Alto, CA) was searched and an EST was identified. This EST showed homology to pancreatic secretory trypsin inhibitor.

The done which included this EST was purchased from Incyte (it came from a uterine cervical tissue library) and sequenced in full to reveal tbe nucleic acid of SEQ ID NO:333, which encodes PR01474.

The entire nucleotide sequence of PR01474 is shown in Figure 193 (SEQ ID NO:333). Clone 35 DNA73739-1645 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 45-47 and a stop codon at nucleotide positions 300-302 (Figure 193; SEQ ID NO:333). The predicted polypeptide precursor is 85 amino acids long. As indicated in Figure 194, the Kazal serine protease inhibitor 456 PCT/US99/20I11 family signature begins at about amino acid 45 of SEQ ID NO:334. Also indicated in Figure 194 is a region conserved in integral alpha chains (beginning at about amino acid 32 of SEQ ID NO:334). Clone DNA73739-1645 has been deposited with the ATCC and is assigned ATCC deposit no. 203270. The full-length PR01474 protein shown in Figure 194 has an estimated molecular weight of about 9,232 daltons and a pi of about 7.94.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence 5 alignment analysis of the full-length sequence shown in Figure 194 (SEQ ID NO:334), revealed sequence identity between the PR01474 amino acid sequence and the following Dayhoff sequences (all ovomucoids, data incorporated herein by reference): IOVO_FRAER, IOVO_FRAAF, IOVO_FRACO, IOVO_CYRMO, IOVOSTRCA, H61492, C6I589, IOVO_POLPL, D61589, and IOVO_TURME.

EXAMPLE 101: Isolation of cDNA clones Encoding Human PRO 1508 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the LIFESEQ® database, designated Incyte Cluster No. 34523, also referred herein as "DNA10047". This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public and private EST databases (e.g., GenBank and (LIFESEQ®) to identify existing 15 homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated "DNA55723".

In light of the sequence homology between the DNA55723 sequence a sequence contained within Incyte EST no. 2989064, the EST clone 2989064 was purchased and the cDNA insert was obtained and sequenced in its entirety. The sequence of this cDNA insert is shown in Figure 195 and is herein designated as "DNA73742-1662".

The full length clone shown in Figure 195 contained a single open reading frame with an apparent 25 translational initiation site at nucleotide positions 70 to 72 and ending at the stop cotton found at nucleotide positions 514 to 516 (Figure 195; SEQ ID NO:335). The predicted polypeptide precursor (Figure 196, SEQ ID NO:335) is 148 amino acids long. Other features of the PR01508 protein include: a signal sequence at about amino acids 1-30; a tyrosine kinase phosphorylation motif at about amino acids 96-103; and N-myristoylation motifs at about amino acids 27-32, 28-33, and 140-145. PR01508 has a calculated molecular weight of 30 approximately 17,183daltonsandanestimatedpIofapproximately8.77. Clone DNA73742-1662 was deposited with the ATCC on October 6, 1998 and is assigned ATCC deposit no. 203316.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 1% (SEQ ID NO-.336), revealed some homology between the PRO1508 amino acid sequence and the following Dayhoff sequences: HSAJ3728 1; P_R74962; 35 P R74941; AF053074 1; F69515; S20706; RPB1 PLAFD; A20587 I; A51861 1; and S75947. 457 EXAMPLE 102: Isolation of cDNA clones Encoding Human PRO 1555 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the LIFESEQ® database, designated EST cluster no. 521, and also referred to herein as "DNA10316". This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and the LIFESEQ® database to identify 5 existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated "DNA56374". 10 In light of the sequence homology between the DNA56374 sequence and an EST sequence contained within Incyte EST no.2855769, EST no.2855769 was purchased and the cDNA insert was obtained and sequenced. EST no. 2855769 was derived from a library constructed from female breast fat tissue. The sequence of this cDNA insert is shown in Figure 197 and is herein designated as DNA73744-1665.

The full length clone shown in Figure 197 contained a single open reading frame with an apparent IS translational initiation site at nucleotide positions 90 to 92 and ending at the stop codon found at nucleotide positions 828 to 830 (Figure 197; SEQ ID NO:337). The predicted polypeptide precursor (Figure 198, SEQ ID NO:338) is 246 amino acids long. PR01555 has a calculated molecular weight of approximately 26,261 daltons and an estimated pi of approximately 5.65. Additional features include: a signal peptide at about amino acids 1-31; transmembrane domains at about amino acids 11-31 and 195-217; a potential N-glycosylation site 20 at about amino acids 111-114; potential casein kinase II phosphorylation sites at about amino acids 2-5,98-101, and 191-194; and potential N-myristoylation sites at about amino acids 146-151, and 192-197.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 198 (SEQ ID NO:338), revealed some homology between the PR01555 amino acid sequence and the following Dayhoff sequences: YKA4 CAEEL, 25 AB014541_l, HVSX99518_2, SSU63019_1, GEN14286, MMU68267_1, XP2_XENLA, ICP4_HSV11, PW40200, and AE001360_1.

Clone DNA73744-1665 was deposited with the ATCC on October 6, 1998, and is assigned ATCC deposit no. 203322.

EXAMPLE 103: Isolation of cDNA clones Encoding Human PRO 1485 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is designated herein "DNA44791". Based on the DNA44791 consensus sequence, oligonucleotides were synthesized: 1) to identiiy by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for 35 PR01485.

PCR primers (2 forward and 2 reverse) were synthesized: forward PCR primer 1: 51CCCTCC AAGG ATG AC A A AGGCGC 3' (SEQ ID NO:341); 458 forward PCR primer 2: 5 'GGTCAGC AGCTTTCTTGCCCTAAATCAGG 3' (SEQ ID NO:342); reverse PCR nrimer I: S'ATCTCAGGCGGCATCCTGTCAGCC 3' (SEQ ID NO:343); and reverse PCR primer 2: 5'GTGGATGCCTGCAAGAAGGTTGGG 3' (SEQ ID NO:344).

Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA44791 sequence which had the following nucleotide sequence: hybridization probe 5' AGCTTTCTTGCCCT A A ATC AGGCC AGCCTC ATC AGTCGCTGTG AC 3' (SEQ ID NO:345) In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR0148S gene using the probe oligonucleotide and one of the PCR primers. RNA 10 for construction of the cDNA libraries was isolated from human testis.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PR01485 (designated herein as DNA73746-1654 [Figure 199, SEQ ID NO:339]; and the derived protein sequence for PR01485.

The entire coding sequence of PR01485 is shown in Figure 199 (SEQ ID N0:339). Clone DNA73746-15 1654 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 151-153 and an apparent stop codon at nucleotide positions 595-597 of SEQ ID NO:339. The predicted polypeptide precursor is 148 amino acids long. The signal peptide is at about amino acids 1-18 of SEQ ID N0:340. The lysozyme C signature, CAAX box, and an N-gycosylation site are shown in Figure 200. Clone DNA73746-1654 has been deposited with ATCC and is assigned ATCC deposit no. 203411. The full-length 20 PRO1485 protein shown in Figure 200 has an estimated molecular weight of about 16,896 daltons and a pi of about 6.05.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of die full-length sequence shown in Figure 200 (SEQ ID N0:340), revealed sequence identity between the PRO1485 amino acid sequence and the following Dayhoff sequences: LYC_PHACO, P_R76684, 25 2HFL_Y, JC2144, JC5544, JC5555, JC5369, LYC2_PIG, P_R12113, and JC5380.

. EXAMPLE 104: Isolation of cDNA clones Encoding Human PRQ1564 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is herein designated DNA67213. Based on the DNA67213 30 consensus sequence, oligonucleotides were synthesized: 1) to identiiy by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01564.

PCR primers (forward and reverse) were synthesized: forward PCR primer r67213.fl) 5'-GGAGAGGTGGTGGCCATGGACAG-3' (SEQ ID NO:348) 35 reverse PCR primer (67213.rU 5'-CTGTCACTGCAAGGAGCCAACACC-3' (SEQ ID NO-.349) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA67213 sequence which had the following nucleotide sequence 459 hybridization probe (67213.dH ' -T ATGTCGCTGCG AGGTGGTG A A AACCTCG A ACTGT CTTTC A AGGC-3' (SEQ ID N0:350) In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01564 gene using the probe oligonucleotide and one of the PCR primers. RNA 5 for construction of the cDNA libraries was isolated from human breast carcinoma tissue.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PR01564 (designated herein as DNA73760-1672 [Figure 201, SEQ ID NO:346]; and the derived protein sequence for PR01564.

The entire nucleotide sequence of DNA73760-1672 is shown in Figure 201 (SEQ ID NO:346). Clone 10 DNA73760-1672 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 462-464 and ending at the stop codon at nucleotide positions 2379-2381 (Figure 201). The predicted polypeptide precursor is 639 amino acids long (Figure 202). The full-length PR01S64 protein shown in Figure 202 has an estimated molecular weight of about 73,063 daltons and a pi of about 6.84. Analysis of the full-length PR01S64 sequence shown in Figure 202 (SEQ ID NO:347) evidences the presence of the following: a 15 signal peptide from about amino acid 1 to about aminn acid 28, a trasnmembrane domain from about amino acid 11 to about amino acid 36, potential N-glycosylation sites from about amino acid 107 to about amino acid 110 and from about amino acid 574 to about amino acid 577, a tyrosine kinase phosphorylation site from about amino acid 50 to about amino acid 57, potential N-myristolation sites from about amino acid 158 to about amino acid 163, from about amino acid 236 to about amino acid 241, from about amino acid 262 to about amino acid 267, 20 from about amino acid 270 to about amino acid 275, from about amino acid 380 to about amino acid 385 and from about amino acid 513 to about amino acid518, an amidation site from about amino acid 110 to about amino acid 113 and a prokaryotic membrane lipoprotein lipid attachment site from about amino acid 15 to about amino acid 25. Clone DNA73760-1672 has been deposited with ATCC on October 6, 1998 and is assigned ATCC deposit no.203314.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 202 (SEQ ID NO:347), evidenced significant homology between the PR01564 amino acid sequence and the following Dayhoff sequences: MMU73819_1, HSY08564 1, P_W34470, P_R66402, PAGTHUMAN, CEGLY5B_1, CEGLY6A1, CEGLY6B1, AP000006_308 and E69322.

EXAMPLE 105: Isolation of cDNA clones Encoding Human PRQ1755 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the LIFESEQ** database, designated EST Cluster No. 141872. This EST cluster sequence was then compared to a variety of ESTs from the databases listed above to identify existing homologies. The 35 homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with 460 WO 00/12708 PCT/US99/20111 the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated "DNA55731".

In light of the sequence homology between the DNASS731 sequence and a sequence contained within Incyte EST no. 2S7323, the EST clone was purchased and the cDNA insert was obtained and sequenced. Incyte clone 2S7323 was derived from a library constructed using RNA isolated from the hNT2 cell line (Stratagene 5 library no. STR9372310), which was derived from a human teratocarcinoma that exhibited properties characteristic of a committed neuronal precursor at an early stage of development. The sequence of this cDNA insert is shown in Figure 203 and is herein designated "DNA76396-1698". Alternatively, the DNA76396-1698 sequence can be obtained by preparing oligonucleotide probes and primers and isolating the sequence from an appropriate library (e.g. STR9372310).

The full length clone shown in Figure 203 contained a single open reading frame with an apparent translational initiation site at nucleotide positions 58 to 60 and ending at the stop codon found at nucleotide positions 886 to 888 (Figure 203; SEQ ID NO:351). The predicted polypeptide precursor (Figure 204, SEQ ID NO-.352) is 276 amino acids long. PR01755 has a calculated molecular weight of approximately 29,426 daltons and an estimated pi of approximately 9.40. Additional features include: a signal peptide sequence at 15 about amino acids 1-31; a transmembrane domain at about amino acids 178-198; a cAMP and cGMP-dependent protein kinase phosphorylation site at about amino acids 210-213; potential N-myristoylation sites at about amino acids 117-122, 154-149, and 214-219; and a cell attachment sequence at about amino acids 149-151.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 204 (SEQ ID NO:352), revealed some homology 20 between the PR01755 amino acid sequence and the following Dayhoff sequences: APG-BRANA, P_R37743, NAU88587J, YHL1_EBV, P_W31855, CET10B10_4, AF039404_1, PRP1_HUMAN, AF038575_1, and AF053091_1.

Clone DNA76396-1698 was deposited with the ATCC on November 17, 1998, and is assigned ATCC deposit no. 203471.

EXAMPLE 106: Isolation of cDNA clones Encoding Human PRQ1757 Use of the signal sequence algorithm described in Example 3 above allowed identification of three EST sequences from the Incyte database, designated Incyte EST clones no. 2007947, 2014962 and 1912034. These EST sequences were thai clustered and assembled into a consensus DNA sequence with the program "phrap" 30 (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated as DNA56054.

In light of the sequence homology between the DNA56054 sequence and a sequence contained within the Incyte EST clone no. 2007947, the Incyte EST clone no. 2007947 was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 205 and is herein designated as 35 DNA76398-1699.

Clone DNA76398-1699 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 59-61 and ending at the stop codon at nucleotide positions 422-424 (Figure 205). The 461 predicted polypeptide precursor is 121 amino acids long (Figure 206). The full-length PR01757 protein shown in Figure 206 has an estimated molecular weight of about 12,073 daltons and a pi of about 4.11. Analysis of the full-length PR01757 sequence shown in Figure 206 (SEQ ID NO:354) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 19, a transmembrane domain from about amino acid 91 to about amino acid 110, a glycosaminoglycan attachment site from about amino acid 44 to about 5 amino acid 47, a cAMP- and cGMP-dependent protein kinase phosphorylation site from about amino acid 116 to about amino acid 119 and a potential N-myristolation site from about amino acid 91 to about amino acid 96. Clone DNA76398-1699 has been deposited with ATCC on November 17, 1998 and is assigned ATCC deposit no. 203474.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence 10 alignment analysis of the full-length sequence shown in Figure 206 (SEQ ID NO:354), evidenced significant homology between the PR01757 amino acid sequence and the following Dayhoff sequences: JQ0964, COLLJHSVS7, HSU70136_1, AF003473_1, D89728_l, MTFl_MOUSE, AF029777_1, HSU88153_1 and PJW05321.

EXAMPLE 107: Isolation of cDNA clones Encoding Hnman PRQ1758 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the LIFESEQ* database, designated EST cluster No. 20926. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) from the databases mentioned above, to identify existing homologies. The homology search was performed using the computer program BLAST or BLAST2 20 (Altshul et al.. Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated DNA56260.

In light of the sequence homology between the DNA56260 sequence and a sequence contained within 25 EST no. 2936330 from the LIFESEQ* database, the EST clone, which originated from a library constructed from thymus tissue of a fetus that died from anencephalus, was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 207 and is herein designated as DNA76399-1700.

The full length clone shown in Figure 207 contained a single open reading frame with an apparent 30 translational initiation site at nucleotide positions 78 to 80 and ending at the stop codon found at nucleotide positions 549-551 (Figure 207; SEQ ID NO:355). The predicted polypeptide precursor (Figure 208, SEQ ID NO:356) is 157 amino acids long. PR01758 has a calculated molecular weight of approximately 17,681 daltons and an estimated pi of approximately 7.65. Additional features include: a signal peptide from about amino acids 1-15; a potential N-glycosylation site at about amino acids 24-27; a cAMP- and cGMP-dependent protein kinase 35 phosphorylation site at about amino acids 27-30; a casein kinase II phosphorylation site at abom amino acids 60-63; potential N-myristoylation sites at about amino acids 17-22,50-55,129-134, and 133-138; a cell attachment sequence at about amino acids 153-155; and a cytochrome c family heme-binding site signature at about amino 462 acids 18-23.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 208 (SEQ ID NO:356), revealed significant homology between the PRO1758 amino acid sequence and Dayhoff sequence no AC005328_2. Homology was also found between the PR01758 amino acid sequence and Dayhoff sequence no. CELC46F21.

Clone DNA76399-1700 was deposited with the ATCC on November 17, 1998 and is assigned ATCC deposit no. 203472.

EXAMPLE 108: Isolation of cDNA clones Encoding Human PRQ1575 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described 10 in Example 1 above. This consensus sequence is designated herein as "DNA35699". Based on the DNA35699 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01575.

PCR primers (forward and reverse) were synthesized: forward PCR primers: CCAGCAGTGCCCATACTCCATAGC (35699.fl; SEQ ID N0.359); TGACGAGTGGGATACACTGC (35699.f2; SEQ ID N0:360) reverse PCR primer: GCTCTACGGAAACTTCTGCTGTGG (35699.rl; SEQ ID NO:361) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA35699 sequence which had the following nucleotide sequence: hybridization probe: ATTCCCAGGCGTGTCATTTGGGATCAGCACTGATTCTGAGGTTCTGACAC (35699.pl; SEQ ID NO:362) In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01575 gene using the probe oligonucleotide and one of the PCR primers. RNA 25 for construction of the cDNA libraries was isolated from human pancreatic tissue.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PR01575 (designated herein as DNA76401-1683 [Figure 209, SEQ ID NO:357]; and the derived protein sequence for PR01575.

The entire coding sequence of PR01575 is shown in Figure 209 (SEQ ID NO:357). Clone DNA76401-30 1683 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 22-24 and an apparent stop codon at nucleotide positions 841-843. The predicted polypeptide precursor is 273 amino acids long. The full-length PR01575 protein shown in Figure 210 has an estimated molecular weight of about 30,480 daltons and a pi of about 4.60. Additional features include: a signal peptide at about amino acids 1-20; a transmembrane domain at about amino acids 143-162; a potential N-glycosylation site at about amino 35 acids 100-103; and potential N-myristoylation sites at about amino acids 84-89,103-108,154-159, and 201-206.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 210 (SEQ ID N0:358), revealed significant 463 homology between the PRO1575 amino acid sequence and Dayhoff sequence A12005 1. Homology was also revealed between the PR01575 amino acid sequence and the following additional Dayhoff sequences: PP80615; PJR25297; P_R51696; A47300; PDI_DROME; P_R49829; P_R63807; DMALPADAP_1; and DRZNF6_1.

Clone DNA76401-1683 was deposited with the ATCC on October 20,1998, and is assigned ATCC deposit no. 203360.

EXAMPT-F. 1QQ- Isolation of cDNA clones Encoding Human PRQ1787 A consensus DNA sequence was assembled relative to other EST sequences using phrap to form an assembly as described in Example 1 above. This consensus sequence is designated herein "DNA45123". Based on homology of DNA45123 to Incyte EST 3618549 identified in the assembly, as well as other discoveries and 10 information provided herein, the clone including this EST was purchased and sequenced. DNA sequencing of the clone gave the full-length DNA sequence for PR01787 and the derived protein sequence for PR01787.

The entire coding sequence of PR01787 is included in Figure 211 (SEQ ID NO:363). Clone DNA76510-2504 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 163-165 and an apparent stop codon at nucleotide positions 970-972 of SEQ ID NO:363. The IS approximate locations of the signal peptide, transmembrane domain, N-glycosylationsites, N-myristoylationsites and a kinase phosphorylation site are indicated in Figure 212. The predicted polypeptide precursor is 269 amino acids long. Clone DNA76510-2504 has been deposited with the ATCC and is assigned ATCC deposit no. 203477. The full-length PR01787 protein shown in Figure 212 has an estimated molecular weight of about 29,082 daltons and a pi of about 9.02.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of die full-length sequence shown in Figure 212 (SEQ ID N0:364), revealed sequence identity between the PR01787 amino acid sequence and the following Dayhoff sequences: MYP0_RAT, MYP0_HUMAN, MYPO_BOVIN, GEN12838, HSSCN2B2_1, AF007783_1, HSU90716_1, P_W42015, XLU43330_1 and AF060231_1.

EXAMPLE 110: Isolation of cDNA clones Engine Human PRQ1781 Initial DNA sequences referred to herein as DNA58070 and DNA56340 were identified using a yeast screen, in a human SK-Lu-1 adenocarcinoma cell line cDNA library that preferentially represents the 5' ends of the primary cDNA clones. These sequences were clustered and assembled into a consensus DNA sequence 30 using the computer program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence is designated herein as "DNA59575".

Based on the DNA59575 consensus sequence, the following oligonucleotides, were synthesized for use as probes to isolate a clone of the full-length coding sequence for PR01781 from a human fetal lung cDNA library: TGG AAAAGAAGTCTGGTC AGAAGGTTTAGG (SEQ ID NO-.367), 35 CATTTGGCTTCATTCTCCTGCTCTG (SEQ ID NO:368), AAAACCTCAGAACAACTCATTTTGCACC (SEQ ID NO:369) and GTCTCACCATGGTTGCTCTTGCCAAATTGTGGGAAGCAGGG(SEQ ID N0:370). The full length DNA76522-2500 clone shown in Figure 213 contained a single open reading frame with 464 an apparent translational initiation site at nucleotide positions 21 to 23 and ending at tbe stop codon found at nucleotide positions 1141-1143 (Figure 213; SEQ ID NO:365). The predicted polypeptide precursor (Figure 214, SEQ ID NO:366) is 373 amino acids long. PR01781 has a calculated molecular weight of approximately 41,221 daltons and an estimated pi of approximately 8.54. Additional features include: a possible signal peptide at about amino acids 1 -19; a transmembrane domain at about amino acids 39-60; a tyrosine phosphorylation site 5 at about amino acids 228-236; potential N-myristoylation sites at about amino acids 16-21,17-22,43-48,45-50, 47-52, 49-54, 53-58, 58-63, 59-64, 62-67, 126-131, and 142-147; amidation sites at about amino acids 22-25 and 280-283; and a prokaryotic membrane lipoprotein lipid attachment site at about amino acids 12-22.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 214 (SEQ ID NO:366), revealed some homology 10 between the PR01781 amino acid sequence and the following Dayhoff sequences: CEY4510D_5, AP000001 146, PJR10676, DACJSTRSQ, CEC40H55, P_R35204, KPU58495J, KPN16781_1, AF010403_1, and AF056116_14.

Clone DNA76522-2500 was deposited with the ATCC on November 17, 1998, and is assigned ATCC deposit no. 203469.

EXAMPLE 111: Isolation of cDNA clones Encoding Human PROI556 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the LIFESEQ* database, designated EST Cluster No. 103158, and also referred to herein as "DNA10398". This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) 20 databases which included public EST databases (e.g., GenBank) and the LIFESEQ* database, to identify existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, 25 Washington). The consensus sequence obtained therefrom is herein designated DNA56417.

In light of the sequence homology between the DNA56417 sequence and a sequence contained within Incyte EST no. 959332, EST no. 959332 was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 215 and is herein designated as DNA76529-1666.

The full length clone shown in Figure 215 contained a single open reading frame with an apparent 30 translational initiation site at nucleotide positions 85 to 87 and ending at the stop codon found at nucleotide positions 892 to 894 (Figure 215; SEQ ID NO:371). The predicted polypeptide precursor (Figure 216, SEQ ID NO:372) is 269 amino acids long. PR01556 has a calculated molecular weight of approximately 28,004 daltons and an estimated pi of approximately 5.80. Additional features include: a signal peptide sequence at about amino acids 1-24; transmembrane domains at about amino acids 11-25 and 226-243; a potential N-35 glycosylation site at about amino acids 182-185, potential cAMP- and cGMP-dependent protein kinase phosphorylation site at about amino acids 70-73; and potential N-myristoylation sites at about amino acids 29-34, 35-39,117-122,121-126,125-130,154-159,166-171,241-246,246-251,247-252,249-254,250-255,251-256, 465 WO 00/12708 PCT/US99/20111 252-257, 253-258, 254-259, 255-260, 256-261, 257-262, and 259-264.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of die full-length sequence shown in Figure 216 (SEQ ID NO:372), revealed some homology between tbe PR01556 amino acid sequence and the following Dayhoff sequences: T8F5_4, R23B MOUSE, CANS HUMAN, P W41640, DSU51091_1, TP2B_CHICK, DVU20660_1, S43296, P_R23962, and 5 BRN1_HUMAN.

Clone DNA76529-1666 was deposited with the ATCC on October 6, 1998, and is assigned ATCC deposit no. 203315.

EXAMPLE 112: Isolation of cDNA clones Encoding Human PRQ1759 10 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the Incyte database, designated DNA10571. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ*, Incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. One or more of the ESTs was derived from pooled eosinophils of allergic asthmatic 15 patients. The homology search was performed using the computer program BLAST or BLAST2 (Altshul etal.. Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated DNA57313.

In light of the sequence homology between the DNA57313 sequence and the Incyte EST 2434255, the clone including this EST was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 217 and is herein designated as DNA76531-1701.

The full length clone shown in Figure 217 contained a single open reading frame with an apparent translational initiation site at nucleotide positions 125-127 and ending at the stop codon found at nucleotide 25 positions 1475-1477 (Figure 217; SEQ ID NO:373). The approximate locations of the signal peptide and transmembrane domains are indicated in Figure 218, whereas the approximate locations for N-myristoylation sites, a lipid attachment site, an amidation site and a kinase phosphorylation site are indicated in Figure 218. The predicted polypeptide precursor (Figure 218, SEQ ID NO:374) is 450 amino acids long. PR01759 has a calculated molecular weight of approximately 49,765 daltons and an estimated pi of approximately 8.14. Clone 30 DNA76531-1701 was deposited with the ATCC on November 17, 1998 and is assigned ATCC deposit no. 203465.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 218 (SEQ ID N0:374), revealed sequence identity between the PR01759 amino acid sequence and the following Dayhoff sequences: OPDE_PSEAE, 35 TH11_TRYBB, S67684, RGT2YEAST, S68362, ATSUGTRPR_1, P W17836 (Patent application W09715668-A2), F69587, A48076, and A45611. 466 EXAMPLE 113: Isolation of cDNA clones Encoding Human PRQ1760 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the Incyte database. This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ*, Incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. One 5 or more of the ESTs was derived from a prostate tumor library. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (19%)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein 10 designated DNAS8798.

In light of the sequence homology between DNA58798 sequence and the Incyte EST 33S874S, the clone including this EST was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 219 and is herein designated as DNA76S32-1702.

The full length clone shown in Figure 219 contained a single open reading frame with an apparent 15 translational initiation site at nucleotide positions 60-62 and ending at the stop codon found at nucleotide positions 624-626 (Figure 219; SEQ ID NO:375). The predicted polypeptide precursor (Figure 220, SEQ ID NO:376) is 188 amino acids long. Motifs are further indicated in Figure 220. PR01760 has a calculated molecular weight of approximately 21,042 daltons and an estimated pi of approximately 5.36. Clone DNA76532-1702 was deposited with the ATCC on November 17, 1998 and is assigned ATCC deposit no. 203473. 20 An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 220 (SEQ ID NO:376), revealed sequence identity between the PRO1760 amino acid sequence and the following Dayhoff sequences: CELT07F12_2, T22J18_16, ATF1C12_3, APE3 YEAST, P_W22471, SAU56908J, SCPA_STRPY, ATAC00423817, SAPURCLUS_2 and AF041468_9.

EXAMPLE 114: Isolation of cDNA clones Encoding Human PRQ1561 A consensus DNA sequence was assembled relative to other EST sequences using phrap and repeated cycles of BLAST and phrap to extend a sequence as far as possible using the EST sequences discussed above as described in Example 1 above. This consensus sequence is herein designated DNA40630. Based on the 30 DNA40630 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01561.

PCR primers (forward and reverse) were synthesized: forward PCR primer (40630.fn 5'-CTGCCTCCACTGCTCTGTGCTGGG-3' (SEQ ID NO:379) 35 reverse PCR primer C40630.rn 5'-CAGAGCAGTGGATGTTCCCCTGGG-3' (SEQ ID N0:380) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA40630 sequence which had the following nucleotide sequence 467 hvhriHi?afif>Ti probe (4063Q.pl) '-CTGAACAAGATGGTCAAGCAAGTGACTGGGAAAATGCCCATCCTC-3' (SEQ ID NO:38I) In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01561 gene using the probe oligonucleotide and one of the PCR primers. RNA 5 for construction of the cDNA libraries was isolated from human breast tumor tissue.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PR01S61 (designated herein as DNA76538-1670 [Figure 221, SEQ ID NO:377]; and the derived protein sequence for PR01561.

The entire nucleotide sequence of DNA76S38-1670 is shown in Figure 221 (SEQ ID NO:377). Clone 10 DNA76538-1670 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 29-31 and ending at the stop codon at nucleotide positions 377-379 (Figure 221). The predicted polypeptide precursor is 116 amino acids long (Figure 222). The full-length PR01561 protein shown in Figure 222 has an estimated molecular weight of about 12,910 daltons and a pi of about 6.41. Analysis of the fiill-length PR01561 sequence shown in Figure 222 (SEQ ID NO:378) evidences the presence of the following: a 15 signal peptide from about amino acid 1 to about amino acid 17, a transmembrane domain from about amino acid 1 to about amino acid 24, a potential N-glycosylation site from about amino acid 86 to about amino acid 89, potential N-myristolation sites from about amino acid 20 to about amino acid 25 and from about amino acid 45 to about amino acid SO and a phospholipase A2 histidine active site from about amino acid 63 to about amino acid 70. Clone DNA76538-1670 has been deposited with ATCC on October 6, 1998 and is assigned ATCC 20 deposit no. 203313.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 222 (SEQ ID N0:378), evidenced significant homology between the PR01561 amino acid sequence and the following Dayhoff sequences: PR63053, PJR25416, PJR63055, P_P93363, P_R63046, PA2A_VIPAA, P_W58476, GEN13747, PA2X_HUMAN and 25 PA2A_CRODU.

In addition to the above, a sequence homology search evidenced significant homology between the DNA40630 consensus sequence and Incyte EST clone no. 1921092. As such, Incyte EST clone no. 1921092 was purchased and the insert obtained and sequenced, thereby giving rise to the DNA76538-1670 sequence shown in Figure 221 (SEQ ID N0:377).

EXAMPLE 115: Isolation of cDNA clones Encoding Human PRQ1567 A cDNA sequence isolated in the amylase screen described in Example 2 above is herein designated DNA47580. The DNA47580 sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database 35 (LIFESEQ1", Incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater 468 that did not encode known proteins were clustered and assembled into consensus DNA sequences with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated "DNA57246".

In light of the sequence homology between the DNA57246 sequence and EST no. 1793996 from the LIFESEQ™ database, the clone containing the EST no. 1793996, which originates from a library constructed 5 from prostate tumor tissue, was purchased and the cDNA insert was obtained and sequenced. The sequence of this cDNA insert is shown in Figure 223 (SEQ ID NO:382) and is herein designated as DNA76541-1675.

A full length clone was identified that contained a single open reading frame with an apparent translational initiation site at nucleotide positions 109-111, and a stop signal at nucleotide positions 643-645 (Fig. 223; SEQ ID NO:382). The predicted polypeptide precursor is 178 amino acids long has a calculated molecular 10 weight of approximately 19,600 daltons and an estimated pi of approximately 5.89. Additional features include a signal peptide at about amino acids 1-22; a potential N-glycosylation site at about amino acids 167-170; a protein kinase C phosphorylation site at about amino acids 107-109; and potential N-myristoylation sites at about amino acids 46-51, 72-77, and 120-125.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence 15 alignment analysis of the full-length sequence shown in Figure 224 (SEQ ID NO:383), evidenced significant homology between the PR01567 amino acid sequence and human colon specific gene CSG6 polypeptide designated Dayhoff sequence "P_W06549". Homology was also found between the PR01567 amino acid sequence and the following additional Dayhoff sequences: HUAC0Q2301_1, P_246880, A49685, SPBP RAT, S42924, SPBP MOUSE, 152115, MMU03711_1, and AF041468_31.

Clone DNA76541-1675 has been deposited with the ATCC on October 27,1998, and is assigned ATCC deposit no. 203409.

EXAMPLE 116: Isolation of cDNA clones Encoding Human PRQ1693 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described 25 in Example 1 above. This consensus sequence is herein designated DNA38251. Based on the DNA38251 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PRO1693.

PCR primers (forward and reverse) were synthesized: forward PCR primer (38251 .fl) 5'-CTGGGATCTGAACAGTTTCGGGGC-3' (SEQ ID NO:386) reverse PCR primer (38251.rl) 5'-GGTCCCCAGGACATGGTCTGTCCC-3' (SEQ ID NO:387) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA38251 sequence which had the following nucleotide sequence hybridization probe (38251.p1) 35 5' -GCTGAGTTTACATTTACGGTCTAACTCCCTGAGAACCATCCCTGTGCG-3' (SEQ ID NO:388) In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to 469 isolate clones encoding the PR01693 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from human fetal kidney tissue.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PR01693 (designated herein as DNA77301-1708 [Figure 225, SEQ ID NO:384]; and the derived protein sequence for PR01693.

The entire nucleotide sequence of DNA77301-1708 is shown in Figure 225 (SEQ ID NO:384). Clone DNA77301-1708 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 508-510 and ending at the stop codon at nucleotide positions 2047-2049 (Figure 225). The predicted polypeptide precursor is 513 amino acids long (Figure 226). The full-length PR01693 protein shown in Figure 226 has an estimated molecular weight of about 58,266 daltons and a pi of about 9.84. Analysis of the full-10 length PR01693 sequence shown in Figure 226 (SEQ ID NO:385) evidences the presence of the following: a signal peptide from about aminn acid 1 to about amino acid 33, a transmembrane domain from about amino acid 420 to about amino acid 442, potential N-glycosylation sites from about amino acid 126 to about amino acid 129, from about amino acid 357 to about amino acid 360, from about amino acid 496 to about amino acid 499 and from about amino acid 504 to about amino acid 507, a cAMP- and cGMP-dependent protein kinase 15 phosphorylation site from about amino acid 465 to about amino acid 468, a tyrosine kinase phosphorylation site from about amino acid 136 to about amino acid 142 and potential N-myristolation sites from about amino acid 11 to about amino acid 16, from about amino acid 33 to about aminn acid 38, from about amino acid 245 to about amino acid 250, from about amino acid 332 to about amino acid 337, from about amino acid 497 to about aminn acid 502 and from about amino acid 507 to about amino acid 512. Clone DNA77301-1708 has been 20 deposited with ATCC on October 27, 1998 and is assigned ATCC deposit no. 203407.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 226 (SEQ ID NO:385), evidenced significant homology between the PR01693 amino acid sequence and the following Dayhoff sequences: AB007876_1, ALS_MOUSE, HSCHON03_1, P_R85889, AF062006_1, AB014462_1, A58532, MUSLRRPA_1, AB007865_1 25 and AF030435_1.

EXAMPLE 117: Isolation of cDNA clones Encoding Human PRQ1784 A cDNA sequence isolated in the amylase screen described in Example 2 above is herein designated DNA43862. Based on the DNA43862 sequence, oligonucleotide probes were generated and used to screen a 30 human fetal kidney library prepared as described in paragraph 1 above. The cloning vector was pRK5B (pRK5B is a precursor of pRK5D that does not contain the Sfil site; see, Holmes et al., Science. 253:1278-1280 (1991)), and the cDNA size cut was less than 2800 bp.

PCR primers (forward and reverse) were synthesized: forward PCR nrimer (ftt 5' -CTTTTCAGTGTCACCTCAGCGATCTC-3' (SEQ ID NO:391); and 35 reverse PCR primer (rl) 5' -CC AAAACATGGAGC AGG A AC AGG-3' (SEQ ID NO:392).

Additionally, a synthetic oligonucleotide hybridization probe was constructed from the DNA43862 sequence which had the following nucleotide sequence: 470 hybridization probe (pi) '-CCAGTTGGTGCTCTCGGACCTACCATGCGAAGAAGATGAAATGTGTG-3' (SEQ ID NO:393).

In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01784 gene using the probe oligonucleotide and one of the PCR primers.

A full length clone was identified that contained a single open reading frame with an apparent translationai initiation site at nucleotide positions 68-70, and a stop signal at nucleotide positions S06-S08 (Fig. 227; SEQ ID NO:389). The predicted polypeptide precursor is 146 amino acids long has a calculated molecular weight of approximately 16,116 daltons and an estimated pi of approximately 4.99. The approximate locations of the signal peptide, transmembrane domain and N-myristoylation site are indicated in Figure 228. Clone 10 DNA77303-2502 has been deposited with the ATCC and is assigned ATCC deposit no. 203479.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 228 (SEQ ID N0:390), evidenced sequence identity between the PR01784 amino acid sequence and the following Dayhoff sequences: RNU87224 1, RNAF000114_1, P W31947, S18038, AE001300_8, AF039833_1, P_W39833_1, P_W39788, HSU87223_1, 15 NTU06712 1, and P_W31946.

RYAMPT.F. 1 ]«• Isolation of cDNA clones Encoding Human PRQ1605 A cDNA clone (DNA77648-1688) encoding a native human PRO1605 polypeptide was identified by a yeast screen, in a human fetal kidney cDNA library that preferentially represents the 5' ends of the primary 20 cDNA clones.

The full-length DNA77648-1688 clone shown in Figure 229 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 425-427 and ending at the stop codon at nucleotide positions 845-847 (Figure 229). The predicted polypeptide precursor is 140 amino acids long (Figure 230). The full-length PRO1605 protein shown in Figure 230 has an estimated molecular weight of about 15,668 daltons 25 and a pi of about 10.14. Analysis of the full-length PR01605 sequence shown in Figure 230 (SEQ ID NO:395) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 26. Clone DNA77648-1688 has been deposited with ATCC on October 27, 1998 and is assigned ATCC deposit no. 203408.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence 30 alignment analysis of the full-length sequence shown in Figure 230 (SEQ ID NO:395), evidenced significant homology between the PR01605 amino acid sequence and the following Dayhoff sequences: GNT5 HUMAN, PR48975, P_W22519, MM26SPROT_l, HSU86782_1, CH60_LEPIN, HMCTHELPY, F65126, HIU08875 1 and P_R41724.

EXAMPLE 119: Isolation of cDNA clones Encoding Human PRQ1788 The extracellular domain (ECD) sequences (including the secretion signal sequence, if any) from about 950 known secreted proteins from the Swiss-Prot public database were used to search EST databases. The EST 471 databases included public EST databases (e.g., GenBank), and a proprietary EST database (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, CA). The search was performed using the computer program BLAST or BLAST2 [Altschul et al., Methods in Enzvmologv. 266:460-480 (1996)] as a comparison of the ECD protein sequences to a 6 frame translation of the EST sequences. Incyte Clone No. 2968304 was identified as a sequence of interest having a BLAST score of 70 or greater that did not encode known proteins. The nucleotide sequence 5 of Incyte Clone No. 2968304 is designated herein as "DNA6612".

In addition, the DNA6612 sequence was extended using repeated cycles of BLAST and phrap (Phil Green, University of Washington, Seattle, Washington) to extend the sequence as far as possible using the sources of EST sequences discussed above. The extended consensus sequence is designated herein as "DNA49648". Based on the DNA49648 consensus sequence, oligonucleotides were synthesized: 1) to identify 10 by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01788.

PCR primers (forward and reverse) were synthesized: forward PCR nrimer: CCCTGCCAGCCGAGAGCTTCACC (49648.fl; SEQ ID NO:398) reverse PCR primer: GGTTGGTGCCCGAAAGGTCCAGC (49648.rl; SEQ ID NO:399) IS Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA49648 sequence which had the following nucleotide sequence: hvbridizationprobe: CAACCCCAAGCTTAACTGGGCAGGAGCTGAGGTGTTTTCAGGCQ49648.pl; SEQ ID N0:400) In order to screen several libraries for a source of a full-length clone, DNA from tbe libraries was 20 screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01788 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from human fetal kidney tissue.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PR01788 (designated herein as DNA77652-2505 [Figure 231, SEQ ID NO:396]; and the derived protein 25 sequence for PRO1788.

The entire coding sequence of PRO1788 is shown in Figure 231 (SEQ ID NO:396). Clone DNA77652-2S0S contains a single open reading frame with an apparent translational initiation site at nucleotide positions 64-66 and an apparent stop codon at nucleotide positions 1123-1125. Thepredictedpolypeptideprecursoris3S3 amino acids long. The full-length PRO1788 protein shown in Figure 232 has an estimated molecular weight of 30 about 37,847 daltons and a pi of about 6.80. Additional features of PRO 1788 include: a signal peptide at about amino acids 1-16; transmembrane domains at about amino acids 215-232 and287-304; potential N-glycosylation sites at about amino acids 74-77 and 137-140; a glycosaminoglycan attachment site at about amino acids 45-48; a tyrosine kinase phosphorylation site at about amino acids 318-325; N-myristoylation sites at about amino acids 13-18, 32-37, 88-93, 214-219, and 223-228; and a leucine zipper pattern at about amino acids 284-305. 35 An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 232 (SEQ ID NO:397), revealed significant homology between the PR01788 amino acid sequence and the following Dayhoff sequences: AF030435_1; 472 AF062006_1; DMTARTAN1; G ARP_HUM AN; S42799; P_R71294; HSU88879 1; DROWHEELER_l; A58532; and AF068920 1.

Clone DNA77652-2505 was deposited with the ATCC on November 17,1998, and is assigned ATCC deposit no. 203480.

EXAMPLE 120: Isolation of cDNA clones Encoding Human PRQ1801 A proprietary expressed sequence tag (EST) DNA database (LIFESEQ*, Incyte Pharmaceuticals, Palo Alto, CA) was searched and an EST was identified which showed homology to the IL-19 protein. This EST sequence is Incyte EST clone no. 819592 and is herein designated DNA79293. Based on the DNA79293 sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence 10 of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR01801.

PCR primers (forward and reverse) were synthesized: forward PCR primer 5'-CTCCTGTGGTCTCCAGATTTCAGGCCTA-3' (SEQ ID N0:403) reverse PCR primer 5'-AGTCCTCCTTAAGATTCTGATGTCAA-3' (SEQ ID N0:404) RNA for construction of the cDNA libraries was isolated from human fetal kidney tissue. The cDNA 15 libraries used to isolated the cDNA clones were constructed by standard methods using commercially available reagents such as those from Invitrogen, San Diego, CA. The cDNA was primed with oligo dT containing a NotI site, linked with blunt to Sail hemikinased adaptors, cleaved with NotI, sized appropriately by gel electrophoresis, and cloned in a defined orientation into a suitable cloning vector (such as pRKB or pRKD; pRKSB is a precursor of pRK5D that does not contain the Sfil site; see, Holmes et al., Science. 253:1278-1280 20 (1991)) in the unique Xhol and NotI sites.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PR01801 (designated herein as DNA83500-2506 [Figure 233, SEQ ID N0:401]; and the derived protein sequence for PR01801.

The entire nucleotide sequence of DNA83500-2506 is shown in Figure 233 (SEQ ID N0:401). Clone 25 DNA83500-2506 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 109-111 and ending at the stop codon at nucleotide positions 892-894 (Figure 233). The predicted polypeptide precursor is 261 aminn acids long (Figure 234). The full-length PR01801 protein shown in Figure 234 has an estimated molecular weight of about 29,667 daltons and a pi of about 8.76. Analysis of the full-length PR01801 sequence shown in Figure 234 (SEQ ID N0:402) evidences the presence of the following: a 30 signal peptide from about amino acid 1 to about amino acid 42, cAMP- and cGMP-dependent protein kinase phosphorylation sites from about amino acid 192 to about amino acid 195 and from about amino acid 225 to about amino acid 228 and potential N-myristolation sites from about aminn acid 42 to about amino acid 47, from about amino acid 46 to about amino acid 51 and from about amino acid 136 to about aminn acid 141. Clone DNA83500-2506 has been deposited with ATCC on October 29, 1998 and is assigned ATCC deposit no. 35 203391.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 234 (SEQ ID N0:402), evidenced significant 473 homology between the PR01801 aminn acid sequence and the following Dayhoff sequences: P_W37935, HGSJB477, P_R32277, IL10JV1ACFA, P_W46585, P_R39714, P_R71471, P_R10159, IL10_RAT and PW57201.

EXAMPLE 121: Isolation of cDNA clones Encoding Human UCP4 5 EST databases, which included public EST databases (e.g., GenBank), and a proprietary EST database (LIFESEQ™, Incyte Pharmaceuticals, Palo Alto, CA), were searched for sequences having homologies to human UCP3. The search was performed using the computer program BLAST or BLAST2 [Altschul et al., Methods in F.nrvmnlngv. 266:460-480 (1996)] as a comparison of the UCP3 protein sequences to a 6 frame translation of the EST sequences. Those comparisons resulting in a BLAST score of 70 (or in some cases, 90) or greater 10 that did not encode known proteins were clustered and assembled into consensus DNA sequences with the program AssemblLIGN and MacVector (Oxford Molecular Group, Inc.).

A DNA sequence ("fromDNA") was assembled relative to other EST sequences using AssemblLIGN software. In addition, the fromDNA sequence was extended using repeated cycles of BLAST and AssemblLIGN to extend the sequence as far as possible using the sources of EST sequences discussed above. Based on this 15 DNA sequence, oligonucleotides were synthesized to isolate a clone of the full-length coding sequences for UCP4 by PCR. Forward and reverse PCR primers generally range from 20 to 30 nucleotides and are often designed to give a PCR product of about 100-1000 bp in length. The probe sequences are typically 40-55 bp in length. In some cases, additional oligonucleotides are synthesized when the consensus sequence is greater than about l-1.5kbp.

PCR primers (forward and reverse) were synthesized: forward PCR primer CGCGGATCCCGTTATCGTCTTGCGCTACTGC (SEQ ID N0:407) reverse PCR Primer GCGGAATTCTTAAAATGGACTGACTCCACTCATC (SEQ ID N0:408) RNA for construction of the cDNA libraries was isolated from brain tissue. The cDNA libraries used to isolated the cDNA clones were constructed by standard methods using commercially available reagents such 25 as those from Invitrogen, San Diego, CA. The cDNA was primed with oligo dT containing a NotI site, linked with blunt to Sail hemikinased adaptors, cleaved with NotI, sized appropriately by gel electrophoresis, and cloned in a defined orientation into a suitable cloning vector (such as pRKB or pRKD; pRK5B is a precursor of pRK5D that does not contain the Sfil site; see. Holmes et al., Science. 253:1278-1280 (1991)) in the unique Xhol and NotI sites.

DNA sequencing of the clone isolated by PCR as described above gave the full-length DNA sequence for UCP4 (designated herein as DNA77568-1626 [Figure 235, SEQ ID N0:405] and the derived protein sequence for UCP4.

The entire coding sequence of UCP4 is shown in Figure 235 (SEQ ID N0:405). Clone DNA77568-1626 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 35 27-29, and an apparent stop codon at nucleotide positions 996-998. (See Figure 235; SEQ ID N0:405). The predicted polypeptide precursor is 323 amino acids long. It is presently believed that UCP4 is a membrane-bound protein and contains at least 6 transmembrane regions. These putative transmembrane regions in the 474 UCP4 amino acid sequence are illustrated in Figure 236. Clone DNA77S68-1626, contained in tbe pcDNA3 vector (Invitrogen) has been deposited with ATCC and is assigned ATCC deposit no. 203134. UCP4 polypeptide is obtained or obtainable by expressing the molecule encoded by the cDNA insert of the deposited ATCC 203134 vector. Digestion of the vector with BamHI and EcoRI restriction enzymes will yield an approximate 972 plus 34 bp insert. The full-length UCP4 protein shown in Figure 236 has an estimated 5 molecular weight of about 36,061 daltons and a pi of about 9.28.

EXAMPLE 122: Isolation of cDNA clones Encoding Human PRQ193 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. Based on this consensus sequence, oligonucleotides were synthesized: 1) to identify by 10 PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for PR0193.

A pair of PCR primers (forward and reverse) were synthesized: forward PCR primer 5'-GTTTGAGGAAGCTGGGATAC-3' (SEQ ID NO:411); and reverse PCR primer 5'-CCAAACTCGAGCACCTGTTC-3' (SEQ ID NO:412).

Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus sequence which had the following nucleotide sequence: hybridization probe '-ATGGCAGGCTTCCTAGATAATTTTCGTTGGCCAGAATGTG-3' (SEQ ID NO:413).

In order to screen several libraries for a source of a full-length clone, DNA from the libraries was 20 screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR0193 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from human retina tissue (LIB94).

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PR0193 [herein designated as DNA23322-1393] (SEQ ID N0:409) and the derived protein sequence for 25 PR0193.

The entire nucleotide sequence of DNA23322-1393 is shown in Figure 237 (SEQ ID N0:409). Clone DNA23322-1393 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 138-140 and ending at the stop codon at nucleotide positions 612-614 (Figure 237). The predicted polypeptide precursor is 158 amino acids long (Figure 238). The full-length PR0193 protein shown in Figure 30 238 has an estimated molecular weight of about 17,936 and a pi of about 5.32. Clone DNA23322-1393 has been deposited with the ATCC. Regarding the sequence, it is understood that the deposited clone contains the correct sequence, and the sequences provided herein are based on known sequencing techniques.

Still analyzing the amino acid sequence of SEQ ID N0:410, transmembrane domains are at about amino acids 23-42,60-80,97-117 and 128-148 of SEQ ID NO:410. A cell attachment sequence is at about amino acids 35 81-83 of SEQ ID N0:410. A peroxidase proximal heme-ligand domain is at about amino acids 81-83 of SEQ ID NQ:410. The corresponding nucleotides can be routinely determined given the sequences provided herein. 475 EXAMPLE 123: Isolation of cDNA clones Encoding Human PROl 130 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example 1 above. This consensus sequence is herein designated DNA34360. Based on the DNA34360 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for 5 PRO 1130.

PCR primers (forward and reverse) were synthesized: forward PCR primer (34360.fn 5'-GCCATAGTCACGACATGGATG-3' (SEQ ID NO:416) forward PCR nrimer (34360. fT> 5'-GGATGGCCAGAGCTGCTG-3' (SEQ ID NO:417) forward PCR primer (3436Q.f31 5'-AAAGTACAAGTGTGGCCTCATCAAGC-3' (SEQ ID NO:418) 10 reverse PCR primer (3436Q.rn 5'-TCTGACTCCTAAGTCAGGCAGGAG-3' (SEQ ID NO:419) reverse PCR primer (3436Q.rTl 5'-ATTCTCTCCACAGACAGCTGGTTC'3' (SEQ ID N0:420) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA34360 sequence which had the following nucleotide sequence hybridization probe (34360.pl) 5' -GTAC AAGTGTGGCCTC ATC AAGCCCTGCCCAGCC A ACT ACTTTGCG-3' (SEQ ID NO:421) In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PROl 130 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from human aortic endothelial cell tissue. 20 DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PR01130 (designated herein as DNA59814-1486 [Figure 239, SEQ ID NO:414]; and the derived protein sequence for PRO 1130.

The entire nucleotide sequence of DNA59814-1486 is shown in Figure 239 (SEQ ID NO:414). Clone DNA59814-1486 contains a single open reading frame with an apparent translational initiation site at nucleotide 25 positions 312-314 and ending at the stop codon at nucleotide positions 984-986 (Figure 239). The predicted polypeptide precursor is 224 amino acids long (Figure 240). The full-length PROl 130 protein shown in Figure 240 has an estimated molecular weight of about 24,963 daltons and a pi of about 9.64. Analysis of the full-length PROl 130 sequence shown in Figure 240 (SEQ ID NO:415) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 15, an ATP/GTP-binding site motif A from about 30 amino acid 184 to about amino acid 191 and a potential N-glycosylation site from about amino acid 107 to about amino acid 110. Clone DNA59814-1486 has been deposited with ATCC on October 20,1998 and is assigned ATCC deposit no. 203359.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 240 (SEQ ID NO:415), evidenced significant 35 homology between the PROl 130 amino acid sequence and the following Dayhoff sequences: PW06547, 216 HUMAN, D87120 1, MMU72677J, LAU04889 1, andD69319. 476 EXAMPLE 124: Isolation of cDNA clones Encoding Human PRO 1335 A consensus DNA sequence was assembled relative to other EST sequences using phrap as described in Example l above. This consensus sequence is herein designated DNA35727. Based on the DNA35727 consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for 5 PR01335.

PCR primers (forward and reverse) were synthesized: forward PCR primer (35727.fl) 5'-GTAAAGTCGCTGGCCAGC-3' (SEQ ID NO:424) forward PCR primer (35727.f2) 5'-CCCGATCTGCCTGCTGTA-3' (SEQ ID NO:425) reverse PCR primer (35727 .rl) 5'-CTGCACTGTATGGCCATTATTGTG-3' (SEQ ID NO:426) 10 Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensus DNA35727 sequence which had the following nucleotide sequence hybridization probe (35727.pl) '-CAGAAACCCATGATACCCTACTGAACACCGAATCCCCTGGAAGCC-3' (SEQ ID NO:427) In order to screen several libraries for a source of a full-length clone, DNA from the libraries was 15 screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the PR01335 gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from human retina tissue.

DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for PR01335 (designated herein as DNA62812-1594 [Figure 241, SEQ ID NO:422]; and the derived protein 20 sequence for PR01335.

The entire nucleotide sequence of DNA62812-1594 is shown in Figure 241 (SEQ ID NO:422). Clone DNA62812-1594 contains a single open reading frame with an apparent translational initiation site at nucleotide positions 271-273 and ending at the stop codon at nucleotide positions 1282-1284 (Figure 241). The predicted polypeptide precursor is 337 amino acids long (Figure 242). The full-length PR01335 protein shown in Figure 25 242 has an estimated molecular weight of about 37,668 daltons and a pi of about 6.27. Analysis of the full-length PR01335 sequence shown in Figure 242 (SEQ ID NO:423) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 15, a transmembrane domain from about amino acid 291 to about amino acid 310, a potential N-glycosylation site from about amino acid 213 to about amino acid 216 and amino acid sequence blocks having homology to eukaryotic-type carbonic anhydrase proteins from about 30 amino acid 197 to about amino acid 245, from about amino acid 104 to about amino acid 140 and from about amino acid 22 to about amino acid 69. Clone DNA62812-1594 has been deposited with ATCC on September 9, 1998 and is assigned ATCC deposit no. 203248.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 242 (SEQ ID NO:423), evidenced significant 35 homology between the PR01335 amino acid sequence and the following Dayhoff sequences: AF037335_1, 138013, PTPG_MOUSE, CAH2 HUMAN , 1CAC, CAH7_HUMAN, CAH3_HUMAN, CAH1HUMAN, CAH5 HUMAN and P R41746. 477 EXAMPLE 125: Isolation of cDNA clones Encoding Human PRQ1329 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST cluster sequence from the LIFESEQ* database, designated Incyte Cluster No. 167544, also referred herein as "DNA10680". This EST cluster sequence was then compared to a variety of expressed sequence tag (EST) databases which included public EST databases (e.g., GenBank) and a proprietary EST DNA database 5 (LIFESEQ*, Incyte Pharmaceuticals, Palo Alto, CA) to identify existing homologies. The homology search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the program "phrap" (Phil Green, University of Washington, Seattle, Washington). One or more of the ESTs was derived from a 10 cDNA library constructed from RNA isolated from synovial membrane tissue removed from the elbow of a female with rheumatoid arthritis. The consensus sequence obtained therefrom is herein designated "DNA58836".

In light of the sequence homology between the DNA58836 sequence and a sequence contained within the Incyte EST clone no. 368774, EST clone 368774 was purchased and the cDNA insert was obtained and 15 sequenced. The sequence of this cDNA insert is shown in Figure 243 and is herein designated as DNA66660-1585.

The Ml length clone shown in Figure 243 contained a single open reading frame with an apparent translational initiation site at nucleotide positions 90 to 92 and ending at the stop codon found at nucleotide positions 717 to 719 (Figure 243; SEQ ID NO:428). The predicted polypeptide precursor (Figure 244, SEQ 20 ID NO:429) is 209 amino acids long, with a signal sequence at about amino acids 1-16. PR01329 has a calculated molecular weight of approximately 21,588 daltons and an estimated pi of approximately 5.50. Clone DNA66660-1585 was deposited with the ATCC on September 22, 1998 and is assigned ATCC deposit no. 203279.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence 25 alignment analysis of the full-length sequence shown in Figure 244 (SEQ ID NO:429), revealed some homology between the PR01329 amino acid sequence and the following Dayhoff sequences: CELK06A9 3, PROA_XANCP, CXU21300_4, MTV037_17, SYN1_RAT, 156542, S60743, BNOLE3_l, AB001573_1, and PJP80671.

F.XAMPT.F. 17fi- Isolation of cDNA clones Encoding Human PRQ1550 Use of the signal sequence algorithm described in Example 3 above allowed identification of an EST sequence from the Merck database, designated CELT15B712, also referred herein as "DNA10022". This EST sequence was then compared to a variety of expressed sequence tag (EST) databases which included public and proprietary EST databases (e.g., GenBank and LIFESEQ*) to identify existing homologies. The homology 35 search was performed using the computer program BLAST or BLAST2 (Altshul et al.. Methods in Enzvmologv 266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into a consensus DNA sequence with the 478 I program "phrap" (Phil Green, University of Washington, Seattle, Washington). The consensus sequence obtained therefrom is herein designated "DNA55708".

In light of die sequence homology between the DNA55708 sequence and a sequence contained within Incyte EST no. 3411659, die EST clone 3411659 was purchased and the cDNA insert was obtained and sequenced in its entirety. The sequence of this cDNA insert is shown in Figure 245 and is herein designated as "DNA76393-1664".

The Ml length clone shown in Figure 245 contained a single open reading frame with an apparent translational initiation site at nucleotide positions 138 to 140 and ending at the stop codon found at nucleotide positions 867 to 869 (Figure 245; SEQ ID NO:231). The predicted polypeptide precursor (Figure 246, SEQ ID NO:232) is 243 amino acids long. Other features of the PR01550 protein include: a signal sequence at about amino acids 1-30; a hydrophobic domain at about amino acids 195-217; and a potential N-glycosylation site at about amino acids 186-189. PRO 1550 has a calculated molecular weight of approximately 26,266 daltons and an estimated pi of approximately 8.43. Clone DNA76393-1664 was deposited with the ATCC on October 6, 1998, and is assigned ATCC deposit no. 203323.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), using a WU-BLAST2 sequence alignment analysis of the full-length sequence shown in Figure 246 (SEQ ID NO:232), revealed some homology between the PR01550 amino acid sequence and the following Dayhoff sequences: CELF59E1211; CA24ASCSU; AF018082J; CA13_BOVIN; CA54HUMAN; CA34 HUMAN; HUMCOL7AlX_l; P W09643; AF053538_1; and HSEMCXIV2_1.

EXAMPLE 127: Use of PRO as a hybridization probe The following method describes use of a nucleotide sequence encoding PRO as a hybridization probe. DNA comprising the coding sequence of full-length or mature PRO as disclosed herein is employed as a probe to screen for homologous DN As (such as those encoding naturally-occurring variants of PRO) in human tissue cDNA libraries or human tissue genomic libraries.

Hybridization and washing of filters containing either library DNAs is performed under the following high stringency conditions. Hybridization of radiolabeled PRO-derived probe to the filters is performed in a solution of 50% formamide, 5x SSC, 0.1% SDS, 0.1% sodium pyrophosphate, 50 mM sodium phosphate, pH 6.8, 2x Denhardt's solution, and 10% dextran sulfate at 42°C for 20 hours. Washing of the filters is performed in an aqueous solution of 0. lx SSC and 0.1 % SDS at 42°C.

DNAs having a desired sequence identity with the DNA encoding full-length native sequence PRO can then be identified using standard techniques known in the art.

EXAMPLE 128: Expression of PRO in E. coli This example illustrates preparation of an unglycosylated form of PRO by recombinant expression in E. coli.

The DNA sequence encoding PRO is initially amplified using selected PCR primers. The primers should contain restriction enzyme sites which correspond to the restriction enzyme sites on the selected 479 r^uECTU^rjqoP^ i ofcjct of N.Z 2 4 OCT 2003 received expression vector. A variety of expression vectors may be employed. An example of a suitable vector is pBR322 (derived from E. coli; see Bolivar et al., Gene. 2:95 (1977)) which contains genes for ampicillin and tetracycline resistance. The vector is digested with restriction enzyme and dephosphorylated. The PCR amplified sequences are then ligated into the vector. The vector will preferably include sequences which encode for an antibiotic resistance gene, a trp promoter, a polyhis leader (including the first six STII codons, polyhis 5 sequence, and enterokinase cleavage site), the PRO coding region, lambda transcriptional terminator, and an argU gene.

The ligation mixture is then used to transform a selected E. coli strain using the methods described in Sambrook et al., supra. Transfbrmants are identified by their ability to grow on LB plates and antibiotic resistant colonies are then selected. Plasmid DNA can be isolated and confirmed by restriction analysis and DNA 10 sequencing.

Selected clones can be grown overnight in liquid culture medium such as LB broth supplemented with antibiotics. The overnight culture may subsequently be used to inoculate a larger scale culture. The cells are then grown to a desired optical density, during which the expression promoter is turned on.

After culturing the cells for several more hours, the cells can be harvested by centrifugation. The cell 15 pellet obtained by the centrifugation can be solubilized using various agents known in the art, and the solubilized PRO protein can then be purified using a metal chelating column under conditions that ailow tight binding of the protein.

PRO may be expressed in E. coli in a poly-His tagged form, using the following procedure. The DNA encoding PRO is initially amplified using selected PCR primers. The primers will contain restriction enzyme 20 sites which correspond to the restriction enzyme sites on the selected expression vector, and other useful sequences providing for efficient and reliable translation initiation, rapid purification on a metal chelation column, and proteolytic removal with enterokinase. The PCR-amplified, poly-His tagged sequences are then ligated into an expression vector, which is used to transform an E. coli host based on strain 52 (W3110 fuhA(tonA) Ion galE rpoHts(htpRts) clpP(lacIq). Transformants are first grown in LB containing 50 mg/ml 25 carbenicillin at 30°C with shaking until an 0,D.600of3-5 is reached. Cultures are then diluted 50-100 fold into CRAP media (prepared by mixing 3.57 g (NH^SO^ 0.71 g sodium citrate*2H20, 1.07 g KC1, 5.36 g Difco yeast extract, 5.36 g Sheffield hycase SF in 500 mL water, as well as 110 mM MPOS, pH 7.3, 0.55% (w/v) glucose and 7 mM MgSO*) and grown for approximately 20-30 hours at 30°C with shaking. Samples are removed to verify expression by SDS-PAGE analysis, and the bulk culture is centrifuged to pellet the cells. Cell 30 pellets are frozen until purification and refolding.

E. coli paste from 0.5 to I L fermentations (6-10 g pellets) is resuspended in 10 volumes (w/v) in 7 M guanidine, 20 mM Tris, pH 8 buffer. Solid sodium sulfite and sodium tetrathionate is added to make final concentrations of 0.1M and 0.02 M, respectively, and the solution is stirred overnight at 4°C. This step results in a denatured protein with all cysteine residues blocked by sulfitolization. The solution is centrifuged at 40,000 35 rpm in a Beckman Ultracentifuge for 30 min. The supernatant is diluted with 3-5 volumes of metal chelate column buffer (6 M guanidine, 20 mM Tris, pH 7.4) and filtered through 0.22 micron filters to clarify. The clarified extract is loaded onto a 5 ml Qiagen Ni-NTA metal chelate column equilibrated in the metal chelate 480 column buffer. The column is washed with additional buffer containing SO mM imidazole (Calbiochem, Utrol grade), pH 7.4. The protein is eluted with buffer containing 250 mM imidazole. Fractions containing the desired protein are pooled and stored at 4°C. Protein concentration is estimated by its absorbance at 280 nm using the calculated extinction coefficient based on its amino acid sequence.

The proteins are refolded by diluting the sample slowly into freshly prepared refolding buffer consisting 5 of: 20 mM Tris, pH 8.6, 0.3 M NaCl, 2.5 M urea, 5 mM cysteine, 20 mM glycine and 1 mM EDTA. Refolding volumes are chosen so that the final protein concentration is between 50 to 100 micrograms/ml. The refolding solution is stirred gently at 4°C for 12-36 hours. The refolding reaction is quenched by the addition of TFA to a final concentration of 0.4 % (pH of approximately 3). Before further purification of the protein, the solution is filtered through a 0.22 micron filter and acetonitrile is added to 2-10% final concentration. The 10 refolded protein is chromatographed on a Poros Rl/H reversed phase column using a mobile buffer of 0.1% TFA with eiution with a gradient of acetonitrile from 10 to 80%. Aliquots of fractions with A280 absorbance are analyzed on SDS polyacrylamide gels and fractions containing homogeneous refolded protein are pooled. Generally, the properly refolded species of most proteins are eluted at the lowest concentrations of acetonitrile since those species are the most compact with their hydrophobic interiors shielded from interaction with the IS reversed phase resin. Aggregated species are usually eluted at higher acetonitrile concentrations. In addition to resolving misfolded forms of proteins from the desired form, the reversed phase step also removes endotoxin from the samples.

Fractions containing the desired folded PRO polypeptide are pooled and the acetonitrile removed using a gentle stream of nitrogen directed at the solution. Proteins are formulated into 20 mM Hepes, pH 6.8 with 20 0.14 M sodium chloride and 4% mannitol by dialysis or by gel filtration using G25 Superfine (Pharmacia) resins equilibrated in the formulation buffer and sterile filtered.

Many of the PRO polypeptides disclosed herein were successfully expressed as described above.

EXAMPLE 129: Expression of PRO in mammalian cells 25 This example illustrates preparation of a potentially glycosylated form of PRO by recombinant expression in mammalian cells.

The vector, pRK5 (see EP 307,247, published March 15,1989), is employed as the expression vector. Optionally, the PRO DNA is ligated into pRK5 with selected restriction enzymes to allow insertion of the PRO DNA using ligation methods such as described in Sambrook et al., supra. The resulting vector is called pRK5-30 PRO.

In oik embodiment, the selected host cells may be 293 cells. Human 293 cells (ATCC CCL 1573) are grown to confluence in tissue culture plates in medium such as DMEM supplemented with fetal calf serum and optionally, nutrient components and/or antibiotics. About 10 ng pRK5-PRO DNA is mixed with about 1 pg DNA encoding the VA RNA gene [Thimmappaya et al., Cell. 31:543 (1982)] and dissolved in 500 /tl of 1 mM 35 Tris-HCl, 0.1 mM EDTA, 0.227 M CaCl2. To this mixture is added, dropwise, 500 jil of 50 mM HEPES (pH 7.35), 280 mM NaCl, 1.5 mM NaPO*, and a precipitate is allowed to form for 10 minutes at 25°C. The precipitate is suspended and added to the 293 cells and allowed to settle for about four hours at 37"C. The 481 PCT/US99/201I1 culture medium is aspirated off and 2 ml of 20% glycerol in PBS is added for 30 seconds. The 293 cells are then washed with serum free medium, fresh medium is added and the cells are incubated for about 5 days.

Approximately 24 hours after the transfections, the culture medium is removed and replaced with culture medium (alone) or culture medium containing 200 pCi/ml 33S-cysteine and 200 pCi/ml33S-methionine. After a 12 hour incubation, the conditioned medium is collected, concentrated on a spin filter, and loaded onto a 15% 5 SDS gel. The processed gel may be dried and exposed to film for a selected period of time to reveal the presence of PRO polypeptide. The cultures containing transfected cells may undergo further incubation (in serum free medium) and the medium is tested in selected bioassays.

In an alternative technique, PRO may be introduced into 293 cells transiently using the dextran sulfate method described by Somparyrac et al., Proc. Natl. Acad. Sci.. 12:7575 (1981). 293 cells are grown to 10 maximal density in a spinner flask and 700 fig pRK5-PRO DNA is added. The cells are first concentrated from the spinner flask by centrifugation and washed with PBS. The DNA-dextran precipitate is incubated on the cell pellet for four hours. The cells are treated with 20% glycerol for 90 seconds, washed with tissue culture medium, and re-introduced into the spinner flask containing tissue culture medium, 5 /tg/ml bovine insulin and 0.1 pg/ml bovine transferrin. After about four days, the conditioned media is centrifuged and filtered to remove IS cells and debris. The sample containing expressed PRO can then be concentrated and purified by any selected method, such as dialysis and/or column chromatography.

In another embodiment, PRO can be expressed in CHO cells. The pRK5-PRO can be transfected into CHO cells using known reagents such as CaP04 or DEAE-dextran. As described above, the cell cultures can be incubated, and the medium replaced with culture medium (alone) or medium containing a radiolabel such as 20 MS-methionine. After determining the presence of PRO polypeptide, the culture medium may be replaced with serum free medium. Preferably, the cultures are incubated for about 6 days, and then the conditioned medium is harvested. The medium containing the expressed PRO can then be concentrated and purified by any selected method.

Epitope-tagged PRO may also be expressed in host CHO cells. The PRO may be subcloned out of the 25 pRK5 vector. The subclone insert can undergo PCR to fuse in frame with a selected epitope tag such as a polyhis tag into a Baculovirus expression vector. The poly-his tagged PRO insert can then be subcloned into a SV40 driven vector containing a selection marker such as DHFR for selection of stable clones. Finally, the CHO cells can be transfected (as described above) with the SV40 driven vector. Labeling may be performed, as described above, to verify expression. The culture medium containing the expressed poly-His tagged PRO can then be 30 concentrated and purified by any selected method, such as by Ni2+-chelate affinity chromatography.

PRO may also be expressed in CHO and/or COS cells by a transient expression procedure or in CHO cells by another stable expression procedure.

Stable expression in CHO cells is performed using the following procedure. The proteins are expressed as an IgG construct (immunoadhesin), in which the coding sequences for the soluble forms (e.g. extracellular 35 domains) of the respective proteins are fused to an IgGl constant region sequence containing the hinge, CH2 and CH2 domains and/or is a poly-His tagged form.

Following PCR amplification, the respective DNAs are subcloned in a CHO expression vector using 482 standard techniques as described in Ausubel et al., Current Protocols of Molecular Biology. Unit 3.16, John Wiley and Sons (1997). CHO expression vectors are constructed to have compatible restriction sites 5' and 3' of the DNA of interest to allow the convenient shuttling of cDNA's. The vector used expression in CHO cells is as described in Lucas et al., Nucl. Acids Res. 24:9 (1774-1779 (1996), and uses the SV40 early promoter/enhancer to drive expression of the cDNA of interest and dihydrofolate reductase (DHFR). DHFR 5 expression permits selection for stable maintenance of the plasmid following transfection.

Twelve micrograms of the desired plasmid DNA is introduced into approximately 10 million CHO cells using commercially available transfection reagents Superfect* (Quiagen), Dosper' or Fugene* (Boehringer Mannheim). The cells are grown as described in Lucas et al., supra. Approximately 3 x IO"7 cells are frozen in an ampule for further growth and production as described below.

The ampules containing the plasmid DNA are thawed by placement into water bath and mixed by vortexing. The contents are pipetted into a centrifuge tube containing 10 mLs of media and centrifuged at 1000 rpm for 5 minutes. The supernatant is aspirated and the cells are resuspended in 10 mL of selective media (0.2 ^m filtered PS20 with 5% 0.2 /um diafiltered fetal bovine serum). The cells are then aliquoted into a 100 mL spinner containing 90 mL of selective media. After 1-2 days, the cells are transferred into a 250 mL spinner 15 filled with 150 mL selective growth medium and incubated at 37°C. After another 2-3 days, 250 mL, 500 mL and 2000 mL spinners are seeded with 3 x 10s cells/mL. The cell media is exchanged with fresh media by centrifugation and resuspension in production medium. Although any suitable CHO media may be employed, a production medium described in U.S. Patent No. 5,122,469, issued June 16, 1992 may actually be used. A 3L production spinner is seeded at 1.2 x lCcells/mL. On day 0, the cell number pH ie determined. On day 20 1, the spinner is sampled and sparging with filtered air is commenced. On day 2, the spinner is sampled, the temperature shifted to 33°C, and 30 mL of 500 g/L glucose and 0.6 mL of 10% antifoam (e.g., 35% polydimethylsiloxane emulsion, Dow Coming 365 Medical Grade Emulsion) taken. Throughout the production, the pH is adjusted as necessary to keep it at around 7.2. After 10 days, or until the viability dropped below 70 %, the cell culture is harvested by centrifugation and filtering through a 0.22 nm filter. The filtrate was either 25 stored at 4°C or immediately loaded onto columns for purification.

For the poly-His tagged constructs, the proteins are purified using a Ni-NTA column (Qiagen). Before purification, imidazole is added to the conditioned media to a concentration of 5 mM. The conditioned media is pumped onto a 6 ml Ni-NTA column equilibrated in 20 mM Hepes, pH 7.4, buffer containing 0.3 M NaCl and 5 mM imidazole at a flow rate of 4-5 ml/min. at 4°C. After loading, the column is washed with additional 30 equilibration buffer and the protein eluted with equilibration buffer containing 0.25 M imidazole. The highly purified protein is subsequently desalted into a storage buffer containing 10 mM Hepes, 0.14 M NaCl and 4% mannitol, pH 6.8, with a 25 ml G25 Superfine (Pharmacia) column and stored at -80°C.

Immunoadhesin (Fc-containing) constructs are purified from the conditioned media as follows. The conditioned medium is pumped onto a 5 ml Protein A column (Pharmacia) which had been equilibrated in 20 35 mM Na phosphate buffer, pH 6.8. After loading, the column is washed extensively with equilibration buffer before elution with 100 mM citric acid, pH 3.5. The eluted protein is immediately neutralized by collecting 1 ml fractions into tubes containing 275 /uL of 1 M Tris buffer, pH 9. The highly purified protein is subsequently 483 desalted into storage buffer as described above for the poly-His tagged proteins. The homogeneity is assessed by SDS polyacrylamide gels and by N-tenninal aminn acid sequencing by Edman degradation.

EXAMPLE 130: Expression of PRO in Yeast 5 The following method describes recombinant expression of PRO in yeast.

First, yeast expression vectors are constructed for intracellular production or secretion of PRO from the ADH2/GAPDH promoter. DNA encoding PRO and the promoter is inserted into suitable restriction enzyme sites in the selected plasmid to direct intracellular expression of PRO. For secretion, DNA encoding PRO can be cloned into the selected plasmid, together with DNA encoding the ADH2/GAPDH promoter, a native PRO 10 signal peptide or other mammalian signal peptide, or, for example, a yeast alpha-factor or invertase secretory signal/leader sequence, and linker sequences (if needed) for expression of PRO.

Yeast cells, such as yeast strain ABl 10, can then be transformed with the expression plasmids described above and cultured in selected fermentation media. The transformed yeast supernatants can be analyzed by precipitation with 10% trichloroacetic acid and separation by SDS-PAGE, followed by staining of the gels with IS Coomassie Blue stain.

Recombinant PRO can subsequently be isolated and purified by removing the yeast cells from the fermentation medium by centrifugation and then concentrating the medium using selected cartridge filters. The concentrate containing PRO may further be purified using selected column chromatography resins.

EXAMPLE 131: Expression of PRO in Baculovirus-Infected Insect Cells The following method describes recombinant expression of PRO in Baculovirus-infected insect cells.

The sequence coding for PRO is fused upstream of an epitope tag contained within a baculovirus expression vector. Such epitope tags include po]y-his tags and immunoglobulin tags (like Fc regions of IgG). 25 A variety of plasmids may be employed, including plasmids derived from commercially available plasmids such as pVL1393 (Novagen). Briefly, the sequence encoding PRO or the desired portion of die coding sequence of PRO such as the sequence encoding the extracellular domain of a transmembrane protein or the sequence encoding the mature protein if the protein is extracellular is amplified by PCR with primers complementary to the 5' and 3' regions. The 5' primer may incorporate flanking (selected) restriction enzyme sites. The product 30 is then digested with those selected restriction enzymes and subcloned into the expression vector.

Recombinant baculovirus is generated by co-transfecting the above plasmid and BaculoGold™ virus DNA (Pharmingen) into Spodopterafrugiperda ("Sf9") cells (ATCC CRL 1711) using lipofectin (commercially available from GIBCO-BRL). After 4-5 days of incubation at 28°C, the released viruses are harvested and used for further amplifications. Viral infection and protein expression are performed as described by O'Reilley et 35 al., Baculovirus expression vectors: A Laboratory Manual. Oxford: Oxford University Press (1994).

Expressed poly-his tagged PRO can then be purified, for example, by Ni2+-chelate affinity chromatography as follows. Extracts are prepared from recombinant virus-infected Sf9 cells as described by 484 Rupen et al., Nature. 362:175-179 (1993). Briefly, Sf9 cells are washed, resuspended in sonication buffer (25 mL Hepes, pH 7.9; 12.5 mM MgCl2; 0.1 mM EDTA; 10% glycerol; 0.1% NP-40; 0.4 M KC1), and sonicated twice for 20 seconds on ice. The sonicates are cleared by centrifugation, and the supernatant is diluted 50-fold in loading buffer (50 mM phosphate, 300 mM NaCl, 10% glycerol, pH 7.8) and filtered through a 0.45 ura filter. A Ni2+-NTA agarose column (commercially available from Qiagen) is prepared with a bed volume of 5 5 mL, washed with 25 mL of water and equilibrated with 25 mL of loading buffer. The filtered cell extract is loaded onto the column at 0.5 mL per minute. The column is washed to baseline A280 with loading buffer, at which point fraction collection is started. Next, the column is washed with a secondary wash buffer (50 mM phosphate; 300 mM NaCl, 10% glycerol, pH 6.0), which elutes nonspecifically bound protein. After reaching A2io baseline again, the column is developed with a 0 to 500 mM Imidazole gradient in the secondary wash 10 buffer. One mL fractions are collected and analyzed by SDS-PAGE and silver staining or Western blot with Ni2+-NTA-conjugated to alkaline phosphatase (Qiagen). Fractions containing the eluted His,0-tagged PRO are pooled and dialyzed against loading buffer.

Alternatively, purification of the IgG tagged (or Fc tagged) PRO can be performed using known chromatography techniques, including for instance, Protein A or protein G column chromatography. 15 Many of the PRO polypeptides disclosed herein were successfully expressed as described above.

EXAMPLE 132: Preparation of Antibodies that Bind PRO This example illustrates preparation of monoclonal antibodies which can specifically bind PRO.

Techniques for producing the monoclonal antibodies are known in the art and are described, for 20 instance, in Goding, supra. Immunogens that may be employed include purified PRO, fusion proteins containing PRO, and cells expressing recombinant PRO on the cell surface. Selection of the immunogen can be made by the skilled artisan without undue experimentation.

Mice, such as Balb/c, are immunized with the PRO immunogen emulsified in complete Freund's adjuvant and injected subcutaneously or intraperitoneal^ in an amount from 1-100 micrograms. Alternatively, 25 the immunogen is emulsified in MPL-TDM adjuvant (Ribi Immunochemical Research, Hamilton, MT) and injected into the animal's hind foot pads. Tbe immunized mice are then boosted 10 to 12 days later with additional immunogen emulsified in the selected adjuvant. Thereafter, for several weeks, the mice may also be boosted with additional immunization injections. Serum samples may be periodically obtained from the mice by retro-orbital bleeding for testing in ELISA assays to detect anti-PRO antibodies.

After a suitable antibody titer has been detected, the animals "positive" for antibodies can be injected with a final intravenous injection of PRO. Three to four days later, the mice are sacrificed and the spleen cells are harvested. The spleen cells are then fused (using 35% polyethylene glycol) to a selected murine myeloma cell line such as P3X63AgU.l, available fiom ATCC, No. CRL 1597. The fusions generate hybridoma cells which can then be plated in 96 well tissue culture plates containing HAT (hypoxanthine, aminopterin, and 35 thymidine) medium to inhibit proliferation of non-fused cells, myeloma hybrids, and spleen cell hybrids.

The hybridoma cells will be screened in an ELISA for reactivity against PRO. Determination of "positive" hybridoma cells secreting the desired monoclonal antibodies against PRO is within the skill in the art. 485 The positive hybridoma cells can be injected intraperitoneal^ into syngeneic Balb/c mice to produce ascites containing the anti-PRO monoclonal antibodies. Alternatively, the hybridoma cells can be grown in tissue culture flasks or roller bottles. Purification of the monoclonal antibodies produced in the ascites can be accomplished using ammonium sulfate precipitation, followed by gel exclusion chromatography. Alternatively, affinity chromatography based upon binding of antibody to protein A or protein G can be employed.

EXAMPT.F. 133: Purification of PRO Polypeptides Using Specific Antibodies Native or recombinant PRO polypeptides may be purified by a variety of standard techniques in the art of protein purification. For example, pro-PRO polypeptide, mature PRO polypeptide, or pre-PRO polypeptide is purified by immunoaffinity chromatography using antibodies specific for the PRO polypeptide of interest. In 10 general, an immunoaffinity column is constructed by covalently coupling the anti-PRO polypeptide antibody to an activated chromatographic resin.

Polyclonal immunoglobulins are prepared from immune sera either by precipitation with ammonium sulfate or by purification on immobilized Protein A (Pharmacia LKB Biotechnology, Piscataway, N.J.). Likewise, monoclonal antibodies are prepared from mouse ascites fluid by ammonium sulfate precipitation or 15 chromatography on immobilized Protein A. Partially purified immunoglobulin is covalently attached to a chromatographic resin such as CnBr-activated SEPHAROSE™ (Pharmacia LKB Biotechnology). The antibody is coupled to the resin, the resin is blocked, and the derivative resin is washed according to the manufacturer's instructions.

Such an immunoaffinity column is utilized in the purification of PRO polypeptide by preparing a fraction 20 from cells containing PRO polypeptide in a soluble form. This preparation is derived by solubilization of the whole cell or of a subcellular fraction obtained via differential centrifugation by the addition of detergent or by other methods well known in the art. Alternatively, soluble PRO polypeptide containing a signal sequence may be secreted in useful quantity into the medium in which the cells are grown.

A soluble PRO polypeptide-containing preparation is passed over the immunoaffinity column, and the 25 column is washed under conditions that allow the preferential absorbance of PRO polypeptide (e.g., high ionic strength buffers in the presence of detergent). Then, the column is eluted under conditions that disrupt antibody/PRO polypeptide binding (e.g., a low pH buffer such as approximately pH 2-3, or a high concentration of a chaotrope such as urea or thiocyanate ion), and PRO polypeptide is collected.

EXAMPLE 134: Drug Screening This invention is particularly useful for screening compounds by using PRO polypeptides or binding fragment thereof in any of a variety of drug screening techniques. The PRO polypeptide or fragment employed in such a test may either be free in solution, affixed to a solid support, borne on a cell surface, or located intracellularly. One method of drug screening utilizes eukaryotic or prokaryotic host cells which are stably 35 transformed with recombinant nucleic acids expressing the PRO polypeptide or fragment. Drugs are screened against such transformed cells in competitive binding assays. Such cells, either in viable or fixed form, can be used for standard binding assays. One may measure, for example, the formation of complexes between PRO 486 WO 00/12708 PCT/US99/20111 polypeptide or a fragment and the agent being tested. Alternatively, one can examine the diminution in complex formation between the PRO polypeptide and its target cell or target receptors caused by the agent being tested.

Thus, the present invention provides methods of screening for drugs or any other agents which can affect a PRO polypeptide-associated disease or disorder. These methods comprise contacting such an agent with an PRO polypeptide or fragment thereof and assaying (I) for the presence of a complex between the agent and 5 the PRO polypeptide or fragment, or (ii) for the presence of a complex between the PRO polypeptide or fragment and the cell, by methods well known in the art. In such competitive binding assays, the PRO polypeptide or fragment is typically labeled. After suitable incubation, free PRO polypeptide or fragment is separated from that present in bound form, and the amount of free or uncomplexed label is a measure of the ability of the particular agent to bind to PRO polypeptide or to interfere with the PRO poiypeptide/cell complex. 10 Another technique for drug screening provides high throughput screeningfor compounds having suitable binding affinity to a polypeptide and is described in detail in WO 84/03564, published on September 13,1984. Briefly stated, large numbers of different small peptide test compounds are synthesized on a solid substrate, such as plastic pins or some other surface. As applied to a PRO polypeptide, the peptide test compounds are reacted with PRO polypeptide and washed. Bound PRO polypeptide is detected by methods well known in the art. IS Purified PRO polypeptide can also be coated directly onto plates for use in the aforementioned drug screening techniques. In addition, non-neutralizing antibodies can be used to capture the peptide and immobilize it on the solid support.

This invention also contemplates the use of competitive drug screening assays in which neutralizing antibodies capable of binding PRO polypeptide specifically compete with a test compound for binding to PRO 20 polypeptide or fragments thereof. In this manner, the antibodies can be used to detect the presence of any peptide which shares one or more antigenic determinants with PRO polypeptide.

EXAMPLE 13.5: Rational Drue Design The goal of rational drug design is to produce structural analogs of biologically active polypeptide of 25 interest (i.e., a PRO polypeptide) or of small molecules with which they interact, e.g., agonists, antagonists, or inhibitors. Any of these examples can be used to fashion drugs which are more active or stable forms of the PRO polypeptide or which enhance or interfere with the function of the PRO polypeptide in vivo (c.f., Hodgson, Bio/Technology. 9: 19-21 (1991)).

In one approach, the three-dimensional structure of the PRO polypeptide, or of an PRO 30 polypeptide-inhibitor complex, is determined by x-ray crystallography, by computer modeling or, most typically, by a combination of the two approaches. Both the shape and charges of the PRO polypeptide must be ascertained to elucidate the structure and to determine active site(s) of the molecule. Less often, useful information regarding the structure of the PRO polypeptide may be gained by modeling based on the structure of homologous proteins. In both cases, relevant structural information is used to design analogous PRO polypeptide-like molecules or to 35 identify efficient inhibitors. Useful examples of rational drug design may include molecules whichhave unproved activity or stability as shown by Braxton and Wells, Biochemistry. 21:7796-7801 (1992) ot which act as inhibitors, agonists, or antagonists of native peptides as shown by Athauda et al., J. Biochem.. 113:742-746 487 (1993).

It is also possible to isolate a target-specific antibody, selected by functional assay, as described above, and then to solve its crystal structure. This approach, in principle, yields a pharmacore upon which subsequent drug design can be based. It is possible to bypass protein crystallography altogether by generating anti-idiotypic antibodies (anti-ids) to a functional, pharmacologically active antibody. As a minor image of a mirror image, the binding site of the anti-ids would be expected to be an analog of the original receptor. The anti-id could then be used to identify and isolate peptides from banks of chemically or biologically produced peptides. The isolated peptides would then act as the pharmacore.

By virtue of the present invention, sufficient amounts of the PRO polypeptide may be made available to perform such analytical studies as X-ray crystallography. In addition, knowledge of the PRO polypeptide amino acid sequence provided herein will provide guidance to those employing computer modeling techniques in place of or in addition to x-ray crystallography.

Deposit of Material The following materials have been deposited with the American Type Culture Collection, 10801 University Blvd., Manassas, VA 20110-2209, USA (ATCC): Material Tid>l?2 ATCC Dep. No.

Deposit Date DNA26846-1397 203406 October 27, 1998 DNA56107-1415 203405 October 27, 1998 DNA56406-1704 203478 November 17, 1998 DNA56529-1647 203293 September 29, 1998 DNA56531-1648 203286 September 29, 1998 DNA56862-1343 203174 September 1, 1998 DNA57254-1477 203289 September 29, 1998 DNA57841-1522 203458 November 3, 1998 DNA58727-1474 203171 September 1, 1998 DNA58730-1607 203221 September 15, 1998 DNA58732-1650 203290 September 29, 1998 DNA58828-1519 203172 September 1, 1998 DNA58852-1637 203271 September 22, 1998 DNA59212-1627 203245 September 9,1998 DNA59218-1559 203287 September 29, 1998 DNA59219-1613 203220 September 15,1998 DNA59586-1520 203288 September 29,1998 DNA59817-1703 203470 November 17,1998 DNA60278-1530 203170 September 1, 1998 DNA60608-1577 203126 August 18, 1998 40 DNA60611-1524 203175 September 1, 1998 DNA60618-1557 203292 September 29, 1998 DNA60740-1615 203456 November 3, 1998 DNA60764-1533 203452 November 10,1998 DNA60775-1532 203173 September 1, 1998 45 DNA61185-1646 203464 November 17, 1998 DNA61608-1606 203239 September 9, 1998 DNA62808-1326 203358 October 2fci19M m. 488 ,TEo!^ALOFp«oreBTy "OCT 2003 _recei\/Fn 40 45 50 55 DNA62809-1531 DNA62815-1578 DNA62845-1684 DNA64842-1632 DNA64849-I604 DNA64863-1573 DNA64881-1602 203237 203247 203361 203278 203468 203251 203240 September 9, 1998 September 9, 1998 October 20, 1998 September 22, 1998 November 17, 1998 September 9, 1998 September 9, 1998 DNA64886-1601 DNA64888-1542 DNA64897-1628 DNA64902-1667 203241 203249 203216 203317 September 9, 1998 September 9, 1998 September 15, 1998 October 6, 1998 DNA64950-1590 DNA64952-1568 DNA65402-1540 DNA65403-1565 DNA65404-1551 DNA65405-1547 DNA65406-1567 DNA65408-1578 DNA65410-1569 DNA65423-1595 DNA66304-1546 DNA66511-1411 DNA66512-1564 DNA66519-1535 DNA66520-1536 DNA66521-1583 DNA66526-1616 DNA66658-1584 DNA66659-1593 DNA66663-1598 DNA66669-1597 DNA66672-1586 DNA66674-1599 DNA66675-1587 DNA67962-1649 DNA68836-1656 DNA68864-1629 DNA68866-1644 DNA68871-1638 DNA68874-1622 DNA68880-1676 DNA68885-1570 DNA71166-1685 DNA71169-1709 DNA71180-1655 DNA71184-1634 DNA71213-1659 DNA71234-1651 DNA71277-1636 DNA71282-1668 203224 203222 203252 203230 203244 203476 203219 203217 203231 203227 203321 203228 203218 203236 203226 203225 203246 203229 203269 203268 203272 203265 203281 203282 203291 203455 203276 203283 203280 203277 203319 203311 203355 203467 203403 203266 203401 203402 203285 203312 September 15, 1998 September 15, 1998 September 9, 1998 September 15, 1998 September 9, 1998 November 17, 1998 September 15, 1998 September 15, 1998 September 15, 1998 September 15, 1998 October 6, 1998 September 15,1998 September 15, 1998 September 15,1998 September 15, 1998 September 15, 1998 September 9, 1998 September 15, 1998 September 22, 1998 September 22, 1998 September 22, 1998 September 22, 1998 September 22, 1998 September 22, 1998 September 29, 1998 November 3, 1998 September 22, 1998 September 22, 1998 September 22, 1998 September 22, 1998 October 6, 1998 October 6,1998 October 20, 1998 November 17,1998 October 27, 1998 September 22,1998 October 27, 1998 October 27, 1998 September 22, 1998 October 6, 1998 489 2 4 OCT 2003 RFrciwcr\ DNA71286-1604 203357 October 20, 1998 DNA71883-1660 203475 November 17, 1998 DNA73401-1633 203273 September 22, 1998 DNA73492-167I 203324 October 6, 1998 DNA73727-1673 203459 November 3, 1998 DNA73730-1679 203320 October 6, 1998 DNA73734-1680 203363 October 20,1998 DNA73735-1681 203356 October 20, 1998 DNA73736-1657 203466 November 17, 1998 DNA73737-1658 203412 October 27, 1998 DNA73739-1645 203270 September 22, 1998 DNA73742-1662 203316 October 6, 1998 DNA73744-1665 203322 October 6, 1998 DNA73746-1654 203411 October 27, 1998 DNA73760-1672 203314 October 6, 1998 DNA76396-1698 203471 November 17, 1998 DNA76398-1699 203474 November 17, 1998 DNA76399-1700 203472 November 17, 1998 DNA76401-1683 203360 October 20, 1998 DNA76510-2504 203477 November 17, 1998 DNA76522-2500 203469 November 17, 1998 DNA76529-1666 203315 October 6, 1998 DNA76531-1701 203465 November 17, 1998 DNA76532-1702 203473 November 17, 1998 •DNA76541-1675 203409 October 27, 1998 DNA77301-1708 203407 October 27, 1998 DNA77303-2502 203479 November 17, 1998 DNA77648-1688 203408 October 27, 1998 DNA77652-2505 203480 November 17, 1998 DNA83500-2506 203391 October 29, 1998 DNA77568-1626 203134 August 18, 1998 DNA23322-1393 203400 October 27, 1998 'DNA62812-1594 203248 September 9, 1998 DNA66660-1585 203279 September 22, 1998 DNA76393-1664 203323 October 6,1998 These deposit were made under the provisions of the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purpose of Patent Procedure and the Regulations thereunder (Budapest 40 Treaty). This assures maintenance of a viable culture of the deposit for 30 years from the date of deposit. The deposits will be made available by ATCC under the terms of the Budapest Treaty, and subject to an agreement between Genentech, Inc. and ATCC, which assures permanent and unrestricted availability of the progeny of the culture of the deposit to the public upon issuance of the pertinent U.S. patent or upon laying open to the public of any U.S. or foreign patent application, whichever comes first, and assures availability of the progeny 45 to one determined by the U.S. Commissioner of Patents and Trademarks to be entitled thereto according to 35 USC §122 and the Commissioner's rules pursuant thereto (including 37 CFR §1.14 with particular reference to 886 OG 638).

The assignee of the present application has agreed that if a culture of the materials on deposit should die or be lost or destroyed when cultivated under suitable conditions, the materials will be promptly replaced on 50 notification with another of the same. Availability of the deposited material is not to be construed as a license 490 INTELLECTUAL PROPERTY OFFICE OF N.Z 2 4 OCT 2003 received PCTAJS99/20U1 to practice the invention in contravention of the rights granted under the authority of any government in accordance with its patent laws.

The foregoing written specification is considered to be sufficient to enable one stalled in the art to practice the invention. The present invention is not to be limited in scope by the construct deposited, since the deposited embodiment is intended as a single illustration of certain aspects of the invention and any constructs 5 that are functionally equivalent are within the scope of this invention. The deposit of material herein does not constitute an admission that the written description herein contained is inadequate to enable the practice of any aspect of the invention, including the best mode thereof, nor is it to be construed as limiting the scope of the claims to the specific illustrations that it represents. Indeed, various modifications of the invention in addition to those shown and described herein will become apparent to those skilled in the art from the foregoing 10 description and fall within the scope of the appended claims. 491 492 Sequence Listing <110> Genentech, Inc. <120> Novel Polypeptides and Nucleic Acids Encoding the Same <130> P2830R1 <140> PCT/US99/20111 <141> 1999-09-01 <150> US 60/098,750 <151> 1998-09-01 <150> US 60/098,803 <151> 1998-09-02 <150> US 60/098,821 <151> 1998-02-09 <150> US 60/098,843 <151> 1998-02-09 <150> US 60/099,536 <151> 1998-09-09 <150> US 60/099,596 <151> 1998-09-09 <150> US 60/099,598 <151> 1998-09-09 <150> US 60/099,602 <151> 1998-09-09 <150> US 60/099,642 <151> 1998-09-09 <150> US 60/099,741 <151> 1998-10-09 <150> US 60/099,754 <151> 1998-10-09 <150> US 60/099,763 <151> 1998-10-09 <150> US 60/099,792 <151> 1998-10-09 <150> US 60/099,808 <151> 1998-10-09 <150> US 60/099,812 <151> 1998-10-09 <150> US 60/099,815 <151> 1998-10-09 <150> US 60/099,816 <151> 1998-10-09 <150> US 60/100,385 <151> 1998-15-09 <150> US 60/100,388 <151> 1998-15-09 <150> US 60/100,390 <151> 1998-15-09 <150> US 60/100,584 <151> 1998-16-09 <150> US 60/100,627 <151> 1998-16-09 <150> US 60/100,661 <151> 1998-16-09 <150> US 60/100,662 <151> 1998-16-09 <150> US 60/100,664 <151> 1998-16-09 <150> US 60/100,683 <151> 1998-17-09 <150> US 60/100,684 <151> 1998-17-09 <150> US 60/100,710 <151> 1998-17-09 <150> US 60/100,711 <151> 1998-17-09 <150> US 60/100,919 <151> 1998-17-09 <150> US 60/100,930 <151> 1998-17-09 <150> US 60/100,848 <151> 1998-18-09 <150> US 60/100,849 <151> 1998-18-09 <150> US 60/101,014 <151> 1998-18-09 <150> US 60/101,068 <151> 1998-18-09 <150> US 60/101,071 <151> 1998-18-09 <150> US 60/101,279 <151> 1998-22-09 <150> US 60/101,471 <151> 1998-23-09 <150> US 60/101,472 <151> 1998-23-09 <150> US 60/101,474 <151> 1998-23-09 <150> US 60/101,475 <151> 1998-23-09 <150> US 60/101,476 <151> 1998-23-09 <150> US 60/101,477 <151> 1998-23-09 <150> US 60/101,479 <151> 1998-23-09 <150> US 60/101,738 <151> 1998-24-09 <150> US 60/101,741 <151> 1998-24-09 <150> US 60/101,743 <151> 1998-24-09 <150> US 60/101,915 <151> 1998-24-09 <150> US 60/101,916 <151> 1998-24-09 <150> US 60/102,207 <151> 1998-29-09 <150> US 60/102,240 <151> 1998-29-09 <150> US 60/102,307 <151> 1998-29-09 <150> US 60/102,330 <151> 1998-29-09 <150> US 60/102,331 <151> 1998-29-09 <150> US 60/102,484 <151> 1998-30-09 <150> US 60/102,487 <151> 1998-30-09 <150> US 60/102,570 <151> 1998-30-09 <150> US 60/102,571 <151> 1998-30-09 <150> US 60/102,684 <151> 1998-01-10 <150> US 60/102,687 <151> 1998-01-10 <150> US 60/102,965 <151> 1998-02-10 <150> US 60/103,258 <151> 1998-06-10 <150> US 60/103,449 <151> 1998-06-10 <150> US 60/103,314 <151> 1998-07-10 <150> US 60/103,315 <151> 1998-07-10 <150> US 60/103,328 <151> 1998-07-10 <150> US 60/103,395 <151> 1998-07-10 <150> US 60/103,396 <151> 1998-07-10 <150> US 60/103,401 <151> 1998-07-10 <150> US 60/103,633 <151> 1998-08-10 <150> US 60/103,678 <151> 1998-08-10 <150> US 60/103,679 <151> 1998-08-10 <150> US 60/103,711 <151> 1998-08-10 <150> US 60/104,257 <151> 1998-14-10 <150> US 60/104,987 <151> 1998-20-10 <150> US 60/105,000 <151> 1998-20-10 <150> US 60/105,002 <151> 1998-20-10 <150> US 60/105,104 <151> 1998-21-10 <150> US 60/105,169 <151> 1998-22-10 <150> US 60/105,266 <151> 1998-22-10 <150> US 60/105,693 <151> 1998-26-10 <150> US 60/105,694 <151> 1998-26-10 <150> US 60/105,807 <151> 1998-27-10 <150> US 60/105,881 <151> 1998-27-10 <150> US 60/105,882 <151> 1998-27-10 <150> US 60/106,062 <151> 1998-27-10 <150> US 60/106,023 <151> 1998-28-10 <150> US 60/106,029 <151> 1998-28-10 <150> US 60/106,030 <151> 1998-28-10 <150> US 60/106,032 <151> 1998-28-10 <150> US 60/106,033 <151> 1998-28-10 <150> US 60/106,178 <151> 1998-28-10 <150> US 60/106,248 <151> 1998-29-10 <150> US 60/106,384 <151> 1998-29-10 <150> US 60/108,500 <151> 1998-29-10 <150> US 60/106,464 <151> 1998-30-10 <150> US 60/106,856 <151> 1998-03-11 <150> US 60/106,902 <151> 1998-03-11 <150> US 60/106,905 <151> 1998-03-11 <150> US 60/106,919 <151> 1998-03-11 <150> US 60/106,932 <151> 1998-03-11 <150> US 60/106,934 <151> 1998-03-11 <150> US 60/107,783 <151> 1998-10-11 <150> US 60/108,775 <151> 1998-17-11 <150> US 60/108,779 <151> 1998-17-11 <150> US 60/108,787 <151> 1998-17-11 <150> US 60/108,788 <151> 1998-17-11 <150> US 60/108,801 <151> 1998-17-11 <150> US 60/108,802 <151> 1998-17-11 <150> US 60/108,806 <151> 1998-17-11 <150> US 60/108,807 <151> 1998-17-11 <150> US 60/108,867 <151> 1998-17-11 <150> US 60/108,925 <151> 1998-17-11 <150> US 60/108,848 <151> 1998-18-11 <150> US 60/108,849 <151> 1998-18-11 <150> US 60/108,850 <151> 1998-18-11 <150> US 60/108,851 <151> 1998-18-11 <150> US 60/108,852 <151> 1998-18-11 <150> US 60/108,858 <151> 1998-18-11 <150> US 60/108,904 <151> 1998-18-11 498 <160> 432 <210> 1 <211> 43 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 1 tgtaaaacga cggccagtta aatagacctg caattattaa tct 43 <210> 2 <211> 41 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 2 caggaaacag ctatgaccac ctgcacacct gcaaatccat t 41 <210> 3 <211> 1110 <212> DNA <213> Homo sapiens <400> 3 ccaatcgccc ggtgcggtgg tgcagggtct cgggctagtc atggcgtccc 50 cgtctcggag actgcagact aaaccagtca ttacttgttt caagagcgtt 100 ctgctaatct acacttttat tttctggatc actggcgtta tccttcttgc 150 agttggcatt tggggcaagg tgagcctgga gaattacttt tctcttttaa 200 atgagaaggc caccaatgtc cccttcgtgc tcattgctac tggtaccgtc 250 attattcttt tgggcacctt tggttgtttt gctacctgcc gagcttctgc 300 atggatgcta aaactgtatg caatgtttct gactctcgtt tttttggtcg 350 aactggtcgc tgccatcgta ggatttgttt tcagacatga gattaagaac 400 agctttaaga ataattatga gaaggctttg aagcagtata actctacagg 450 agattataga agccatgcag tagacaagat ccaaaatacg ttgcattgtt 500 gtggtgtcac cgattataga gattggacag atactaatta ttactcagaa 550 aaaggatttc ctaagagttg ctgtaaactt gaagattgta ctccacagag 600 agatgcagac aaagtaaaca atgaaggttg ttttataaag gtgatgacca 650 ttatagagtc agaaatggga gtcgttgcag gaatttcctt tggagttgct 700 tgcttccaac tgattggaat ctttctcgcc tactgccwct ctcgtgccat 750 aacaaataac cagtatgaga tagtgtaacc caatgtatct gtgggcctat 800 tcctctctac ctttaaggac atttagggtc ccccctgtga attagaaagt 850 499 tgcttggctg gagaactgac aacactactt actgatagac caaaaaacta 900 caccagtagg ttgattcaat caagatgtat gtagacctaa aactacacca 950 ataggctgat tcaatcaaga tccgtgctcg cagtgggctg attcaatcaa 1000 gatgtatgtt tgctatgttc taagtccacc ttctatccca ttcatgttag 1050 atcgttgaaa ccctgtatcc ctctgaaaca ctggaagagc tagtaaattg 1100 taaatgaagt 1110 <210> 4 <211> 245 <212> PRT <213> Homo sapiens <220> <221> sig_peptide <222> 1-42 <223> Signal Peptide <220> <221> TRANSMEM <222> 19-42, 61-83, 92-114, 209-230 <223> Transmembrane Domains <220> <221> misc_feature <222> 69-80, 211-222 <223> Prokaryotic Membrane Lipoprotein Lipid Attachment Site. <220> <221> misc_feature <222> 75-81, 78-84, 210-216, 214-220, 226-232 <223> N-Myristoylation Site. <220> <221> misc_feature <222> 134-138 <223> N-Glycosylation Site. <220> <221> misc_feature <222> 160-168, 160-169 <223> Tyrosine Kinase Phosphorylation Site. <220> <221> unsure <222> 233 <223> unknown amino acid <400> 4 Met Ala Ser Pro Ser Arg Arg Leu Gin Thr Lys Pro Val Ile Thr 15 10 15 Cys Phe Lys Ser Val Leu Leu Ile Tyr Thr Phe Ile Phe Trp Ile 20 25 30 Thr Gly Val Ile Leu Leu Ala Val Gly Ile Trp Gly Lys Val Ser 35 40 45 500 Leu Glu Asn Tyr Phe Ser Leu Leu Asn Glu Lys Ala Thr Asn Val 50 55 60 Pro Phe Val Leu Ile Ala Thr Gly Thr Val Ile Ile Leu Leu Gly 65 70 75 Thr Phe Gly Cys Phe Ala Thr Cys Arg Ala Ser Ala Trp Met Leu 80 85 90 Lys Leu Tyr Ala Met Phe Leu Thr Leu Val Phe Leu Val Glu Leu 95 100 105 Val Ala Ala Ile Val Gly Phe Val Phe Arg His Glu Ile Lys Asn 110 115 120 Ser Phe Lys Asn Asn Tyr Glu Lys Ala Leu Lys Gin Tyr Asn Ser 125 130 135 Thr Gly Asp Tyr Arg Ser His Ala Val Asp Lys Ile Gin Asn Thr 140 145 150 Leu His Cys Cys Gly Val Thr Asp Tyr Arg Asp Trp Thr Asp Thr 155 160 165 Asn Tyr Tyr Ser Glu Lys Gly Phe Pro Lys Ser Cys Cys Lys Leu 170 175 180 Glu Asp Cys Thr Pro Gin Arg Asp Ala Asp Lys Val Asn Asn Glu 185 190 195 Gly Cys Phe Ile Lys Val Met Thr Ile Ile Glu Ser Glu Met Gly 200 205 210 Val Val Ala Gly Ile Ser Phe Gly Val Ala Cys Phe Gin Leu Ile 215 220 225 Gly Ile Phe Leu Ala Tyr Cys Xaa Ser Arg Ala Ile Thr Asn Asn 230 235 240 Gin Tyr Glu Ile Val 245 <210> 5 <211> 1218 <212> DNA <213> Homo sapiens <400> 5 cccacgcgtc cggcgccgtg gcctcgcgtc catctttgcc gttctctcgg 50 acctgtcaca aaggagtcgc gccgccgccg ccgccccctc cctccggtgg 100 gcccgggagg tagagaaagt cagtgccaca gcccgaccgc gctgctctga 150 gccctgggca cgcggaacgg gagggagtct gagggttggg gacgtctgtg 200 agggagggga acagccgctc gagcctgggg cgggcggacc ggactggggc 250 cggggtaggc tctggaaagg gcccgggaga gaggtggcgt tggtcagaac 300 ctgagaaaca gccgagaggt tttccaccga ggcccgcgct tgagggatct 350 501 gaagaggttc ctagaagagg gtgttccctc tttcgggggt cctcaccaga 400 agaggttctt gggggtcgcc cttctgagga ggctgcggct aacagggccc 450 agaactgcca ttggatgtcc agaatcccct gtagttgata atgttgggaa 500 taagctctgc aactttcttt ggcattcagt tgttaaaaac aaataggatg 550 caaattcctc aactccaggt tatgaaaaca gtacttggaa aactgaaaac 600 tacctaaatg atcgtctttg gttgggccgt gttcttagcg agcagaagcc 650 ttggccaggg tctgttgttg actctcgaag agcacatagc ccacttccta 700 gggactggag gtgccgctac taccatgggt aattcctgta tctgccgaga 750 tgacagtgga acagatgaca gtgttgacac ccaacagcaa caggccgaga 800 acagtgcagt acccactgct gacacaagga gccaaccacg ggaccctgtt 850 cggccaccaa ggaggggccg aggacctcat gagccaagga gaaagaaaca 900 aaatgtggat gggctagtgt tggacacact ggcagtaata cggactcttg 950 tagataagta agtatctgac tcacggtcac ctccagtgga atgaaaagtg 1000 ttctgcccgg aaccatgact ttaggactcc ttcagttcct ttaggacata 1050 ctcgccaagc cttgtgctca cagggcaaag gagaatattt taatgctccg 1100 ctgatggcag agtaaatgat aagatttgat gtttttgctt gctgtcatct 1150 actttgtctg gaaatgtcta aatgtttctg tagcagaaaa cacgataaag 1200 ctatgatctt tattagag 1218 <210> 6 <211> 117 <212> PRT <213> Homo sapiens <220> <221> sig_peptide <222> 1-16 <223> Signal Peptide <220> <221> misc_feature <222> 18-24, 32-38, 34-40, 35-41, 51-57 <223> N-Myristoylation Site. <220> <221> misc_feature <222> 22-26, 50-54, 113-117 <223> Casein Kinase II Phosphorylation Site. <400> 6 Met Ile Val Phe Gly Trp Ala Val Phe Leu Ala Ser Arg Ser Leu 15 10 15 Gly Gin Gly Leu Leu Leu Thr Leu Glu Glu His Ile Ala His Phe 502 Leu Gly Thr Gly Gly Ala Ala Thr Thr Met Gly Asn Ser Cys Ile 35 40 - 45 Cys Arg Asp Asp Ser Gly Thr Asp Asp Ser Val Asp Thr Gin Gin 50 55 60 Gin Gin Ala Glu Asn Ser Ala Val Pro Thr Ala Asp Thr Arg Ser 65 70 75 Gin Pro Arg Asp Pro Val Arg Pro Pro Arg Arg Gly Arg Gly Pro 80 85 90 His Glu Pro Arg Arg Lys Lys Gin Asn Val Asp Gly Leu Val Leu 95 100 105 Asp Thr Leu Ala Val Ile Arg Thr Leu Val Asp Lys 110 115 <210> 7 <211> 756 <212> DNA <213> Homo sapiens <400> 7 ggcacgaggc gctgtccacc cgggggcgtg ggagtgaggt accagattca 50 gcccatttgg ccccgacgcc tctgttctcg gaatccgggt gctgcggatt 100 gaggtcccgg ttcctaacgg actgcaagat ggaggaaggc gggaacctag 150 gaggcctgat taagatggtc catctactgg tcttgtcagg tgcctggggc 200 atgcaaatgt gggtgacctt cgtctcaggc ttcctgcttt tccgaagcct 250 tccccgacat accttcggac tagtgcagag caaactcttc cccttctact 300 tccacatctc catgggctgt gccttcatca acctctgcat cttggcttca 350 cagcatgctt gggctcagct cacattctgg gaggccagcc agctttacct 400 gctgttcctg agccttacgc tggccactgt caacgcccgc tggctggaac 450 cccgcaccac agctgccatg tgggccctgc aaaccgtgga gaaggagcga 500 ggcctgggtg gggaggtacc aggcagccac cagggtcccg atccctaccg 550 ccagctgcga gagaaggacc ccaagtacag tgctctccgc cagaatttct 600 tccgctacca tgggctgtcc tctctttgca atctgggctg cgtcctgagc 650 aatgggctct gtctcgctgg ccttgccctg gaaataagga gcctctagca 700 tgggccctgc atgctaataa atgcttcttc agaaatgaaa aaaaaaaaaa 750 aaaaaa 756 <210> 8 <211> 189 <212> PRT <213> Homo sapiens 503 <220> <221> sig_peptide <222> 1-24 <223> Signal Peptide <220> <221> misc_feature <222> 4-10, 5-11, 47-53, 170-176, 176-182 <223> N-Myristoylation Site. <220> <221> misc_feature <222> 44-85 <223> G-protein Coupled Receptors Proteins. <220> <221> misc_feature <222> 54-65 <223> Prokaryotic Mmembrane Lipoprotein Lipid Attachment Site. <220> <221> misc_feature <222> 82-86 <223> Casein Kinase II Phosphorylation Site. <220> <221> TRANSMEM <222> 86-103, 60-75 <223> Transmembrane Domain <220> <221> misc_feature <222> 144-151 <223> Tyrosine Kinase Phosphorylation Site. <400> 8 Met Glu Glu Gly Gly Asn Leu Gly Gly Leu Ile Lys Met Val His 15 10 15 Leu Leu Val Leu Ser Gly Ala Trp Gly Met Gin Met Trp Val Thr 20 25 30 Phe Val Ser Gly Phe Leu Leu Phe Arg Ser Leu Pro Arg His Thr 35 40 45 Phe Gly Leu Val Gin Ser Lys Leu Phe Pro Phe Tyr Phe His Ile 50 55 60 Ser Met Gly Cys Ala Phe Ile Asn Leu Cys Ile Leu Ala Ser Gin 65 70 75 His Ala Trp Ala Gin Leu Thr Phe Trp Glu Ala Ser Gin Leu Tyr 80 85 90 Leu Leu Phe Leu Ser Leu Thr Leu Ala Thr Val Asn Ala Arg Trp 95 100 105 Leu Glu Pro Arg Thr Thr Ala Ala Met Trp Ala Leu Gin Thr Val 110 115 120 Glu Lys Glu Arg Gly Leu Gly Gly Glu Val Pro Gly Ser His Gin 125 130 135 504 Gly Pro Asp Pro Tyr Arg Gin Leu Arg Glu Lys Asp Pro Lys Tyr 140 145 150 Ser Ala Leu Arg Gin Asn Phe Phe Arg Tyr His Gly Leu Ser Ser 155 160 165 Leu Cys Asn Leu Gly Cys Val Leu Ser Asn Gly Leu Cys Leu Ala 170 175 180 Gly Leu Ala Leu Glu Ile Arg Ser Leu 185 <210> 9 <211> 1508 <212> DNA <213> Homo sapiens <400> 9 aattcagatt ttaagcccat tctgcagtgg aatttcatga actagcaaga 50 ggacaccatc ttcttgtatt atacaagaaa ggagtgtacc tatcacacac 100 agggggaaaa atgctctttt gggtgctagg cctcctaatc ctctgtggtt 150 ttctgtggac tcgtaaagga aaactaaaga ttgaagacat cactgataag 200 tacattttta tcactggatg tgactcgggc tttggaaact tggcagccag 250 aacttttgat aaaaagggat ttcatgtaat cgctgcctgt ctgactgaat 300 caggatcaac agctttaaag gcagaaacct cagagagact tcgtactgtg 350 cttctggatg tgaccgaccc agagaatgtc aagaggactg cccagtgggt 400 gaagaaccaa gttggggaga aaggtctctg gggtctgatc aataatgctg 450 gtgttcccgg cgtgctggct cccactgact ggctgacact agaggactac 500 agagaaccta ttgaagtgaa cctgtttgga ctcatcagtg tgacactaaa 550 tatgcttcct ttggtcaaga aagctcaagg gagagttatt aatgtctcca 600 gtgttggagg tcgccttgca atcgttggag ggggctatac tccatccaaa 650 tatgcagtgg aaggtttcaa tgacagctta agacgggaca tgaaagcttt 700 tggtgtgcac gtctcatgca ttgaaccagg attgttcaaa acaaacttgg 750 cagatccagt aaaggtaatt gaaaaaaaac tcgccatttg ggagcagctg 800 tctccagaca tcaaacaaca atatggagaa ggttacattg aaaaaagtct 850 agacaaactg aaaggcaata aatcctatgt gaacatggac ctctctccgg 900 tggtagagtg catggaccac gctctaacaa gtctcttccc taagactcat 950 tatgccgctg gaaaagatgc caaaattttc tggatacctc tgtctcacat 1000 gccagcagct ttgcaagact ttttattgtt gaaacagaaa gcagagctgg 1050 ctaatcccaa ggcagtgtga ctcagctaac cacaaatgtc tcctccaggc 1100 505 tatgaaattg gccgatttca agaacacatc tccttttcaa ccccattcct 1150 tatctgctcc aacctggact catttagatc gtgcttattt ggattgcaaa 12 00 agggagtccc accatcgctg gtggtatccc agggtccctg ctcaagtttt 1250 ctttgaaaag gagggctgga atggtacatc acataggcaa gtcctgccct 1300 gtatttaggc tttgcctgct tggtgtgatg taagggaaat tgaaagactt 1350 gcccattcaa aatgatcttt accgtggcct gccccatgct tatggtcccc 1400 agcatttaca gtaacttgtg aatgttaagt atcatctctt atctaaatat 1450 taaaagataa gtcaacccaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1500 aaaaaaaa 1508 <210> 10 <211> 319 <212> PRT <213> Homo sapiens <220> <221> sig_peptide <222> 1-17 <223> Signal Peptide <220> <221> misc_feature <222> 36-47, 108-113, 166-171,198-203, 207-212 <223> N-myristoylation Sites. <220> <221> misc_feature <222> 39-42 <223> Glycosaminoglycan Attachment Site. <220> <221> TRANSMEM <222> 136-152 <223> Transmembrane Domain <220> <221> misc_feature <222> 161-163, 187-190 and 253-256 <223> N-glycosylation Sites. <400> 10 Met Leu Phe Trp Val Leu Gly Leu Leu 1 5 Trp Thr Arg Lys Gly Lys Leu Lys Ile 20 Tyr Ile Phe Ile Thr Gly Cys Asp Ser 35 Ala Arg Thr Phe Asp Lys Lys Gly Phe 50 Leu Thr Glu Ser Gly Ser Thr Ala Leu 65 Ile Leu Cys Gly Phe Leu 10 15 Glu Asp Ile Thr Asp Lys 25 30 Gly Phe Gly Asn Leu Ala 40 45 His Val lie Ala Ala Cys 55 60 Lys Ala Glu Thr Ser Glu 70 75 506 Arg Leu Arg Thr Val Leu Leu Asp Val Thr Asp Pro Glu Asn Val 80 85 90 Lys Arg Thr Ala Gin Trp Val Lys Asn Gin Val Gly Glu Lys Gly 95 100 105 Leu Trp Gly Leu Ile Asn Asn Ala Gly Val Pro Gly Val Leu Ala 110 115 120 Pro Thr Asp Trp Leu Thr Leu Glu Asp Tyr Arg Glu Pro Ile Glu 125 130 135 Val Asn Leu Phe Gly Leu Ile Ser Val Thr Leu Asn Met Leu Pro 140 145 150 Leu Val Lys Lys Ala Gin Gly Arg Val Ile Asn Val Ser Ser Val 155 160 165 Gly Gly Arg Leu Ala Ile Val Gly Gly Gly Tyr Thr Pro Ser Lys 170 175 180 Tyr Ala Val Glu Gly Phe Asn Asp Ser Leu Arg Arg Asp Met Lys 185 190 195 Ala Phe Gly Val His Val Ser Cys Ile Glu Pro Gly Leu Phe Lys 200 205 210 Thr Asn Leu Ala Asp Pro Val Lys Val Ile Glu Lys Lys Leu Ala 215 220 225 Ile Trp Glu Gin Leu Ser Pro Asp Ile Lys Gin Gin Tyr Gly Glu 230 235 240 Gly Tyr Ile Glu Lys Ser Leu Asp Lys Leu Lys Gly Asn Lys Ser 245 250 255 Tyr Val Asn Met Asp Leu Ser Pro Val Val Glu Cys Met Asp His 260 265 270 Ala Leu Thr Ser Leu Phe Pro Lys Thr His Tyr Ala Ala Gly Lys 275 280 285 Asp Ala Lys Ile Phe Trp Ile Pro Leu Ser His Met Pro Ala Ala 290 295 300 Leu Gin Asp Phe Leu Leu Leu Lys Gin Lys Ala Glu Leu Ala Asn 305 310 315 Pro Lys Ala Val <210> 11 <211> 2720 <212> DNA <213> Homo sapines <400> 11 gcgggctgtt gacggcgctg cgatggctgc ctgcgagggc aggagaagcg 50 gagctctcgg ttcctctcag tcggacttcc tgacgccgcc agtgggcggg 100 507 gccccttggg ccgtcgccac cactgtagtc atgtacccac cgccgccgcc 150 gccgcctcat cgggacttca tctcggtgac gctgagcttt ggcgagagct 200 atgacaacag caagagttgg cggcggcgct cgtgctggag gaaatggaag 250 caactgtcga gattgcagcg gaatatgatt ctcttcctcc ttgcctttct 300 gcttttctgt ggactcctct tctacatcaa cttggctgac cattggaaag 350 ctctggcttt caggctagag gaagagcaga agatgaggcc agaaattgct 400 gggttaaaac cagcaaatcc acccgtctta ccagctcctc agaaggcgga 450 caccgaccct acatccagcg gagaacttac gggaccacct ctgagatttc cacctgcaga gtcacagaag ttagaccccc acacaaagac aagccaagac 500 550 ctgaaggatg ggacccagga ggaggccaca aaaaggcaag aagcccctgt 600 ggatccccgc ccggaaggag atccgcagag gacagtcatc agctggaggg 650 gagcggtgat cgagcctgag cagggcaccg agctcccttc aagaagagca 700 gaagtgccca ccaagcctcc cctgccaccg gccaggacac agggcacacc 750 agtgcatctg aactatcgcc agaagggcgt gattgacgtc ttcctgcatg 800 catggaaagg ataccgcaag tttgcatggg gccatgacga gctgaagcct 850 gtgtccaggt ccttcagtga gtggtttggc ctcggtctca cactgatcga 900 cgcgctggac accatgtgga tcttgggtct gaggaaagaa tttgaggaag 950 ccaggaagtg ggtgtcgaag aagttacact ttgaaaagga cgtggacgtc 1000 aacctgtttg agagcacgat ccgcatcctg ggggggctcc tgagtgccta 1050 ccacctgtct ggggacagcc tcttcctgag gaaagctgag gattttggaa 1100 atcggctaat gcctgccttc agaacaccat ccaagattcc ttactcggat 1150 gtgaacatcg gtactggagt tgcccacccg ccacggtgga cctccgacag 1200 cactgtggcc gaggtgacca gcattcagct ggagttccgg gagctctccc 1250 gtctcacagg ggataagaag tttcaggagg cagtggagaa ggtgacacag 1300 cacatccacg gcctgtctgg gaagaaggat gggctggtgc ccatgttcat 1350 caatacccac agtggcctct tcacccacct gggcgtattc acgctgggcg 1400 ccagggccga cagctactat gagtacctgc tgaagcagtg gatccagggc 1450 gggaagcagg agacacagct gctggaagac tacgtggaag ccatcgaggg 1500 tgtcagaacg cacctgctgc ggcactccga gcccagtaag ctcacctttg 1550 tgggggagct tgcccacggc cgcttcagtg ccaagatgga ccacctggtg 1600 tgcttcctgc cagggacgct ggctctgggc gtctaccacg gcctgcccgc 1650 cagccacatg gagctggccc aggagctcat ggagacttgt taccagatga 1700 508 accggcagat ggagacgggg ctgagtcccg agatcgtgca cttcaacctt 1750 tacccccagc cgggccgtcg ggacgtggag gtcaagccag cagacaggca 1800 caacctgctg cggccagaga ccgtggagag cctgttctac ctgtaccgcg 1850 tcacagggga ccgcaaatac caggactggg gctgggagat tctgcagagc 1900 ttcagccgat tcacacgggt cccctcgggt ggctattctt ccatcaacaa 1950 tgtccaggat cctcagaagc ccgagcctag ggacaagatg gagagcttct 2000 tcctggggga gacgctcaag tatctgttct tgctcttctc cgatgaccca 2050 aacctgctca gcctatctgg gcctggacgc acccctgcct ctacgtgttc agggtggatg aacaccgaag gctgctggtg cccaccctct tggggacttc 2100 2150 gggtgggcag aggcaccttg ctgggtctgt ggcattttcc aagggcccac 2200 gtagcaccgg caaccgccaa gtggcccagg ctctgaactg gctctgggct 2250 cctcctcgtc tctgctttaa tcaggacacc gtgaggacaa gtgaggccgt 2300 cagtcttggt gtgatgcggg gtgggctggg ccgctggagc ctccgcctgc 2350 ttcctccaga agacacgaat catgactcac gattgctgaa gcctgagcag 2400 gtctctgtgg gccgaccaga ggggggcttc gaggtggtcc ctggtactgg 2450 ggtgaccgag tggacagccc agggtgcagc tctgcccggg ctcgtgaagc 2500 ctcagatgtc cccaatccaa gggtctggag gggctgccgt gactccagag 2550 gcctgaggct ccagggctgg ctctggtgtt tacaagctgg actcagggat 2600 cctcctggcc gccccgcagg gggcttggag ggctggacgg caagtccgtc 2650 tagctcacgg gcccctccag tggaatgggt cttttcggtg gagataaaag 2700 ttgatttgct ctaaccgcaa 2720 <210> 12 <211> 699 <212> PRT <213> Homo sapiens <220> <221> TRANSMEM <222> 21-40 and 84-105 <223> Transmembrane Domain (type II) <400> 12 Met Ala Ala Cys Glu Gly Arg Arg Ser Gly Ala Leu Gly Ser Ser 15 10 15 Gin Ser Asp Phe Leu Thr Pro Pro Val Gly Gly Ala Pro Trp Ala 20 25 30 Val Ala Thr Thr Val Val Met Tyr Pro Pro Pro Pro Pro Pro Pro 35 40 45 509 His Arg Asp Phe Ile Ser Val Thr Leu Ser Phe Gly Glu Ser Tyr 50 55 60 Asp Asn Ser Lys Ser Trp Arg Arg Arg Ser Cys Trp Arg Lys Trp 65 70 75 Lys Gin Leu Ser Arg Leu Gin Arg Asn Met Ile Leu Phe Leu Leu 80 85 90 Ala Phe Leu Leu Phe Cys Gly Leu Leu Phe Tyr Ile Asn Leu Ala 95 100 105 Asp His Trp Lys Ala Leu Ala Phe Arg Leu Glu Glu Glu Gin Lys 110 115 120 Met Arg Pro Glu Ile Ala Gly Leu Lys Pro Ala Asn Pro Pro Val 125 130 135 Leu Pro Ala Pro Gin Lys Ala Asp Thr Asp Pro Glu Asn Leu Pro 140 145 150 Glu Ile Ser Ser Gin Lys Thr Gin Arg His Ile Gin Arg Gly Pro 155 160 165 Pro His Leu Gin Ile Arg Pro Pro Ser Gin Asp Leu Lys Asp Gly 170 175 180 Thr Gin Glu Glu Ala Thr Lys Arg Gin Glu Ala Pro Val Asp Pro 185 ' 190 195 Arg Pro Glu Gly Asp Pro Gin Arg Thr Val Ile Ser Trp Arg Gly 200 205 210 Ala Val Ile Glu Pro Glu Gin Gly Thr Glu Leu Pro Ser Arg Arg 215 220 225 Ala Glu Val Pro Thr Lys Pro Pro Leu Pro Pro Ala Arg Thr Gin 230 235 240 Gly Thr Pro Val His Leu Asn Tyr Arg Gin Lys Gly Val Ile Asp 245 250 255 Val Phe Leu His Ala Trp Lys Gly Tyr Arg Lys Phe Ala Trp Gly 260 265 270 His Asp Glu Leu Lys Pro Val Ser Arg Ser Phe Ser Glu Trp Phe 275 280 285 Gly Leu Gly Leu Thr Leu Ile Asp Ala Leu Asp Thr Met Trp Ile 290 295 300 Leu Gly Leu Arg Lys Glu Phe Glu Glu Ala Arg Lys Trp Val Ser 305 310 315 Lys Lys Leu His Phe Glu Lys Asp Val Asp Val Asn Leu Phe Glu 320 325 330 Ser Thr Ile Arg Ile Leu Gly Gly Leu Leu Ser Ala Tyr His Leu 335 340 345 Ser Gly Asp Ser Leu Phe Leu Arg Lys Ala Glu Asp Phe Gly Asn 350 355 360 510 Arg Leu Met Pro Ala Phe Arg Thr Pro Ser Lys Ile Pro Tyr Ser 365 370 375 Asp Val Asn Ile Gly Thr Gly Val Ala His Pro Pro Arg Trp Thr 380 385 390 Ser Asp Ser Thr Val Ala Glu Val Thr Ser Ile Gin Leu Glu Phe 395 400 405 Arg Glu Leu Ser Arg Leu Thr Gly Asp Lys Lys Phe Gin Glu Ala 410 415 420 Val Glu Lys Val Thr Gin His Ile His Gly Leu Ser Gly Lys Lys 425 430 435 Asp Gly Leu Val Pro Met Phe Ile Asn Thr His Ser Gly Leu Phe 440 445 450 Thr His Leu Gly Val Phe Thr Leu Gly Ala Arg Ala Asp Ser Tyr 455 460 465 Tyr Glu Tyr Leu Leu Lys Gin Trp Ile Gin Gly Gly Lys Gin Glu 470 475 480 Thr Gin Leu Leu Glu Asp Tyr Val Glu Ala Ile Glu Gly Val Arg 485 490 495 Thr His Leu Leu Arg His Ser Glu Pro Ser Lys Leu Thr Phe Val 500 505 510 Gly Glu Leu Ala His Gly Arg Phe Ser Ala Lys Met Asp His Leu 515 520 525 Val Cys Phe Leu Pro Gly Thr Leu Ala Leu Gly Val Tyr His Gly 530 535 540 Leu Pro Ala Ser His Met Glu Leu Ala Gin Glu Leu Met Glu Thr 545 550 555 Cys Tyr Gin Met Asn Arg Gin Met Glu Thr Gly Leu Ser Pro Glu 560 565 570 Ile Val His Phe Asn Leu Tyr Pro Gin Pro Gly Arg Arg Asp Val 575 580 585 Glu Val Lys Pro Ala Asp Arg His Asn Leu Leu Arg Pro Glu Thr 590 595 600 Val Glu Ser Leu Phe Tyr Leu Tyr Arg Val Thr Gly Asp Arg Lys 605 610 615 Tyr Gin Asp Trp Gly Trp Glu Ile Leu Gin Ser Phe Ser Arg Phe 620 625 630 Thr Arg Val Pro Ser Gly Gly Tyr Ser Ser Ile Asn Asn Val Gin 635 640 645 Asp Pro Gin Lys Pro Glu Pro Arg Asp Lys Met Glu Ser Phe Phe 650 655 660 Leu Gly Glu Thr Leu Lys Tyr Leu Phe Leu Leu Phe Ser Asp Asp 665 670 675 511 Pro Asn Leu Leu Ser Leu Asp Ala Tyr Val Phe Asn Thr Glu Ala 680 685 690 His Pro Leu Pro Ile Trp Thr Pro Ala 695 <210> 13 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 13 cgccagaagg gcgtgattga cgtc 24 <210> 14 <211> 24 <212> DNA <213> Artificial sequence <220> <223> Synthetic oligonucleotide probe <400> 14 ccatccttct tcccagacag gccg 24 <210> 15 <211> 44 <212> DNA <213> Artificial sequence <220> <223> Synthetic oligonucleotide probe <400> 15 gaagcctgtg tccaggtcct <210> 16 <211> 1524 <212> DNA <213> Homo sapiens <400> 16 ggcgccgcgt aggcccggga cccatgcgcc gccgcctctc gcgcagctgc cctgggagga ccctcggaag tgttccgtct gcttcttctc cctactctgg cgggcagtca ggggacaagg ccccccagag ccgccccctg cccaccgcct ggcagtgctg tcagtgagtg gtttggcctc ggtc 44 ggccgggccg gccgggctgc gagcgcctgc 50 cgcacgatgt tcccctcgcg gaggaaagcg 100 cggcaggtcc gggttgctct ccggcggcct 150 tccacctgtt cgtggcctgc ctctcgctgg 2 00 ctgcagctca gctgctctgg ggacgtggcc 2 50 gcaggagacc tcgggccctc cccgtgcctg 300 agcactggga agaagacgca tcctggggcc 350 gtgcccttcc gcgaacgctt cgaggagctc 400 512 ctggtcttcg tgccccacat gcgccgcttc ctgagcagga agaagatccg 450 gcaccacatc tacgtgctca accaggtgga ccacttcagg ttcaaccggg 500 cagcgctcat caacgtgggc ttcctggaga gcagcaacag cacggactac 550 attgccatgc acgacgttga cctgctccct ctcaacgagg agctggacta 600 tggctttcct gaggctgggc ccttccacgt ggcctccccg gagctccacc 650 ctctctacca ctacaagacc tatgtcggcg gcatcctgct gctctccaag 700 cagcactacc ggctgtgcaa tgggatgtcc aaccgcttct ggggctgggg 750 ccgcgaggac gacgagttct accggcgcat taagggagct gggctccagc 800 ttttccgccc ctcgggaatc acaactgggt acaagacatt tcgccacctg 850 catgacccag cctggcggaa gagggaccag aagcgcatcg cagctcaaaa 900 acaggagcag ttcaaggtgg acagggaggg aggcctgaac actgtgaagt 950 accatgtggc ttcccgcact gccctgtctg tgggcggggc cccctgcact 1000 gtcctcaaca tcatgttgga ctgtgacaag accgccacac cctggtgcac 1050 attcagctga gctggatgga cagtgaggaa gcctgtacct acaggccata 1100 ttgctcaggc tcaggacaag gcctcaggtc gtgggcccag ctctgacagg 1150 atgtggagtg gccaggacca agacagcaag ctacgcaatt gcagccaccc 1200 ggccgccaag gcaggcttgg gctgggccag gacacgtggg gtgcctggga 1250 cgctgcttgc catgcacagt gatcagagag aggctggggt gtgtcctgtc 1300 cgggaccccc cctgccttcc tgctcaccct actctgacct ccttcacgtg 1350 cccaggcctg tgggtagtgg ggagggctga acaggacaac ctctcatcac 1400 cctactctga cctccttcac gtgcccaggc ctgtgggtag tggggagggc 1450 tgaacaggac aacctctcat cacccccaaa aaaaaaaaaa aaaaaaaaaa 1500 aaaaaaaaaa aaaaaaaaaa aaaa 1524 <210> 17 <211> 327 <212> PRT <213> Homo sapiens <220> <221> sig_peptide <222> 1-42 <223> Signal peptide. <220> <221> misc_feature <222> 19-25,65-71,247-253,285-291,303-310 <223> N-myristoylation site. <220> 513 <221> misc_feature <222> 27-31 <223> cAMP- and cGMP-dependent protein kinase phosphorylation site. <220> <221> TRANSMEM <222> 29-49 <223> Transmembrane domain (type II). <220> <221> misc_feature <222> 154-158 <223> N-glycosylation site. <220> <221> misc_feature <222> 226-233 <223> Tyrosine kinase phosphorylation site. <400> 17 Met Phe Pro Ser Arg Arg Lys Ala Ala Gin Leu Pro Trp Glu Asp 15 10 15 Gly Arg Ser Gly Leu Leu Ser Gly Gly Leu Pro Arg Lys Cys Ser 20 25 30 Val Phe His Leu Phe Val Ala Cys Leu Ser Leu Gly Phe Phe Ser 35 40 45 Leu Leu Trp Leu Gin Leu Ser Cys Ser Gly Asp Val Ala Arg Ala 50 55 60 Val Arg Gly Gin Gly Gin Glu Thr Ser Gly Pro Pro Arg Ala Cys 65 70 75 Pro Pro Glu Pro Pro Pro Glu His Trp Glu Glu Asp Ala Ser Trp 80 85 90 Gly Pro Glu Glu Arg Lys His Phe His Arg Leu Ala Val Leu Val Pro Phe Arg Glu Arg 95 100 Leu Leu Val Phe Val Pro His Met Arg Arg Phe Leu 110 115 Lys Ile Arg His His Ile Tyr Val Leu Asn Gin Val 125 130 Arg Phe Asn Arg Ala Ala Leu Ile Asn Val 140 145 Glu Ser Ser Asn Ser Thr Asp Tyr Ile Ala Met His 155 160 Gly Asp Phe Val Phe 105 Ser 120 Asp 135 Leu 150 Asp 165 Leu Leu Pro Leu Asn Glu Glu Leu Asp Tyr Gly Phe Pro Glu Ala 170 175 180 Gly Pro Phe His Val Ala Ser Pro Glu Leu His Pro Leu Tyr His 185 190 195 Tyr Lys Thr Tyr Val Gly Gly Ile Leu Leu Leu Ser Lys Gin His Tyr Arg Leu Arg Glu Asp Gin Leu Phe Arg His Leu Ile Ala Ala Gly Leu Asn Ser Val Gly Cys Asp Lys <210> 18 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 18 gcgaacgctt cgaggagtcc tgg 23 <210> 19 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 19 gcagtgcggg aagccacatg gtac 24 <210> 20 <211> 46 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 20 cttcctgagc aggaagaaga tccggcacca catctacgtg ctcaac 46 <210> 21 <211> 494 <212> DNA <213> Homo sapiens 514 200 205 210 Cys Asn Gly Met Ser Asn Arg Phe Trp Gly Trp Gly 215 220 225 Asp Glu Phe Tyr Arg Arg Ile Lys Gly Ala Gly Leu 230 235 240 Arg Pro Ser Gly Ile Thr Thr Gly Tyr Lys Thr Phe 245 250 255 His Asp Pro Ala Trp Arg Lys Arg Asp Gin Lys Arg 260 265 270 Gin Lys Gin Glu Gin Phe Lys Val Asp Arg Glu Gly 275 280 285 Thr Val Lys Tyr His Val Ala Ser Arg Thr Ala Leu 290 295 300 Gly Ala Pro Cys Thr Val Leu Asn Ile Met Leu Asp 305 310 315 Thr Ala Thr Pro Trp Cys Thr Phe Ser 320 325 515 <400> 21 caatgtttgc ctatccacct cccccaagcc cctttaccta tgctgctgct 50 aacgctgctg ctgctgctgc tgctgcttaa aggctcatgc ttggagtggg 100 gactggtcgg tgcccagaaa gtctcttctg ccactgacgc ccccatcagg 150 gattgggcct tctttccccc ttcctttctg tgtctcctgc ctcatcggcc 200 tgccatgacc tgcagccaag cccagccccg tggggaaggg gagaaagtgg 250 gggatggcta agaaagctgg gagataggga acagaagagg gtagtgggtg 300 ggctaggggg gctgccttat ttaaagtggt tgtttatgat tcttatacta 350 atttatacaa agatattaag gccctgttca ttaagaaatt gttcccttcc 400 cctgtgttca atgtttgtaa agattgttct gtgtaaatat gtctttataa 450 taaacagtta aaagctgaaa aaaaaaaaaa aaaaaaaaaa aaaa 494 <210> 22 <211> 73 <212> PRT <213> Homo sapiens <220> <221> sig_peptide <222> 1-15 <223> Signal peptide. <220> <221> misc_feature <222> 3-18 <223> Growth factor and cytokines receptors family. <400> 22 Met Leu Leu Leu Thr Leu Leu Leu Leu Leu Leu Leu Leu Lys Gly 15 10 15 Ser Cys Leu Glu Trp Gly Leu Val Gly Ala Gin Lys Val Ser Ser 20 25 30 Ala Thr Asp Ala Pro Ile Arg Asp Trp Ala Phe Phe Pro Pro Ser 35 40 45 Phe Leu Cys Leu Leu Pro His Arg Pro Ala Met Thr Cys Ser Gin 50 55 60 Ala Gin Pro Arg Gly Glu Gly Glu Lys Val Gly Asp Gly 65 70 <210> 23 <211> 2883 <212> DNA <213> Homo sapiens <400> 23 gggacccatg cggccgtgac ccccggctcc ctagaggccc agcgcagccg 50 cagcggacaa aggagcatgt ccgcgccggg gaaggcccgt cctccggccg 100 516 ccataaggct ccggtcgccg ctgggcccgc gccgcgctcc tgcccgcccg 150 ggctccgggg cggcccgcta ggccagtgcg ccgccgctcg ccccgcaggc 200 cccggcccgc agcatggagc cacccggacg ccggcggggc cgcgcgcagc 250 cgccgctgtt gctgccgctc tcgctgttag cgctgctcgc gctgctggga 300 ggcggcggcg gcggcggcgc cgcggcgctg cccgccggct gcaagcacga 350 tgggcggccc cgaggggctg gcagggcggc gggcgccgcc gagggcaagg 400 tggtgtgcag cagcctggaa ctcgcgcagg tcctgccccc agatactctg 450 cccaaccgca cggtcaccct gattctgagt aacaataaga tatccgagct 500 gaagaatggc tcattttctg ggttaagtct ccttgaaaga ttggacctcc 550 gaaacaatct tattagtagt atagatccag gtgccttctg gggactgtca 600 tctctaaaaa gattggatct gacaaacaat cgaataggat gtctgaatgc 650 agacatattt atttgttttc cgaggactca ttcattatct ccaatctggt caaggaactt tcggctaaac ttgattatct ctttcgggga tgcgtcatta 700 750 cggtctttgg aattccagac tgagtatctt ttgtgtgact gtaacatact 800 gtggatgcat cgctgggtaa aggagaagaa catcacggta cgggatacca 850 ggtgtgttta tcctaagtca ctgcaggccc aaccagtcac aggcgtgaag 900 caggagctgt tgacatgcga ccctccgctt gaattgccgt ctttctacat 950 gactccatct catcgccaag ttgtgtttga aggagacagc cttcctttcc 1000 agtgcatggc ttcatatatt gatcaggaca tgcaagtgtt gtggtatcag 1050 gatgggagaa tagttgaaac cgatgaatcg caaggtattt ttgttgaaaa 1100 gaacatgatt cacaactgct ccttgattgc aagtgcccta accatttcta 1150 atattcaggc tggatctact ggaaattggg gctgtcatgt ccagaccaaa 1200 cgtgggaata atacgaggac tgtggatatt gtggtattag agagttctgc 1250 acagtactgt cctccagaga gggtggtaaa caacaaaggt gacttcagat 1300 ggcccagaac attggcaggc attactgcat atctgcagtg tacgcggaac 1350 acccatggca gtgggatata tcccggaaac ccacaggatg agagaaaagc 1400 ttggcgcaga tgtgatagag gtggcttttg ggcagatgat gattattctc 1450 gctgtcagta tgcaaatgat gtcactagag ttctttatat gtttaatcag 1500 atgcccctca atcttaccaa tgccgtggca acagctcgac agttactggc 1550 ttacactgtg gaagcagcca acttttctga caaaatggat gttatatttg 1600 tggcagaaat gattgaaaaa tttggaagat ttaccaagga ggaaaaatca 1650 517 aaagagctag gtgacgtgat ggttgacatt gcaagtaaca tcatgttggc 1700 tgatgaacgt gtcctgtggc tggcgcagag ggaagctaaa gcctgcagta 1750 ggattgtgca gtgtcttcag cgcattgcta cctaccggct agccggtgga 1800 gctcacgttt attcaacata ttcacccaat attgctctgg aagcttatgt 1850 catcaagtct actggcttca cggggatgac ctgtaccgtg ttccagaaag 1900 tggcagcctc tgatcgtaca ggactttcgg attatgggag gcgggatcca 1950 gagggaaacc tggataagca gctgagcttt aagtgcaatg tttcaaatac 2000 attttcgagt ctggcactaa aggtatgtta cattctgcaa tcatttaaga 2050 ctatttacag ttaaattaga atgctccaaa tgttctgctt cgcaaaataa 2100 ccttattaaa agattttttt ttgcaggaag ataggtatta ttgcttttgc 2150 tactgtttta aagaaaacta accaggaaga actgcattac gactttcaag 2200 ggccctaggc atttttgcct ttgattccct ttcttcacat aaaaatatca 2250 gaaattacat acatgtgaaa tttataactg aaattttatt cagtggtata tgacttaaaa aatgcaaata gtttatttat tactattgtt ttgttttttt 2300 2350 gctcctgatt ttaagacaat aagatgtttt catgggcccc taaaagtatc 2400 atgagccttt ggcactgcgc ctgccaagcc tagtggagaa gtcaaccctg 2450 agaccaggtg tttaatcaag caagctgtat atcaaaattt ttggcagaaa 2500 acacaaatat gtcatatatc tttttttaaa aaaagtattt cattgaagca 2550 agcaaaatga aagcattttt actgattttt aaaattggtg ctttagatat 2600 atttgactac actgtattga agcaaataga ggaggcacaa ctccagcacc 2650 ctaatggaac cacatttttt tcacttagct ttctgtgggc atgtgtaatt 2700 gtattctctg cggtttttaa tctcacagta ctttatttct gtcttgtccc 2750 tcaataatat cacaaacaat attccagtca ttttaatggc tgcataataa 2800 ctgatccaac aggtgttagg tgttctggtt tagtgtgagc actcaataaa 2850 tattgaatga atgaacgaaa aaaaaaaaaa aaa 2883 <210> 24 <211> 616 <212> PRT <213> Homo sapiens <220> <221> sig_peptide <222> 1-33 <223> Signal peptide. <220> <221> TRANSMEM <222> 13-40 518 <223> Transmembrane domain (type II). <400> 24 Met Glu Pro Pro Gly Arg Arg Arg Gly Arg Ala Gin Pro Pro Leu 15 10 15 Leu Leu Pro Leu Ser Leu Leu Ala Leu Leu Ala Leu Leu Gly Gly 20 25 30 Gly Gly Gly Gly Gly Ala Ala Ala Leu Pro Ala Gly Cys Lys His 35 40 45 Asp Gly Arg Pro Arg Gly Ala Gly Arg Ala Ala Gly Ala Ala Glu 50 55 60 Gly Lys Val Val Cys Ser Ser Leu Glu Leu Ala Gin Val Leu Pro 65 70 75 Pro Asp Thr Leu Pro Asn Arg Thr Val Thr Leu Ile Leu Ser Asn 80 85 90 Asn Lys Ile Ser Glu Leu Lys Asn Gly Ser Phe Ser Gly Leu Ser 95 100 105 Leu Leu Glu Arg Leu Asp Leu Arg Asn Asn Leu Ile Ser Ser Ile 110 115 120 Asp Pro Gly Ala Phe Trp Gly Leu Ser Ser Leu Lys Arg Leu Asp 125 130 135 Leu Thr Asn Asn Arg Ile Gly Cys Leu Asn Ala Asp Ile Phe Arg 140 145 150 Gly Leu Thr Asn Leu Val Arg Leu Asn Leu Ser Gly Asn Leu Phe 155 160 165 Ser Ser Leu Ser Gin Gly Thr Phe Asp Tyr Leu Ala Ser Leu Arg 170 175 180 Ser Leu Glu Phe Gin Thr Glu Tyr Leu Leu Cys Asp Cys Asn Ile 185 190 195 Leu Trp Met His Arg Trp Val Lys Glu Lys Asn Ile Thr Val Arg 200 205 210 Asp Thr Arg Cys Val Tyr Pro Lys Ser Leu Gin Ala Gin Pro Val 215 220 225 Thr Gly Val Lys Gin Glu Leu Leu Thr Cys Asp Pro Pro Leu Glu 230 235 240 Leu Pro Ser Phe Tyr Met Thr Pro Ser His Arg Gin Val Val Phe 245 250 255 Glu Gly Asp Ser Leu Pro Phe Gin Cys Met Ala Ser Tyr Ile Asp 260 265 270 Gin Asp Met Gin Val Leu Trp Tyr Gin Asp Gly Arg Ile Val Glu 275 280 285 Thr Asp Glu Ser Gin Gly Ile Phe Val Glu Lys Asn Met Ile His 290 295 300 519 Asn Cys Ser Leu Ile Ala Ser Ala Leu Thr Ile Ser Asn Ile Gin 305 310 315 Ala Gly Ser Thr Gly Asn Trp Gly Cys His Val Gin Thr Lys Arg 320 325 330 Gly Asn Asn Thr Arg Thr Val Asp Ile Val Val Leu Glu Ser Ser 335 340 345 Ala Gin Tyr Cys Pro Pro Glu Arg Val Val Asn Asn Lys Gly Asp 350 355 360 Phe Arg Trp Pro Arg Thr Leu Ala Gly Ile Thr Ala Tyr Leu Gin 365 370 375 Cys Thr Arg Asn Thr His Gly Ser Gly lie Tyr Pro Gly Asn Pro 380 385 390 Gin Asp Glu Arg Lys Ala Trp Arg Arg Cys Asp Arg Gly Gly Phe 395 400 405 Trp Ala Asp Asp Asp Tyr Ser Arg Cys Gin Tyr Ala Asn Asp Val 410 415 420 Thr Arg Val Leu Tyr Met Phe Asn Gin Met Pro Leu Asn Leu Thr 425 430 435 Asn Ala Val Ala Thr Ala Arg Gin Leu Leu Ala Tyr Thr Val Glu 440 445 450 Ala Ala Asn Phe Ser Asp Lys Met Asp Val Ile Phe Val Ala Glu 455 460 465 Met Ile Glu Lys Phe Gly Arg Phe Thr Lys Glu Glu Lys Ser Lys 470 475 480 Glu Leu Gly Asp Val Met Val Asp Ile Ala Ser Asn Ile Met Leu 485 490 495 Ala Asp Glu Arg Val Leu Trp Leu Ala Gin Arg Glu Ala Lys Ala 500 505 510 Cys Ser Arg Ile Val Gin Cys Leu Gin Arg Ile Ala Thr Tyr Arg 515 520 525 Leu Ala Gly Gly Ala His Val Tyr Ser Thr Tyr Ser Pro Asn Ile 530 535 540 Ala Leu Glu Ala Tyr Val Ile Lys Ser Thr Gly Phe Thr Gly Met 545 550 555 Thr Cys Thr Val Phe Gin Lys Val Ala Ala Ser Asp Arg Thr Gly 560 565 570 Leu Ser Asp Tyr Gly Arg Arg Asp Pro Glu Gly Asn Leu Asp Lys 575 580 585 Gin Leu Ser Phe Lys Cys Asn Val Ser Asn Thr Phe Ser Ser Leu 590 595 600 Ala Leu Lys Val Cys Tyr Ile Leu Gin Ser Phe Lys Thr Ile Tyr 605 610 615 520 Ser <210> 25 <211> 24 <212> DNA <213> Artificial sequence <220> <223> Synthetic oligonucleotide probe <400> 25 gaggactcac caatctggtt cggc 24 <210> 26 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 26 aactggaaag gaaggctgtc tccc 24 <210> 27 <211> 50 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 27 gtaaaggaga agaacatcac ggtacgggat accaggtgtg tttatcctaa 50 <210> 28 <211> 683 <212> DNA <213> Homo sapiens <400> 28 gcgtggggat gtctaggagc tcgaaggtgg tgctgggcct ctcggtgctg 50 ctgacggcgg ccacagtggc cggcgtacat gtgaagcagc agtgggacca 100 gcagaggctt cgtgacggag ttatcagaga cattgagagg caaattcgga 150 aaaaagaaaa cattcgtctt ttgggagaac agattatttt gactgagcaa 200 cttgaagcag aaagagagaa gatgttattg gcaaaaggat ctcaaaaatc 250 atgacttgaa tgtgaaatat ctgttggaca gacaacacga gtttgtgtgt 300 gtgtgttgat ggagagtagc ttagtagtat cttcatcttt ttttttggtc 350 actgtccttt taaacttgat caaataaagg acagtgggtc atataagtta 400 ctgctttcag ggtcccttat atctgaataa aggagtgtgg gcagacactt 450 tttggaagag tctgtctggg tgatcctggt agaagcccca ttagggtcac 500 521 tgtccagtgc ttagggttgt tactgagaag cactgccgag cttgtgagaa 550 ggaagggatg gatagtagca tccacctgag tagtctgatc agtcggcatg 600 atgacgaagc cacgagaaca tcgacctcag aaggactgga ggaaggtgaa 650 gtggagggag agacgctcct gatcgtcgaa tcc 683 <210> 29 <211> 81 <212> PRT <213> Homo sapiens <220> <221> sig_peptide <222> 1-21 <223> Signal peptide. <400> 29 Met Ser Arg Ser Ser Lys Val Val Leu Gly Leu Ser Val Leu Leu 15 10 15 Thr Ala Ala Thr Val Ala Gly Val His Val Lys Gin Gin Trp Asp 20 25 30 Gin Gin Arg Leu Arg Asp Gly Val Ile Arg Asp Ile Glu Arg Gin 35 40 45 Ile Arg Lys Lys Glu Asn Ile Arg Leu Leu Gly Glu Gin Ile Ile 50 55 60 Leu Thr Glu Gin Leu Glu Ala Glu Arg Glu Lys Met Leu Leu Ala 65 70 75 Lys Gly Ser Gin Lys Ser 80 <210> 30 <211> 2128 <212> DNA <213> Homo sapiens <400> 30 ctgtcgtctt tgcttcagcc gcagtcgcca ctggctgcct gaggtgctct 50 tacagcctgt tccaagtgtg gcttaatccg tctccaccac cagatctttc 100 tccgtggatt cctctgctaa gaccgctgcc atgccagtga cggtaacccg 150 caccaccatc acaaccacca cgacgtcatc ttcgggcctg gggtccccca 200 tgatcgtggg gtcccctcgg gccctgacac agcccctggg tctccttcgc 250 ctgctgcagc tggtgtctac ctgcgtggcc ttctcgctgg tggctagcgt 300 gggcgcctgg acggggtcca tgggcaactg gtccatgttc acctggtgct 350 tctgcttctc cgtgaccctg atcatcctca tcgtggagct gtgcgggctc 400 caggcccgct tccccctgtc ttggcgcaac ttccccatca ccttcgcctg 450 522 ctatgcggcc ctcttctgcc tctcggcctc catcatctac cccaccacct 500 atgtccagtt cctgtcccac ggccgttcgc gggaccacgc catcgccgcc 550 accttcttct cctgcatcgc gtgtgtggct tacgccaccg aagtggcctg 600 gacccgggcc cggcccggcg agatcactgg ctatatggcc accgtacccg 650 ggctgctgaa ggtgctggag accttcgttg cctgcatcat cttcgcgttc 700 atcagcgacc ccaacctgta ccagcaccag ccggccctgg agtggtgcgt 750 ggcggtgtac gccatctgct tcatcctagc ggccatcgcc atcctgctga 800 acctggggga gtgcaccaac gtgctaccca tccccttccc cagcttcctg 850 tcggggctgg ccttgctgtc tgtcctcctc tatgccaccg cccttgttct 900 ctggcccctc taccagttcg atgagaagta tggcggccag cctcggcgct 950 cgagagatgt aagctgcagc cgcagccatg cctactacgt gtgtgcctgg 1000 gaccgccgac tggctgtggc catcctgacg gccatcaacc tactggcgta 1050 tgtggctgac ctggtgcact ctgcccacct ggtttttgtc aaggtctaag 1100 actctcccaa gaggctcccg ttccctctcc aacctctttg ttcttcttgc 1150 ccgagttttc tttatggagt acttctttcc tccgcctttc ctctgttttc 1200 ctcttcctgt ctcccctccc tcccaccttt ttctttcctt cccaattcct 1250 tgcactctaa ccagttcttg gatgcatctt cttccttccc tttcctcttg 1300 ctgtttcctt cctgtgttgt tttgttgccc acatcctgtt ttcacccctg 1350 agctgtttct ctttttcttt tctttctttt tttttttttt ttttaagacg 1400 gattctcact ctgtggccca ggctggagtg cagtggtgcg atctcagctc 1450 actgcaaccc ccgcctcctg ggttcaagcg attctcctcc cccagcctcc 1500 caagtagctg ggaggacagg tgtgagctgc cgcacccagc ctgtttctct 1550 ttttccactc ttcttttttc tcatctcttt tctgggttgc ctgtcggctt 1600 tcttatctgc ctgttttgca agcaccttct cctgtgtcct tgggagccct 1650 gagacttctt tctctccttg cctccaccca cctccaaagg tgctgagctc 1700 acatccacac cccttgcagc cgtccatgcc acagcccccc aaggggcccc 1750 attgccaaag catgcctgcc caccctcgct gtgccttagt cagtgtgtac 1800 gtgtgtgtgt gtgtgtgttt ggggggtggg gggtgggtag ctggggattg 1850 ggccctcttt ctcccagtgg aggaaggtgt gcagtgtact tcccctttaa 1900 attaaaaaac atatatatat atatatttgg aggtcagtaa tttccaatgg 1950 gcgggaggca ttaagcaccg accctgggtc cctaggcccc gcctggcact 2000 523 cagccttgcc agagattggc tccagaattt ttgccaggct tacagaacac 2050 ccactgccta gaggccatct taaaggaagc aggggctgga tgcctttcat 2100 cccaactatt ctctgtggta tgaaaaag 2128 <210> 31 <211> 322 <212> PRT <213> Homo sapiens <400> 31 Met Pro Val Thr Val Thr Arg Thr Thr Ile Thr Thr Thr Thr Thr 15 10 15 Ser Ser Ser Gly Leu Gly Ser Pro Met Ile Val Gly Ser Pro Arg 20 25 30 Ala Leu Thr Gin Pro Leu Gly Leu Leu Arg Leu Leu Gin Leu Val 35 40 45 t Ser Thr Cys Val Ala Phe Ser Leu Val Ala Ser Val Gly Ala Trp 50 55 60 Thr Gly Ser Met Gly Asn Trp Ser Met Phe Thr Trp Cys Phe Cys 65 70 75 Phe Ser Val Thr Leu Ile Ile Leu Ile Val Glu Leu Cys Gly Leu 80 85 90 Gin Ala Arg Phe Pro Leu Ser Trp Arg Asn Phe Pro Ile Thr Phe 95 100 105 Ala Cys Tyr Ala Ala Leu Phe Cys Leu Ser Ala Ser Ile Ile Tyr 110 115 120 Pro Thr Thr Tyr Val Gin Phe Leu Ser His Gly Arg Ser Arg Asp 125 130 135 His Ala Ile Ala Ala Thr Phe Phe Ser Cys Ile Ala Cys Val Ala 140 145 150 Tyr Ala Thr Glu Val Ala Trp Thr Arg Ala Arg Pro Gly Glu Ile 155 160 165 Thr Gly Tyr Met Ala Thr Val Pro Gly Leu Leu Lys Val Leu Glu 170 175 180 Thr Phe Val Ala Cys Ile Ile Phe Ala Phe Ile Ser Asp Pro Asn 185 190 195 Leu Tyr Gin His Gin Pro Ala Leu Glu Trp Cys Val Ala Val Tyr 200 205 210 Ala Ile Cys Phe Ile Leu Ala Ala Ile Ala Ile Leu Leu Asn Leu 215 220 225 Gly Glu Cys Thr Asn Val Leu Pro Ile Pro Phe Pro Ser Phe Leu 230 235 240 Ser Gly Leu Ala Leu Leu Ser Val Leu Leu Tyr Ala Thr Ala Leu 245 250 255 524 Val Leu Trp Pro Leu Tyr Gin Phe Asp Glu Lys Tyr Gly Gly Gin 260 265 270 Pro Arg Arg Ser Arg Asp Val Ser Cys Ser Arg Ser His Ala Tyr 275 280 285 Tyr Val Cys Ala Trp Asp Arg Arg Leu Ala Val Ala Ile Leu Thr 290 295 300 Ala Ile Asn Leu Leu Ala Tyr Val Ala Asp Leu Val His Ser Ala 305 310 315 His Leu Val Phe Val Lys Val 320 <210> 32 <211> 3680 <212> DNA <213> Homo sapiens <400> 32 gaacgtgcca ccatgcccag ctaatttttg tatttttagt agagacgggg 50 tttcaccatg ttggccaggc tggtcttgaa ctcgtgacct catgatccgc 100 tcacctcggc ctcccaaagt gctgggatta caggcatgag ccactgacgc 150 ctggccagcc tatgcatttt taagaaatta ttctgtatta ggtgctgtgc 200 taaacattgg gcactacagt gaccaaaaca gactgaattc cccaagagcc 250 aaagaccagt gagggagacc aacaagaaac aggaaatgca aaagagacca 300 ttattactca ctatgactaa gggtcacaaa tggggtacgt tgatggagag 350 tgatttgtta agagactaca gagggaggac agactaccaa gaggggggcc 400 aggaaagctc ctctgacgag gtggtatttc agcccaaact ggaagaatga 450 gaaagagcta gccagccatc agaatagtcc agaagagatg gggagcacta 500 cactcactac actttggcct gagaaaatag catgggattg gaggaggctg 550 ggggaacacc acttctgccg acctgggcag gaggcattga gggcttgaga 600 aagggcaatg gcagtagcag tagaaaggac agggtaggag cagggacttt 650 gcaggtggaa tcattaggtc ttatcaacag atatgggcaa gcaaagccag 700 gggagaattg atggtaatgc tgaggtttgg agccaggcta gatgggacag 750 tggtgggtga tgcaaaggaa agaggtcagg aagcagggcc agacgtgggg 800 agaaggtgtg ggggtttggt ttccatcttg ccgagtctgc cggaatgtgg 850 atgggaagac caagaggagg agcaaggggc agaggggaag ggaatcttaa 900 agaagtcctg gatgccacac tcttcttcct tcctcctctt ccctctcctc 950 agaggtctca ctcgtggttc ttcatttcct gccctgcctc catctcctct 1000 525 gggtgctggg aaagtggagg attagctgaa gttttgcttc tcggggcctg 1050 tctgaatctc cattgctttc tgggaggaca taattcacct gtcctagctt 1100 cttatcatct tacatttccc tgtagccact gggacatatg tggtgttcct 1150 tcctagctcc tgtctcctcc tcatgccttt gctgggtatg ggcatgttag 1200 ggggaaggtc attgctgtca gaggggcact gactttctaa tggtgttacc 1250 caaggtgaat gttggagaca cagtcgcgat gctgcccaag tcccggcgag 1300 ccctaactat ccaggagatc gctgcgctgg ccaggtcctc cctgcatggt 1350 atgcagcccc tcccatgttt ctggccactt tgtcctttct cctcccgttt 1400 gcacatccct ttggaactgt ttcctgtgag tacatgctgg ggtctcccct 1450 ttcttccctt gctcaggtga atctcagccc cttctcccac ccaaaggttc 1500 acatggatcc taactactgc cacccttcca cctccctgca cctgtgctcc 1550 ctggcctggt cctttaccag gcttctccac cctcccctat ctccaggtat 1600 ttcccaggtg gtgaaggacc acgtgaccaa gcctaccgcc atggcccagg 1650 gccgagtggc tcacctcatt gagtggaagg gctggagcaa gccgagtgac 1700 tcacctgctg ccctggaatc agccttttcc tcctattcag acctcagcga 1750 gggcgaacaa gaggctcgct ttgcagcagg agtggctgag cagtttgcca 1800 tcgcggaagc actgatgact caagctccga cctatgatga gcatggtctt ggactttgct cggtggatgg gggggaatgg cgaggactcc acacagacat 1850 1900 ggctgggcag ctgcccctgg ggccgcacct ccaggacctg ttcaccggcc 1950 accggttctc ccggcctgtg cgccagggct ccgtggagcc tgagagcgac 2000 tgctcacaga ccgtgtcccc agacaccctg tgctctagtc tgtgcagcct 2050 ggaggatggg ttgttgggct ccccggcccg gctggcctcc cagctgctgg 2100 gcgatgagct gcttctcgcc aaactgcccc ccagccggga aagtgccttc 2150 cgcagcctgg gcccactgga ggcccaggac tcactctaca actcgcccct 2200 cacagagtcc tgcctttccc ccgcggagga ggagccagcc ccctgcaagg 2250 actgccagcc actctgccca ccactaacgg gcagctggga acggcagcgg 2300 caagcctctg acctggcctc ttctggggtg gtgtccttag atgaggatga 2350 ggcagagcca gaggaacagt gacccacatc atgcctggca gtggcatgca 2400 tcccccggct gctgccaggg gcagagcctc tgtgcccaag tgtgggctca 2450 aggctcccag cagagctcca cagcctagag ggctcctggg agcgctcgct 2500 tctccgttgt gtgttttgca tgaaagtgtt tggagaggag gcaggggctg 2550 ggctgggggc gcatgtcctg cccccactcc cggggcttgc cgggggttgc' 2600 526 ccggggcctc tggggcatgg ctacagctgt ggcagacagt gatgttcatg 2650 ttcttaaaat gccacacaca catttcctcc tcggataatg tgaaccacta 2700 agggggttgt gactgggctg tgtgagggtg gggtgggagg gggcccagca 2750 accccccacc ctccccatgc ctctctcttc tctgcttttc ttctcacttc 2800 cgagtccatg tgcagtgctt gatagaatca cccccacctg gaggggctgg 2850 ctcctgccct cccggagcct atgggttgag ccgtccctca agggcccctg 2900 cccagctggg ctcgtgctgt gcttcattca cctctccatc gtctctaaat 2950 cttcctcttt tttcctaaag acagaaggtt tttggtctgt tttttcagtc 3000 ggatcttctc ttctctggga ggctttggaa tgatgaaagc atgtaccctc 3050 cacccttttc ctggccccct aatggggcct gggccctttc ccaacccctc 3100 ctaggatgtg cgggcagtgt gctggcgcct cacagccagc cgggctgccc 3150 attcacgcag agctctctga gcgggaggtg gaagaaagga tggctctggt 3200 tgccacagag ctgggacttc atgttcttct agagagggcc acaagagggc 3250 cacaggggtg gccgggagtt gtcagctgat gcctgctgag aggcaggaat 3300 tgtgccagtg agtgacagtc atgagggagt gtctcttctt ggggaggaaa 3350 gaaggtagag cctttctgtc tgaatgaaag gccaaggcta cagtacaggg 3400 ccccgcccca atcctgcatt gccagggtgt ccaaggtcac taatgcccac tggactgtac gtagtggagg gtttttatgg cctctggcag ttgtgggaag 3450 3500 ggtgggtggc tttagaatta agggccttgt aggctttggc aggtaagagg 3550 gcccaaggta agaacgagag ccaacgggca caagcattct atatataagt 3600 ggctcattag gtgtttattt tgttctattt aagaatttgt tttattaaat 3650 taatataaaa atctttgtaa atctctaaaa 3680 <210> 33 <211> 335 <212> PRT <213> Homo sapiens <400> 33 Met Phe Leu Ala Thr Leu Ser Phe Leu Leu Pro Phe Ala His Pro 15 10 15 Phe Gly Thr Val Ser Cys Glu Tyr Met Leu Gly Ser Pro Leu Ser 20 25 30 Ser Leu Ala Gin Val Asn Leu Ser Pro Phe Ser His Pro Lys Val 35 40 45 His Met Asp Pro Asn Tyr Cys His Pro Ser Thr Ser Leu His Leu 50 55 60 527 Cys Ser Leu Ala Trp Ser Phe Thr Arg Leu Leu His Pro Pro Leu 65 70 75 Ser Pro Gly Ile Ser Gin Val Val Lys Asp His Val Thr Lys Pro 80 85 90 Thr Ala Met Ala Gin Gly Arg Val Ala His Leu Ile Glu Trp Lys 95 100 105 . Gly Trp Ser Lys Pro Ser Asp Ser Pro Ala Ala Leu Glu Ser Ala 110 115 120 Phe Ser Ser Tyr Ser Asp Leu Ser Glu Gly Glu Gin Glu Ala Arg 125 130 135 Phe Ala Ala Gly Val Ala Glu Gin Phe Ala Ile Ala Glu Ala Lys 140 145 150 Leu Arg Ala Trp Ser Ser Val Asp Gly Glu Asp Ser Thr Asp Asp 155 160 165 Ser Tyr Asp Glu Asp Phe Ala Gly Gly Met Asp Thr Asp Met Ala 170 175 180 Gly Gin Leu Pro Leu Gly Pro His Leu Gin Asp Leu Phe Thr Gly 185 190 195 His Arg Phe Ser Arg Pro Val Arg Gin Gly Ser Val Glu Pro Glu 200 205 210 Ser Asp Cys Ser Gin Thr Val Ser Pro Asp Thr Leu Cys Ser Ser 215 220 225 Leu Cys Ser Leu Glu Asp Gly Leu Leu Gly Ser Pro Ala Arg Leu 230 235 240 Ala Ser Gin Leu Leu Gly Asp Glu Leu Leu Leu Ala Lys Leu Pro 245 250 255 Pro Ser Arg Glu Ser Ala Phe Arg Ser Leu Gly Pro Leu Glu Ala 260 265 270 Gin Asp Ser Leu Tyr Asn Ser Pro Leu Thr Glu Ser Cys Leu Ser 275 280 285 Pro Ala Glu Glu Glu Pro Ala Pro Cys Lys Asp Cys Gin Pro Leu 290 295 300 Cys Pro Pro Leu Thr Gly Ser Trp Glu Arg Gin Arg Gin Ala Ser 305 310 315 Asp Leu Ala Ser Ser Gly Val Val Ser Leu Asp Glu Asp Glu Ala 320 325 330 Glu Pro Glu Glu Gin 335 <210> 34 <211> 25 <212> DNA <213> Artificial Sequence <220> 528 <223> Synthetic oligonucleotide probe <400> 34 tgtcctttgt cccagacttc tgtcc 25 <210> 35 <211> 50 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 35 ctggatgcta atgtgtccag taaatgatcc ccttatcccg tcgcgatgct 50 <210> 36 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 36 ttccactcaa tgaggtgagc cactc 25 <210> 37 <211> 23 <212> DNA <213> Artificial Sequence <22 0> <223> Synthetic oligonucleotide probe <400> 37 ggcgagccct aactatccag gag 23 <210> 38 <211> 39 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 38 ggagatcgct gcgctggcca ggtcctccct gcatggtat 39 <210> 39 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 39 ctgctgcaaa gcgagcctct tg 22 <210> 40 <211> 2084 ;212> DNA ;213> Homo sapiens 529 :400> 40 ggttcctggg cgctctgtta cacaagcaag atacagccag ccccacctaa 50 ttttgtttcc ctggcaccct cctgctcagt gcgacattgt cacacttaac 100 ccatctgttt tctctaatgc acgacagatt cctttcagac aggacaactg 150 tgatatttca gttcctgatt gtaaatacct cctaagcctg aagcttctgt 200 tactagccat tgtgagcttc agtttcttca tctgcaaaat gggcataata 250 caatctattc ttgccacatc aagggattgt tattccttta aaaaaaaacc 300 aataccaaag aagcctacaa tgttggcctt agccaaaatt ctgttgattt 350 caacgttgtt ttattcactt ctatcgggga gccatggaaa agaaaatcaa 400 gacataaaca caacacagaa cattgcagaa gtttttaaaa caatggaaaa 450 taaacctatt tctttggaaa gtgaagcaaa cttaaactca gataaagaaa 500 atataaccac ctcaaatctc aaggcgagtc attcccctcc tttgaatcta 550 cccaacaaca gccacggaat aacagatttc tccagtaact catcagcaga 600 gcattctttg ggcagtctaa aacccacatc taccatttcc acaagccctc 650 ccttgatcca tagctttgtt tctaaagtgc cttggaatgc acctatagca 700 gatgaagatc ttttgcccat ctcagcacat cccaatgcta cacctgctct 750 gtcttcagaa aacttcactt ggtctttggt caatgacacc gtgaaaactc 800 ctgataacag ccatctgtga ttccattaca cccccttgat gttagcatcc agtggaacca tctcttcaga agtggatggc accaacttct ttaccacaaa 850 900 cagtgatagc ttcactgggt ttacccctta tcaagaaaaa acaactctac 950 agcctacctt aaaattcacc aataattcaa aactctttcc aaatacgtca 1000 gatccccaaa aagaaaatag aaatacagga atagtattcg gggccatttt 1050 aggtgctatt ctgggtgtct cattgcttac tcttgtgggc tacttgttgt 1100 gtggaaaaag gaaaacggat tcattttccc atcggcgact ttatgacgac 1150 agaaatgaac cagttctgcg attagacaat gcaccggaac cttatgatgt 1200 gagttttggg aattctagct actacaatcc aactttgaat gattcagcca 1250 tgccagaaag tgaagaaaat gcacgtgatg gcattcctat ggatgacata 1300 cctccacttc gtacttctgt atagaactaa cagcaaaaag gcgttaaaca 1350 gcaagtgtca tctacatcct agccttttga caaattcatc tttcaaaagg 1400 ttacacaaaa ttactgtcac gtggattttg tcaaggagaa tcataaaagc 1450 aggagaccag tagcagaaat gtagacagga tgtatcatcc aaaggttttc 1500 530 tttcttacaa tttttggcca tcctgaggca tttactaagt agccttaatt 1550 tgtattttag tagtattttc ttagtagaaa atatttgtgg aatcagataa 1600 aactaaaaga tttcaccatt acagccctgc ctcataacta aataataaaa 1650 attattccac caaaaaattc taaaacaatg aagatgactc tttactgctc 1700 tgcctgaagc cctagtacca taattcaaga ttgcattttc ttaaatgaaa 1750 attgaaaggg tgctttttaa agaaaatttg acttaaagct aaaaagagga 1800 catagcccag agtttctgtt attgggaaat tgaggcaata gaaatgacag 1850 acctgtattc tagtacgtta taattttcta gatcagcaca cacatgatca 1900 gcccactgag ttatgaagct gacaatgact gcattcaacg gggccatggc 1950 aggaaagctg accctaccca ggaaagtaat agcttcttta aaagtcttca 2000 aaggttttgg gaattttaac ttgtcttaat atatcttagg cttcaattat 2050 ttgggtgcct taaaaactca atgagaatca tggt 2084 <210> 41 <211> 334 <212> PRT <213> Homo sapiens <400> 41 Met Leu Ala Leu Ala Lys Ile Leu Leu Ile Ser Thr Leu Phe Tyr 15 10 15 Ser Leu Leu Ser Gly Ser His Gly Lys Glu Asn Gin Asp Ile Asn 20 25 30 Thr Thr Gin Asn Ile Ala Glu Val Phe Lys Thr Met Glu Asn Lys 35 40 45 Pro Ile Ser Leu Glu Ser Glu Ala Asn Leu Asn Ser Asp Lys Glu 50 55 60 Asn Ile Thr Thr Ser Asn Leu Lys Ala Ser His Ser Pro Pro Leu 65 70 75 Asn Leu Pro Asn Asn Ser His Gly Ile Thr Asp Phe Ser Ser Asn 80 85 90 Ser Ser Ala Glu His Ser Leu Gly Ser Leu Lys Pro Thr Ser Thr 95 100 105 Ile Ser Thr Ser Pro Pro Leu Ile His Ser Phe Val Ser Lys Val 110 115 120 Pro Trp Asn Ala Pro Ile Ala Asp Glu Asp Leu Leu Pro Ile Ser 125 130 135 Ala His Pro Asn Ala Thr Pro Ala Leu Ser Ser Glu Asn Phe Thr 140 145 150 Trp Ser Leu Val Asn Asp Thr Val Lys Thr Pro Asp Asn Ser Ser 531 155 160 165 Ile Thr Val Ser Ile Leu Ser Ser Glu Pro Thr Ser Pro Ser Val 170 175 180 Thr Pro Leu Ile Val Glu Pro Ser Gly Trp Leu Thr Thr Asn Ser 185 190 195 Asp Ser Phe Thr Gly Phe Thr Pro Tyr Gin Glu Lys Thr Thr Leu 200 205 210 Gin Pro Thr Leu Lys Phe Thr Asn Asn Ser Lys Leu Phe Pro Asn 215 220 225 Thr Ser Asp Pro Gin Lys Glu Asn Arg Asn Thr Gly Ile Val Phe 230 235 240 Gly Ala Ile Leu Gly Ala Ile Leu Gly Val Ser Leu Leu Thr Leu 245 250 255 Val Gly Tyr Leu Leu Cys Gly Lys Arg Lys Thr Asp Ser Phe Ser 260 265 270 His Arg Arg Leu Tyr Asp Asp Arg Asn Glu Pro Val Leu Arg Leu 275 280 285 Asp Asn Ala Pro Glu Pro Tyr Asp Val Ser Phe Gly Asn Ser Ser 290 295 300 Tyr Tyr Asn Pro Thr Leu Asn Asp Ser Ala Met Pro Glu Ser Glu 305 310 315 Glu Asn Ala Arg Asp Gly Ile Pro Met Asp Asp Ile Pro Pro Leu 320 325 330 Arg Thr Ser Val <210> 42 <211> 1594 <212> DNA <213> Homo sapiens <400> 42 aacaggatct cctcttgcag tctgcagccc aggacgctga ttccagcagc 50 gccttaccgc gcagcccgaa gattcactat ggtgaaaatc gccttcaata 100 cccctaccgc cgtgcaaaag gaggaggcgc ggcaagacgt ggaggccctc 150 ctgagccgca cggtcagaac tcagatactg accggcaagg agctccgagt 200 tgccacccag gaaaaagagg gctcctctgg gagatgtatg cttactctct 250 taggcctttc attcatcttg gcaggactta ttgttggtgg agcctgcatt 300 tacaagtact tcatgcccaa gagcaccatt taccgtggag agatgtgctt 350 ttttgattct gaggatcctg caaattccct tcgtggagga gagcctaact 400 tcctgcctgt gactgaggag gctgacattc gtgaggatga caacattgca 450 532 atcattgatg tgcctgtccc cagtttctct gatagtgacc ctgcagcaat 500 tattcatgac tttgaaaagg gaatgactgc ttacctggac ttgttgctgg 550 ggaactgcta tctgatgccc ctcaatactt ctattgttat gcctccaaaa 600 aatctggtag agctctttgg caaactggcg agtggcagat atctgcctca 650 aacttatgtg gttcgagaag acctagttgc tgtggaggaa attcgtgatg 700 ttagtaacct tggcatcttt atttaccaac tttgcaataa cagaaagtcc 750 ttccgccttc gtcgcagaga cctcttgctg ggtttcaaca aacgtgccat 800 tgataaatgc tggaagatta gacacttccc caacgaattt attgttgaga 850 ccaagatctg tcaagagtaa gaggcaacag atagagtgtc cttggtaata 900 agaagtcaga gatttacaat atgactttaa cattaaggtt tatgggatac 950 tcaagatatt tactcatgca tttactctat tgcttatgct ttaaaaaaag 1000 gaaaaaaaaa aaaactacta accactgcaa gctcttgtca aattttagtt 1050 taattggcat tgcttgtttt ttgaaactga aattacatga gtttcatttt 1100 ttctttgcat ttatagggtt tagatttctg aaagcagcat gaatatatca 1150 cctaacatcc tgacaataaa ttccatccgt tgtttttttt gtttgtttgt 1200 tttttctttt cctttaagta agctctttat tcatcttatg gtggagcaat 1250 tttaaaattt gaaatatttt aaattgtttt tgaacttttt gtgtaaaata 1300 tatcagatct caacattgtt ggtttctttt gtttttcatt ttgtacaact 1350 ttcttgaatt tagaaattac atctttgcag ttctgttagg tgctctgtaa 1400 ttaacctgac ttatatgtga acaattttca tgagacagtc atttttaact 1450 aatgcagtga ttctttctca ctactatctg tattgtggaa tgcacaaaat 1500 tgtgtaggtg ctgaatgctg taaggagttt aggttgtatg aattctacaa 1550 ccctataata aattttactc tatacaaaaa aaaaaaaaaa aaaa 1594 <210> 43 <211> 263 <212> PRT <213> Homo sapiens <400> 43 Met Val Lys Ile Ala Phe Asn Thr Pro Thr Ala Val Gin Lys Glu 15 10 15 Glu Ala Arg Gin Asp Val Glu Ala Leu Leu Ser Arg Thr Val Arg 20 25 30 Thr Gin Ile Leu Thr Gly Lys Glu Leu Arg Val Ala Thr Gin Glu 35 40 45 Lys Glu Gly Ser Ser Gly Arg Cys Met Leu Thr Leu Leu Gly Leu 533 50 55 60 Ser Phe Ile Leu Ala Gly Leu Ile Val Gly Gly Ala Cys lie Tyr 65 70 75 Lys Tyr Phe Met Pro Lys Ser Thr Ile Tyr Arg Gly Glu Met Cys 80 85 90 Phe Phe Asp Ser Glu Asp Pro Ala Asn Ser Leu Arg Gly Gly Glu 95 100 105 Pro Asn Phe Leu Pro Val Thr Glu Glu Ala Asp Ile Arg Glu Asp 110 115 120 Asp Asn Ile Ala Ile Ile Asp Val Pro Val Pro Ser Phe Ser Asp 125 130 135 Ser Asp Pro Ala Ala Ile Ile His Asp Phe Glu Lys Gly Met Thr 140 145 150 Ala Tyr Leu Asp Leu Leu Leu Gly Asn Cys Tyr Leu Met Pro Leu 155 160 165 Asn Thr Ser Ile Val Met Pro Pro Lys Asn L'eu Val Glu Leu Phe 170 175 180 Gly Lys Leu Ala Ser Gly Arg Tyr Leu Pro Gin Thr Tyr Val Val 185 190 195 Arg Glu Asp Leu Val Ala Val Glu Glu Ile Arg Asp Val Ser Asn 200 205 210 Leu Gly Ile Phe Ile Tyr Gin Leu Cys Asn Asn Arg Lys Ser Phe 215 220 225 Arg Leu Arg Arg Arg Asp Leu Leu Leu Gly Phe Asn Lys Arg Ala 230 235 240 Ile Asp Lys Cys Trp Lys Ile Arg His Phe Pro Asn Glu Phe Ile 245 250 255 Val Glu Thr Lys Ile Cys Gin Glu 260 <210> 44 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 44 gaaagacacg acacagcagc ttgc 24 <210> 45 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe 534 <400> 45 gggaactgct atctgatgcc 20 <210> 46 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 46 caggatctcc tcttgcagtc tgcagc 2 6 <210> 47 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 47 cttctcgaac cacataagtt tgaggcag 28 <210> 48 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 48 cacgattccc tccacagcaa ctggg 25 <210> 49 <211> 1969 <212> DNA <213> Homo sapiens <400> 49 ggaggaggga gggcgggcag gcgccagccc agagcagccc cgggcaccag 50 cacggactct ctcttccagc ccaggtgccc cccactctcg ctccattcgg 100 cgggagcacc cagtcctgta cgccaaggaa ctggtcctgg gggcaccatg 150 gtttcggcgg cagcccccag cctcctcatc cttctgttgc tgctgctggg 200 gtctgtgcct gctaccgacg cccgctctgt gcccctgaag gccacgttcc 250 tggaggatgt ggcgggtagt ggggaggccg agggctcgtc ggcctcctcc 300 ccgagcctcc cgccaccctg gaccccggcc ctcagcccca catcgatggg 350 gccccagccc acaaccctgg ggggcccatc accccccacc aacttcctgg 400 atgggatagt ggacttcttc cgccagtacg tgatgctgat tgctgtggtg 450 ggctccctgg cctttctgct gatgttcatc gtctgtgccg cggtcatcac 500 535 ccggcagaag cagaaggcct cggcctatta cccatcgtcc ttccccaaga 550 agaagtacgt ggaccagagt gaccgggccg ggggcccccg ggccttcagt 600 gaggtccccg acagagcccc cgacagcagg cccgaggaag ccctggattc 650 ctcccggcag ctccaggccg acatcttggc cgccacccag aacctcaagt 700 cccccaccag ggctgcactg ggcggtgggg acggagccag gatggtggag 750 ggcaggggcg cagaggaaga ggagaagggc agccaggagg gggaccagga 800 agtccaggga catggggtcc cagtggagac accagaggcg caggaggagc 850 cgtgctcagg ggtccttgag ggggctgtgg tggccggtga gggccaaggg 900 gagctggaag ggtctctctt gttagcccag gaagcccagg gaccagtggg 950 tccccccgaa agcccctgtg cttgcagcag tgtccacccc agtgtctaac 1000 agtcctcccg ggctgccagc cctgactgtc gggcccccaa gtggtcacct 1050 ccccgtgtat gaaaaggcct tcagccctga ctgcttcctg acactccctc 1100 cttggcctcc ctgtggtgcc aatcccagca tgtgctgatt ctacagcagg 1150 cagaaatgct ggtccccggt gccccggagg aatcttacca agtgccatca 1200 tccttcacct cagcagcccc aaagggctac atcctacagc acagctcccc 1250 tgacaaagtg agggagggca cgtgtccctg tgacagccag gataaaacat 1300 cccccaaagt gctgggatta caggcgtgag ccaccgtgcc cggcccaaac 1350 tactttttaa aacagctaca gggtaaaatc ctgcagcacc cactctggaa 1400 aatactgctc ttaattttcc tgaaggtggc cccctgtttc tagttggtcc 1450 aggattaggg atgtggggta tagggcattt aaatcctctc aagcgctctc 1500 caagcacccc cggcctgggg gtgagtttct catcccgcta ctgctgctgg 1550 gatcaggttg aatgaatgga actcttcctg tctggcctcc aaagcagcct 1600 agaagctgag gggctgtgtt tgaggggacc tccaccctgg ggaagtccga 1650 ggggctgggg aagggtttct gacgcccagc ctggagcagg ggggccctgg 1700 ccaccccctg ttgctcacac attgtctggc agcctgtgtc cacaatattc 1750 gtcagtcctc gacagggagc ctgggctccg tcctgcttta gggaggctct 1800 ggcaggaggt cctctccccc atccctccat ctggggctcc cccaacctct 1850 gcacagctct ccaggtgctg agatataatg caccagcaca ataaaccttt 1900 attccggcct gaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1950 aaaaaaaaaa aaaaaaaga 1969 ;210> 50 536 <211> 283 <212> PRT <213> Homo sapiens <400> 50 Met Val Ser Ala Ala Ala Pro Ser Leu Leu Ile Leu Leu Leu Leu 15 10 15 Leu Leu Gly Ser Val Pro Ala Thr Asp Ala Arg Ser Val Pro Leu 20 25 30 Lys Ala Thr Phe Leu Glu Asp Val Ala Gly Ser Gly Glu Ala Glu 35 40 45 Gly Ser Ser Ala Ser Ser Pro Ser Leu Pro Pro Pro Trp Thr Pro 50 55 60 Ala Leu Ser Pro Thr Ser Met Gly Pro Gin Pro Thr Thr Leu Gly 65 70 75 Gly Pro Ser Pro Pro Thr Asn Phe Leu Asp Gly Ile Val Asp Phe 80 85 90 Phe Arg Gin Tyr Val Met Leu Ile Ala Val Val Gly Ser Leu Ala 95 100 105 Phe Leu Leu Met Phe Ile Val Cys Ala Ala Val Ile Thr Arg Gin 110 115 120 Lys Gin Lys Ala Ser Ala Tyr Tyr Pro Ser Ser Phe Pro Lys Lys 125 130 135 Lys Tyr Val Asp Gin Ser Asp Arg Ala Gly Gly Pro Arg Ala Phe 140 145 150 Ser Glu Val Pro Asp Arg Ala Pro Asp Ser Arg Pro Glu Glu Ala 155 160 165 Leu Asp Ser Ser Arg Gin Leu Gin Ala Asp Ile Leu Ala Ala Thr 170 175 180 Gin Asn Leu Lys Ser Pro Thr Arg Ala Ala Leu Gly Gly Gly Asp 185 190 195 Gly Ala Arg Met Val Glu Gly Arg Gly Ala Glu Glu Glu Glu Lys 200 205 210 Gly Ser Gin Glu Gly Asp Gin Glu Val Gin Gly His Gly Val Pro 215 220 225 Val Glu Thr Pro Glu Ala Gin Glu Glu Pro Cys Ser Gly Val Leu 230 235 240 Glu Gly Ala Val Val Ala Gly Glu Gly Gin Gly Glu Leu Glu Gly 245 250 255 Ser Leu Leu Leu Ala Gin Glu Ala Gin Gly Pro Val Gly Pro Pro 260 265 270 Glu Ser Pro Cys Ala Cys Ser Ser Val His Pro Ser Val 275 280 537 <210> 51 <211> 1734 <212> DNA <213> Homo sapiens <400> 51 gtggactctg agaagcccag gcagttgagg acaggagaga gaaggctgca 50 gacccagagg gagggaggac agggagtcgg aaggaggagg acagaggagg 100 gcacagagac gcagagcaag ggcggcaagg aggagaccct ggtgggagga 150 agacactctg gagagagagg gggctgggca gagatgaagt tccaggggcc 200 cctggcctgc ctcctgctgg ccctctgcct gggcagtggg gaggctggcc 250 ccctgcagag cggagaggaa agcactggga caaatattgg ggaggccctt 300 ggacatggcc tgggagacgc cctgagcgaa ggggtgggaa aggccattgg 350 caaagaggcc ggaggggcag ctggctctaa agtcagtgag gcccttggcc 400 aagggaccag agaagcagtt ggcactggag tcaggcaggt tccaggcttt 450 ggcgcagcag atgctttggg caacagggtc ggggaagcag cccatgctct 500 gggaaacact gggcacgaga ttggcagaca ggcagaagat gtcattcgac 550 acggagcaga tgctgtccgc ggctcctggc agggggtgcc tggccacagt 600 ggtgcttggg aaacttctgg aggccatggc atctttggct ctcaaggtgg 650 ccttggaggc cagggccagg gcaatcctgg aggtctgggg actccgtggg 700 tccacggata ccccggaaac tcagcaggca gctttggaat gaatcctcag 750 ggagctccct ggggtcaagg aggcaatgga gggccaccaa actttgggac 800 caacactcag ggagctgtgg cccagcctgg ctatggttca gtgagagcca 850 gcaaccagaa tgaagggtgc acgaatcccc caccatctgg ctcaggtgga 900 ggctccagca actctggggg aggcagcggc tcacagtcgg gcagcagtgg 950 cagtggcagc gcagtggcag aatggtgaca cagcagtggc acaacaatgg agcagcagtg cagcagcagt gcggcagcag ggtggcagca tggcggcagc 1000 1050 agtggtggca gcagtggcaa cagtggtggc agcagaggtg acagcggcag 1100 tgagtcctcc tggggatcca gcaccggctc ctcctccggc aaccacggtg 1150 ggagcggcgg aggaaatgga cataaacccg ggtgtgaaaa gccagggaat 1200 gaagcccgcg ggagcgggga atctgggatt cagggcttca gaggacaggg 1250 agtttccagc aacatgaggg aaataagcaa agagggcaat cgcctccttg 1300 gaggctctgg agacaattat cgggggcaag ggtcgagctg gggcagtgga 1350 ggaggtgacg ctgttggtgg agtcaatact gtgaactctg agacgtctcc 1400 tgggatgttt aactttgaca ctttctggaa gaattttaaa tccaagctgg 1450 538 gtttcatcaa ctgggatgcc ataaacaagg accagagaag ctctcgcatc 1500 ccgtgacctc cagacaagga gccaccagat tggatgggag cccccacact 1550 ccctccttaa aacaccaccc tctcatcact aatctcagcc cttgcccttg 1600 aaataaacct tagctgcccc acaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1650 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1700 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaa 1734 <210> 52 <211> 440 <212> PRT <213> Homo sapiens <400> 52 Met Lys Phe Gin Gly Pro Leu Ala Cys Leu Leu Leu Ala Leu Cys 1 5 10 15 Leu Gly Ser Gly Glu Ala Gly Pro Leu Gin Ser Gly Glu Glu Ser 20 25 30 Thr Gly Thr Asn Ile Gly Glu Ala Leu Gly His Gly Leu Gly Asp 35 40 45 Ala Leu Ser Glu Gly Val Gly Lys Ala Ile Gly Lys Glu Ala Gly 50 55 60 Gly Ala Ala Gly Ser Lys Val Ser Glu Ala Leu Gly Gin Gly Thr 65 70 75 Arg Glu Ala Val Gly Thr Gly Val Arg Gin Val Pro Gly Phe Gly 80 85 90 Ala Ala Asp Ala Leu Gly Asn Arg Val Gly Glu Ala Ala His Ala 95 100 105 Leu Gly Asn Thr Gly His Glu Ile Gly Arg Gin Ala Glu Asp Val 110 115 120 Ile Arg His Gly Ala Asp Ala Val Arg Gly Ser Trp Gin Gly Val 125 130 135 Pro Gly His Ser Gly Ala Trp Glu Thr Ser Gly Gly His Gly Ile 140 145 150 Phe Gly Ser Gin Gly Gly Leu Gly Gly Gin Gly Gin Gly Asn Pro 155 160 165 Gly Gly Leu Gly Thr Pro Trp Val His Gly Tyr Pro Gly Asn Ser 170 175 180 Ala Gly Ser Phe Gly Met Asn Pro Gin Gly Ala Pro Trp Gly Gin 185 190 195 Gly Gly Asn Gly Gly Pro Pro Asn Phe Gly Thr Asn Thr Gin Gly 200 205 210 Ala Val Ala Gin Pro Gly Tyr Gly Ser Val Arg Ala Ser Asn Gin 539 215 220 225 Asn Glu Gly Cys Thr Asn Pro Pro Pro Ser Gly Ser Gly Gly Gly 230 235 240 Ser Ser Asn Ser Gly Gly Gly Ser Gly Ser Gin Ser Gly Ser Ser 245 250 255 Gly Ser Gly Ser Asn Gly Asp Asn Asn Asn Gly Ser Ser Ser Gly 260 265 270 Gly Ser Ser Ser Gly Ser Ser Ser Gly Ser Ser Ser Gly Gly Ser 275 280 285 Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Asn Ser Gly Gly Ser 290 295 300 Arg Gly Asp Ser Gly Ser Glu Ser Ser Trp Gly Ser Ser Thr Gly 305 310 315 Ser Ser Ser Gly Asn His Gly Gly Ser Gly Gly Gly Asn Gly His 320 325 330 Lys Pro Gly Cys Glu Lys Pro Gly Asn Glu Ala Arg Gly Ser Gly 335 340 345 Glu Ser Gly Ile Gin Gly Phe Arg Gly Gin Gly Val Ser Ser Asn 350 355 360 Met Arg Glu Ile Ser Lys Glu Gly Asn Arg Leu Leu Gly Gly Ser 365 370 375 Gly Asp Asn Tyr Arg Gly Gin Gly Ser Ser Trp Gly Ser Gly Gly 380 385 390 Gly Asp Ala Val Gly Gly Val Asn Thr Val Asn Ser Glu Thr Ser 395 400 405 Pro Gly Met Phe Asn Phe Asp Thr Phe Trp Lys Asn Phe Lys Ser 410 415 420 Lys Leu Gly Phe Ile Asn Trp Asp Ala Ile Asn Lys Asp Gin Arg 425 430 435 Ser Ser Arg Ile Pro 440 <210> 53 <211> 3580 <212> DNA <213> Homo sapiens <400> 53 gaccggtccc tccggtcctg gatgtgcgga ctctgctgca gcgagggctg 50 caggcccgcc gggcggtgct caccgtgccc tggctggtgg agtttctctc 100 ctttgctgac catgttgttc ccttgctgga atattaccgg gacatcttca 150 ctctcctgct gcgcctgcac cggagcttgg tgttgtcgca ggagagtgag 200 gggaagatgt gtttcctgaa caagctgctg ctacttgctg tcctgggctg 250 540 gcttttccag attcccacag tccctgagga cttgttcttt ctggaagagg 300 gtccctcata tgcctttgag gtggacacag tagccccaga gcatggcttg 350 gacaatgcgc ctgtggtgga ccagcagctg ctctacacct gctgccccta 400 catcggagag ctccggaaac tgctcgcttc gtgggtgtca ggcagtagtg 450 gacggagtgg gggcttcatg aggaaaatca cccccaccac taccaccagc 500 ctgggagccc agccttccca gaccagccag gggctgcagg cacagctcgc 550 ccaggccttt ttccacaacc agccgccctc cttgcgccgg accgtagagt 600 tcgtggcaga aagaattgga tcaaactgtg tcaaacatat caaggctaca 650 ctggtggcag atctggtgcg ccaggcagag tcacttctcc aagagcagct 700 ggtgacacag ggagaggaag ggggagaccc agcccagctg ttggagatct 750 tgtgttccca gctgtgccct cacggggccc aggcattggc cctggggcgg 800 gagttctgtc aaaggaagag ccctggggct gtgcgggcgc tgcttccaga 850 ggagaccccg gcagccgttc tgagcagtgc agagaacatt gctgtggggc 900 ttgcaacaga gaaagcctgt gcttggctgt cagccaacat cacagcactg 950 atcaggaggg aggtgaaagc agcagtgagt cgcacacttc gagcccaggg 1000 tcctgaacct gctgcccggg gggagcggag gggctgctcc cgcgcctgac 1050 gtgctctcct tggccgtggg gccacgggac cctgacgagg gagtctcccc 1100 agagcatctg gaacagctcc taggccagct gggccagacg ctgcggtgcc 1150 gccagttcct gtgcccacct gctgagcagc atctggcaaa gtgctctgtg 1200 gagttagctt ccctcctcgt tgcagatcaa attcctatcc tagggccccc 1250 ggcacagtac aggctggaga gagggcaggc tcgaaggctt ctgcacatgc 1300 tgctttcctt gtggaaggaa gactttcagg ggccggttcc gctgcagctg 1350 ctgctgagcc caagaaatgt ggggcttctg gcagacacaa ggccaaggga 1400 gtgggacttg tgggacggat ctgctattct ggagatagag tgctacggga gcctgcctgg gctggtggag gcagcctcca aagggtctga ccaggcccag 1450 1500 tggccagggg actttgctga agaattagca acactgtcta atctgtttct 1550 agccgagccc cacctgccag aaccccagct aagagcctgt gagttggtgc 1600 agccaaaccg gggcactgtg ctggcccaga gctagggctg agaagtggcc 1650 ctgccttggg cattgcacca gaaccctgga cccccgcctc acgaggaggc 1700 ccaagtgccc aatgcagacc ctcactggtt ggggtgtagc tgggtctaca 1750 gtcagacttc ctgctctaag ggtgtcactg cctggcatcc caccacgcga 1800 541 atcctagagg aaggagagtt ggcctgattt gggattatgg cagaaaagtc 1850 cagagatgcc agtcctggag tagaagaggt ggtgtttgtt tatctcttgg 1900 atactaaatg aaatgaggtg tgtgggcttg tcaacacaga attcaagcct 1950 catttgctat cccagcatct cttaaaactt tgtagtcttg gaattcatga 2000 cagaggcaaa tgactcctgc ttaacttatg aagaaagtta aaacatgaat 2050 cttgggagtc tacattttct tatcaccagg agctggactg ccatctcctt 2100 ataaatgcct aacacaggcc gggtctggtg gctcatgcct gtaatcccag 2150 cactttgaga ggcctgaggt cggcggactg cctgaggtca ggaattcaag 2200 accagcctgg ccaacatggc aaaaccccat ctctactaaa aataaaaaaa 2250 ttattagctg ggcatggtgg tgtgtgcctg taatcccagc tactcaggag 2300 gatgaggcag gagacctgct tgaacctgga ggtggaggtt gcagtgagcc 2350 gaggtcgcac cactgcactc cagtctgggt aacagagcga gactttctag 2400 aaaaagccta acaaacagat aaggtaggac tcaaccaact gaaacctgac 2450 tttccccctg taccttcagc ccctgtgcag gtagtaacct cttgagacct 2500 ctccctgacc agggaccaag cacagggcat ttagagcttt ttagaataaa 2550 ctggttttct ttaaaaaaaa aaaaaaaaaa agggcggccg cccttttttt 2600 tttttttttt tttttttttt tttttttttt tttttttttt taaaaagggc 2650 ttttattaaa attctcccca cacgatggct cctgcaatct gccacagctc 2700 tggggcgtgt cctgtaggga aaggccctgt tttccctgag gcggggctgg 2750 gcttgtccat gggtccgcgg agctggccgt gcttggcgcc ctggcgtgtg 2800 tctagctgct tcttgccggg cacagagctg cggggtctgg gggcaccggg 2850 agctaagagc aggctctggt gcaggggtgg aggcctgtct cttaaccgac 2900 accctgaggt gctcctgaga tgctgggtcc accctgagtg gcacggggag 2950 cagctgtggc cggtgctcct tcytaggcca gtcctgggga aactaagctc 3000 gggcccttct gggaatggcc ttgcaaagac tgaggagcta cgaggatggg cgtgtgaaga gtgggtgtgg gggcgccggt gggactcatg ttgttggctg 3050 3100 cagcggcctg gagcgcctct ctcctgagcc tcagtttccc tttccgtcta 3150 atgaagaaca tgccgtctcg gtgtctcagg gctattagga cttgccctca 3200 ggaagtggcc ttggacgagc gtcatgttat tttcacaact gtcctgcgac 3250 gttggcctgg gcacgtcatg gaatggccca tgtccctctg ctgcgtggac 3300 gtcgcggtcg ggagtgcgca gccagaggcg gggccagacg tgcgcctggg 3350 ggtgagggga ggcgccccgg gagggcctca caggaagttg ggctcccgca 3400 542 ccaccaggca gggcgggctc ccgccgccgc cgccgccacc accgtccagg 3450 ggccggtaga caaagtggaa gtcgcgcttg ggctcgctgc gcagcaggta 3500 gcccttgatg cagtgcggca gcgcgtcgtc cgccagctgg aagcagcgcc 3550 cgtccaccag cacgaacagc cggtgcgcct 3580 <210> 54 <211> 280 <212> PRT <213> Homo sapiens <400> 54 Met Cys Phe Leu Asn Lys Leu Leu Leu Leu Ala Val Leu Gly Trp 15 10 15 Leu Phe Gin Ile Pro Thr Val Pro Glu Asp Leu Phe Phe Leu Glu 20 25 30 Glu Gly Pro Ser Tyr Ala Phe Glu Val Asp Thr Val Ala Pro Glu 35 40 45 His Gly Leu Asp Asn Ala Pro Val Val Asp Gin Gin Leu Leu Tyr 50 55 60 Thr Cys Cys Pro Tyr Ile Gly Glu Leu Arg Lys Leu Leu Ala Ser 65 70 75 Trp Val Ser Gly Ser Ser Gly Arg Ser Gly Gly Phe Met Arg Lys 80 85 90 Ile Thr Pro Thr Thr Thr Thr Ser Leu Gly Ala Gin Pro Ser Gin 95 100 105 Thr Ser Gin Gly Leu Gin Ala Gin Leu Ala Gin Ala Phe Phe His 110 115 120 Asn Gin Pro Pro Ser Leu Arg Arg Thr Val Glu Phe Val Ala Glu 125 130 135 Arg Ile Gly Ser Asn Cys Val Lys His Ile Lys Ala Thr Leu Val 140 145 150 Ala Asp Leu Val Arg Gin Ala Glu Ser Leu Leu Gin Glu Gin Leu 155 160 165 Val Thr Gin Gly Glu Glu Gly Gly Asp Pro Ala Gin Leu Leu Glu 170 175 180 Ile Leu Cys Ser Gin Leu Cys Pro His Gly Ala Gin Ala Leu Ala 185 190 195 Leu Gly Arg Glu Phe Cys Gin Arg Lys Ser Pro Gly Ala Val Arg 200 205 210 Ala Leu Leu Pro Glu Glu Thr Pro Ala Ala Val Leu Ser Ser Ala 215 220 225 Glu Asn Ile Ala Val Gly Leu Ala Thr Glu Lys Ala Cys Ala Trp 230 235 240 543 Leu Ser Ala Asn Ile Thr Ala Leu Ile Arg Arg Glu Val Lys Ala 245 250 255 Ala Val Ser Arg Thr Leu Arg Ala Gin Gly Pro Glu Pro Ala Ala 260 265 270 Arg Gly Glu Arg Arg Gly Cys Ser Arg Ala 275 280 <210> 55 <211> 2401 <212> DNA <213> Homo sapiens <400> 55 tcccttgaca ggtctggtgg ctggttcggg gtctactgaa ggctgtcttg 50 atcaggaaac tgaagactct ctgcttttgc cacagcagtt cctgcagctt 100 ccttgaggtg tgaacccaca tccctgcccc cagggccacc tgcaggacgc 150 cgacacctac ccctcagcag acgccggaga gaaatgagta gcaacaaaga 200 gcagcggtca gcagtgttcg tgatcctctt tgccctcatc accatcctca 250 tcctctacag ctccaacagt gccaatgagg tcttccatta cggctccctg 300 cggggccgta gccgccgacc tgtcaacctc aagaagtgga gcatcactga 350 cggctatgtc cccattctcg gcaacaagac actgccctct cggtgccacc 400 agtgtgtgat tgtcagcagc tccagccacc tgctgggcac caagctgggc 450 cctgagatcg agcgggctga gtgtacaatc cgcatgaatg atgcacccac 500 cactggctac tcagctgatg tgggcaacaa gaccacctac cgcgtcgtgg 550 cccattccag tgtgttccgc gtgctgagga ggccccagga gtttgtcaac 600 cggacccctg aaaccgtgtt catcttctgg gggcccccga gcaagatgca 650 gaagccccag ggcagcctcg tgcgtgtgat ccagcgagcg ggcctggtgt 700 tccccaacat ggaagcatat gccgtctctc ccggccgcat gcggcaattt 750 gacgacctct tccggggtga gacgggcaag gacagggaga agtctcattc 800 gtggttgagc acaggctggt ttaccatggt gatcgcggtg gagttgtgtg 850 accacgtgca tgtctatggc atggtccccc ccaactactg cagccagcgg 900 ccccgcctcc agcgcatgcc ctaccactac tacgagccca aggggccgga 950 cgaatgtgtc acctacatcc agaatgagca cagtcgcaag ggcaaccacc 1000 accgcttcat caccgagaaa agggtcttct catcgtgggc ccagctgtat 1050 ggcatcacct tctcccaccc ctcctggacc taggccaccc agcctgtggg 1100 acctcaggag ggtcagagga gaagcagcct ccgcccagcc gctaggccag 1150 ggaccatctt ctggccaatc aaggcttgct ggagtgtctc ccagccaatc 1200 544 agggccttga ggaggatgta tcctccagcc aatcagggcc tggggaatct 1250 gttggcgaat cagggatttg ggagtctatg tggttaatca ggggtgtctt 1300 tcttgtgcag tcagggtctg cgcacagtca atcagggtag agggggtatt 1350 tctgagtcaa tctgaggcta aggacatgtc ctttcccatg aggccttggt 1400 tcagagcccc aggaatggac cccccaatca ctccccactc tgctgggata 1450 atggggtcct gtcccaagga gctgggaact tggtgttgcc ccctcaattt 1500 ccagcaccag aaagagagat tgtgtggggg tagaagctgt ctggaggccc 1550 ggccagagaa tttgtggggt tgtggaggtt gtgggggcgg tggggaggtc 1600 ccagaggtgg gaggctggca tccaggtctt ggctctgccc tgagaccttg 1650 gacaaaccct tccccctctc tgggcaccct tctgcccaca ccagtttcca 1700 gtgcggagtc tgagaccctt tccacctccc ctacaagtgc cctcgggtct 1750 gtcctccccg tctggaccct cccagccact atcccttgct ggaaggctca 1800 gctctttggg gggtctgggg tgacctcccc acctcctgga aaactttagg 1850 gtatttttgc gcaaactcct tcagggttgg gggactctga aggaaacggg 1900 acaaaacctt aagctgtttt cttagcccct cagccagctg ccattagctt 1950 ggctcttaaa gggccaggcc tccttttctg ccctctagca gggaggtttt 2000 ccaactgttg gaggcgcctt tggggctgcc cctttgtctg gagtcactgg 2050 gggcttccga gggtctccct cgaccctctg tcgtcctggg atggctgtcg 2100 ggagctgtat cacctgggtt ctgtcccctg gctctgtatc aggcacttta 2150 ttaaagctgg gcctcagtgg ggtgtgtttg tctcctgctc ttctggagcc 2200 tggaaggaaa gggcttcagg aggaggctgt gaggctggag ggaccagatg 2250 gaggaggcca gcagctagcc attgcacact ggggtgatgg gtgggggcgg 2300 tgactgcccc agacttggtt ttgtaatgat ttgtacagga ataaacacac 2350 ctacgctccg gaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2400 a 2401 <210> 56 <211> 299 <212> PRT <213> Homo sapiens <400> 56 Met Ser Ser Asn Lys Glu Gin Arg Ser Ala Val Phe Val Ile Leu 15 10 15 Phe Ala Leu Ile Thr Ile Leu Ile Leu Tyr Ser Ser Asn Ser Ala 20 25 30 545 Asn Glu Val Phe His Tyr Gly Ser Leu Arg Gly Arg Ser Arg Arg 35 40 45 Pro Val Asn Leu Lys Lys Trp Ser Ile Thr Asp Gly Tyr Val Pro 50 55 60 Ile Leu Gly Asn Lys Thr Leu Pro Ser Arg Cys His Gin Cys Val 65 70 75 Ile Val Ser Ser Ser Ser His Leu Leu Gly Thr Lys Leu Gly Pro 80 85 90 Glu Ile Glu Arg Ala Glu Cys Thr Ile Arg Met Asn Asp Ala Pro 95 100 105 Thr Thr Gly Tyr Ser Ala Asp Val Gly Asn Lys Thr Thr Tyr Arg 110 115 120 Val Val Ala His Ser Ser Val Phe Arg Val Leu Arg Arg Pro Gin 125 130 135 Glu Phe Val Asn Arg Thr Pro Glu Thr Val Phe Ile Phe Trp Gly 140 145 150 Pro Pro Ser Lys Met Gin Lys Pro Gin Gly Ser Leu Val Arg Val 155 160 165 Ile Gin Arg Ala Gly Leu Val Phe Pro Asn Met Glu Ala Tyr Ala 170 175 180 Val Ser Pro Gly Arg Met Arg Gin Phe Asp Asp Leu Phe Arg Gly 185 190 195 Glu Thr Gly Lys Asp Arg Glu Lys Ser His Ser Trp Leu Ser Thr 200 205 210 Gly Trp Phe Thr Met Val Ile Ala Val Glu Leu Cys Asp His Val 215 220 225 His Val Tyr Gly Met Val Pro Pro Asn Tyr Cys Ser Gin Arg Pro 230 235 240 Arg Leu Gin Arg Met Pro Tyr His Tyr Tyr Glu Pro Lys Gly Pro 245 250 255 Asp Glu Cys Val Thr Tyr Ile Gin Asn Glu His Ser Arg Lys Gly 260 265 270 Asn His His Arg Phe Ile Thr Glu Lys Arg Val Phe Ser Ser Trp 275 280 285 Ala Gin Leu Tyr Gly Ile Thr Phe Ser His Pro Ser Trp Thr 290 295 <210> 57 <211> 4277 <212> DNA <213> Homo sapiens <400> 57 gtttctcata gttggcgtct tctaaaggaa aaacactaaa atgaggaact 50 546 cagcggaccg ggagcgacgc agcttgaggg aagcatccct agctgttggc 100 gcagaggggc gaggctgaag ccgagtggcc cgaggtgtct gaggggctgg 150 ggcaaaggtg aaagagtttc agaacaagct tcctggaacc catgacccat 200 gaagtcttgt cgacatttat accgtctgag ggtagcagct cgaaactaga 250 agaagtggag tgttgccagg gacggcagta tctctttgtg tgaccctggc 300 ggcctatggg acgttggctt cagacctttg tgatacacca tgctgcgtgg 350 gacgatgacg gcgtggagag gaatgaggcc tgaggtcaca ctggcttgcc 400 tcctcctagc cacagcaggc tgctttgctg acttgaacga ggtccctcag 450 gtcaccgtcc agcctgcgtc caccgtccag aagcccggag gcactgtgat 500 cttgggctgc gtggtggaac ctccaaggat gaatgtaacc tggcgcctga 550 atggaaagga gctgaatggc tcggatgatg ctctgggtgt cctcatcacc 600 cacgggaccc tcgtcatcac tgcccttaac aaccacactg tgggacggta 650 ccagtgtgtg gcccggatgc ctgcgggggc tgtggccagc gtgccagcca 700 ctgtgacact agccaatctc caggacttca agttagatgt gcagcacgtg 750 attgaagtgg atgagggaaa cacagcagtc attgcctgcc acctgcctga 800 gagccacccc aaagcccagg tccggtacag cgtcaaacaa gagtggctgg 850 aggcctccag aggtaactac ctgatcatgc cctcagggaa cctccagatt 900 gtgaatgcca gccaggagga cgagggcatg tacaagtgtg cagcctacaa 950 cccagtgacc caggaagtga aaacctccgg ctccagcgac aggctacgtg 1000 tgcgccgctc caccgctgag gctgcccgca tcatctaccc cccagaggcc 1050 caaaccatca tcgtcaccaa aggccagagt ctcattctgg agtgtgtggc 1100 cagtggaatc ccacccccac gggtcacctg ggccaaggat gggtccagtg 1150 tcaccggcta caacaagacg cgcttcctgc tgagcaacct cctcatcgac 1200 accaccagcg aggaggactc aggcacctac cgctgcatgg ccgacaatgg 1250 ggttgggcag cccggggcag cggtcatcct ctacaatgtc caggtgtttg 1300 aaccccctga ggtcaccatg gagctatccc agctggtcat cccctggggc 1350 cagagtgcca gctgtggctg agcttacctg aggaatgctg tgaggtgcgt tgcccctcat gggaaccccc ctccagccag cgccctccgt cgcctccggc 1400 1450 tctcccgcag ggccctgcgc gtgctcagca tggggcctga ggacgaaggc 1500 gtctaccagt gcatggccga gaacgaggtt gggagcgccc atgccgtagt 1550 ccagctgcgg acctccaggc caagcataac cccaaggcta tggcaggatg 1600 547 ctgagctggc tactggcaca cctcctgtat caccctccaa actcggcaac 1650 cctgagcaga tgctgagggg gcaaccggcg ctccccagac ccccaacgtc 1700 agtggggcct gcttccccga agtgtccagg agagaagggg cagggggctc 1750 ccgccgaggc tcccatcatc ctcagctcgc cccgcacctc caagacagac 1800 tcatatgaac tggtgtggcg gcctcggcat gagggcagtg gccgggcgcc 1850 aatcctctac tatgtggtga aacaccgcaa gcaggtcaca aattcctctg 1900 acgattggac catctctggc attccagcca accagcaccg cctgaccctc 1950 accagacttg accccgggag cttgtatgaa gtggagatgg cagcttacaa 2000 ctgtgcggga gagggccaga cagccatggt caccttccga actggacggc 2050 ggcccaaacc cgagatcatg gccagcaaag agcagcagat ccagagagac 2100 gaccctggag ccagtcccca gagcagcagc cagccagacc acggccgcct 2150 ctccccccca gaagctcccg acaggcccac catctccacg gcctccgaga 2200 cctcagtgta cgtgacctgg attccccgtg ggaatggtgg gttcccaatc 2250 cagtccttcc gtgtggagta caagaagcta aagaaagtgg gagactggat 2300 tctggccacc agcgccatcc ccccatcgcg gctgtccgtg gagatcacgg 2350 gcctagagaa aggcacctcc tacaagtttc gagtccgggc tctgaacatg 2400 ctgggggaga gcgagcccag cgccccctct cggccctacg tggtgtcggg 2450 ctacagcggt cgcgtgtacg agaggcccgt ggcaggtcct tatatcacct 2500 tcacggatgc ggtcaatgag accaccatca tgctcaagtg gatgtacatc 2550 ccagcaagta acaacaacac cccaatccat ggcttttata tctattatcg 2600 acccacagac agtgacaatg atagtgacta caagaaggat atggtggaag 2650 gggacaagta ctggcactcc atcagccacc tgcagccaga gacctcctac 2700 gacattaaga tgcagtgctt caatgaagga ggggagagcg agttcagcaa 2750 cgtgatgatc tgtgagacca aagctcggaa gtcttctggc cagcctggtc 2800 gactgccacc cccaactctg gccccaccac agccgcccct tcctgaaacc 2850 atagagcggc cggtgggcac tggggccatg gtggctcgct ccagcgacct 2900 gccctatctg attgtcgggg tcgtcctggg ctccatcgtt ctcatcatcg 2950 tcaccttcat acaacagacc ccccttctgc tgggttttcc ttgtggaggg tcgaagtgcc cctggtctaa cttccaccct gcaaaaacat cctgcccgta 3000 3050 tactatggtg ccattgggag gactcccagg ccaccaggcc agtggacagc 3100 cctacctcag tggcatcagt ggacgggcct gtgctaatgg gatccacatg 3150 aataggggct gcccctcggc tgcagtgggc tacccgggca tgaagcccca 3200 548 gcagcactgc ccaggcgagc ttcagcagca gagtgacacc agcagcctgc 3250 tgaggcagac ccatcttggc aatggatatg acccccaaag tcaccagatc 3300 acgaggggtc ccaagtctag cccggacgag ggctctttct tatacacact 3350 gcccgacgac tccactcacc agctgctgca gccccatcac gactgctgcc 3400 aacgccagga gcagcctgct gctgtgggcc agtcaggggt gaggagagcc 3450 cccgacagtc ctgtcctgga agcagtgtgg gaccctccat ttcactcagg 3500 gcccccatgc tgcttgggcc ttgtgccagt tgaagaggtg gacagtcctg 3550 actcctgcca agtgagtgga ggagactggt gtccccagca ccccgtaggg 3600 gcctacgtag gacaggaacc tggaatgcag ctctccccgg ggccactggt 3650 gcgtgtgtct tttgaaacac cacctctcac aatttaggca gaagctgata 3700 tcccagaaag actatatatt gttttttttt taaaaaaaaa agaagaaaaa 3750 agagacagag aaaattggta tttatttttc tattatagcc atatttatat 3800 atttatgcac ttgtaaataa atgtatatgt tttataattc tggagagaca 3850 taaggagtcc tacccgttga ggttggagag ggaaaataaa gaagctgcca 3900 cctaacagga gtcacccagg aaagcaccgc acaggctggc gcgggacaga 3950 ctcctaacct ggggcctctg cagtggcagg cgaggctgca ggaggcccac 4000 agataagctg gcaagaggaa ggatcccagg cacatggttc atcacgagca 4050 tgagggaaca gcaaggggca cggtatcaca gcctggagac acccacacag 4100 atggctggat ccggtgctac gggaaacatt ttcctaagat gcccatgaga 4150 acagaccaag atgtgtacag cactatgagc attaaaaaac cttccagaat 4200 caataatccg tggcaacata tctctgtaaa aacaaacact gtaacttcta 4250 aataaatgtt tagtcttccc tgtaaaa 4277 <210> 58 <211> 1115 <212> PRT <213> Homo sapiens <400> 58 Met Leu Arg Gly Thr Met Thr Ala Trp Arg Gly Met Arg Pro Glu 15 10 15 Val Thr Leu Ala Cys Leu Leu Leu Ala Thr Ala Gly Cys Phe Ala 25 30 Asp Leu Asn Glu Val Pro Gin Val Thr Val Gin Pro Ala Ser Thr 40 45 Val Gin Lys Pro Gly Gly Thr Val Ile Leu Gly Cys Val Val Glu 50 55 60 549 Pro Pro Arg Met Asn Val Thr Trp Arg Leu Asn Gly Lys Glu Leu 65 70 75 Asn Gly Ser Asp Asp Ala Leu Gly Val Leu Ile Thr His Gly Thr 80 85 90 Leu Val Ile Thr Ala Leu Asn Asn His Thr Val Gly Arg Tyr Gin 95 100 105 Cys Val Ala Arg Met Pro Ala Gly Ala Val Ala Ser Val Pro Ala 110 115 120 Thr Val Thr Leu Ala Asn Leu Gin Asp Phe Lys Leu Asp Val Gin 125 130 135 His Val Ile Glu Val Asp Glu Gly Asn Thr Ala Val Ile Ala Cys 140 145 150 His Leu Pro Glu Ser His Pro Lys Ala Gin Val Arg Tyr Ser Val 155 160 165 Lys Gin Glu Trp Leu Glu Ala Ser Arg Gly Asn Tyr Leu Ile Met 170 175 180 Pro Ser Gly Asn Leu Gin Ile Val Asn Ala Ser Gin Glu Asp Glu 185 190 195 Gly Met Tyr Lys Cys Ala Ala Tyr Asn Pro Val Thr Gin Glu Val 200 205 210 Lys Thr Ser Gly Ser Ser Asp Arg Leu Arg Val Arg Arg Ser Thr 215 220 225 Ala Glu Ala Ala Arg Ile Ile Tyr Pro Pro Glu Ala Gin Thr Ile 230 235 240 Ile Val Thr Lys Gly Gin Ser Leu Ile Leu Glu Cys Val Ala Ser 245 250 255 Gly Ile Pro Pro Pro Arg Val Thr Trp Ala Lys Asp Gly Ser Ser 260 265 270 Val Thr Gly Tyr Asn Lys Thr Arg Phe Leu Leu Ser Asn Leu Leu 275 280 285 Ile Asp Thr Thr Ser Glu Glu Asp Ser Gly Thr Tyr Arg Cys Met 290 295 300 Ala Asp Asn Gly Val Gly Gin Pro Gly Ala Ala Val Ile Leu Tyr 305 310 315 Asn Val Gin Val Phe Glu Pro Pro Glu Val Thr Met Glu Leu Ser 320 325 330 Gin Leu Val Ile Pro Trp Gly Gin Ser Ala Lys Leu Thr Cys Glu 335 340 345 Val Arg Gly Asn Pro Pro Pro Ser Val Leu Trp Leu Arg Asn Ala 350 355 360 Val Pro Leu Ile Ser Ser Gin Arg Leu Arg Leu Ser Arg Arg Ala 365 370 375 550 Leu Arg Val Leu Ser Met Gly Pro Glu Asp Glu Gly Val Tyr Gin 380 385 390 Cys Met Ala Glu Asn Glu Val Gly Ser Ala His Ala Val Val Gin 395 400 405 Leu Arg Thr Ser Arg Pro Ser Ile Thr Pro Arg Leu Trp Gin Asp 410 415 420 Ala Glu Leu Ala Thr Gly Thr Pro Pro Val Ser Pro Ser Lys Leu 425 430 435 Gly Asn Pro Glu Gin Met Leu Arg Gly Gin Pro Ala Leu Pro Arg 440 445 450 Pro Pro Thr Ser Val Gly Pro Ala Ser Pro Lys Cys Pro Gly Glu 455 460 465 Lys Gly Gin Gly Ala Pro Ala Glu Ala Pro Ile Ile Leu Ser Ser 470 475 480 Pro Arg Thr Ser Lys Thr Asp Ser Tyr Glu Leu Val Trp Arg Pro 485 490 495 Arg His Glu Gly Ser Gly Arg Ala Pro Ile Leu Tyr Tyr Val Val 500 505 510 Lys His Arg Lys Gin Val Thr Asn Ser Ser Asp Asp Trp Thr Ile 515 520 525 Ser Gly Ile Pro Ala Asn Gin His Arg Leu Thr Leu Thr Arg Leu 530 535 540 Asp Pro Gly Ser Leu Tyr Glu Val Glu Met Ala Ala Tyr Asn Cys 545 550 555 Ala Gly Glu Gly Gin Thr Ala Met Val Thr Phe Arg Thr Gly Arg 560 565 570 Arg Pro Lys Pro Glu Ile Met Ala Ser Lys Glu Gin Gin Ile Gin 575 580 585 Arg Asp Asp Pro Gly Ala Ser Pro Gin Ser Ser Ser Gin Pro Asp 590 595 600 His Gly Arg Leu Ser Pro Pro Glu Ala Pro Asp Arg Pro Thr Ile 605 610 . 615 Ser Thr Ala Ser Glu Thr Ser Val Tyr Val Thr Trp Ile Pro Arg 620 625 630 Gly Asn Gly Gly Phe Pro Ile Gin Ser Phe Arg Val Glu Tyr Lys 635 640 645 Lys Leu Lys Lys Val Gly Asp Trp Ile Leu Ala Thr Ser Ala Ile 650 655 660 Pro Pro Ser Arg Leu Ser Val Glu Ile Thr Gly Leu Glu Lys Gly 665 670 675 Thr Ser Tyr Lys Phe Arg Val Arg Ala Leu Asn Met Leu Gly Glu 551 680 685 690 Ser Glu Pro Ser Ala Pro Ser Arg Pro Tyr Val Val Ser Gly Tyr 695 700 705 Ser Gly Arg Val Tyr Glu Arg Pro Val Ala Gly Pro Tyr Ile Thr 710 715 720 Phe Thr Asp Ala Val Asn Glu Thr Thr Ile Met Leu Lys Trp Met 725 730 735 Tyr Ile Pro Ala Ser Asn Asn Asn Thr Pro Ile His Gly Phe Tyr 740 745 750 Ile Tyr Tyr Arg Pro Thr Asp Ser Asp Asn Asp Ser Asp Tyr Lys 755 760 765 Lys Asp Met Val Glu Gly Asp Lys Tyr Trp His Ser Ile Ser His 770 775 780 Leu Gin Pro Glu Thr Ser Tyr Asp Ile Lys Met Gin Cys Phe Asn 785 790 795 Glu Gly Gly Glu Ser Glu Phe Ser Asn Val Met Ile Cys Glu Thr 800 805 810 Lys Ala Arg Lys Ser Ser Gly Gin Pro Gly Arg Leu Pro Pro Pro 815 820 825 Thr Leu Ala Pro Pro Gin Pro Pro Leu Pro Glu Thr Ile Glu Arg 830 835 840 Pro Val Gly Thr Gly Ala Met Val Ala Arg Ser Ser Asp Leu Pro 845 850 855 Tyr Leu lie Val Gly Val Val Leu Gly Ser Ile Val Leu Ile Ile 860 865 870 Val Thr Phe Ile Pro Phe Cys Leu Trp Arg Ala Trp Ser Lys Gin 875 880 885 Lys His Thr Thr Asp Leu Gly Phe Pro Arg Ser Ala Leu Pro Pro 890 895 900 Ser Cys Pro Tyr Thr Met Val Pro Leu Gly Gly Leu Pro Gly His 905 910 915 Gin Ala Ser Gly Gin Pro Tyr Leu Ser Gly lie Ser Gly Arg Ala 920 925 930 Cys Ala Asn Gly Ile His Met Asn Arg Gly Cys Pro Ser Ala Ala 935 940 945 Val Gly Tyr Pro Gly Met Lys Pro Gin Gin His Cys Pro Gly Glu 950 955 960 Leu Gin Gin Gin Ser Asp Thr Ser Ser Leu Leu Arg Gin Thr His 965 970 975 Leu Gly Asn Gly Tyr Asp Pro Gin Ser His Gin Ile Thr Arg Gly 980 985 990 552 Pro Lys Ser Ser Pro Asp Glu Gly Ser Phe Leu Tyr Thr Leu Pro 995 1000 1005 Asp Asp Ser Gin Arg Gin Arg Ala Pro Phe His Ser Glu Val Asp Cys Pro Gin Met Gin Leu Pro Pro Leu <210> 59 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 59 gggaaacaca gcagtcattg cctgc 25 <210> 60 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 60 gcacacgtag cctgtcgctg gage 24 <210> 61 <211> 42 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 61 caccccaaag cccaggtccg gtacagcgtc aaacaagagt gg 42 Thr His Gin Leu Leu Gin Pro His His Asp Cys Cys 1010 1015 1020 Glu Gin Pro Ala Ala Val Gly Gin Ser Gly Val Arg 1025 1030 1035 Asp Ser Pro Val Leu Glu Ala Val Trp Asp Pro Pro 1040 1045 1050 Gly Pro Pro Cys Cys Leu Gly Leu Val Pro Val Glu 1055 1060 1065 Ser Pro Asp Ser Cys Gin Val Ser Gly Gly Asp Trp 1070 1075 1080 His Pro Val Gly Ala Tyr Val Gly Gin Glu Pro Gly 1085 1090 1095 Ser Pro Gly Pro Leu Val Arg Val Ser Phe Glu Thr 1100 1105 1110 Thr Ile 1115 <210> 62 <211> 1661 553 <212> DNA <213> Homo sapiens <220> <221> unsure <222> 678 <223> unknown base <400> 62 cgggaggctg ggtcgtcatg atccggaccc cattgtcggc ctctgcccat 50 cgcctgctcc tcccaggctc ccgcggccga cccccgcgca acatgcagcc 100 cacgggccgc gagggttccc gcgcgctcag ccggcggtat ctgcggcgtc 150 tgctgctcct gctactgctg ctgctgctgc ggcagcccgt aacccgcgcg 200 gagaccacgc cgggcgcccc cagagccctc tccacgctgg gctcccccag 250 cctcttcacc acgccgggtg tccccagcgc cctcactacc ccaggcctca 300 ctacgccagg cacccccaaa accctggacc ttcggggtcg cgcgcaggcc 350 ctgatgcgga gtttcccact cgtggacggc cacaatgacc tgccccaggt 400 cctgagacag cgttacaaga atgtgcttca ggatgttaac ctgcgaaatt 450 tcagccatgg tcagaccagc ctggacaggc ttagagacgg cctcgtgggt 500 gcccagttct ggtcagcctc cgtctcatgc cagtcccagg accagactgc 550 cgtgcgcctc gccctggagc agattgacct cattcaccgc atgtgtgcct 600 cctactctga actcgagctt gtgacctcag ctgaaggtct gaacagctct 650 caaaagctgg cctgcctcat tggcgtgnag ggtggtcact cactggacag 700 cagcctctct gtgctgcgca gtttctatgt gctgggggtg cgctacctga 750 cacttacctt cacctgcagt acaccatggg cagagagttc caccaagttc 800 agacaccaca tgtacaccaa cgtcagcgga ttgacaagct ttggtgagaa 850 agtagtagag gagttgaacc gcctgggcat gatgatagat ttgtcctatg 900 catcggacac cttgataaga agggtcctgg aagtgtctca ggctcctgtg 950 atcttctccc actcagctgc cagagctgtg tgtgacaatt tgttgaatgt 1000 tcccgatgat atcctgcagc ttctgaagaa cggtggcatc gtgatggtga 1050 cactgtccat gggggtgctg cagtgcaacc tgcttgctaa cgtgtccact 1100 gtggcagatc actttgacca catcagggca gtcattggat ctgagttcat 1150 cgggattggt ggaaattatg acgggactgg ccggttccct caggggctgg 1200 aggatgtgtc cacataccca gtcctgatag aggagttgct gagtcgtasc 1250 tggagcgagg aagagcttca aggtgtcctt cgtggaaacc tgctgcgggt 1300 cttcagacaa gtggaaaagg tgagagagga gagcagggcg cagagccccg 1350 554 tggaggctga gtttccatat gggcaactga gcacatcctg ccactcccac 1400 ctcgtgcctc agaatggaca ccaggctact catctggagg tgaccaagca 1450 gccaaccaat cgggtcccct ggaggtcctc aaatgcctcc ccataccttg 1500 ttccaggcct tgtggctgct gccaccatcc caaccttcac ccagtggctc 1550 tgctgacaca gtcggtcccc gcagaggtca ctgtggcaaa gcctcacaaa 1600 gccccctctc ctagttcatt cacaagcata tgctgagaat aaacatgtta 1650 cacatggaaa a 1661 <210> 63 <211> 487 <212> PRT <213> Homo sapiens <220> <221> unsure <222> 196, 386 <223> unknown amino acid <400> 63 Met Gin Pro Thr Gly Arg Glu Gly Ser Arg Ala Leu Ser Arg Arg 15 10 15 Tyr Leu Arg Arg Leu Leu Leu Leu Leu Leu Leu Leu Leu Leu Arg 20 25 30 Gin Pro Val Thr Arg Ala Glu Thr Thr Pro Gly Ala Pro Arg Ala 35 40 45 Leu Ser Thr Leu Gly Ser Pro Ser Leu Phe Thr Thr Pro Gly Val 50 55 60 Pro Ser Ala Leu Thr Thr Pro Gly Leu Thr Thr Pro Gly Thr Pro 65 70 75 Lys Thr Leu Asp Leu Arg Gly Arg Ala Gin Ala Leu Met Arg Ser 80 85 90 Phe Pro Leu Val Asp Gly His Asn Asp Leu Pro Gin Val Leu Arg 95 100 105 Gin Arg Tyr Lys Asn Val Leu Gin Asp Val Asn Leu Arg Asn Phe 110 115 120 Ser His Gly Gin Thr Ser Leu Asp Arg Leu Arg Asp Gly Leu Val 125 130 135 Gly Ala Gin Phe Trp Ser Ala Ser Val Ser Cys Gin Ser Gin Asp 140 145 150 Gin Thr Ala Val Arg Leu Ala Leu Glu Gin Ile Asp Leu Ile His 155 160 165 Arg Met Cys Ala Ser Tyr Ser Glu Leu Glu Leu Val Thr Ser Ala 170 175 180 555 Glu Gly Leu Asn Ser Ser Gin Lys Leu Ala Cys Leu Ile Gly Val 185 190 195 Xaa Gly Gly His Ser Leu Asp Ser Ser Leu Ser Val Leu Arg Ser 200 205 210 Phe Tyr Val Leu Gly Val Arg Tyr Leu Thr Leu Thr Phe Thr Cys 215 220 225 Ser Thr Pro Trp Ala Glu Ser Ser Thr Lys Phe Arg His His Met 230 235 240 Tyr Thr Asn Val Ser Gly Leu Thr Ser Phe Gly Glu Lys Val Val 245 250 255 Glu Glu Leu Asn Arg Leu Gly Met Met Ile Asp Leu Ser Tyr Ala 260 265 270 Ser Asp Thr Leu Ile Arg Arg Val Leu Glu Val Ser Gin Ala Pro 275 280 285 Val Ile Phe Ser His Ser Ala Ala Arg Ala Val Cys Asp Asn Leu 290 295 300 Leu Asn Val Pro Asp Asp Ile Leu Gin Leu Leu Lys Asn Gly Gly 305 310 315 Ile Val Met Val Thr Leu Ser Met Gly Val Leu Gin Cys Asn Leu 320 325 330 Leu Ala Asn Val Ser Thr Val Ala Asp His Phe Asp His Ile Arg 335 340 345 Ala Val Ile Gly Ser Glu Phe Ile Gly Ile Gly Gly Asn Tyr Asp 350 355 360 Gly Thr Gly Arg Phe Pro Gin Gly Leu Glu Asp Val Ser Thr Tyr 365 370 375 Pro Val Leu Ile Glu Glu Leu Leu Ser Arg Xaa Trp Ser Glu Glu 380 385 390 Glu Leu Gin Gly Val Leu Arg Gly Asn Leu Leu Arg Val Phe Arg 395 400 405 Gin Val Glu Lys Val Arg Glu Glu Ser Arg Ala Gin Ser Pro Val 410 415 420 Glu Ala Glu Phe Pro Tyr Gly Gin Leu Ser Thr Ser Cys His Ser 425 430 435 His Leu Val Pro Gin Asn Gly His Gin Ala Thr His Leu Glu Val 440 445 450 Thr Lys Gin Pro Thr Asn Arg Val Pro Trp Arg Ser Ser Asn Ala 455 460 465 Ser Pro Tyr Leu Val Pro Gly Leu Val Ala Ala Ala Thr Ile Pro 470 475 480 Thr Phe Thr Gin Trp Leu Cys 485 556 <210> 64 <211> 25 <212> DNA <213> Artificial sequence <220> <223> Synthetic oligonucleotide probe <400> 64 ccttcacctg cagtacacca tgggc 25 <210> 65 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 65 gtcacacaca gctctggcag ctgag 25 <210> 66 <211> 47 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 66 ccaagttcag acaccacatg tacaccaacg tcagcggatt gacaagc 47 <210> 67 <211> 1564 <212> DNA <213> Homo sapiens <400> 67 tgctaggctc tgtcccacaa tgcacccgag agcaggagct gaaagcctct 50 aacacccaca gatccctcta tgactgcaat gtgaggtgtc cggctttgct 100 ggcccagcaa gcctgataag catgaagctc ttatctttgg tggctgtggt 150 cgggtgtttg ctggtgcccc cagctgaagc caacaagagt tctgaagata 200 tccggtgcaa atgcatctgt ccaccttata gaaacatcag tgggcacatt 250 tacaaccaga atgtatccca gaaggactgc aactgcctgc acgtggtgga 300 gcccatgcca gtgcctggcc atgacgtgga ggcctactgc ctgctgtgcg 350 agtgcaggta cgaggagcgc agcaccacca ccatcaaggt catcattgtc 400 atctacctgt ccgtggtggg tgccctgttg ctctacatgg ccttcctgat 450 gctggtggac cctctgatcc gaaagccgga tgcatacact gagcaactgc 500 acaatgagga ggagaatgag gatgctcgct ctatggcagc agctgctgca 550 557 tccctcgggg gaccccgagc aaacacagtc ctggagcgtg tggaaggtgc 600 ccagcagcgg tggaagctgc aggtgcagga gcagcggaag acagtcttcg 650 atcggcacaa gatgctcagc tagatgggct ggtgtggttg ggtcaaggcc 700 ccaacaccat ggctgccagc ttccaggctg gacaaagcag ggggctactt 750 ctcccttccc tcggttccag tcttcccttt aaaagcctgt ggcatttttc 800 ctccttctcc ctaactttag aaatgttgta cttggctatt ttgattaggg 850 aagagggatg tggtctctga tctctgttgt cttcttgggt ctttggggtt 900 gaagggaggg ggaaggcagg ccagaaggga atggagacat tcgaggcggc 950 ctcaggagtg gatgcgatct gtctctcctg gctccactct tgccgccttc 1000 cagctctgag tcttgggaat gttgttaccc ttggaagata aagctgggtc 1050 ttcaggaact cagtgtctgg gaggaaagca tggcccagca ttcagcatgt 1100 gttcctttct gcagtggttc ttatcaccac ctccctccca gccccggcgc 1150 ctcagcccca gccccagctc cagccctgag gacagctctg atgggagagc 1200 tgggccccct gagcccactg ggtcttcagg gtgcactgga agctggtgtt 1250 cgctgtcccc tgtgcacttc tcgcactggg gcatggagtg cccatgcata 1300 ctctgctgcc ggtcccctca cctgcacttg aggggtctgg gcagtccctc 1350 ctctccccag tgtccacagt cactgagcca gacggtcggt tggaacatga 1400 gactcgaggc tgagcgtgga tctgaacacc acagcccctg tacttgggtt 1450 gcctcttgtc cctgaacttc gttgtaccag tgcatggaga gaaaattttg 1500 tcctcttgtc ttagagttgt gtgtaaatca aggaagccat cattaaattg 1550 ttttatttct ctca 1564 <210> 68 <211> 183 <212> PRT <213> Homo sapiens <400> 68 Met Lys Leu Leu Ser Leu Val Ala Val Val Gly Cys Leu Leu Val 15 10 15 Pro Pro Ala Glu Ala Asn Lys Ser Ser Glu Asp Ile Arg Cys Lys 20 25 30 Cys Ile Cys Pro Pro Tyr Arg Asn Ile Ser Gly His Ile Tyr Asn 35 40 45 Gin Asn Val Ser Gin Lys Asp Cys Asn Cys Leu His Val Val Glu 50 55 60 Pro Met Pro Val Pro Gly His Asp Val Glu Ala Tyr Cys Leu Leu 65 70 75 558 Cys Glu Cys Arg Tyr 80 Ile Ile Val Ile Tyr 95 Met Ala Phe Leu Met 110 Ala Tyr Thr Glu Gin 125 Arg Ser Met Ala Ala 140 Asn Thr Val Leu Glu 155 Leu Gin Val Gin Glu 170 Met Leu Ser <210> 69 <211> 3170 <212> DNA <213> Homo sapiens <400> 69 agcgggtctc gcttgggttc cgctaatttc tgtcctgagg cgtgagactg 50 agttcatagg gtcctgggtc cccgaaccag gaagggttga gggaacacaa 100 tctgcaagcc cccgcgaccc aagtgagggg ccccgtgttg gggtcctccc 150 tccctttgca ttcccacccc tccgggcttt gcgtcttcct ggggaccccc 200 tcgccgggag atggccgcgt tgatgcggag caaggattcg tcctgctgcc 250 tgctcctact ggccgcggtg ctgatggtgg agagctcaca gatcggcagt 300 tcgcgggcca aactcaactc catcaagtcc tctctgggcg gggagacgcc 350 tggtcaggcc gccaatcgat ctgcgggcat gtaccaagga ctggcattcg 400 gcggcagtaa gaagggcaaa aacctggggc aggcctaccc ttgtagcagt 450 gataaggagt gtgaagttgg gaggtattgc cacagtcccc accaaggatc 500 atcggcctgc atggtgtgtc ggagaaaaaa gaagcgctgc caccgagatg 550 gcatgtgctg ccccagtacc cgctgcaata atggcatctg tatcccagtt 600 actgaaagca tcttaacccc tcacatcccg gctctggatg gtactcggca 650 cagagatcga aaccacggtc attactcaaa ccatgacttg ggatggcaga 700 atctaggaag accacacact aagatgtcac atataaaagg gcatgaagga 750 gacccctgcc tacgatcatc agactgcatt gaagggtttt gctgtgctcg 800 Glu Glu Arg Ser Thr Thr Thr Ile Lys Val 85 90 Leu Ser Val Val Gly Ala Leu Leu Leu Tyr 100 105 Leu Val Asp Pro Leu Ile Arg Lys Pro Asp 115 120 Leu His Asn Glu Glu Glu Asn Glu Asp Ala 130 135 Ala Ala Ala Ser Leu Gly Gly Pro Arg Ala 145 150 Arg Val Glu Gly Ala Gin Gin Arg Trp Lys 160 165 Gin Arg Lys Thr Val Phe Asp Arg His Lys 175 180 tcatttctgg gtaccaaaca tgcgactgtg ctcctccaaa ggaacatcat catggtggaa gtgataagaa aatagattag caacttgtct agagaacaag aagagtttag ttatacaaat aaaatactcc gctaaacaag taccttttga agataagaaa cagttgttta ccacaaatac actgatacaa atctctcttt aactataccc ttcacagatg gctaacagag gatagaatta agagacttaa aaaacttttt aggcacaagt tgaatatctg tcagtgtgag tgctgagatc tcctgaagta accaaaatct acgcaagaag cgaagggcct gccagactcc caattgcaga aataaggttc tatagatgat aatgggtgac atgtaaataa cacacagtgg gttgtgctgg aacctacatg tagaataact aaatgaaaac tttgtaacac aaaatcagtc ggaaggcctt ttttttttca gacaaaaaca atcctatgtg ataaattgtg gcaaaaaaat agatcattat gattggtaaa gctggatctg cgtttgttca tggctgttca catgggattt gtcctgtgtc ctcaaataat gacagagtag gcaaaccagt ggttctcatg gtcttgcaaa atgtgtgtca ctgtgaagtt agatgcagaa cacaaaaagg aaatgcagtg tgtacacatt aaattactga aggagaggtt ccagatttct tgttatacaa atggagcatt tacttctgct aatatttcca taggaagaca aaattttagt gttccttcag attcctgctc actagtaaaa ttaaagatgt ttcttaaaga tacatgtatt tactgcactg ggttttggca tctttgaaac gctatcataa cgtactatcc ctcaatttca tgaggtttca 559 gctccatcag ggctggaaat gtatggaaag gaaaatttga gtgtatttaa gaatggctaa gagaaagaaa cagccagtgt tgtggaaaat tgagtagcat tccttcagat attcaacgtt taggttctaa gttaatttac gttcaatcaa aataattgca aataaataac tttacctgta attctacgga tgaatgcatt tacttacaca ccaatatatg ttggccataa catacatact gagtaagcaa acacatagat caggggatgc tatttactat tcaaattatt ggaggtttca ttgccctcta ggggaagtct 850 tttccagcgt 900 atgccaccta 950 tcaccattga 1000 tgcattatag 1050 aataagaaac 1100 acatgaactg 1150 ttccattatg 12 00 gctattatta 1250 gtgactttcc 1300 tgctgattgc 1350 agagtttaac 1400 aaataaaatt 1450 aacagaaaat 1500 gagtcttggt 1550 aaataatggc 1600 aaacaaacag 1650 attaataaga 1700 atgacagtat 1750 atattttcca 1800 gagcagaatt 1850 tgggaaaaga 1900 cctatatttt 1950 ctgtggtaat 2 000 gaaaattggg 2050 catatgtctg 2100 acagtctaaa '2150 gcagatgaat 22 00 tattttatag 2250 caaaatgtac 23 00 taagcttctg 2350 560 actagccaat ggcatcatcc aattttcttc ccaaacctct gcagcatctg 2400 ctttattgcc aaagggctag tttcggtttt ctgcagccat tgcggttaaa 2450 aaatataagt aggataactt gtaaaacctg catattgcta atctatagac 2 500 accacagttt ctaaattctt tgaaaccact ttactacttt ttttaaactt 2550 aactcagttc taaatacttt gtctggagca caaaacaata aaaggttatc 2600 ttatagtcgt gactttaaac ttttgtagac cacaattcac tttttagttt 2 650 tcttttactt aaatcccatc tgcagtctca aatttaagtt ctcccagtag 2700 agattgagtt tgagcctgta tatctattaa aaatttcaac ttcccacata 2750 tatttactaa gatgattaag acttacattt tctgcacagg tctgcaaaaa 2800 caaaaattat aaactagtcc atccaagaac caaagtttgt ataaacaggt 2850 tgctataagc ttgtgaaatg aaaatggaac atttcaatca aacatttcct 2900 atataacaat tattatattt acaatttggt ttctgcaata tttttcttat 2950 gtccaccctt ttaaaaatta ttatttgaag taatttattt acaggaaatg 3000 ttaatgagat gtattttctt atagagatat ttcttacaga aagctttgta 3050 gcagaatata tttgcagcta ttgactttgt aatttaggaa aaatgtataa 3100 taagataaaa tctattaaat ttttctcctc taaaaactga aaaaaaaaaa 3150 aaaaaaaaaa aaaaaaaaaa 3170 <210> 70 <211> 259 <212> PRT <213> Homo sapiens <400> 70 Met Ala Ala Leu Met Arg Ser Lys Asp 1 5 Leu Leu Ala Ala Val Leu Met Val Glu 20 Ser Arg Ala Lys Leu Asn Ser Ile Lys 35 Thr Pro Gly Gin Ala Ala Asn Arg Ser 50 Leu Ala Phe Gly Gly Ser Lys Lys Gly 65 Tyr Pro Cys Ser Ser Asp Lys Glu Cys 80 His Ser Pro His Gin Gly Ser Ser Ala 95 Lys Lys Lys Arg Cys His Arg Asp Gly 110 Ser 10 Ser 25 Ser 40 Ala 55 Lys 70 Glu 85 Cys 100 Met 115 Ser Ser Ser Gly Asn Val Met Cys Cys Cys Gin Ile Leu Gly Met Tyr Leu Gly Gly Arg Val Cys Cys Pro Leu Leu 15 Gly Ser 30 Gly Glu 45 Gin Gly 60 Gin Ala 75 Tyr Cys 90 Arg Arg 105 Ser Thr 120 561 Arg Cys Asn Thr Pro His Asn His Gly Gly Arg Pro Asp Pro Cys Ala Arg His Gly Glu Val Glu Ile Phe Val Trp Lys Cys Gin Lys <210> 71 <211> 1809 <212> DNA <213> Homo s< <400> 71 tctcaatctg ctgacctcgt gatccgcctg accttgtaat ccacctacct 50 tggcctccca aagtgttggg attacaggcg tgagccaccg cgcccggcca 100 acatcacgtt tttaaaaatt gatttcttca aattcatggc aaatatttcc 150 cttcccttta acttcttatg tcagaatgag gaaggatagc tgcatttatt 200 tagtcagttt tcattgcata gtaatatttt catgtagtat tttctaagtt 250 atattttagt aattcatatg ttttagatta taggttttaa catacttgtg 300 aaaatacttg atgtgtttta aagccttggg cagaaattct gtattgttga 350 ggatttgttc ttttatcccc cttttaaagt catccgtcct tggctcagga 400 tttggagagc ttgcaccacc aaaaatggca aacatcacca gctcccagat 450 tttggaccag ttgaaagctc cgagtttggg ccagtttacc accaccccaa 500 gtacacagca gaatagtaca agtcacccta caactactac ttcttgggac 550 ctcaagcccc caacatccca gtcctcagtc ctcagtcatc ttgacttcaa 600 atctcaacct gagccatccc cagttcttag ccagttgagc cagcgacaac 650 Asn Gly Ile Cys Ile Pro Val Thr Glu Ser Ile Leu 125 130 135 Ile Pro Ala Leu Asp Gly Thr Arg His Arg Asp Arg 140 145 150 His Tyr Ser Asn His Asp Leu Gly Trp Gin Asn Leu 155 160 165 His Thr Lys Met Ser His Ile Lys Gly His Glu Gly 170 175 180 Leu Arg Ser Ser Asp Cys Ile Glu Gly Phe Cys Cys 185 190 195 Phe Trp Thr Lys Ile Cys Lys Pro Val Leu His Gin 200 205 210 Cys Thr Lys Gin Arg Lys Lys Gly Ser His Gly Leu 215 220 225 Gin Arg Cys Asp Cys Ala Lys Gly Leu Ser Cys Lys 230 235 240 Asp Ala Thr Tyr Ser Ser Lys Ala Arg Leu His Val 245 250 255 Ile apiens 562 agcaccagag ccaggcagtc actgttcctc ctcctggttt ggagtccttt 700 ccttcccagg caaaacttcg agaatcaaca cctggagaca gtccctccac 750 tgtgaacaag cttttgcagc ttcccagcac gaccattgaa aatatctctg 800 tgtctgtcca atacccccag ccagccacag cttctaagat cccaaacaca cccagcttct tcaaacttgc gcagtggaaa taagcggcgg tgcctggttc 850 900 agcagatgtc acaggattaa atgtgcagtt tggggctctg gaatttgggt 950 cagaaccttc tctctctgaa tttggatcag ctccaagcag tgaaaatagt 1000 aatcagattc ccatcagctt gtattcgaag tctttaagtg agcctttgaa 1050 tacatcttta tcaatgacca gtgcagtaca gaactccaca tatacaactt 1100 ccgtcattac ctcctgcagt ctgacaagct catcactgaa ttctgctagt 1150 ccagtagcaa tgtcttcctc ttatgaccag agttctgtgc ataacaggat 1200 cccataccaa agccctgtga gttcatcaga gtcagctcca ggaaccatca 1250 tgaatggaca tggtggtggt cgaagtcagc agacactaga cagtaagtat 1300 agcagcaagc tactcttgtc atggctggtg ccaaccaaac agaggaagag 1350 gatagctcac gtgatgtgga aaacaccagt tggtcaatgg ctcattcgtt 1400 aaaaagcagc ccttttgctt ttttgttttt ggaccaggtg ttggctgtgg 1450 tgttattaga aatgtcttaa ccacagcaag aaggaggtgg tggtctcata 1500 ttcttctgcc ctaatcagac tgcaccacaa gtgcagcata cagtatgcat 1550 tttaaagatg cttgggccag gcggggtggc tgatgcccat aatcccagtg 1600 ctttgggggg ccaaggcagg cagattgccc aagctcagga gtttgagacc 1650 accctgggca acatggtgaa actctgtctc tactaaaata cgaaaaacta 1700 gccgggtgtg gtggcggcgc gtgcctgtaa tcccagctac ttgggaggct 1750 gaggcacaag aatcgcttga gccagcttgg gctacaaagt gagactccgt 1800 ctgaaaaga 1809 <210> 72 <211> 363 <212> PRT <213> Homo sapiens <400> 72 Met Cys Phe Lys Ala Leu Gly Arg Asn Ser Val Leu Leu Arg lie 15 10 15 Cys Ser Phe Ile Pro Leu Leu Lys Ser Ser Val Leu Gly Ser Gly 20 25 30 Phe Gly Glu Leu Ala Pro Pro Lys Met Ala Asn Ile Thr Ser Ser 35 40 45 563 Gin Ile Leu Asp Gin Leu Lys Ala Pro Ser Leu Gly Gin Phe Thr 50 55 60 Thr Thr Pro Ser Thr Gin Gin Asn Ser Thr Ser His Pro Thr Thr 65 70 75 Thr Thr Ser Trp Asp Leu Lys Pro Pro Thr Ser Gin Ser Ser Val 80 85 90 Leu Ser His Leu Asp Phe Lys Ser Gin Pro Glu Pro Ser Pro Val 95 100 105 Leu Ser Gin Leu Ser Gin Arg Gin Gin His Gin Ser Gin Ala Val 110 115 120 Thr Val Pro Pro Pro Gly Leu Glu Ser Phe Pro Ser Gin Ala Lys 125 130 135 Leu Arg Glu Ser Thr Pro Gly Asp Ser Pro Ser Thr Val Asn Lys 140 145 150 Leu Leu Gin Leu Pro Ser Thr Thr Ile Glu Asn Ile Ser Val Ser 155 160 165 Val His Gin Pro Gin Pro Lys His Ile Lys Leu Ala Lys Arg Arg 170 175 180 Ile Pro Pro Ala Ser Lys Ile Pro Ala Ser Ala Val Glu Met Pro 185 190 195 Gly Ser Ala Asp Val Thr Gly Leu Asn Val Gin Phe Gly Ala Leu 200 205 210 Glu Phe Gly Ser Glu Pro Ser Leu Ser Glu Phe Gly Ser Ala Pro 215 220 225 Ser Ser Glu Asn Ser Asn Gin Ile Pro Ile Ser Leu Tyr Ser Lys 230 235 240 Ser Leu Ser Glu Pro Leu Asn Thr Ser Leu Ser Met Thr Ser Ala 245 250 255 Val Gin Asn Ser Thr Tyr Thr Thr Ser Val Ile Thr Ser Cys Ser 260 265 270 Leu Thr Ser Ser Ser Leu Asn Ser Ala Ser Pro Val Ala Met Ser 275 280 285 Ser Ser Tyr Asp Gin Ser Ser Val His Asn Arg Ile Pro Tyr Gin 290 295 300 Ser Pro Val Ser Ser Ser Glu Ser Ala Pro Gly Thr Ile Met Asn 305 310 315 Gly His Gly Gly Gly Arg Ser Gin Gin Thr Leu Asp Ser Lys Tyr 320 325 330 Ser Ser Lys Leu Leu Leu Ser Trp Leu Val Pro Thr Lys Gin Arg 335 340 345 Lys Arg Ile Ala His Val Met Trp Lys Thr Pro Val Gly Gin Trp 350 355 360 Leu Ile Arg 564 <210> 73 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 73 aattcatggc aaatatttcc cttccc 26 <210> 74 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 74 tggtaaactg gcccaaactc gg 22 <210> 75 <211> 50 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 75 ttaaagtcat ccgtccttgg ctcaggattt ggagagcttg caccaccaaa 50 <210> 76 <211> 1989 <212> DNA <213> Homo sapiens <400> 76 gccgagtggg acaaagcctg gggctgggcg ggggccatgg cgctgccatc 50 ccgaatcctg ctttggaaac ttgtgcttct gcagagctct gctgttctcc 100 tgcactcagc ggtggaggag acggacgcgg ggctgtacac ctgcaacctg 150 caccatcact actgccacct ctacgagagc ctggccgtcc gcctggaggt 200 caccgacggc cccccggcca cccccgccta ctgggacggc gagaaggagg 250 tgctggcggt ggcgcgcggc gcacccgcgc ttctgacctg cgtgaaccgc 300 gggcacgtgt ggaccgaccg gcacgtggag gaggctcaac aggtggtgca 350 ctgggaccgg cagccgcccg gggtcccgca cgaccgcgcg gaccgcctgc 400 tggacctcta cgcgtcgggc gagcgccgcg cctacgggcc cctttttctg 450 cgcgaccgcg tggctgtggg cgcggatgcc tttgagcgcg gtgacttctc 500 565 actgcgtatc gagccgctgg aggtcgccga cgagggcacc tactcctgcc 550 acctgcacca ccattactgt ggcctgcacg aacgccgcgt cttccacctg 600 acggtcgccg aaccccacgc ggagccgccc ccccggggct ctccgggcaa 650 cggctccagc cacagcggcg ccccaggccc agaccccaca ctggcgcgcg 700 gccacaacgt catcaatgtc atcgtccccg agagccgagc ccacttcttc 750 cagcagctgg gctacgtgct ggccacgctg ctgctcttca tcctgctact 800 ggtcactgtc ctcctggccg cccgcaggcg ccgcggaggc tacgaatact 850 cggaccagaa gtcgggaaag tcaaagggga aggatgttaa cttggcggag 900 ttcgctgtgg ctgcagggga ccagatgctt tacaggagtg aggacatcca 950 gctagattac aaaaacaaca tcctgaagga gagggcggag ctggcccaca 1000 gccccctgcc tgccaagtac atcgacctag acaaagggtt ccggaaggag 1050 aactgcaaat agggaggccc tgggctcctg gctgggccag cagctgcacc 1100 tctcctgtct gtgctcctcg gggcatctcc tgatgctccg gggctcaccc 1150 cccttccagc ggctggtccc gctttcctgg aatttggcct gggcgtatgc 1200 agaggccgcc tccacacccc tcccccaggg gcttggtggc agcatagccc 1250 ccacccctgc ggcctttgct cacgggtggc cctgcccacc cctggcacaa 1300 ccaaaatccc actgatgccc atcatgccct cagacccttc tgggctctgc 1350 ccgctggggg cctgaagaca ttcctggagg acactcccat cagaacctgg 1400 cagccccaaa actggggtca gcctcagggc aggagtccca ctcctccagg 1450 gctctgctcg tccggggctg ggagatgttc ctggaggagg acactcccat 1500 cagaacttgg cagccttgaa gttggggtca gcctcggcag gagtcccact 1550 cctcctgggg tgctgcctgc caccaagagc tcccccacct gtaccaccat 1600 gtgggactcc aggcaccatc tgttctcccc agggacctgc tgacttgaat 1650 gccagccctt gctcctctgt gttgctttgg gccacctggg gctgcacccc 1700 ctgccctttc tctgccccat ccctacccta gccttgctct cagccacctt 1750 gatagtcact gggctccctg tgacttctga ccctgacacc cctcccttgg 1800 actctgcctg ggctggagtc tagggctggg gctacatttg gcttctgtac 1850 tggctgagga caggggaggg agtgaagttg gtttggggtg gcctgtgttg 1900 ccactctcag caccccacat ttgcatctgc tggtggacct gccaccatca 1950 caataaagtc cccatctgat ttttaaaaaa aaaaaaaaa : 1989 <210> 77 <211> 341 566 <212> PRT <213> Homo sapiens <400> 77 Met Ala Leu Pro Ser Arg Ile Leu Leu Trp Lys Leu Val Leu Leu 15 10 15 Gin Ser Ser Ala Val Leu Leu His Ser Ala Val Glu Glu Thr Asp 20 25 30 Ala Gly Leu Tyr Thr Cys Asn Leu His His His Tyr Cys His Leu 35 40 45 Tyr Glu Ser Leu Ala Val Arg Leu Glu Val Thr Asp Gly Pro Pro 50 55 60 Ala Thr Pro Ala Tyr Trp Asp Gly Glu Lys Glu Val Leu Ala Val 65 70 75 Ala Arg Gly Ala Pro Ala Leu Leu Thr Cys Val Asn Arg Gly His 80 85 90 Val Trp Thr Asp Arg His Val Glu Glu Ala Gin Gin Val Val His 95 100 105 Trp Asp Arg Gin Pro Pro Gly Val Pro His Asp Arg Ala Asp Arg 110 115 120 Leu Leu Asp Leu Tyr Ala Ser Gly Glu Arg Arg Ala Tyr Gly Pro 125 130 135 Leu Phe Leu Arg Asp Arg Val Ala Val Gly Ala Asp Ala Phe Glu 140 145 150 Arg Gly Asp Phe Ser Leu Arg Ile Glu Pro Leu Glu Val Ala Asp 155 160 165 Glu Gly Thr Tyr Ser Cys His Leu His His His Tyr Cys Gly Leu 170 175 180 His Glu Arg Arg Val Phe His Leu Thr Val Ala Glu Pro His Ala 185 190 195 Glu Pro Pro Pro Arg Gly Ser Pro Gly Asn Gly Ser Ser His Ser 200 205 210 Gly Ala Pro Gly Pro Asp Pro Thr Leu Ala Arg Gly His Asn Val 215 220 225 Ile Asn Val Ile Val Pro Glu Ser Arg Ala His Phe Phe Gin Gin 230 235 240 Leu Gly Tyr Val Leu Ala Thr Leu Leu Leu Phe Ile Leu Leu Leu 245 250 255 Val Thr Val Leu Leu Ala Ala Arg Arg Arg Arg Gly Gly Tyr Glu 260 265 270 Tyr Ser Asp Gin Lys Ser Gly Lys Ser Lys Gly Lys Asp Val Asn 275 280 285 Leu Ala Glu Phe Ala Val Ala Ala Gly Asp Gin Met Leu Tyr Arg 567 290 295 300 Ser Glu Asp Ile Gin Leu Asp Tyr Lys Asn Asn Ile Leu Lys Glu 305 310 315 Arg Ala Glu Leu Ala His Ser Pro Leu Pro Ala Lys Tyr lie Asp 320 325 330 Leu Asp Lys Gly Phe Arg Lys Glu Asn Cys Lys 335 340 <210> 78 <211> 2243 <212> DNA <213> Homo sapiens <400> 78 cgccggaggc agcggcggcg tggcgcagcg gcgacatggc cgttgtctca 50 gaggacgact ttcagcacag ttcaaactcc acctacggaa ccacaagcag 100 cagtctccga gctgaccagg aggcactgct tgagaagctg ctggaccgcc 150 cgccccctgg cctgcagagg cccgaggacc gcttctgtgg cacatacatc 200 atcttcttca gcctgggcat tggcagtcta ctgccatgga acttctttat 250 cactgccaag gagtactgga tgttcaaact ccgcaactcc tccagcccag 300 ccaccgggga ggaccctgag ggctcagaca tcctgaacta ctttgagagc 350 taccttgccg ttgcctccac cgtgccctcc atgctgtgcc tggtggccaa 400 cttcctgctt gtcaacaggg ttgcagtcca catccgtgtc ctggcctcac 450 tgacggtcat cctggccatc ttcatggtga taactgcact ggtgaaggtg 500 gacacttcct cctggacccg tggttttttt gcggtcacca ttgtctgcat 550 ggtgatcctc agcggtgcct ccactgtctt cagcagcagc atctacggca 600 tgaccggctc ctttcctatg aggaactccc aagcactgat atcaggagga 650 gccatgggcg ggacggtcag cgccgtggcc tcattggtgg acttggctgc 700 atccagtgat gtgaggaaca gcgccctggc cttcttcctg acggccacca 750 tcttcctcgt gctctgcatg ggactctacc tgctgctgtc caggctggag 800 tatgccaggt actacatgag gcctgttctt gcggcccatg tgttttctgg 850 tgaagaggag cttccccagg actccctcag tgccccttcg gtggcctcca 900 gattcattga ttcccacaca ccccctctcc gccccatcct gaagaagacg 950 gccagcctgg gcttctgtgt cacctacgtc ttcttcatca ccagcctcat 1000 ctaccccgcc gtctgcacca acatcgagtc cctcaacaag ggctcgggct 1050 cactgtggac caccaagttt ttcatccccc tcactacctt cctcctgtac 1100 aactttgctg acctatgtgg ccggcagctc accgcctgga tccaggtgcc 1150 568 agggcccaac agcaaggcgc tcccagggtt cgtgctcctc cggacctgcc 1200 tcatccccct cttcgtgctc tgtaactacc agccccgcgt ccacctgaag 1250 actgtggtct tccagtccga tgtgtacccc gcactcctca gctccctgct 1300 ggggctcagc aacggctacc tcagcaccct ggccctcctc tacgggccta 1350 agattgtgcc cagggagctg gctgaggcca cgggagtggt gatgtccttt 1400 tatgtgtgct tgggcttaac actgggctca gcctgctcta ccctcctggt 1450 gcacctcatc tagaagggag gacacaagga cattggtgct tcagagcctt 1500 tgaagatgag aagagagtgc aggagggctg ggggccatgg aggaaaggcc 1550 taaagtttca cttggggaca gagagcagag cacactcggg cctcatccct 1600 cccaagatgc cagtgagcca cgtccatgcc cattccgtgc aaggcagata 1650 ttccagtcat attaacagaa cactcctgag acagttgaag aagaaatagc 1700 acaaatcagg ggtactccct tcacagctga tggttaacat tccaccttct 1750 ttctagccct tcaaagatgc tgccagtgtt cgccctagag ttattacaaa 1800 gccagtgcca aaacccagcc atgggctctt tgcaacctcc cagctgcgct 1850 cattccagct gacagcgaga tgcaagcaaa tgctcagctc tccttaccct 1900 gaaggggtct ccctggaatg gaagtcccct ggcatggtca gtcctcaggc 1950 ccaagactca agtgtgcaca gacccctgtg ttctgcgggt gaacaactgc 2000 ccactaacca gactggaaaa cccagaaaga tgggccttcc atgaatgctt 2050 cattccagag ggaccagagg gcctccctgt gcaagggatc aagcatgtct 2100 ggcctgggtt ttcaaaaaaa gagggatcct catgacctgg tggtctatgg 2150 cctgggtcaa gatgagggtc tttcagtgtt cctgtttaca acatgtcaaa 2200 gccattggtt caagggcgta ataaatactt gcgtattcaa aaa 2243 <210> 79 <211> 475 <212> PRT <213> Homo sapiens <400> 79 Met Ala Val Val Ser Glu Asp Asp Phe Gin His Ser Ser Asn Ser 15 10 15 Thr Tyr Gly Thr Thr Ser Ser Ser Leu Arg Ala Asp Gin Glu Ala 20 25 30 Leu Leu Glu Lys Leu Leu Asp Arg Pro Pro Pro Gly Leu Gin Arg 35 40 45 Pro Glu Asp Arg Phe Cys Gly Thr Tyr Ile Ile Phe Phe Ser Leu 50 55 60 569 Gly Ile Gly Ser Leu Leu Pro Trp Asn Phe Phe Ile Thr Ala Lys 65 70 75 Glu Tyr Trp Met Phe Lys Leu Arg Asn Ser Ser Ser Pro Ala Thr 80 85 90 Gly Glu Asp Pro Glu Gly Ser Asp Ile Leu Asn Tyr Phe Glu Ser 95 100 105 Tyr Leu Ala Val Ala Ser Thr Val Pro Ser Met Leu Cys Leu Val 110 115 120 Ala Asn Phe Leu Leu Val Asn Arg Val Ala Val His Ile Arg Val 125 130 135 Leu Ala Ser Leu Thr Val Ile Leu Ala Ile Phe Met Val Ile Thr 140 145 150 Ala Leu Val Lys Val Asp Thr Ser Ser Trp Thr Arg Gly Phe Phe 155 160 165 Ala Val Thr Ile Val Cys Met Val Ile Leu Ser Gly Ala Ser Thr 170 175 180 Val Phe Ser Ser Ser Ile Tyr Gly Met Thr Gly Ser Phe Pro Met 185 190 195 Arg Asn Ser Gin Ala Leu Ile Ser Gly Gly Ala Met Gly Gly Thr 200 205 210 Val Ser Ala Val Ala Ser Leu Val Asp Leu Ala Ala Ser Ser Asp 215 220 225 Val Arg Asn Ser Ala Leu Ala Phe Phe Leu Thr Ala Thr Ile Phe 230 235 240 Leu Val Leu Cys Met Gly Leu Tyr Leu Leu Leu Ser Arg Leu Glu 245 250 255 Tyr Ala Arg Tyr Tyr Met Arg Pro Val Leu Ala Ala His Val Phe 260 265 270 Ser Gly Glu Glu Glu Leu Pro Gin Asp Ser Leu Ser Ala Pro Ser 275 280 285 Val Ala Ser Arg Phe Ile Asp Ser His Thr Pro Pro Leu Arg Pro 290 295 300 Ile Leu Lys Lys Thr Ala Ser Leu Gly Phe Cys Val Thr Tyr Val 305 310 315 Phe Phe Ile Thr Ser Leu Ile Tyr Pro Ala Val Cys Thr Asn Ile 320 325 330 Glu Ser Leu Asn Lys Gly Ser Gly Ser Leu Trp Thr Thr Lys Phe 335 340 345 Phe Ile Pro Leu Thr Thr Phe Leu Leu Tyr Asn Phe Ala Asp Leu 350 355 360 Cys Gly Arg Gin Leu Thr Ala Trp Ile Gin Val Pro Gly Pro Asn 365 570 370 375 Ser Lys Ala Pro Leu Phe Thr Val Val Leu Leu Gly Tyr Gly Pro Val Val Met Ala Cys Ser <210> 80 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 80 ttttgcggtc accattgtct gc 22 <210> 81 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 81 cgtaggtgac acagaagccc agg 23 <210> 82 <211> 49 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 82 tacggcatga ccggctcctt tcctatgagg aactcccagg cactgatat 49 <210> 83 <211> 1844 <212> DNA <213> Homo sapiens Leu Pro Gly Phe Val Leu Leu Arg Thr Cys Leu Ile 380 385 390 Val Leu Cys Asn Tyr Gin Pro Arg Val His Leu Lys 395 400 405 Phe Gin Ser Asp Val Tyr Pro Ala Leu Leu Ser Ser 410 415 420 Leu Ser Asn Gly Tyr Leu Ser Thr Leu Ala Leu Leu 425 430 435 Lys Ile Val Pro Arg Glu Leu Ala Glu Ala Thr Gly 440 445 450 Ser Phe Tyr Val Cys Leu Gly Leu Thr Leu Gly Ser 455 460 465 Thr Leu Leu Val His Leu Ile 470 475 <400> 83 571 gacagtggag ggcagtggag aggaccgcgc tgtcctgctg tcaccaagag 50 ctggagacac catctcccac cgagagtcat ggccccattg gccctgcacc 100 tcctcgtcct cgtccccatc ctcctcagcc tggtggcctc ccaggactgg 150 aaggctgaac gcagccaaga ccccttcgag aaatgcatgc aggatcctga 200 ctatgagcag ctgctcaagg tggtgacctg ggggctcaat cggaccctga 250 agccccagag ggtgattgtg gttggcgctg gtgtggccgg gctggtggcc 300 gccaaggtgc tcagcgatgc tggacacaag gtcaccatcc tggaggcaga 350 taacaggatc gggggccgca tcttcaccta ccgggaccag aacacgggct 400 ggattgggga gctgggagcc atgcgcatgc ccagctctca caggatcctc 450 cacaagctct gccagggcct ggggctcaac ctgaccaagt tcacccagta 500 cgacaagaac acgtggacgg aggtgcacga agtgaagctg cgcaactatg 550 tggtggagaa ggtgcccgag aagctgggct acgccttgcg tccccaggaa 600 aagggccact cgcccgaaga catctaccag atggctctca accaggccct 650 caaagacctc aaggcactgg gctgcagaaa ggcgatgaag aagtttgaaa 700 ggcacacgct cttggaatat cttctcgggg aggggaacct gagccggccg 750 gccgtgcagc ttctgggaga cgtgatgtcc gaggatggct tcttctatct 800 cagcttcgcc gaggccctcc gggcccacag ctgcctcagc gacagactcc 850 agtacagccg catcgtgggt ggctgggacc tgctgccgcg cgcgctgctg 900 agctcgctgt ccgggcttgt gctgttgaac gcgcccgtgg tggcgatgac 950 ccagggaccg cacgatgtgc acgtgcagat cgagacctct cccccggcgc 1000 ggaatctgaa ggtgctgaag gccgacgtgg tgctgctgac ggcgagcgga 1050 ccggcggtga agcgcatcac cttctcgccg ccgctgcccc gccacatgca 1100 ggaggcgctg cggaggctgc actacgtgcc ggccaccaag gtgttcctaa 1150 gcttccgcag gcccttctgg cgcgaggagc acattgaagg cggccactca 1200 aacaccgatc gcccgtcgcg catgattttc tacccgccgc cgcgcgaggg 1250 cgcgctgctg ctggcctcgt acacgtggtc ggacgcggcg gcagcgttcg 1300 ccggcttgag ccgggaagag gcgttgcgct tggcgctcga cgacgtggcg 1350 gcattgcacg ggcctgtcgt gcgccagctc tgggacggca ccggcgtcgt 1400 caagcgttgg gcggaggacc agcacagcca gggtggcttt gtggtacagc 1450 cgccggcgct ctggcaaacc gaaaaggatg actggacggt cccttatggc 1500 cgcatctact ttgccggcga gcacaccgcc tacccgcacg gctgggtgga 1550 572 gacggcggtc aagtcggcgc tgcgcgccgc catcaagatc aacagccgga 1600 aggggcctgc atcggacacg gccagccccg aggggcacgc atctgacatg 1650 gaggggcagg ggcatgtgca tggggtggcc agcagcccct cgcatgacct 17 00 ggcaaaggaa gaaggcagcc accctccagt ccaaggccag ttatctctcc 1750 aaaacacgac ccacacgagg acctcgcatt aaagtatttt cggaaaaaaa 1800 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaa 1844 <210> 84 <211> 567 <212> PRT <213> Homo sapiens <400> 84 Met Ala Pro Leu Ala Leu His Leu Leu Val Leu Val Pro Ile Leu 15 10 15 Leu Ser Leu Val Ala Ser Gin Asp Trp Lys Ala Glu Arg Ser Gin 20 25 30 Asp Pro Phe Glu Lys Cys Met Gin Asp Pro Asp Tyr Glu Gin Leu 35 40 45 Leu Lys Val Val Thr Trp Gly Leu Asn Arg Thr Leu Lys Pro Gin 50 55 60 Arg Val Ile Val Val Gly Ala Gly Val Ala Gly Leu Val Ala Ala 65 70 75 Lys Val Leu Ser Asp Ala Gly His Lys Val Thr Ile Leu Glu Ala 80 85 90 Asp Asn Arg Ile Gly Gly Arg Ile Phe Thr Tyr Arg Asp Gin Asn 95 100 105 Thr Gly Trp Ile Gly Glu Leu Gly Ala Met Arg Met Pro Ser Ser 110 115 120 His Arg Ile Leu His Lys Leu Cys Gin Gly Leu Gly Leu Asn Leu 125 130 135 Thr Lys Phe Thr Gin Tyr Asp Lys Asn Thr Trp Thr Glu Val His 140 145 150 Glu Val Lys Leu Arg Asn Tyr Val Val Glu Lys Val Pro Glu Lys 155 160 165 Leu Gly Tyr Ala Leu Arg Pro Gin Glu Lys Gly His Ser Pro Glu 170 175 • 180 Asp Ile Tyr Gin Met Ala Leu Asn Gin Ala Leu Lys Asp Leu Lys 185 190 195 Ala Leu Gly Cys Arg Lys Ala Met Lys Lys Phe Glu Arg His Thr 200 205 210 Leu Leu Glu Tyr Leu Leu Gly Glu Gly Asn Leu Ser Arg Pro Ala 215 220 225 573 Val Gin Leu Leu Gly Asp Val Met Ser Glu Asp Gly Phe Phe Tyr 230 235 240 Leu Ser Phe Ala Glu Ala Leu Arg Ala His Ser Cys Leu Ser Asp 245 250 255 Arg Leu Gin Tyr Ser Arg Ile Val Gly Gly Trp Asp Leu Leu Pro 260 265 270 Arg Ala Leu Leu Ser Ser Leu Ser Gly Leu Val Leu Leu Asn Ala 275 280 285 Pro Val Val Ala Met Thr Gin Gly Pro His Asp Val His Val Gin 290 295 300 Ile Glu Thr Ser Pro Pro Ala Arg Asn Leu Lys Val Leu Lys Ala 305 310 315 Asp Val Val Leu Leu Thr Ala Ser Gly Pro Ala Val Lys Arg Ile 320 325 330 Thr Phe Ser Pro Pro Leu Pro Arg His Met Gin Glu Ala Leu Arg 335 340 345 Arg Leu His Tyr Val Pro Ala Thr Lys Val Phe Leu Ser Phe Arg 350 355 360 Arg Pro Phe Trp Arg Glu Glu His Ile Glu Gly Gly His Ser Asn 365 370 375 Thr Asp Arg Pro Ser Arg Met Ile Phe Tyr Pro Pro Pro Arg Glu 380 385 390 Gly Ala Leu Leu Leu Ala Ser Tyr Thr Trp Ser Asp Ala Ala Ala 395 400 405 Ala Phe Ala Gly Leu Ser Arg Glu Glu Ala Leu Arg Leu Ala Leu 410 415 420 Asp Asp Val Ala Ala Leu His Gly Pro Val Val Arg Gin Leu Trp 425 430 435 Asp Gly Thr Gly Val Val Lys Arg Trp Ala Glu Asp Gin His Ser 440 445 450 Gin Gly Gly Phe Val Val Gin Pro Pro Ala Leu Trp Gin Thr Glu 455 460 465 Lys Asp Asp Trp Thr Val Pro Tyr Gly Arg Ile Tyr Phe Ala Gly 470 475 480 Glu His Thr Ala Tyr Pro His Gly Trp Val Glu Thr Ala Val Lys 485 490 495 Ser Ala Leu Arg Ala Ala Ile Lys Ile Asn Ser Arg Lys Gly Pro 500 505 510 Ala Ser Asp Thr Ala Ser Pro Glu Gly His Ala Ser Asp Met Glu 515 520 525 Gly Gin Gly His Val His Gly Val Ala Ser Ser Pro Ser His Asp 530 535 540 574 Leu Ala Lys Glu Glu Gly Ser His Pro Pro Val Gin Gly Gin Leu 545 550 555 Ser Leu Gin Asn Thr Thr His Thr Arg Thr Ser His 560 565 <210> 85 <211> 3316 <212> DNA <213> Homo sapiens <400> 85 ctgacatggc ctgactcggg acagctcaga gcagggcaga actggggaca 50 ctctgggccg gccttctgcc tgcatggacg ctctgaagcc accctgtctc 100 tggaggaacc acgagcgagg gaagaaggac agggactcgt gtggcaggaa 150 gaactcagag ccgggaagcc cccattcact agaagcactg agagatgcgg 200 ccccctcgca gggtctgaat ttcctgctgc tgttcacaaa gatgcttttt 250 atctttaact ttttgttttc cccacttccg accccggcgt tgatctgcat 300 cctgacattt ggagctgcca tcttcttgtg gctgatcacc agacctcaac 350 ccgtcttacc tcttcttgac ctgaacaatc agtctgtggg aattgaggga 400 ggagcacgga agggggtttc ccagaagaac aatgacctaa caagttgctg 450 cttctcagat gccaagacta tgtatgaggt tttccaaaga ggactcgctg 500 tgtctgacaa tgggccctgc ttgggatata gaaaaccaaa ccagccctac 550 agatggctat cttacaaaca ggtgtctgat agagcagagt acctgggttc 600 ctgtctcttg cataaaggtt ataaatcatc accagaccag tttgtcggca 650 tctttgctca gaataggcca gagtggatca tctccgaatt ggcttgttac 700 acgtactcta tggtagctgt acctctgtat gacaccttgg gaccagaagc 750 catcgtacat attgtcaaca aggctgatat cgccatggtg atctgtgaca 800 caccccaaaa ggcattggtg ctgataggga atgtagagaa aggcttcacc 850 ccgagcctga aggtgatcat ccttatggac ccctttgatg atgacctgaa 900 gcaaagaggg gagaagagtg gaattgagat cttatcccta tatgatgctg 950 agaacctagg caaagagcac ttcagaaaac ctgtgcctcc tagcccagaa 1000 gacctgagcg tcatctgctt caccagtggg accacaggtg accccaaagg 1050 agccatgata acccatcaaa atattgtttc aaatgctgct gcctttctca 1100 aatgtgtgga gcatgcttat gagcccactc ctgatgatgt ggccatatcc 1150 tacctccctc tggctcatat gtttgagagg attgtacagg ctgttgtgta 1200 cagctgtgga gccagagttg gattcttcca aggggatatt cggttgctgg 1250 575 ctgacgacat gaagactttg aagcccacat tgtttcccgc ggtgcctcga 1300 ctccttaaca ggatctacga taaggtacaa aatgaggcca agacaccctt 1350 gaagaagttc ttgttgaagc tggctgtttc cagtaaattc aaagagcttc 1400 aaaagggtat catcaggcat gatagtttct gggacaagct catctttgca 1450 aagatccagg acagcctggg cggaagggtt cgtgtaattg tcactggagc 1500 tgcccccatg tccacttcag tcatgacatt cttccgggca gcaatgggat 1550 gtcaggtgta tgaagcttat ggtcaaacag aatgcacagg tggctgtaca 1600 tttacattac ctggggactg gacatcaggt cacgttgggg tgcccctggc 1650 ttgcaattac gtgaagctgg aagatgtggc tgacatgaac tactttacag 1700 tgaataatga tacctgaagg aggagaggtc accctgagaa tgcatcaagg gacacaggaa gtacaaacgt gccctggaca gttcaaagga gtgatggctg 1750 1800 gcttcacaca ggagacattg gtcgctggct cccgaatgga actctgaaga 1850 tcatcgaccg taaaaagaac attttcaagc tggcccaagg agaatacatt 1900 gcaccagaga agatagaaaa tatctacaac aggagtcaac cagtgttaca 1950 aatttttgta cacggggaga gcttacggtc atccttagta ggagtggtgg 2000 ttcctgacac agatgtactt ccctcatttg cagccaagct tggggtgaag 2050 ggctcctttg aggaactgtg ccaaaaccaa gttgtaaggg aagccatttt 2100 agaagacttg cagaaaattg ggaaagaaag tggccttaaa acttttgaac 2150 aggtcaaagc catttttctt catccagagc cattttccat tgaaaatggg 2200 ctcttgacac caacattgaa agcaaagcga ggagagcttt ccaaatactt 2250 tcggacccaa attgacagcc tgtatgagca catccaggat taggataagg 2300 tacttaagta cctgccggcc cactgtgcac tgcttgtgag aaaatggatt 2350 aaaaactatt cttacatttg ttttgccttt cctcctattt ttttttaacc 2400 tgttaaactc taaagccata gcttttgttt tatattgaga catataatgt 2450 gtaaacttag ttcccaaata aatcaatcct gtctttccca tcttcgatgt 2500 tgctaatatt aaggcttcag ggctactttt atcaacatgc ctgtcttcaa 2550 gatcccagtt tatgttctgt gtccttcctc atgatttcca accttaatac 2600 tattagtaac cacaagttca agggtcaaag ggaccctctg tgccttcttc 2650 tttgttttgt gataaacata acttgccaac agtctctatg cttatttaca 2700 tcttctactg ttcaaactaa gagattttta aattctgaaa aactgcttac 2750 aattcatgtt ttctagccac tccacaaacc actaaaattt tagttttagc 2800 576 ctatcactca tgtcaatcat atctatgaga caaatgtctc cgatgctctt 2850 ctgcgtaaat taaattgtgt actgaaggga aaagtttgat cataccaaac 2900 atttcctaaa ctctctagtt agatatctga cttgggagta ttaaaaattg 2950 ggtctatgac atactgtcca aaaggaatgc tgttcttaaa gcattattta 3000 cagtaggaac tggggagtaa atctgttccc tacagtttgc tgctgagctg 3050 gaagctgtgg gggaaggagt tgacaggtgg gcccagtgaa cttttccagt 3100 aaatgaagca agcactgaat aaaaacctcc tgaactggga acaaagatct 3150 acaggcaagc aagatgccca cacaacaggc ttattttctg tgaaggaacc 3200 aactgatctc ccccaccctt ggattagagt tcctgctcta ccttacccac 32 50 agataacaca tgttgtttct acttgtaaat gtaaagtctt taaaataaac 3300 tattacagat aaaaaa 3316 <210> 86 <211> 739 <212> PRT <213> Homo sapiens <400> 86 Met Asp Ala Leu Lys Pro Pro Cys Leu Trp Arg Asn His Glu Arg 15 10 15 Gly Lys Lys Asp Arg Asp Ser Cys Gly Arg Lys Asn Ser Glu Pro 20 25 30 Gly Ser Pro His Ser Leu Glu Ala Leu Arg Asp Ala Ala Pro Ser 35 40 45 Gin Gly Leu Asn Phe Leu Leu Leu Phe Thr Lys Met Leu Phe Ile 50 55 60 Phe Asn Phe Leu Phe Ser Pro Leu Pro Thr Pro Ala Leu Ile Cys 65 70 75 Ile Leu Thr Phe Gly Ala Ala Ile Phe Leu Trp Leu Ile Thr Arg 80 85 90 Pro Gin Pro Val Leu Pro Leu Leu Asp Leu Asn Asn Gin Ser Val 95 100 105 Gly Ile Glu Gly Gly Ala Arg Lys Gly Val Ser Gin Lys Asn Asn 110 115 120 Asp Leu Thr Ser Cys Cys Phe Ser Asp Ala Lys Thr Met Tyr Glu 125 130 135 Val Phe Gin Arg Gly Leu Ala Val Ser Asp Asn Gly Pro Cys Leu 140 145 150 Gly Tyr Arg Lys Pro Asn Gin Pro Tyr Arg Trp Leu Ser Tyr Lys 155 160 165 Gin Val Ser Asp Arg Ala Glu Tyr Leu Gly Ser Cys Leu Leu His 170 175 180 577 Lys Gly Tyr Lys Ser Ser Pro Asp Gin Phe Val Gly lie Phe Ala 185 190 195 Gin Asn Arg Pro Glu Trp Ile Ile Ser Glu Leu Ala Cys Tyr Thr 200 205 210 Tyr Ser Met Val Ala Val Pro Leu Tyr Asp Thr Leu Gly Pro Glu 215 220 225 Ala Ile Val His Ile Val Asn Lys Ala Asp Ile Ala Met Val Ile 230 235 240 Cys Asp Thr Pro Gin Lys Ala Leu Val Leu Ile Gly Asn Val Glu 245 250 255 Lys Gly Phe Thr Pro Ser Leu Lys Val lie Ile Leu Met Asp Pro 260 265 270 Phe Asp Asp Asp Leu Lys Gin Arg Gly Glu Lys Ser Gly Ile Glu 275 280 285 Ile Leu Ser Leu Tyr Asp Ala Glu Asn Leu Gly Lys Glu His Phe 290 295 300 Arg Lys Pro Val Pro Pro Ser Pro Glu Asp Leu Ser Val Ile Cys 305 310 315 Phe Thr Ser Gly Thr Thr Gly Asp Pro Lys Gly Ala Met Ile Thr 320 325 330 His Gin Asn Ile Val Ser Asn Ala Ala Ala Phe Leu Lys Cys Val 335 340 345 Glu His Ala Tyr Glu Pro Thr Pro Asp Asp Val Ala Ile Ser Tyr 350 355 360 Leu Pro Leu Ala His Met Phe Glu Arg Ile Val Gin Ala Val Val 365 370 375 Tyr Ser Cys Gly Ala Arg Val Gly Phe Phe Gin Gly Asp Ile Arg 380 385 390 Leu Leu Ala Asp Asp Met Lys Thr Leu Lys Pro Thr Leu Phe Pro 395 400 405 Ala Val Pro Arg Leu Leu Asn Arg Ile Tyr Asp Lys Val Gin Asn 410 415 420 Glu Ala Lys Thr Pro Leu Lys Lys Phe Leu Leu Lys Leu Ala Val 425 430 435 Ser Ser Lys Phe Lys Glu Leu Gin Lys Gly Ile Ile Arg His Asp 440 445 450 Ser Phe Trp Asp Lys Leu Ile Phe Ala Lys Ile Gin Asp Ser Leu 455 460 465 Gly Gly Arg Val Arg Val Ile Val Thr Gly Ala Ala Pro Met Ser 470 475 480 Thr Ser Val Met Thr Phe Phe Arg Ala Ala Met Gly Cys Gin Val 578 485 490 495 Tyr Glu Ala Tyr Gly Gin Thr Glu Cys Thr Gly Gly Cys Thr Phe 500 505 510 Thr Leu Pro Gly Asp Trp Thr Ser Gly His Val Gly Val Pro Leu 515 520 525 Ala Cys Asn Tyr Val Lys Leu Glu Asp Val Ala Asp Met Asn Tyr 530 535 540 Phe Thr Val Asn Asn Glu Gly Glu Val Cys Ile Lys Gly Thr Asn 545 550 555 Val Phe Lys Gly Tyr Leu Lys Asp Pro Glu Lys Thr Gin Glu Ala 560 565 570 Leu Asp Ser Asp Gly Trp Leu His Thr Gly Asp Ile Gly Arg Trp 575 580 585 Leu Pro Asn Gly Thr Leu Lys Ile Ile Asp Arg Lys Lys Asn Ile 590 595 600 Phe Lys Leu Ala Gin Gly Glu Tyr Ile Ala Pro Glu Lys Ile Glu 605 610 615 Asn Ile Tyr Asn Arg Ser Gin Pro Val Leu Gin Ile Phe Val His 620 625 630 Gly Glu Ser Leu Arg Ser Ser Leu Val Gly Val Val Val Pro Asp 635 640 645 Thr Asp Val Leu Pro Ser Phe Ala Ala Lys Leu Gly Val Lys Gly 650 655 660 Ser Phe Glu Glu Leu Cys Gin Asn Gin Val Val Arg Glu Ala Ile 665 670 675 Leu Glu Asp Leu Gin Lys Ile Gly Lys Glu Ser Gly Leu Lys Thr 680 685 690 Phe Glu Gin Val Lys Ala Ile Phe Leu His Pro Glu Pro Phe Ser 695 700 705 Ile Glu Asn Gly Leu Leu Thr Pro Thr Leu Lys Ala Lys Arg Gly 710 715 720 Glu Leu Ser Lys Tyr Phe Arg Thr Gin Ile Asp Ser Leu Tyr Glu 725 730 735 His Ile Gin Asp <210> 87 <211> 2725 <212> DNA <213> Homo sapiens <400> 87 ggaggcggag gccgcggcga gccgggccga gcagtgaggg ccctagcggg 50 gcccgagcgg ggcccggggc ccctaagcca ttcctgaagt catgggctgg 100 579 ccaggacatt ggtgacccgc caatccggta tggacgactg gaagcccagc 150 cccctcatca agccctttgg ggctcggaag aagcggagct ggtaccttac 200 ctggaagtat aaactgacaa accagcgggc cctgcggaga ttctgtcaga 250 caggggccgt gcttttcctg ctggtgactg tcattgtcaa tatcaagttg 300 atcctggaca ctcggcgagc catcagtgaa gccaatgaag acccagagcc 350 agagcaagac tatgatgagg ccctaggccg cctggagccc ccacggcgca 400 gaggcagtgg tccccggcgg gtcctggacg tagaggtgta ttcaagtcgc 450 agcaaagtat atgtggcagt ggatggcacc acggtgctgg aggatgaggc 500 ccgggagcag ggccggggca tccatgtcat tgtcctcaac caggccacgg 550 gccacgtgat ggcaaaacgt gtgtttgaca cgtactcacc tcatgaggat 600 gaggccatgg tgctattcct caacatggta gcgcccggcc gagtgctcat 650 ctgcactgtc ctctgctgag aaggatgagg gagcctgggc gctccttcca agccaggctg cctcaaggac gccctgccct acagccaagg gggctggagg 700 750 gacacatggg ccttcgtggg acgaaaagga ggtcctgtct tcggggagaa 800 acattctaag tcacctgccc tctcttcctg gggggaccca gtcctgctga 850 agacagatgt gccattgagc tcagcagaag aggcagagtg ccactgggca 900 gacacagagc tgaaccgtcg ccgccggcgc ttctgcagca aagttgaggg 950 ctatggaagt gtatgcagct gcaaggaccc cacacccatc gagttcagcc 1000 ctgacccact cccagacaac aaggtcctca atgtgcctgt ggctgtcatt 1050 gcagggaacc gacccaatta cctgtacagg atgctgcgct ctctgctttc 1100 agcccagggg gtgtctcctc agatgataac agttttcatt gacggctact 1150 atgaggaacc catggatgtg gtggcactgt ttggtctgag gggcatccag 1200 catactccca tcagcatcaa gaatgcccgc gtgtctcagc actacaaggc 1250 cagcctcact gccactttca acctgtttcc ggaggccaag tttgctgtgg 1300 ttctggaaga ggacctggac attgctgtgg attttttcag tttcctgagc 1350 caatccatcc acctactgga ggaggatgac agcctgtact gcatctctgc 1400 ctggaatgac caggggtatg aacacacggc tgaggaccca gcactactgt 1450 accgtgtgga gaccatgcct gggctgggct gggtgctcag gaggtccttg 1500 tacaaggagg agcttgagcc caagtggcct acaccggaaa agctctggga 1550 ttgggacatg tggatgcgga tgcctgaaca acgccggggc cgagagtgca 1600 tcatccctga cgtttcccga tcctaccact ttggcatcgt cggcctcaac 1650 580 atgaatggct actttcacga ggcctacttc aagaagcaca agttcaacac 17 00 ggttccaggt gtccagctca ggaatgtgga cagtctgaag aaagaagctt 1750 atgaagtgga agttcacagg ctgctcagtg aggctgaggt tctggaccac 1800 agcaagaacc cttgtgaaga ctctttcctg ccagacacag agggccacac 1850 ctacgtggcc tttattcgaa tggagaaaga tgatgacttc accacctgga 1900 cccagcttgc caagtgcctc catatctggg acctggatgt gcgtggcaac 1950 catcggggcc tgtggagatt gtttcggaag aagaaccact tcctggtggt 2000 gggggtcccg gcttccccct actcagtgaa gaagccaccc tcagtcaccc 2050 caattttcct ggagccaccc ccaaaggagg agggagcccc aggagcccca 2100 gaacagacat gagacctcct ccaggaccct gcggggctgg gtactgtgta 2150 cccccaggct ggctagccct tccctccatc ctgtaggatt ttgtagatgc 2200 tggtaggggc tggggctacc ttgtttttaa catgagactt aattactaac 2250 tccaagggga ctatttattt gggttcccct acttccttgt gctccaacac tggagaaggg cccgttcctg caggagagta agttaaaagt cctgggaatc 2300 2350 attacgatcc ctagcagctc atcctgccct ttgaataccc tcactttcca 2400 ggcctggctc agaatctaac ctatttattg actgtcctga gggccttgaa 2450 aacaggccga acctggaggg cctggatttc tttttgggct ggaatgctgc 2500 cctgagggtg gggctggctc ttactcagga aactgctgtg cccaacccat 2550 ggacaggccc agctggggcc cacatgctga cacagactca ctcagagacc 2600 cttagacact ggaccaggcc tcctctcagc cttctctttg tccagatttc 2650 caaagctgga taagttggtc attgattaaa aaaggagaag ccctctggga 2700 aaaaaaaaaa aaaaaaaaaa aaaaa 2725 <210> 88 <211> 660 <212> PRT <213> Homo sapiens <400> 88 Met Asp Asp Trp Lys Pro Ser Pro Leu Ile Lys Pro Phe Gly Ala 15 10 15 Arg Lys Lys Arg Ser Trp Tyr Leu Thr Trp Lys Tyr Lys Leu Thr 20 25 30 Asn Gin Arg Ala Leu Arg Arg Phe Cys Gin Thr Gly Ala Val Leu 35 40 45 Phe Leu Leu Val Thr Val Ile Val Asn Ile Lys Leu Ile Leu Asp 50 55 60 Thr Arg Arg Ala Ile Ser Glu Ala Asn Glu Asp Pro Glu Pro Glu 65 581 70 75 Gin Asp Tyr Asp Glu Ala Leu Gly Arg Leu Glu Pro Pro Arg Arg 80 85 90 Arg Gly Ser Gly Pro Arg Arg Val Leu Asp Val Glu Val Tyr Ser 95 100 105 Ser Arg Ser Lys Val Tyr Val Ala Val Asp Gly Thr Thr Val Leu 110 115 120 Glu Asp Glu Ala Arg Glu Gin Gly Arg Gly Ile His Val Ile Val 125 130 135 Leu Asn Gin Ala Thr Gly His Val Met Ala Lys Arg Val Phe-Asp 140 145 150 Thr Tyr Ser Pro His Glu Asp Glu Ala Met Val Leu Phe Leu Asn 155 160 165 Met Val Ala Pro Gly Arg Val Leu Ile Cys Thr Val Lys Asp Glu 170 175 180 Gly Ser Phe His Leu Lys Asp Thr Ala Lys Ala Leu Leu Arg Ser 185 190 195 Leu Gly Ser Gin Ala Gly Pro Ala Leu Gly Trp Arg Asp Thr Trp 200 205 210 Ala Phe Val Gly Arg Lys Gly Gly Pro Val Phe Gly Glu Lys His 215 220 225 Ser Lys Ser Pro Ala Leu Ser Ser Trp Gly Asp Pro Val Leu Leu 230 235 240 Lys Thr Asp Val Pro Leu Ser Ser Ala Glu Glu Ala Glu Cys His 245 250 255 Trp Ala Asp Thr Glu Leu Asn Arg Arg Arg Arg Arg Phe Cys Ser 260 265 270 Lys Val Glu Gly Tyr Gly Ser Val Cys Ser Cys Lys Asp Pro Thr 275 280 285 Pro Ile Glu Phe Ser Pro Asp Pro Leu Pro Asp Asn Lys Val Leu 290 295 300 Asn Val Pro Val Ala Val Ile Ala Gly Asn Arg Pro Asn Tyr Leu 305 310 315 Tyr Arg Met Leu Arg Ser Leu Leu Ser Ala Gin Gly Val Ser Pro 320 325 330 Gin Met Ile Thr Val Phe Ile Asp Gly Tyr Tyr Glu Glu Pro Met 335 340 345 Asp Val Val Ala Leu Phe Gly Leu Arg Gly Ile Gin His Thr Pro 350 355 360 Ile Ser Ile Lys Asn Ala Arg Val Ser Gin His Tyr Lys Ala Ser 365 370 375 582 Leu Thr Ala Thr Phe Asn Leu Phe Pro Glu Ala Lys Phe Ala Val 380 385 390 Val Leu Glu Glu Asp Leu Asp Ile Ala Val Asp Phe Phe Ser Phe 395 400 405 Leu Ser Gin Ser Ile His Leu Leu Glu Glu Asp Asp Ser Leu Tyr 410 415 420 Cys Ile Ser Ala Trp Asn Asp Gin Gly Tyr Glu His Thr Ala Glu 425 430 435 Asp Pro Ala Leu Leu Tyr Arg Val Glu Thr Met Pro Gly Leu Gly 440 445 450 Trp Val Leu Arg Arg Ser Leu Tyr Lys Glu Glu Leu Glu Pro Lys 455 460 465 Trp Pro Thr Pro Glu Lys Leu Trp Asp Trp Asp Met Trp Met Arg 470 475 480 Met Pro Glu Gin Arg Arg Gly Arg' Glu Cys lie Ile Pro Asp Val 485 490 495 Ser Arg Ser Tyr His Phe Gly Ile Val Gly Leu Asn Met Asn Gly 500 505 510 Tyr Phe His Glu Ala Tyr Phe Lys Lys His Lys Phe Asn Thr Val 515 520 525 Pro Gly Val Gin Leu Arg Asn Val Asp Ser Leu Lys Lys Glu Ala 530 535 540 Tyr Glu Val Glu Val His Arg Leu Leu Ser Glu Ala Glu Val Leu 545 550 555 Asp His Ser Lys Asn Pro Cys Glu Asp Ser Phe Leu Pro Asp Thr 560 565 570 Glu Gly His Thr Tyr Val Ala Phe Ile Arg Met Glu Lys Asp Asp 575 580 585 Asp Phe Thr Thr Trp Thr Gin Leu Ala Lys Cys Leu His Ile Trp 590 595 600 Asp Leu Asp Val Arg Gly Asn His Arg Gly Leu Trp Arg Leu Phe 605 610 615 Arg Lys Lys Asn His Phe Leu Val Val Gly Val Pro Ala Ser Pro 620 625 630 Tyr Ser Val Lys Lys Pro Pro Ser Val Thr Pro Ile Phe Leu Glu 635 640 645 Pro Pro Pro Lys Glu Glu Gly Ala Pro Gly Ala Pro Glu Gin Thr 650 655 660 <210> 89 <211> 25 <212> DNA <213> Artificial Sequence 583 <220> <223> Synthetic oligonucleotide probe <400> 89 gatggcaaaa cgtgtgtttg acacg 25 <210> 90 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 90 cctcaaccag gccacgggcc ac 22 <210> 91 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 91 cccaggcaga gatgcagtac aggc 24 <210> 92 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 92 cctccagtag gtggatggat tggctc 26 <210> 93 <211> 47 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 93 ctcacctcat gaggatgagg ccatggtgct attcctcaac atggtag 47 <210> 94 <211> 3037 <212> DNA <213> Homo sapiens <400> 94 cggacgcgtg ggctgctggt gggaaggcct aaagaactgg aaagcccact 50 ctcttggaac caccacacct gtttaaagaa cctaagcacc atttaaagcc 100 actggaaatt tgttgtctag tggttgtggg tgaataaagg agggcagaat 150 584 ggatgatttc atctccatta gcctgctgtc tctggctatg ttggtgggat 200 gttacgtggc cggaatcatt cccttggctg ttaatttctc agaggaacga 250 ctgaagctgg tgactgtttt gggtgctggc cttctctgtg gaactgctct 300 ggcagtcatc gtgcctgaag gagtacatgc cctttatgaa gatattcttg 350 agggaaaaca ccaccaagca agtgaaacac ataatgtgat tgcatcagac 400 aaagcagcag aaaaatcagt tgtccatgaa catgagcaca gccacgacca 450 cacacagctg catgcctata ttggtgtttc cctcgttctg ggcttcgttt 500 tcatgttgct ggtggaccag attggtaact cccatgtgca ttctactgac 550 gatccagaag cagcaaggtc tagcaattcc aaaatcacca ccacgctggg 600 tctggttgtc catgctgcag ctgatggtgt tgctttggga gcagcagcat 650 ctacttcaca gaccagtgtc cagttaattg tgtttgtggc aatcatgcta 700 cataaggcac cagctgcttt tggactggtt tccttcttga tgcatgctgg 750 cttagagcgg aatcgaatca gaaagcactt gctggtcttt gcattggcag 800 caccagttat gtccatggtg acatacttag gactgagtaa gagcagtaaa 850 gaagcccttt cgggacattt cagaggtgaa ctttatgttg cgccacggga ccacagtaca gtggccatgc tgtcctccct ttttctctgc gaggtgggcg 900 950 gaatagggca cagccacaag cccgatgcca cgggagggag aggcctcagc 1000 cgcctggaag tggcagccct ggttctgggt tgcctcatcc ctctcatcct 1050 gtcagtagga caccagcatt aaatgttcaa ggtccagcct tggtccaggg 1100 ccgtttgcca tccagtgaga acagccggca cgtgacagct actcacttcc 1150 tcagtctctt gtctcacctt gcgcatctct acatgtattc ctagagtcca 1200 gaggggaggt gaggttaaaa cctgagtaat ggaaaagctt ttagagtaga 1250 aacacattta cgttgcagtt agctatagac atcccattgt gttatctttt 1300 aaaaggccct tgacattttg cgttttaata tttctcttaa ccctattctc 1350 agggaagatg gaatttagtt ttaaggaaaa gaggagaact tcatactcac 1400 aatgaaatag tgattatgaa aatacagtgt tctgtaatta agctatgtct 1450 ctttcttctt agtttagagg ctctgctact ttatccattg atttttaaca 1500 tggttcccac catgtaagac tggtgcttta gcatctatgc cacatgcgtt 1550 gatggaaggt catagcaccc actcacttag atgctaaagg tgattctagt 1600 taatctggga ttagggtcag gaaaatgata gcaagacaca ttgaaagctc 1650 tctttatact caaaagagat atccattgaa aagggatgtc tagagggatt 1700 taaacagctc ctttggcacg tgcctctctg aatccagcct gccattccat 1750 585 caaatggagc aggagaggtg ggaggagctt ctaaagaggt gactggtatt 1800 ttgtagcatt ccttgtcaag ttctcctttg cagaatacct gtctccacat 1850 tcctagagag gagccaagtt ctagtagttt cagttctagg ctttccttca 1900 agaacagtca gatcacaaag tgtctttgga aattaaggga tattaaattt 1950 taagtgattt ttggatggtt attgatatct ttgtagtagc tttttttaaa 2000 agactaccaa aatgtatggt tgtccttttt ttttgttttt ttttttttta 2050 attatttctc ttagcagatc agcaatccct ctagggacct aaatactagg 2100 tcagctttgg cgacactgtg tcttctcaca taaccacctg tagcaagatg 2150 gatcataaat gagaagtgtt tgcctattga tttaaagctt attggaatca 2200 tgtctcttgt ctcttcgtct tttctttgct tttcttctaa cttttccctc 2250 tagcctctcc tcgccacaat ttgctgctta ctgctggtgt taatatttgt 2300 gtgggatgaa ttcttatcag gacaaccact tctcgaactg taataatgaa 2350 gataataata tctttattct ttatcccctt caaagaaatt acctttgtgt 2400 caaatgccgc tttgttgagc ccttaaaata ccacctcctc atgtgtaaat 2450 tgacacaatc ttaacagact actaatctgg aggataattt taatttaaac ttttttcata aattgagata tttgccaaaa gcaaaagtgt tttttgtaaa 2500 2550 ccctgtcttg tcaaataagt gtataatatt gtattattaa tttattttta 2600 ctttctatac catttcaaaa cacattacac taagggggaa ccaagactag 2650 tttcttcagg gcagtggacg tagtagtttg taaaaacgtt ttctatgacg 2700 cataagctag catgcctatg atttatttcc ttcatgaatt tgtcactgga 2750 tcagcagctg tggaaataaa gcttgtgagc cctctgctgg ccacagtgag 2800 gaaagtagca caaataggat acagttgtat gtagtcattg gcaacaattg 2850 catacaattt tactaccaag agaaggtata gtatggaaag tccaaatgac 2900 ttccttgatt ggatgttaac agctgactgg tgtgagactt gaggtttcat 2950 ctagtccttc aaaactatat ggttgcctag attctctctg gaaactgact 3000 ttgtcaaata aatagcagat tgtagtgtca aaaaaaa 3 037 <210> 95 <211> 307 <212> PRT <213> Homo sapiens <400> 95 Met Asp Asp Phe Ile Ser Ile Ser Leu Leu Ser Leu Ala Met Leu 1 5 10 15 Val Gly Cys Tyr Val Ala Gly Ile Ile Pro Leu Ala Val Asn Phe 586 Ser Glu Glu Arg Leu Lys Leu Val Thr Val Leu Gly Ala Gly Leu 40 45 Leu Cys Gly Thr Ala Leu Ala Val Ile Val Pro Glu Gly Val His 50 55 60 Ala Leu Tyr Glu Asp Ile Leu Glu Gly Lys His His Gin Ala Ser 65 70 75 Glu Thr His Asn Val Ile Ala Ser Asp Lys Ala Ala Glu Lys Ser 80 85 90 Val Val His Glu His Glu His Ser His Asp His Thr Gin Leu His 95 100 105 Ala Tyr Ile Gly Val Ser Leu Val Leu Gly Phe Val Phe Met Leu 110 115 120 Leu Val Asp Gin Ile Gly Asn Ser His Val His Ser Thr Asp Asp 125 130 135 Pro Glu Ala Ala Arg Ser Ser Asn Ser Lys Ile Thr Thr Thr Leu 140 145 150 Gly Leu Val Val His Ala Ala Ala Asp Gly Val Ala Leu Gly Ala 155 160 165 Ala Ala Ser Thr Ser Gin Thr Ser Val Gin Leu Ile Val Phe Val 170 175 180 Ala Ile Met Leu His Lys Ala Pro Ala Ala Phe Gly Leu Val Ser 185 190 195 Phe Leu Met His Ala Gly Leu Glu Arg Asn Arg Ile Arg Lys His 200 205 210 Leu Leu Val Phe Ala Leu Ala Ala Pro Val Met Ser Met Val Thr 215 220 225 Tyr Leu Gly Leu Ser Lys Ser Ser Lys Glu Ala Leu Ser Glu Val 230 235 240 Asn Ala Thr Gly Val Ala Met Leu Phe Ser Ala Gly Thr Phe Leu 245 250 255 Tyr Val Ala Thr Val His Val Leu Pro Glu Val Gly Gly Ile Gly 260 265 270 His Ser His Lys Pro Asp Ala Thr Gly Gly Arg Gly Leu Ser Arg 275 280 285 Leu Glu Val Ala Ala Leu Val Leu Gly Cys Leu Ile Pro Leu Ile 290 295 300 Leu Ser Val Gly His Gin His 305 <210> 96 <211> 25 <212> DNA <213> Artificial Sequence 587 <22 0> <223> Synthetic oligonucleotide probe <400> 96 gttgtgggtg aataaaggag ggcag 25 <210> 97 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 97 ctgtgctcat gttcatggac aactg 25 <210> 98 <211> 50 <212> DNA <213> Artificial Sequence <22 0> <223> Synthetic oligonucleotide probe <400> 98 ggatgatttc atctccatta gcctgctgtc tctggctatg ttggtgggat 50 <210> 99 <211> 1429 <212> DNA <213> Homo sapiens <400> 99 gctcgaggcc ggcggcggcg ggagagcgac ccgggcggcc tcgtagcggg 50 gccccggatc cccgagtggc ggccggagcc tcgaaaagag attctcagcg 100 ctgattttga gatgatgggc ttgggaaacg ggcgtcgcag catgaagtcg 150 ccgcccctcg tgctggccgc cctggtggcc tgcatcatcg tcttgggctt 200 caactactgg attgcgagct cccggagcgt ggacctccag acacggatca 250 tggagctgga aggcagggtc cgcagggcgg ctgcagagag aggcgccgtg 300 gagctgaaga agaacgagtt ccagggagag ctggagaagc agcgggagca 350 gcttgacaaa atccagtcca gccacaactt ccagctggag agcgtcaaca 400 agctgtacca ggacgaaaag gcggttttgg tgaataacat caccacaggt 450 gagaggctca tccgagtgct gcaagaccag ttaaagaccc tgcagaggaa 500 ttacggcagg ctgcagcagg atgtcctcca gtttcagaag aaccagacca 550 acctggagag gaagttctcc tacgacctga gccagtgcat caatcagatg 600 aaggaggtga aggaacagtg tgaggagcga atagaagagg tcaccaaaaa 650 ggggaatgaa gctgtagctt ccagagacct gagtgaaaac aacgaccaga 700 588 gacagcagct ccaagccctc agtgagcctc agcccaggct gcaggcagca 750 ggcctgccac acacagaggt gccacaaggg aagggaaacg tgcttggtaa 800 cagcaagtcc cagacaccag cccccagttc cgaagtggtt ttggattcaa 850 agagacaagt tgagaaagag gaaaccaatg agatccaggt ggtgaatgag 900 gagcctcaga gggacaggct gccgcaggag ccaggccggg agcaggtggt 950 ggaagacaga cctgtaggtg gaagaggctt cgggggagcc ggagaactgg 1000 gccagacccc acaggtgcag gctgccctgt cagtgagcca ggaaaatcca 1050 gagatggagg gccctgagcg agaccagctt gtcatccccg acggacagga 1100 ggaggagcag gaagctgccg gggaagggag aaaccagcag aaactgagag 1150 gagaagatga ctacaacatg gatgaaaatg aagcagaatc tgagacagac 1200 aagcaagcag ccctggcagg gaatgacaga aacatagatg tttttaatgt 1250 tgaagatcag aaaagagaca ccataaattt acttgatcag cgtgaaaagc 1300 ggaatcatac actctgaatt gaactggaat cacatatttc acaacagggc 1350 cgaagagatg actataaaat gttcatgagg gactgaatac tgaaaactgt 1400 gaaatgtact aaataaaatg tacatctga : 1429 <210> 100 <211> 401 <212> PRT <213> Homo sapiens <400> 100 Met Met Gly Leu Gly Asn Gly Arg Arg Ser Met Lys Ser Pro Pro 1 5 10 15 Leu Val Leu Ala Ala Leu Val Ala Cys Ile Ile Val Leu Gly Phe 25 30 Asn Tyr Trp Ile Ala Ser Ser Arg Ser Val Asp Leu Gin Thr Arg 40 45 Ile Met Glu Leu Glu Gly Arg Val Arg Arg Ala Ala Ala Glu Arg 50 55 60 Gly Ala Val Glu Leu Lys Lys Asn Glu Phe Gin Gly Glu Leu Glu 65 70 75 Lys Gin Arg Glu Gin Leu Asp Lys Ile Gin Ser Ser His Asn Phe 80 85 90 Gin Leu Glu Ser Val Asn Lys Leu Tyr Gin Asp Glu Lys Ala Val 95 100 105 Leu Val Asn Asn Ile Thr Thr Gly Glu Arg Leu Ile Arg Val Leu 110 115 120 Gin Asp Gin Leu Lys Thr Leu Gin Arg Asn Tyr Gly Arg Leu Gin 589 125 130 135 Gin Asp Val Leu Gin Phe Gin Lys Asn Gin Thr Asn Leu Glu Arg 140 145 150 Lys Phe Ser Tyr Asp Leu Ser Gin Cys Ile Asn Gin Met Lys Glu 155 160 165 Val Lys Glu Gin Cys Glu Glu Arg Ile Glu Glu Val Thr Lys Lys 170 175 180 Gly Asn Glu Ala Val Ala Ser Arg Asp Leu Ser Glu Asn Asn Asp 185 190 195 Gin Arg Gin Gin Leu Gin Ala Leu Ser Glu Pro Gin Pro Arg Leu 200 205 210 Gin Ala Ala Gly Leu Pro His Thr Glu Val Pro Gin Gly Lys Gly 215 220 225 Asn Val Leu Gly Asn Ser Lys Ser Gin Thr Pro Ala Pro Ser Ser 230 235 240 Glu Val Val Leu Asp Ser Lys Arg Gin Val Glu Lys Glu Glu Thr 245 250 255 Asn Glu Ile Gin Val Val Asn Glu Glu Pro Gin Arg Asp Arg Leu 260 265 270 Pro Gin Glu Pro Gly Arg Glu Gin Val Val Glu Asp Arg Pro Val 275 280 285 Gly Gly Arg Gly Phe Gly Gly Ala Gly Glu Leu Gly Gin Thr Pro 290 295 300 Gin Val Gin Ala Ala Leu Ser Val Ser Gin Glu Asn Pro Glu Met 305 310 315 Glu Gly Pro Glu Arg Asp Gin Leu Val Ile Pro Asp Gly Gin Glu 320 325 330 Glu Glu Gin Glu Ala Ala Gly Glu Gly Arg Asn Gin Gin Lys Leu 335 340 345 Arg Gly Glu Asp Asp Tyr Asn Met Asp Glu Asn Glu Ala Glu Ser 350 355 360 Glu Thr Asp Lys Gin Ala Ala Leu Ala Gly Asn Asp Arg Asn Ile 365 370 375 Asp Val Phe Asn Val Glu Asp Gin Lys Arg Asp Thr Ile Asn Leu 380 385 390 Leu Asp Gin Arg Glu Lys Arg Asn His Thr Leu 395 400 <210> 101 <211> 3671 <212> DNA <213> Homo sapiens <400> 101 ggatgcagaa agcctcagtg ttgctcttcc tggcctgggt ctgcttcctc 50 590 ttctacgctg gcattgccct cttcaccagt ggcttcctgc tcacccgttt 100 ggagctcacc aaccatagca gctgccaaga gcccccaggc cctgggtccc 150 tgccatgggg gagccaaggg aaacctgggg cctgctggat ggcttcccga 200 ttttcgcggg ttgtgttggt gctgatagat gctctgcgat ttgacttcgc 250 ccagccccag cattcacacg tgcctagaga gcctcctgtc tccctaccct 300 tcctgggcaa actaagctcc ttgcagagga tcctggagat tcagccccac 350 catgcccggc tctaccgatc tcaggttgac cctcctacca ccaccatgca 400 gcgcctcaag gccctcacca ctggctcact gcctaccttt attgatgctg 450 gtagtaactt cgccagccac gccatagtgg aagacaatct cattaagcag 500 ctcaccagtg caggaaggcg tgtagtcttc atgggagatg atacctggaa 550 agaccttttc cctggtgctt tctccaaagc tttcttcttc ccatccttca 600 atgtcagaga cctagacaca gtggacaatg gcatcctgga acacctctac 650 cccaccatgg acagtggtga atgggacgtg ctgattgctc acttcctggg 700 tgtggaccac tgtggccaca agcatggccc tcaccaccct gaaatggcca 750 agaaacttag ccagatggac caggtgatcc agggacttgt ggagcgtctg 800 gagaatgaca cactgctggt agtggctggg gaccatggga tgaccacaaa 850 tggagaccat ggaggggaca gtgagctgga ggtctcagct gctctctttc 900 tgtatagccc cacagcagtc ttccccagca ccccaccaga ggagccagag 950 gtgattcctc aagttagcct tgtgcccacg ctggccctgc tgctgggcct 1000 gcccatccca tttgggaata tcggggaagt gatggctgag ctattctcag 1050 ggggtgagga ctcccagccc cactcctctg ctttagccca agcctcagct 1100 ctccatctca atgctcagca ggtgtcccga tttcttcata cctactcagc 1150 tgctactcag gaccttcaag ctaaggagct tcatcagctg cagaacctct 1200 tctccaaggc ctctgctgac taccagtggc ttctccagag ccccaagggg 1250 gctgaggcga cactgccgac tgtgattgct gagctgcagc agttcctgcg 1300 gggagctcgg gccatgtgca tcgagtcttg ggctcgtttc tctctggtcc 1350 gcatggcggg gggtactgct ctcttggctg cttcctgctt tatctgcctg 1400 ctggcatctc agtgggcaat atccccaggc tttccattct gccctctact 1450 cctgacacct gtggcctggg gcctggttgg ggccatagcg tatgctggac 1500 tcctgggaac tattgagctg aagctagatc tagtgcttct aggggctgtg 1550 gctgcagtga gctcattcct cccttttctg tggaaagcct gggctggctg 1600 591 ggggtccaag aggcccctgg caaccctgtt tcccatccct gggcccgtcc 1650 tgttactcct gctgtttcgc ttggctgtgt tcttctctga tagttttgtt 1700 gtagctgagg ccagggccac ccccttcctt ttgggctcat tcatcctgct 1750 cctggttgtc cagcttcact gggagggcca gctgcttcca cctaagctac 1800 tcacaatgcc ccgccttggc acttcagcca caacaaaccc cccacggcac 1850 aatggtgcat atgccctgag gcttggaatt gggttgcttt tatgtacaag 1900 gctagctggg ctttttcatc gttgccctga agagacacct gtttgccact 1950 cctctccctg gctgagtcct ctggcatcca tggtgggtgg tcgagccaag 2000 aatttatggt atggagcttg tgtggcggcg ctggtggccc tgttagctgc 2050 cgtgcgcttg tggcttcgcc gctatggtaa tctcaagagc cccgagccac 2100 ccatgctctt tgtgcgctgg ggactgcccc taatggcatt gggtactgct 2150 gcctactggg cattggcgtc gggggcagat gaggctcccc cccgtctccg 2200 ggtcctggtc tctggggcat ccatggtgct gcctcgggct gtagcagggc 2250 tggctgcttc agggctcgcg ctgctgctct ggaagcctgt gacagtgctg 2300 gtgaaggctg gggcaggcgc tccaaggacc aggactgtcc tcactccctt 2350 ctcaggcccc cccacttctc aagctgactt ggattatgtg gtccctcaaa 2400 tctaccgaca catgcaggag gagttccggg gccggttaga gaggaccaaa 2450 tctcagggtc agctgctatg ccctgactgt gtcacagccc ggctgcttat tcaccctgtt cagttgggga ggccttccca gtgtctactc cttctgctgt 2500 2550 tgcatgcgga gcgcatcagc cttgtgttcc tgcttctgtt tctgcagagc 2600 ttccttctcc tacatctgct tgctgctggg atacccgtca ccacccctgg 2650 tccttttact gtgccatggc aggcagtctc ggcttgggcc ctcatggcca 2700 cacagacctt ctactccaca ggccaccagc ctgtctttcc agccatccat 2750 tggcatgcag ccttcgtggg attcccagag ggtcatggct cctgtacttg 2800 gctgcctgct ttgctagtgg gagccaacac ctttgcctcc cacctcctct 2850 ttgcagtagg ttgcccactg ctcctgctct ggcctttcct gtgtgagagt 2900 caagggctgc ggaagagaca gcagccccca gggaatgaag ctgatgccag 2950 agtcagaccc gaggaggaag aggagccact gatggagatg cggctccggg 3000 atgcgcctca gcacttctat gcagcactgc tgcagctggg cctcaagtac 3050 ctctttatcc ttggtattca gattctggcc tgtgccttgg cagcctccat 3100 ccttcgcagg catctcatgg tctggaaagt gtttgcccct aagttcatat 3150 592 ttgaggctgt gggcttcatt gtgagcagcg tgggacttct cctgggcata 3200 gctttggtga tgagagtgga tggtgctgtg agctcctggt tcaggcagct 3250 atttctggcc cagcagaggt agcctagtct gtgattactg gcacttggct 3300 acagagagtg ctggagaaca gtgtagcctg gcctgtacag gtactggatg 3350 atctgcaaga caggctcagc catactctta ctatcatgca gccaggggcc 3400 gctgacatct aggacttcat tattctataa ttcaggacca cagtggagta 3450 tgatccctaa ctcctgattt ggatgcatct gagggacaag gggggcggtc 3500 tccgaagtgg aataaaatag gccgggcgtg gtgacttgca cctataatcc 3550 cagcactttg ggaggcagag gtgggaggat tgcttggtcc caggagttca 3600 agaccagcct gtggaacata acaagacccc gtctctacta tttaaaaaaa 3650 agtgtaataa aatgataata t 3671 <210> 102 <211> 1089 <212> PRT <213> Homo sapiens <400> 102 Met Gin Lys Ala Ser Val Leu Leu Phe Leu Ala Trp Val Cys Phe 15 10 15 Leu Phe Tyr Ala Gly lie Ala Leu Phe Thr Ser Gly Phe Leu Leu 20 25 30 Thr Arg Leu Glu Leu Thr Asn His Ser Ser Cys Gin Glu Pro Pro 35 40 45 Gly Pro Gly Ser Leu Pro Trp Gly Ser Gin Gly Lys Pro Gly Ala 50 55 60 Cys Trp Met Ala Ser Arg Phe Ser Arg Val Val Leu Val Leu Ile 65 70 75 Asp Ala Leu Arg Phe Asp Phe Ala Gin Pro Gin His Ser His Val 80 85 90 Pro Arg Glu Pro Pro Val Ser Leu Pro Phe Leu Gly Lys Leu Ser 95 100 105 Ser Leu Gin Arg Ile Leu Glu Ile Gin Pro His His Ala Arg Leu 110 115 120 Tyr Arg Ser Gin Val Asp Pro Pro Thr Thr Thr Met Gin Arg Leu 125 130 135 Lys Ala Leu Thr Thr Gly Ser Leu Pro Thr Phe Ile Asp Ala Gly 140 145 150 Ser Asn Phe Ala Ser His Ala Ile Val Glu Asp Asn Leu Ile Lys 155 160 165 Gin Leu Thr Ser Ala Gly Arg Arg Val Val Phe Met Gly Asp Asp 170 593 175 180 Thr Trp Lys Asp Leu Phe Pro Gly Ala Phe Ser Lys Ala Phe Phe 185 190 195 Phe Pro Ser Phe Asn Val Arg Asp Leu Asp Thr Val Asp Asn Gly 200 205 210 Ile Leu Glu His Leu Tyr Pro Thr Met Asp Ser Gly Glu Trp Asp 215 220 225 Val Leu Ile Ala His Phe Leu Gly Val Asp His Cys Gly His Lys 230 235 240 His Gly Pro His His Pro Glu Met Ala Lys Lys Leu Ser Gin Met 245 250 255 Asp Gin Val Ile Gin Gly Leu Val Glu Arg Leu Glu Asn Asp Thr 260 265 270 Leu Leu Val Val Ala Gly Asp His Gly Met Thr Thr Asn Gly Asp 275 280 285 His Gly Gly Asp Ser Glu Leu Glu Val Ser Ala Ala Leu Phe Leu 290 295 300 Tyr Ser Pro Thr Ala Val Phe Pro Ser Thr Pro Pro Glu Glu Pro 305 310 315 Glu Val Ile Pro Gin Val Ser Leu Val Pro Thr Leu Ala Leu Leu 320 325 330 Leu Gly Leu Pro Ile Pro Phe Gly Asn Ile Gly Glu Val Met Ala 335 340 345 Glu Leu Phe Ser Gly Gly Glu Asp Ser Gin Pro His Ser Ser Ala 350 355 360 Leu Ala Gin Ala Ser Ala Leu His Leu Asn Ala Gin Gin Val Ser 365 370 375 Arg Phe Leu His Thr Tyr Ser Ala Ala Thr Gin Asp Leu Gin Ala 380 385 390 Lys Glu Leu His Gin Leu Gin Asn Leu Phe Ser Lys Ala Ser Ala 395 400 405 Asp Tyr Gin Trp Leu Leu Gin Ser Pro Lys Gly Ala Glu Ala Thr 410 415 420 Leu Pro Thr Val Ile Ala Glu Leu Gin Gin Phe Leu Arg Gly Ala 425 430 435 Arg Ala Met Cys Ile Glu Ser Trp Ala Arg Phe Ser Leu Val Arg 440 445 450 Met Ala Gly Gly Thr Ala Leu Leu Ala Ala Ser Cys Phe Ile Cys 455 460 465 Leu Leu Ala Ser Gin Trp Ala Ile Ser Pro Gly Phe Pro Phe Cys 470 475 480 594 Pro Leu Leu Leu Thr Pro Val Ala Trp Gly Leu Val Gly Ala Ile 485 490 495 Ala Tyr Ala Gly Leu Leu Gly Thr Ile Glu Leu Lys Leu Asp Leu 500 505 510 Val Leu Leu Gly Ala Val Ala Ala Val Ser Ser Phe Leu Pro Phe 515 520 525 Leu Trp Lys Ala Trp Ala Gly Trp Gly Ser Lys Arg Pro Leu Ala 530 535 540 Thr Leu Phe Pro Ile Pro Gly Pro Val Leu Leu Leu Leu Leu Phe 545 550 555 Arg Leu Ala Val Phe Phe Ser Asp Ser Phe Val Val Ala Glu Ala 560 565 570 Arg Ala Thr Pro Phe Leu Leu Gly Ser Phe Ile Leu Leu Leu Val 575 580 585 Val Gin Leu His Trp Glu Gly Gin Leu Leu Pro Pro Lys Leu Leu 590 595 600 Thr Met Pro Arg Leu Gly Thr Ser Ala Thr Thr Asn Pro Pro Arg 605 610 615 His Asn Gly Ala Tyr Ala Leu Arg Leu Gly Ile Gly Leu Leu Leu 620 625 630 Cys Thr Arg Leu Ala Gly Leu Phe His Arg Cys Pro Glu Glu Thr 635 640 645 Pro Val Cys His Ser Ser Pro Trp Leu Ser Pro Leu Ala Ser Met 650 655 660 Val Gly Gly Arg Ala Lys Asn Leu Trp Tyr Gly Ala Cys Val Ala 665 670 675 Ala Leu Val Ala Leu Leu Ala Ala Val Arg Leu Trp Leu Arg Arg 680 685 690 Tyr Gly Asn Leu Lys Ser Pro Glu Pro Pro Met Leu Phe Val Arg 695 700 705 Trp Gly Leu Pro Leu Met Ala Leu Gly Thr Ala Ala Tyr Trp Ala 710 715 720 Leu Ala Ser Gly Ala Asp Glu Ala Pro Pro Arg Leu Arg Val Leu 725 730 735 Val Ser Gly Ala Ser Met Val Leu Pro Arg Ala Val Ala Gly Leu 740 745 750 Ala Ala Ser Gly Leu Ala Leu Leu Leu Trp Lys Pro Val Thr Val 755 760 765 Leu Val Lys Ala Gly Ala Gly Ala Pro Arg Thr Arg Thr Val Leu 770 775 780 Thr Pro Phe Ser Gly Pro Pro Thr Ser Gin Ala Asp Leu Asp Tyr 785 790 795 595 Val Val Pro Gin Ile Tyr Arg His Met Gin Glu Glu Phe Arg Gly 800 805 810 Arg Leu Glu Arg Thr Lys Ser Gin Gly Pro Leu Thr Val Ala Ala 815 820 825 Tyr Gin Leu Gly Ser Val Tyr Ser Ala Ala Met Val Thr Ala Leu 830 835 840 Thr Leu Leu Ala Phe Pro Leu Leu Leu Leu His Ala Glu Arg Ile 845 850 855 Ser Leu Val Phe Leu Leu Leu Phe Leu Gin Ser Phe Leu Leu Leu 860 865 870 His Leu Leu Ala Ala Gly Ile Pro Val Thr Thr Pro Gly Pro Phe 875 880 885 Thr Val Pro Trp Gin Ala Val Ser Ala Trp Ala Leu Met Ala Thr 890 895 900 Gin Thr Phe Tyr Ser Thr Gly His Gin Pro Val Phe Pro Ala Ile 905 910 915 His Trp His Ala Ala Phe Val Gly Phe Pro Glu Gly His Gly Ser 920 925 930 Cys Thr Trp Leu Pro Ala Leu Leu Val Gly Ala Asn Thr Phe Ala 935 940 945 Ser His Leu Leu Phe Ala Val Gly Cys Pro Leu Leu Leu Leu Trp 950 955 960 Pro Phe Leu Cys Glu Ser Gin Gly Leu Arg Lys Arg Gin Gin Pro 965 970 975 Pro Gly Asn Glu Ala Asp Ala Arg Val Arg Pro Glu Glu Glu Glu 980 985 990 Glu Pro Leu Met Glu Met Arg Leu Arg Asp Ala Pro Gin His Phe 995 1000 1005 Tyr Ala Ala Leu Leu Gin Leu Gly Leu Lys Tyr Leu Phe Ile Leu 1010 1015 1020 Gly Ile Gin Ile Leu Ala Cys Ala Leu Ala Ala Ser Ile Leu Arg 1025 1030 1035 Arg His Leu Met Val Trp Lys Val Phe Ala Pro Lys Phe Ile Phe 1040 . 1045 1050 Glu Ala Val Gly Phe Ile Val Ser Ser Val Gly Leu Leu Leu Gly 1055 1060 1065 Ile Ala Leu Val Met Arg Val Asp Gly Ala Val Ser Ser Trp Phe 1070 1075 1080 Arg Gin Leu Phe Leu Ala Gin Gin Arg 1085 <210> 103 596 <211> 1743 <212> DNA <213> Homo sapiens <400> 103 tgccgctgcc gccgctgctg ctgttgctcc tggcggcgcc ttggggacgg 50 gcagttccct gtgtctctgg tggtttgcct aaacctgcaa acatcacctt 100 cttatccatc aacatgaaga atgtcctaca atggactcca ccagagggtc 150 ttcaaggagt taaagttact tacactgtgc agtatttcat cacaaattgg 200 cccaccagag gtggcactga ctacagatga gaagtccatt tctgttgtcc 250 tgacagctcc agagaagtgg aagagaaatc cagaagacct tcctgtttcc 300 atgcaacaaa tatactccaa tctgaagtat aacgtgtctg tgttgaatac 350 taaatcaaac agaacgtggt cccagtgtgt gaccaaccac acgctggtgc 400 tcacctggct ggagccgaac actctttact gcgtacacgt ggagtccttc 450 gtcccagggc cccctcgccg tgctcagcct tctgagaagc agtgtgccag 500 gactttgaaa gatcaatcat cagagttcaa ggctaaaatc atcttctggt 550 atgttttgcc catatctatt accgtgtttc ttttttctgt gatgggctat 600 tccatctacc gatatatcca cgttggcaaa gagaaacacc cagcaaattt 650 gattttgatt tatggaaatg aatttgacaa aagattcttt gtgcctgctg 700 aaaaaatcgt gattaacttt atcaccctca atatctcgga tgattctaaa 750 atttctcatc aggatatgag tttactggga aaaagcagtg atgtatccag 800 ccttaatgat cctcagccca gcgggaacct gaggccccct caggaggaag 850 aggaggtgaa acatttaggg tatgcttcgc atttgatgga aattttttgt 900 gactctgaag aaaacacgga aggtacttct ctcacccagc aagagtccct 950 cagcagaaca atacccccgg ataaaacagt cattgaatat gaatatgatg 1000 tcagaaccac tgacatttgt gcggggcctg aagagcagga gctcagtttg 1050 caggaggagg tgtccacaca aggaacatta ttggagtcgc aggcagcgtt 1100 ggcagtcttg ggcccgcaaa cgttacagta ctcatacacc cctcagctcc 1150 aagacttaga ccccctggcg caggagcaca cagactcgga ggaggggccg 1200 gaggaagagc catcgacgac cctggtcgac tgggatcccc aaactggcag 1250 gctgtgtatt ccttcgctgt ccagcttcga ccaggattca gagggctgcg 1300 agccttctga gggggatggg ctcggagagg agggtcttct atctagactc 1350 tatgaggagc cggctccaga caggccacca ggagaaaatg aaacctatct 1400 catgcaattc atggaggaat gggggttata tgtgcagatg gaaaactgat 1450 597 gccaacactt ccttttgcct tttgtttcct gtgcaaacaa gtgagtcacc 1500 cctttgatcc cagccataaa gtacctggga tgaaagaagt tttttccagt 1550 ttgtcagtgt ctgtgagaat tacttatttc ttttctctat tctcatagca 1600 cgtgtgtgat tggttcatgc atgtaggtct cttaacaatg atggtgggcc 1650 tctggagtcc aggggctggc cggttgttct atgcagagaa agcagtcaat 1700 aaatgtttgc cagactgggt gcagaattta ttcaggtggg tgt 1743 <210> 104 <211> 442 <212> PRT <213> Homo sapiens <400> 104 Met Ser Tyr Asn Gly Leu His Gin. Arg Val Phe Lys Glu Leu Lys 15 10 15 Leu Leu Thr Leu Cys Ser Ile Ser Ser Gin Ile Gly Pro Pro Glu 20 25 30 Val Ala Leu Thr Thr Asp Glu Lys Ser Ile Ser Val Val Leu Thr 35 40 45 Ala Pro Glu Lys Trp Lys Arg Asn Pro Glu Asp Leu Pro Val Ser 50 55 60 Met Gin Gin Ile Tyr Ser Asn Leu Lys Tyr Asn Val Ser Val Leu 65 70 75 Asn Thr Lys Ser Asn Arg Thr Trp Ser Gin Cys Val Thr Asn His 80 85 90 Thr Leu Val Leu Thr Trp Leu Glu Pro Asn Thr Leu Tyr Cys Val 95 100 105 His Val Glu Ser Phe Val Pro Gly Pro Pro Arg Arg Ala Gin Pro 110 115 120 Ser Glu Lys Gin Cys Ala Arg Thr Leu Lys Asp Gin Ser Ser Glu 125 130 135 Phe Lys Ala Lys Ile Ile Phe Trp Tyr Val Leu Pro Ile Ser Ile 140 145 150 Thr Val Phe Leu Phe Ser Val Met Gly Tyr Ser Ile Tyr Arg Tyr 155 160 165 Ile His Val Gly Lys Glu Lys His Pro Ala Asn Leu Ile Leu Ile 170 175 180 Tyr Gly Asn Glu Phe Asp Lys Arg Phe Phe Val Pro Ala Glu Lys 185 190 195 Ile Val Ile Asn Phe Ile Thr Leu Asn Ile Ser Asp Asp Ser Lys 200 205 210 Ile Ser His Gin Asp Met Ser Leu Leu Gly Lys Ser Ser Asp Val 215 220 225 598 Ser Ser Leu Asn Asp Pro Gin Pro Ser Gly Asn Leu Arg Pro Pro 230 235 240 Gin Glu Glu Glu Glu Val Lys His Leu Gly Tyr Ala Ser His Leu 245 250 255 Met Glu Ile Phe Cys Asp Ser Glu Glu Asn Thr Glu Gly Thr Ser 260 265 270 Leu Thr Gin Gin Glu Ser Leu Ser Arg Thr Ile Pro Pro Asp Lys 275 280 285 Thr Val Ile Glu Tyr Glu Tyr Asp Val Arg Thr Thr Asp Ile Cys 290 295 300 Ala Gly Pro Glu Glu Gin Glu Leu Ser Leu Gin Glu Glu Val Ser 305 310 315 Thr Gin Gly Thr Leu Leu Glu Ser Gin Ala Ala Leu Ala Val Leu 320 325 330 Gly Pro Gin Thr Leu Gin Tyr Ser Tyr Thr Pro Gin Leu Gin Asp 335 340 345 Leu Asp Pro Leu Ala Gin Glu His Thr Asp Ser Glu Glu Gly Pro 350 355 360 Glu Glu Glu Pro Ser Thr Thr Leu Val Asp Trp Asp Pro Gin Thr 365 370 375 Gly Arg Leu Cys Ile Pro Ser Leu Ser Ser Phe Asp Gin Asp Ser 380 385 390 Glu Gly Cys Glu Pro Ser Glu Gly Asp Gly Leu Gly Glu Glu Gly 395 400 405 Leu Leu Ser Arg Leu Tyr Glu Glu Pro Ala Pro Asp Arg Pro Pro 410 415 420 Gly Glu Asn Glu Thr Tyr Leu Met Gin Phe Met Glu Glu Trp Gly 425 430 435 Leu Tyr Val Gin Met Glu Asn 440 <210> 105 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 105 cgctgctgct gttgctcctg g 21 <210> 106 <211> 18 <212> DNA <213> Artificial Sequence 599 <220> <223> Synthetic oligonucleotide probe <400> 106 cagtgtgcca ggactttg 18 <210> 107 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 107 agtcgcaggc agcgttgg 18 <210> 108 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 108 ctcctccgag tctgtgtgct cctgc 25 <210> 109 <211> 51 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 109 ggacgggcag ttccctgtgt ctctggtggt ttgcctaaac ctgcaaacat 50 c 51 <210> 110 <211> 1114 <212> DNA <213> Homo sapiens <400> 110 cggacgcgtg ggcggacgcg tgggcggacg cgtgggtctc tgcggggaga 50 cgccagcctg cgtctgccat ggggctcggg ttgaggggct ggggacgtcc 100 tctgctgact gtggccaccg ccctgatgct gcccgtgaag ccccccgcag 150 gctcctgggg ggcccagatc atcgggggcc acgaggtgac cccccactcc 200 aggccctaca tggcatccgt gcgcttcggg ggccaacatc actgcggagg 250 cttcctgctg cgagcccgct gggtggtctc ggccgcccac tgcttcagcc 300 acagagacct ccgcactggc ctggtggtgc tgggcgccca cgtcctgagt 350 actgcggagc ccacccagca ggtgtttggc atcgatgctc tcaccacgca 400 600 ccccgactac caccccatga cccacgccaa cgacatctgc ctgctgcggc 450 tgaacggctc tgctgtcctg ggccctgcag tggggctgct gaggctgcca 500 gggagaaggg ccaggccccc cacagcgggg acacggtgcc gggtggctgg 550 ctggggcttc gtgtctgact ttgaggagct gccgcctgga ctgatggagg 600 ccaaggtccg agtgctggac ccggacgtct gcaacagctc ctggaagggc 650 cacctgacac ttaccatgct ctgcacccgc agtggggaca gccacagacg 700 gggcttctgc tcggccgact ccggagggcc cctggtgtgc aggaaccggg 750 ctcacggcct cgtttccttc tcgggcctct ggtgcggcga ccccaagacc 800 cccgacgtgt acacgcaggt gtccgccttt gtggcctgga tctgggacgt 850 ggttcggcgg agcagtcccc agcccggccc cctgcctggg accaccaggc 900 ccccaggaga agccgcctga gccacaacct tgcggcatgc aaatgagatg 950 gccgctccag gcctggaatg ttccgtggct gggccccacg ggaagcctga 1000 tgttcagggt tggggtggga cgggcagcgg tggggcacac ccattccaca 1050 tgcaaagggc agaagcaaac ccagtaaaat gttaactgac aaaaaaaaaa 1100 aaaaaaaaaa gaaa 1114 <210> 111 <211> 283 <212> PRT <213> Homo sapiens <400> 111 Met Gly Leu Gly Leu Arg Gly Trp Gly Arg Pro Leu Leu Thr Val 15 10 15 Ala Thr Ala Leu Met Leu Pro Val Lys Pro Pro Ala Gly Ser Trp 20 25 30 Gly Ala Gin Ile Ile Gly Gly His Glu Val Thr Pro His Ser Arg 40 45 Pro Tyr Met Ala Ser Val Arg Phe Gly Gly Gin His His Cys Gly 50 55 60 Gly Phe Leu Leu Arg Ala Arg Trp Val Val Ser Ala Ala His Cys 65 70 75 Phe Ser His Arg Asp Leu Arg Thr Gly Leu Val Val Leu Gly Ala 80 85 90 His Val Leu Ser Thr Ala Glu Pro Thr Gin Gin Val Phe Gly Ile 95 100 105 Asp Ala Leu Thr Thr His Pro Asp Tyr His Pro Met Thr His Ala 110 115 120 Asn Asp Ile Cys Leu Leu 125 Arg Leu Asn Gly Ser Ala Val Leu Gly 130 135 601 Pro Ala Val Gly Leu Leu Arg Leu Pro Gly Arg Arg Ala Arg Pro 140 145 150 Pro Thr Ala Gly Thr Arg Cys Arg Val Ala Gly Trp Gly Phe Val 155 160 165 Ser Asp Phe Glu Glu Leu Pro Pro Gly Leu Met Glu Ala Lys Val 170 175 180 Arg Val Leu Asp Pro Asp Val Cys Asn Ser Ser Trp Lys Gly His 185 190 195 Leu Thr Leu Thr Met Leu Cys Thr Arg Ser Gly Asp Ser His Arg 200 205 210 Arg Gly Phe Cys Ser Ala Asp Ser Gly Gly Pro L6u Val Cys Arg 215 220 225 Asn Arg Ala His Gly Leu Val Ser Phe Ser Gly Leu Trp Cys Gly 230 235 240 Asp Pro Lys Thr Pro Asp Val Tyr Thr Gin Val Ser Ala Phe Val 245 250 255 Ala Trp Ile Trp Asp Val Val Arg Arg Ser Ser Pro Gin Pro Gly 260 265 270 Pro Leu Pro Gly Thr Thr Arg Pro Pro Gly Glu Ala Ala 275 280 <21.0> 112 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 112 gacgtctgca acagctcctg gaag 24 <210> 113 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 113 cgagaaggaa acgaggccgt gag 23 <210> 114 <211> 44 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 114 tgacacttac catgctctgc acccgcagtg gggacagcca caga 44 602 <210> 115 <211> 1808 <212> DNA <213> Homo sapiens <400> 115 gagctaccca ggcggctggt gtgcagcaag ctccgcgccg actccggacg 50 cctgacgcct gacgcctgtc cccggcccgg catgagccgc tacctgctgc 100 cgctgtcggc gctgggcacg gtagcaggcg ccgccgtgct gctcaaggac 150 tatgtcaccg gtggggcttg ccccagcaag gccaccatcc ctgggaagac 200 ggtcatcgtg acgggcgcca acacaggcat cgggaagcag accgccttgg 250 aactggccag gagaggaggc aacatcatcc tggcctgccg agacatggag 300 aagtgtgagg cggcagcaaa ggacatccgc ggggagaccc tcaatcacca 350 tgtcaacgcc cggcacctgg acttggcttc cctcaagtct atccgagagt 400 ttgcagcaaa gatcattgaa gaggaggagc gagtggacat tctaatcaac 450 aacgcgggtg tgatgcggtg cccccactgg accaccgagg acggcttcga 500 gatgcagttt ggcgttaacc acctgggtca ctttctcttg acaaacttgc 550 tgctggacaa gctgaaagcc tcagcccctt cgcggatcat caacctctcg 600 tccctggccc atgttgctgg gcacatagac tttgacgact tgaactggca 650 gacgaggaag tataacacca aagccgccta ctgccagagc aagctcgcca 700 tcgtcctctt caccaaggag ctgagccggc ggctgcaagg ctctggtgtg 750 actgtcaacg ccctgcaccc cggcgtggcc aggacagagc tgggcagaca 800 cacgggcatc catggctcca ccttctccag caccacactc gggcccatct 850 tctggctgct ggtcaagagc cccgagctgg ccgcccagcc cagcacatac 900 ctggccgtgg cggaggaact ggcggatgtt tccggaaagt acttcgatgg 950 actcaaacag aaggccccgg cccccgaggc tgaggatgag gaggtggccc 1000 ggaggctttg ggctgaaagt gcccgcctgg tgggcttaga ggctccctct 1050 gtgagggagc agcccctccc cagataacct ctggagcaga tttgaaagcc 1100 aggatggcgc ctccagaccg aggacagctg tccgccatgc ccgcagcttc 1150 ctggcactac ctgagccggg agacccagga ctggcggccg ccatgcccgc 1200 agtaggttct agggggcggt gctggccgca gtggactggc ctgcaggtga 1250 gcactgcccc gggctctggc tggttccgtc tgctctgctg ccagcagggg 1300 agaggggcca tctgatgctt cccctgggaa tctaaactgg gaatggccga 1350 ggaggaaggg gctctgtgca cttgcaggcc acgtcaggag agccagcggt 1400 603 gcctgtcggg gagggttcca aggtgctccg tgaagagcat gggcaagttg 1450 tctgacactt ggtggattct tgggtccctg tgggaccttg tgcatgcatg 1500 gtcctctctg agccttggtt tcttcagcag tgagatgctc agaataactg 1550 ctgtctccca tgatggtgtg gtacagcgag ctgttgtctg gctatggcat 1600 ggctgtgccg ggggtgtttg ctgagggctt cctgtgccag agcccagcca 1650 gagagcaggt gcaggtgtca tcccgagttc aggctctgca cggcatggag 1700 tgggaacccc accagctgct gctacaggac ctgggattgc ctgggactcc 1750 caccttccta tcaattctca tggtagtcca aactgcagac tctcaaactt 1800 gctcattt 1808 <210> 116 <211> 331 <212> PRT <213> Homo sapiens <400> 116 Met Ser Arg Tyr Leu Leu Pro Leu Ser Ala Leu Gly Thr Val Ala 1 5 10 15 Gly Ala Ala Val Leu Leu Lys Asp Tyr Val Thr Gly Gly Ala Cys 20 25 30 Pro Ser Lys Ala Thr Ile Pro Gly Lys Thr Val Ile Val Thr Gly 35 40 45 Ala Asn Thr Gly Ile Gly Lys Gin Thr Ala Leu Glu Leu Ala Arg 50 55 60 Arg Gly Gly Asn Ile Ile Leu Ala Cys Arg Asp Met Glu Lys Cys 65 70 75 Glu Ala Ala Ala Lys Asp Ile Arg Gly Glu Thr Leu Asn His His 80 85 90 Val Asn Ala Arg His Leu Asp Leu Ala Ser Leu Lys Ser Ile Arg 95 100 105 Glu Phe Ala Ala Lys Ile Ile Glu Glu Glu Glu Arg Val Asp Ile 110 115 120 Leu Ile Asn Asn Ala Gly Val Met Arg Cys Pro His Trp Thr Thr 125 130 135 Glu Asp Gly Phe Glu Met Gin Phe Gly Val Asn His Leu Gly His 140 145 150 Phe Leu Leu Thr Asn Leu Leu Leu Asp Lys Leu Lys Ala Ser Ala 155 160 165 Pro Ser Arg Ile Ile Asn Leu Ser Ser Leu Ala His Val Ala Gly 170 175 180 His Ile Asp Phe Asp Asp Leu Asn Trp Gin Thr Arg Lys Tyr Asn 185 190 195 604 Thr Lys Ala Ala Tyr Cys Gin Ser Lys Leu Ala Ile Val Leu Phe 200 205 210 Thr Lys Glu Leu Ser Arg Arg Leu Gin Gly Ser Gly Val Thr Val 215 220 225 Asn Ala Leu His Pro Gly Val Ala Arg Thr Glu Leu Gly Arg His 230 235 240 Thr Gly Ile His Gly Ser Thr Phe Ser Ser Thr Thr Leu Gly Pro 245 250 255 Ile Phe Trp Leu Leu Val Lys Ser Pro Glu Leu Ala Ala Gin Pro 260 265 270 Ser Thr Tyr Leu Ala Val Ala Glu Glu Leu Ala Asp Val Ser Gly 275 280 285 Lys Tyr Phe Asp Gly Leu Lys Gin Lys Ala Pro Ala Pro Glu Ala 290 295 300 Glu Asp Glu Glu Val Ala Arg Arg Leu Trp Ala Glu Ser Ala Arg 305 310 315 Leu Val Gly Leu Glu Ala Pro Ser Val Arg Glu Gin Pro Leu Pro 320 325 330 Arg <210> 117 <211> 2249 <212> DNA <213> Homo sapiens <400> 117 gaagttcgcg agcgctggca tgtggtcctg gggcgcggct ggcggcgctg 50 ctggcggtgc tggcgctcgg gacaggagac ccagaaaggg ctgcggctcg 100 gggcgacacg ttctcggcgc tgaccagcgt ggcgcgcgcc ctggcgcccg 150 agcgccggct gctggggctg ctgaggcggt acctgcgcgg ggaggaggcg 200 cggctgcggg acctgactag attctacgac aaggtacttt ctttgcatga 250 ggattcaaca acccctgtgg ctaaccctct gcttgcattt actctcatca 300 aacgcctgca gtctgactgg aggaatgtgg tacatagtct ggaggccagt 350 gagaacatcc gagctctgaa ggatggctat gagaaggtgg agcaagacct 400 tccagccttt gaggaccttg agggagcagc aagggccctg atgcggctgc 450 aggacgtgta catgctcaat gtgaaaggcc tggcccgagg tgtctttcag 500 agagtcactg gctctgccat cactgacctg tacagcccca aacggctctt 550 ttctctcaca ggggatgact gcttccaagt tggcaaggtg gcctatgaca 600 tgggggatta ttaccatgcc attccatggc tggaggaggc tgtcagtctc 650 605 ttccgaggat cttacggaga gtggaagaca gaggatgagg caagtctaga 700 agatgccttg gatcacttgg cctttgctta tttccgggca ggaaatgttt 750 cgtgtgccct cagcctctct cgggagtttc ttctctacag cccagataat 800 aagaggatgg ccaggaatgt cttgaaatat gaaaggctct tggcagagag 850 ccccaaccac gtggtagctg aggctgtcat ccagaggccc aatatacccc 900 acctgcagac cagagacacc tacgaggggc tatgtcagac cctgggttcc 950 cagcccactc tctaccagat ccctagcctc tactgttcct atgagaccaa 1000 ttccaacgcc tacctgctgc tccagcccat ccggaaggag gtcatccacc 1050 tggagcccta cattgctctc taccatgact tcgtcagtga ctcagaggct 1100 cagaaaatta gagaacttgc agaaccatgg ctacagaggt cagtggtggc 1150 atcaggggag aagcagttac aagtggagta ccgcatcagc aaaagtgcct 1200 ggctgaagga cactgttgac ccaaaactgg tgaccctcaa ccaccgcatt 1250 gctgccctca caggccttga tgtccggcct ccctatgcag agtatctgca 1300 ggtggtgaac tatggcatcg gaggacacta tgagcctcac tttgaccatg 1350 ctacgtcacc aagcagcccc ctctacagaa tgaagtcagg aaaccgagtt 1400 gcaacattta tgatctatct gagctcggtg gaagctggag gagccacagc 1450 cttcatctat gccaacctca gcgtgcctgt ggttaggaat gcagcactgt 1500 tttggtggaa cctgcacagg agtggtgaag gggacagtga cacacttcat 1550 gctggctgtc ctgtcctggt gggagataag tgggtggcca acaagtggat 1600 acatgagtat ggacaggaat tccgcagacc ctgcagctcc agccctgaag 1650 actgaactgt tggcagagag aagctggtgg agtcctgtgg ctttccagag 1700 aagccaggag ccaaaagctg gggtaggaga ggagaaagca gagcagcctc 1750 ctggaagaag gccttgtcag ctttgtctgt gcctcgcaaa tcagaggcaa 1800 gggagaggtt gttaccaggg gacactgaga atgtacattt gatctgcccc 1850 agccacggaa ggcctgagag gtcagagtag ggaagtttct gatgcacagt ggagttcaga acaaaggagg tactctctgt ggggagtgga tgggaacagg 1900 1950 acatctcaac agtctcaggt tcgatcagtg ggtcttttgg cactttgaac 2000 cttgaccaca gggaccaaga agtggcaatg aggacacctg caggaggggc 2050 tagcctgact cccagaactt taagactttc tccccactgc cttctgctgc 2100 agcccaagca gggagtgtcc ccctcccaga agcatatccc agatgagtgg 2150 tacattatat aaggattttt tttaagttga aaacaacttt cttttctttt 2200 606 tgtatgatgg ttttttaaca cagtcattaa aaatgtttat aaatcaaaa 2249 <210> 118 <211> 544 <212> PRT <213> Homo sapiens <400> 118 Met Gly Pro Gly Ala Arg Leu Ala Ala Leu Leu Ala Val Leu Ala 10 15 Leu Gly Thr Gly Asp Pro Glu Arg Ala Ala Ala Arg Gly Asp Thr 25 30 Phe Ser Ala Leu Thr Ser Val Ala Arg Ala Leu Ala Pro Glu Arg 40 45 Arg Leu Leu Gly Leu Leu Arg Arg Tyr Leu Arg Gly Glu Glu Ala 50 55 60 Arg Leu Arg Asp Leu Thr Arg Phe Tyr Asp Lys Val Leu Ser Leu 65 70 75 His Glu Asp Ser Thr Thr Pro Val Ala Asn Pro Leu Leu Ala Phe 80 85 90 Thr Leu Ile Lys Arg Leu Gin Ser Asp Trp Arg Asn Val Val His 95 100 105 Ser Leu Glu Ala Ser Glu Asn Ile Arg Ala Leu Lys Asp Gly Tyr 110 115 120 Glu Lys Val Glu Gin Asp Leu Pro Ala Phe Glu Asp Leu Glu Gly 125 130 135 Ala Ala Arg Ala Leu Met Arg Leu Gin Asp Val Tyr Met Leu Asn 140 145 150 Val Lys Gly Leu Ala Arg Gly Val Phe Gin Arg Val Thr Gly Ser 155 160 165 Ala Ile Thr Asp Leu Tyr Ser Pro Lys Arg Leu Phe Ser Leu Thr 170 175 180 Gly Asp Asp Cys Phe Gin Val Gly Lys Val Ala Tyr Asp Met Gly 185 190 195 Asp Tyr Tyr His Ala Ile Pro Trp Leu Glu Glu Ala Val Ser Leu 200 205 210 Phe Arg Gly Ser Tyr Gly Glu Trp Lys Thr Glu Asp Glu Ala Ser 215 220 225 Leu Glu Asp Ala Leu Asp His Leu Ala Phe Ala Tyr Phe Arg Ala 230 235 240 Gly Asn Val Ser Cys Ala Leu Ser Leu Ser Arg Glu Phe Leu Leu 245 250 255 Tyr Ser Pro Asp Asn Lys Arg Met Ala Arg Asn Val Leu Lys Tyr 260 265 270 607 Glu Arg Leu Leu Ala Glu Ser Pro Asn His Val Val Ala Glu Ala 275 280 285 Val Ile Gin Arg Pro Asn Ile Pro His Leu Gin Thr Arg Asp Thr 290 295 300 Tyr Glu Gly Leu Cys Gin Thr Leu Gly Ser Gin Pro Thr Leu Tyr 305 310 315 Gin Ile Pro Ser Leu Tyr Cys Ser Tyr Glu Thr Asn Ser Asn Ala 320 325 330 Tyr Leu Leu Leu Gin Pro Ile Arg Lys Glu Val Ile His Leu Glu 335 340 345 Pro Tyr Ile Ala Leu Tyr His Asp Phe Val Ser Asp Ser Glu Ala 350 355 360 Gin Lys Ile Arg Glu Leu Ala Glu Pro Trp Leu Gin Arg Ser Val 365 370 375 Val Ala Ser Gly Glu Lys Gin Leu Gin Val Glu Tyr Arg Ile Ser 380 385 390 Lys Ser Ala Trp Leu Lys Asp Thr Val Asp Pro Lys Leu Val Thr 395 400 405 Leu Asn His Arg Ile Ala Ala Leu Thr Gly Leu Asp Val Arg Pro 410 415 420 Pro Tyr Ala Glu Tyr Leu Gin Val Val Asn Tyr Gly Ile Gly Gly 425 430 435 His Tyr Glu Pro His Phe Asp His Ala Thr Ser Pro Ser Ser Pro 440 445 450 Leu Tyr Arg Met Lys Ser Gly Asn Arg Val Ala Thr Phe Met Ile 455 460 465 Tyr Leu Ser Ser Val Glu Ala Gly Gly Ala Thr Ala Phe Ile Tyr 470 475 480 Ala Asn Leu Ser Val Pro Val Val Arg Asn Ala Ala Leu Phe Trp 485 490 495 Trp Asn Leu His Arg Ser Gly Glu Gly Asp Ser Asp Thr Leu His 500 505 510 Ala Gly Cys Pro Val Leu Val Gly Asp Lys Trp Val Ala Asn Lys 515 520 525 Trp Ile His Glu Tyr Gly Gin Glu Phe Arg Arg Pro Cys Ser Ser 530 535 540 Ser Pro Glu Asp <210> 119 <211> 23 <212> DNA <213> Artificial Sequence 608 <220> <223> Synthetic oligonucleotide probe <400> 119 cgggacagga gacccagaaa ggg 23 <210> 120 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 120 ggccaagtga tccaaggcat cttc 24 <210> 121 <211> 49 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 121 ctgcgggacc tgactagatt ctacgacaag gtactttctt tgcatgggg 49 <210> 122 <211> 1778 <212> DNA <213> Homo sapiens <400> 122 gagataggga gtctgggttt aagttcctgc tccatctcag gagcccctgc 50 tcccacccct aggaagccac cagactccac ggtgtggggc caatcaggtg 100 gaatcggccc tggcaggtgg ggccacgagc gctggctgag ggaccgagee 150 ggagagcccc ggagcccccg taacccgcgc ggggagegee caggatgccg 200 cgcggggact cggagcaggt gcgctactgc gcgcgcttct cctacctctg 250 gctcaagttt tcacttatca tctattccac cgtgttctgg ctgattgggg 300 ccctggtcct gtctgtgggc atetatgeag aggttgagcg gcagaaatat 350 aaaacccttg aaagtgcctt cctggctcca gccatcatcc tcatcctcct 400 gggcgtcgtc atgttcatgg tctccttcat tggtgtgctg gcgtccctcc 450 gtgacaacct ctcatcatgg gtaccttctc ageteattgg caagcattca tggcgtggtg tgtacatcct gccttgacct tgggatctgc tccggaacca 500 550 gaccattgac ttcctgaacg acaacattcg aagaggaatt gagaactact 600 atgatgatct ggacttcaaa aacatcatgg actttgttca gaaaaagttc 650 aagtgctgtg gcggggagga ctaccgagat tggagcaaga atcagtacca 700 cgactgcagt gcccctggac ccctggcctg tggggtgccc tacacctgct 750 609 gcatcaggaa cacgacagaa gttgtcaaca ccatgtgtgg ctacaaaact 800 atcgacaagg agcgtttcag tgtgcaggat gtcatctacg tgcggggctg 850 caccaacgcc gtgatcatct ggttcatgga caactacacc atcatggcgt 900 gcatcctcct gggcatcctg cttccccagt tcctgggggt gctgctgacg 950 ctgctgtaca tcacccgggt ggaggacatc atcatggagc actctgtcac 1000 tgatgggctc ctggggcccg gtgccaagcc cagcgtggag gcggcaggca 1050 cgggatgctg cttgtgctac cccaattagg gcccagcctg ccatggcagc 1100 tccaacaagg accgtctggg atagcacctc tcagtcaaca tcgtggggct 1150 ggacagggct gcggcccctc tgcccacact cagtactgac caaagccagg 1200 gctgtgtgtg cctgtgtgta ggtcccacgg cctctgcctc cccagggagc 1250 agagcctggg cctcccctaa gaggctttcc ccgaggcagc tctggaatct 1300 gtgcccacct ggggcctggg gaacaaggcc ctcctttctc caggcctggg 1350 ctacagggga gggagagcct gaggctctgc tcagggccca tttcatctct 1400 ggcagtgcct tggcggtggt attcaaggca gttttgtagc acctgtaatt 1450 ggggagaggg agtgtgcccc tcggggcagg agggaagggc atctggggaa 1500 gggcaggagg gaagagctgt ccatgcagcc acgcccatgg ccaggttggc 1550 ctcttctcag cctcccaggt gccttgagcc ctcttgcaag ggcggctgct 1600 tccttgagcc tagttttttt ttacgtgatt tttgtaacat tcattttttt 1650 gtacagataa caggagtttc tgactaatca aagctggtat ttccccgcat 1700 gtcttattct tgcccttccc ccaaccagtt tgttaatcaa acaataaaaa 1750 catgttttgt tttgttttta aaaaaaaa 1778 <210> 123 <211> 294 <212> PRT <213> Homo sapiens <400> 123 Met Pro Arg Gly Asp Ser Glu Gin Val Arg Tyr Cys Ala Arg Phe 10 15 Ser Tyr Leu Trp Leu Lys Phe Ser Leu Ile Ile Tyr Ser Thr Val 25 30 Phe Trp Leu Ile Gly Ala Leu Val Leu Ser Val Gly Ile Tyr Ala 40 45 Glu Val Glu Arg Gin Lys Tyr Lys Thr Leu Glu Ser Ala Phe Leu 50 55 60 Ala Pro Ala Ile Ile Leu Ile Leu Leu Gly Val Val Met Phe Met 65 70 75 610 Val Ser Phe Ile Gly Val Leu Ala Ser Leu Arg Asp Asn Leu Tyr 80 85 90 Leu Leu Gin Ala Phe Met Tyr Ile Leu Gly Ile Cys Leu Ile Met 95 100 105 Glu Leu Ile Gly Gly Val Val Ala Leu Thr Phe Arg Asn Gin Thr 110 115 120 Ile Asp Phe Leu Asn Asp Asn Ile Arg Arg Gly Ile Glu Asn Tyr 125 130 135 Tyr Asp Asp Leu Asp Phe Lys Asn Ile Met Asp Phe Val Gin Lys 140 145 150 Lys Phe Lys Cys Cys Gly Gly Glu Asp Tyr Arg Asp Trp Ser Lys 155 160 165 Asn Gin Tyr His Asp Cys Ser Ala Pro Gly Pro Leu Ala Cys Gly 170 175 180 Val Pro Tyr Thr Cys Cys Ile Arg Asn Thr Thr Glu Val Val Asn 185 190 195 Thr Met Cys Gly Tyr Lys Thr Ile Asp Lys Glu Arg Phe Ser Val 200 205 210 Gin Asp Val Ile Tyr Val Arg Gly Cys Thr Asn Ala Val Ile Ile 215 220 225 Trp Phe Met Asp Asn Tyr Thr Ile Met Ala Cys Ile Leu Leu Gly 230 235 240 Ile Leu Leu Pro Gin Phe Leu Gly Val Leu Leu Thr Leu Leu Tyr 245 250 255 Ile Thr Arg Val Glu Asp Ile Ile Met Glu His Ser Val Thr Asp 260 265 270 Gly Leu Leu Gly Pro Gly Ala Lys Pro Ser Val Glu Ala Ala Gly 275 280 285 Thr Gly Cys Cys Leu Cys Tyr Pro Asn 290 <210> 124 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 124 atcatctatt ccaccgtgtt ctggc 25 <210> 125 <211> 25 <212> DNA <213> Artificial Sequence 611 <220> <223> Synthetic oligonucleotide probe <400> 125 gacagagtgc tccatgatga tgtcc 25 <210> 126 <211> 50 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 126 cctgtctgtg ggcatctatg cagaggttga gcggcagaaa tataaaaccc 50 <210> 127 <211> 1636 <212> DNA <213> Homo sapiens <400> 127 gaggagcggg ccgaggactc cagcgtgccc aggtctggca tcctgcactt 50 gctgccctct gacacctggg aagatggccg gcccgtggac cttcaccctt 100 ctctgtggtt tgctggcagc caccttgatc caagccaccc tcagtcccac 150 tgcagttctc atcctcggcc caaaagtcat caaagaaaag ctgacacagg 200 agctgaagga ccacaacgcc accagcatcc tgcagcagct gccgctgctc 250 agtgccatgc gggaaaagcc agccggaggc atccctgtgc tgggcagcct 300 ggtgaacacc gtcctgaagc acatcatctg gctgaaggtc atcacagcta 350 acatcctcca gctgcaggtg aagccctcgg ccaatgacca ggagctgcta 400 gtcaagatcc ccctggacat ggtggctgga ttcaacacgc ccctggtcaa 450 gaccatcgtg gagttccaca tgacgactga ggcccaagcc accatccgca 500 tggacaccag tgcaagtggc cccacccgcc tggtcctcag tgactgtgcc 550 accagccatg ggagcctgcg catccaactg ctgtataagc tctccttcct 600 ggtgaacgcc ttagctaagc aggtcatgaa cctcctagtg ccatccctgc 650 ccaatctagt gaaaaaccag ctgtgtcccg tgatcgaggc ttccttcaat 700 ggcatgtatg cagacctcct gcagctggtg aaggtgccca tttccctcag 750 cattgaccgt ctggagtttg accttctgta tcctgccatc aagggtgaca 800 ccattcagct accaagtggt ctacctgggg tcaataactc gccaagttgt tgcagcttcc tggactcaca ctgacaatgc gggaaaggtg ccaccctgga 850 900 caacatcccg ttcagcctca tcgtgagtca ggacgtggtg aaagctgcag 950 tggctgctgt gctctctcca gaagaattca tggtcctgtt ggactctgtg 1000 612 cttcctgaga gtgcccatcg gctgaagtca agcatcgggc tgatcaatga 1050 aaaggctgca gataagctgg gatctaccca gatcgtgaag atcctaactc 1100 aggacactcc cgagtttttt atagaccaag gccatgccaa ggtggcccaa 1150 ctgatcgtgc tggaagtgtt tccctccagt gaagccctcc gccctttgtt 1200 caccctgggc atcgaagcca gctcggaagc tcagttttac accaaaggtg 1250 accaacttat actcaacttg aataacatca gctctgatcg gatccagctg 1300 atgaactctg ggattggctg gttccaacct gatgttctga aaaacatcat 1350 cactgagatc atccactcca tcctgctgcc gaaccagaat ggcaaattaa 1400 gatctggggt cccagtgtca ttggtgaagg ccttgggatt cgaggcagct 1450 gagtcctcac tgaccaagga tgcccttgtg cttactccag cctccttgtg 1500 gaaacccagc tctcctgtct cccagtgaag acttggatgg cagccatcag 1550 ggaaggctgg gtcccagctg ggagtatggg tgtgagctct atagaccatc 1600 cctctctgca atcaataaac acttgcctgt gaaaaa 1636 <210> 128 <211> 484 <212> PRT <213> Homo sapiens <400> 128 Met Ala Gly Pro Trp Thr Phe Thr Leu Leu Cys Gly Leu Leu Ala 1 5 10 15 Ala Thr Leu Ile Gin Ala Thr Leu Ser Pro Thr Ala Val Leu Ile 20 25 30 Leu Gly Pro Lys Val Ile Lys Glu Lys Leu Thr Gin Glu Leu Lys 35 40 45 Asp His Asn Ala Thr Ser Ile Leu Gin Gin Leu Pro Leu Leu Ser 50 55 60 Ala Met Arg Glu Lys Pro Ala Gly Gly Ile Pro Val Leu Gly Ser 65 70 75 Leu Val Asn Thr Val Leu Lys His Ile Ile Trp Leu Lys Val Ile 80 85 90 Thr Ala Asn Ile Leu Gin Leu Gin Val Lys Pro Ser Ala Asn Asp 95 100 105 Gin Glu Leu Leu Val Lys Ile Pro Leu Asp Met Val Ala Gly Phe 110 115 120 Asn Thr Pro Leu Val Lys Thr Ile Val Glu Phe His Met Thr Thr 125 130 135 Glu Ala Gin Ala Thr Ile Arg Met Asp Thr Ser Ala Ser Gly Pro 140 145 150 613 Thr Arg Leu Val Leu Ser Asp Cys Ala Thr Ser His Gly Ser Leu 155 160 165 Arg Ile Gin Leu Leu Tyr Lys Leu Ser Phe Leu Val Asn Ala Leu 170 175 180 Ala Lys Gin Val Met Asn Leu Leu Val Pro Ser Leu Pro Asn Leu 185 190 195 Val Lys Asn Gin Leu Cys Pro Val Ile Glu Ala Ser Phe Asn Gly 200 205 210 Met Tyr Ala Asp Leu Leu Gin Leu Val Lys Val Pro Ile Ser Leu 215 220 225 Ser Ile Asp Arg Leu Glu Phe Asp Leu Leu Tyr Pro Ala Ile Lys 230 235 240 Gly Asp Thr Ile Gin Leu Tyr Leu Gly Ala Lys Leu Leu Asp Ser 245 250 255 Gin Gly Lys Val Thr Lys Trp Phe Asn Asn Ser Ala Ala Ser Leu 260 265 270 Thr Met Pro Thr Leu Asp Asn Ile Pro Phe Ser Leu Ile Val Ser 275 280 285 Gin Asp Val Val Lys Ala Ala Val Ala Ala Val Leu Ser Pro Glu 290 295 300 Glu Phe Met Val Leu Leu Asp Ser Val Leu Pro Glu Ser Ala His 305 310 315 Arg Leu Lys Ser Ser Ile Gly Leu Ile Asn Glu Lys Ala Ala Asp 320 325 330 Lys Leu Gly Ser Thr Gin Ile Val Lys Ile Leu Thr Gin Asp Thr 335 340 345 Pro Glu Phe Phe Ile Asp Gin Gly His Ala Lys Val Ala Gin Leu 350 355 360 lie Val Leu Glu Val Phe Pro Ser Ser Glu Ala Leu Arg Pro Leu 365 370 375 Phe Thr Leu Gly Ile Glu Ala Ser Ser Glu Ala Gin Phe Tyr Thr 380 385 390 Lys Gly Asp Gin Leu Ile Leu Asn Leu Asn Asn Ile Ser Ser Asp 395 400 405 Arg Ile Gin Leu Met Asn Ser Gly Ile Gly Trp Phe Gin Pro Asp 410 415 420 Val Leu Lys Asn Ile Ile Thr Glu Ile Ile His Ser Ile Leu Leu 425 430 435 Pro Asn Gin Asn Gly Lys Leu Arg Ser Gly Val Pro Val Ser Leu 440 445 450 Val Lys Ala Leu Gly Phe Glu Ala Ala Glu Ser Ser Leu Thr Lys 455 460 465 614 Asp Ala Leu Val Leu Thr Pro Ala Ser Leu Trp Lys Pro Ser Ser 470 475 480 Pro Val Ser Gin <210> 129 <211> 2213 <212> DNA <213> Homo sapiens <400> 129 gagcgaacat ggcagcgcgt tggcggtttt ggtgtgtctc tgtgaccatg 50 gtggtggcgc tgctcatcgt ttgcgacgtt ccctcagcct ctgcccaaag 100 aaagaaggag atggtgttat ctgaaaaggt tagtcagctg atggaatgga 150 ctaacaaaag acctgtaata agaatgaatg gagacaagtt ccgtcgcctt 200 gtgaaagccc caccgagaaa ttactccgtt atcgtcatgt tcactgctct 250 ccaactgcat agacagtgtg tcgtttgcaa gcaagctgat gaagaattcc 300 agatcctggc aaactcctgg cgatactcca gtgcattcac caacaggata 350 ttttttgcca tggtggattt tgatgaaggc tctgatgtat ttcagatgct 400 aaacatgaat tcagctccaa ctttcatcaa ctttcctgca aaagggaaac 450 ccaaacgggg tgatacatat gagttacagg tgcggggttt ttcagctgag 500 cagattgccc ggtggatcgc cgacagaact gatgtcaata ttagagtgat 550 tagaccccca aattatgctg gtccccttat gttgggattg cttttggctg 600 ttattggtgg acttgtgtat cttcgaagaa gtaatatgga atttctcttt 650 aataaaactg gatgggcttt tgcagctttg tgttttgtgc ttgctatgac 700 atctggtcaa atgtggaacc atataagagg accaccatat gcccataaga 750 atccccacac gggacatgtg aattatatcc atggaagcag tcaagcccag 800 tttgtagctg aaacacacat tgttcttctg tttaatggtg gagttacctt 850 aggaatggtg cttttatgtg aagctgctac ctctgacatg gatattggaa 900 agcgaaagat aatgtgtgtg gctggtattg gacttgttgt attattcttc 950 agttggatgc tctctatttt tagatctaaa tatcatggct acccatacag 1000 ctttctgatg agttaaaaag gtcccagaga tatatagaca ctggagtact 1050 ggaaattgaa aaacgaaaat cgtgtgtgtt tgaaaagaag aatgcaactt 1100 gtatattttg tattacctct ttttttcaag tgatttaaat agttaatcat 1150 ttaaccaaag aagatgtgta gtgccttaac aagcaatcct ctgtcaaaat 1200 ctgaggtatt tgaaaataat tatcctctta accttctctt cccagtgaac 1250 615 tttatggaac atttaattta gtacaattaa gtatattata aaaattgtaa 1300 aactactact ttgttttagt tagaacaaag ctcaaaacta ctttagttaa 1350 cttggtcatc tgattttata ttgccttatc caaagatggg gaaagtaagt 1400 cctgaccagg tgttcccaca tatgcctgtt acagataact acattaggaa 1450 ttcattctta gcttcttcat ctttgtgtgg atgtgtatac tttacgcatc 1500 tttccttttg agtagagaaa ttatgtgtgt catgtggtct tctgaaaatg 1550 gaacaccatt cttcagagca cacgtctagc cctcagcaag acagttgttt 16 00 ctcctcctcc ttgcatattt cctactgcgc tccagcctga gtgatagagt 1650 gagactctgt ctcaaaaaaa agtatctcta aatacaggat tataatttct 1700 gcttgagtat ggtgttaact accttgtatt tagaaagatt tcagattcat 1750 tccatctcct tagttttctt ttaaggtgac ccatctgtga taaaaatata 1800 gcttagtgct aaaatcagtg taacttatac atggcctaaa atgtttctac 1850 aaattagagt ttgtcactta ttccatttgt acctaagaga aaaataggct 1900 cagttagaaa aggactccct ggccaggcgc agtgacttac gcctgtaatc 1950 tcagcacttt gggaggccaa ggcaggcaga tcacgaggtc aggagttcga 2000 gaccatcctg gccaacatgg tgaaaccccg tctctactaa aaatataaaa 2050 attagctggg tgtggtggca ggagcctgta atcccagcta cacaggaggc 2100 tgaggcacga gaatcacttg aactcaggag atggaggttt cagtgagccg 2150 agatcacgcc actgcactcc agcctggcaa cagagcgaga ctccatctca 2200 aaaaaaaaaa aaa 2213 <210> 130 <211> 335 <212> PRT <213> Homo sapiens <400> 130 Met Ala Ala Arg Trp Arg Phe Trp Cys Val Ser Val Thr Met Val 15 10 15 Val Ala Leu Leu Ile Val Cys Asp Val Pro Ser Ala Ser Ala Gin 20 25 30 Arg Lys Lys Glu Met Val Leu Ser Glu Lys Val Ser Gin Leu Met 35 40 45 Glu Trp Thr Asn Lys Arg Pro Val Ile Arg Met Asn Gly Asp Lys 50 55 60 Phe Arg Arg Leu Val Lys Ala Pro Pro Arg Asn Tyr Ser Val Ile 65 70 75 616 Val Met Phe Thr Ala Leu Gin Leu His Arg Gin Cys Val Val Cys 80 85 90 Lys Gin Ala Asp Glu Glu Phe Gin Ile Leu Ala Asn Ser Trp Arg 95 100 105 Tyr Ser Ser Ala Phe Thr Asn Arg Ile Phe Phe Ala Met Val Asp 110 115 120 Phe Asp Glu Gly Ser Asp Val Phe Gin Met Leu Asn Met Asn Ser 125 130 135 Ala Pro Thr Phe Ile Asn Phe Pro Ala Lys Gly Lys Pro Lys Arg 140 145 150 Gly Asp Thr Tyr Glu Leu Gin Val Arg Gly Phe Ser Ala Glu Gin 155 160 165 Ile Ala Arg Trp Ile Ala Asp Arg Thr Asp Val Asn Ile Arg Val 170 175 180 Ile Arg Pro Pro Asn Tyr Ala Gly Pro Leu Met Leu Gly Leu Leu 185 190 195 Leu Ala Val Ile Gly Gly Leu Val Tyr Leu Arg Arg Ser Asn Met 200 205 210 Glu Phe Leu Phe Asn Lys Thr Gly Trp Ala Phe Ala Ala Leu Cys 215 220 225 Phe Val Leu Ala Met Thr Ser Gly Gin Met Trp Asn His Ile Arg 230 235 240 Gly Pro Pro Tyr Ala His Lys Asn Pro His Thr Gly His Val Asn 245 250 255 Tyr Ile His Gly Ser Ser Gin Ala Gin Phe Val Ala Glu Thr His 260 265 270 Ile Val Leu Leu Phe Asn Gly Gly Val Thr Leu Gly Met Val Leu 275 280 285 Leu Cys Glu Ala Ala Thr Ser Asp Met Asp Ile Gly Lys Arg Lys 290 295 300 Ile Met Cys Val Ala Gly Ile Gly Leu Val Val Leu Phe Phe Ser 305 310 315 Trp Met Leu Ser Ile Phe Arg Ser Lys Tyr His Gly Tyr Pro Tyr 320 325 330 Ser Phe Leu Met Ser 335 <210> 131 <211> 2476 <212> DNA <213> Homo sapiens <400> 131 aagcaaccaa actgcaagct ttgggagttg ttcgctgtcc ctgccctgct 50 ctgctaggga gagaacgcca gagggaggcg gctggcccgg cggcaggctc 100 617 tcagaaccgc taccggcgat gctactgctg tgggtgtcgg tggtcgcagc 150 cttggcgctg gcggtactgg cccccggagc aggggagcag aggcggagag 200 cagccaaagc gcccaatgtg gtgctggtcg tgagcgactc cttcgatgga 250 aggttaacat ttcatccagg aagtcaggta gtgaaacttc cttttatcaa 300 ctttatgaag acacgtggga cttcctttct gaatgcctac acaaactctc 350 caatttgttg cccatcacgc gcagcaatgt ggagtggcct cttcactcac 400 ttaacagaat cttggaataa ttttaagggt ctagatccaa attatacaac 450 atggatggat gtcatggaga ggcatggcta ccgaacacag aaatttggga 500 aactggacta tacttcagga catcactcca ttagtaatcg tgtggaagcg 550 tggacaagag atgttgcttt cttactcaga caagaaggca ggcccatggt 600 taatcttatc cgtaacagga ctaaagtcag agtgatggaa agggattggc 650 agaatacaga caaagcagta aactggttaa gaaaggaagc aattaattac 700 actgaaccat ttgttattta cttgggatta aatttaccac acccttaccc 750 ttcaccatct tctggagaaa attttggatc ttcaacattt cacacatctc 800 tttattggct tgaaaaagtg tctcatgatg ccatcaaaat cccaaagtgg 850 tcacctttgt cagaaatgca ccctgtagat tattactctt cttatacaaa 900 aaactgcact ggaagattta caaaaaaaga aattaagaat attagagcat 950 tttattatgc tatgtgtgct gagacagatg ccatgcttgg tgaaattatt 1000 ttggcccttc atcaattaga tcttcttcag aaaactattg tcatatactc 1050 ctcagaccat ggagagctgg ccatggaaca tcgacagttt tataaaatga 1100 gcatgtacga ggctagtgca catgttccgc ttttgatgat gggaccagga 1150 attaaagccg gcctacaagt atcaaatgtg gtttctcttg tggatattta 1200 ccctaccatg cttgatattg ctggaattcc tctgcctcag aacctgagtg 1250 gatactcttt gttgccgtta tcatcagaaa catttaagaa tgaacataaa 1300 gtcaaaaacc tgcatccacc ctggattctg agtgaattcc atggatgtaa 1350 tgtgaatgcc tccacctaca tgcttcgaac taaccactgg aaatatatag 1400 cctattcgga tggtgcatca atattgcctc aactctttga tctttcctcg 1450 gatccagatg aattaacaaa tgttgctgta aaatttccag aaattactta 1500 ttctttggat cagaagcttc attccattat aaactaccct aaagtttctg 1550 cttctgtcca ccagtataat aaagagcagt ttatcaagtg gaaacaaagt 1600 ataggacaga attattcaaa cgttatagca aatcttaggt ggcaccaaga 1650 ctggcagaag gaaccaagga agtatgaaaa 618 tgcaattgat cagtggctta 1700 aaacccatat gaatccaaga gcagtttgaa caaaaagttt aaaaatagtg 1750 ttctagagat acatataaat atattacaag atcataatta tgtattttaa 1800 atgaaacagt tttaataatt accaagtttt ggccgggcac agtggctcac 1850 acctgtaatc ccaggacttt gggaggctga ggaaagcaga tcacaaggtc 1900 aagagattga gaccatcctg gccaacatgg tgaaaccctg tctctactaa 1950 aaatacaaaa attagctggg cgcggtggtg cacacctata gtctcagcta 2000 ctcagaggct gaggcaggag gatcgcttga acccgggagg cagcagttgc 2050 agtgagctga gattgcgcca ctgtactcca gcctggcaac agagtgagac 2100 tgtgtcgcaa aaaaataaaa ataaaataat aataattacc aatttttcat 2150 tattttgtaa gaatgtagtg tattttaaga taaaatgcca atgattataa 2200 aatcacatat tttcaaaaat ggttattatt taggcctttg tacaatttct 2250 aacaatttag tggaagtatc aaaaggattg aagcaaatac tgtaacagtt 2300 atgttccttt aaataataga gaatataaaa tattgtaata atatgtatca 2350 taaaatagtt gtatgtgagc atttgatggt gaaaaaaaaa aaaaaaaaaa 2400 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2450 aaaaaaaaaa aaaaaaaaaa aaaaaa 2476 <210> 132 <211> 536 <212> PRT <213> Homo sapiens <400> 132 Met Leu Leu Leu Trp Val Ser Val Val Ala Ala Leu Ala Leu Ala 15 10 15 Val Leu Ala Pro Gly Ala Gly Glu Gin Arg Arg Arg Ala Ala Lys 20 25 30 Ala Pro Asn Val Val Leu Val Val Ser Asp Ser Phe Asp Gly Arg 35 40 45 Leu Thr Phe His Pro Gly Ser Gin Val Val Lys Leu Pro Phe Ile 50 55 60 Asn Phe Met Lys Thr Arg Gly Thr Ser Phe Leu Asn Ala Tyr Thr 65 70 75 Asn Ser Pro Ile Cys Cys Pro Ser Arg Ala Ala Met Trp Ser Gly 80 85 90 Leu Phe Thr His Leu Thr Glu Ser Trp Asn Asn Phe Lys Gly Leu 95 100 105 Asp Pro Asn Tyr Thr Thr Trp Met Asp Val Met Glu Arg His Gly 619 110 115 120 Tyr Arg Thr Gin Lys Phe Gly Lys Leu Asp Tyr Thr Ser Gly His 125 130 135 His Ser Ile Ser Asn Arg Val Glu Ala Trp Thr Arg Asp Val Ala 140 145 150 Phe Leu Leu Arg Gin Glu Gly Arg Pro Met Val Asn Leu Ile Arg 155 160 165 Asn Arg Thr Lys Val Arg Val Met Glu Arg Asp Trp Gin Asn Thr 170 175 180 Asp Lys Ala Val Asn Trp Leu Arg Lys Glu Ala Ile Asn Tyr Thr 185 190 195 Glu Pro Phe Val Ile Tyr Leu Gly Leu Asn Leu Pro His Pro Tyr 200 205 210 Pro Ser Pro Ser Ser Gly Glu Asn Phe Gly Ser Ser Thr Phe His 215 220 225 Thr Ser Leu Tyr Trp Leu Glu Lys Val Ser His Asp Ala Ile Lys 230 235 240 Ile Pro Lys Trp Ser Pro Leu Ser Glu Met His Pro Val Asp Tyr 245 250 255 Tyr Ser Ser Tyr Thr Lys Asn Cys Thr Gly Arg Phe Thr Lys Lys 260 265 270 Glu Ile Lys Asn Ile Arg Ala Phe Tyr Tyr Ala Met Cys Ala Glu 275 280 285 Thr Asp Ala Met Leu Gly Glu Ile Ile Leu Ala Leu His Gin Leu 290 295 300 Asp Leu Leu Gin Lys Thr Ile Val Ile Tyr Ser Ser Asp His Gly 305 310 315 Glu Leu Ala Met Glu His Arg Gin Phe Tyr Lys Met Ser Met Tyr 320 325 330 Glu Ala Ser Ala His Val Pro Leu Leu Met Met Gly Pro Gly Ile 335 340 345 Lys Ala Gly Leu Gin Val Ser Asn Val Val Ser Leu Val Asp Ile 350 355 360 Tyr Pro Thr Met Leu Asp Ile Ala Gly Ile Pro Leu Pro Gin Asn 365 370 375 Leu Ser Gly Tyr Ser Leu Leu Pro Leu Ser Ser Glu Thr Phe Lys 380 385 390 Asn Glu His Lys Val Lys Asn Leu His Pro Pro Trp Ile Leu Ser 395 400 405 Glu Phe His Gly Cys Asn Val Asn Ala Ser Thr Tyr Met Leu Arg 410 415 420 Thr Asn His Trp Lys Tyr Ile Ala Tyr Ser Asp Gly Ala Ser Ile 425 Leu Pro Gin Leu Phe Asp 440 Asn Val Ala Val Lys Phe 455 Lys Leu His Ser Ile Ile 470 His Gin Tyr Asn Lys Glu 485 Gly Gin Asn Tyr Ser Asn 500 Asp Trp Gin Lys Glu Pro 515 Trp Leu Lys Thr His Met 530 <210> 133 <211> 1475 <212> DNA <213> Homo sapiens <400> 133 gagagaagtc agcctggcag agagactctg aaatgaggga ttagaggtgt 50 tcaaggagca agagcttcag cctgaagaca agggagcagt ccctgaagac 100 gcttctactg agaggtctgc catggcctct cttggcctcc aacttgtggg 150 ctacatccta ggccttctgg ggcttttggg cacactggtt gccatgctgc 200 tccccagctg gaaaacaagt tcttatgtcg gtgccagcat tgtgacagca 250 gttggcttct ccaagggcct ctggatggaa tgtgccacac acagcacagg 300 catcacccag tgtgacatct atagcaccct tctgggcctg cccgctgaca 350 tccaggctgc ccaggccatg atggtgacat ccagtgcaat ctcctccctg 400 gcctgcatta tctctgtggt gggcatgaga tgcacagtct tctgccagga 450 atcccgagcc aaagacagag tggcggtagc aggtggagtc tttttcatcc 500 ttggaggcct cctgggattc attcctgttg cctggaatct tcatgggatc 550 ctacgggact tctactcacc actggtgcct gacagcatga aatttgagat 600 tggagaggct ctttacttgg gcattatttc ttccctgttc tccctgatag 650 ctggaatcat cctctgcttt tcctgctcat cccagagaaa tcgctccaac 700 tactacgatg cctaccaagc ccaacctctt gccacaagga gctctccaag 750 gcctggtcaa cctcccaaag tcaagagtga gttcaattcc tacagcctga 800 cagggtatgt gtgaagaacc aggggccaga gctggggggt ggctgggtct 850 620 430 435 Leu Ser Ser Asp Pro Asp Glu Leu Thr 445 450 Pro Glu Ile Thr Tyr Ser Leu Asp Gin 460 465 Asn Tyr Pro Lys Val Ser Ala Ser Val 475 480 Gin Phe Ile Lys Trp Lys Gin Ser Ile 490 495 Val Ile Ala Asn Leu Arg Trp His Gin 505 510 Arg Lys Tyr Glu Asn Ala Ile Asp Gin 520 525 Asn Pro Arg Ala Val 535 621 gtgaaaaaca gtggacagca ccccgagggc cacaggtgag ggacactacc 900 actggatcgt gtcagaaggt gctgctgagg atagactgac tttggccatt 950 ggattgagca aaggcagaaa tgggggctag tgtaacagca tgcaggttga 1000 attgccaagg atgctcgcca tgccagcctt tctgttttcc tcaccttgct 1050 gctcccctgc cctaagtccc caaccctcaa cttgaaaccc cattccctta 1100 agccaggact cagaggatcc ctttgccctc tggtttacct gggactccat 1150 ccccaaaccc actaatcaca tcccactgac tgaccctctg tgatcaaaga 1200 ccctctctct ggctgaggtt ggctcttagc tcattgctgg ggatgggaag 1250 gagaagcagt ggcttttgtg ggcattgctc taacctactt ctcaagcttc 1300 cctccaaaga aactgattgg ccctggaacc tccatcccac tcttgttatg 1350 actccacagt gtccagacta atttgtgcat gaactgaaat aaaaccatcc 1400 tacggtatcc agggaacaga aagcaggatg caggatggga ggacaggaag 1450 gcagcctggg acatttaaaa aaata 147 5 <210> 134 <211> 230 <212> PRT <213> Homo sapiens <400> 134 Met Ala Ser.Leu Gly Leu Gin Leu Val Gly Tyr Ile Leu Gly Leu 15 10 15 Leu Gly Leu Leu Gly Thr Leu Val Ala Met Leu Leu Pro Ser Trp 20 25 30 Lys Thr Ser Ser Tyr Val Gly Ala Ser Ile Val Thr Ala Val Gly 35 40 45 Phe Ser Lys Gly Leu Trp Met Glu Cys Ala Thr His Ser Thr Gly 50 55 60 Ile Thr Gin Cys Asp Ile Tyr Ser Thr Leu Leu Gly Leu Pro Ala 65 70 75 Asp Ile Gin Ala Ala Gin Ala Met Met Val Thr Ser Ser Ala Ile 80 85 90 Ser Ser Leu Ala Cys Ile Ile Ser Val Val Gly Met Arg Cys Thr 95 100 105 Val Phe Cys Gin Glu Ser Arg Ala Lys Asp Arg Val Ala Val Ala 110 115 120 Gly Gly Val Phe Phe Ile Leu Gly Gly Leu Leu Gly Phe Ile Pro 125 130 135 Val Ala Trp Asn Leu His Gly Ile Leu Arg Asp Phe Tyr Ser Pro 140 145 150 622 Leu Val Pro Asp Ser Met 155 Leu Gly Ile Ile Ser Ser 170 Leu Cys Phe Ser Cys Ser 185 Asp Ala Tyr Gin Ala Gin 200 Pro Gly Gin Pro Pro Lys 215 Leu Thr Gly Tyr Val 230 <210> 135 <211> 610 <212> DNA <213> Homo sapiens <400> 135 gcactgctgc tgtcccatca gctgctctga agctccatgg tgcccagaat 50 cttcgctcct gcttatgtgt cagtctgtct cctcctcttg tgtccaaggg 100 aagtcatcgc tcccgctggc tcagaaccat ggctgtgcca gccggcaccc 150 aggtgtggag acaagatcta caaccccttg gagcagtgct gttacaatga 200 cgccatcgtg tccctgagcg agacccgcca atgtggtccc ccctgcacct 250 tctggccctg ctttgagctc tgctgtcttg attcctttgg cctcacaaac 300 gattttgttg tgaagctgaa ggttcagggt gtgaattccc agtgccactc 350 atctcccatc tccagtaaat gtgaaagcag aagacgtttt ccctgagaag 400 acatagaaag aaaatcaact ttcactaagg catctcagaa acataggcta 450 aggtaatatg tgtaccagta gagaagcctg aggaatttac aaaatgatgc 500 agctccaagc cattgtatgg cccatgtggg agactgatgg gacatggaga 550 atgacagtag attatcagga aataaataaa gtggtttttc caatgtacac 600 acctgtaaaa 610 <210> 136 <211> 119 <212> PRT <213> Homo sapiens <400> 136 Met Val Pro Arg Ile Phe Ala Pro Ala Tyr Val Ser Val Cys Leu 15 10 15 Leu Leu Leu Cys Pro Arg Glu Val Ile Ala Pro Ala Gly Ser Glu 20 25 30 Lys Phe Glu Ile Gly Glu Ala Leu Tyr 160 165 Leu Phe Ser Leu Ile Ala Gly Ile Ile 175 180 Ser Gin Arg Asn Arg Ser Asn Tyr Tyr 190 195 Pro Leu Ala Thr Arg Ser Ser Pro Arg 205 210 Val Lys Ser Glu Phe Asn Ser Tyr Ser 220 225 623 Pro Trp Leu Cys Gin Pro Ala Pro Arg Cys Gly Asp Lys lie Tyr 35 40 45 Asn Pro Leu Glu Gin Cys Cys Tyr Asn Asp Ala Ile Val Ser Leu 50 55 60 Ser Glu Thr Arg Gin Cys Gly Pro Pro Cys Thr Phe Trp Pro Cys 65 70 75 Phe Glu Leu Cys Cys Leu Asp Ser Phe Gly Leu Thr Asn Asp Phe 80 85 90 Val Val Lys Leu Lys Val Gin Gly Val Asn Ser Gin Cys His Ser 95 100 105 Ser Pro Ile Ser Ser Lys Cys Glu Ser Arg Arg Arg Phe Pro 110 115 <210> 137 <211> 771 <212> DNA <213> Homo sapiens <400> 137 ctccactgca accacccaga gccatggctc cccgaggctg catcgtagct 50 gtctttgcca ttttctgcat ctccaggctc ctctgctcac acggagcccc 100 agtggccccc atgactcctt acctgatgct gtgccagcca cacaagagat 150 gtggggacaa gttctacgac cccctgcagc actgttgcta tgatgatgcc 200 gtcgtgccct tggccaggac ccagacgtgt ggaaactgca ccttcagagt 250 ctgctttgag cagtgctgcc cctggacctt catggtgaag ctgataaacc 300 agaactgcga ctcagcccgg acctcggatg acaggctttg tcgcagtgtc 350 agctaatgga acatcagggg aacgatgact cctggattct ccttcctggg 400 tgggcctgga gaaagaggct ggtgttacct gagatctggg atgctgagtg 450 gctgtttggg ggccagagaa acacacactc aactgcccac ttcattctgt 500 gacctgtctg aggcccaccc tgcagctgcc ctgaggaggc ccacaggtcc 550 ccttctagaa ttctggacag catgagatgc gtgtgctgat gggggcccag 600 ggactctgaa ccctcctgat gacccctatg gccaacatca acccggcacc 650 accccaaggc tggctgggga acccttcacc cttctgtgag attttccatc 700 atctcaagtt ctcttctatc caggagcaaa gcacaggatc ataataaatt 750 tatgtacttt ataaatgaaa a 771 <210> 138 <211> 110 <212> PRT <213> Homo sapiens 624 <400> 138 Met Ala Pro Arg Gly Cys Ile Val Ala Val Phe Ala Ile Phe Cys 15 10 15 Ile Ser Arg Leu Leu Cys Ser His Gly Ala Pro Val Ala Pro Met 20 25 30 Thr Pro Tyr Leu Met Leu Cys Gin Pro His Lys Arg Cys Gly Asp 35 40 45 Lys Phe Tyr Asp Pro Leu Gin His Cys Cys Tyr Asp Asp Ala Val 50 55 60 Val Pro Leu Ala Arg Thr Gin Thr Cys Gly Asn Cys Thr Phe Arg 65 70 75 Val Cys Phe Glu Gin Cys Cys Pro Trp Thr Phe Met Val Lys Leu 80 85 90 Ile Asn Gin Asn Cys Asp Ser Ala Arg Thr Ser Asp Asp Arg Leu 95 100 105 Cys Arg Ser Val Ser 110 <210> 139 <211> 2044 <212> DNA <213> Homo sapiens <400> 139 gggggcgggt gcctggagca cggcgctggg gccgcccgca gcgctcactc 50 gctcgcactc agtcgcggga ggcttccccg cgccggccgc gtcccgcccg 100 ctccccggca ccagaagttc ctctgcgcgt ccgacggcga catgggcgtc 150 cccacggccc tggaggccgg cagctggcgc tggggatccc tgctcttcgc 200 tctcttcctg gctgcgtccc taggtccggt ggcagccttc aaggtcgcca 250 cgccgtattc cctgtatgtc tgtcccgagg ggcagaacgt caccctcacc 300 tgcaggctct tgggccctgt ggacaaaggg cacgatgtga ccttctacaa 350 gacgtggtac cgcagctcga ggggcgaggt gcagacctgc tcagagcgcc 400 ggcccatccg caacctcacg ttccaggacc ttcacctgca ccatggaggc 450 caccaggctg ccaacaccag ccacgacctg gctcagcgcc acgggctgga 500 gtcggcctcc gaccaccatg gcaacttctc catcaccatg cgcaacctga 550 ccctgctgga tagcggcctc tactgctgcc tggtggtgga gatcaggcac 600 caccactcgg agcacagggt ccatggtgcc atggagctgc aggtgcagac 650 aggcaaagat gcaccatcca actgtgtggt gtacccatcc tcctcccagg 700 atagtgaaaa catcacggct gcagccctgg ctacgggtgc ctgcatcgta 750 ggaatcctct gcctccccct catcctgctc ctggtctaca agcaaaggca 800 625 ggcagcctcc aaccgccgtg cccaggagct ggtgcggatg gacagcaaca 850 ttcaagggat tgaaaacccc ggctttgaag cctcaccacc tgcccagggg 900 atacccgagg ccaaagtcag gcaccccctg tcctatgtgg cccagcggca 950 gccttctgag ctcctccagg tctgggcggc ccccggagac atctgctttc gtcttcttcc ggagcccagc catccctgga acccccctgt ccctgtccct 1000 1050 gactctccaa actttgaggt catctagccc agctggggga cagtgggctg 1100 ttgtggctgg gtctggggca ggtgcatttg agccagggct ggctctgtga 1150 gtggcctcct tggcctcggc cctggttccc tccctcctgc tctgggctca 1200 gatactgtga catcccagaa gcccagcccc tcaacccctc tggatgctac 1250 atggggatgc tggacggctc agcccctgtt ccaaggattt tggggtgctg 1300 agattctccc ctagagacct gaaattcacc agctacagat gccaaatgac 1350 ttacatctta agaagtctca gaacgtccag cccttcagca gctctcgttc 1400 tgagacatga gccttgggat gtggcagcat cagtgggaca agatggacac 1450 tgggccaccc tcccaggcac cagacacagg gcacggtgga gagacttctc 1500 ccccgtggcc gccttggctc ccccgttttg cccgaggctg ctcttctgtc 1550 agacttcctc tttgtaccac agtggctctg gggccaggcc tgcctgccca 1600 ctggccatcg ccaccttccc cagctgcctc ctaccagcag tttctctgaa 1650 gatctgtcaa caggttaagt caatctgggg cttccactgc ctgcattcca 1700 gtccccagag cttggtggtc ccgaaacggg aagtacatat tggggcatgg 1750 tggcctccgt gagcaaatgg tgtcttgggc aatctgaggc caggacagat 1800 gttgccccac ccactggaga tggtgctgag ggaggtgggt ggggccttct 1850 gggaaggtga gtggagaggg gcacctgccc cccgccctcc ccatccccta 1900 ctcccactgc tcagcgcggg ccattgcaag ggtgccacac aatgtcttgt 1950 ccaccctggg acacttctga gtatgaagcg ggatgctatt aaaaactaca 2000 tggggaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaga 2 044 <210> 140 <211> 311 <212> PRT <213> Homo sapiens <400> 140 Met Gly Val Pro Thr Ala Leu Glu Ala Gly Ser Trp Arg Trp Gly 1,5 10 15 Ser Leu Leu Phe Ala Leu Phe Leu Ala Ala Ser Leu Gly Pro Val 20 25 30 Ala Ala Phe Lys Val Ala Thr Pro Tyr Ser Leu Tyr Val Cys Pro 626 40 45 Glu Gly Gin Asn Val Thr Leu Thr Cys Arg Leu Leu Gly Pro Val 50 55 60 Asp Lys Gly His Asp Val Thr Phe Tyr Lys Thr Trp Tyr Arg Ser 65 70 75 Ser Arg Gly Glu Val Gin Thr Cys Ser Glu Arg Arg Pro Ile Arg 80 85 90 Asn Leu Thr Phe Gin Asp Leu His Leu His His Gly Gly His Gin 95 100 105 Ala Ala Asn Thr Ser His Asp Leu Ala Gin Arg His Gly Leu Glu 110 115 120 Ser Ala Ser Asp His His Gly Asn Phe Ser Ile Thr Met Arg Asn 125 130 135 Leu Thr Leu Leu Asp Ser Gly Leu Tyr Cys Cys Leu Val Val Glu 140 145 150 Ile Arg His His His Ser Glu His Arg Val His Gly Ala Met Glu 155 160 165 Leu Gin Val Gin Thr Gly Lys Asp Ala Pro Ser Asn Cys Val Val 170 175 180 Tyr Pro Ser Ser Ser Gin Asp Ser Glu Asn Ile Thr Ala Ala Ala 185 190 195 Leu Ala Thr Gly Ala Cys Ile Val Gly Ile Leu Cys Leu Pro Leu 200 205 210 Ile Leu Leu Leu Val Tyr Lys Gin Arg Gin Ala Ala Ser Asn Arg 215 220 225 Arg Ala Gin Glu Leu Val Arg Met Asp Ser Asn Ile Gin Gly Ile 230 235 240 Glu Asn Pro Gly Phe Glu Ala Ser Pro Pro Ala Gin Gly Ile Pro 245 250 255 Glu Ala Lys Val Arg His Pro Leu Ser Tyr Val Ala Gin Arg Gin 260 265 270 Pro Ser Glu Ser Gly Arg His Leu Leu Ser Glu Pro Ser Thr Pro 275 280 285 Leu Ser Pro Pro Gly Pro Gly Asp Val Phe Phe Pro Ser Leu Asp 290 295 300 Pro Val Pro Asp Ser Pro Asn Phe Glu Val Ile 305 310 <210> 141 <211> 1732 <212> DNA <213> Homo sapiens <400> 141 50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000 1050 1100 1150 1200 1250 1300 1350 1400 1450 1500 1550 1600 cgcgcctctc ctttccccgc ccttcctgcc ccccgctcta ctgtgcctcc accagcggcc tcctccttgc tcgagcccgc ccggcgagag ctgcgctgta ctgtccgcct gtcccaagtg aagtcctgcc tgcccatgag gctgcacaga ggctgcccag agatgaggca atggggtgag agaggcccgg catccctcgc tcgtcctgaa tactcccacg gccctgcatc tgacct'gtcc aagtgctgca gatcagttct catcggtatc gaggcctcgg ggaaactgag agaatcttcc gaaagaggca ggaacgtctt ccttctgctg gttctctttc ctcctttcct gcagcagacc gtgtcctttt tgaccctggg tgggactcgc ccagacatgt ctggcacccc cctgctcaga gtccactgcc tgtggaacct agcacaacgg ctgttcccct gggccagatc cacccctccc agtgagcaat acatcctcag gcaccccagc cacttcagac ggagaaacat gggaggtgtg ctatgcacct caccgagtac agatttgccc accaggtgtc cccaagccca acttggtgga gctcagagag acttgactca cagcacttcc cctagcccag 627 gaccttcctt cacctttctc gcccaccgct tcctggggtc cgtctccctt gaaaggatgg gctgctctgg tctgcctttt tacttggagc gggcgcccat cccagcctgt cacactccct gaccatgtac cccgcctgcc tactgcggcc actgccagac cggatgaaga gatccatgtt ccccactggc ccaagggagc aagaaagcct gcacccggcc gtgaggatgg ccctgccgtc agaggacaaa ccaaggcacc gacaacctgc gatctacctc gtgaagtacc gatcaagaaa gactgctcgc accctggagc cgtctctcca ttcttcccac gcttcctggc tgtgggttga cctcccgact ttcccgaggt ttccccctgg ccatgggaag cacaaggcct gtgagttgtt gacggagcca ctggactccg caacacggag caaccagtgt tcacaacctg tcctgctgcc ggacagtgtg ccagtgatgc ctcagcgccc aggcagcaca gtgtgcatgg ttccgtgcct ccgccaggac accccgagaa gcagaccctg gggccgggtc gtcgctttgc tggaagctgg tggcccaagg gtcaggaagc tggcccccac tgaaggtcac 628 ggccagtcca gacaaagtga ccaagacata acaaagacct aacagttgca 1650 gatatgagct gtataattgt tgttattata tattaataaa taagaagttg 17 00 cattaccctc aaaaaaaaaa aaaaaaaaaa aa 1732 <210> 142 <211> 451 <212> PRT <213> Homo sapiens <400> 142 Met Val Pro Glu Val Arg Val Leu Ser Ser Leu Leu Gly Leu Ala 15 10 15 Leu Leu Trp Phe Pro Leu Asp Ser His Ala Arg Ala Arg Pro Asp 20 25 30 Met Phe Cys Leu Phe His Gly Lys Arg Tyr Ser Pro Gly Glu Ser 35 40 45 Trp His Pro Tyr Leu Glu Pro Gin Gly Leu Met Tyr Cys Leu Arg 50 55 60 Cys Thr Cys Ser Glu Gly Ala His Val Ser Cys Tyr Arg Leu His 65 70 75 Cys Pro Pro Val His Cys Pro Gin Pro Val Thr Glu Pro Gin Gin 80 85 90 Cys Cys Pro Lys Cys Val Glu Pro His Thr Pro Ser Gly Leu Arg 95 100 105 Ala Pro Pro Lys Ser Cys Gin His Asn Gly Thr Met Tyr Gin His 110 115 120 Gly Glu Ile Phe Ser Ala His Glu Leu Phe Pro Ser Arg Leu Pro 125 130 135 Asn Gin Cys Val Leu Cys Ser Cys Thr Glu Gly Gin Ile Tyr Cys 140 145 150 Gly Leu Thr Thr Cys Pro Glu Pro Gly Cys Pro Ala Pro Leu Pro 155 160 165 Leu Pro Asp Ser Cys Cys Gin Ala Cys Lys Asp Glu Ala Ser Glu 170 175 180 Gin Ser Asp Glu Glu Asp Ser Val Gin Ser Leu His Gly Val Arg 185 190 195 His Pro Gin Asp Pro Cys Ser Ser Asp Ala Gly Arg Lys Arg Gly 200 205 210 Pro Gly Thr Pro Ala Pro Thr Gly Leu Ser Ala Pro Leu Ser Phe 215 220 225 Ile Pro Arg His Phe Arg Pro Lys Gly Ala Gly Ser Thr Thr Val 230 235 240 Lys Ile Val Leu Lys Glu Lys His Lys Lys Ala Cys Val His Gly 629 245 250 255 Gly Lys Thr Tyr Ser His Gly Glu Val Trp His Pro Ala Phe Arg 260 265 270 Ala Phe Gly Pro Leu Pro Cys Ile Leu Cys Thr Cys Glu Asp Gly 275 280 285 Arg Gin Asp Cys Gin Arg Val Thr Cys Pro Thr Glu Tyr Pro Cys 290 295 300 Arg His Pro Glu Lys Val Ala Gly Lys Cys Cys Lys Ile Cys Pro 305 310 315 Glu Asp Lys Ala Asp Pro Gly His Ser Glu Ile Ser Ser Thr Arg 320 325 330 Cys Pro Lys Ala Pro Gly Arg Val Leu Val His Thr Ser Val Ser 335 340 345 Pro Ser Pro Asp Asn Leu Arg Arg Phe Ala Leu Glu His Glu Ala 350 355 360 Ser Asp Leu Val Glu Ile Tyr Leu Trp Lys Leu Val Lys Asp Glu 365 370 375 Glu Thr Glu Ala Gin Arg Gly Glu Val Pro Gly Pro Arg Pro His 380 385 390 Ser Gin Asn Leu Pro Leu Asp Ser Asp Gin Glu Ser Gin Glu Ala 395 400 405 Arg Leu Pro Glu Arg Gly Thr Ala Leu Pro Thr Ala Arg Trp Pro 410 415 420 Pro Arg Arg Ser Leu Glu Arg Leu Pro Ser Pro Asp Pro Gly Ala 425 430 435 Glu Gly His Gly Gin Ser Arg Gin Ser Asp Gin Asp Ile Thr Lys 440 445 450 Thr <210> 143 <211> 693 <212> DNA <213> Homo sapiens <400> 143 ctagcctgcg ccaaggggta gtgagaccgc gcggcaacag cttgcggctg 50 cggggagctc ccgtgggcgc tccgctggct gtgcaggcgg ccatggattc 100 cttgcggaaa atgctgatct cagtcgcaat gctgggcgca ggggctggcg 150 tgggctacgc gctcctcgtt atcgtgaccc cgggagagcg gcggaagcag 2 00 gaaatgctaa aggagatgcc actgcaggac ccaaggagca gggaggaggc 2 50 ggccaggacc cagcagctat tgctggccac tctgcaggag gcagcgacca 300 cgcaggagaa cgtggcctgg aggaagaact 630 ggatggttgg cggcgaaggc 350 ggcgccagcg ggaggtcacc gtgagaccgg acttgcctcc gtgggcgccg 400 gaccttggct tgggcgcagg aatccgaggc agcctttctc cttcgtgggc 450 ccagcggaga gtccggaccg agataccatg ccaggactct ccggggtcct 500 gtgagctgcc gtcgggtgag cacgtttccc ccaaaccctg gactgactgc 550 tttaaggtcc gcaaggcggg ccagggccga gacgcgagtc ggatgtggtg 600 aactgaaaga accaataaaa tcatgttcct ccaaaaaaaa aaaaaaaaaa 650 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaa 693 <210> 144 <211> 93 <212> PRT <213> Homo sapiens <400> 144 Met Asp Ser Leu Arg 1 5 Ala Gly Ala Gly Val 20 Gly Glu Arg Arg Lys 35 Asp Pro Arg Ser Arg 50 Leu Ala Thr Leu Gin 65 Trp Arg Lys Asn Trp 80 Arg Ser Pro <210> 145 <211> 1883 <212> DNA <213> Homo sapiens <400> 145 caggagagaa ggcaccgccc ccaccccgcc tccaaagcta accctcgggc 50 ttgaggggaa gaggctgact gtacgttcct tctactctgg caccactctc 100 caggctgcca tggggcccag cacccctctc ctcatcttgt tccttttgtc 150 atggtcggga cccctccaag gacagcagca ccaccttgtg gagtacatgg 200 aacgccgact agctgcttta gaggaacggc tggcccagtg ccaggaccag 250 agtagtcggc atgctgctga gctgcgggac ttcaagaaca agatgctgcc 300 actgctggag gtggcagaga aggagcggga ggcactcaga actgaggccg 350 Lys Met Leu Ile Ser Val Ala Met Leu Gly 10 15 Gly Tyr Ala Leu Leu Val Ile Val Thr Pro 25 30 Gin Glu Met Leu Lys Glu Met Pro Leu Gin 40 45 Glu Glu Ala Ala Arg Thr Gin Gin Leu Leu 55 60 Glu Ala Ala Thr Thr Gin Glu Asn Val Ala 70 75 Met Val Gly Gly Glu Gly Gly Ala Ser Gly 85 90 631 acaccatctc cgggagagtg gatcgtctgg agcgggaggt agactatctg 400 gagacccaga acccagctct gccctgtgta gagtttgatg agaaggtgac 450 tggaggccct gggaccaaag gcaagggaag aaggaatgag aagtacgata 500 tggtgacaga ctgtggctac acaatctctc aagtgagatc aatgaagatt 550 ctgaagcgat ttggtggccc agctggtcta tggaccaagg atccactggg 600 gcaaacagag aagatctacg tgttagatgg gacacagaat gacacagcct 650 ttgtcttccc aaggctgcgt gacttcaccc ttgccatggc tgcccggaaa 700 gcttcccgag tccgggtgcc cttcccctgg gtaggcacag ggcagctggt 750 atatggtggc tttctttatt ttgctcggag gcctcctgga agacctggtg 800 gaggtggtga gatggagaac actttgcagc taatcaaatt ccacctggca 850 aaccgaacag tggtggacag ctcagtattc ccagcagagg ggctgatccc 900 cccctacggc ttgacagcag acacctacat cgacctggta gctgatgagg 950 aaggtctttg ggctgtctat gccacccggg aggatgacag gcacttgtgt 1000 ctggccaagt tagatccaca gacactggac acagagcagc agtgggacac 1050 accatgtccc agagagaatg ctgaggctgc ctttgtcatc tgtgggaccc 1100 tctatgtcgt ctataacacc cgtcctgcca gtcgggcccg catccagtgc 1150 tcctttgatg ccagcggcac cctgacccct gaacgggcag cactccctta 1200 ttttccccgc agatatggtg cccatgccag cctccgctat aacccccgag 1250 aacgccagct ctatgcctgg gatgatggct accagattgt ctataagctg 1300 gagatgagga agaaagagga ggaggtttga ggagctagcc ttgttttttg 1350 catctttctc actcccatac atttatatta tatccccact aaatttcttg 1400 ttcctcattc ttcaaatgtg ggccagttgt ggctcaaatc ctctatattt 1450 ttagccaatg gcaatcaaat tctttcagct cctttgtttc atacggaact 1500 ccagatcctg agtaatcctt ttagagcccg aagagtcaaa accctcaatg 1550 ttccctcctg ctctcctgcc ccatgtcaac aaatttcagg ctaaggatgc 1600 cccagaccca gggctctaac cttgtatgcg ggcaggccca gggagcaggc 1650 agcagtgttc ttcccctcag agtgacttgg ggagggagaa ataggaggag 1700 acgtccagct ctgtcctctc ttcctcactc ctcccttcag tgtcctgagg 1750 aacaggactt tctccacatt gttttgtatt gcaacatttt gcattaaaag 1800 gaaaatccac aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1850 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaa 1883 632 <210> 146 <211> 406 <212> PRT <213> Homo sapiens <400> 146 Met Gly Pro Ser Thr Pro Leu Leu Ile Leu Phe Leu Leu Ser Trp 15 10 15 Ser Gly Pro Leu Gin Gly Gin Gin His His Leu Val Glu Tyr Met 20 25 30 Glu Arg Arg Leu Ala Ala Leu Glu Glu Arg Leu Ala Gin Cys Gin 35 40 45 Asp Gin Ser Ser Arg His Ala Ala Glu Leu Arg Asp Phe Lys Asn 50 55 60 Lys Met Leu Pro Leu Leu Glu Val Ala Glu Lys Glu Arg Glu Ala 65 70 75 Leu Arg Thr Glu Ala Asp Thr Ile Ser Gly Arg Val Asp Arg Leu 80 85 90 Glu Arg Glu Val Asp Tyr Leu Glu Thr Gin Asn Pro Ala Leu Pro 95 100 105 Cys Val Glu Phe Asp Glu Lys Val Thr Gly Gly Pro Gly Thr Lys 110 115 120 Gly Lys Gly Arg Arg Asn Glu Lys Tyr Asp Met Val Thr Asp Cys 125 130 135 Gly Tyr Thr Ile Ser Gin Val Arg Ser Met Lys Ile Leu Lys Arg 140 145 150 Phe Gly Gly Pro Ala Gly Leu Trp Thr Lys Asp Pro Leu Gly Gin 155 160 165 Thr Glu Lys Ile Tyr Val Leu Asp Gly Thr Gin Asn Asp Thr Ala 170 175 180 Phe Val Phe Pro Arg Leu Arg Asp Phe Thr Leu Ala Met Ala Ala 185 190 195 Arg Lys Ala Ser Arg Val Arg Val Pro Phe Pro Trp Val Gly Thr 200 205 210 Gly Gin Leu Val Tyr Gly Gly Phe Leu Tyr Phe Ala Arg Arg Pro 215 220 225 Pro Gly Arg Pro Gly Gly Gly Gly Glu Met Glu Asn Thr Leu Gin 230 235 240 Leu Ile Lys Phe His Leu Ala Asn Arg Thr Val Val Asp Ser Ser 245 250 255 Val Phe Pro Ala Glu Gly Leu lie Pro Pro Tyr Gly Leu Thr Ala 260 265 270 Asp Thr Tyr Ile Asp Leu Val Ala Asp Glu Glu Gly Leu Trp Ala 275 633 280 285 Val Tyr Ala Thr Arg Glu Asp Asp Arg His Leu Cys Leu Ala Lys 290 295 300 Leu Asp Pro Gin Thr Leu Asp Thr Glu Gin Gin Trp Asp Thr Pro 305 310 315 Cys Pro Arg Glu Asn Ala Glu Ala Ala Phe Val Ile Cys Gly Thr 320 325 330 Leu Tyr Val Val Tyr Asn Thr Arg Pro Ala Ser Arg Ala Arg Ile 335 340 345 Gin Cys Ser Phe Asp Ala Ser Gly Thr Leu Thr Pro Glu Arg Ala 350 355 360 Ala Leu Pro Tyr Phe Pro Arg Arg Tyr Gly Ala His Ala Ser Leu 365 370 375 Arg Tyr Asn Pro Arg Glu Arg Gin Leu Tyr Ala Trp Asp Asp Gly 380 385 390 Tyr Gin Ile Val Tyr Lys Leu Glu Met Arg Lys Lys Glu Glu Glu 395 400 405 Val <210> 147 <211> 2052 <212> DNA <213> Homo sapiens <400> 147 gacagctgtg tctcgatgga gtagactctc agaacagcgc agtttgccct 50 ccgctcacgc agagcctctc cgtggcttcc gcaccttgag cattaggcca 100 gttctcctct tctctctaat ccatccgtca cctctcctgt catccgtttc 150 catgccgtga ggtccattca cagaacacat ccatggctct catgctcagt 200 ttggttctga gtctcctcaa gctgggatca gggcagtggc aggtgtttgg 250 gccagacaag cctgtccagg ccttggtggg ggaggacgca gcattctcct 300 gtttcctgtc tcctaagacc aatgcagagg ccatggaagt gcggttcttc 350 aggggccagt tctctagcgt ggtccacctc tacagggacg ggaaggacca 400 gccatttatg cagatgccac agtatcaagg caggacaaaa ctggtgaagg 450 attctattgc ggaggggcgc atctctctga ggctggaaaa cattactgtg 500 ttggatgctg gcctctatgg gtgcaggatt agttcccagt cttactacca 550 gaaggccatc tgggagctac aggtgtcagc actgggctca gttcctctca 600 tttccatcac gggatatgtt gatagagaca tccagctact ctgtcagtcc 650 tcgggctggt tcccccggcc cacagcgaag tggaaaggtc cacaaggaca 700 634 ggatttgtcc acagactcca ggacaaacag agacatgcat ggcctgtttg 750 atgtggagat ctctctgacc gtccaagaga acgccgggag catatcctgt 800 tccatgcggc atgctcatct gagccgagag gtggaatcca gggtacagat 850 aggagatacc tttttcgagc ctatatcgtg gcacctggct accaaagtac 900 tgggaatact ctgctgtggc ctattttttg gcattgttgg actgaagatt 950 ttcttctcca aattccagtg gaaaatccag gcggaactgg actggagaag 1000 aaagcacgga caggcagaat tgagagacgc ccggaaacac gcagtggagg 1050 tgactctgga aaaactgtaa tccagagacg cccatagaaa gctcacccga agctccccag agctctgcgt gaggtgcctc ttctgatctg actctgagaa 1100 1150 gagatttaca aggaagagtg tggtggcttc tcagagtttc caagcaggga 1200 aacattactg ggaggtggac ggaggacaca ataaaaggtg gcgcgtggga 1250 gtgtgccggg atgatgtgga caggaggaag gagtacgtga ctttgtctcc 1300 cgatcatggg tactgggtcc teagactgaa tggagaacat ttgtatttca 1350 cattaaatcc ccgttttatc agcgtcttcc ccaggacccc acctacaaaa 1400 ataggggtct tcctggacta tgagtgtggg accatctcct tcttcaacat 1450 aaatgaccag tcccttattt ataccctgac atgtcggttt gaaggcttat 1500 tgaggcccta cattgagtat ccgtcctata atgagcaaaa tggaactccc 1550 atagtcatct gcccagtcac ccaggaatca gagaaagagg cctcttggca 1600 aagggcctct gcaatcccag agacaagcaa cagtgagtcc tcctcacagg 1650 caaccacgcc cttcctcccc aggggtgaaa tgtaggatga atcacatccc 1700 acattcttct ttagggatat taaggtctct ctcccagatc caaagtcccg 1750 cagcagccgg ccaaggtggc ttccagatga agggggactg gcctgtccac 1800 atgggagtca ggtgtcatgg ctgccctgag ctgggaggga agaaggctga 1850 cattacattt agtttgctct cactccatct ggctaagtga tcttgaaata 1900 ccacctctca ggtgaagaac cgtcaggaat tcccatctca caggctgtgg 1950 tgtagattaa gtagacaagg aatgtgaata atgcttagat cttattgatg 2000 acagagtgta tcctaatggt ttgttcatta tattacactt tcagtaaaaa 2050 aa 2052 <210> 148 <211> 500 <212> PRT <213> Homo sapiens <400> 148 635 Met Ala Leu Met Leu Ser Leu Val Leu Ser Leu Leu Lys Leu Gly 15 10 15 Ser Gly Gin Trp Gin Val Phe Gly Pro Asp Lys Pro Val Gin Ala 20 25 30 Leu Val Gly Glu Asp Ala Ala Phe Ser Cys Phe Leu Ser Pro Lys 35 40 45 Thr Asn Ala Glu Ala Met Glu Val Arg Phe Phe Arg Gly Gin Phe 50 55 60 Ser Ser* Val Val His Leu Tyr Arg Asp Gly Lys Asp Gin Pro Phe 65 70 75 Met Gin Met Pro Gin Tyr Gin Gly Arg Thr Lys Leu Val Lys Asp 80 85 90 Ser Ile Ala Glu Gly Arg Ile Ser Leu Arg Leu Glu Asn Ile Thr 95 100 105 Val Leu Asp Ala Gly Leu Tyr Gly Cys Arg Ile Ser Ser Gin Ser 110 115 120 Tyr Tyr Gin Lys Ala Ile Trp Glu Leu Gin Val Ser Ala Leu Gly 125 130 135 Ser Val Pro Leu Ile Ser Ile Thr Gly Tyr Val Asp Arg Asp Ile 140 145 150 Gin Leu Leu Cys Gin Ser Ser Gly Trp Phe Pro Arg Pro Thr Ala 155 160 165 Lys Trp Lys Gly Pro Gin Gly Gin Asp Leu Ser Thr Asp Ser Arg 170 175 180 Thr Asn Arg Asp Met His Gly Leu Phe Asp Val Glu Ile Ser Leu 185 190 195 Thr Val Gin Glu Asn Ala Gly Ser Ile Ser Cys Ser Met Arg His 200 205 210 Ala His Leu Ser Arg Glu Val Glu Ser Arg Val Gin Ile Gly Asp 215 220 225 Thr Phe Phe Glu Pro Ile Ser Trp His Leu Ala Thr Lys Val Leu 230 235 240 Gly Ile Leu Cys Cys Gly Leu Phe Phe Gly Ile Val Gly Leu Lys 245 250 255 Ile Phe Phe Ser Lys Phe Gin Trp Lys Ile Gin Ala Glu Leu Asp 260 265 270 Trp Arg Arg Lys His Gly Gin Ala Glu Leu Arg Asp Ala Arg Lys 275 280 285 His Ala Val Glu Val Thr Leu Asp Pro Glu Thr Ala His Pro Lys 290 295 300 Leu Cys Val Ser Asp Leu Lys Thr Val Thr His Arg Lys Ala Pro 305 310 315 636 Gin Glu Val Pro His Ser Glu Lys Arg Phe Thr Arg Lys Ser Val 320 325 330 Val Ala Ser Gin Ser Phe Gin Ala Gly Lys His Tyr Trp Glu Val 335 340 345 Asp Gly Gly His Asn Lys Arg Trp Arg Val Gly Val Cys Arg Asp 350 355 360 Asp Val Asp Arg Arg Lys Glu Tyr Val Thr Leu Ser Pro Asp His 365 370 375 Gly Tyr Trp Val Leu Arg Leu Asn Gly Glu His Leu Tyr Phe Thr 380 385 390 Leu Asn Pro Arg Phe lie Ser Val Phe Pro Arg Thr Pro Pro Thr 395 400 405 Lys Ile Gly Val Phe Leu Asp Tyr Glu Cys Gly Thr Ile Ser Phe 410 415 420 Phe Asn Ile Asn Asp Gin Ser Leu Ile Tyr Thr Leu Thr Cys Arg 425 430 435 Phe Glu Gly Leu Leu Arg Pro Tyr Ile Glu Tyr Pro Ser Tyr Asn 440 445 450 Glu Gin Asn Gly Thr Pro Ile Val Ile Cys Pro Val Thr Gin Glu 455 460 465 Ser Glu Lys Glu Ala Ser Trp Gin Arg Ala Ser Ala Ile Pro Glu 470 475 480 Thr Ser Asn Ser Glu Ser Ser Ser Gin Ala Thr Thr Pro Phe Leu 485 490 495 Pro Arg Gly Glu Met 500 <210> 149 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 149 gcgtggtcca cctctacagg gacg 24 <210> 150 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 150 ggaactgacc cagtgctgac acc 23 <210> 151 637 <211> 45 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 151 gcagatgcca cagtatcaag gcaggacaaa actggtgaag gattc 45 <210> 152 <211> 2294 <212> DNA <213> Homo sapiens <400> 152 gcgatggtgc gcccggtggc ggtggcggcg gcggttgcgg aggcttcctt 50 ggtcggattg caacgaggag aagatgactg accaaccgac tggctgaatg 100 aatgaatggc ggagccgagc gcgccatgag gagcctgccg agcctgggcg 150 gcctcgccct gttgtgctgc gccgccgccg ccgccgccgt cgcctcagcc 200 gcctcggcgg ggaatgtcac cggtggcggc ggggccgcgg ggcaggtgga 2 50 cgcgtcgccg ggccccgggt tgcggggcga gcccagccac cccttcccta 300 gggcgacggc tcccacggcc caggccccga ggaccgggcc cccgcgcgcc 3 50 accgtccacc gacccctggc tgcgacttct ccagcccagt ccccggagac 400 cacccctctt tgggcgactg ctggaccctc ttccaccacc tttcaggcgc 450 cgctcggccc ctcgccgacc acccctccgg cggcggaacg cacttcgacc 500 acctctcagg cgccgaccag acccgcgccg accacccttt cgacgaccac 550 tggcccggcg ccgaccaccc ctgtagcgac caccgtaccg gcgcccacga 600 ctccccggac cccgaccccc gatctcccca gcagcagcaa cagcagcgtc 650 ctccccaccc cacctgccac cgaggccccc tcttcgcctc ctccagagta 700 tgtatgtaac tgctctgtgg ttggaagcct gaatgtgaat cgctgcaacc 750 agaccacagg gcagtgtgag tgtcggccag gttatcaggg gcttcactgt 800 gaaacctgca aagagggctt ttacctaaat tacacttctg ggctctgtca 850 gccatgtgac tgtagtccac atggagctct cagcataccg tgcaacaggt 900 aagcaacaga gggtggaact gaagtttatt ttattttagc aagggaaaaa 950 aaaaggctgc tactctcaag gaccatactg gtttaaacaa aggaggatga 1000 gggtcataga tttacaaaat attttatata cttttattct cttactttat 1050 atgttatatt taatgtcagg atttaaaaac atctaattta ctgatttagt 1100 tcttcaaaag cactagagtc gccaattttt ctctgggata atttctgtaa 1150 atttcatggg aaaaaattat tgaagaataa atctgctttc tggaagggct 12 00 638 ttcaggcatg aaacctgcta ggaggtttag aaatgttctt atgtttatta 1250 atataccatt ggagtttgag gaaatttgtt gtttggttta tttttctctc 1300 taatcaaaat tctacatttg tttctttgga catctaaagc ttaacctggg 1350 ggtaccctaa tttatttaac tagtggtaag tagactggtt ttactctatt 1400 taccagtaca tttttgagac caaaagtaga ttaagcagga attatcttta 1450 aactattatg ttatttggag gtaatttaat ctagtggaat aatgtactgt 1500 tatctaagca tttgccttgt actgcactga aagtaattat tctttgacct 1550 tatgtgaggc acttggcttt ttgtggaccc caagtcaaaa aactgaagag 1600 acagtattaa ataatgaaaa aaataatgac aggttatact cagtgtaacc 1650 tgggtataac agtaatttcc ccaagatctg tttcactgag ctgccactta cttgtttctt cgagctgtgt ctcaaggttg tccttgggca ttgtgaagat 1700 1750 taaatgagtt gatatatata aaatgcctag cacatgtcac tcaataaatt 1800 ctggtttgtt ttaatttcaa aggaatatta tggactgaaa tgagagaaca 1850 tgttttaaga acttttagct ccttgacaaa gaagtgcttt atactttagc 1900 actaaatatt ttaaatgctt tataaatgat attatactgt tatggaatat 1950 tgtatcatat tgtagtttat taaaaatgta gaagaggctg ggcgcggtgg 2000 ctcacgcctg taatcctagc actttgggag gccaaggcgg gtggatcact 2050 tgaggccagg agttctagat gagcctggcc agcacagtga aaccccgtct 2100 ctactaaaaa tacaaacaaa ttagctgggc gtggtggcac acacctgtag 2150 tcccagctac tcgggaggct gaggcaggag aatcggttga acccgggagg 2200 tggaggttgc agtgagctga gatcgcgcca ctgcactcca gcctggtgag 2250 agagggagac tctgtcttaa aaaaaaaaaa aaaaaaaaaa aaaa 2294 <210> 153 <211> 258 <212> PRT <213> Homo sapiens <400> 153 Met Arg Ser Leu Pro Ser Leu Gly Gly Leu Ala Leu Leu Cys Cys 15 10 15 Ala Ala Ala Ala Ala Ala Val Ala Ser Ala Ala Ser Ala Gly Asn 20 25 30 Val Thr Gly Gly Gly Gly Ala Ala Gly Gin Val Asp Ala Ser Pro 35 40 45 Gly Pro Gly Leu Arg Gly Glu Pro Ser His Pro Phe Pro Arg Ala 50 55 60 639 Thr Ala Pro Thr Ala Gin Ala Pro Arg Thr Gly Pro Pro Arg Ala 65 70 75 Thr Val His Arg Pro Leu Ala Ala Thr Ser Pro Ala Gin Ser Pro 80 85 90 Glu Thr Thr Pro Leu Trp Ala Thr Ala Gly Pro Ser Ser Thr Thr 95 100 105 Phe Gin Ala Pro Leu Gly Pro Ser Pro Thr Thr Pro Pro Ala Ala 110 115 120 Glu Arg Thr Ser Thr Thr Ser Gin Ala Pro Thr Arg Pro Ala Pro 125 130 135 Thr Thr Leu Ser Thr Thr Thr Gly Pro Ala Pro Thr Thr Pro Val 140 145 150 Ala Thr Thr Val Pro Ala Pro Thr Thr Pro Arg Thr Pro Thr Pro 155 160 165 Asp Leu Pro Ser Ser Ser Asn Ser Ser Val Leu Pro Thr Pro Pro 170 175 180 Ala Thr Glu Ala Pro Ser Ser Pro Pro Pro Glu Tyr Val Cys Asn 185 190 195 Cys Ser Val Val Gly Ser Leu Asn Val Asn Arg Cys Asn Gin Thr 200 205 210 Thr Gly Gin Cys Glu Cys Arg Pro Gly Tyr Gin Gly Leu His Cys 215 220 225 Glu Thr Cys Lys Glu Gly Phe Tyr Leu Asn Tyr Thr Ser Gly Leu 230 235 240 Cys Gin Pro Cys Asp Cys Ser Pro His Gly Ala Leu Ser Ile Pro 245 250 255 Cys Asn Arg <210> 154 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 154 aactgctctg tggttggaag cctg 24 <210> 155 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 155 640 cagtcacatg gctgacagac ccac 24 <210> 156 <211> 38 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 156 aggttatcag gggcttcact gtgaaacctg caaagagg 38 <210> 157 <211> 689 <212> DNA <213> Homo sapiens <400> 157 tgcggcgcag tgtagacctg ggaggatggg cggcctgctg ctggctgctt 50 ttctggcttt ctggaccctg ggtctcggtg agcagcttct cccagggccc tgggccctgg aggccgtgtg tacgtgcttg gttgggaaga cggtggcctc 100 150 ccgggaaaag ggctttgcca tggagaagga catgaagaac gtcgtggggg 200 tggtggtgac cctcactcca gaaaacaacc tgcggacgct gtcctctcag 250 cacgggctgg gagggtgtga ccagagtgtc atggacctga taaagcgaaa 300 ctccggatgg gtgtttgaga atccctcaat aggcgtgctg gagctctggg 350 tgctggccac caacttcaga gactatgcca tcatcttcac tcagctggag 400 ttcggggacg agcccttcaa caccgtggag ctgtacagtc tgacggagac 450 agccagccag gaggccatgg ggctcttcac caagtggagc aggagcctgg 500 gcttcctgtc acagtagcag gcccagctgc agaaggacct cacctgtgct 550 cacaagatcc ttctgtgagt gctgcgtccc cagtagggat ggcgcccaca 600 gggtcctgtg acctcggcca gtgtccaccc acctcgctca gcggctcccg 650 gggcccagca ccagctcaga ataaagcgat tccacagca i 689 <210> 158 <211> 163 <212> PRT <213> Homo sapiens <400> 158 Met Gly Gly Leu 1 Pro Arg Ala Gin Leu Leu Gly Pro Gly Phe Ala Met Leu Leu Ala Ala Phe Leu Ala Leu Val Ser Val 5 10 15 Ala Val Trp Leu Gly Arg Leu Asp Pro Glu Gin 20 25 30 Trp Tyr Val Leu Ala Val Ala Ser Arg Glu Lys 35 40 45 Glu Lys Asp Met Lys Asn Val Val Gly Val Val 50 Val Thr Leu Thr Pro Glu 65 His Gly Leu Gly Gly Cys 80 Arg Asn Ser Gly Trp Val 95 Glu Leu Trp Val Leu Ala 110 Phe Thr Gin Leu Glu Phe 125 Leu Tyr Ser Leu Thr Glu 140 Phe Thr Lys Trp Ser Arg 155 <210> 159 <211> 1665 <212> DNA <213> Homo sapiens <400> 159 aacagacgtt ccctcgcggc cctggcacct ctaaccccag acatgctgct 50 gctgctgctg cccctgctct gggggaggga gagggcggaa ggacagacaa 100 gtaaactgct gacgatgcag agttccgtga cggtgcagga aggcctgtgt 150 gtccatgtgc cctgctcctt ctcctacccc tcgcatggct ggatttaccc 200 tggcccagta gttcatggct actggttccg ggaaggggcc aatacagacc 250 aggatgctcc agtggccaca aacaacccag ctcgggcagt gtgggaggag 300 actcgggacc gattccacct ccttggggac ccacatacca agaattgcac 350 cctgagcatc agagatgcca gaagaagtga tgcggggaga tacttctttc 400 gtatggagaa aggaagtata aaatggaatt ataaacatca ccggctctct 450 gtgaatgtga cagccttgac ccacaggccc aacatcctca tcccaggcac 500 cctggagtcc ggctgccccc agaatctgac ctgctctgtg ccctgggcct 550 gtgagcaggg gacaccccct atgatctcct ggatagggac ctccgtgtcc 600 cccctggacc cctccaccac ccgctcctcg gtgctcaccc tcatcccaca 650 gccccaggac catggcacca gcctcacctg tcaggtgacc ttccctgggg 700 ccagcgtgac cacgaacaag accgtccatc tcaacgtgtc ctacccgcct 750 cagaacttga ccatgactgt cttccaagga gacggcacag tatccacagt 800 cttgggaaat ggctcatctc tgtcactccc agagggccag tctctgcgcc 850 641 55 60 Asn Asn Leu Arg Thr Leu Ser Ser Gin 70 75 Asp Gin Ser Val Met Asp Leu Ile Lys 85 90 Phe Glu Asn Pro Ser Ile Gly Val Leu 100 105 Thr Asn Phe Arg Asp Tyr Ala Ile Ile 115 120 Gly Asp Glu Pro Phe Asn Thr Val Glu 130 135 Thr Ala Ser Gin Glu Ala Met Gly Leu 145 150 Ser Leu Gly Phe Leu Ser Gin 160 642 tggtctgtgc agttgatgca gttgacagca atccccctgc caggctgagc 900 ctgagctgga gaggcctgac cctgtgcccc tcacagccct caaacccggg 950 ggtgctggag ctgccttggg tgcacctgag ggatgcagct gaattcacct 1000 gcagagctca gaaccctctc ggctctcagc aggtctacct gaacgtctcc 1050 ctgcagagca aagccacatc aggagtgact cagggggtgg tcgggggagc 1100 tggagccaca gccctggtct tcctgtcctt ctgcgtcatc ttcgttgtag 1150 tgaggtcctg caggaagaaa tcggcaaggc cagcagcggg cgtgggagat 12 00 acgggcatag aggatgcaaa cgctgtcagg ggttcagcct ctcaggggcc 1250 cctgactgaa ccttgggcag aagacagtcc cccagaccag cctcccccag 1300 cttctgcccg ctcctcagtg ggggaaggag agctccagta tgcatccctc 13 50 agcttccaga tggtgaagcc ttgggactcg cggggacagg aggccactga 1400 caccgagtac tcggagatca agatccacag atgagaaact gcagagactc 1450 accctgattg agggatcaca gcccctccag gcaagggaga agtcagaggc 1500 tgattcttgt agaattaaca gccctcaacg tgatgagcta tgataacact 1550 atgaattatg tgcagagtga aaagcacaca ggctttagag tcaaagtatc 1600 tcaaacctga atccacactg tgccctccct tttatttttt taactaaaag 1650 acagacaaat tccta 1665 <210> 160 <211> 463 <212> PRT <213> Homo sapiens <400> 160 Met Leu Leu Leu Leu Leu Pro Leu Leu Trp Gly Arg Glu Arg Ala 15 10 15 Glu Gly Gin Thr Ser Lys Leu Leu Thr Met Gin Ser Ser Val Thr 20 25 30 Val Gin Glu Gly Leu Cys Val His Val Pro Cys Ser Phe Ser Tyr 35 40 45 Pro Ser His Gly Trp Ile Tyr Pro Gly Pro Val Val His Gly Tyr 50 55 60 Trp Phe Arg Glu Gly Ala Asn Thr Asp Gin Asp Ala Pro Val Ala 65 70 75 Thr Asn Asn Pro Ala Arg Ala Val Trp Glu Glu Thr Arg Asp Arg 80 85 90 Phe His Leu Leu Gly Asp Pro His Thr Lys Asn Cys Thr Leu Ser 95 100 105 Ile Arg Asp Ala Arg Arg Ser Asp Ala Gly Arg Tyr Phe Phe Arg 643 110 115 120 Met Glu Lys Gly Ser Ile Lys Trp Asn Tyr Lys His His Arg Leu 125 130 135 Ser Val Asn Val Thr Ala Leu Thr His Arg Pro Asn Ile Leu Ile 140 145 150 Pro Gly Thr Leu Glu Ser Gly Cys Pro Gin Asn Leu Thr Cys Ser 155 160 165 Val Pro Trp Ala Cys Glu Gin Gly Thr Pro Pro Met Ile Ser Trp 170 175 180 Ile Gly Thr Ser Val Ser Pro Leu Asp Pro Ser Thr Thr Arg Ser 185 190 195 Ser Val Leu Thr Leu Ile Pro Gin Pro Gin Asp His Gly Thr Ser 200 205 210 Leu Thr Cys Gin Val Thr Phe Pro Gly Ala Ser Val Thr Thr Asn 215 220 225 Lys Thr Val His Leu Asn Val Ser Tyr Pro Pro Gin Asn Leu Thr 230 235 240 Met Thr Val Phe Gin Gly Asp Gly Thr Val Ser Thr Val Leu Gly 245 250 255 Asn Gly Ser Ser Leu Ser Leu Pro Glu Gly Gin Ser Leu Arg Leu 260 265 270 Val Cys Ala Val Asp Ala Val Asp Ser Asn Pro Pro Ala Arg Leu 275 280 285 Ser Leu Ser Trp Arg Gly Leu Thr Leu Cys Pro Ser Gin Pro Ser 290 295 300 Asn Pro Gly Val Leu Glu Leu Pro Trp Val His Leu Arg Asp Ala 305 310 315 Ala Glu Phe Thr Cys Arg Ala Gin Asn Pro Leu Gly Ser Gin Gin 320 325 330 Val Tyr Leu Asn Val Ser Leu Gin Ser Lys Ala Thr Ser Gly Val 335 340 345 Thr Gin Gly Val Val Gly Gly Ala Gly Ala Thr Ala Leu Val Phe 350 355 360 Leu Ser Phe Cys Val Ile Phe Val Val Val Arg Ser Cys Arg Lys 365 370 375 Lys Ser Ala Arg Pro Ala Ala Gly Val Gly Asp Thr Gly Ile Glu 380 385 390 Asp Ala Asn Ala Val Arg Gly Ser Ala Ser Gin Gly Pro Leu Thr 395 400 405 Glu Pro Trp Ala Glu Asp Ser Pro Pro Asp Gin Pro Pro Pro Ala 410 415 420 Ser Ala Arg Ser Ser Val Gly Glu Gly Glu Leu Gin Tyr Ala Ser 644 425 430 435 Leu Ser Phe Gin Met Val Lys Pro Trp Asp Ser Arg Gly Gin Glu 440 445 450 Ala Thr Asp Thr Glu Tyr Ser Glu Ile Lys Ile His Arg 455 460 <210> 161 <211> 739 <212> DNA <213> Homo sapiens <400> 161 gacgcccagt gacctgccga ggtcggcagc acagagctct ggagatgaag 50 accctgttcc tgggtgtcac gctcggcctg gccgctgccc tgtccttcac 100 cctggaggag gaggatatca cagggacctg gtacgtgaag gccatggtgg 150 tcgataagga ctttccggag gacaggaggc ccaggaaggt gtccccagtg 200 aaggtgacag ccctgggcgg tgggaagttg gaagccacgt tcaccttcat 250 gagggaggat cggtgcatcc agaagaaaat cctgatgcgg aagacggagg 300 agcctggcaa atacagcgcc tatgggggca ggaagctcat gtacctgcag 350 gagctgccca ggagggacca ctacatcttt tactgcaaag accagcacca 400 tgggggcctg ctccacatgg gaaagcttgt gggtaggaat tctgatacca 450 accgggaggc cctggaagaa tttaagaaat tggtgcagcg caagggactc 500 tcggaggagg acattttcac gcccctgcag acgggaagct gcgttcccga 550 acactaggca gcccccgggt ctgcacctcc agagcccacc ctaccaccag 600 acacagagcc cggaccacct ggacctaccc tccagccatg acccttccct 650 gctcccaccc acctgactcc aaataaagtc cttttccccc aaaaaaaaaa 700 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaa 739 <210> 162 <211> 170 <212> PRT <213> Homo sapiens <400> 162 Met Lys Thr Leu Phe Leu Gly Val Thr Leu Gly Leu Ala Ala Ala 1 5 10 15 Leu Ser Phe Thr Leu Glu Glu Glu Asp Ile Thr Gly Thr Trp Tyr 20 25 30 Val Lys Ala Met Val Val Asp Lys Asp Phe Pro Glu Asp Arg Arg 35 40 45 Pro Arg Lys Val Ser Pro Val Lys Val Thr Ala Leu Gly Gly Gly 50 55 60 645 Lys Leu Glu Ala Thr Phe Thr Phe Met Arg Glu Asp Arg Cys Ile 65 70 75 Gin Lys Lys Ile Leu Met Arg Lys Thr Glu Glu Pro Gly Lys Tyr 80 85 . 90 Ser Ala Tyr Gly Gly Arg Lys Leu Met Tyr Leu Gin Glu Leu Pro 95 100 105 Arg Arg Asp His Tyr Ile Phe Tyr Cys Lys Asp Gin His His Gly 110 115 120 Gly Leu Leu His Met Gly Lys Leu Val Gly Arg Asn Ser Asp Thr 125 130 135 Asn Arg Glu Ala Leu Glu Glu Phe Lys Lys Leu Val Gin Arg Lys 140 145 150 Gly Leu Ser Glu Glu Asp Ile Phe Thr Pro Leu Gin Thr Gly Ser 155 160 165 Cys Val Pro Glu His 170 <210> 163 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 163 ggagatgaag accctgttcc tg 22 <210> 164 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 164 ggagatgaag accctgttcc tgggtg 26 <210> 165 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 165 gtcctccgga aagtccttat c 21 <210> 166 <211> 25 <212> DNA <213> Artificial Sequence 646 <220> <223> Synthetic oligonucleotide probe <400> 166 gcctagtgtt cgggaacgca gcttc 25 <210> 167 <211> 50 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 167 cagggacctg gtacgtgaag gccatggtgg tcgataagga ctttccggag 50 <210> 168 <211> 45 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 168 ctgtccttca ccctggagga ggaggatatc acagggacct ggtac 45 <210> 169 <211> 1204 <212> DNA <213> Homo sapiens <400> 169 gttccgcaga tgcagaggtt gaggtggctg cgggactgga agtcatcggg 50 cagaggtctc acagcagcca aggaacctgg ggcccgctcc tcccccctcc 100 aggccatgag gattctgcag ttaatcctgc ttgctctggc aacagggctt 150 gtagggggag agaccaggat catcaagggg ttcgagtgca agcctcactc 200 ccagccctgg caggcagccc tgttcgagaa gacgcggcta ctctgtgggg 250 cgacgctcat cgcccccaga tggctcctga cagcagccca ctgcctcaag 300 ccccgctaca tagttcacct ggggcagcac aacctccaga aggaggaggg 350 ctgtgagcag acccggacag ccactgagtc cttcccccac cccggcttca 400 acaacagcct ccccaacaaa gaccaccgca atgacatcat gctggtgaag 450 atggcatcgc cagtctccat cacctgggct gtgcgacccc tcaccctctc 500 ctcacgctgt gtcactgctg gcaccagctg cctcatttcc ggctggggca 550 gcacgtccag cccccagtta cgcctgcctc acaccttgcg atgcgccaac 600 atcaccatca ttgagcacca gaagtgtgag aacgcctacc ccggcaacat 650 cacagacacc atggtgtgtg ccagcgtgca ggaagggggc aaggactcct 700 647 gccagggtga ctccgggggc cctctggtct gtaaccagtc tcttcaaggc 750 attatctcct ggggccagga tccgtgtgcg atcacccgaa agcctggtgt 800 ctacacgaaa gtctgcaaat atgtggactg gatccaggag acgatgaaga 850 acaattagac tggacccacc caccacagcc catcaccctc catttccact 900 tggtgtttgg ttcctgttca ctctgttaat aagaaaccct aagccaagac 950 cctctacgaa cattctttgg gcctcctgga ctacaggaga tgctgtcact 1000 taataatcaa cctggggttc gaaatcagtg agacctggat tcaaattctg 1050 ccttgaaata ttgtgactct gggaatgaca acacctggtt tgttctctgt 1100 tgtatcccca gccccaaaga cagctcctgg ccatatatca aggtttcaat 1150 aaatatttgc taaatgaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 12 00 aaaa 12 04 <210> 170 <211> 250 <212> PRT <213> Homo sapiens <400> 170 Met Arg Ile Leu Gin Leu Ile Leu Leu Ala Leu Ala Thr Gly Leu 15 10 15 Val Gly Gly Glu Thr Arg Ile Ile Lys Gly Phe Glu Cys Lys Pro 20 25 30 His Ser Gin Pro Trp Gin Ala Ala Leu Phe Glu Lys Thr Arg Leu 35 40 45 Leu Cys Gly Ala Thr Leu Ile Ala Pro Arg Trp Leu Leu Thr Ala 50 55 60 Ala His Cys Leu Lys Pro Arg Tyr Ile Val His Leu Gly Gin His 65- 70 75 Asn Leu Gin Lys Glu Glu Gly Cys Glu Gin Thr Arg Thr Ala Thr 80 85 90 Glu Ser Phe Pro His Pro Gly Phe Asn Asn Ser Leu Pro Asn Lys 95 100 105 Asp His Arg Asn Asp Ile Met Leu Val Lys Met Ala Ser Pro Val 110 115 120 Ser Ile Thr Trp Ala Val Arg Pro Leu Thr Leu Ser Ser Arg Cys 125 130 135 Val Thr Ala Gly Thr Ser Cys Leu Ile Ser Gly Trp Gly Ser Thr 140 145 150 Ser Ser Pro Gin Leu Arg Leu Pro His Thr Leu Arg Cys Ala Asn 155 160 165 Ile Thr Ile Ile Glu His Gin Lys Cys Glu Asn Ala Tyr Pro Gly 170 648 175 180 Asn Ile Thr Asp Thr Met Val Cys Ala Ser Val Gin Glu Gly Gly 185 190 195 Lys Asp Ser Cys Gin Gly Asp Ser Gly Gly Pro Leu Val Cys Asn 200 205 210 Gin Ser Leu Gin Gly Ile Ile Ser Trp Gly Gin Asp Pro Cys Ala 215 220 225 Ile Thr Arg Lys Pro Gly Val Tyr Thr Lys Val Cys Lys Tyr Val 230 235 240 Asp Trp Ile Gin Glu Thr Met Lys Asn Asn 245 250 <210> 171 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 171 ggctgcggga ctggaagtca tcggg 25 <210> 172 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 172 ctccaggcca tgaggattct gcag 24 <210> 173 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 173 cctctggtct gtaaccag 18 <210> 174 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 174 tctgtgatgt tgccggggta ggcg 24 <210> 175 649 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 175 cgtgtagaca ccaggctttc gggtg 25 <210> 176 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 176 cccttgatga tcctggtc 18 <210> 177 <211> 50 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 177 aggccatgag gattctgcag ttaatcctgc ttgctctggc aacagggctt 50 <210> 178 <211> 43 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 178 gagagaccag gatcatcaag gggttcgagt gcaagcctca ctc 43 <210> 179 <211> 907 <212> DNA <213> Homo sapiens <400> 179 gagcagtgtt ctgctggagc cgatgccaaa aaccatgcat ttcttattca 50 gattcattgt tttcttttat ctgtggggcc tttttactgc tcagagacaa 100 aagaaagagg agagcaccga agaagtgaaa atagaagttt tgcatcgtcc 150 agaaaactgc tctaagacaa gcaagaaggg agacctacta aatgcccatt 2 00 atgacggcta cctggctaaa gacggctcga aattctactg cagccggaca 2 50 caaaatgaag gccaccccaa atggtttgtt cttggtgttg ggcaagtcat 300 aaaaggccta gacattgcta tgacagatat gtgccctgga gaaaagcgaa 350 650 aagtagttat acccccttca tttgcatacg gaaaggaagg ctatgcagaa 400 ggcaagattc caccggatgc tacattgatt tttgagattg aactttatgc 450 tgtgaccaaa ggaccacgga gcattgagac atttaaacaa atagacatgg 500 acaatgacag gcagctctct aaagccgaga taaacctcta cttgcaaagg 550 gaatttgaaa aagatgagaa gccacgtgac aagtcatatc aggatgcagt 600 tttagaagat atttttaaga agaatgacca tgatggtgat ggcttcattt 650 ctcccaagga atacaatgta taccaacacg atgaactata gcatatttgt 700 atttctactt ttttttttta gctatttact gtactttatg tataaaacaa 750 agtcactttt ctccaagttg tatttgctat ttttccccta tgagaagata 800 ttttgatctc cccaatacat tgattttggt ataataaatg tgaggctgtt 850 ttgcaaactt aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 900 aaaaaaa 907 <210> 180 <211> 222 <212> PRT <213> Homo sapiens <400> 180 Met Pro Lys Thr Met His Phe Leu Phe Arg Phe Ile Val Phe Phe 15 10 15 Tyr Leu Trp Gly Leu Phe Thr Ala Gin Arg Gin Lys Lys Glu Glu 20 25 30 Ser Thr Glu Glu Val Lys Ile Glu Val Leu His Arg Pro Glu Asn 35 40 45 Cys Ser Lys Thr Ser Lys Lys Gly Asp Leu Leu Asn Ala His Tyr 50 55 60 Asp Gly Tyr Leu Ala Lys Asp Gly Ser Lys Phe Tyr Cys Ser Arg 65 70 75 Thr Gin Asn Glu Gly His Pro Lys Trp Phe Val Leu Gly Val Gly 80 85 90 Gin Val Ile Lys Gly Leu Asp Ile Ala Met Thr Asp Met Cys Pro 95 100 105 Gly Glu Lys Arg Lys Val Val Ile Pro Pro Ser Phe Ala Tyr Gly 110 115 120 Lys Glu Gly Tyr Ala Glu Gly Lys Ile Pro Pro Asp Ala Thr Leu 125 130 135 Ile Phe Glu Ile Glu Leu Tyr Ala Val Thr Lys Gly Pro Arg Ser 140 145 150 Ile Glu Thr Phe Lys Gin Ile Asp Met Asp Asn Asp Arg Gin Leu 155 160 165 651 Ser Lys Ala Asp Glu Lys Asp Ile Phe Pro Lys Glu <210> 181 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 181 gtgttctgct ggagccgatg cc 22 <210> 182 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 182 gacatggaca atgacagg 18 <210> 183 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 183 cctttcagga tgtaggag 18 <210> 184 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 184 gatgtctgcc accccaag 18 <210> 185 <211> 27 <212> DNA <213> Artificial Sequence Glu Ile Asn Leu Tyr Leu Gin Arg Glu Phe Glu Lys 170 175 180 Pro Arg Asp Lys Se'r Tyr Gin Asp Ala Val Leu Glu 185 190 195 Lys Lys Asn Asp His Asp Gly Asp Gly Phe Ile Ser 200 205 210 Tyr Asn Val Tyr Gin His Asp Glu Leu 215 220 <220> <223> Synthetic oligonucleotide probe 652 <400> 185 gcatcctgat atgacttgtc acgtggc 27 <210> 186 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 186 tacaagaggg aagaggagtt gcac 24 <210> 187 <211> 52 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 187 gcccattatg acggctacct ggctaaagac ggctcgaaat tctactgcag 50 cc 52 <210> 188 <211> 573 <212> DNA <213> Homo sapiens <400> 188 cagaaatgca gggaccattg cttcttccag gcctctgctt tctgctgagc 50 ctctttggag ctgtgactca gaaaaccaaa acttcctgtg ctaagtgccc 100 cccaaatgct tcctgtgtca ataacactca ctgcacctgc aaccatggat 150 atacttctgg atctgggcag aaactattca cattcccctt ggagacatgt 200 aacgccaggc atggtggctc gcgcctgtaa tcccagttct ttgggaagcc 250 aaggcaggtg gatcacctga ggtcaggagt ttgagaccag cctggccaac 300 atagtgaaac cccgtgtcta ctaaaaatac aaaaatcagc cgggcgtggt 350 ggtgcatgcc tgcaatccca gttactcggg aggctgaggc aggagaatcg 400 cttgaactca ggaggcagaa gttgcagtga acccagatcc tgccattgca 450 ctccagcatg gatgacagag caagactccg tctcaaaaag aaaagatagt 500 ttcttgtttc atttcgcgac tgccctctca gtgtttcctg ggatcccctc 550 ccaaataaag tacttatatt ctc 573 <210> 189 <211> 74 <212> PRT <213> Homo sapiens 653 <400> 189 Met Gin Gly Pro Leu Leu Leu Pro Gly Leu Cys Phe Leu Leu Ser 15 10 15 Leu Phe Gly Ala Val Thr Gin Lys Thr Lys Thr Ser Cys Ala Lys 20 25 30 Cys Pro Pro Asn Ala Ser Cys Val Asn Asn Thr His Cys Thr Cys 35 40 45 Asn His Gly Tyr Thr Ser Gly Ser Gly Gin Lys Leu Phe Thr Phe 50 55 60 Pro Leu Glu Thr Cys Asn Ala Arg His Gly Gly Ser Arg Leu 65 70 <210> 190 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 190 agggaccatt gcttcttcca ggcc 24 <210> 191 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 191 cgttacatgt ctccaagggg aatg 24 <210> 192 <211> 50 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 192 cctgtgctaa gtgcccccca aatgcttcct gtgtcaataa cactcactgc 50 <210> 193 <211> 1091 <212> DNA <213> Homo sapiens <400> 193 caagcaggtc atccccttgg tgaccttcaa agagaagcag agagggcaga 50 ggtggggggc acagggaaag ggtgacctct gagattcccc ttttccccca 100 gactttggaa gtgacccacc atggggctca gcatcttttt gctcctgtgt 150 gttcttgggc tcagccaggc agccacaccg aagattttca atggcactga 200 654 gtgtgggcgt aactcacagc cgtggcaggt ggggctgttt gagggcacca 250 gcctgcgctg cgggggtgtc cttattgacc acaggtgggt cctcacagcg 300 gctcactgca gcggcagcag gtactgggtg cgcctggggg aacacagcct 350 cagccagctc gactggaccg agcagatccg gcacagcggc ttctctgtga 400 cccatcccgg ctacctggga gcctcgacga gccacgagca cgacctccgg 450 ctgctgcggc tgcgcctgcc cgtccgcgta accagcagcg ttcaacccct 500 gcccctgccc aatgactgtg caaccgctgg caccgagtgc cacgtctcag 550 gctggggcat caccaaccac ccacggaacc cattcccgga tctgctccag 600 tgcctcaacc tctccatcgt ctcccatgcc acctgccatg gtgtgtatcc 650 cgggagaatc acgagcaaca tggtgtgtgc aggcggcgtc ccggggcagg 700 atgcctgcca gggtgattct gggggccccc tggtgtgtgg gggagtcctt 750 caaggtctgg tgtcctgggg gtctgtgggg ccctgtggac aagatggcat 800 ccctggagtc tacacctata tttgcaagta tgtggactgg atccggatga 850 tcatgaggaa caactgacct gtttcctcca cctccacccc caccccttaa 900 cttgggtacc cctctggccc tcagagcacc aatatctcct ccatcacttc 950 ccctagctcc actcttgttg gcctgggaac ttcttggaac tttaactcct 1000 gccagccctt ctaagaccca cgagcggggt gagagaagtg tgcaatagtc 1050 tggaataaat ataaatgaag gaggggcaaa aaaaaaaaaa a 1091 <210> 194 <211> 248 <212> PRT <213> Homo sapiens <400> 194 Met Gly Leu Ser Ile Phe Leu Leu Leu Cys Val Leu Gly Leu Ser 15 10 15 Gin Ala Ala Thr Pro Lys Ile Phe Asn Gly Thr Glu Cys Gly Arg 20 25 30 Asn Ser Gin Pro Trp Gin Val Gly Leu Phe Glu Gly Thr Ser Leu 35 40 45 Arg Cys Gly Gly Val Leu Ile Asp His Arg Trp Val Leu Thr Ala 50 55 60 Ala His Cys Ser Gly Ser Arg Tyr Trp Val Arg Leu Gly Glu His 65 70 75 Ser Leu Ser Gin Leu Asp Trp Thr Glu Gin Ile Arg His Ser Gly 80 85 90 Phe Ser Val Thr His Pro Gly Tyr Leu Gly Ala Ser Thr Ser His 95 100 105 655 Glu His Asp Leu Arg Leu Leu Arg Leu Arg Leu Pro Val Arg Val 110 115 120 Thr Ser Ser Val Gin Pro Leu Pro Leu Pro Asn Asp Cys Ala Thr 125 130 135 Ala Gly Thr Glu Cys His Val Ser Gly Trp Gly Ile Thr Asn His 140 145 150 Pro Arg Asn Pro Phe Pro Asp Leu Leu Gin Cys Leu Asn Leu Ser 155 160 165 Ile Val Ser His Ala Thr Cys His Gly Val Tyr Pro Gly Arg Ile 170 175 180 Thr Ser Asn Met Val Cys Ala Gly Gly Val Pro Gly Gin Asp Ala 185 190 195 Cys Gin Gly Asp Ser Gly Gly Pro Leu Val Cys Gly Gly Val Leu 200 205 210 Gin Gly Leu Val Ser Trp Gly Ser Val Gly Pro Cys Gly Gin Asp 215 220 225 Gly Ile Pro Gly Val Tyr Thr Tyr Ile Cys Lys Tyr Val Asp Trp 230 235 240 Ile Arg Met Ile Met Arg Asn Asn 245 <210> 195 <211> 1485 <212> DNA <213> Homo sapiens <400> 195 gcggccacac gcagctagcc ggagcccgga ccaggcgcct gtgcctcctc 50 ctcgtccctc gccgcgtccg cgaagcctgg agccggcggg agccccgcgc 100 tcgccatgtc gggcgagctc agcaacaggt tccaaggagg gaaggcgttc 150 ggcttgctca aagcccggca ggagaggagg ctggccgaga tcaaccggga 200 gtttctgtgt gaccagaagt acagtgatga agagaacctt ccagaaaagc 250 tcacagcctt caaagagaag tacatggagt ttgacctgaa caatgaaggc 300 gagattgacc tgatgtcttt aaagaggatg atggagaagc ttggtgtccc 350 caagacccac ctggagatga agaagatgat ctcagaggtg acaggagggg 400 tcagtgacac tatatcctac cgagactttg tgaacatgat gctggggaaa 450 cggtcggctg tcctcaagtt agtcatgatg tttgaaggaa aagccaacga 500 gagcagcccc aagccagttg gcccccctcc agagagagac attgctagcc 550 tgccctgagg accccgcctg gactccccag ccttcccacc ccatacctcc 600 ctcccgatct tgctgccctt cttgacacac tgtgatctct ctctctctca 650 656 tttgtttggt cattgagggt ttgtttgtgt tttcatcaat gtctttgtaa 700 agcacaaatt atctgcctta aaggggctct gggtcgggga atcctgagcc 750 ttgggtcccc tccctctctt cttccctcct tccccgctcc ctgtgcagaa 800 gggctgatat caaaccaaaa actagagggg gcagggccag ggcagggagg 850 cttccagcct gtgttcccct cacttggagg aaccagcact ctccatcctt 900 tcagaaagtc tccaagccaa gttcaggctc actgacctgg ctctgacgag 950 gaccccaggc cactctgaga agaccttgga gtagggacaa ggctgcaggg 1000 cctctttcgg gtttccttgg acagtgccat ggttccagtg ctctggtgtc 1050 acccaggaca cagccactcg gggccccgct gccccagctg atccccactc 1100 attccacacc tcttctcatc ctcagtgatg tgaaggtggg aaggaaagga 1150 gcttggcatt gggagccctt caagaaggta ccagaaggaa ccctccagtc 12 00 ctgctctctg gccacacctg tgcaggcagc tgagaggcag cgtgcagccc 12 50 tactgtccct tactggggca gcagagggct tcggaggcag aagtgaggcc 13 00 tggggtttgg ggggaaaggt cagctcagtg ctgttccacc ttttagggag 1350 gatactgagg ggaccaggat gggagaatga ggagtaaaat gctcacggca 1400 aagtcagcag cactggtaag ccaagactga gaaatacaag gttgcttgtc 1450 tgaccccaat ctgcttgaaa aaaaaaaaaa aaaaa 1485 <210> 196 <211> 150 <212> PRT <213> Homo sapiens <400> 196 Met Ser Gly Glu Leu Ser Asn Arg Phe Gin Gly Gly Lys Ala Phe 15 10 15 Gly Leu Leu Lys Ala Arg Gin Glu Arg Arg Leu Ala Glu Ile Asn 20 25 30 Arg Glu Phe Leu Cys Asp Gin Lys Tyr Ser Asp Glu Glu Asn Leu 35 40 45 Pro Glu Lys Leu Thr Ala Phe Lys Glu Lys Tyr Met Glu Phe Asp 50 55 60 Leu Asn Asn Glu Gly Glu Ile Asp Leu Met Ser Leu Lys Arg Met 65 70 75 Met Glu Lys Leu Gly Val Pro Lys Thr His Leu Glu Met Lys Lys 80 85 90 Met Ile Ser Glu Val Thr Gly Gly Val Ser Asp Thr Ile Ser Tyr 95 100 105 657 Arg Asp Phe Val Asn Met Met Leu Gly Lys Arg Ser Ala Val Leu 110 115 120 Lys Leu Val Met Met Phe Glu Gly Lys Ala Asn Glu Ser Ser Pro 125 130 135 Lys Pro Val Gly Pro Pro Pro Glu Arg Asp Ile Ala Ser Leu Pro 140 145 150 <210> 197 <211> 4842 <212> DNA <213> Homo sapiens <400> 197 cgcgctcccc gcgcgcctcc tcgggctcca cgcgtcttgc cccgcagagg 50 cagcctcctc caggagcggg gccctgcaca ccatggcccc cgggtgggca 100 ggggtcggcg ccgccgtgcg cgcccgcctg gcgctggcct tggcgctggc 150 gagcgtcctg agtgggcctc cagccgtcgc ctgccccacc aagtgtacct 200 gctccgctgc cagcgtggac tgccacgggc tgggcctccg cgcggttcct 250 cggggcatcc cccgcaacgc tgagcgcctt gacctggaca gaaataatat 300 caccaggatc accaagatgg acttcgctgg gctcaagaac ctccgagtct 350 tgcatctgga agacaaccag gtcagcgtca tcgagagagg cgccttccag 400 gacctgaagc agctagagcg actgcgcctg aacaagaata agctgcaagt 450 ccttccagaa ttgcttttcc agagcacgcc gaagctcacc agactagatt 500 tgagtgaaaa ccagatccag gggatcccga ggaaggcgtt ccgcggcatc 550 accgatgtga agaacctgca actggacaac aaccacatca gctgcattga 600 agatggagcc ttccgagcgc tgcgcgattt ggagatcctt accctcaaca 650 acaacaacat cagtcgcatc ctggtcacca gcttcaacca catgccgaag 700 atccgaactc tgcgcctcca ctccaaccac ctctactgcg actgccacct 750 ggcctggctc tcggattggc tgcgacagcg acggacagtt ggccagttca 800 cactctgcat ggctcctgtg catttgaggg gcttcaacgt ggcggatgtg 850 cagaagaagg agtacgtgtg cccagccccc cactcggagc ccccatcctg 900 caatgccaac tccatctcct gcccttcgcc ctgcacgtgc agcaataaca 950 tcgtggactg tcgaggaaag ggcttgatgg agattcctgc caacttgccg 1000 gagggcatcg tcgaaatacg cctagaacag aactccatca aagccatccc 1050 tgcaggagcc ttcacccagt acaagaaact gaagcgaata gacatcagca 1100 agaatcagat atcggatatt gctccagatg ccttccaggg cctgaaatca 1150 ctcacatcgc tggtcctgta tgggaacaag atcaccgaga ttgccaaggg 1200 658 actgtttgat gggctggtgt ccctacagct gctcctcctc aatgccaaca 1250 agatcaactg cctgcgggtg aacacgtttc aggacctgca gaacctcaac 1300 ttgctctccc tgtatgacaa caagctgcag accatcagca aggggctctt 1350 cgcccctctg cagtccatcc agacactcca cttagcccaa aacccatttg 1400 tgtgcgactg ccacttgaag tggctggccg actacctcca ggacaacccc 1450 atcgagacaa gcggggcccg ctgcagcagc ccgcgccgac tcgccaacaa 1500 gcgcatcagc cagatcaaga gcaagaagtt ccgctgctca ggctccgagg 1550 attaccgcag caggttcagc agcgagtgct tcatggacct cgtgtgcccc 1600 gagaagtgtc gctgtgaggg cacgattgtg gactgctcca accagaagct 1650 ggtccgcatc ccaagccacc tccctgaata tgtcaccgac ctgcgactga 1700 atgacaatga ggtatctgtt ctggaggcca ctggcatctt caagaagttg 1750 cccaacctgc ggaaaataaa tctgagtaac aataagatca aggaggtgcg 1800 agagggagct ttcgatggag cagccagcgt gcaggagctg atgctgacag 1850 ggaaccagct ggagaccgtg cacgggcgcg tgttccgtgg cctcagtggc 1900 ctcaaaacct tgatgctgag gagtaacttg atcagctgtg tgagtaatga 1950 cacctttgcc ggcctgagtt cggtgagact gctgtccctc tatgacaatc 2000 ggatcaccac catcacccct ggggccttca ccacgcttgt ctccctgtcc 2050 accataaacc tcctgtccaa ccccttcaac tgcaactgcc acctggcctg 2100 gctcggcaag tggttgagga agaggcggat cgtcagtggg aaccctaggt 2150 gccagaagcc caggacttca atttttcctc cctgtgatgg aaggagattc caacgaggag ccatccagga agtagctgcc tgtggccatc agctgagccc 2200 2250 gcgctgcccg gagcagtgca cctgtatgga gacagtggtg cgatgcagca 2300 acaaggggct ccgcgccctc cccagaggca tgcccaagga tgtgaccgag 2350 ctgtacctgg aaggaaacca cctaacagcc gtgcccagag agctgtccgc 2400 cctccgacac ctgacgctta ttgacctgag caacaacagc atcagcatgc 2450 tgaccaatta caccttcagt aacatgtctc acctctccac tctgatcctg 2500 agctacaacc ggctgaggtg catccccgtc cacgccttca acgggctgcg 2550 gtccctgcga gtgctaaccc tccatggcaa tgacatttcc agcgttcctg 2600 aaggctcctt caacgacctc acatctcttt cccatctggc gctgggaacc 2650 aacccactcc actgtgactg cagtcttcgg tggctgtcgg agtgggtgaa 2700 ggcggggtac aaggagcctg gcatcgcccg ctgcagtagc cctgagccca 2750 659 tggctgacag gctcctgctc accaccccaa cccaccgctt ccagtgcaaa 2800 gggccagtgg acatcaacat tgtggccaaa tgcaatgcct gcctctccag 2850 cccgtgcaag aataacggga catgcaccca ggaccctgtg gagctgtacc 2900 gctgtgcctg cccctacagc tacaagggca aggactgcac tgtgcccatc 2950 aacacctgca tccagaaccc ctgtcagcat ggaggcacct gccacctgag 3000 tgacagccac aaggatgggt tcagctgctc ctgccctctg ggctttgagg 3050 ggcagcggtg tgagatcaac ccagatgact gtgaggacaa cgactgcgaa 3100 aacaatgcca cctgcgtgga cgggatcaac aactacgtgt gtatctgtcc 3150 gcctaactac acaggtgagc tatgcgacga ggtgattgac cactgtgtgc 3200 ctgagctgaa cctctgtcag catgaggcca agtgcatccc cctggacaaa 3250 ggattcagct gcgagtgtgt ccctggctac agcgggaagc tctgtgagac 3300 agacaatgat gactgtgtgg cccacaagtg ccgccacggg gcccagtgcg 3350 tggacacaat caatggctac acatgcacct gcccccaggg cttcagtgga 3400 cccttctgtg aacacccccc acccatggtc ctactgcaga ccagcccatg 3450 cgaccagtac gagtgccaga acggggccca gtgcatcgtg gtgcagcagg 3500 agcccacctg ccgctgccca ccaggcttcg ccggccccag atgcgagaag 3550 ctcatcactg tcaacttcgt gggcaaagac tcctacgtgg aactggcctc 3600 cgccaaggtc cgaccccagg ccaacatctc cctgcaggtg gccactgaca 3650 aggacaacgg catccttctc tacaaaggag acaatgaccc cctggcactg 3700 gagctgtacc agggccacgt gcggctggtc tatgacagcc tgagttcccc 3750 tccaaccaca gtgtggagct gtgtacagtg ggtgacgcta tggagacagt aaccagaccc gaatgatggg tgaacctagt cagtttcaca agtggacaaa 3800 3850 ggaactccaa agagcctggg gaagctccag aagcagccag cagtgggcat 3900 caacagcccc ctctaccttg gaggcatccc cacctccacc ggcctctccg 3950 ccttgcgcca gggcacggac cggcctctag gcggcttcca cggatgcatc 4000 catgaggtgc gcatcaacaa cgagctgcag gacttcaagg ccctcccacc 4050 acagtccctg ggggtgtcac caggctgcaa gtcctgcacc gtgtgcaagc 4100 acggcctgtg ccgctccgtg gagaaggaca gcgtggtgtg cgagtgccgc 4150 ccaggctgga ccggcccact ctgcgaccag gaggcccggg acccctgcct 4200 cggccacaga tgccaccatg gaaaatgtgt ggcaactggg acctcataca 4250 tgtgcaagtg tgccgagggc tatggagggg acttgtgtga caacaagaat 4300 gactctgcca atgcctgctc agccttcaag tgtcaccatg ggcagtgcca 4350 660 catctcagac caaggggagc cctactgcct gtgccagccc ggctttagcg 4400 gcgagcactg ccaacaagag aatccgtgcc tgggacaagt agtccgagag 4450 gtgatccgcc gccagaaagg ttatgcatca tgtgccacag cctccaaggt 4500 gcccatcatg gaatgtcgtg ggggctgtgg gccccagtgc tgccagccca 4550 cccgcagcaa gcggcggaaa tacgtcttcc agtgcacgga cggctcctcg 4600 tttgtagaag aggtggagag acacttagag tgcggctgcc tcgcgtgttc 4650 ctaagcccct gcccgcctgc ctgccacctc tcggactcca gcttgatgga 4700 gttgggacag ccatgtggga ccccctggtg attcagcatg aaggaaatga 4750 agctggagag gaaggtaaag aagaagagaa tattaagtat attgtaaaat 4800 aaacaaaaaa tagaacttaa aaaaaaaaaa aaaaaaaaaa aa 4842 <210> 198 <211> 1523 <212> PRT <213> Homo sapiens <400> 198 Met Ala Pro Gly Trp Ala Gly Val Gly Ala Ala Val Arg Ala Arg 15 10 15 Leu Ala Leu Ala Leu Ala Leu Ala Ser Val Leu Ser Gly Pro Pro 20 25 30 Ala Val Ala Cys Pro Thr Lys Cys Thr Cys Ser Ala Ala Ser Val 35 40 45 Asp Cys His Gly Leu Gly Leu Arg Ala Val Pro Arg Gly Ile Pro 50 55 60 Arg Asn Ala Glu Arg Leu Asp Leu Asp Arg Asn Asn Ile Thr Arg 65 70 75 Ile Thr Lys Met Asp Phe Ala Gly Leu Lys Asn Leu Arg Val Leu 80 85 90 His Leu Glu Asp Asn Gin Val Ser Val Ile Glu Arg Gly Ala Phe 95 100 105 Gin Asp Leu Lys Gin Leu Glu Arg Leu Arg Leu Asn Lys Asn Lys 110 115 120 Leu Gin Val Leu Pro Glu Leu Leu Phe Gin Ser Thr Pro Lys Leu 125 130 135 Thr Arg Leu Asp Leu Ser Glu Asn Gin Ile Gin Gly Ile Pro Arg 140 145 150 Lys Ala Phe Arg Gly Ile Thr Asp Val Lys Asn Leu Gin Leu Asp 155 160 165 Asn Asn His Ile Ser Cys Ile Glu Asp Gly Ala Phe Arg Ala Leu 170 175 180 661 Arg Asp Leu Glu Ile Leu Thr Leu Asn Asn Asn Asn Ile Ser Arg 185 190 195 Ile Leu Val Thr Ser Phe Asn His Met Pro Lys Ile Arg Thr Leu 200 205 210 Arg Leu His Ser Asn His Leu Tyr Cys Asp Cys His Leu Ala Trp 215 220 225 Leu Ser Asp Trp Leu Arg Gin Arg Arg Thr Val Gly Gin Phe Thr 230 235 240 Leu Cys Met Ala Pro Val His Leu Arg Gly Phe Asn Val Ala Asp 245 250 255 Val Gin Lys Lys Glu Tyr Val Cys Pro Ala Pro His Ser Glu Pro 260 265 270 Pro Ser Cys Asn Ala Asn Ser Ile Ser Cys Pro Ser Pro Cys Thr 275 280 285 Cys Ser Asn Asn Ile Val Asp Cys Arg Gly Lys Gly Leu Met Glu 290 295 300 Ile Pro Ala Asn Leu Pro Glu Gly Ile Val Glu Ile Arg Leu Glu 305 310 315 Gin Asn Ser Ile Lys Ala Ile Pro Ala Gly Ala Phe Thr Gin Tyr 320 325 330 Lys Lys Leu Lys Arg Ile Asp Ile Ser Lys Asn Gin Ile Ser Asp 335 340 345 Ile Ala Pro Asp Ala Phe Gin Gly Leu Lys Ser Leu Thr Ser Leu 350 355 360 Val Leu Tyr Gly Asn Lys Ile Thr Glu Ile Ala Lys Gly Leu Phe 365 370 375 Asp Gly Leu Val Ser Leu Gin Leu Leu Leu Leu Asn Ala Asn Lys 380 385 390 Ile Asn Cys Leu Arg Val Asn Thr Phe Gin Asp Leu Gin Asn Leu 395 400 405 Asn Leu Leu Ser Leu Tyr Asp Asn Lys Leu Gin Thr Ile Ser Lys 410 415 420 Gly Leu Phe Ala Pro Leu Gin Ser Ile Gin Thr Leu His Leu Ala 425 430 435 Gin Asn Pro Phe Val Cys Asp Cys His Leu Lys Trp Leu Ala Asp 440 445 450 Tyr Leu Gin Asp Asn Pro Ile Glu Thr Ser Gly Ala Arg Cys Ser 455 460 465 Ser Pro Arg Arg Leu Ala Asn Lys Arg Ile Ser Gin Ile Lys Ser 470 475 480 Lys Lys Phe Arg Cys Ser Gly Ser Glu Asp Tyr Arg Ser Arg Phe 662 485 490 495 Ser Ser Glu Cys Phe Met Asp Leu Val Cys Pro Glu Lys Cys Arg 500 505 510 Cys Glu Gly Thr Ile Val Asp Cys Ser Asn Gin Lys Leu Val Arg 515 520 525 lie Pro Ser His Leu Pro Glu Tyr Val Thr Asp Leu Arg Leu Asn 530 535 540 Asp Asn Glu Val Ser Val Leu Glu Ala. Thr Gly Ile Phe Lys Lys 545 550 555 Leu Pro Asn Leu Arg Lys Ile Asn Leu Ser Asn Asn Lys Ile Lys 560 565 570 Glu Val Arg Glu Gly Ala Phe Asp Gly Ala Ala Ser Val Gin Glu 575 580 585 Leu Met Leu Thr Gly Asn Gin Leu Glu Thr Val His Gly Arg Val 590 595 600 Phe Arg Gly Leu Ser Gly Leu Lys Thr Leu Met Leu Arg Ser Asn 605 610 615 Leu Ile Ser Cys Val Ser Asn Asp Thr Phe Ala Gly Leu Ser Ser 620 625 630 Val Arg Leu Leu Ser Leu Tyr Asp Asn Arg Ile Thr Thr Ile Thr 635 640 645 Pro Gly Ala Phe Thr Thr Leu Val Ser Leu Ser Thr Ile Asn Leu 650 655 660 Leu Ser Asn Pro Phe Asn Cys Asn Cys His Leu Ala Trp Leu Gly 665 670 675 Lys Trp Leu Arg Lys Arg Arg Ile Val Ser Gly Asn Pro Arg Cys 680 685 690 Gin Lys Pro Phe Phe Leu Lys Glu Ile Pro Ile Gin Asp Val Ala 695 700 705 Ile Gin Asp Phe Thr Cys Asp Gly Asn Glu Glu Ser Ser Cys Gin 710 715 720 Leu Ser Pro Arg Cys Pro Glu Gin Cys Thr Cys Met Glu Thr Val 725 730 735 Val Arg Cys Ser Asn Lys Gly Leu Arg Ala Leu Pro Arg Gly Met 740 745 750 Pro Lys Asp Val Thr Glu Leu Tyr Leu Glu Gly Asn His Leu Thr 755 760 765 Ala Val Pro Arg Glu Leu Ser Ala Leu Arg His Leu Thr Leu Ile 770 775 780 Asp Leu Ser Asn Asn Ser Ile Ser Met Leu Thr Asn Tyr Thr Phe 785 790 795 Ser Asn Met Ser His 800 Leu Ser Thr Leu Ile 805 Leu Ser Tyr Asn Arg 810 Leu Arg Cys Ile Pro 815 Val His Ala Phe Asn 820 Gly Leu Arg Ser Leu 825 Arg Val Leu Thr Leu 830 His Gly Asn Asp Ile 835 Ser Ser Val Pro Glu 840 Gly Ser Phe Asn Asp 845 Leu Thr Ser Leu Ser 850 His Leu Ala Leu Gly 855 Thr Asn Pro Leu His 860 Cys Asp Cys Ser Leu 865 Arg Trp Leu Ser Glu 870 Trp Val Lys Ala Gly 875 Tyr Lys Glu Pro Gly 880 Ile Ala Arg Cys Ser 885 Ser Pro Glu Pro Met 890 Ala Asp Arg Leu Leu 895 Leu Thr Thr Pro Thr 900 His Arg Phe Gin Cys 905 Lys Gly Pro Val Asp 910 Ile Asn Ile Val Ala 915 Lys Cys Asn Ala Cys 920 Leu Ser Ser Pro Cys 925 Lys Asn Asn Gly Thr 930 Cys Thr Gin Asp Pro 935 Val Glu Leu Tyr Arg 940 Cys Ala Cys Pro Tyr 945 Ser Tyr Lys Gly Lys 950 Asp Cys Thr Val Pro 955 Ile Asn Thr Cys Ile 960 Gin Asn Pro Cys Gin 965 His Gly Gly Thr Cys 970 His Leu Ser Asp Ser 975 His Lys Asp Gly Phe 980 Ser Cys Ser Cys Pro 985 Leu Gly Phe Glu Gly 990 Gin Arg Cys Glu Ile 995 Asn Pro Asp Asp Cys 1000 Glu Asp Asn Asp Cys 1005 Glu Asn Asn Ala Thr 1010 Cys Val Asp Gly Ile 1015 Asn Asn Tyr Val Cys 1020 Ile Cys Pro Pro Asn 1025 Tyr Thr Gly Glu Leu 1030 Cys Asp Glu Val Ile 1035 Asp His Cys Val Pro 1040 Glu Leu Asn Leu Cys 1045 Gin His Glu Ala Lys 1050 Cys Ile Pro Leu Asp 1055 Lys Gly Phe Ser Cys 1060 Glu Cys Val Pro Gly 1065 Tyr Ser Gly Lys Leu 1070 Cys Glu Thr Asp Asn 1075 Asp Asp Cys Val Ala 1080 His Lys Cys Arg His 1085 Gly Ala Gin Cys Val 1090 Asp Thr Ile Asn Gly 1095 Tyr Thr Cys Thr Cys 1100 Pro Gin Gly Phe Ser 1105 Gly Pro Phe Cys Glu 1110 664 His Pro Pro Pro Met Val Leu Leu Gin Thr Ser Pro - Cys Asp Gin 1115 1120 1125 Tyr Glu Cys Gin Asn Gly Ala Gin Cys Ile Val Val Gin Gin Glu 1130 1135 1140 Pro Thr Cys Arg Cys Pro Pro Gly Phe Ala Gly Pro Arg Cys Glu 1145 1150 1155 Lys Leu Ile Thr Val Asn Phe Val Gly Lys Asp Ser Tyr Val Glu 1160 1165 1170 Leu Ala Ser Ala Lys Val Arg Pro Gin Ala Asn Ile Ser Leu Gin 1175 1180 1185 Val Ala Thr Asp Lys Asp Asn Gly Ile Leu Leu Tyr Lys Gly Asp 1190 1195 1200 Asn Asp Pro Leu Ala Leu Glu Leu Tyr Gin Gly His Val Arg Leu 1205 1210 1215 Val Tyr Asp Ser Leu Ser Ser Pro Pro Thr Thr Val Tyr Ser Val 1220 1225 1230 Glu Thr Val Asn Asp Gly Gin Phe His Ser Val Glu Leu Val Thr 1235 1240 1245 Leu Asn Gin Thr Leu Asn Leu Val Val Asp Lys Gly Thr Pro Lys 1250 1255 1260 Ser Leu Gly Lys Leu Gin Lys Gin Pro Ala Val Gly Ile Asn Ser 1265 1270 1275 Pro Leu Tyr Leu Gly Gly Ile Pro Thr Ser Thr Gly Leu Ser Ala 1280 1285 1290 Leu Arg Gin Gly Thr Asp Arg Pro Leu Gly Gly Phe His Gly Cys 1295 1300 1305 Ile His Glu Val Arg Ile Asn Asn Glu Leu Gin Asp Phe Lys Ala 1310 1315 1320 Leu Pro Pro Gin Ser Leu Gly Val Ser Pro Gly Cys Lys Ser Cys 1325 1330 1335 Thr Val Cys Lys His Gly Leu Cys Arg Ser Val Glu Lys Asp Ser 1340 1345 1350 Val Val Cys Glu Cys Arg Pro Gly Trp Thr Gly Pro Leu Cys Asp 1355 1360 1365 Gin Glu Ala Arg Asp Pro Cys Leu Gly His Arg Cys His His Gly 1370 1375 1380 Lys Cys Val Ala Thr Gly Thr Ser Tyr Met Cys Lys Cys Ala Glu 1385 1390 1395 Gly Tyr Gly Gly Asp Leu Cys Asp Asn Lys Asn Asp Ser Ala Asn 1400 1405 1410 Ala Cys Ser Ala Phe Lys Cys His His Gly Gin Cys His Ile Ser 1415 665 1420 1425 Asp Gin Gly Glu Pro 1430 Glu His Cys Gin Gin 1445 Glu Val Ile Arg Arg 1460 Ser Lys Val Pro Ile 1475 Cys Cys Gin Pro Thr 1490 Cys Thr Asp Gly Ser 1505 Glu Cys Gly Cys Leu 1520 <210> 199 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 199 atggagattc ctgccaactt gccg 24 <210> 200 <211> 24 <212> DNA <213> Artificial Service <220> <221> Artificial Sequence <222> full <223> Synthetic oligonucleotide probe <400> 200 ttgttggcat tgaggaggag cagc 24 <210> 201 <211> 50 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 201 gagggcatcg tcgaaatacg cctagaacag aactccatca aagccatccc 50 <210> 202 <211> 753 <212> DNA <213> Homo sapiens Tyr Cys Leu Cys Gin Pro Gly Phe Ser Gly 1435 1440 Glu Asn Pro Cys Leu Gly Gin Val Val Arg 1450 1455 Gin Lys Gly Tyr Ala Ser Cys Ala Thr Ala 1465 1470 Met Glu Cys Arg Gly Gly Cys Gly Pro Gin 1480 1485 Arg Ser Lys Arg Arg Lys Tyr Val Phe Gin 1495 1500 Ser Phe Val Glu Glu Val Glu Arg His Leu 1510 1515 Ala Cys Ser 666 <400> 202 ggatgcagga cgctcccctg agctgcctgt caccgactag gtggagcagt 50 gtttcttccg cagactcaac tgagaagtca gcctctgggg caggcaccag 100 gaatctgcct tttcagttct gtctccggca ggctttgagg atgaaggctg 150 cgggcattct gaccctcatt ggctgcctgg tcacaggcgc cgagtccaaa 200 atctacactc gttgcaaact ggcaaaaata ttetcgaggg ctggcctgga 250 caattactgg ggcttcagcc ttggaaactg gatctgcatg gcatattatg 300 agagcggcta caacaccaca gccccgacgg tcctggatga cggcagcatc 350 gactatggca tcttccagat caacagcttc gcgtggtgca gacgcggaaa 400 gctgaaggag aacaaccact gccatgtcgc ctgctcagcc ttgatcactg 450 atgacctcac agatgcaatt atctgtgcca ggaaaattgt taaagagaca 500 caaggaatga actattggca aggctggaag aaacattgtg agggcagaga 550 cctgtccgag tggaaaaaag gctgtgaggt ttcctaaact ggaactggac 600 ccaggatgct ttgcagcaac gccctaggat ttgcagtgaa tgtccaaatg 650 cctgtgtcat cttgtcccgt ttcctcccaa tattccttct caaacttgga 700 gagggaaaat taagctatac ttttaagaaa ataaatattt ccatttaaat 750 gtc 753 <210> 203 <211> 148 <212> PRT <213> Homo sapiens <400> 203 Met Lys Ala Ala Gly Ile Leu Thr Leu Ile Gly Cys Leu Val Thr 10 15 Gly Ala Glu Ser Lys Ile Tyr Thr Arg Cys Lys Leu Ala Lys Ile 25 30 Phe Ser Arg Ala Gly Leu Asp Asn Tyr Trp Gly Phe Ser Leu Gly 40 45 Asn Trp Ile Cys Met Ala Tyr Tyr Glu Ser Gly Tyr Asn Thr Thr 50 55 60 Ala Pro Thr Val Leu Asp Asp Gly Ser Ile Asp Tyr Gly Ile Phe 65 70 75 Gin Ile Asn Ser Phe Ala Trp Cys Arg Arg Gly Lys Leu Lys Glu 80 85 90 Asn Asn His Cys His Val Ala Cys Ser Ala Leu Ile Thr Asp Asp 95 100 105 Leu Thr Asp Ala Ile Ile Cys Ala Arg Lys Ile Val Lys Glu Thr 110 115 120 667 Gin Gly Met Asn Tyr Trp Gin Gly Trp Lys Lys His Cys Glu Gly 125 130 135 Arg Asp Leu Ser Glu Trp Lys Lys Gly Cys Glu Val Ser 140 145 <210> 204 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 204 gcaggctttg aggatgaagg ctgc 24 <210> 205 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 205 ctcattggct gcctggtcac aggc 24 <210> 206 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 206 ccagtcggac aggtctctcc cctc 24 <210> 207 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 207 tcagtgacca aggctgagca ggcg 24 <210> 208 <211> 47 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 208 ctacactcgt tgcaaactgg caaaaatatt ctcgagggct ggcctgg 47 668 <210> 209 <211> 1648 <212> DNA <213> Homo sapiens <400> 209 caggccattt gcatcccact gtccttgtgt tcggagccag gccacaccgt 50 cctcagcagt gtcatgtgtt aaaaacgcca agctgaatat atcatgcccc 100 tattaaaact tgtacatggc tccccattgg tttttggaga aaagttcaag 150 ctttttacct tggtgtctgc ctgtatccca gtgttcaggc tggctagacg 200 gcggaagaag atcctatttt actgtcactt cccagatctg cttctcacca 250 agagagattc ttttcttaaa cgactataca gggccccaat tgactggata 300 gaggaataca ccacaggcat ggcagactgc atcttagtca acagccagtt 350 cacagctgct gtttttaagg aaacattcaa gtccctgtct cacatagacc 400 ctgatgtcct ctatccatct ctaaatgtca ccagctttga ctcagttgtt 450 cctgaaaagc tggatgacct agtccccaag gggaaaaaat tcctgctgct 500 ctccatcaac agatacgaaa ggaagaaaaa tctgactttg gcactggaag 550 ccctagtaca gctgcgtgga agattgacat cccaagattg ggagagggtt 600 catctgatcg tggcaggtgg ttatgacgag agagtcctgg agaatgtgga 650 acattatcag gaattgaaga aaatggtcca acagtccgac cttggccagt 700 atgtgacctt cttgaggtct ttctcagaca aacagaaaat ctccctcctc 750 cacagctgca cgtgtgtgct ttacacacca agcaatgagc actttggcat 800 tgtccctctg gaagccatgt acatgcagtg cccagtcatt gctgttaatt 850 cgggtggacc cttggagtcc attgaccaca gtgtcacagg gtttctgtgt 900 gagcctgacc cggtgcactt ctcagaagca atagaaaagt tcatccgtga 950 accttcctta aaagccacca tgggcctggc tggaagagcc agagtgaagg 1000 aaaaattttc ccctgaagca tttacagaac agctctaccg atatgttacc 1050 aaactgctgg tataatcaga ttgtttttaa gatctccatt aatgtcattt 1100 ttatggattg tagacccagt tttgaaacca aaaaagaaac ctagaatcta 1150 atgcagaaga gatcttttaa aaaataaact tgagtcttga atgtgagcca 1200 ctttcctata taccacacct ccctgtccac ttttcagaaa aaccatgtct 1250 tttatgctat aatcattcca aattttgcca gtgttaagtt acaaatgtgg 1300 tgtcattcca tgttcagcag agtattttaa ttatattttc tcgggattat 1350 tgctcttctg tctataaatt ttgaatgata ctgtgcctta attggttttc 1400 669 atagtttaag tgtgtatcat tatcaaagtt gattaatttg gcttcatagt 1450 ataatgagag cagggctatt gtagttccca gattcaatcc accgaagtgt 1500 tcactgtcat ctgttaggga atttttgttt gtcctgtctt tgcctggatc 1550 catagcgaga gtgctctgta ttttttttaa gataatttgt atttttgcac 1600 actgagatat aataaaaggt gtttatcata aaaaaaaaaa aaaaaaaa 1648 <210> 210 <211> 323 <212> PRT <213> Homo sapiens <400> 210 Met Pro Leu Leu Lys Leu Val His Gly Ser Pro Leu Val Phe Gly 1 5 10 15 Glu Lys Phe Lys Leu Phe Thr Leu Val Ser Ala Cys Ile Pro Val 20 25 30 Phe Arg Leu Ala Arg Arg Arg Lys Lys Ile Leu Phe Tyr Cys His 35 40 45 Phe Pro Asp Leu Leu Leu Thr Lys Arg Asp Ser Phe Leu Lys Arg 50 55 60 Leu Tyr Arg Ala Pro Ile Asp Trp Ile Glu Glu Tyr Thr Thr Gly 65 70 75 Met Ala Asp Cys Ile Leu Val Asn Ser Gin Phe Thr Ala Ala Val 80 85 90 Phe Lys Glu Thr Phe Lys Ser Leu Ser His Ile Asp Pro Asp Val 95 100 105 Leu Tyr Pro Ser Leu Asn Val Thr Ser Phe Asp Ser Val Val Pro 110 115 120 Glu Lys Leu Asp Asp Leu Val Pro Lys Gly Lys Lys Phe Leu Leu 125 130 135 Leu Ser Ile Asn Arg Tyr Glu Arg Lys Lys Asn Leu Thr Leu Ala 140 145 150 Leu Glu Ala Leu Val Gin Leu Arg Gly Arg Leu Thr Ser Gin Asp 155 160 165 Trp Glu Arg Val His Leu Ile Val Ala Gly Gly Tyr Asp Glu Arg 170 175 180 Val Leu Glu Asn Val Glu His Tyr Gin Glu Leu Lys Lys Met Val 185 190 195 Gin Gin Ser Asp Leu Gly Gin Tyr Val Thr Phe Leu Arg Ser Phe 200 205 210 Ser Asp Lys Gin Lys Ile Ser Leu Leu His Ser Cys Thr Cys Val 215 220 225 Leu Tyr Thr Pro Ser Asn Glu His Phe Gly Ile Val Pro Leu Glu 230 235 240 670 Ala Met Tyr Met Gin Cys Pro Val Ile Ala Val Asn Ser Gly Gly 245 250 255 Pro Leu Glu Ser Ile Asp His Ser Val Thr Gly Phe Leu Cys Glu 260 265 270 Pro Asp Pro Val His Phe Ser Glu Ala Ile Glu Lys Phe Ile Arg 275 280 285 Glu Pro Ser Leu Lys Ala Thr Met Gly Leu Ala Gly Arg Ala Arg 290 295 300 Val Lys Glu Lys Phe Ser Pro Glu Ala Phe Thr Glu Gin Leu Tyr 305 310 315 Arg Tyr Val Thr Lys Leu Leu Val 320 <210> 211 <211> 1554 <212> DNA <213> Homo sapiens <400> 211 gactacgccg atccgagacg tggctccctg ggcggcagaa ccatgttgga 50 cttcgcgatc ttcgccgtta ccttcttgct ggcgttggtg ggagccgtgc 100 tctacctcta tccggcttcc agacaagctg caggaattcc agggattact 150 ccaactgaag aaaaagatgg taatcttcca gatattgtga atagtggaag 200 tttgcatgag ttcctggtta atttgcatga gagatatggg cctgtggtct 250 ccttctggtt tggcaggcgc ctcgtggtta gtttgggcac tgttgatgta 300 ctgaagcagc atatcaatcc caataagaca tcggaccctt ttgaaaccat 350 gctgaagtca ttattaaggt atcaatctgg tggtggcagt gtgagtgaaa 400 accacatgag gaaaaaattg tatgaaaatg gtgtgactga ttctctgaag 450 agtaactttg ccctcctcct aaagctttca gaagaattat tagataaatg 500 gctctcctac ccagagaccc agcacgtgcc cctcagccag catatgcttg 550 gttttgctat gaagtctgtt acacagatgg taatgggtag tacatttgaa 600 gatgatcagg aagtcattcg cttccagaag aatcatggca cagtttggtc 650 tgagattgga ggaaaaaaca aaaggctttc atatgaagat tagatgggtc gccctcatgc acttgataaa aactggagtc aacatgactc tgttttaagg 700 750 aacatcataa aagaacgaaa aggaaggaac ttcagtcaac atattttcat 800 tgactcctta gtacaaggga accttaatga ccaacagatc ctagaagaca 850 gtatgatatt ttctctggcc agttgcataa taactgcaaa attgtgtacc 900 tgggcaatct gttttttaac cacctctgaa gaagttcaaa aaaaattata 950 671 tgaagagata aaccaagttt ttggaaatgg tcctgttact ccagagaaaa 1000 ttgagcagct cagatattgt cagcatgtgc tttgtgaaac tgttcgaact 1050 gccaaactga ctccagtttc tgcccagctt caagatattg aaggaaaaat 1100 tgaccgattt attattccta gagagaccct cgtcctttat gcccttggtg 1150 tggtacttca ggatcctaat acttggccat ctccacacaa gtttgatcca 1200 gatcggtttg atgatgaatt agtaatgaaa actttttcct cacttggatt 1250 ctcaggcaca caggagtgtc cagagttgag gtttgcatat atggtgacca 1300 cagtacttct tagtgtattg gtgaagagac tgcacctact ttctgtggag 1350 ggacaggtta ttgaaacaaa gtatgaactg gtaacatcat caagggaaga 1400 agcttggatc actgtctcaa agagatatta aaattttata catttaaaat 1450 cattgttaaa ttgattgagg aaaacaacca tttaaaaaaa atctatgttg 1500 aatcctttta taaaccagta tcactttgta atataaacac ctatttgtac 1550 ttaa 1554 <210> 212 <211> 462 <212> PRT <213> Homo sapiens <400> 212 Met Leu Asp Phe Ala Ile Phe Ala Val Thr Phe Leu Leu Ala Leu 15 10 15 Val Gly Ala Val Leu Tyr Leu Tyr Pro Ala Ser Arg Gin Ala Ala 20 25 30 Gly Ile Pro Gly Ile Thr Pro Thr Glu Glu Lys Asp Gly Asn Leu 35 40 45 Pro Asp Ile Val Asn Ser Gly Ser Leu His Glu Phe Leu Val Asn 50 55 60 Leu His Glu Arg Tyr Gly Pro Val Val Ser Phe Trp Phe Gly Arg 65 70 75 Arg Leu Val Val Ser Leu Gly Thr Val Asp Val Leu Lys Gin His 80 85 90 Ile Asn Pro Asn Lys Thr Ser Asp Pro Phe Glu Thr Met Leu Lys 95 100 105 Ser Leu Leu Arg Tyr Gin Ser Gly Gly Gly Ser Val Ser Glu Asn 110 115 120 His Met Arg Lys Lys Leu Tyr Glu Asn Gly Val Thr Asp Ser Leu 125 130 135 Lys Ser Asn Phe Ala Leu Leu Leu Lys Leu Ser Glu Glu Leu Leu 140 145 150 672 Asp Lys Trp Leu Ser Tyr Pro Glu Thr Gin His Val Pro Leu Ser 155 160 165 Gin His Met Leu Gly Phe Ala Met Lys Ser Val Thr Gin Met Val 170 175 180 Met Gly Ser Thr Phe Glu Asp Asp Gin Glu Val Ile Arg Phe Gin 185 190 195 Lys Asn His Gly Thr Val Trp Ser Glu Ile Gly Lys Gly Phe Leu 200 205 210 Asp Gly Ser Leu Asp Lys Asn Met Thr Arg Lys Lys Gin Tyr Glu 215 220 225 Asp Ala Leu Met Gin Leu Glu Ser Val Leu Arg Asn Ile Ile Lys 230 235 240 Glu Arg Lys Gly Arg Asn Phe Ser Gin His Ile Phe Ile Asp Ser 245 250 255 Leu Val Gin Gly Asn Leu Asn Asp Gin Gin Ile Leu Glu Asp Ser 260 265 270 Met Ile Phe Ser Leu Ala Ser Cys Ile Ile Thr Ala Lys Leu Cys 275 280 285 Thr Trp Ala Ile Cys Phe Leu Thr Thr Ser Glu Glu Val Gin Lys 290 295 300 Lys Leu Tyr Glu Glu Ile Asn Gin Val Phe Gly Asn Gly Pro Val 305 310 315 Thr Pro Glu Lys Ile Glu Gin Leu Arg Tyr Cys Gin His Val Leu 320 325 330 Cys Glu Thr Val Arg Thr Ala Lys Leu Thr Pro Val Ser Ala Gin 335 340 345 Leu Gin Asp Ile Glu Gly Lys Ile Asp Arg Phe Ile Ile Pro Arg 350 355 360 Glu Thr Leu Val Leu Tyr Ala Leu Gly Val Val Leu Gin Asp Pro 365 370 ' 375 Asn Thr Trp Pro Ser Pro His Lys Phe Asp Pro Asp Arg Phe Asp 380 385 390 Asp Glu Leu Val Met Lys Thr Phe Ser Ser Leu Gly Phe Ser Gly 395 400 405 Thr Gin Glu Cys Pro Glu Leu Arg Phe Ala Tyr Met Val Thr Thr 410 415 420 Val Leu Leu Ser Val Leu Val Lys Arg Leu His Leu Leu Ser Val 425 430 435 Glu Gly Gin Val Ile Glu Thr Lys Tyr Glu Leu Val Thr Ser Ser 440 445 450 Arg Glu Glu Ala Trp Ile Thr Val Ser Lys Arg Tyr 455 460 673 <210> 213 <211> 759 <212> DNA <213> Homo sapiens <400> 213 ctagatttgt cggcttgcgg ggagacttca ggagtcgctg tctctgaact 50 tccagcctca gagaccgccg cccttgtccc cgagggccat gggccgggtc 100 tcagggcttg tgccctctcg cttcctgacg ctcctggcgc atctggtggt 150 cgtcatcacc ttattctggt cccgggacag caacatacag gcctgcctgc 200 ctctcacgtt cacccccgag gagtatgaca agcaggacat tcagctggtg 250 gccgcgctct ctgtcaccct gggcctcttt gcagtggagc tggccggttt 300 cctctcagga gtctccatgt tcaacagcac ccagagcctc atctccattg 350 gggctcactg tagtgcatcc gtggccctgt ccttcttcat attcgagcgt 400 tgggagtgca ctacgtattg gtacattttt gtcttctgca gtgcccttcc 450 agctgtcact gaaatggctt tattcgtcac cgtctttggg ctgaaaaaga 500 aacccttctg attaccttca tgacgggaac ctaaggacga agcctacagg 550 ggcaagggcc gcttcgtatt cctggaagaa ggaaggcata ggcttcggtt 600 ttcccctcgg aaactgcttc tgctggagga tatgtgttgg aataattacg 650 tcttgagtct gggattatcc gcattgtatt tagtgctttg taataaaata 700 tgttttgtag taacattaag acttatatac agttttaggg gacaattaaa 750 aaaaaaaaa ' 759 <210> 214 <211> 140 <212> PRT <213> Homo sapiens <400> 214 Met Gly Arg Val Ser Gly Leu Val Pro Ser Arg Phe Leu Thr Leu 1 5 10 15 Leu Ala His Leu Val Val Val Ile Thr Leu Phe Trp Ser Arg Asp 20 25 30 Ser Asn Ile Gin Ala Cys Leu Pro Leu Thr Phe Thr Pro Glu Glu 35 40 45 Tyr Asp Lys Gin Asp Ile Gin Leu Val Ala Ala Leu Ser Val Thr 50 55 60 Leu Gly Leu Phe Ala Val Glu Leu Ala Gly Phe Leu Ser Gly Val 65 70 75 Ser Met Phe Asn Ser Thr Gin Ser Leu Ile Ser Ile Gly Ala His 80 85 90 674 Cys Ser Ala Ser Val Ala Leu Ser Phe Phe Ile Phe Glu Arg Trp 95 100 105 Glu Cys Thr Thr Tyr Trp Tyr Ile Phe Val Phe Cys Ser Ala Leu 110 115 120 Pro Ala Val Thr Glu Met Ala Leu Phe Val Thr Val Phe Gly Leu 125 130 135 Lys Lys Lys Pro Phe 140 <210> 215 <211> 697 <212> DNA <213> Homo sapiens <400> 215 tcccggaccc tgccgccctg ccactatgtc ccgccgctct atgctgcttg 50 cctgggctct ccccagcctc cttcgactcg gagcggctca ggagacagaa 100 gacccggcct gctgcagccc catagtgccc cggaacgagt ggaaggccct 150 ggcatcagag tgcgcccagc acctgagcct gcccttacgc tatgtggtgg 200 tatcgcacac ggcgggcagc agctgcaaca cccccgcctc gtgccagcag 250 caggcccgga atgtgcagca ctaccacatg aagacactgg gctggtgcga 300 cgtgggctac aacttcctga ttggagaaga cgggctcgta tacgagggcc 350 gtggctggaa cttcacgggt gcccactcag gtcacttatg gaaccccatg 400 tccattggca tcagcttcat gggcaactac atggatcggg tgcccacacc 450 ccaggccatc cgggcagccc agggtctact ggcctgcggt gtggctcagg 500 gagccctgag gtccaactat gtgctcaaag gacaccggga tgtgcagcgt 550 acactctctc caggcaacca gctctaccac ctcatccaga attggccaca 600 ctaccgctcc ccctgaggcc ctgctgatcc gcaccccatt cctcccctcc 650 catggccaaa aaccccactg tctccttctc caataaagat gtagctc 697 <210> 216 <211> 196 <212> PRT <213> Homo sapiens <400> 216 Met Ser Arg Arg Ser Met Leu Leu Ala Trp Ala Leu Pro Ser Leu 15 10 15 Leu Arg Leu Gly Ala Ala Gin Glu Thr Glu Asp Pro Ala Cys Cys 20 25 30 Ser Pro Ile Val Pro Arg Asn Glu Trp Lys Ala Leu Ala Ser Glu 35 40 45 Cys Ala Gin His Thr Ala Gin Ala Arg Cys Asp Val Tyr Glu Gly Leu Trp Asn Met Asp Arg Leu Leu Ala Val Leu Lys Asn Gin Leu Pro <210> 217 <211> 1871 <212> DNA <213> Homo sapiens <400> 217 ctgggacccc gaaaagagaa ggggagagcg aggggacgag agcggaggag 50 gaagatgcaa ctgactcgct gctgcttcgt gttcctggtg cagggtagcc 100 tctatctggt catctgtggc caggatgatg gtcctcccgg ctcagaggac 150 cctgagcgtg atgaccacga gggccagccc cggccccggg tgcctcggaa 200 gcggggccac atctcaccta agtcccgccc catggccaat tccactctcc 250 tagggctgct ggccccgcct ggggaggctt ggggcattct tgggcagccc 300 cccaaccgcc cgaaccacag ccccccaccc tcagccaagg tgaagaaaat 350 ctttggctgg ggcgacttct actccaacat caagacggtg gccctgaacc 400 tgctcgtcac agggaagatt gtggaccatg gcaatgggac cttcagcgtc 450 cacttccaac acaatgccac aggccaggga aacatctcca tcagcctcgt 500 gccccccagt aaagctgtag agttccacca ggaacagcag atcttcatcg 550 aagccaaggc ctccaaaatc ttcaactgcc ggatggagtg ggagaaggta 600 675 His Leu Ser Leu Pro Leu Arg Tyr Val Val Val Ser 50 55 60 Gly Ser Ser Cys Asn Thr Pro Ala Ser Cys Gin Gin 65 70 75 Asn Val Gin His Tyr His Met Lys Thr Leu Gly Trp 80 85 90 Gly Tyr Asn Phe Leu Ile Gly Glu Asp Gly Leu Val 95 100 105 Arg Gly Trp Asn Phe Thr Gly Ala His Ser Gly His 110 115 120 Pro Met Ser Ile Gly Ile Ser Phe Met Gly Asn Tyr 125 130 135 Val Pro Thr Pro Gin Ala Ile Arg Ala Ala Gin Gly 140 145 150 Cys Gly Val Ala Gin Gly Ala Leu Arg Ser Asn Tyr 155 160 165 Gly His Arg Asp Val Gin Arg Thr Leu Ser Pro Gly 170 175 180 Tyr His Leu Ile Gin Asn Trp Pro His Tyr Arg Ser 185 190 195 676 gaacggggcc gccggacctc gctttgcacc cacgacccag ccaagatctg 650 ctcccgagac cacgctcaga gctcagccac ctggagctgc tcccagccct 700 tcaaagtcgt ctgtgtctac atcgccttct acagcacgga ctatcggctg 750 gtccagaagg tgtgcccaga ttacaactac catagtgata ccccctacta 800 cccatctggg tgacccgggg caggccacag aggccaggcc agggctggaa 850 ggacaggcct gcqcatgcag gagaccatct ggacaccggg cagggaaggg 900 gttgggcctc aggcagggag gggggtggag acgaggagat gccaagtggg 950 gccagggcca agtctcaagt ggcagagaaa gggtcccaag tgctggtccc 1000 aacctgaagc tgtggagtga ctagatcaca ggagcactgg aggaggagtg 1050 ggctctctgt gcagcctcac agggctttgc cacggagcca cagagagatg 1100 ctgggtcccc gaggcctgtg ggcaggccga tcagtgtggc cccagatcaa 1150 gtcatgggag gaagctaagc ccttggttct tgccatcctg aggaaagata 1200 gcaacaggga gggggagatt tcatcagtgt ggacagcctg tcaacttagg 1250 atggatggct gagagggctt cctaggagcc agtcagcagg gtggggtggg 1300 gccagaggag ctctccagcc ctgcctagtg ggcgccctga gccccttgtc 1350 gtgtgctgag catggcatga ggctgaagtg gcaaccctgg ggtctttgat 1400 gtcttgacag attgaccatc tgtctccagc caggccaccc ctttccaaaa 1450 ttccctcttc tgccagtact ccccctgtac cacccattgc tgatggcaca 1500 cccatcctta agctaagaca ggacgattgt ggtcctccca cactaaggcc 1550 acagcccatc cgcgtgctgt gtgtccctct tccaccccaa cccctgctgg 1600 ctcctctggg agcatccatg tcccggagag gggtccctca acagtcagcc 1650 tcacctgtca gaccggggtt ctcccggatc tggatggcgc cgccctctca 1700 gcagcgggca cgggtggggc ggggccgggc cgcagagcat gtgctggatc 1750 tgttctgtgt gtctgtctgt gggtgggggg aggggaggga agtcttgtga 1800 aaccgctgat tgctgacttt tgtgtgaaga atcgtgttct tggagcagga 1850 aataaagctt gccccggggc a 1871 <210> 218 <211> 252 <212> PRT <213> Homo sapiens <400> 218 Met Gin Leu Thr Arg Cys Cys Phe Val Phe Leu Val Gin Gly Ser 15 10 15 677 Leu Tyr Leu Val Ile Cys Gly Gin Asp Asp Gly Pro Pro Gly Ser 20 25 30 Glu Asp Pro Glu Arg Asp Asp His Glu Gly Gin Pro Arg Pro Arg 35 40 45 Val Pro Arg Lys Arg Gly His Ile Ser Pro Lys Ser Arg Pro Met 50 55 60 Ala Asn Ser Thr Leu Leu Gly Leu Leu Ala Pro Pro Gly Glu Ala 65 70 75 Trp Gly Ile Leu Gly Gin Pro Pro Asn Arg Pro Asn His Ser Pro 80 85 90 Pro Pro Ser Ala Lys Val Lys Lys Ile Phe Gly Trp Gly Asp Phe 95 100 105 Tyr Ser Asn Ile Lys Thr Val Ala Leu Asn Leu Leu Val Thr Gly 110 115 120 Lys Ile Val Asp His Gly Asn Gly Thr Phe Ser Val His Phe Gin 125 130 135 His Asn Ala Thr Gly Gin Gly Asn Ile Ser Ile Ser Leu Val Pro 140 145 150 Pro Ser Lys Ala Val Glu Phe His Gin Glu Gin Gin Ile Phe Ile 155 160 165 Glu Ala Lys Ala Ser Lys Ile Phe Asn Cys Arg Met Glu Trp Glu 170 175 180 Lys Val Glu Arg Gly Arg Arg Thr Ser Leu Cys Thr His Asp Pro 185 190 195 Ala Lys Ile Cys Ser Arg Asp His Ala Gin Ser Ser Ala Thr Trp 200 205 210 Ser Cys Ser Gin Pro Phe Lys Val Val Cys Val Tyr Ile Ala Phe 215 220 225 Tyr Ser Thr Asp Tyr Arg Leu Val Gin Lys Val Cys Pro Asp Tyr 230 235 240 Asn Tyr His Ser Asp Thr Pro Tyr Tyr Pro Ser Gly 245 250 <210> 219 <211> 2065 <212> DNA <213> Homo sapiens <400> 219 gtgaatgtga gggtttgatg actttcagat gtctaggaac cagagtgggt 50 gcaggggccc caggcagggc tgattcttgg gcggaggaga gtagggtaaa 100 gggttctgca tgagctcctt aaaggacaaa ggtaacagag ccagcgagag 150 agctcgaggg gagactttga cttcaagcca cagaattggt ggaagtgtgc 200 gcgccgccgc cgccgtcgct cctgcagcgc tgtcgaccta gccgctagca 250 678 tcttcccgag caccgggatc ccggggtagg aggcgacgcg ggcgagcacc 300 agcgccagcc ggctgcggct gcccacacgg ctcaccatgg gctccgggcg 350 ccgggcgctg tccgcggtgc cggccgtgct gctggtcctc acgctgccgg 400 ggctgcccgt ctgggcacag aacgacacgg agcccatcgt gctggagggc 450 aagtgtctgg tggtgtgcga ctcgaacccg gccacggact ccaagggctc 500 ctcttcctcc ccgctgggga tatcggtccg ggcggccaac tccaaggtcg 550 ccttctcggc ggtgcggagc accaaccacg agccatccga gatgagcaac 600 aagacgcgca tcatttactt cgatcagatc ctggtgaatg tgggtaattt 650 tttcacattg gagtctgtct ttgtagcacc aagaaaagga atttacagtt 700 tcagttttca cgtgattaaa gtctaccaga gccaaactat ccaggttaac 750 ttgatgttaa atggaaaacc agtaatatct gcctttgcgg gggacaaaga 800 tgttactcgt gaagctgcca cgaatggtgt cctgctctac ctagataaag 850 aggataaggt ttacctaaaa ctggagaaag gtaatttggt tggaggctgg 900 cagtattcca cgttttctgg ctttctggtg ttccccctat aggattcaat 950 ttctccatga tgttcatcca ggtgagggat gacccactcc tgagttattg 1000 gaagatcatt ttttcatcat tggattgatg tcttttattg gtttctcatg 1050 ggtggatatg gattctaagg attctagcct gtctgaacca atacaaaatt 1100 tcacagatta tttgtgtgtg tctgtttcag tatatttgga ttgggactct 1150 aagcagataa tacctatgct taaatgtaac agtcaaaagc tgtctgcaag 1200 acttattctg aatttcattt cctgggatta ctgaattagt tacagatgtg 1250 gaattttatt tgtttagttt taaaagactg gcaaccaggt ctaaggatta 1300 gaaaactcta aagttctgac ttcaatcaac ggttagtgtg atactgccaa 1350 agaactgtat actgtgttaa tatattgatt atatttgttt ttattccttt 1400 ggaattagtt tgtttggttc ttgtaaaaaa cttggatttt ttttttcagt 1450 aactggtatt atgttttctc ttaaaataag gtaatgaatg gcttgcccac 1500 aaatttacct tgactacgat atcatcgaca tgacttctct caaaaaaaaa 1550 gaatgcttca tagttgtatt ttaattgtat atgtgaaaga gtcatatttt 1600 ccaagttata ttttctaaga agaagaatag atcataaatc tgacaaggaa 1650 aaagttgctt acccaaaatc taagtgctca atccctgagc ctcagcaaaa 1700 cagctcccct aatgattgat ccgagggaaa aataaccact tcttatactt ttattaaaaa tattgctcaa cctaaggttt ctttaattaa tttttttttc 1750 1800 679 cgtagacatg accactttat taactggtgg tgggatgctg ttgtttctaa 1850 ttatacctat ttttcaaggc ttctgttgta tttgaagtat catctggttt 1900 tgccttaact ctttaaattg tatatattta tctgtttagc taatattaaa 1950 ttcaaatatc ccatatctaa atttagtgca atatcttgtc ttttgtatag 2000 gtcatatgaa ttcataaaat tatttatgtc tgttatagaa taaagattaa 2050 tatatgttaa aaaaa 2065 <210> 220 <211> 201 <212> PRT <213> Homo sapiens <400> 220 Met Gly Ser Gly Arg Arg Ala Leu Ser Ala Val Pro Ala Val Leu 15 10 15 Leu Val Leu Thr Leu Pro Gly Leu Pro Val Trp Ala Gin Asn Asp 20 25 30 Thr Glu Pro Ile Val Leu Glu Gly Lys Cys Leu Val Val Cys Asp 35 40 45 Ser Asn Pro Ala Thr Asp Ser Lys Gly Ser Ser Ser Ser Pro Leu 50 55 60 Gly Ile Ser Val Arg Ala Ala Asn Ser Lys Val Ala Phe Ser Ala 65 70 75 Val Arg Ser Thr Asn His Glu Pro Ser Glu Met Ser Asn Lys Thr 80 85 90 Arg Ile Ile Tyr Phe Asp Gin Ile Leu Val Asn Val Gly Asn Phe 95 100 105 Phe Thr Leu Glu Ser Val Phe Val Ala Pro Arg Lys Gly Ile Tyr 110 115 120 Ser Phe Ser Phe His Val Ile Lys Val Tyr Gin Ser Gin Thr Ile 125 130 135 Gin Val Asn Leu Met Leu Asn Gly Lys Pro Val Ile Ser Ala Phe 140 145 150 Ala Gly Asp Lys Asp Val Thr Arg Glu Ala Ala Thr Asn Gly Val 155 160 165 Leu Leu Tyr Leu Asp Lys Glu Asp Lys Val Tyr Leu Lys Leu Glu 170 175 180 Lys Gly Asn Leu Val Gly Gly Trp Gin Tyr Ser Thr Phe Ser Gly 185 190 195 Phe Leu Val Phe Pro Leu 200 <210> 221 <211> 20 680 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 221 acggctcacc atgggctccg 20 <210> 222 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 222 aggaagagga gcccttggag tccg 24 <210> 223 <211> 40 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 223 cgtgctggag ggcaagtgtc tggtggtgtg cgactcgaac 40 <210> 224 <211> 902 <212> DNA <213> Homo sapiens <400> 224 cggtggccat gactgcggcc gtgttcttcg gctgcgcctt cattgccttc 50 gggcctgcgc tcgcccttta tgtcttcacc atcgccatcg agccgttgcg 100 tatcatcttc ctcatcgccg gagctttctt ctggttggtg tctctactga 150 tttcgtccct tgtttggttc atggcaagag tcattattga caacaaagat 200 ggaccaacac agaaatatct gctgatcttt ggagcgtttg tctctgtcta 250 tatccaagaa atgttccgat ttgcatatta taaactctta aaaaaagcca 300 gtgaaggttt gaagagtata aacccaggtg agacagcacc ctctatgcga 350 ctgctggcct atgtttctgg cttgggcttt ggaatcatga gtggagtatt 400 ttcctttgtg aataccctat ctgactcctt ggggccaggc acagtgggca 450 ttcatggaga ttctcctcaa ttcttccttt attcagcttt catgacgctg 500 gtcattatct tgctgcatgt attctggggc attgtatttt ttgatggctg 550 tgagaagaaa aagtggggca tcctccttat cgttctcctg acccacctgc 600 tggtgtcagc ccagaccttc ataagttctt attatggaat aaacctggcg 650 681 tcagcattta taatcctggt gctcatgggc acctgggcat tcttagctgc 700 gggaggcagc tgccgaagcc tgaaactctg cctgctctgc caagacaaga 750 actttcttct ttacaaccag cgctccagat aacctcaggg aaccagcact 800 tcccaaaccg cagactacat ctttagagga agcacaactg tgcctttttc 850 tgaaaatccc tttttctggt ggaattgaga aagaaataaa actatgcaga 900 ta 902 <210> 225 <211> 257 <212> PRT <213> Homo sapiens <400> 225 Met Thr Ala Ala Val Phe Phe Gly Cys Ala Phe Ile Ala Phe Gly 1 5 10 15 Pro Ala Leu Ala Leu Tyr Val Phe Thr Ile Ala Ile Glu Pro Leu 20 25 30 Arg Ile Ile Phe Leu Ile Ala Gly Ala Phe Phe Trp Leu Val Ser 35 40 45 Leu Leu Ile Ser Ser Leu Val Trp Phe Met Ala Arg Val Ile Ile 50 55 60 Asp Asn Lys Asp Gly Pro Thr Gin Lys Tyr Leu Leu Ile Phe Gly 65 70 75 Ala Phe Val Ser Val Tyr lie Gin Glu Met Phe Arg Phe Ala Tyr 80 85 90 Tyr Lys Leu Leu Lys Lys Ala Ser Glu Gly Leu Lys Ser Ile Asn 95 100 105 Pro Gly Glu Thr Ala Pro Ser Met Arg Leu Leu Ala Tyr Val Ser 110 115 120 Gly Leu Gly Phe Gly Ile Met Ser Gly Val Phe Ser Phe Val Asn 125 130 _ 135 Thr Leu Ser Asp Ser Leu Gly Pro Gly Thr Val Gly Ile His Gly 140 145 150 Asp Ser Pro Gin Phe Phe Leu Tyr Ser Ala Phe Met Thr Leu Val 155 160 165 Ile Ile Leu Leu His Val Phe Trp Gly Ile Val Phe Phe Asp Gly 170 175 180 Cys Glu Lys Lys Lys Trp Gly Ile Leu Leu Ile Val Leu Leu Thr 185 190 195 His Leu Leu Val Ser Ala Gin Thr Phe Ile Ser Ser Tyr Tyr Gly 200 205 210 Ile Asn Leu Ala Ser Ala Phe Ile Ile Leu Val Leu Met Gly Thr 215 220 225 682 Trp Ala Phe Leu Ala Ala Gly Gly Ser Cys Arg Ser Leu Lys Leu 230 235 240 Cys Leu Leu Cys Gin Asp Lys Asn Phe Leu Leu Tyr Asn Gin Arg 245 250 255 Ser Arg <210> 226 <211> 3939 <212> DNA <213> Homo sapiens <400> 226 cggcaaccag ccgccgccac caccgctgcc actgccgccc tgccggggcc 50 atgttcgctc tgggcttgcc cttcttggtg ctcttggtgg cctcggtcga 100 gagccatctg ggggttctgg ggcccaagaa cgtctcgcag aaagacgccg 150 agtttgagcg cacctacgtg gacgaggtca acagcgagct ggtcaacatc 200 tacaccttca accatactgt gacccgcaac aggacagagg gcgtgcgtgt 250 gtctgtgaac gtcctgaaca agcagaaggg ggcgccgttg ctgtttgtgg 300 tccgccagaa ggaggctgtg gtgtccttcc aggtgcccct aatcctgcga 350 gggatgtttc agcgcaagta cctctaccaa aaagtggaac gaaccctgtg 400 tcagcccccc accaagaatg agtcggagat tcagttcttc tacgtggatg 450 tgtccaccct gtcaccagtc aacaccacat accagctccg ggtcagccgc 500 atggacgatt ttgtgctcag gactggggag cagttcagct tcaataccac 550 agcagcacag ccccagtact tcaagtatga gttccctgaa ggcgtggact 600 cggtaattgt caaggtgacc tccaacaagg ccttcccctg ctcagtcatc 650 tccattcagg atgtgctgtg tcctgtctat gacctggaca acaacgtagc 700 cttcatcggc atgtaccaga cgatgaccaa gaaggcggcc atcaccgtac 750 agcgcaaaga cttccccagc aacagctttt atgtggtggt ggtggtgaag 800 accgaagacc aagcctgcgg gggctccctg cctttctacc ccttcgcaga 850 agatgaaccg gtcgatcaag ggcaccgcca gaaaaccctg tcagtgctgg 900 tgtctcaagc agtcacgtct gaggcatacg tcagtgggat gctcttttgc 950 ctgggtatat ttctctcctt ttacctgctg accgtcctcc tggcctgctg 1000 ggagaactgg aggcagaaga agaagaccct gctggtggcc attgaccgag 1050 cctgcccaga aagcggtcac cctcgagtcc tggctgattc ttttcctggc 1100 agttcccctt atgagggtta caactatggc tcctttgaga atgtttctgg 1150 683 atctaccgat ggtctggttg acagcgctgg cactggggac ctctcttacg 1200 gttaccaggg ccgctccttt gaacctgtag gtactcggcc ccgagtggac 1250 tccatgagct ctgtggagga ggatgactac gacacattga ccgacatcga 1300 ttccgacaag aatgtcattc gcaccaagca atacctctat gtggctgacc 1350 tggcacggaa ggacaagcgt gttctgcgga aaaagtacca gatctacttc 1400 tggaacattg ccaccattgc tgtcttctat gcccttcctg tggtgcagct 1450 ggtgatcacc taccagacgg tggtgaatgt cacagggaat caggacatct 1500 gctactacaa cttcctctgc gcccacccac tgggcaatct cagcgccttc 1550 aacaacatcc tcagcaacct ggggtacatc ctgctggggc tgcttttcct 1600 gctcatcatc ctgcaacggg agatcaacca caaccgggcc ctgctgcgca 1650 atgacctctg tgccctggaa tgtgggatcc ccaaacactt tgggcttttc 1700 tacgccatgg gcacagccct gatgatggag gggctgctca gtgcttgcta 1750 tcatgtgtgc cccaactata ccaatttcca gtttgacaca tcgttcatgt 1800 acatgatcgc cggactctgc atgctgaagc tctaccagaa gcggcacccg 1850 gacatcaacg ccagcgccta cagtgcctac gcctgcctgg ccattgtcat 1900 cttcttctct gtgctgggcg tggtctttgg caaagggaac acggcgttct 1950 ggatcgtctt ctccatcatt cacatcatcg ccaccctgct cctcagcacg 2000 cagctctatt acatgggccg gtggaaactg gactcgggga tcttccgccg 2050 catcctccac gtgctctaca cagactgcat ccggcagtgc agcgggccgc 2100 tctacgtgga ccgcatggtg ctgctggtca tgggcaacgt catcaactgg 2150 tcgctggctg cctatgggct tatcatgcgc cccaatgatt tcgcttccta 2200 cttgttggcc attggcatct gcaacctgct cctttacttc gccttctaca 2250 tcatcatgaa gctccggagt ggggagagga tcaagctcat ccccctgctc 2300 tgcatcgttt gcacctccgt ggtctggggc ttcgcgctct tcttcttctt 2350 ccagggactc agcacctggc agaaaacccc tgcagagtcg agggagcaca 2400 accgggactg catcctcctc gacttctttg acgaccacga catctggcac 2450 ttcctctcct ccatcgccat gttcgggtcc ttcctggtgt tgctgacact 2500 ggatgacgac ctggatactg tgcagcggga caagatctat gtcttctagc 2550 aggagctggg cccttcgctt cacctcaagg ggccctgagc tcctttgtgt 2600 catagaccgg tcactctgtc gtgctgtggg gatgagtccc agcaccgctg 2650 cccagcactg gatggcagca ggacagccag gtctagctta ggcttggcct 2700 684 gggacagcca tggggtggca tggaaccttg cagctgccct ctgccgagga 2750 gcaggcctgc ttctcagtgt tcccctggaa tggggccttc cccccagatg catgggcccc ttggccaaat tgtcctttgg tgctgctttc ctctccattt 2800 2850 gtccctttgc aagaggaagg atggaaggga caccctcccc atttcatgcc 2900 ttgcattttg cccgtcctcc tccccacaat gccccagcct gggacctaag 2950 gcctcttttt cctcccatac tcccactcca gggcctagtc tggggcctga 3000 atctctgtcc tgtatcaggg ccccagttct ctttgggctg tccctggctg 3050 ccatcactgc ccattccagt cagccaggat ggatgggggt atgagatttt 3100 gggggttggc cagctggtgc cagacttttg gtgctaaggc ctgcaagggg 3150 cctggggcag tgcgtattct cttccctctg acctgtgctc agggctggct 3200 ctttagcaat gcgctcagcc caatttgaga accgccttct gattcaagag 3250 gctgaattca gaggtcacct cttcatccca tcagctccca gactgatgcc 3300 agcaccagga ctggagggag aagcgcctca ccccttccct tccttctttc 3350 caggccctta gtcttgccaa accccagctg gtggcctttc agtgccattg 3400 acactgccca agaatgtcca ggggcaaagg agggatgata cagagttcag 3450 cccgttctgc ctccacagct gtgggcaccc cagtgcctac cttagaaagg 3500 ggcttcagga agggatgtgc tgtttccctc tacgtgccca gtcctagcct 3550 cgctctagga cccagggctg gcttctaagt ttccgtccag tcttcaggca 3600 agttctgtgt tagtcatgca cacacatacc tatgaaacct tggagtttac 3650 aaagaattgc cccagctctg ggcaccctgg ccaccctggt ccttggatcc 3700 ccttcgtccc acctggtcca ccccagatgc tgaggatggg ggagctcagg 3750 cggggcctct gctttgggga tgggaatgtg tttttctccc aaacttgttt 3800 ttatagctct gcttgaaggg ctgggagatg aggtgggtct ggatcttttc 3850 tcagagcgtc tccatgctat ggttgcattt ccgttttcta tgaatgaatt 3900 tgcattcaat aaacaaccag actcaaaaaa aaaaaaaaa 3 939 <210> 227 <211> 832 <212> PRT <213> Homo sapiens <400> 227 Met Phe Ala Leu Gly Leu Pro Phe Leu Val Leu Leu Val Ala Ser 15 10 15 Val Glu Ser His Leu Gly Val Leu Gly Pro Lys Asn Val Ser Gin 20 25 30 Lys Asp Ala Glu Phe Glu Arg Thr Tyr Val Asp Glu Val Asn Ser 685 40 45 Glu Leu Val Asn Ile Tyr Thr Phe Asn His Thr Val Thr Arg Asn 50 55 60 Arg Thr Glu Gly Val Arg Val Ser Val Asn Val Leu Asn Lys Gin 65 70 75 Lys Gly Ala Pro Leu Leu Phe Val Val Arg Gin Lys Glu Ala Val 80 85 90 Val Ser Phe Gin Val Pro Leu Ile Leu Arg Gly Met Phe Gin Arg 95 100 105 Lys Tyr Leu Tyr Gin Lys Val Glu Arg Thr Leu Cys Gin Pro Pro 110 115 120 Thr Lys Asn Glu Ser Glu Ile Gin Phe Phe Tyr Val Asp Val Ser 125 130 135 Thr Leu Ser Pro Val Asn Thr Thr Tyr Gin Leu Arg Val Ser Arg 140 145 150 Met Asp Asp Phe Val Leu Arg Thr Gly Glu Gin Phe Ser Phe Asn 155 160 165 Thr Thr Ala Ala Gin Pro Gin Tyr Phe Lys Tyr Glu Phe Pro Glu 170 175 180 Gly Val Asp Ser Val Ile Val Lys Val Thr Ser Asn Lys Ala Phe 185 190 195 Pro Cys Ser Val Ile Ser Ile Gin Asp Val Leu Cys Pro Val Tyr 200 205 210 Asp Leu Asp Asn Asn Val Ala Phe Ile Gly Met Tyr Gin Thr Met 215 220 225 Thr Lys Lys Ala Ala Ile Thr Val Gin Arg Lys Asp Phe Pro Ser 230 235 240 Asn Ser Phe Tyr Val Val Val Val Val Lys Thr Glu Asp Gin Ala 245 250 255 Cys Gly Gly Ser Leu Pro Phe Tyr Pro Phe Ala Glu Asp Glu Pro 260 265 270 Val Asp Gin Gly His Arg Gin Lys Thr Leu Ser Val Leu Val Ser 275 280 285 Gin Ala Val Thr Ser Glu Ala Tyr Val Ser Gly Met Leu Phe Cys 290 295 300 Leu Gly Ile Phe Leu Ser Phe Tyr Leu Leu Thr Val Leu Leu Ala 305 310 315 Cys Trp Glu Asn Trp Arg Gin Lys Lys Lys Thr Leu Leu Val Ala 320 325 330 Ile Asp Arg Ala Cys Pro Glu Ser Gly His Pro Arg Val Leu Ala 335 340 345 Asp Ser Phe Pro Gly Ser Ser Pro Tyr Glu Gly Tyr Asn Tyr Gly 350 686 355 360 Ser Phe Glu Asn Val Ser Gly Ser Thr Asp Gly Leu Val Asp Ser 365 370 375 Ala Gly Thr Gly Asp Leu Ser Tyr Gly Tyr Gin Gly Arg Ser Phe 380 385 390 Glu Pro Val Gly Thr Arg Pro Arg Val Asp Ser Met Ser Ser Val 395 400 405 Glu Glu Asp Asp Tyr Asp Thr Leu Thr Asp Ile Asp Ser Asp Lys 410 415 420 Asn Val Ile Arg Thr Lys Gin Tyr Leu Tyr Val Ala Asp Leu Ala 425 430 435 Arg Lys Asp Lys Arg Val Leu Arg Lys Lys Tyr Gin Ile Tyr Phe 440 445 450 Trp Asn Ile Ala Thr Ile Ala Val Phe Tyr Ala Leu Pro Val Val 455 460 465 Gin Leu Val Ile Thr Tyr Gin Thr Val Val Asn Val Thr Gly Asn 470 475 480 Gin Asp Ile Cys Tyr Tyr Asn Phe Leu Cys Ala His Pro Leu Gly 485 490 495 Asn Leu Ser Ala Phe Asn Asn Ile Leu Ser Asn Leu Gly Tyr Ile 500 505 510 Leu Leu Gly Leu Leu Phe Leu Leu Ile Ile Leu Gin Arg Glu Ile 515 520 525 Asn His Asn Arg Ala Leu Leu Arg Asn Asp Leu Cys Ala Leu Glu 530 535 540 Cys Gly Ile Pro Lys His Phe Gly Leu Phe Tyr Ala Met Gly Thr 545 550 555 Ala Leu Met Met Glu Gly Leu Leu Ser Ala Cys Tyr His Val Cys 560 565 570 Pro Asn Tyr Thr Asn Phe Gin Phe Asp Thr Ser Phe Met Tyr Met 575 580 585 Ile Ala Gly Leu Cys Met Leu Lys Leu Tyr Gin Lys Arg His Pro 590 595 600 Asp Ile Asn Ala Ser Ala Tyr Ser Ala Tyr Ala Cys Leu Ala Ile 605 610 615 Val Ile Phe Phe Ser Val Leu Gly Val Val Phe Gly Lys Gly Asn 620 625 630 Thr Ala Phe Trp Ile Val Phe Ser Ile Ile His Ile Ile Ala Thr 635 640 645 Leu Leu Leu Ser Thr Gin Leu Tyr Tyr Met Gly Arg Trp Lys Leu 650 655 660 687 Asp Ser Gly Ile Phe Arg Arg Ile Leu His Val Leu Tyr Thr Asp 665 670 675 Cys Ile Arg Gin Cys Ser Gly Pro Leu Tyr Val Asp Arg Met Val 680 685 690 Leu Leu Val Met Gly Asn Val Ile Asn Trp Ser Leu Ala Ala Tyr 695 700 705 Gly Leu Ile Met Arg Pro Asn Asp Phe Ala Ser Tyr Leu Leu Ala 710 715 720 Ile Gly Ile Cys Asn Leu Leu Leu Tyr Phe Ala Phe Tyr Ile Ile 725 730 " 735 Met Lys Leu Arg Ser Gly Glu Arg Ile Lys Leu Ile Pro Leu Leu 740 745 750 Cys Ile Val Cys Thr Ser Val Val Trp Gly Phe Ala Leu Phe Phe 755 760 765 Phe Phe Gin Gly Leu Ser Thr Trp Gin Lys Thr Pro Ala Glu Ser 770 775 780 Arg Glu His Asn Arg Asp Cys Ile Leu Leu Asp Phe Phe Asp Asp 785 790 795 His Asp lie Trp His Phe Leu Ser Ser Ile Ala Met Phe Gly Ser 800 805 810 Phe Leu Val Leu Leu Thr Leu Asp Asp Asp Leu Asp Thr Val Gin 815 820 825 Arg Asp Lys Ile Tyr Val Phe 830 <210> 228 <211> 2848 <212> DNA <213> Homo sapiens <400> 228 gctcaagtgc cctgccttgc cccacccagc ccagcctggc cagagccccc 50 tggagaagga gctctcttct tgcttggcag ctggaccaag ggagccagtc 100 ttgggcgctg gagggcctgt cctgaccatg gtccctgcct ggctgtggct 150 gctttgtgtc tccgtccccc aggctctccc caaggcccag cctgcagagc 200 tgtctgtgga agttccagaa aactatggtg gaaatttccc tttatacctg 250 accaagttgc cgctgccccg tgagggggct gaaggccaga tcgtgctgtc 300 aggggactca ggcaaggcaa ctgagggccc atttgctatg gatccagatt 350 ctggcttcct gctggtgacc agggccctgg accgagagga gcaggcagag 400 taccagctac aggtcaccct ggagatgcag gatggacatg tcttgtgggg 450 tccacagcct gtgcttgtgc acgtgaagga tgagaatgac caggtgcccc 500 688 atttctctca agccatctac agagctcggc tgagccgggg taccaggcct 550 ggcatcccct tcctcttcct tgaggcttca gaccgggatg agccaggcac 600 agccaactcg gatcttcgat tccacatcct gagccaggct ccagcccagc 650 cttccccaga agccccaagg catgttccag ggagcaccag ctggagcctc ccttgaccac ggctgggggc gccctggaga tctggccctc ggacctacca 700 750 gctgttggta caggtcaagg acatgggtga ccaggcctca ggccaccagg 800 ccactgccac cgtggaagtc tccatcatag agagcacctg ggtgtcccta 850 gagcctatcc acctggcaga gaatctcaaa gtcctatacc cgcaccacat 900 ggcccaggta cactggagtg ggggtgatgt gcactatcac ctggagagcc 950 atcccccggg accctttgaa gtgaatgcag agggaaacct ctacgtgacc 1000 agagagctgg acagagaagc ccaggctgag tacctgctcc aggtgcgggc 1050 tcagaattcc catggcgagg actatgcggc ccctctggag ctgcacgtgc 1100 tggtgatgga tgagaatgac aacgtgccta tctgccctcc ccgtgacccc 1150 acagtcagca tccctgagct cagtccacca ggtactgaag tgactagact 1200 gtcagcagag gatgcagatg cccccggctc ccccaattcc cacgttgtgt 1250 atcagctcct gagccctgag cctgaggatg gggtagaggg gagagccttc 1300 caggtggacc ccacttcagg cagtgtgacg ctgggggtgc tcccactccg 1350 agcaggccag aacatcctgc ttctggtgct ggccatggac ctggcaggcg 1400 cagagggtgg cttcagcagc acgtgtgaag tcgaagtcgc agtcacagat 1450 atcaatgatc acgcccctga gttcatcact tcccagattg ggcctataag 1500 cctccctgag gatgtggagc ccgggactct ggtggccatg ctaacagcca 1550 ttgatgctga cctcgagccc gccttccgcc tcatggattt tgccattgag 1600 aggggagaca cagaagggac ttttggcctg gattgggagc cagactctgg 1650 gcatgttaga ctcagactct gcaagaacct cagttatgag gcagctccaa 1700 gtcatgaggt ggtggtggtg gtgcagagtg tggcgaagct ggtggggcca 1750 ggcccaggcc ctggagccac cgccacggtg actgtgctag tggagagagt 1800 gatgccaccc cccaagttgg accaggagag ctacgaggcc agtgtcccca 1850 tcagtgcccc agccggctct ttcctgctga ccatccagcc ctccgacccc 1900 atcagccgaa ccctcaggtt ctccctagtc aatgactcag agggctggct 1950 ctgcattgag aaattctccg gggaggtgca caccgcccag tccctgcagg 2000 gcgcccagcc tggggacacc tacacggtgc ttgtggaggc ccaggataca 2050 gccctgactc ttgcccctgt gccctcccaa tacctctgca caccccgcca 2100 689 agaccatggc ttgatcgtga gtggacccag caaggacccc gatctggcca 2150 gtgggcacgg tccctacagc ttcacccttg gtcccaaccc cacggtgcaa 2200 cgggattggc gcctccagac tctcaatggt tcccatgcct acctcacctt 2250 ggccctgcat gccacaatgc tgggtggagc ccagatgtgg cacgtgaaca cagctcctgg cataatcccc ttcgagtgat gtggtggtca cgtgtgtcgc 2300 2350 tgcaacgtgg aggggcagtg catgcgcaag gtgggccgca tgaagggcat 2400 gcccacgaag ctgtcggcag tgggcatcct tgtaggcacc ctggtagcaa 2450 taggaatctt cctcatcctc attttcaccc actggaccat gtcaaggaag 2500 aaggacccgg atcaaccagc agacagcgtg cccctgaagg cgactgtctg 2550 aatggcccag gcagctctag ctgggagctt ggcctctggc tccatctgag 2600 tcccctggga gagagcccag cacccaagat ccagcagggg acaggacaga 2650 gtagaagccc ctccatctgc cctggggtgg aggcaccatc accatcacca 2700 ggcatgtctg cagagcctgg acaccaactt tatggactgc ccatgggagt 2750 gctccaaatg tcagggtgtt tgcccaataa taaagcccca gagaactggg 2800 ctgggcccta tgggaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaag 2848 <210> 229 <211> 807 <212> PRT <213> Homo sapiens <400> 229 Met Val Pro Ala Trp Leu Trp Leu Leu Cys Val Ser Val Pro Gin 1 5 10 15 Ala Leu Pro Lys Ala Gin Pro Ala Glu Leu Ser Val Glu Val Pro 20 25 30 Glu Asn Tyr Gly Gly Asn Phe Pro Leu Tyr Leu Thr Lys Leu Pro 35 40 45 Leu Pro Arg Glu Gly Ala Glu Gly Gin Ile Val Leu Ser Gly Asp 50 55 60 Ser Gly Lys Ala Thr Glu Gly Pro Phe Ala.Met Asp Pro Asp Ser 65 70 75 Gly Phe Leu Leu Val Thr Arg Ala Leu Asp Arg Glu Glu Gin Ala 80 85 90 Glu Tyr Gin Leu Gin Val Thr Leu Glu Met Gin Asp Gly His Val 95 100 105 Leu Trp Gly Pro Gin Pro Val Leu Val His Val Lys Asp Glu Asn 110 115 120 Asp Gin Val Pro His Phe Ser Gin Ala Ile Tyr Arg Ala Arg Leu 125 130 135 690 Ser Arg Gly Thr Arg Pro Gly Ile Pro Phe Leu Phe Leu Glu Ala 140 145 150 Ser Asp Arg Asp Glu Pro Gly Thr Ala Asn Ser Asp Leu Arg Phe 155 160 165 His Ile Leu Ser Gin Ala Pro Ala Gin Pro Ser Pro Asp Met Phe 170 175 180 Gin Leu Glu Pro Arg Leu Gly Ala Leu Ala Leu Ser Pro Lys Gly 185 190 195 Ser Thr Ser Leu Asp His Ala Leu Glu Arg Thr Tyr Gin Leu Leu 200 205 210 Val Gin Val Lys Asp Met Gly Asp Gin Ala Ser Gly His Gin Ala 215 220 225 Thr Ala Thr Val Glu Val Ser Ile Ile Glu Ser Thr Trp Val Ser 230 235 240 Leu Glu Pro Ile His Leu Ala Glu Asn Leu Lys Val Leu Tyr Pro 245 250 255 His His Met Ala Gin Val His Trp Ser Gly Gly Asp Val His Tyr 260 265 270 His Leu Glu Ser His Pro Pro Gly Pro Phe Glu Val Asn Ala Glu 275 280 285 Gly Asn Leu Tyr Val Thr Arg Glu Leu Asp Arg Glu Ala Gin Ala 290 295 300 Glu Tyr Leu Leu Gin Val Arg Ala Gin Asn Ser His Gly Glu Asp 305 310 315 Tyr Ala Ala Pro Leu Glu Leu His Val Leu Val Met Asp Glu Asn 320 325 330 Asp Asn Val Pro Ile Cys Pro Pro Arg Asp Pro Thr Val Ser Ile 335 340 345 Pro Glu Leu Ser Pro Pro Gly Thr Glu Val Thr Arg Leu Ser Ala 350 355 360 Glu Asp Ala Asp Ala Pro Gly Ser Pro Asn Ser His Val Val Tyr 365 370 375 Gin Leu Leu Ser Pro Glu Pro Glu Asp Gly Val Glu Gly Arg Ala 380 385 390 Phe Gin Val Asp Pro Thr Ser Gly Ser Val Thr Leu Gly Val Leu 395 400 405 Pro Leu Arg Ala Gly Gin Asn Ile Leu Leu Leu Val Leu Ala Met 410 415 420 Asp Leu Ala Gly Ala Glu Gly Gly Phe Ser Ser Thr Cys Glu Val 425 430 435 Glu Val Ala Val Thr Asp Ile Asn Asp His Ala Pro Glu Phe Ile 440 445 450 691 Thr Ser Gin Ile Gly Pro Ile Ser Leu Pro Glu Asp Val Glu Pro 455 460 465 Gly Thr Leu Val Ala Met Leu Thr Ala Ile Asp Ala Asp Leu Glu 470 475 480 Pro Ala Phe Arg Leu Met Asp Phe Ala Ile Glu Arg Gly Asp Thr 485 490 495 Glu Gly Thr Phe Gly Leu Asp Trp Glu Pro Asp Ser Gly His Val 500 505 510 Arg Leu Arg Leu Cys Lys Asn Leu Ser Tyr Glu Ala Ala Pro Ser 515 520 525 His Glu Val Val Val Val Val Gin Ser Val Ala Lys Leu Val Gly 530 535 540 Pro Gly Pro Gly Pro Gly Ala Thr Ala Thr Val Thr Val Leu Val 545 550 555 Glu Arg Val Met Pro Pro Pro Lys Leu Asp Gin Glu Ser Tyr Glu 560 565 570 Ala Ser Val Pro Ile Ser Ala Pro Ala Gly Ser Phe Leu Leu Thr 575 580 585 Ile Gin Pro Ser Asp Pro Ile Ser Arg Thr Leu Arg Phe Ser Leu 590 595 600 Val Asn Asp Ser Glu Gly Trp Leu Cys Ile Glu Lys Phe Ser Gly 605 610 615 Glu Val His Thr Ala Gin Ser Leu Gin Gly Ala Gin Pro Gly Asp 620 625 630 Thr Tyr Thr Val Leu Val Glu Ala Gin Asp Thr Ala Leu Thr Leu 635 640 645 Ala Pro Val Pro Ser Gin Tyr Leu Cys Thr Pro Arg Gin Asp His 650 655 660 Gly Leu Ile Val Ser Gly Pro Ser Lys Asp Pro Asp Leu Ala Ser 665 670 675 Gly His Gly Pro Tyr Ser Phe Thr Leu Gly Pro Asn Pro Thr Val 680 685 690 Gin Arg Asp Trp Arg Leu Gin Thr Leu Asn Gly Ser His Ala Tyr 695 700 705 Leu Thr Leu Ala Leu His Trp Val Glu Pro Arg Glu His Ile Ile 710 715 720 Pro Val Val Val Ser His Asn Ala Gin Met Trp Gin Leu Leu Val 725 730 735 Arg Val Ile Val Cys Arg Cys Asn Val Glu Gly Gin Cys Met Arg 740 745 750 Lys Val Gly Arg Met Lys Gly Met Pro Thr Lys Leu Ser Ala Val 692 755 760 765 Gly Ile Leu Val Gly Thr Leu Val Ala Ile Gly Ile Phe Leu Ile 770 775 780 Leu Ile Phe Thr His Trp Thr Met Ser Arg Lys Lys Asp Pro Asp 785 790 795 Gin Pro Ala Asp Ser Val Pro Leu Lys Ala Thr Val 800 805 <210> 230 <211> 50 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 230 cgccttaccg cgcagcccga agattcacta tggtgaaaat cgccttcaat 50 <210> 231 <211> 1257 <212> DNA <213> Homo sapiens <400> 231 ggagagaggc gcgcgggtga aaggcgcatt gatgcagcct gcggcggcct 50 cggagcgcgg cggagccaga cgctgaccac gttcctctcc tcggtctcct 100 ccgcctccag ctccgcgctg cccggcagcc gggagccatg cgaccccagg 150 gccccgccgc ctccccgcag cggctccgcg gcctcctgct gctcctgctg 200 ctgcagctgc ccgcgccgtc gagcgcctct gagatcccca aggggaagca 250 aaaggcgcag ctccggcaga gggaggtggt ggacctgtat aatggaatgt 300 gcttacaagg gccagcagga gtgcctggtc gagacgggag ccctggggcc 350 aatgttattc cgggtacacc tgggatccca ggtcgggatg gattcaaagg 400 agaaaagggg gaatgtctga gggaaagctt tgaggagtcc tggacaccca 450 actacaagca gtgttcatgg agttcattga attatggcat agatcttggg 500 aaaattgcgg agtgtacatt tacaaagatg cgttcaaata gtgctctaag 550 agttttgttc agtggctcac ttcggctaaa atgcagaaat gcatgctgtc 600 agcgttggta tttcacattc aatggagctg aatgttcagg acctcttccc 650 attgaagcta taatttattt ggaccaagga agccctgaaa tgaattcaac 700 aattaatatt catcgcactt cttctgtgga aggactttgt gaaggaattg 750 gtgctggatt agtggatgtt gctatctggg ttggcacttg ttcagattac 800 ccaaaaggag atgcttctac tggatggaat tcagtttctc gcatcattat 850 693 tgaagaacta ccaaaataaa tgctttaatt ttcatttgct acctcttttt 900 ttattatgcc ttggaatggt tcacttaaat gacattttaa ataagtttat 950 gtatacatct gaatgaaaag caaagctaaa tatgtttaca gaccaaagtg 1000 tgatttcaca ctgtttttaa atctagcatt attcattttg cttcaatcaa 1050 aagtggtttc aatatttttt ttagttggtt agaatacttt cttcatagtc 1100 acattctctc aacctataat ttggaatatt gttgtggtct tttgtttttt 1150 ctcttagtat agcattttta aaaaaatata aaagctacca atctttgtac 12 00 aatttgtaaa tgttaagaat tttttttata tctgttaaat aaaaattatt 12 50 tccaaca 1257 <210> 232 <211> 243 <212> PRT <213> Homo sapiens <400> 232 Met Arg Pro Gin Gly Pro Ala Ala Ser Pro Gin Arg Leu Arg Gly 15 10 15 Leu Leu Leu Leu Leu Leu Leu Gin Leu Pro Ala Pro Ser Ser Ala 20 25 30 Ser Glu Ile Pro Lys Gly Lys Gin Lys Ala Gin Leu Arg Gin Arg 35 40 45 Glu Val Val Asp Leu Tyr Asn Gly Met Cys Leu Gin Gly Pro Ala 50 55 60 Gly Val Pro Gly Arg Asp Gly Ser Pro Gly Ala Asn Val Ile Pro 65 70 75 Gly Thr Pro Gly Ile Pro Gly Arg Asp Gly Phe Lys Gly Glu Lys 80 85 90 Gly Glu Cys Leu Arg Glu Ser Phe Glu Glu Ser Trp Thr Pro Asn 95 100 105 Tyr Lys Gin Cys Ser Trp Ser Ser Leu Asn Tyr Gly Ile Asp Leu 110 115 120 Gly Lys Ile Ala Glu Cys Thr Phe Thr Lys Met Arg Ser Asn Ser 125 130 135 Ala Leu Arg Val Leu Phe Ser Gly Ser Leu Arg Leu Lys Cys Arg 140 145 150 Asn Ala Cys Cys Gin Arg Trp Tyr Phe Thr Phe Asn Gly Ala Glu 155 160 165 Cys Ser Gly Pro Leu Pro Ile Glu Ala Ile Ile Tyr Leu Asp Gin 170 175 180 Gly Ser Pro Glu Met Asn Ser Thr Ile Asn Ile His Arg Thr Ser 185 190 195 694 Ser Val Glu Gly Leu Cys Glu Gly Ile Gly Ala Gly Leu Val Asp 200 205 210 Val Ala Ile Trp Val Gly Thr Cys Ser Asp Tyr Pro Lys Gly Asp 215 220 225 Ala Ser Thr Gly Trp Asn Ser Val Ser Arg Ile Ile Ile Glu Glu 230 235 240 Leu Pro Lys <210> 233 <211> 2786 <212> DNA <213> Homo sapiens <400> 233 ccggggacat gaggtggata ctgttcattg gggcccttat tgggtccagc 50 atctgtggcc aagaaaaatt ttttggggac caagttttga ggattaatgt 100 cagaaatgga gacgagatca gcaaattgag tcaactagtg aattcaaaca 150 acttgaagct caatttctgg aaatctccct cctccttcaa tcggcctgtg 200 gatgtcctgg tcccatctgt cagtctgcag gcatttaaat ccttcctgag 250 atcccagggc ttagagtacg cagtgacaat tgaggacctg caggcccttt 300 tagacaatga agatgatgaa atgcaacaca atgaagggca agaacggagc 350 agtaataact tcaactacgg ggcttaccat tccctggaag ctatttacca 400 cgagatggac aacattgccg cagactttcc tgacctggcg aggagggtga 450 agattggaca ttcgtttgaa aaccggccga tgtatgtact gaagttcagc 500 actgggaaag gcgtgaggcg gccggccgtt tggctgaatg caggcatcca 550 ttcccgagag tggatctccc aggccactgc aatctggacg gcaaggaaga 600 ttgtatctga ttaccagagg gatccagcta tcacctccat cttggagaaa 650 atggatattt tcttgttgcc tgtggccaat cctgatggat atgtgtatac 700 tcaaactcaa aaccgattat ggaggaagac gcggtcccga aatcctggaa 750 gctcctgcat tggtgctgac ccaaatagaa actggaacgc tagttttgca 800 ggaaagggag ccagcgacaa cccttgctcc gaagtgtacc atggacccca 850 cgccaattcg gaagtggagg tgaaatcagt ggtagatttc atccaaaaac 900 atgggaattt caagggcttc atcgacctgc acagctactc gcagctgctg 950 atgtatccat atgggtactc agtcaaaaag gccccagatg ccgaggaact 1000 cgacaaggtg gcgaggcttg cggccaaagc tctggcttct gtgtcgggca 1050 ctgagtacca agtgggtccc acctgcacca ctgtctatcc agctagcggg 1100 695 agcagcatcg actgggcgta tgacaacggc atcaaatttg cattcacatt 1150 tgagttgaga gataccggga cctatggctt cctcctgcca gctaaccaga 1200 tcatccccac tgcagaggag acgtggctgg ggctgaagac catcatggag 1250 catgtgcggg acaacctcta ctaggcgatg gctctgctct gtctacattt 1300 atttgtaccc acacgtgcac gcactgaggc cattgttaaa ggagctcttt 1350 cctacctgtg tgagtcagag ccctctgggt ttgtggagca cacaggcctg 1400 cccctctcca aagaactggt gccagctccc tctgccagcc tggagtcgtg tgctcaattt tgtcctggcg tggtcctgct gtgtccctgc gtttttgatg 1450 1500 agccttttgt ctgtttctcc ttccaccctg ctggctgggc ggctgcactc 1550 agcatcaccc cttcctgggt ggcatgtctc tctctacctc atttttagaa 1600 ccaaagaaca tctgagatga ttctctaccc tcatccacat ctagccaagc 1650 cagtgacctt gctctggtgg cactgtggga gacaccactt gtctttaggt 1700 gggtctcaaa gatgatgtag aatttccttt aatttctcgc agtcttcctg 1750 gaaaatattt tcctttgagc agcaaatctt gtagggatat cagtgaaggt 1800 ctctccctcc ctcctctcct gttttttttt tttttgagac agagttttgc 1850 tcttgttgcc caggctggag tgtgatggct cgatcttggc tcaccacaac 1900 ctctgcctcc tgggttcaag caattctcct gcctcagcct cttgagtagc 1950 ttggtttata ggcgcatgcc accatgcctg gctaattttg tgtttttagt 2000 agagacaggg tttctccatg ttggtcaggc tggtctcaaa ctcccaacct 2050 caggtgatct gccctccttg gcctcccaga gtgctgggat tacaggtgtg 2100 agccactgtg ccgggcccgt cccctccttt tttaggcctg aatacaaagt 2150 agaagatcac tttccttcac tgtgctgaga atttctagat actacagttc 2200 ttactcctct cttccctttg ttattcagtg tgaccaggat ggcgggaggg 2250 gatctgtgtc actgtaggta ctgtgcccag gaaggctggg tgaagtgacc 2300 atctaaattg caggatggtg aaattatccc catctgtcct aatgggctta 2350 cctcctcttt gccttttgaa ctcacttcaa agatetaggc ctcatcttac 2400 aggtcctaaa tcactcatct ggcctggata atctcactgc cctggcacat 2450 tcccatttgt gctgtggtgt atcctgtgtt tccttgtcct ggtttgtgtg 2500 tgtgtgtgtg tgtgtgtgtg tgtgtgtgtt tgtgtgtgtg tgtctgtcta 2550 ttttgtatcc tggaccacaa gttcctaagt agagcaagaa ttcatcaacc 2600 agctgcctct tgtttcattt cacctcagca cgtaccatct gtccttttgt 2650 696 tgttgttgtt ttgtttttgt ttttttgctt ttaccaaaca tgtctgtaaa 2700 tcttaacctc ctgcctagga tttgtacagc atctggtgtg tgcttataag 2750 ccaataaata ttcaatgtga aaaaaaaaaa aaaaaa 2786 <210> 234 <211> 421 <212> PRT <213> Homo sapiens <400> 234 Met Arg Trp Ile Leu Phe Ile Gly Ala Leu Ile Gly Ser Ser Ile 15 10 15 Cys Gly Gin Glu Lys Phe Phe Gly Asp Gin Val Leu Arg Ile Asn 20 25 30 Val Arg Asn Gly Asp Glu Ile Ser Lys Leu Ser Gin Leu Val Asn 35 40 45 Ser Asn Asn Leu Lys Leu Asn Phe Trp Lys Ser Pro Ser Ser Phe 50 55 . 60 Asn Arg Pro Val Asp Val Leu Val Pro Ser Val Ser Leu Gin Ala 65 70 75 Phe Lys Ser Phe Leu Arg Ser Gin Gly Leu Glu Tyr Ala Val Thr 80 85 90 Ile Glu Asp Leu Gin Ala Leu Leu Asp Asn Glu Asp Asp Glu Met 95 100 105 Gin His Asn Glu Gly Gin Glu Arg Ser Ser Asn Asn Phe Asn Tyr 110 115 120 Gly Ala Tyr His Ser Leu Glu Ala Ile Tyr His Glu Met Asp Asn 125 130 135 Ile Ala Ala Asp Phe Pro Asp Leu Ala Arg Arg Val Lys Ile Gly 140 145 150 His Ser Phe Glu Asn Arg Pro Met Tyr Val Leu Lys Phe Ser Thr 155 160 165 Gly Lys Gly Val Arg Arg Pro Ala Val Trp Leu Asn Ala Gly Ile 170 175 180 His Ser Arg Glu Trp Ile Ser Gin Ala Thr Ala Ile Trp Thr Ala 185 190 195 Arg Lys Ile Val Ser Asp Tyr Gin Arg Asp Pro Ala Ile Thr Ser 200 205 210 Ile Leu Glu Lys Met Asp Ile Phe Leu Leu Pro Val Ala Asn Pro 215 220 225 Asp Gly Tyr Val' Tyr Thr Gin Thr Gin Asn Arg Leu Trp Arg Lys 230 235 240 Thr Arg Ser Arg Asn Pro Gly Ser Ser Cys Ile Gly Ala Asp Pro 245 250 255 697 Asn Arg Asn Trp Asn Ala Ser Phe Ala Gly Lys Gly Ala Ser Asp 260 265 270 Asn Pro Cys Ser Glu Val Tyr His Gly Pro His Ala Asn Ser Glu 275 280 285 Val Glu Val Lys Ser Val Val Asp Phe Ile Gin Lys His Gly Asn 290 295 300 Phe Lys Gly Phe Ile Asp Leu His Ser Tyr Ser Gin Leu Leu Met 305 310 315 Tyr Pro Tyr Gly Tyr Ser Val Lys Lys Ala Pro Asp Ala Glu Glu 320 325 330 Leu Asp Lys Val Ala Arg Leu Ala Ala Lys Ala Leu Ala Ser Val 335 340 345 Ser Gly Thr Glu Tyr Gin Val Gly Pro Thr Cys Thr Thr Val Tyr 350 355 360 Pro Ala Ser Gly Ser Ser Ile Asp Trp Ala Tyr Asp Asn Gly Ile 365 370 375 Lys Phe Ala Phe Thr Phe Glu Leu Arg Asp Thr Gly Thr Tyr Gly 380 385 390 Phe Leu Leu Pro Ala Asn Gin Ile Ile Pro Thr Ala Glu Glu Thr 395 400 405 Trp Leu Gly Leu Lys Thr Ile Met Glu His Val Arg Asp Asn Leu 410 415 420 Tyr <210> 235 <211> 1743 <212> DNA <213> Homo sapiens <400> 235 caaccatgca aggacagggc aggagaagag gaacctgcaa agacatattt 50 tgttccaaaa tggcatctta cctttatgga gtactctttg ctgttggcct 100 ctgtgctcca atctactgtg tgtccccggc caatgccccc agtgcatacc 150 cccgcccttc ctccacaaag agcacccctg cctcacaggt gtattccctc 200 aacaccgact ttgccttccg cctataccgc aggctggttt tggagacccc 250 gagtcagaac atcttcttct cccctgtgag tgtctccact tccctggcca 300 tgctctccct tggggcccac tcagtcacca agacccagat tctccagggc 350 ctgggcttca acctcacaca cacaccagag tctgccatcc accagggctt 400 ccagcacctg gttcactcac tgactgttcc cagcaaagac ctgaccttga 450 agatgggaag tgccctcttc gtcaagaagg agctgcagct gcaggcaaat 500 698 ttcttgggca atgtcaagag gctgtatgaa gcagaagtct tttctacaga 550 tttctccaac ccctccattg cccaggcgag gatcaacagc catgtgaaaa 600 agaagaccca agggaaggtt gtagacataa tccaaggcct tgaccttctg 650 acggccatgg ttctggtgaa tcacattttc tttaaagcca agtgggagaa 700 gccctttcac cttgaatata caagaaagaa cttcccattc ctggtgggcg 750 agcaggtcac tgtgcaagtc cccatgatgc accagaaaga gcagttcgct 800 tttggggtgg atacagagct gaactgcttt gtgctgcaga tggattacaa 850 gggagatgcc gtggccttct ttgtcctccc tagcaagggc aagatgaggc 900 aactggaaca ggccttgtca gccagaacac tgataaagtg gagccactca 950 ctccagaaaa ggtggataga ggtgttcatc cccagatttt ccatttctgc 1000 ctcctacaat ctggaaacca tcctcccgaa gatgggcatc caaaatgcct 1050 ttgacaaaaa tgctgatttt tctggaattg caaagagaga ctccctgcag 1100 gtttctaaag caacccacaa ggctgtgctg gatgtcagtg aagagggcac 1150 tgaggccaca gcagctacca ccaccaagtt catagtccga tcgaaggatg 1200 gtccctctta cttcactgtc tccttcaata ggaccttcct gatgatgatt 1250 acaaataaag ccacagacgg tattctcttt ctagggaaag tggaaaatcc 1300 cactaaatcc taggtgggaa atggcctgtt aactgatggc acattgctaa 1350 tgcacaagaa ataacaaacc acatccctct ttctgttctg agggtgcatt 1400 tgaccccagt ggagctggat tcgctggcag ggatgccact tccaaggctc 1450 aatcaccaaa ccatcaacag ggaccccagt cacaagccaa cacccattaa 1500 ccccagtcag tgcccttttc cacaaattct cccaggtaac tagcttcatg 1550 ggatgttgct gggttaccat atttccattc cttggggctc ccaggaatgg 1600 aaatacgcca acccaggtta ggcacctcta ttgcagaatt acaataacac 1650 attcaataaa actaaaatat gaattcaaaa aaaaaaaaaa aaaaaaaaaa 1700 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaa 1743 <210> 236 <211> 417 <212> PRT <213> Homo sapiens <400> 236 Met Ala Ser Tyr Leu Tyr Gly Val Leu Phe Ala Val Gly Leu Cys 15 10 15 Ala Pro Ile Tyr Cys Val Ser Pro Ala Asn Ala Pro Ser Ala Tyr 20 25 30 699 Pro Arg Pro Ser Ser Thr Lys Ser Thr Pro Ala Ser Gin Val Tyr 35 40 45 Ser Leu Asn Thr Asp Phe Ala Phe Arg Leu Tyr Arg Arg Leu Val 50 55 60 Leu Glu Thr Pro Ser Gin Asn Ile Phe Phe Ser Pro Val Ser Val 65 70 75 Ser Thr Ser Leu Ala Met Leu Ser Leu Gly Ala His Ser Val Thr 80 85 90 Lys Thr Gin Ile Leu Gin Gly Leu Gly Phe Asn Leu Thr His Thr 95 100 105 Pro Glu Ser Ala Ile His Gin Gly Phe Gin His Leu Val His Ser 110 115 120 Leu Thr Val Pro Ser Lys Asp Leu Thr Leu Lys Met Gly Ser Ala 125 130 135 Leu Phe Val Lys Lys Glu Leu Gin Leu Gin Ala Asn Phe Leu Gly 140 145 150 Asn Val Lys Arg Leu Tyr Glu Ala Glu Val Phe Ser Thr Asp Phe 155 160 165 Ser Asn Pro Ser Ile Ala Gin Ala Arg Ile Asn Ser His Val Lys 170 175 180 Lys Lys Thr Gin Gly Lys Val Val Asp Ile Ile Gin Gly Leu Asp 185 190 195 Leu Leu Thr Ala Met Val Leu Val Asn His Ile Phe Phe Lys Ala 200 205 210 Lys Trp Glu Lys Pro Phe His Leu Glu Tyr Thr Arg Lys Asn Phe 215 220 225 Pro Phe Leu Val Gly Glu Gin Val Thr Val Gin Val Pro Met Met 230 235 240 His Gin Lys Glu Gin Phe Ala Phe Gly Val Asp Thr Glu Leu Asn 245 250 255 Cys Phe Val Leu Gin Met Asp Tyr Lys Gly Asp Ala Val Ala Phe 260 265 270 Phe Val Leu Pro Ser Lys Gly Lys Met Arg Gin Leu Glu Gin Ala 275 280 285 Leu Ser Ala Arg Thr Leu Ile Lys Trp Ser His Ser Leu Gin Lys 290 295 300 Arg Trp Ile Glu Val Phe Ile Pro Arg Phe Ser Ile Ser Ala Ser 305 310 315 Tyr Asn Leu Glu Thr Ile Leu Pro Lys Met Gly Ile Gin Asn Ala 320 325 330 Phe Asp Lys Asn Ala Asp Phe Ser Gly Ile Ala Lys Arg Asp Ser 335 340 345 700 Leu Gin Val Glu Glu Gly Val Arg Ser Arg Thr Phe Leu Phe Leu <210> 237 <211> 23 <212> DNA <213> Artificial <220> <221> misc_feature <222> 1-23 <223> Synthetic construct. <400> 237 caaccatgca aggacagggc agg 23 <210> 238 <211> 47 <212> DNA <213> Artificial <220> <221> misc_feature <222> 1-47 <223> Synthetic construct. <400> 238 ctttgctgtt ggcctctgtg ctcccaacca tgcaaggaca gggcagg 47 <210> 239 <211> 24 <212> DNA <213> Artificial <220> <221> misc_feature <222> 1-24 <223> Synthetic construct. <400> 239 tgactcgggg tctccaaaac cagc 24 <210> 240 <211> 24 <212> DNA <213> Artificial <220> <221> misc_feature Ser Lys Ala Thr His Lys Ala Val Leu Asp Val Ser 350 355 360 Thr Glu Ala Thr Ala Ala Thr Thr Thr Lys Phe Ile 365 370 375 Lys Asp Gly Pro Ser Tyr Phe Thr Val Ser Phe Asn 380 385 390 Leu Met Met Ile Thr Asn Lys Ala Thr Asp Gly Ile 395 400 405 Gly Lys Val Glu Asn Pro Thr Lys Ser 410 415 701 <222> 1-24 <223> Synthetic construct. <400> 240 ggtataggcg gaaggcaaag tcgg 24 <210> 241 <211> 48 <212> DNA <213> Artificial <220> <221> misc_feature <222> 1-48 <223> Synthetic construct. <400> 241 ggcatcttac ctttatggag tactctttgc tgttggcctc tgtgctcc 48 <210> 242 <211> 2436 <212> DNA <213> Homo sapiens <400> 242 ggctgaccgt gctacattgc ctggaggaag cctaaggaac ccaggcatcc 50 agctgcccac gcctgagtcc aagattcttc ccaggaacac aaacgtagga 100 gacccacgct cctggaagca ccagccttta tctcttcacc ttcaagtccc 150 ctttctcaag aatcctctgt tctttgccct ctaaagtctt ggtacatcta 200 ggacccaggc atcttgcttt ccagccacaa agagacagat gaagatgcag 250 aaaggaaatg ttctccttat gtttggtcta ctattgcatt tagaagctgc 300 aacaaattcc aatgagacta gcacctctgc caacactgga tccagtgtga 350 tctccagtgg agccagcaca gccaccaact ctgggtccag tgtgacctcc 400 agtggggtca gcacagccac catctcaggg tccagcgtga cctccaatgg 450 ggtcagcata gtcaccaact ctgagttcca tacaacctcc agtgggatca 500 gcacagccac caactctgag ttcagcacag cgtccagtgg gatcagcata 550 gccaccaact ctgagtccag cacaacctcc agtggggcca gcacagccac 600 caactctgag tccagcacac cctccagtgg ggccagcaca gtcaccaact 650 ctgggtccag tgtgacctcc agtggagcca gcactgccac caactctgag 700 tccagcacag tgtccagtag ggccagcact gccaccaact ctgagtctag 750 cacactctcc agtggggcca gcacagccac caactctgac tccagcacaa 800 cctccagtgg ggctagcaca gccaccaact ctgagtccag cacaacctcc 850 agtggggcca gcacagccac caactctgag tccagcacag tgtccagtag 900 ggccagcact gccaccaact ctgagtccag cacaacctcc agtggggcca 950 702 gcacagccac caactctgag tccagaacga cctccaatgg ggctggcaca 1000 gccaccaact ctgagtccag cacgacctcc agtggggcca gcacagccac 1050 caactctgac tccagcacag tgtccagtgg ggccagcact gccaccaact 1100 ctgagtccag cacgacctcc agtggggcca gcacagccac caactctgag 1150 tccagcacga cctccagtgg ggctagcaca gccaccaact ctgactccag 1200 cacaacctcc agtggggccg gcacagccac caactctgag tccagcacag 1250 tgtccagtgg gatcagcaca gtcaccaatt ctgagtccag cacaccctcc 1300 agtggggcca acacagccac caactctgag tccagtacga cctccagtgg 1350 ggccaacaca gccaccaact ctgagtccag cacagtgtcc agtggggcca 1400 gcactgccac caactctgag tccagcacaa cctccagtgg ggtcagcaca 1450 gccaccaact ctgagtccag cacaacctcc agtggggcta gcacagccac 1500 caactctgac tccagcacaa cctccagtga ggccagcaca gccaccaact 1550 ctgagtctag cacagtgtcc agtgggatca gcacagtcac caattctgag 1600 tccagcacaa cctccagtgg ggccaacaca gccaccaact ctgggtccag 1650 tgtgacctct gcaggctctg gaacagcagc tctgactgga atgcacacaa 1700 cttcccatag tgcatctact gcagtgagtg aggcaaagcc tggtgggtcc 1750 ctggtgccgt gggaaatctt cctcatcacc ctggtctcgg ttgtggcggc 1800 cgtggggctc tttgctgggc tcttcttctg tgtgagaaac agcctgtccc 1850 tgagaaacac ctttaacaca gctgtctacc accctcatgg cctcaaccat 1900 ggccttggtc caggccctgg agggaatcat ggagcccccc acaggcccag 1950 gtggagtcct aactggttct ggaggagacc agtatcatcg atagccatgg 2000 agatgagcgg gaggaacagc gggccctgag cagccccgga agcaagtgcc 2050 gcattcttca ggaaggaaga gacctgggca cccaagaicct ggtttccttt 2100 cattcatccc aggagacccc tcccagcttt gtttgagatc ctgaaaatct 2150 tgaagaaggt attcctcacc tttcttgcct ttaccagaca ctggaaagag 2200 aatactatat tgctcattta gctaagaaat aaatacatct catctaacac 2250 acacgacaaa gagaagctgt gcttgccccg gggtgggtat ctagctctga 2300 gatgaactca gttataggag aaaacctcca tgctggactc catctggcat 2350 tcaaaatctc cacagtaaaa tccaaagacc tcaaaaaaaa aaaaaaaaaa 2400 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaa 2436 <210> 243 703 <211> 596 <212> PRT <213> Homo sapiens <400> 243 Met Lys Met Gin Lys Gly Asn Val Leu Leu Met Phe Gly Leu Leu 10 15 Leu His Leu Glu Ala Ala Thr Asn Ser Asn Glu Thr Ser Thr Ser 25 30 Ala Asn Thr Gly Ser Ser Val Ile Ser Ser Gly Ala Ser Thr Ala 40 45 Thr Asn Ser Gly Ser Ser Val Thr Ser Ser Gly Val Ser Thr Ala 50 55 60 Thr Ile Ser Gly Ser Ser Val Thr Ser Asn Gly Val Ser Ile Val 65 70 75 Thr Asn Ser Glu Phe His Thr Thr Ser Ser Gly Ile Ser Thr Ala 80 85 90 Thr Asn Ser Glu Phe Ser Thr Ala Ser Ser Gly Ile Ser Ile Ala 95 100 105 Thr Asn Ser Glu Ser Ser Thr Thr Ser Ser Gly Ala Ser Thr Ala 110 115 120 Thr Asn Ser Glu Ser Ser Thr Pro Ser Ser Gly Ala Ser Thr Val 125 130 135 Thr Asn Ser Gly Ser Ser Val Thr Ser Ser Gly Ala Ser Thr Ala 140 145 150 Thr Asn Ser Glu Ser Ser Thr Val Ser Ser Arg Ala Ser Thr Ala 155 160 165 Thr Asn Ser Glu Ser Ser Thr Leu Ser Ser Gly Ala Ser Thr Ala 170 175 180 Thr Asn Ser Asp Ser Ser Thr Thr Ser Ser Gly Ala Ser Thr Ala 185 190 195 Thr Asn Ser Glu Ser Ser Thr Thr Ser Ser Gly Ala Ser Thr Ala 200 205 210 Thr Asn Ser Glu Ser Ser Thr Val Ser Ser Arg Ala Ser Thr Ala 215 220 225 Thr Asn Ser Glu Ser Ser Thr Thr Ser Ser Gly Ala Ser Thr Ala 230 235 240 Thr Asn Ser Glu Ser Arg Thr Thr Ser Asn Gly Ala Gly Thr Ala 245 250 255 Thr Asn Ser Glu Ser Ser Thr Thr Ser Ser Gly Ala Ser Thr Ala 260 265 270 Thr Asn Ser Asp Ser Ser Thr Val Ser Ser Gly Ala Ser Thr Ala 275 280 285 Thr Asn Ser Glu Ser Ser Thr Thr Ser Ser Gly Ala Ser Thr Ala 704 290 295 300 Thr Asn Ser Glu Ser Ser Thr Thr Ser Ser Gly Ala Ser Thr Ala 305 310 315 Thr Asn Ser Asp Ser Ser Thr Thr Ser Ser Gly Ala Gly Thr Ala 320 325 330 Thr Asn Ser Glu Ser Ser Thr Val Ser Ser Gly Ile Ser Thr Val 335 340 345 Thr Asn Ser Glu Ser Ser Thr Pro Ser Ser Gly Ala Asn Thr Ala 350 355 360 Thr Asn Ser Glu Ser Ser Thr Thr Ser Ser Gly Ala Asn Thr Ala 365 370 375 Thr Asn Ser Glu Ser Ser Thr Val Ser Ser Gly Ala Ser Thr Ala 380 385 390 Thr Asn Ser Glu Ser Ser Thr Thr Ser Ser Gly Val Ser Thr Ala 395 400 405 Thr Asn Ser Glu Ser Ser Thr Thr Ser Ser Gly Ala Ser Thr Ala 410 415 420 Thr Asn Ser Asp Ser Ser Thr Thr Ser Ser Glu Ala Ser Thr Ala 425 430 435 Thr Asn Ser Glu Ser Ser Thr Val Ser Ser Gly Ile Ser Thr Val 440 445 450 Thr Asn Ser Glu Ser Ser Thr Thr Ser Ser Gly Ala Asn Thr Ala 455 460 465 Thr Asn Ser Gly Ser Ser Val Thr Ser Ala Gly Ser Gly Thr Ala 470 475 480 Ala Leu Thr Gly Met His Thr Thr Ser His Ser Ala Ser Thr Ala 485 490 495 Val Ser Glu Ala Lys Pro Gly Gly Ser Leu Val Pro Trp Glu Ile 500 505 510 Phe Leu Ile Thr Leu Val Ser Val Val Ala Ala Val Gly Leu Phe 515 520 525 Ala Gly Leu Phe Phe Cys Val Arg Asn Ser Leu Ser Leu Arg Asn 530 535 540 Thr Phe Asn Thr Ala Val Tyr His Pro His Gly Leu Asn His Gly 545 550 555 Leu Gly Pro Gly Pro Gly Gly Asn His Gly Ala Pro His Arg Pro 560 565 570 Arg Trp Ser Pro Asn Trp Phe Trp Arg Arg Pro Val Ser Ser Ile 575 580 585 Ala Met Glu Met Ser Gly Arg Asn Ser Gly Pro 590 595 705 <210> 244 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 244 gaagcaccag cctttatctc ttcacc 26 <210> 245 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 245 gtcagagttg gtggctgtgc tagc 24 <210> 246 <211> 48 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 246 ggacccaggc atcttgcttt ccagccacaa agagacagat gaagatgc 48 <210> 247 <211> 957 <212> DNA <213> Homo sapiens <400> 247 gggagagagg ataaatagca gcgtggcttc cctggctcct ctctgcatcc 50 ttcccgacct tcccagcaat atgcatcttg cacgtctggt cggctcctgc 100 tccctccttc tgctactggg ggccctgtct ggatgggcgg ccagcgatga 150 ccccattgag aaggtcattg aagggatcaa ccgagggctg agcaatgcag 200 agagagaggt gggcaaggcc ctggatggca tcaacagtgg aatcacgcat 250 gccggaaggg aagtggagaa ggttttcaac ggacttagca acatggggag 300 ccacaccggc aaggagttgg acaaaggcgt ccaggggctc aaccacggca 350 tggacaaggt tgcccatgag atcaaccatg gtattggaca agcaggaaag 400 gaagcagaga agcttggcca tggggtcaac aacgctgctg gacaggccgg 450 gaaggaagca gacaaagcgg tccaagggtt ccacactggg gtccaccagg 500 ctgggaagga agcagagaaa cttggccaag gggtcaacca tgctgctgac 550 caggctggaa aggaagtgga gaagcttggc caaggtgccc accatgctgc 600 706 tggccaggcc gggaaggagc tgcagaatgc tcataatggg gtcaaccaag 650 ccagcaagga ggccaaccag ctgctgaatg gcaaccatca aagcggatct 7 00 tccagccatc aaggaggggc cacaaccacg ccgttagcct ctggggcctc 750 agtcaacacg cctttcatca accttcccgc cctgtggagg agcgtcgcca 800 acatcatgcc ctaaactggc atccggcctt gctgggagaa taatgtcgcc 850 gttgtcacat cagctgacat gacctggagg ggttgggggt gggggacagg 900 tttctgaaat ccctgaaggg ggttgtactg ggatttgtga ataaacttga 950 tacacca 957 <210> 248 <211> 247 <212> PRT <213> Homo sapiens <400> 248 Met His Leu Ala Arg Leu Val Gly Ser Cys Ser Leu Leu Leu Leu 15 10 15 Leu Gly Ala Leu Ser Gly Trp Ala Ala Ser Asp Asp Pro Ile Glu 20 25 30 Lys Val Ile Glu Gly Ile Asn Arg Gly Leu Ser Asn Ala Glu Arg 35 40 45 Glu Val Gly Lys Ala Leu Asp Gly Ile Asn Ser Gly Ile Thr His 50 55 60 Ala Gly Arg Glu Val Glu Lys Val Phe Asn Gly Leu Ser Asn Met 65 70 75 Gly Ser His Thr Gly Lys Glu Leu Asp Lys Gly Val Gin Gly Leu 80 85 90 Asn His Gly Met Asp Lys Val Ala His Glu Ile Asn His Gly Ile 95 100 105 Gly Gin Ala Gly Lys Glu Ala Glu Lys Leu Gly His Gly Val Asn 110 115 120 Asn Ala Ala Gly Gin Ala Gly Lys Glu Ala Asp Lys Ala Val Gin 125 • 130 135 Gly Phe His Thr Gly Val His Gin Ala Gly Lys Glu Ala Glu Lys 140 145 150 Leu Gly Gin Gly Val Asn His Ala Ala Asp Gin Ala Gly Lys Glu 155 160 165 Val Glu Lys Leu Gly Gin Gly Ala His His Ala Ala Gly Gin Ala 170 175 180 Gly Lys Glu Leu Gin Asn Ala His Asn Gly Val Asn Gin Ala Ser 185 190 195 Lys Glu Ala Asn Gin Leu Leu Asn Gly Asn His Gin Ser Gly Ser 200 707 205 210 Ser Ser His Gin Gly Gly Ala Thr Thr Thr Pro Leu Ala Ser Gly 215 220 225 Ala Ser Val Asn Thr Pro Phe Ile Asn Leu Pro Ala Leu Trp Arg 230 235 240 Ser Val Ala Asn Ile Met Pro 245 <210> 249 <211> 23 <212> DNA <213> Artificial Sequence <22 0> <223> Synthetic oligonucleotide probe <400> 249 caatatgcat cttgcacgtc tgg 23 <210> 250 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 250 aagcttctct gcttcctttc ctgc 24 <210> 251 <211> 43 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 251 tgaccccatt gagaaggtca ttgaagggat caaccgaggg ctg 43 <210> 252 <211> 3781 <212> DNA <213> Homo sapiens <400> 252 ctccgggtcc ccaggggctg cgccgggccg gcctggcaag ggggacgagt 50 cagtggacac tccaggaaga gcggccccgc ggggggcgat gaccgtgcgc 100 tgaccctgac tcactccagg tccggaggcg ggggcccccg gggcgactcg 150 ggggcggacc gcggggcgga gctgccgccc gtgagtccgg ccgagccacc 200 tgagcccgag ccgcgggaca ccgtcgctcc tgctctccga atgctgcgca 250 ccgcgatggg cctgaggagc tggctcgccg ccccatgggg cgcgctgccg 300 cctcggccac cgctgctgct gctcctgctg ctgctgctcc tgctgcagcc 350 708 gccgcctccg acctgggcgc tcagcccccg gatcagcctg cctctgggct 400 ctgaagagcg gccattcctc agattcgaag ctgaacacat ctccaactac 450 acagcccttc tgctgagcag ggatggcagg accctgtacg tgggtgctcg 500 agaggccctc tttgcactca gtagcaacct cagcttcctg ccaggcgggg 550 agtaccagga gctgctttgg ggtgcagacg cagagaagaa acagcagtgc 600 agcttcaagg gcaaggaccc acagcgcgac tgtcaaaact acatcaagat 650 cctcctgccg ctcagcggca gtcacctgtt cacctgtggc acagcagcct 700 tcagccccat gtgtacctac atcaacatgg agaacttcac cctggcaagg 750 gacgagaagg ggaatgtcct cctggaagat ggcaagggcc gttgtccctt 800 cgacccgaat ttcaagtcca ctgccctggt ggttgatggc gagctctaca 850 ctggaacagt cagcagcttc caagggaatg acccggccat ctcgcggagc 900 caaagccttc gccccaccaa gaccgagagc tccctcaact ggctgcaaga 950 cccagctttt gtggcctcag cctacattcc tgagagcctg ggcagcttgc 1000 aaggcgatga tgacaagatc tactttttct tcagcgagac tggccaggaa 1050 tttgagttct ttgagaacac cattgtgtcc cgcattgccc gcatctgcaa 1100 gggcgatgag ggtggagagc gggtgctaca gcagcgctgg acctccttcc 1150 tcaaggccca gctgctgtgc tcacggcccg acgatggctt ccccttcaac 1200 gtgctgcagg atgtcttcac gctgagcccc agcccccagg actggcgtga 1250 cacccttttc tatggggtct tcacttccca gtggcacagg ggaactacag 1300 aaggctctgc cgtctgtgtc ttcacaatga aggatgtgca gagagtcttc 1350 agcggcctct acaaggaggt gaaccgtgag acacagcagt ggtacaccgt 1400 gacccacccg gtgcccacac cccggcctgg agcgtgcatc accaacagtg 1450 cccgggaaag gaagatcaac tcatccctgc agctcccaga ccgcgtgctg 1500 aacttcctca aggaccactt cctgatggac gggcaggtcc gaagccgcat 1550 gctgctgctg cagccccagg ctcgctacca gcgcgtggct gtacaccgcg 1600 tccctggcct gcaccacacc tacgatgtcc tcttcctggg cactggtgac 1650 ggccggctcc acaaggcagt gagcgtgggc ccccgggtgc acatcattga 1700 ggagctgcag atcttctcat cgggacagcc cgtgcagaat ctgctcctgg 1750 acacccacag ggggctgctg tatgcggcct cacactcggg cgtagtccag 1800 gtgcccatgg ccaactgcag cctgtaccgg agctgtgggg actgcctcct 1850 cgcccgggac ccctactgtg cttggagcgg ctccagctgc aagcacgtca 1900 709 gcctctacca gcctcagctg gccaccaggc cgtggatcca ggacatcgag 1950 ggagccagcg ccaaggacct ttgcagcgcg tcttcggttg tgtccccgtc 2000 ttttgtacca acaggggaga agccatgtga gcaagtccag ttccagccca 2050 acacagtgaa cactttggcc tgcccgctcc tctccaacct ggcgacccga 2100 ctctggctac gcaacggggc ccccgtcaat gcctcggcct cctgccacgt 2150 gctacccact ggggacctgc tgctggtggg cacccaacag ctgggggagt 2200 tccagtgctg gtcactagag gagggcttcc agcagctggt agccagctac 2250 tgcccagagg tggtggagga cggggtggca gaccaaacag atgagggtgg 2300 cagtgtaccc gtcattatca gcacatcgcg tgtgagtgca ccagctggtg 2350 gcaaggccag ctggggtgca gacaggtcct actggaagga gttcctggtg 2400 atgtgcacgc tctttgtgct ggccgtgctg ctcccagttt tattcttgct 2450 ctaccggcac cggaacagca tgaaagtctt cctgaagcag ggggaatgtg 2500 ccagcgtgca ccccaagacc tgccctgtgg tgctgccccc tgagacccgc 2550 ccactcaacg ccagtccctg gcctagggcc tcagacagcc ccctagcacc ccccgggggc ccgctcgatc ccgagtcttc accgagggta actgagtcag 2600 2650 agaagaggcc actcagcatc caagacagct tcgtggaggt atccccagtg 2700 tgcccccggc cccgggtccg ccttggctcg gagatccgtg actctgtggt 2750 gtgagagctg acttccagag gacgctgccc tggcttcagg ggctgtgaat 2800 gctcggagag ggtcaactgg acctcccctc cgctctgctc ttcgtggaac 2850 acgaccgtgg tgcccggccc ttgggagcct tggagccagc tggcctgctg 2900 ctctccagtc aagtagcgaa gctcctacca cccagacacc caaacagccg 2950 tggccccaga ggtcctggcc aaatatgggg gcctgcctag gttggtggaa 3000 cagtgctcct tatgtaaact gagccctttg tttaaaaaac aattccaaat 3050 gtgaaactag aatgagaggg aagagatagc atggcatgca gcacacacgg 3100 ctgctccagt tcatggcctc ccaggggtgc tggggatgca tccaaagtgg 3150 ttgtctgaga cagagttgga aaccctcacc aactggcctc ttcaccttcc 3200 acattatccc gctgccaccg gctgccctgt ctcactgcag attcaggacc 3250 agcttgggct gcgtgcgttc tgccttgcca gtcagccgag gatgtagttg 3300 ttgctgccgt cgtcccacca cctcagggac cagagggcta ggttggcact 3350 gcggccctca ccaggtcctg ggctcggacc caactcctgg acctttccag 3400 cctgtatcag gctgtggcca cacgagagga cagcgcgagc tcaggagaga 3450 710 tttcgtgaca atgtacgcct ttccctcaga attcagggaa gagactgtcg 3500 cctgccttcc tccgttgttg cgtgagaacc cgtgtgcccc ttcccaccat 3550 atccaccctc gctccatctt tgaactcaaa cacgaggaac taactgcacc 3600 ctggtcctct ccccagtccc cagttcaccc tccatccctc accttcctcc 3650 actctaaggg atatcaacac tgcccagcac aggggccctg aatttatgtg 3700 gtttttatac attttttaat aagatgcact ttatgtcatt ttttaataaa 3750 gtctgaagaa ttactgttta aaaaaaaaaa a 3781 <210> 253 <211> 837 <212> PRT <213> Homo sapiens <400> 253 Met Leu Arg Thr Ala Met Gly Leu Arg Ser Trp Leu Ala Ala Pro 15 10 15 Trp Gly Ala Leu Pro Pro Arg Pro Pro Leu Leu Leu Leu Leu Leu 20 25 30 Leu Leu Leu Leu Leu Gin Pro Pro Pro Pro Thr Trp Ala Leu Ser 35 40 45 Pro Arg Ile Ser Leu Pro Leu Gly Ser Glu Glu Arg Pro Phe Leu 50 55 60 Arg Phe Glu Ala Glu His Ile Ser Asn Tyr Thr Ala Leu Leu Leu 65 70 75 Ser Arg Asp Gly Arg Thr Leu Tyr Val Gly Ala Arg Glu Ala Leu 80 85 90 Phe Ala Leu Ser Ser Asn Leu Ser Phe Leu Pro Gly Gly Glu Tyr 95 100 105 Gin Glu Leu Leu Trp Gly Ala Asp Ala Glu Lys Lys Gin Gin Cys 110 115 120 Ser Phe Lys Gly Lys Asp Pro Gin Arg Asp Cys Gin Asn Tyr Ile 125 130 135 Lys Ile Leu Leu Pro Leu Ser Gly Ser His Leu Phe Thr Cys Gly 140 145 150 Thr Ala Ala Phe Ser Pro Met Cys Thr Tyr Ile Asn Met Glu Asn 155 160 165 Phe Thr Leu Ala Arg Asp Glu Lys Gly Asn Val Leu Leu Glu Asp 170 175 • 180 Gly Lys Gly Arg Cys Pro Phe Asp Pro Asn Phe Lys Ser Thr Ala 185 190 195 Leu Val Val Asp Gly Glu Leu Tyr Thr Gly Thr Val Ser Ser Phe 200 205 210 711 Gin Gly Asn Asp Pro Ala Ile Ser Arg Ser Gin Ser Leu Arg Pro 215 220 225 Thr Lys Thr Glu Ser Ser Leu Asn Trp Leu Gin Asp Pro Ala Phe 230 235 240 Val Ala Ser Ala Tyr Ile Pro Glu Ser Leu Gly Ser Leu Gin Gly 245 250 255 Asp Asp Asp Lys Ile Tyr Phe Phe Phe Ser Glu Thr Gly Gin Glu 260 265 270 Phe Glu Phe Phe Glu Asn Thr Ile Val Ser Arg Ile Ala Arg Ile 275 280 285 Cys Lys Gly Asp Glu Gly Gly Glu Arg Val Leu Gin Gin Arg Trp 290 295 300 Thr Ser Phe Leu Lys Ala Gin Leu Leu Cys Ser Arg Pro Asp Asp 305 310 315 Gly Phe Pro Phe Asn Val Leu Gin Asp Val Phe Thr Leu Ser Pro 320 325 330 Ser Pro Gin Asp Trp Arg Asp Thr Leu Phe Tyr Gly Val Phe Thr 335 340 345 Ser Gin Trp His Arg Gly Thr Thr Glu Gly Ser Ala Val Cys Val 350 355 360 Phe Thr Met Lys Asp Val Gin Arg Val Phe Ser Gly Leu Tyr Lys 365 370 375 Glu Val Asn Arg Glu Thr Gin Gin Trp Tyr Thr Val Thr His Pro 380 385 390 Val Pro Thr Pro Arg Pro Gly Ala Cys Ile Thr Asn Ser Ala Arg 395 400 405 Glu Arg Lys Ile Asn Ser Ser Leu Gin Leu Pro Asp Arg Val Leu 410 415 420 Asn Phe Leu Lys Asp His Phe Leu Met Asp Gly Gin Val Arg Ser 425 430 435 Arg Met Leu Leu Leu Gin Pro Gin Ala Arg Tyr Gin Arg Val Ala 440 445 450 Val His Arg Val Pro Gly Leu His His Thr Tyr Asp Val Leu Phe 455 460 465 Leu Gly Thr Gly Asp Gly Arg Leu His Lys Ala Val Ser Val Gly 470 475 480 Pro Arg Val His lie Ile Glu Glu Leu Gin Ile Phe Ser Ser Gly 485 490 495 Gin Pro Val Gin Asn Leu Leu Leu Asp Thr His Arg Gly Leu Leu 500 505 510 Tyr Ala Ala Ser His Ser Gly Val Val Gin Val Pro Met Ala Asn 515 520 525 712 Cys Ser Leu Tyr Arg Ser Cys Gly Asp Cys Leu Leu Ala Arg Asp 530 535 540 Pro Tyr Cys Ala Trp Ser Gly Ser Ser Cys Lys His Val Ser Leu 545 550 555 Tyr Gin Pro Gin Leu Ala Thr Arg Pro Trp Ile Gin Asp Ile Glu 560 565 570 Gly Ala Ser Ala Lys Asp Leu Cys Ser Ala Ser Ser Val Val Ser 575 580 585 Pro Ser Phe Val Pro Thr Gly Glu Lys Pro Cys Glu Gin Val Gin 590 595 600 Phe Gin Pro Asn Thr Val Asn Thr Leu Ala Cys Pro Leu Leu Ser 605 610 615 Asn Leu Ala Thr Arg Leu Trp Leu Arg Asn Gly Ala Pro Val Asn 620 625 630 Ala Ser Ala Ser Cys His Val Leu Pro Thr Gly Asp Leu Leu Leu 635 640 645 Val Gly Thr Gin Gin Leu Gly Glu Phe Gin Cys Trp Ser Leu Glu 650 655 660 Glu Gly Phe Gin Gin Leu Val Ala Ser Tyr Cys Pro Glu Val Val 665 670 675 Glu Asp Gly Val Ala Asp Gin Thr Asp Glu Gly Gly Ser Val Pro 680 685 690 Val Ile Ile Ser Thr Ser Arg Val Ser Ala Pro Ala Gly Gly Lys 695 700 705 Ala Ser Trp Gly Ala Asp Arg Ser Tyr Trp Lys Glu Phe Leu Val 710 715 720 Met Cys Thr Leu Phe Val Leu Ala Val Leu Leu Pro Val Leu Phe 725 730 735 Leu Leu Tyr Arg His Arg Asn Ser Met Lys Val Phe Leu Lys Gin 740 745 750 Gly Glu Cys Ala Ser Val His Pro Lys Thr Cys Pro Val Val Leu 755 760 765 Pro Pro Glu Thr Arg Pro Leu Asn Gly Leu Gly Pro Pro Ser Thr 770 775 780 Pro Leu Asp His Arg Gly Tyr Gin Ser Leu Ser Asp Ser Pro Pro 785 790 795 Gly Ala Arg Val Phe Thr Glu Ser Glu Lys Arg Pro Leu Ser Ile 800 805 810 Gin Asp Ser Phe Val Glu Val Ser Pro Val Cys Pro Arg Pro Arg 815 820 825 Val Arg Leu Gly Ser Glu Ile Arg Asp Ser Val Val 713 830 835 <210> 254 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 254 agcccgtgca gaatctgctc ctgg 24 <210> 255 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 255 tgaagccagg gcagcgtcct ctgg 24 <210> 256 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 256 gtacaggctg cagttggc 18 <210> 257 <211> 41 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 257 agaagccatg tgagcaagtc cagttccagc ccaacacagt g 41 <210> 258 <211> 45 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 258 gagctgcaga tcttctcatc gggacagccc gtgcagaatc tgctc 45 <210> 259 <211> 4563 <212> DNA <213> Homo sapiens 714 <220> <221> unsure <222> 3635 <223> unknown base <400> 259 ctaagccgga ggatgtgcag ctgcggcggc ggcgccggct acgaagagga 50 cggggacagg cgccgtgcga accgagccca gccagccgga ggacgcgggc 100 agggcgggac gggagcccgg actcgtctgc cgccgccgtc gtcgccgtcg 150 tgccggcccc gcgtccccgc gcgcgagcgg gaggagccgc cgccacctcg 200 cgcccgagcc gccgctagcg cgcgccgggc atggtcccct cttaaaggcg 250 caggccgcgg cggcgggggc gggtgtgcgg aacaaagcgc cggcgcgggg 300 cctgcgggcg gctcgggggc cgcgatgggc gcggcgggcc cgcggcggcg 350 gcggcgctgc ccgggccggg cctcgcggcg ctagggcggg ctggcctccg 400 tgggcggggg cagcgggctg agggcgcgcg gagcctgcgg cggcggcggc 450 ggcggcggcg gcggcccggc gggcggagcg gcgcgggcat ggccgcgcgc 500 ggccggcgcg cctggctcag cgtgctgctc gggctcgtcc tgggcttcgt 550 gctggcctcg cggctcgtcc tgccccgggc ttccgagctg aagcgagcgg 600 gcccacggcg ccgcgccagc cccgagggct gccggtccgg gcaggcggcg 650 gcttcccagg ccggcggggc gcgcggcgat gcgcgcgggg cgcagctctg 700 gccgcccggc tcggacccag atggcggccc gcgcgacagg aactttctct 750 tcgtgggagt catgaccgcc cagaaatacc tgcagactcg ggccgtggcc 800 gcctacagaa catggtccaa gacaattcct gggaaagttc agttcttctc 850 aagtgagggt tctgacacat ctgtaccaat tccagtagtg ccactacggg 900 gtgtggacga ctcctacccg ccccagaaga agtccttcat gatgctcaag 950 tacatgcacg accactactt ggacaagtat gaatggttta tgagagcaga 1000 tgatgacgtg tacatcaaag gagaccgtct ggagaacttc ctgaggagtt 1050 tgaacagcag cgagcccctc tttcttgggc agacaggcct gggcaccacg 1100 gaagaaatgg gaaaactggc cctggagcct ggtgagaact tctgcatggg 1150 ggggcctggc gtgatcatga gccgggaggt gcttcggaga atggtgccgc 1200 acattggcaa gtgtctccgg gagatgtaca ccacccatga ggacgtggag 12 50 gtgggaaggt gtgtccggag gtttgcaggg gtgcagtgtg tctggtctta 1300 tgagatgcgg cagctttttt atgagaatta cgagcagaac aaaaaggggt 1350 acattagaga tctccataac agtaaaattc accaagctat cacattacac 1400 cccaacaaaa acccacccta ccagtacagg ctccacagct acatgctgag 1450 715 ccgcaagata tccgagctcc gccatcgcac aatacagctg caccgcgaaa 1500 ttgtcctgat gagcaaatac agcaacacag aaattcataa agaggacctc 1550 cagctgggaa tccctccctc cttcatgagg tttcagcccc gccagcgaga 1600 ggagattctg gaatgggagt ttctgactgg aaaatacttg tattcggcag 1650 ttgacggcca gccccctcga agaggaatgg actccgccca gagggaagcc 1700 ttggacgaca ttgtcatgca ggtcatggag atgatcaatg ccaacgccaa 1750 gaccagaggg cgcatcattg acttcaaaga gatccagtac ggctaccgcc 1800 gggtgaaccc catgtatggg gctgagtaca tcctggacct gctgcttctg 1850 tacaaaaagc acaaagggaa gaaaatgacg gtccctgtga ggaggcacgc 1900 gtatttacag cagactttca gcaaaatcca gtttgtggag catgaggagc 1950 tggatgcaca agagttggcc aagagaatca atcaggaatc tggatccttg 2000 tcctttctct caaactccct gaagaagctc gtcccctttc agctccctgg 2050 gtcgaagagt gagcacaaag aacccaaaga taaaaagata aacatactga 2100 ttcctttgtc tgggcgtttc gacatgtttg tgagatttat gggaaacttt 2150 gagaagacgt gtcttatccc caatcagaac gtcaagctcg tggttctgct 2200 tttcaattct gactccaacc ctgacaaggc caaacaagtt gaactgatga 2250 gagattaccg tctggagagt cattaagtac tttcaagagc cctaaagccg cctggccctg acatgcagat gaagtaggat tttgcctgtg cctcccagtt 2300 2350 taacaatgaa tctttgctct tcttctgcga cgtcgacctc gtgtttacta 2400 cagaattcct tcagcgatgt cgagcaaata cagttctggg ccaacaaata 2450 tattttccaa tcatcttcag ccagtatgac ccaaagattg tttatagtgg 2500 gaaagttccc agtgacaacc attttgcctt tactcagaaa actggcttct 2550 ggagaaacta tgggtttggc atcacgtgta tttataaggg agatcttgtc 2600 cgagtgggtg gctttgatgt ttccatccaa ggctgggggc tggaggatgt 2650 ggaccttttc aacaaggttg tccaggcagg tttgaagacg tttaggagcc 2700 aggaagtagg agtagtccac gtccaccatc ctgtcttttg tgatcccaat 2750 cttgacccca aacagtacaa aatgtgcttg gggtccaaag catcgaccta 2800 tgggtccacc cagcagctgg ctgagatgtg gctggaaaaa aatgatccaa 2850 gttacagtaa aagcagcaat aataatggct cagtgaggac agcctaatgt 2900 ccagctttgc tggaaaagac gtttttaatt atctaattta tttttcaaaa 2950 attttttgta tgatcagttt ttgaagtccg tatacaagga tatattttac 3000 716 aagtggtttt cttacatagg actcctttaa gattgagctt tctgaacaag 3050 aaggtgatca gtgtttgcct ttgaacacat cttcttgctg aacattatgt 3100 agcagacctg cttaactttg acttgaaatg tacctgatga acaaaacttt 3150 tttaaaaaaa tgttttcttt tgagaccctt tgctccagtc ctatggcaga 3200 aaacgtgaac attcctgcaa agtattattg taacaaaaca ctgtaactct 3250 ggtaaatgtt ctgttgtgat tgttaacatt ccacagattc taccttttgt 3300 gttttgtttt ttttttttac aattgtttta aagccatttc atgttccagt 3350 tgtaagataa ggaaatgtga taatagctgt ttcatcattg tcttcaggag 3400 agctttccag agttgatcat ttcctctcat ggtactctgc tcagcatggc 3450 cacgtaggtt ttttgtttgt tttgttttgt tctttttttg agacggagtc 3500 tcactctgtt acccaggctg gaatgcagtg gcgcaatctt ggctcacttt 3550 aacctccact tccctggttc aagcaattcc cctgcctttg cctcccgagt 3600 agctgggatt acaggcacac accaccacgc ccagntagtt tttttgtatt 3650 tttagtagag acggggtttc accatgcaag cccagctggc cacgtaggtt 3700 ttaaagcaag gggcgtgaag aaggcacagt gaggtatgtg gctgttctcg 3750 tggtagttca ttcggcctaa atagacctgg cattaaattt caagaaggat 3800 ttggcatttt ctcttcttga cccttctctt taaagggtaa aatattaatg 3850 tttagaatga gaaacataca caaagatgaa cacatacacc ttattacaat ctaatcaaaa aaatctgatg cgttggggaa tacacagact aaatgtattt 3900 3950 ggttttgttc ctttcatcct gtctgtgtta tgtgggtgga gatggttttc 4000 attctttcat tactgttttg ttttatcctt tgtatctgaa atacctttaa 4050 tttatttaat atctgttgtt cagagctctg ccatttcttg agtacctgtt 4100 agttagtatt atttatgtgt atcgggagtg tgtttagtct gttttatttg 4150 cagtaaaccg atctccaaag atttcctttt ggaaacgctt tttcccctcc 4200 ttaattttta tattccttac tgttttacta aatattaagt gttctttgac 4250 aattttggtg ctcatgtgtt ttggggacaa aagtgaaatg aatctgtcat 4300 tataccagaa agttaaattc tcagatcaaa tgtgccttaa taaatttgtt 4350 ttcatttaga tttcaaacag tgatagactt gccattttaa tacacgtcat 4400 tggagggctg cgtatttgta aatagcctga tgctcatttg gaaaaataaa 4450 ccagtgaaca atatttttct attgtacttt tcgaaccatt ttgtctcatt 4500 attcctgttt tagctgaaga attgtattac atttggagag taaaaaactt 4550 aaacacgaaa aaa 4563 717 <210> 260 <211> 802 <212> PRT <213> Homo sapiens <400> 260 Met Ala Ala Arg Gly Arg Arg Ala Trp Leu Ser Val Leu Leu Gly 15 10 15 Leu Val Leu Gly Phe Val Leu Ala Ser Arg Leu Val Leu Pro Arg 20 25 30 Ala Ser Glu Leu Lys Arg Ala Gly Pro Arg Arg Arg Ala Ser Pro 35 40 45 Glu Gly Cys Arg Ser Gly Gin Ala Ala Ala Ser Gin Ala Gly Gly 50 55 60 Ala Arg Gly Asp Ala Arg Gly Ala Gin Leu Trp Pro Pro Gly Ser 65 70 75 Asp Pro Asp Gly Gly Pro Arg Asp Arg Asn Phe Leu Phe Val Gly 80 85 90 Val Met Thr Ala Gin Lys Tyr Leu Gin Thr Arg Ala Val Ala Ala 95 100 105 Tyr Arg Thr Trp Ser Lys Thr Ile Pro Gly Lys Val Gin Phe Phe 110 115 120 Ser Ser Glu Gly Ser Asp Thr Ser Val Pro Ile Pro Val Val Pro 125 130 135 Leu Arg Gly Val Asp Asp Ser Tyr Pro Pro Gin Lys Lys Ser Phe 140 145 150 Met Met Leu Lys Tyr Met His Asp His Tyr Leu Asp Lys Tyr Glu 155 160 165 Trp Phe Met Arg Ala Asp Asp Asp Val Tyr Ile Lys Gly Asp Arg 170 175 180 Leu Glu Asn Phe Leu Arg Ser Leu Asn Ser Ser Glu Pro Leu Phe 185 190 195 Leu Gly Gin Thr Gly Leu Gly Thr Thr Glu Glu Met Gly Lys Leu 200 205 210 Ala Leu Glu Pro Gly Glu Asn Phe Cys Met Gly Gly Pro Gly Val 215 220 225 Ile Met Ser Arg Glu Val Leu Arg Arg Met Val Pro His Ile Gly 230 235 240 Lys Cys Leu Arg Glu Met Tyr Thr Thr His Glu Asp Val Glu Val 245 250 255 Gly Arg Cys Val Arg Arg Phe Ala Gly Val Gin Cys Val Trp Ser 260 265 270 Tyr Glu Met Arg Gin Leu Phe Tyr Glu Asn Tyr Glu Gin Asn Lys 275 280 285 718 Lys Gly Tyr Ile Arg Asp Leu His Asn Ser Lys Ile His Gin Ala 290 295 300 Ile Thr Leu His Pro Asn Lys Asn Pro Pro Tyr Gin Tyr Arg Leu 305 310 315 His Ser Tyr Met Leu Ser Arg Lys Ile Ser Glu Leu Arg His Arg 320 325 330 Thr Ile Gin Leu His Arg Glu Ile Val Leu Met Ser Lys Tyr Ser 335 340 345 Asn Thr Glu Ile His Lys Glu Asp Leu Gin Leu Gly Ile Pro Pro 350 355 360 Ser Phe Met Arg Phe Gin Pro Arg Gin Arg Glu Glu Ile Leu Glu 365 370 375 Trp Glu Phe Leu Thr Gly Lys Tyr Leu Tyr Ser Ala Val Asp Gly 380 385 390 Gin Pro Pro Arg Arg Gly Met Asp Ser Ala Gin Arg Glu Ala Leu 395 400 405 Asp Asp Ile Val Met Gin Val Met Glu Met Ile Asn Ala Asn Ala 410 415 420 Lys Thr Arg Gly Arg Ile Ile Asp Phe Lys Glu Ile Gin Tyr Gly 425 430 435 Tyr Arg Arg Val Asn Pro Met Tyr Gly Ala Glu Tyr Ile Leu Asp 440 445 450 Leu Leu Leu Leu Tyr Lys Lys His Lys Gly Lys Lys Met Thr Val 455 460 465 Pro Val Arg Arg His Ala Tyr Leu Gin Gin Thr Phe Ser Lys Ile 470 475 480 Gin Phe Val Glu His Glu Glu Leu Asp Ala Gin Glu Leu Ala Lys 485 490 495 Arg Ile Asn Gin Glu Ser Gly Ser Leu Ser Phe Leu Ser Asn Ser 500 505 510 Leu Lys Lys Leu Val Pro Phe Gin Leu Pro Gly Ser Lys Ser Glu 515 520 525 His Lys Glu Pro Lys Asp Lys Lys Ile Asn Ile Leu Ile Pro Leu 530 535 540 Ser Gly Arg Phe Asp Met Phe Val Arg Phe Met Gly Asn Phe Glu 545 550 555 Lys Thr Cys Leu Ile Pro Asn Gin Asn Val Lys Leu Val Val Leu 560 565 570 Leu Phe Asn Ser Asp Ser Asn Pro Asp Lys Ala Lys Gin Val Glu 575 580 585 Leu Met Arg Asp Tyr Arg Ile Lys Tyr Pro Lys Ala Asp Met Gin 719 590 595 600 Ile Leu Pro Val Ser Gly Glu Phe Ser Arg Ala Leu Ala Leu Glu 605 610 615 Val Gly Ser Ser Gin Phe Asn Asn Glu Ser Leu Leu Phe Phe Cys 620 625 630 Asp Val Asp Leu Val Phe Thr Thr Glu Phe Leu Gin Arg Cys Arg 635 640 645 Ala Asn Thr Val Leu Gly Gin Gin Ile Tyr Phe Pro Ile Ile Phe 650 655 660 Ser Gin Tyr Asp Pro Lys Ile Val Tyr Ser Gly Lys Val Pro Ser 665 670 675 Asp Asn His Phe Ala Phe Thr Gin Lys Thr Gly Phe Trp Arg Asn 680 685 690 Tyr Gly Phe Gly Ile Thr Cys Ile Tyr Lys Gly Asp Leu Val Arg 695 700 705 Val Gly Gly Phe Asp Val Ser Ile Gin Gly Trp Gly Leu Glu Asp 710 715 720 Val Asp Leu Phe Asn Lys Val Val Gin Ala Gly Leu Lys Thr Phe 725 730 735 Arg Ser Gin Glu Val Gly Val Val His Val His His Pro Val Phe 740 745 750 Cys Asp Pro Asn Leu Asp Pro Lys Gin Tyr Lys Met Cys Leu Gly 755 760 765 Ser Lys Ala Ser Thr Tyr Gly Ser Thr Gin Gin Leu Ala Glu Met 770 775 780 Trp Leu Glu Lys Asn Asp Pro Ser Tyr Ser Lys Ser Ser Asn Asn 785 790 795 Asn Gly Ser Val Arg Thr Ala 800 <210> 261 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 261 gtgccactac ggggtgtgga cgac 24 <210> 262 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 262 tcccatttct tccgtggtgc ccag 24 <210> 263 <211> 46 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 263 ccagaagaag tccttcatga tgctcaagta catgcacgac cactac 46 <210> 264 <211> 1419 <212> DNA <213> Homo sapiens <400> 264 ggacaaccgt tgctgggtgt cccagggcct gaggcaggac ggtactccgc 50 tgacaccttc cctttcggcc ttgaggttcc cagcctggtg gccccaggac 100 gttccggtcg catggcagag tgctacggac gacgcctatg aagcccttag 150 tccttctagt tgcgcttttg ctatggcctt cgtctgtgcc ggcttatccg 200 agcataactg tgacacctga tgaagagcaa aacttgaatc attatataca 250 agttttagag aacctagtac gaagtgttcc ctctggggag ccaggtcgtg 300 agaaaaaatc taactctcca aaacatgttt attctatagc atcaaaggga 350 tcaaaattta aggagctagt tacacatgga gacgcttcaa ctgagaatga 400 tgttttaacc aatcctatca gtgaagaaac tacaactttc cctacaggag 450 gcttcacacc ggaaatagga aagaaaaaac acacggaaag taccccattc 500 tggtcgatca aaccaaacaa tgtttccatt gttttgcatg cagaggaacc 550 . ttatattgaa aatgaagagc cagagccaga gccggagcca gctgcaaaac 600 aaactgaggc accaagaatg ttgccagttg ttactgaatc atctacaagt 650 ccatatgtta cctcatacaa gtcacctgtc accactttag ataagagcac 700 tggcattgag atctctacag aatcagaaga tgttcctcag ctctcaggtg 750 aaactgcgat agaaaaaccc gaagagtttg gaaagcaccc agagagttgg 800 aataatgatg acattttgaa aaaaatttta gatattaatt cacaagtgca 850 acaggcactt cttagtgaca ccagcaaccc agcatataga gaagatattg 900 aagcctctaa agatcaccta aaacgaagcc ttgctctagc agcagcagca 950 gaacataaat taaaaacaat gtataagtcc cagttattgc cagtaggacg 1000 aacaagtaat aaaattgatg acatcgaaac tgttattaac atgctgtgta 1050 721 attctagatc taaactctat gaatatttag atattaaatg tgttccacca 1100 gagatgagag aaaaagctgc tacagtattc aatacattaa aaaatatgtg 1150 tagatcaagg agagtcacag ccttattaaa agtttattaa acaataatat 1200 aaaaatttta aacctacttg atattccata acaaagctga tttaagcaaa 1250 ctgcattttt tcacaggaga aataatcata ttcgtaattt caaaagttgt 1300 ataaaaatat tttctattgt agttcaaatg tgccaacatc tttatgtgtc 1350 atgtgttatg aacaattttc atatgcacta aaaacctaat ttaaaataaa 1400 attttggttc aggaaaaaa 1419 <210> 265 <211> 350 <212> PRT <213> Homo sapiens <400> 265 Met Lys Pro Leu Val Leu Leu Val Ala Leu Leu Leu Trp Pro Ser 15 10 15 Ser Val Pro Ala Tyr Pro Ser Ile Thr Val Thr Pro Asp Glu Glu 20 25 30 Gin Asn Leu Asn His Tyr Ile Gin Val Leu Glu Asn Leu Val Arg 35 40 45 Ser Val Pro Ser Gly Glu Pro Gly Arg Glu Lys Lys Ser Asn Ser 50 55 60 Pro Lys His Val Tyr Ser Ile Ala Ser Lys Gly Ser Lys Phe Lys 65 70 75 Glu Leu Val Thr His Gly Asp Ala Ser Thr Glu Asn Asp Val Leu 80 85 90 Thr Asn Pro Ile Ser Glu Glu Thr Thr Thr Phe Pro Thr Gly Gly 95 100 105 Phe Thr Pro Glu Ile Gly Lys Lys Lys His Thr Glu Ser Thr Pro 110 115 120 Phe Trp Ser Ile Lys Pro Asn Asn Val Ser Ile Val Leu His Ala 125 130 135 Glu Glu Pro Tyr Ile Glu Asn Glu Glu Pro Glu Pro Glu Pro Glu 140 145 150 Pro Ala Ala Lys Gin Thr Glu Ala Pro Arg Met Leu Pro Val Val 155 160 165 Thr Glu Ser Ser Thr Ser Pro Tyr Val Thr Ser Tyr Lys Ser Pro 170 175 180 Val Thr Thr Leu Asp Lys Ser Thr Gly lie Glu Ile Ser Thr Glu 185 190 195 Ser Glu Asp Val Pro Gin Leu Ser Gly Glu Thr Ala Ile Glu Lys 722 200 205 210 Pro Glu Glu Phe Gly Lys His Pro Glu Ser Trp Asn Asn Asp Asp 215 220 225 Ile Leu Lys Lys Ile Leu Asp Ile Asn Ser Gin Val Gin Gin Ala 230 235 240 Leu Leu Ser Asp Thr Ser Asn Pro Ala Tyr Arg Glu Asp Ile Glu 245 250 255 Ala Ser Lys Asp His Leu Lys Arg Ser Leu Ala Leu Ala Ala Ala 260 265 270 Ala Glu His Lys Leu Lys Thr Met Tyr Lys Ser Gin Leu Leu Pro 275 280 285 Val Gly Arg Thr Ser Asn Lys Ile Asp Asp Ile Glu Thr Val Ile 290 295 300 Asn Met Leu Cys Asn Ser Arg Ser Lys Leu Tyr Glu Tyr Leu Asp 305 310 315 Ile Lys Cys Val Pro Pro Glu Met Arg Glu Lys Ala Ala Thr Val 320 325 330 Phe Asn Thr Leu Lys Asn Met Cys Arg Ser Arg Arg Val Thr Ala 335 340 345 Leu Leu Lys Val Tyr 350 <210> 266 <211> 2403 <212> DNA <213> Homo sapiens <400> 266 cggctcgagc ggctcgagtg aagagcctct ccacggctcc tgcgcctgag 50 acagctggcc ttcatagtgt tgacctccaa gagatcaacc atcatccatc cacaggaata cacccctgct tccatggctt gtcatctgtt ttgtgctcat 100 150 tttggttctc agtttctacg agctggtgtc aggacagtgg caagtcactg 200 gaccgggcaa gtttgtccag gccttggtgg gggaggacgc cgtgttctcc 250 tgctccctct ttcctgagac cagtgcagag gctatggaag tgcggttctt 300 caggaatcag ttccatgctg tggtccacct ctacagagat ggggaagact 350 gggaatctaa gcagatgcca cagtatcgag ggagaactga gtttgtgaag 400 gactccattg caggggggcg tgtctctcta aggctaaaaa acatcactcc 450 ctcggacatc ggcctgtatg ggtgctggtt cagttcccag atttacgatg 500 aggaggccac ctgggagctg cgggtggcag cactgggctc acttcctctc 550 atttccatcg tgggatatgt tgacggaggt atccagttac tctgcctgtc 600 ctcaggctgg ttcccccagc ccacagccaa gtggaaaggt ccacaaggac 650 723 aggatttgtc ttcagactcc agagcaaatg cagatgggta cagcctgtat 700 gatgtggaga tctccattat agtccaggaa aatgctggga gcatattgtg 750 ttccatccac cttgctgagc agagtcatga ggtggaatcc aaggtattga 800 taggagagac gtttttccag ccctcacctt ggcgcctggc ttctatttta 850 ctcgggttac tctgtggtgc cctgtgtggt gttgtcatgg ggatgataat 900 tgttttcttc aaatccaaag ggaaaatcca ggcggaactg gactggagaa 950 gaaagcacgg acaggcagaa ttgagagacg cccggaaaca cgcagtggag 1000 gtgactctgg atccagagac ggctcacccg aagctctgcg tttctgatct 1050 gaaaactgta acccatagaa aagctcccca ggaggtgcct cactctgaga 1100 agagatttac aaggaagagt gtggtggctt ctcagggttt ccaagcaggg 1150 agacattact gggaggtgga cgtgggacaa aatgtagggt ggtatgtggg 1200 agtgtgtcgg gatgacgtag acagggggaa gaacaatgtg actttgtctc 1250 ccaacaatgg gtattgggtc ctcagactga caacagaaca tttgtatttc 1300 acattcaatc cccattttat cagcctcccc cccagcaccc ctcctacacg 1350 agtaggggtc ttcctggact atgagggtgg gaccatctcc ttcttcaata 1400 caaatgacca gtcccttatt tataccctgc tgacatgtca gtttgaaggc 1450 ttgttgagac cctatatcca gcatgcgatg tatgacgagg aaaaggggac 1500 tcccatattc atatgtccag tgtcctgggg atgagacaga gaagaccctg 1550 cttaaagggc cccacaccac agacccagac acagccaagg gagagtgctc 1600 ccgacaggtg gccccagctt cctctccgga gcctgcgcac agagagtcac 1650 gccccccact agcagcggca ctcctttagg gtcacagctt gagctgaggt ccagatgagg tcttctgccc ggggattggc tgagccctgc ctgaccctgt 1700 1750 gggagtcaga agccatggct gccctgaagt ggggacggaa tagactcaca 1800 ttaggtttag tttgtgaaaa ctccatccag ctaagcgatc ttgaacaagt 1850 cacaacctcc caggctcctc atttgctagt cacggacagt gattcctgcc 1900 tcacaggtga agattaaaga gacaacgaat gtgaatcatg cttgcaggtt 1950 tgagggcaca gtgtttgcta atgatgtgtt tttatattat acattttccc 2000 accataaact ctgtttgctt attccacatt aatttacttt tctctatacc 2050 aaatcaccca tggaatagtt attgaacacc tgctttgtga ggctcaaaga 2100 ataaagagga ggtaggattt ttcactgatt ctataagccc agcattacct 2150 gataccaaaa ccaggcaaag aaaacagaag aagaggaagg aaaactacag 2200 724 gtccatatcc ctcattaaca cagacacaaa aattctaaat aaaattttaa 22 50 caaattaaac taaacaatat atttaaagat gatatataac tactcagtgt 2300 ggtttgtccc acaaatgcag agttggttta atatttaaat atcaaccagt 23 50 gtaattcagc acattaataa agtaaaaaag aaaaccataa aaaaaaaaaa 2400 aaa 2403 <210> 267 <211> 466 <212> PRT <213> Homo sapiens <400> 267 Met Ala Phe Val Leu lie Leu Val Leu Ser Phe Tyr Glu Leu Val 15 10 15 Ser Gly Gin Trp Gin Val Thr Gly Pro Gly Lys Phe Val Gin Ala 20 25 30 Leu Val Gly Glu Asp Ala Val Phe Ser Cys Ser Leu Phe Pro Glu 35 40 45 Thr Ser Ala Glu Ala Met Glu Val Arg Phe Phe Arg Asn Gin Phe 50 55 60 His Ala Val Val His Leu Tyr Arg Asp Gly Glu Asp Trp Glu Ser 65 70 75 Lys Gin Met Pro Gin Tyr Arg Gly Arg Thr Glu Phe Val Lys Asp 80 85 90 Ser Ile Ala Gly Gly Arg Val Ser Leu Arg Leu Lys Asn Ile Thr 95 100 105 Pro Ser Asp Ile Gly Leu Tyr Gly Cys Trp Phe Ser Ser Gin Ile 110 115 120 Tyr Asp Glu Glu Ala Thr Trp Glu Leu Arg Val Ala Ala Leu Gly 125 130 135 Ser Leu Pro Leu Ile Ser Ile Val Gly Tyr Val Asp Gly Gly Ile 140 145 150 Gin Leu Leu Cys Leu Ser Ser Gly Trp Phe Pro Gin Pro Thr Ala 155 160 165 Lys Trp Lys Gly Pro Gin Gly Gin Asp Leu Ser Ser Asp Ser Arg 170 175 180 Ala Asn Ala Asp Gly Tyr Ser Leu Tyr Asp Val Glu Ile Ser Ile 185 190 195 Ile Val Gin Glu Asn Ala Gly Ser Ile Leu Cys Ser Ile His Leu 200 205 210 Ala Glu Gin Ser His Glu Val Glu Ser Lys Val Leu Ile Gly Glu 215 220 225 Thr Phe Phe Gin Pro Ser Pro Trp Arg Leu Ala Ser Ile Leu Leu 230 725 235 240 Gly Leu Leu Cys Gly Ala Leu Cys Gly Val Val Met Gly Met Ile 245 250 255 Ile Val Phe Phe Lys Ser Lys Gly Lys Ile Gin Ala Glu Leu Asp 260 265 270 Trp Arg Arg Lys His Gly Gin Ala Glu Leu Arg Asp Ala Arg Lys 275 280 285 His Ala Val Glu Val Thr Leu Asp Pro Glu Thr Ala His Pro Lys 290 295 300 Leu Cys Val Ser Asp Leu Lys Thr Val Thr His Arg Lys Ala Pro 305 310 315 Gin Glu Val Pro His Ser Glu Lys Arg Phe Thr Arg Lys Ser Val 320 325 330 Val Ala Ser Gin Gly Phe Gin Ala Gly Arg His Tyr Trp Glu Val 335 340 345 Asp Val Gly Gin Asn Val Gly Trp Tyr Val Gly Val Cys Arg Asp 350 355 360 Asp Val Asp Arg Gly Lys Asn Asn Val Thr Leu Ser Pro Asn Asn 365 370 375 Gly Tyr Trp Val Leu Arg Leu Thr Thr Glu His Leu Tyr Phe Thr 380 385 390 Phe Asn Pro His Phe Ile Ser Leu Pro Pro Ser Thr Pro Pro Thr 395 400 405 Arg Val Gly Val Phe Leu Asp Tyr Glu Gly Gly Thr Ile Ser Phe 410 415 420 Phe Asn Thr Asn Asp Gin Ser Leu Ile Tyr Thr Leu Leu Thr Cys 425 430 435 Gin Phe Glu Gly Leu Leu Arg'Pro Tyr Ile Gin His Ala Met Tyr 440 445 450 Asp Glu Glu Lys Gly Thr Pro Ile Phe Ile Cys Pro Val Ser Trp 455 460 465 Gly <210> 268 <211> 2103 <212> DNA <213> Homo sapiens <400> 268 ccttcacagg actcttcatt gctggttggc aatgatgtat cggccagatg 50 tggtgagggc taggaaaaga gtttgttggg aaccctgggt tatcggcctc 100 gtcatcttca tatccctgat tgtcctggca gtgtgcattg gactcactgt 150 726 tcattatgtg agatataatc aaaagaagac ctacaattac tatagcacat 200 tgtcatttac aactgacaaa ctatatgctg agtttggcag agaggcttct 250 aacaatttta cagaaatgag ccagagactt gaatcaatgg tgaaaaatgc 300 attttataaa tctccattaa gggaagaatt tgtcaagtct caggttatca 350 agttcagtca acagaagcat ggagtgttgg ctcatatgct gttgatttgt 400 agatttcact ctactgagga tcctgaaact gtagataaaa ttgttcaact 450 tgttttacat gaaaagctgc aagatgctgt aggaccccct aaagtagatc 500 ctcactcagt taaaattaaa aaaatcaaca agacagaaac agacagctat 550 ctaaaccatt gctgcggaac acgaagaagt aaaactctag gtcagagtct 600 caggatcgtt ggtgggacag aagtagaaga gggtgaatgg ccctggcagg 650 ctagcctgca gtgggatggg agtcatcgct gtggagcaac cttaattaat 700 gccacatggc ttgtgagtgc tgctcactgt tttacaacat ataagaaccc 750 tgccagatgg actgcttcct ttggagtaac aataaaacct tcgaaaatga 800 aacggggtct ccggagaata attgtccatg aaaaatacaa acacccatca 850 catgactatg atatttctct tgcagagctt tctagccctg ttccctacac 900 aaatgcagta catagagttt gtctccctga tgcatcctat gagtttcaac 950 caggtgatgt gatgtttgtg acaggatttg gagcactgaa aaatgatggt 1000 tacagtcaaa atcatcttcg acaagcacag gtgactctca tagacgctac 1050 aacttgcaat gaacctcaag cttacaatga cgccataact cctagaatgt 1100 tatgtgctgg ctccttagaa ggaaaaacag atgcatgcca gggtgactct 1150 ggaggaccac tggttagttc agatgctaga gatatctggt accttgctgg 1200 aatagtgagc tggggagatg aatgtgcgaa acccaacaag cctggtgttt 1250 atactagagt taagagacaa tacggccttg aagcctcatg cgggactgga gaacagataa ttacttcaaa catttttttt aactggtatc tgttttttgg 1300 1350 gtgtggaggc catttttaga gatacagaat tggagaagac ttgcaaaaca 1400 gctagatttg actgatctca ataaactgtt tgcttgatgc atgtattttc 1450 ttcccagctc tgttccgcac gtaagcatcc tgcttctgcc agatcaactc 1500 tgtcatctgt gagcaatagt tgaaacttta tgtacataga gaaatagata 1550 atacaatatt acattacagc ctgtattcat ttgttctcta gaagttttgt 1600 cagaattttg acttgttgac ataaatttgt aatgcatata tacaatttga 1650 agcactcctt ttcttcagtt cctcagctcc tctcatttca gcaaatatcc 1700 attttcaagg tgcagaacaa ggagtgaaag aaaatataag aagaaaaaaa 1750 727 tcccctacat tttattggca cagaaaagta ttaggtgttt ttcttagtgg 1800 aatattagaa atgatcatat tcattatgaa aggtcaagca aagacagcag 1850 aataccaatc acttcatcat ttaggaagta tgggaactaa gttaaggaag 1900 tccagaaaga agccaagata tatccttatt ttcatttcca aacaactact 1950 atgataaatg tgaagaagat tctgtttttt tgtgacctat aataattata 2000 caaacttcat gcaatgtact tgttctaagc aaattaaagc aaatatttat 2050 ttaacattgt tactgaggat gtcaacatat aacaataaaa tataaatcac 2100 cca 2103 <210> 269 <211> 423 <212> PRT <213> Homo sapiens <400> 269 Met Met Tyr Arg Pro Asp Val Val Arg Ala Arg Lys Arg Val Cys 15 10 15 Trp Glu Pro Trp Val Ile Gly Leu Val Ile Phe Ile Ser Leu Ile 20 25 30 Val Leu Ala Val Cys Ile Gly Leu Thr Val His Tyr Val Arg Tyr 35 40 45 Asn Gin Lys Lys Thr Tyr Asn Tyr Tyr Ser Thr Leu Ser Phe Thr 50 55 60 Thr Asp Lys Leu Tyr Ala Glu Phe Gly Arg Glu Ala Ser Asn Asn 65 70 75 Phe Thr Glu Met Ser Gin Arg Leu Glu Ser Met Val Lys Asn Ala 80 85 90 Phe Tyr Lys Ser Pro Leu Arg Glu Glu Phe Val Lys Ser Gin Val 95 100 105 Ile Lys Phe Ser Gin Gin Lys His Gly Val Leu Ala His Met Leu 110 115 120 Leu Ile Cys Arg Phe His Ser Thr Glu Asp Pro Glu Thr Val Asp 125 130 135 Lys Ile Val Gin Leu Val Leu His Glu Lys Leu Gin Asp Ala Val 140 145 150 Gly Pro Pro Lys Val Asp Pro His Ser Val Lys Ile Lys Lys Ile 155 160 165 Asn Lys Thr Glu Thr Asp Ser Tyr Leu Asn His Cys Cys Gly Thr 170 175 180 Arg Arg Ser Lys Thr Leu Gly Gin Ser Leu Arg Ile Val Gly Gly 185 190 195 Thr Glu Val Glu Glu Gly Glu Trp Pro Trp Gin Ala Ser Leu Gin 200 728 205 210 Trp Asp Gly Ser His Arg Cys Gly Ala Thr Leu Ile Asn Ala Thr 215 220 225 Trp Leu Val Ser Ala Ala His Cys Phe Thr Thr Tyr Lys Asn Pro 230 235 240 Ala Arg Trp Thr Ala Ser Phe Gly Val Thr Ile Lys Pro Ser Lys 245 250 255 Met Lys Arg Gly Leu Arg Arg Ile Ile Val His Glu Lys Tyr Lys 260 265 270 His Pro Ser His Asp Tyr Asp Ile Ser Leu Ala Glu Leu Ser Ser 275 280 285 Pro Val Pro Tyr Thr Asn Ala Val His Arg Val Cys Leu Pro Asp 290 295 300 Ala Ser Tyr Glu Phe Gin Pro Gly Asp Val Met Phe Val Thr Gly 305 310 315 Phe Gly Ala Leu Lys Asn Asp Gly Tyr Ser Gin Asn His Leu Arg 320 325 330 Gin Ala Gin Val Thr Leu Ile Asp Ala Thr Thr Cys Asn Glu Pro 335 340 345 Gin Ala Tyr Asn Asp Ala Ile Thr Pro Arg Met Leu Cys Ala Gly 350 355 360 Ser Leu Glu Gly Lys Thr Asp Ala Cys Gin Gly Asp Ser Gly Gly 365 370 375 Pro Leu Val Ser Ser Asp Ala Arg Asp Ile Trp Tyr Leu Ala Gly 380 385 390 Ile Val Ser Trp Gly Asp Glu Cys Ala Lys Pro Asn Lys Pro Gly 395 400 405 Val Tyr Thr Arg Val Thr Ala Leu Arg Asp Trp Ile Thr Ser Lys 410 415 420 Thr Gly Ile <210> 270 <211> 1170 <212> DNA <213> Homo sapiens <400> 270 gtcgaaggtt ataaaagctt ccagccaaac ggcattgaag ttgaagatac 50 aacctgacag cacagcctga gatcttgggg atccctcagc ctaacaccca 100 cagacgtcag ctggtggatt cccgctgcat caaggcctac ccactgtctc 150 catgctgggc tctccctgcc ttctgtggct cctggccgtg accttcttgg 200 ttcccagagc tcagcccttg gcccctcaag actttgaaga agaggaggca 250 729 gatgagactg agacggcgtg gccgcctttg ccggctgtcc cctgcgacta 3 00 cgaccactgc cgacacctgc aggtgccctg caaggagcta cagagggtcg 350 ggccggcggc ctgcctgtgc ccaggactct ccagccccgc ccagccgccc 400 gacccgccgc gcatgggaga agtgcgcatt gcggccgaag agggccgcgc 450 agtggtccac tggtgtgccc ccttctcccc ggtcctccac tactggctgc 500 tgctttggga cggcagcgag gctgcgcaga aggggccccc gctgaacgct 550 acggtccgca gagccgaact gaaggggctg aagccagggg gcatttatgt 600 cgtttgcgta gtggccgcta acgaggccgg ggcaagccgc gtgccccagg 650 ctggaggaga gggcctcgag ggggccgaca tccctgcctt cgggccttgc 700 agccgccttg cggtgccgcc caacccccgc actctggtcc acgcggccgt 750 cggggtgggc acggccctgg ccctgctaag ctgtgccgcc ctggtgtggc 800 acttctgcct gcgcgatcgc tggggctgcc cgcgccgagc cgccgcccga 850 gccgcagggg cgctctgaaa ggggcctggg ggcatctcgg gcacagacag 900 ccccacctgg ggcgctcagc ctggcccccg ggaaagagga aaacccgctg 950 cctccaggga gggctggacg gcgagctggg agccagcccc aggctccagg 1000 gccacggcgg agtcatggtt ctcaggactg agcgcttgtt taggtccggt 1050 acttggcgct ttgtttcctg gctgaggtct gggaaggaat agaaaggggc 1100 ccccaatttt tttttaagcg gccagataat aaataatgta acctttgcgg 1150 ttaaaaaaaa aaaaaaaaaa 1170 <210> 271 <211> 238 <212> PRT <213> Homo sapiens <400> 271 Met Leu Gly Ser Pro Cys Leu Leu Trp Leu Leu Ala Val Thr Phe 15 10 15 Leu Val Pro Arg Ala Gin Pro Leu Ala Pro Gin Asp Phe Glu Glu 20 25 30 Glu Glu Ala Asp Glu Thr Glu Thr Ala Trp Pro Pro Leu Pro Ala 35 40 45 Val Pro Cys Asp Tyr Asp His Cys Arg His Leu Gin Val Pro Cys 50 55 60 Lys Glu Leu Gin Arg Val Gly Pro Ala Ala Cys Leu Cys Pro Gly 65 70 75 Leu Ser Ser Pro Ala Gin Pro Pro Asp Pro Pro Arg Met Gly Glu 80 85 90 730 Val Arg Ile Ala Ala Glu Glu Gly Arg Ala Val Val His Trp Cys 95 100 • 105 Ala Pro Phe Ser Pro Val Leu His Tyr Trp Leu Leu Leu Trp Asp 110 115 120 Gly Ser Glu Ala Ala Gin Lys Gly Pro Pro Leu Asn Ala Thr Val 125 130 135 Arg Arg Ala Glu Leu Lys Gly Leu Lys Pro Gly Gly Ile Tyr Val 140 145 150 Val Cys Val Val Ala Ala Asn Glu Ala Gly Ala Ser Arg Val Pro 155 160 165 Gin Ala Gly Gly Glu Gly Leu Glu Gly Ala Asp Ile Pro Ala Phe 170 175 180 Gly Pro Cys Ser Arg Leu Ala Val Pro Pro Asn Pro Arg Thr Leu 185 190 195 Val His Ala Ala Val Gly Val Gly Thr Ala Leu Ala Leu Leu Ser 200 205 210 Cys Ala Ala Leu Val Trp His Phe Cys Leu Arg Asp Arg Trp Gly 215 220 225 Cys Pro Arg Arg Ala Ala Ala Arg Ala Ala Gly Ala Leu 230 235 <210> 272 <211> 2397 <212> DNA <213> Homo sapiens <400> 272 agagaaagaa gcgtctccag ctgaagccaa tgcagccctc cggctctccg 50 cgaagaagtt ccctgccccg atgagccccc gccgtgcgtc cccgactatc 100 cccaggcggg cgtggggcac cgggcccagc gccgacgatc gctgccgttt 150 tgcccttggg agtaggatgt ggtgaaagga tggggcttct cccttacggg 200 gctcacaatg gccagagaag attccgtgaa gtgtctgcgc tgcctgctct 250 acgccctcaa tctgctcttt tggttaatgt ccatcagtgt gttggcagtt 300 tctgcttgga tgagggacta cctaaataat gttctcactt taactgcaga 350 aacgagggta gaggaagcag tcattttgac ttactttcct gtggttcatc 400 cggtcatgat tgctgtttgc tgtttcctta tcattgtggg gatgttagga 450 tattgtggaa cggtgaaaag aaatctgttg cttcttgcat ggtactttgg 500 aagtttgctt gtcattttct gtgtagaact ggcttgtggc gtttggacat 550 atgaacagga acttatggtt ccagtacaat ggtcagatat ggtcactttg 600 aaagccagga tgacaaatta tggattacct agatatcggt ggcttactca 650 731 tgcttggaat ttttttcaga gagagtttaa gtgctgtgga gtagtatatt 700 tcactgactg gttggaaatg acagagatgg actggccccc agattcctgc 750 tgtgttagag aattcccagg atgttccaaa caggcccacc aggaagatct 800 cagtgacctt tatcaagagg gttgtgggaa gaaaatgtat tcctttttga 850 gaggaaccaa acaactgcag gtgctgaggt ttctgggaat ctccattggg 900 gtgacacaaa tcctggccat gattctcacc attactctgc tctgggctct 950 gtattatgat agaagggagc ctgggacaga ccaaatgatg tccttgaaga 1000 atgacaactc tcagcacctg tcatgtccct cagtagaact gttgaaacca 1050 agcctgtcaa gaatctttga acacacatcc atggcaaaca gctttaatac 1100 acactttgag atggaggagt tataaaaaga aatgtcacag aagaaaacca 1150 caaacttgtt ttattggact tgtgaatttt tgagtacata ctatgtgttt 1200 cagaaatatg tagaaataaa aatgttgcca taaaataaca cctaagcata 1250 tactattcta tgctttaaaa tgaggatgga aaagtttcat gtcataagtc 1300 accacctgga caataattga tgcccttaaa atgctgaaga cagatgtcat 1350 acccactgtg tagcctgtgt atgactttta ctgaacacag ttatgttttg 1400 aggcagcatg gtttgattag catttccgca tccatgcaaa cgagtcacat 1450 atggtgggac tggagccata gtaaaggttg atttacttct accaactagt 1500 atataaagta ctaattaaat gctaacatag gaagttagaa aatactaata 1550 acttttatta ctcagcgatc tattcttctg atgctaaata aattatatat 1600 cagaaaactt tcaatattgg tgactaccta aatgtgattt ttgctggtta 1650 ctaaaatatt cttaccactt aaaagagcaa gctaacacat tgtcttaagc 1700 tgatcaggga ttttttgtat ataagtctgt gttaaatctg tataattcag 1750 tcgatttcag ttctgataat gttaagaata accattatga aaaggaaaat 1800 ttgtcctgta tagcatcatt atttttagcc tttcctgtta ataaagcttt 1850 actattctgt taaccactaa cctgggctta ttttgaaaat tattacacat taccagtgtg ataactgtta atacatagga tttaaatact atcattattc 1900 1950 agaatgtagt ctggtcttta ggaagtatta ataagaaaat ttgcacataa 2000 cttagttgat tcagaaagga cttgtatgct gtttttctcc caaatgaaga 2050 ctctttttga cactaaacac tttttaaaaa gcttatcttt gccttctcca 2100 aacaagaagc aatagtctcc aagtcaatat aaattctaca gaaaatagtg 2150 ttctttttct ccagaaaaat gcttgtgaga atcattaaaa catgtgacaa 2200 732 tttagagatt ctttgtttta tttcactgat taatatactg tggcaaatta 22 50 cacagattat taaatttttt tacaagagta tagtatattt atttgaaatg 23 00 ggaaaagtgc attttactgt attttgtgta ttttgtttat ttctcagaat 2350 atggaaagaa aattaaaatg tgtcaataaa tattttctag agagtaa 2397 <210> 273 <211> 305 <212> PRT <213> Homo sapiens <400> 273 Met Ala Arg Glu Asp Ser Val Lys Cys Leu Arg Cys Leu Leu Tyr 15 10 15 Ala Leu Asn Leu Leu Phe Trp Leu Met Ser Ile Ser Val Leu Ala 20 25 30 Val Ser Ala Trp Met Arg Asp Tyr Leu Asn Asn Val Leu Thr Leu 35 40 45 Thr Ala Glu Thr Arg Val Glu Glu Ala Val Ile Leu Thr Tyr Phe 50 55 60 Pro Val Val His Pro Val Met Ile Ala Val Cys Cys Phe Leu Ile 65 70 75 lie Val Gly Met Leu Gly Tyr Cys Gly Thr Val Lys Arg Asn Leu 80 85 90 Leu Leu Leu Ala Trp Tyr Phe Gly Ser Leu Leu Val Ile Phe Cys 95 100 105 Val Glu Leu Ala Cys Gly Val Trp Thr Tyr Glu Gin Glu Leu Met 110 115 120 Val Pro Val Gin Trp Ser Asp Met Val Thr Leu Lys Ala Arg Met 125 130 135 Thr Asn Tyr Gly Leu Pro Arg Tyr Arg Trp Leu Thr His Ala Trp 140 145 150 Asn Phe Phe Gin Arg Glu Phe Lys Cys Cys Gly Val Val Tyr Phe 155 160 165 Thr Asp Trp Leu Glu Met Thr Glu Met Asp Trp Pro Pro Asp Ser 170 175 180 Cys Cys Val Arg Glu Phe Pro Gly Cys Ser Lys Gin Ala His Gin 185 190 195 Glu Asp Leu Ser Asp Leu Tyr Gin Glu Gly Cys Gly Lys Lys Met 200 205 210 Tyr Ser Phe Leu Arg Gly Thr Lys Gin Leu Gin Val Leu Arg Phe 215 220 225 Leu Gly Ile Ser Ile Gly Val Thr Gin Ile Leu Ala Met Ile Leu 230 235 240 Thr Ile Thr Leu Leu 245 Gly Thr Asp Gin Met 260 Leu Ser Cys Pro Ser 275 Ile Phe Glu His Thr 290 Glu Met Glu Glu Leu 305 <210> 274 <211> 2063 <212> DNA <213> Homo sapiens <400> 274 gagagaggca gcagcttgct cagcggacaa ggatgctggg cgtgagggac 50 caaggcctgc cctgcactcg ggcctcctcc agccagtgct gaccagggac 100 ttctgacctg ctggccagcc aggacctgtg tggggaggcc ctcctgctgc 150 cttggggtga caatctcagc tccaggctac agggagaccg ggaggatcac 200 agagccagca tgttacagga tcctgacagt gatcaacctc tgaacagcct 250 cgatgtcaaa cccctgcgca aaccccgtat ccccatggag accttcagaa 300 aggtggggat ccccatcatc atagcactac tgagcctggc gagtatcatc 350 attgtggttg tcctcatcaa ggtgattctg gataaatact acttcctctg 400 cgggcagcct ctccacttca tcccgaggaa gcagctgtgt gacggagagc 450 tggactgtcc cttgggggag gacgaggagc actgtgtcaa gagcttcccc 500 gaagggcctg cagtggcagt ccgcctctcc aaggaccgat ccacactgca 550 ggtgctggac tcggccacag ggaactggtt ctctgcctgt ttcgacaact 600 tcacagaagc tctcgctgag acagcctgta ggcagatggg ctacagcaga 650 gctgtggaga ttggcccaga ccaggatctg gatgttgttg aaatcacaga 700 aaacagccag gagcttcgca tgcggaactc aagtgggccc tgtctctcag 750 gctccctggt ccccgtgtgg ctccctgcac tgggtgggga tgtcttgcct ggaggcctct gtgggaagag gtggattctt cctgaagacc ggccttggca 800 850 ggtcagcatc cagtacgaca aacagcacgt ctgtggaggg agcatcctgg 900 acccccactg ggtcctcacg gcagcccact gcttcaggaa acataccgat 950 gtgttcaact ggaaggtgcg ggcaggctca gacaaactgg gcagcttccc 1000 atccctggct gtggccaaga tcatcatcat tgaattcaac cccatgtacc 1050 733 Trp Ala Leu Tyr Tyr Asp Arg Arg Glu Pro 250 255 Met Ser Leu Lys Asn Asp Asn Ser Gin His 265 270 Val Glu Leu Leu Lys Pro Ser Leu Ser Arg 280 285 Ser Met Ala Asn Ser Phe Asn Thr His Phe 295 300 734 ccaaagacaa tgacatcgcc ctcatgaagc tgcagttccc actcactttc 1100 tcaggcacag tcaggcccat ctgtctgccc ttctttgatg aggagctcac 1150 tccagccacc ccactctgga tcattggatg gggctttacg aagcagaatg 1200 gagggaagat gtctgacata ctgctgcagg cgtcagtcca ggtcattgac 1250 agcacacggt gcaatgcaga cgatgcgtac cagggggaag tcaccgagaa 1300 gatgatgtgt gcaggcatcc cggaaggggg tgtggacacc tgccagggtg 1350 acagtggtgg gcccctgatg taccaatctg accagtggca tgtggtgggc 1400 atcgttagct ggggctatgg ctgcgggggc ccgagcaccc caggagtata 1450 caccaaggtc tcagcctatc tcaactggat ctacaatgtc tggaaggctg 1500 agctgtaatg ctgctgcccc tttgcagtgc tgggagccgc ttccttcctg 1550 ccctgcccac ctggggatcc cccaaagtca gacacagagc aagagtcccc 1600 ttgggtacac ccctctgccc acagcctcag catttcttgg agcagcaaag 1650 ggcctcaatt cctgtaagag accctcgcag cccagaggcg cccagaggaa 1700 gtcagcagcc ctagctcggc cacacttggt gctcccagca tcccagggag 1750 agacacagcc cactgaacaa ggtctcaggg gtattgctaa gccaagaagg 1800 aactttccca cactactgaa tggaagcagg ctgtcttgta aaagcccaga 1850 tcactgtggg ctggagagga gaaggaaagg gtctgcgcca gccctgtccg 1900 tcttcaccca tccccaagcc tactagagca agaaaccagt tgtaatataa 1950 aatgcactgc cctactgttg gtatgactac cgttacctac tgttgtcatt 2000 gttattacag ctatggccac tattattaaa gagctgtgta acatctctgg 2050 caaaaaaaaa aaa 2063 <210> 275 <211> 432 <212> PRT <213> Homo sapiens <400> 275 Met Leu Gin Asp Pro Asp Ser Asp Gin Pro Leu Asn Ser Leu Asp 15 10 15 Val Lys Pro Leu Arg Lys Pro Arg Ile Pro Met Glu Thr Phe Arg 20 25 30 Lys Val Gly Ile Pro Ile Ile Ile Ala Leu Leu Ser Leu Ala Ser 35 40 45 Ile Ile Ile Val Val Val Leu Ile Lys Val Ile Leu Asp Lys Tyr 50 55 60 Tyr Phe Leu Cys Gly Gin Pro Leu His Phe Ile Pro Arg Lys Gin 65 70 75 735 Leu Cys Asp Gly Glu Leu Asp Cys Pro Leu Gly Glu Asp Glu Glu 80 85 90 His Cys Val Lys Ser Phe Pro Glu Gly Pro Ala Val Ala Val Arg 95 100 105 Leu Ser Lys Asp Arg Ser Thr Leu Gin Val Leu Asp Ser Ala Thr 110 115 120 Gly Asn Trp Phe Ser Ala Cys Phe Asp Asn Phe Thr Glu Ala Leu 125 130 135 Ala Glu Thr Ala Cys Arg Gin Met Gly Tyr Ser Arg Ala Val Glu 140 145 150 lie Gly Pro Asp Gin Asp Leu Asp Val Val Glu Ile Thr Glu Asn 155 160 165 Ser Gin Glu Leu Arg Met Arg Asn Ser Ser Gly Pro Cys Leu Ser 170 175 180 Gly Ser Leu Val Ser Leu His Cys Leu Ala Cys Gly Lys Ser Leu 185 190 195 Lys Thr Pro Arg Val Val Gly Gly Glu Glu Ala Ser Val Asp Ser 200 205 210 Trp Pro Trp Gin Val Ser Ile Gin Tyr Asp Lys Gin His Val Cys 215 220 225 Gly Gly Ser Ile Leu Asp Pro His Trp Val Leu Thr Ala Ala His 230 235 240 Cys Phe Arg Lys His Thr Asp Val Phe Asn Trp Lys Val Arg Ala 245 250 255 Gly Ser Asp Lys Leu Gly Ser Phe Pro Ser Leu Ala Val Ala Lys 260 265 270 Ile Ile Ile Ile Glu Phe Asn Pro Met Tyr Pro Lys Asp Asn Asp 275 280 285 Ile Ala Leu Met Lys Leu Gin Phe Pro Leu Thr Phe Ser Gly Thr 290 295 300 Val Arg Pro Ile Cys Leu Pro Phe Phe Asp Glu Glu Leu Thr Pro 305 310 315 Ala Thr Pro Leu Trp Ile Ile Gly Trp Gly Phe Thr Lys Gin Asn 320 325 330 Gly Gly Lys Met Ser Asp Ile Leu Leu Gin Ala Ser Val Gin Val 335 340 345 Ile Asp Ser Thr Arg Cys Asn Ala Asp Asp Ala Tyr Gin Gly Glu 350 355 360 Val Thr Glu Lys Met Met Cys Ala Gly Ile Pro Glu Gly Gly Val 365 370 375 Asp Thr Cys Gin Gly Asp Ser Gly Gly Pro Leu Met Tyr Gin Ser 380 385 390 736 Asp Gin Trp His Val Val Gly Ile Val Ser Trp Gly Tyr Gly Cys 395 400 405 Gly Gly Pro Ser Thr Pro Gly Val Tyr Thr Lys Val Ser Ala Tyr 410 415 420 Leu Asn Trp Ile Tyr Asn Val Trp Lys Ala Glu Leu 425 430 <210> 276 <211> 3143 <212> DNA <213> Homo sapiens <400> 276 gggctgaggc actgagagac cggaaagcct ggcattccag agggagggaa 50 acgcagcggc atccccaggc tccagagctc cctggtgaca gtctgtggct 100 gagcatggcc ctcccagccc tgggcctgga cccctggagc ctcctgggcc 150 ttttcctctt ccaactgctt cagctgctgc tgccgacgac gaccgcgggg 200 ggaggcgggc aggggcccat gcccagggtc agatactatg caggggatga 250 acgtagggca cttagcttct tccaccagaa gggcctccag gattttgaca 300 ctctgctcct gagtggtgat ggaaatactc tctacgtggg ggctcgagaa 350 gccattctgg ccttggatat ccaggatcca ggggtcccca ggctaaagaa 400 catgataccg tggccagcca gtgacagaaa aaagagtgaa tgtgccttta 450 agaagaagag caatgagaca cagtgtttca acttcatccg tgtcctggtt 500 tcttacaatg tcacccatct ctacacctgc ggcaccttcg ccttcagccc 550 tgcttgtacc ttcattgaac ttcaagattc ctacctgttg cccatctcgg 600 aggacaaggt catggaggga aaaggccaaa gcccctttga ccccgctcac 650 aagcatacgg ctgtcttggt ggatgggatg ctctattctg gtactatgaa 700 caacttcctg ggcagtgagc ccatcctgat gcgcacactg ggatcccagc 750 ctgtcctcaa gaccgacaac ttcctccgct ggctgcatca tgacgcctcc 800 tttgtggcag ccatcccttc gacccaggtc gtctacttct tcttcgagga 850 gacagccagc gagtttgact tctttgagag gctccacaca tcgcgggtgg 900 ctagagtctg caagaatgac gtgggcggcg aaaagctgct gcagaagaag 950 tggaccacct gcccttcaac tcctgaaggc gtcatccgcc ccagctgctc acgcggtcct tgcacccagc gctccccgcc cggggcagct gattctccca 1000 1050 cagctcccca catctacgca gtcttcacct cccagtggca ggttggcggg 1100 accaggagct ctgcggtttg tgccttctct ctcttggaca ttgaacgtgt 1150 ctttaagggg aaatacaaag agttgaacaa agaaacttca cgctggacta 1200 737 cttatagggg ccctgagacc aacccccggc caggcagttg ctcagtgggc 1250 ccctcctctg ataaggccct gaccttcatg aaggaccatt tcctgatgga 1300 tgagcaagtg gtggggacgc ccctgctggt gaaatctggc gtggagtata 1350 cacggcttgc agtggagaca gcccagggcc ttgatgggca cagccatctt 1400 gtcatgtacc tgggaaccac cacagggtcg ctccacaagg ctgtggtaag 1450 tggggacagc agtgctcatc tggtggaaga gattcagctg ttccctgacc 1500 ctgaacctgt tcgcaacctg cagctggccc ccacccaggg tgcagtgttt 1550 gtaggcttct caggaggtgt ctggagggtg ccccgagcca actgtagtgt 1600 ctatgagagc tgtgtggact gtgtccttgc ccgggacccc cactgtgcct 1650 gggaccctga gtcccgaacc tgttgcctcc tgtctgcccc caacctgaac 1700 tcctggaagc aggacatgga gcgggggaac ccagagtggg catgtgccag 1750 tggccccatg agcaggagcc ttcggcctca gagccgcccg caaatcatta 1800 aagaagtcct ggctgtcccc aactccatcc tggagctccc ctgcccccac 1850 ctgtcagcct tggcctctta ttattggagt catggcccag cagcagtccc 1900 agaagcctct tccactgtct acaatggctc cctcttgctg atagtgcagg 1950 atggagttgg gggtctctac cagtgctggg caactgagaa tggcttttca 2000 taccctgtga tctcctactg ggtggacagc caggaccaga ccctggccct 2050 ggatcctgaa ctggcaggca tcccccggga gcatgtgaag gtcccgttga 2100 ccagggtcag tggtggggcc gccctggctg cccagcagtc ctactggccc 2150 cactttgtca ctgtcactgt cctctttgcc ttagtgcttt caggagccct 2200 catcatcctc gtggcctccc cattgagagc actccgggct cggggcaagg 2250 ttcagggctg tgagaccctg cgccctgggg agaaggcccc gttaagcaga 2300 gagcaacacc tccagtctcc caaggaatgc aggacctctg ccagtgatgt 2350 ggacgctgac aacaactgcc taggcactga ggtagcttaa actctaggca 2400 caggccgggg ctgcggtgca ggcacctggc catgctggct gggcggccca 2450 agcacagccc tgactaggat gacagcagca caaaagacca cctttctccc 2500 ctgagaggag cttctgctac tctgcatcac tgatgacact cagcagggtg 2550 atgcacagca agctctctaa gtctgcctcc cagggtgggg cctatgggac gctaccccca tcccttctac gacctgctcc caagcacatg tacactgata 2600 2650 ttgaagaacc tggagaggat ccttcagttc tggccattcc agggaccctc 2700 cagaaacaca gtgtttcaag agaccctaaa aaacctgcct gtcccaggac 2750 738 cctatggtaa tgaacaccaa acatctaaac aatcatatgc taacatgcca 2800 ctcctggaaa ctccactctg aagctgccgc tttggacacc aacactccct 2850 tctcccaggg tcatgcaggg atctgctccc tcctgcttcc cttaccagtc 2900 gtgcaccgct gactcccagg aagtctttcc tgaagtctga ccacctttct 2950 tcttgcttca gttggggcag actctgatcc cttctgccct ggcagaatgg 3000 caggggtaat ctgagccttc ttcactcctt taccctagct gaccccttca 3050 cctctccccc tcccttttcc tttgttttgg gattcagaaa actgcttgtc 3100 agagactgtt tattttttat taaaaatata aggcttaaaa aaa 3143 <210> 277 <211> 761 <212> PRT <213> Homo sapiens <400> 277 Met Ala Leu Pro Ala Leu Gly Leu Asp Pro Trp Ser Leu Leu Gly 15 10 15 Leu Phe Leu Phe Gin Leu Leu Gin Leu Leu Leu Pro Thr Thr Thr 20 25 30 Ala Gly Gly Gly Gly Gin Gly Pro Met Pro Arg Val Arg Tyr Tyr 35 40 45 Ala Gly Asp Glu Arg Arg Ala Leu Ser Phe Phe His Gin Lys Gly 50 55 60 Leu Gin Asp Phe Asp Thr Leu Leu Leu Ser Gly Asp Gly Asn Thr 65 70 75 Leu Tyr Val Gly Ala Arg Glu Ala Ile Leu Ala Leu Asp Ile Gin 80 85 90 Asp Pro Gly Val Pro Arg Leu Lys Asn Met Ile Pro Trp Pro Ala 95 100 105 Ser Asp Arg Lys Lys Ser Glu Cys Ala Phe Lys Lys Lys Ser Asn 110 115 120 Glu Thr Gin Cys Phe Asn Phe Ile Arg Val Leu Val Ser Tyr Asn 125 130 135 Val Thr His Leu Tyr Thr Cys Gly Thr Phe Ala Phe Ser Pro Ala 140 145 150 Cys Thr Phe Ile Glu Leu Gin Asp Ser Tyr Leu Leu Pro Ile Ser 155 160 165 Glu Asp Lys Val Met Glu Gly Lys Gly Gin Ser Pro Phe Asp Pro 170 175 180 Ala His Lys His Thr Ala Val Leu Val Asp Gly Met Leu Tyr Ser 185 190 195 Gly Thr Met Asn Asn Phe Leu Gly Ser Glu Pro Ile Leu Met Arg 200 205 210 739 Thr Leu Gly Ser Gin Pro Val Leu Lys Thr Asp Asn Phe Leu Arg 215 220 225 Trp Leu His His Asp Ala Ser Phe Val Ala Ala Ile Pro Ser Thr 230 235 240 Gin Val Val Tyr Phe Phe Phe Glu Glu Thr Ala Ser Glu Phe Asp 245 250 255 Phe Phe Glu Arg Leu His Thr Ser Arg Val Ala Arg Val Cys Lys 260 265 270 Asn Asp Val Gly Gly Glu Lys Leu Leu Gin Lys Lys Trp Thr Thr 275 280 285 Phe Leu Lys Ala Gin Leu Leu Cys Thr Gin Pro Gly Gin Leu Pro 290 295 300 Phe Asn Val Ile Arg His Ala Val Leu Leu Pro Ala Asp Ser Pro 305 310 315 Thr Ala Pro His Ile Tyr Ala Val Phe Thr Ser Gin Trp Gin Val 320 325 330 Gly Gly Thr Arg Ser Ser Ala Val Cys Ala Phe Ser Leu Leu Asp 335 340 345 Ile Glu Arg Val Phe Lys Gly Lys Tyr Lys Glu Leu Asn Lys Glu 350 355 360 Thr Ser Arg Trp Thr Thr Tyr Arg Gly Pro Glu Thr Asn Pro Arg 365 370 375 Pro Gly Ser Cys Ser Val Gly Pro Ser Ser Asp Lys Ala Leu Thr 380 385 390 Phe Met Lys Asp His Phe Leu Met Asp Glu Gin Val Val Gly Thr 395 400 405 Pro Leu Leu Val Lys Ser Gly Val Glu Tyr Thr Arg Leu Ala Val 410 415 420 Glu Thr Ala Gin Gly Leu Asp Gly His Ser His Leu Val Met Tyr 425 430 435 Leu Gly Thr Thr Thr Gly Ser Leu His Lys Ala Val Val Ser Gly 440 445 450 Asp Ser Ser Ala His Leu Val Glu Glu Ile Gin Leu Phe Pro Asp 455 460 465 Pro Glu Pro Val Arg Asn Leu Gin Leu Ala Pro Thr Gin Gly Ala 470 475 480 Val Phe Val Gly Phe Ser Gly Gly Val Trp Arg Val Pro Arg Ala 485 490 495 Asn Cys Ser Val Tyr Glu Ser Cys Val Asp Cys Val Leu Ala Arg 500 505 510 Asp Pro His Cys Ala Trp Asp Pro Glu Ser Arg Thr Cys Cys Leu 515 740 520 525 Leu Ser Ala Pro Asn Leu Asn Ser Trp Lys Gin Asp Met Glu Arg 530 535 540 Gly Asn Pro Glu Trp Ala Cys Ala Ser Gly Pro Met Ser Arg Ser 545 550 555 Leu Arg Pro Gin Ser Arg Pro Gin Ile Ile Lys Glu Val Leu Ala 560 565 570 Val Pro Asn Ser Ile Leu Glu Leu Pro Cys Pro His Leu Ser Ala 575 580 585 Leu Ala Ser Tyr Tyr Trp Ser His Gly Pro Ala Ala Val Pro Glu 590 595 600 Ala Ser Ser Thr Val Tyr Asn Gly Ser Leu Leu Leu Ile Val Gin 605 610 615 Asp Gly Val Gly Gly Leu Tyr Gin Cys Trp Ala Thr Glu Asn Gly 620 625 630 Phe Ser Tyr Pro Val Ile Ser Tyr Trp Val Asp Ser Gin Asp Gin 635 640 645 Thr Leu Ala Leu Asp Pro Glu Leu Ala Gly Ile Pro Arg Glu His 650 655 660 Val Lys Val Pro Leu Thr Arg Val Ser Gly Gly Ala Ala Leu Ala 665 670 675 Ala Gin Gin Ser Tyr Trp Pro His Phe Val Thr Val Thr Val Leu 680 685 690 Phe Ala Leu Val Leu Ser Gly Ala Leu Ile Ile Leu Val Ala Ser 695 700 705 Pro Leu Arg Ala Leu Arg Ala Arg Gly Lys Val Gin Gly Cys Glu 710 715 720 Thr Leu Arg Pro Gly Glu Lys Ala Pro Leu Ser Arg Glu Gin His 725 730 735 Leu Gin Ser Pro Lys Glu Cys Arg Thr Ser Ala Ser Asp Val Asp 740 745 750 Ala Asp Asn Asn Cys Leu Gly Thr Glu Val Ala 755 760 <210> 278 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 278 ctgctggtga aatctggcgt ggag 24 <210> 279 741 <211> 24 " <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 279 gtctggtcct ggctgtccac ccag 24 <210> 280 <211> 45 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 280 catcttgtca tgtacctggg aaccaccaca gggtcgctcc acaag 45 <210> 281 <211> 2320 <212> DNA <213> Homo sapiens <400> 281 agggtccctt agccgggcgc agggcgcgca gcccaggctg agatccgcgg 50 cttccgtaga agtgagcatg gctgggcagc gagtgcttct tctagtgggc 100 ttccttctcc ctggggtcct gctctcagag gctgccaaaa tcctgacaat 150 atctacagta ggtggaagcc attatctact gatggaccgg gtttctcaga 200 ttcttcaaga tcacggtcat aatgtcacca tgcttaacca caaaagaggt 250 ccttttatgc cagattttaa aaaggaagaa aaatcatatc aagttatcag 300 ttggcttgca cctgaagatc atcaaagaga atttaaaaag agttttgatt 350 tctttctgga agaaacttta ggtggcagag gaaaatttga aaacttatta 400 aatgttctag aatacttggc gttgcagtgc agtcattttt taaatagaaa 450 ggatatcatg gattccttaa agaatgagaa cttcgacatg gtgatagttg 500 aaacttttga ctactgtcct ttcctgattg ctgagaagct tgggaagcca 550 tttgtggcca ttctttccac ttcattcggc tctttggaat ttgggctacc 600 aatccccttg tcttatgttc cagtattccg ttccttgctg actgatcaca 650 tggacttctg gggccgagtg aagaattttc tgatgttctt tagtttctgc 700 aggaggcaac agcacatgca gtctacattt gacaacacca tcaaggaaca 750 tttcacagaa ggctctaggc cagttttgtc tcatcttcta ctgaaagcag 800 agttgtggtt cttcccaaca cattaactct ctgtttatgt gactttgcct tggaggcttg ttgattttgc atggaaaaac tcgacctctg ctattaaacc 850 900 742 agtaccacaa gacttggaga acttcattgc caagtttggg gactctggtt 950 ttgtccttgt gaccttgggc tccatggtga acacctgtca gaatccggaa 1000 atcttcaagg agatgaacaa tgcctttgct cacctacccc aaggggtgat 1050 atggaagtgt cagtgttctc attggcccaa agatgtccac ctggctgcaa 1100 atgtgaaaat tgtggactgg cttcctcaga gtgacctcct ggctcaccca 1150 agcatccgtc tgtttgtcac ccacggcggg cagaatagca taatggaggc 1200 catccagcat ggtgtgccca tggtggggat ccctctcttt ggagaccagc 1250 ctgaaaacat ggtccgagta gaagccaaaa agtttggtgt ttctattcag 1300 ttaaagaagc tcaaggcaga gacattggct cttaagatga aacaaatcat 1350 ggaagacaag agatacaagt ccgcggcagt ggctgccagt gtcatcctgc 1400 gctcccaccc gctcagcccc acacagcggc tggtgggctg gattgaccac 1450 gtcctccaga cagggggcgc gacgcacctc aagccctatg tctttcagca 1500 gccctggcat gagcagtacc tgttcgacgt ttttgtgttt ctgctggggc 1550 tcactctggg gactctatgg ctttgtggga agctgctggg catggctgtc 1600 tggtggctgc gtggggccag aaaggtgaag gagacataag gccaggtgca 1650 gccttggcgg ggtctgtttg gtgggcgatg tcaccatttc tagggagctt 1700 cccactagtt ctggcagccc cattctctag tccttctagt tatctcctgt 1750 tttcttgaag aacaggaaaa atggccaaaa atcatccttt ccacttgcta 1800 attttgctac aaattcatcc ttactagctc ctgcctgcta gcagaaatct 1850 ttccagtcct cttgtcctcc tttgtttgcc atcagcaagg gctatgctgt 1900 gattctgtct ctgagtgact tggaccactg accctcagat ttccagcctt 1950 aaaatccacc ttccttctca tgcgcctctc cgaatcacac cctgactctt 2000 ccagcctcca tgtccagacc tagtcagcct ctctcactcc tgcccctact 2050 atctatcatg gaataacatc caagaaagac accttgcata ttctttcagt 2100 ttctgttttg ttctcccaca tattctcttc aatgctcagg aagcctgccc 2150 tgtgcttgag agttcagggc cggacacagg ctcacaggtc tccacattgg 2200 gtccctgtct ctggtgccca cagtgagctc cttcttggct gagcaggcat 2250 ggagactgta ggtttccaga tttcctgaaa aataaaagtt tacagcgtta 2300 tctctcccca acctcactaa 2320 <210> 282 <211> 523 <212> PRT <213> Homo sapiens 743 <400> 282 Met Ala Gly Gin Arg Val Leu Leu Leu Val Gly Phe Leu Leu Pro 15 10 15 Gly Val Leu Leu Ser Glu Ala Ala Lys Ile Leu Thr Ile Ser Thr 20 25 30 Val Gly Gly Ser His Tyr Leu Leu Met Asp Arg Val Ser Gin Ile 35 40 45 Leu Gin Asp His Gly His Asn Val Thr Met Leu Asn His Lys Arg 50 55 60 Gly Pro Phe Met Pro Asp Phe Lys Lys Glu Glu Lys Ser Tyr Gin 65 70 75 Val Ile Ser Trp Leu Ala Pro Glu Asp His Gin Arg Glu Phe Lys 80 85 90 Lys Ser Phe Asp Phe Phe Leu Glu Glu Thr Leu Gly Gly Arg Gly 95 100 105 Lys Phe Glu Asn Leu Leu Asn Val Leu Glu Tyr Leu Ala Leu Gin 110 115 120 Cys Ser His Phe Leu Asn Arg Lys Asp Ile Met Asp Ser Leu Lys 125 130 135 Asn Glu Asn Phe Asp Met Val Ile Val Glu Thr Phe Asp Tyr Cys 140 145 150 Pro Phe Leu Ile Ala Glu Lys Leu Gly Lys Pro Phe Val Ala Ile 155 160 165 Leu Ser Thr Ser Phe Gly Ser Leu Glu Phe Gly Leu Pro Ile Pro 170 175 180 Leu Ser Tyr Val Pro Val Phe Arg Ser Leu Leu Thr Asp His Met 185 190 195 Asp Phe Trp Gly Arg Val Lys Asn Phe Leu Met Phe Phe Ser Phe 200 205 210 Cys Arg Arg Gin Gin His Met Gin Ser Thr Phe Asp Asn Thr Ile 215 220 225 Lys Glu His Phe Thr Glu Gly Ser Arg Pro Val Leu Ser His Leu 230 235 240 Leu Leu Lys Ala Glu Leu Trp Phe Ile Asn Ser Asp Phe Ala Phe 245 250 255 Asp Phe Ala Arg Pro Leu Leu Pro Asn Thr Val Tyr Val Gly Gly 260 265 270 Leu Met Glu Lys Pro Ile Lys Pro Val Pro Gin Asp Leu Glu Asn 275 280 285 Phe Ile Ala Lys Phe Gly Asp Ser Gly Phe Val Leu Val Thr Leu 290 295 300 744 Gly Ser Met Val Asn Thr Cys Gin Asn Pro Glu Ile Phe Lys Glu 305 310 315 Met Asn Asn Ala Phe Ala His Leu Pro Gin Gly Val Ile Trp Lys 320 325 330 Cys Gin Cys Ser His Trp Pro Lys Asp Val His Leu Ala Ala Asn 335 340 345 Val Lys Ile Val Asp Trp Leu Pro Gin Ser Asp Leu Leu Ala His 350 355 360 Pro Ser Ile Arg Leu Phe Val Thr His Gly Gly Gin Asn Ser Ile 365 370 375 Met Glu Ala Ile Gin His Gly Val Pro Met Val Gly Ile Pro Leu 380 385 390 Phe Gly Asp Gin Pro Glu Asn Met Val Arg Val Glu Ala Lys Lys 395 400 405 Phe Gly Val Ser Ile Gin Leu Lys Lys Leu Lys Ala Glu Thr Leu 410 415 420 Ala Leu Lys Met Lys Gin Ile Met Glu Asp Lys Arg Tyr Lys Ser 425 430 435 Ala Ala Val Ala Ala Ser Val Ile Leu Arg Ser His Pro Leu Ser 440 445 450 Pro Thr Gin Arg Leu Val Gly Trp Ile Asp His Val Leu Gin Thr 455 460 465 Gly Gly Ala Thr His Leu Lys Pro Tyr Val Phe Gin Gin Pro Trp 470 475 480 His Glu Gin Tyr Leu Phe Asp Val Phe Val Phe Leu Leu Gly Leu 485 490 495 Thr Leu Gly Thr Leu Trp Leu Cys Gly Lys Leu Leu Gly Met Ala 500 505 510 Val Trp Trp Leu Arg Gly Ala Arg Lys Val Lys Glu Thr 515 520 <210> 283 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 283 tgcctttgct cacctacccc aagg 24 <210> 284 <211> 24 <212> DNA <213> Artificial Sequence <220> 745 <223> Synthetic oligonucleotide probe <400> 284 tcaggctggt ctccaaagag aggg 24 <210> 285 <211> 45 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 285 cccaaagatg tccacctggc tgcaaatgtg aaaattgtgg actgg 45 <210> 286 <211> 2340 <212> DNA <213> Homo sapiens <400> 286 gggctgttga tttgtggggg attttgaaga gaggaggaat aggaggaagg 50 ggttgagggg ctgcctctgg catatgcaca cactcacaca ttctgtcaca 100 cccgtcacac acacatacca tgttctccat ccccccaggt ccagccctca 150 gtgctgtccc atccagcagg gctaccctga agctctggct gcagccctcc 200 cgtccagtgg gcaggcggct tcatccctcc tttctctccc aaagcccaac 250 tgctgtcact gcatgctctg ccaaggagga gggaactgca gtgacagcag 300 gagtaagagt gggaggcagg acagagctgg gacacaggta tggagagggg 350 gttcagcgag cctagagagg gcagactatc agggtgccgg cggtgagaat 400 ccagggagag gagcggaaac agaagagggg cagaagaccg gggcacttgt 450 gggttgcaga gcccctcagc catgttggga gccaagccac actggctacc 500 aggtccccta cacagtcccg ggctgccctt ggttctggtg cttctggccc 550 tgggggccgg gtgggcccag gaggggtcag agcccgtcct gctggagggg 600 gagtgcctgg tggtctgtga gcctggccga gctgctgcag gggggcccgg 650 gggagcagcc ctgggagagg caccccctgg gcgagtggca tttgctgcgg 700 tccgaagcca ccaccatgag ccagcagggg aaaccggcaa tggcaccagt 750 ggggccatct acttcgacca ggtcctggtg aacgagggcg gtggctttga 800 ccgggcctct ggctccttcg tagcccctgt ccggggtgtc tacagcttcc 850 ggttccatgt ggtgaaggtg tacaaccgcc aaactgtcca ggtgagcctg 900 atgctgaaca cgtggcctgt catctcagcc tttgccaatg atcctgacgt 950 gacccgggag gcagccacca gctctgtgct actgcccttg gaccctgggg 1000 accgagtgtc tctgcgcctg cgtcggggga atctactggg tggttggaaa 1050 746 tactcaagtt tttcaagcac tctctggctt aagaatccag cctcatcttc cccctgacaa cctctctgag ctttcttctg gacccaagtc ccctctcttg 1100 1150 ccccagaaac agcagaggca ggagagagac tccctctggc tcctatccca 1200 cctctttgca tgggaccctg tgccaaacac ccaagtttaa gagaagagta 1250 gagctgtggc atctccagac caggcctttc cacccaccca cccccagtta 1300 ccctcccagc cacctgctgc atctgttcct gcctgcagcc ctaggatcag 1350 ggcaaggttt ggcaagaagg aagatctgca ctactttgcg gcctctgctc 1400 ctccggttcc cccaccccag cttcctgctc aatgctgatc agggacaggt 1450 ggcgcaggtg agcctgacag gcccccacag gagcccagat ggacaagcct 1500 cagcgtaccc tgcaggcttc ttcctgtgag gaaagccagc atcacggatc 1550 tcagccagca ccgtcagaag ctgagccagc accgtatggg ctagggtggg 1600 aggctcagcc acaggcagaa gggtgggaag ggcctggagt ctgtggctgg 1650 tgaggaagga aggagggtgt attgtctaga ctgaacatgg tacacattct 1700 gcatgtatag cagagcagcc agcaggtagc aatcctggct gtccttctat 1750 gctggatccc agatggactc tggcccttac ctccccacct gagattaggg 1800 tgagtgtgtt tgctctggct gagagcagag ctgagagcag gtatacagag 1850 ctggaagtgg accatggaaa acatcgataa ccatgcatcc tcttgcttgg 1900 ccacctcctg aaactgctcc acctttgaag tttgaacttt agtccctcca 1950 cactctgact gctgcctcct tcctcccagc tctctcactg agttatcttc 2000 actgtacctg ttccagcata tccccactat ctctctttct cctgatctgt 2050 gctgtcttat tctcctcctt aggcttccta ttacctggga ttccatgatt 2100 cattccttca gaccctctcc tgccagtatg ctaaaccctc cctctctctt 2150 tcttatcccg ctgtcccatt ggcccagcct ggatgaatct atcaataaaa 2200 caactagaga atggtggtca gtgagacact atagaattac taaggagaag 2250 atgcctctgg agtttggatc gggtgttaca ggtacaagta ggtatgttgc 2300 agaggaaaat aaatatcaaa ctgtatacta aaattaaaaa 2340 <210> 287 <211> 205 <212> PRT <213> Homo sapiens <400> 287 Met Leu Gly Ala Lys Pro His Trp Leu Pro Gly Pro Leu His Ser 15 10 15 Pro Gly Leu Pro Leu Val Leu Val Leu Leu Ala Leu Gly Ala Gly 747 25 30 Trp Ala Gin Glu Gly Ser Glu Pro Val Leu Leu Glu Gly Glu Cys 35 40 45 Leu Val Val Cys Glu Pro Gly Arg Ala Ala Ala Gly Gly Pro Gly 50 55 60 Gly Ala Ala Leu Gly Glu Ala Pro Pro Gly Arg Val Ala Phe Ala 65 70 75 Ala Val Arg Ser His His His Glu Pro Ala Gly Glu Thr Gly Asn 80 85 90 Gly Thr Ser Gly Ala Ile Tyr Phe Asp Gin Val Leu Val Asn Glu 95 100 105 Gly Gly Gly Phe Asp Arg Ala Ser Gly Ser Phe Val Ala Pro Val 110 115 120 Arg Gly Val Tyr Ser Phe Arg Phe His Val Val Lys Val Tyr Asn 125 130 135 Arg Gin Thr Val Gin Val Ser Leu Met Leu Asn Thr Trp Pro Val 140 145 150 Ile Ser Ala Phe Ala Asn Asp Pro Asp Val Thr Arg Glu Ala Ala 155 160 165 Thr Ser Ser Val Leu Leu Pro Leu Asp Pro Gly Asp Arg Val Ser 170 175 180 Leu Arg Leu Arg Arg Gly Asn Leu Leu Gly Gly Trp Lys Tyr Ser 185 190 195 Ser Phe Ser Gly Phe Leu Ile Phe Pro Leu 200 205 <210> 288 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 288 aggcagccac cagctctgtg ctac 24 <210> 289 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 289 cagagaggga agatgaggaa gccagag 27 <210> 290 <211> 42 748 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 290 ctgtgctact gcccttggac cctggggacc gagtgtctct gc 42 <210> 291 <211> 1570 <212> DNA <213> Homo sapiens <400> 291 gctgtttctc tcgcgccacc actggccgcc ggccgcagct ccaggtgtcc 50 tagccgccca gcctcgacgc cgtcccggga cccctgtgct ctgcgcgaag 100 ccctggcccc gggggccggg gcatgggcca ggggcgcggg gtgaagcggc 150 ttcccgcggg gccgtgactg ggcgggcttc agccatgaag accctcatag 200 ccgcctactc cggggtcctg cgcggcgagc gtcaggccga ggctgaccgg 250 agccagcgct ctcacggagg acctgcgctg tcgcgcgagg ggtctgggag 300 atggggcact ggatccagca tcctctccgc cptccaggac ctcttctctg 350 tcacctggct caataggtcc aaggtggaaa agcagctaca ggtcatctca 400 gtgctccagt gggtcctgtc cttccttgta ctgggagtgg cctgcagtgc 450 catcctcatg tacatattct gcactgattg ctggctcatc gctgtgctct 500 acttcacttg gctggtgttt gactggaaca cacccaagaa aggtggcagg 550 aggtcacagt gggtccgaaa ctgggctgtg tggcgctact ttcgagacta 600 ctttcccatc cagctggtga agacacacaa cctgctgacc accaggaact 650 atatctttgg ataccacccc catggtatca tgggcctggg tgccttctgc 700 aacttcagca cagaggccac agaagtgagc aagaagttcc caggcatacg 750 gccttacctg gctacactgg caggcaactt ccgaatgcct gtgttgaggg 800 agtacctgat gtctggaggt atctgccctg tcagccggga caccatagac 850 tatttgcttt caaagaatgg gagtggcaat gctatcatca tcgtggtcgg 900 gggtgcggct gagtctctga gctccatgcc tggcaagaat gcagtcaccc 950 tgcggaaccg caagggcttt gtgaaactgg ccctgcgtca tggagctgac 1000 ctggttccca tctactcctt tggagagaat gaagtgtaca agcaggtgat 1050 cttcgaggag ggctcctggg gccgatgggt ccagaagaag ttccagaaat 1100 acattggttt cgccccatgc atcttccatg gtcgaggcct cttctcctcc 1150 gacacctggg ggctggtgcc ctactccaag cccatcacca ctgttgtggg 1200 749 agagcccatc accatcccca agctggagca cccaacccag caagacatcg 1250 acctgtacca caccatgtac atggaggccc tggtgaagct cttcgacaag 13 00 cacaagacca agttcggcct cccggagact gaggtcctgg aggtgaactg 13 50 agccagcctt cggggccaat tccctggagg aaccagctgc aaatcacttt 1400 tttgctctgt aaatttggaa gtgtcatggg tgtctgtggg ttatttaaaa 1450 gaaattataa caattttgct aaaccaaaaa aaaaaaaaaa aaaaaaaaaa 1500 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1550 aaaaaaaaaa aaaaaaaaaa 157 0 <210> 292 <211> 388 <212> PRT <213> Homo sapiens <400> 292 Met Lys Thr Leu Ile Ala Ala Tyr Ser Gly Val Leu Arg Gly Glu 15 10 15 Arg Gin Ala Glu Ala Asp Arg Ser Gin Arg Ser His Gly Gly Pro 20 25 30 Ala Leu Ser Arg Glu Gly Ser Gly Arg Trp Gly Thr Gly Ser Ser 35 40 45 Ile Leu Ser Ala Leu Gin Asp Leu Phe Ser Val Thr Trp Leu Asn 50 55 60 Arg Ser Lys Val Glu Lys Gin Leu Gin Val Ile Ser Val Leu Gin 65 70 75 Trp Val Leu Ser Phe Leu Val Leu Gly Val Ala Cys Ser Ala Ile 80 85 90 Leu Met Tyr Ile Phe Cys Thr Asp Cys Trp Leu Ile Ala Val Leu 95 100 105 Tyr Phe Thr Trp Leu Val Phe Asp Trp Asn Thr E?ro Lys Lys Gly 110 115 120 Gly Arg Arg Ser Gin Trp Val Arg Asn Trp Ala Val Trp Arg Tyr 125 130 135 Phe Arg Asp Tyr Phe Pro Ile Gin Leu Val Lys Thr His Asn Leu 140 145 150 Leu Thr Thr Arg Asn Tyr Ile Phe Gly Tyr His Pro His Gly Ile 155 160 165 Met Gly Leu Gly Ala Phe Cys Asn Phe Ser Thr Glu Ala Thr Glu 170 175 180 Val Ser Lys Lys Phe Pro Gly Ile Arg Pro Tyr Leu Ala Thr Leu 185 190 195 750 Ala Gly Asn Phe Arg Met Pro Val Leu Arg Glu Tyr Leu Met Ser 200 205 210 Gly Gly Ile Cys Pro Val Ser Arg Asp Thr Ile Asp Tyr Leu Leu 215 220 225 Ser Lys Asn Gly Ser Gly Asn Ala Ile Ile Ile Val Val Gly Gly 230 235 240 Ala Ala Glu Ser Leu Ser Ser Met Pro Gly Lys Asn Ala Val Thr 245 250 255 Leu Arg Asn Arg Lys Gly Phe Val Lys Leu Ala Leu Arg His Gly 260 265 270 Ala Asp Leu Val Pro Ile Tyr Ser Phe Gly Glu Asn Glu Val Tyr 275 280 285 Lys Gin Val Ile Phe Glu Glu Gly Ser Trp Gly Arg Trp Val Gin 290 295 300 Lys Lys Phe Gin Lys Tyr Ile Gly Phe Ala Pro Cys Ile Phe His 305 310 315 Gly Arg Gly Leu Phe Ser Ser Asp Thr Trp Gly Leu Val Pro Tyr 320 325 330 Ser Lys Pro Ile Thr Thr Val Val Gly Glu Pro Ile Thr Ile Pro 335 340 345 Lys Leu Glu His Pro Thr Gin Gin Asp Ile Asp Leu Tyr His Thr 350 355 360 Met Tyr Met Glu Ala Leu Val Lys Leu Phe Asp Lys His Lys Thr 365 370 375 Lys Phe Gly Leu Pro Glu Thr Glu Val Leu Glu Val Asn 380 385 <210> 293 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 293 gctgacctgg ttcccatcta ctcc 24 <210> 294 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 294 cccacagaca cccatgacac ttcc 24 <210> 295 751 <211> 50 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 295 aagaatgaat tgtacaaagc aggtgatctt cgaggagggc tcctggggcc 50 <210> 296 <211> 3060 <212> DNA <213> Homo sapiens <400> 296 gggcggcggg atgggggccg ggggcggcgg gcgccgcact cgctgaggcc 50 ccgacgcagg gccgggccgg gcccagggcc gaggagcgcg gcggccagag 100 cggggccgcg gaggcgacgc cggggacgcc cgcgcgacga gcaggtggcg 150 gcggctgcag gcttgtccag ccggaagccc tgagggcagc tgttcccact 200 ggctctgctg accttgtgcc ttggacggct gtcctcagcg aggggccgtg 250 cacccgctcc tgagcagcgc catgggcctg ctggccttcc tgaagaccca 300 gttcgtgctg cacctgctgg tcggctttgt cttcgtggtg agtggtctgg 350 tcatcaactt cgtccagctg tgcacgctgg cgctctggcc ggtcagcaag 400 cagctctacc gccgcctcaa ctgccgcctc gcctactcac tctggagcca 450 actggtcatg ctgctggagt ggtggtcctg cacggagtgt acactgttca 500 cggaccaggc cacggtagag cgctttggga aggagcacgc agtcatcatc 550 ctcaaccaca acttcgagat cgacttcctc tgtgggtgga ccatgtgtga 600 gcgcttcgga gtgctgggga gctccaaggt cctcgctaag aaggagctgc 650 tctacgtgcc cctcatcggc tggacgtggt actttctgga gattgtgttc 700 tgcaagcgga agtgggagga ggaccgggac accgtggtcg aagggctgag 750 gcgcctgtcg gactaccccg agtacatgtg gtttctcctg tactgcgagg 800 ggacgcgctt cacggagacc aagcaccgcg ttagcatgga ggtggcggct 850 gctaaggggc ttcctgtcct caagtaccac ctgctgccgc ggaccaaggg 900 cttcaccacc gcagtcaagt gcctccgggg gacagtcgca gctgtctatg 950 atgtaaccct gaacttcaga ggaaacaaga acccgtccct gctggggatc 1000 ctctacggga agaagtacga ggcggacatg tgcgtgagga gatttcctct 1050 ggaagacatc ccgctggatg aaaaggaagc agctcagtgg cttcataaac 1100 tgtaccagga gaaggacgcg ctccaggaga tatataatca gaagggcatg 1150 752 tttccagggg agcagtttaa gcctgcccgg aggccgtgga ccctcctgaa 1200 cttcctgtcc tgggccacca ttctcctgtc tcccctcttc agttttgtct 1250 tgggcgtctt tgccagcgga tcacctctcc tgatcctgac tttcttgggg 1300 tttgtgggag cagcttcctt tggagttcgc agactgatag gagaatcgct 1350 tgaacctggg aggtggagat tgcagtgagc tgagatggca tcactgtact 1400 ccagcctagg caacagagca agactcagtc tcaaaaaaaa aaaaaaacaa 1450 aaaaacccca gaaattctgg agttgaactg tgtagttact gacatgaaaa 1500 attcactaga ggctgaacag cagatttgag caggcagaaa aaaatcagca 1550 agcttgaaga tggtaccttg agatttttca ggctaatgaa aaaagaatga 1600 aggaaaatta acagcctcag agacccatgg tgcaccgtca cacaaatcaa 1650 catatgcatg atgagagtcc cagaaggaga ggagagaaag ggtcagaaag 1700 aatggccaca agctgatgaa aaacagtaac ctacccactc aggaagctca 1750 gtgaactcca atgaggatga atatcagaga tccacaccta gatatttcat 1800 aatcaaagtg tcaaatgaca aagaatcttg aaagcagcaa gagatgagca 1850 acttatcttg ttcaaaggat ctttgatcag attaacagct catttctcct 1900 cagaaatcat gggagccagg agatagtggg atgaacactg ttgaaggcaa 1950 aaccttcaac tgtaattatt ggacttttga gtcttagatg gtcctgacct 2000 ctttgtcttc agggacagtt tttcaattta atccctaata acaattagtc 2050 aagcttcctt gacctgtagg aaggcctgtc tttaggccgg gcacagtggc 2100 ttacacctgt aatcccagca ctttgggagg cccagacggg tggatcattt 2150 ggggtcaggc tgatctcaaa ctcctgagtt caggtgatct gcccgcctca 2200 gcctcccaaa gtgttgtgat tgcaggcgtg agccactgcg cctggccgga 2250 atttcttttt aaggctgaat gatgggggcc aggcacgatg gctcacgcct 2300 gtgatcccaa gtagcttgga ttgtaaacat gcaccaccat gcctggctaa 2350 tttttgtatt tttagtagag acgtgttagc caggctggtc tcgatctcct 2400 gacctcaagt gaccacctgc ctcagcctcc caaagtactg ggattacagg 2450 cgtgagccac tgtgcctggc cttgagcatc ttgtgatgtg cttattggcc 2500 atttgtatat cttctatctt ctttggggaa atgtctgttc aagtcctttg 2550 cctttttaaa tttttattat ttatttattt atttattttg agacagggtc 2600 ttgttctgtt gcccaggctg gagtacagtg gcacagtctt ggctcactgc 2650 agcctcgacc tcctgggctg cagtgatcct cccacctcag cctcccttgt 2700 753 agctgtattt ttttgtattt tgtattttgt agctgtagtt tttgtatttt 2750 ttgtggagac agcatttcac catgatgccc aggctggtct tgaactcctg 2800 agctcaagtg atctgcctgc ttcagcctcc caaagtgctg ggattacaga 2850 catgagccac tgcacctggc aaactcccaa aattcaacac acacacacaa 2900 aaaaccacct gattcaaaat gggcagaggg gccgggtgtg gccccaacta 2950 ccagggagac tgaagtggga ggatcgcttg ggcatgagaa gtcgaggctg 3000 cagtgagtcg aggttgtgcg actgcattcc agcctggaca acagagtgag 3050 accctgtctc 3060 <210> 297 <211> 368 <212> PRT <213> Homo sapiens <400> 297 Met Gly Leu Leu Ala Phe Leu Lys Thr Gin Phe Val Leu His Leu 15 10 15 Leu Val Gly Phe Val Phe Val Val Ser Gly Leu Val Ile Asn Phe 20 25 30 Val Gin Leu Cys Thr Leu Ala Leu Trp Pro Val Ser Lys Gin Leu 35 40 45 Tyr Arg Arg Leu Asn Cys Arg Leu Ala Tyr Ser Leu Trp Ser Gin 50 55 60 Leu Val Met Leu Leu Glu Trp Trp Ser Cys Thr Glu Cys Thr Leu 65 70 75 Phe Thr Asp Gin Ala Thr Val Glu Arg Phe Gly Lys Glu His Ala 80 85 90 Val Ile Ile Leu Asn His Asn Phe Glu Ile Asp Phe Leu Cys Gly 95 100 105 Trp Thr Met Cys Glu Arg Phe Gly Val Leu Gly Ser Ser Lys Val 110 115 120 Leu Ala Lys Lys Glu Leu Leu Tyr Val Pro Leu Ile Gly Trp Thr 125 130 135 Trp Tyr Phe Leu Glu Ile Val Phe Cys Lys Arg Lys Trp Glu Glu 140 145 150 Asp Arg Asp Thr Val Val Glu Gly Leu Arg Arg Leu Ser Asp Tyr 155 160 165 Pro Glu Tyr Met Trp Phe Leu Leu Tyr Cys Glu Gly Thr Arg Phe 170 175 180 Thr Glu Thr Lys His Arg Val Ser Met Glu Val Ala Ala Ala Lys 185 190 195 Gly Leu Pro Val Leu Lys Tyr His Leu Leu Pro Arg Thr Lys Gly 200 205 210 754 Phe Thr Thr Ala Val Lys Cys Leu Arg Gly Thr Val Ala Ala Val 215 220 225 Tyr Asp Val Thr Leu Asn Phe Arg Gly Asn Lys Asn Pro Ser Leu 230 235 240 Leu Gly Ile Leu Tyr Gly Lys Lys Tyr Glu Ala Asp Met Cys Val 245 250 255 Arg Arg Phe Pro Leu Glu Asp Ile Pro Leu Asp Glu Lys Glu Ala 260 265 270 Ala Gin Trp Leu His Lys Leu Tyr Gin Glu Lys Asp Ala Leu Gin 275 280 285 Glu Ile Tyr Asn Gin Lys Gly Met Phe Pro Gly Glu Gin Phe Lys 290 295 300 Pro Ala Arg Arg Pro Trp Thr Leu Leu Asn Phe Leu Ser Trp Ala 305 310 315 Thr Ile Leu Leu Ser Pro Leu Phe Ser Phe Val Leu Gly Val Phe 320 325 330 Ala Ser Gly Ser Pro Leu Leu Ile Leu Thr Phe Leu Gly Phe Val 335 340 345 Gly Ala Ala Ser Phe Gly Val Arg Arg Leu Ile Gly Glu Ser Leu 350 355 360 Glu Pro Gly Arg Trp Arg Leu Gin 365 <210> 298 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 298 cttcctctgt gggtggacca tgtg 24 <210> 299 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 299 gccacctcca tgctaacgcg g 21 <210> 300 <211> 45 <212> DNA <213> Artificial Sequence <220> 755 <223> Synthetic oligonucleotide probe <400> 300 ccaaggtcct cgctaagaag gagctgctct acgtgcccct catcg 45 <210> 301 <211> 1334 <212> DNA <213> Homo sapiens <400> 301 gatattcttt atttttaaga atctgaagta ctatgcatca ctccctccaa 50 tgtcctgggg cagccaccag gcatattcat ctttgtgtgt gtttttcttt 100 tgctttagca ctggggcact tcttgcttat ttctttggta ggaaaggggc 150 tcagtttgtc ttgtggggtt ggtggcaggc aggccggctt acgcctgata 200 cggccctggg ttagaaggga agggaagata aacttttata caaatgggga 250 tagctggggt ctgagacctg cttcctcagt aaaattcctg ggatctgcct 300 ataccttctt ttctctaacc tggcataccc tgcttaaagc ctctcagggc 350 ttctctctgt tcttaggatc aaagtattta gagctacaag agccctcatg 400 gtctggcccc tgcccccctg gccagcttca ttgtacatgt ggtgttctct 450 tgtcgttcct gtaatgtggt atgccatggg gtctttgcac aagcctttcc 500 tctttggctg gacactgttc cctgcccccc ccatactctt cctacttaat 550 atgtagtcat cctgcagatt tcaattctaa catcattttc tccagggatc 600 ctggcctgac agaatctcat cttgtttaat gctctcataa gaccacttgt 650 ttcccttttg cagcacttgc cactcagttg tatctttatg tgcgtttgtg 700 gttgtatggg ttgtgtctgt tccccagaat gcccagctct gagctgcgtg 750 agggtcaagg gcattgctgt gcctgccagg tatagtgcct acatgtggtg 800 ggtgctcatg ttttagagac taaatggagg aggagatgag gaaaagattg 850 aaatctctca gttcaccaga tggtgtaggg cccagcattg taaattcaca 900 cgttgactgt gcttgtgaat tatctgggga tgcaggtcct gattcagtag 950 gcccaggttg ggcatctcta acaaactccc acgtgatgct gatgctggtc 1000 ctatgaacta tactaaatag taagaatcta tggagccagg ctgggcatgg 1050 tggctcacac ctatgatccc agcactttgg gaggctgagg caggctgatc 1100 acctggagtc aggatttcaa gactagcctg gccaacatgg tggaacccca 1150 tctgtactaa aaatacacaa attagctggg catggtggca catgcctgta 1200 gtcccagcta cttgggaggc tgaagcaaga gaatcgcttg aacctgggag 1250 gcggaggttg cagtgagccg agatcaggcc actgtattcc aaccagggtg 1300 756 acagagtgag actctatgtc caaaaaaaaa aaaa 1334 <210> 302 <211> 143 <212> PRT <213> Homo sapiens <400> 302 Met His His Ser Leu Gin Cys Pro Gly Ala Ala Thr Arg His Ile 15 10 15 His Leu Cys Val Cys Phe Ser Phe Ala Leu Ala Leu Gly His Phe 20 25 30 Leu Leu Ile Ser Leu Val Gly Lys Gly Leu Ser Leu Ser Cys Gly 35 40 45 Val Gly Gly Arg Gin Ala Gly Leu Arg Leu Ile Arg Pro Trp Val 50 55 60 Arg Arg Glu Gly Lys Ile Asn Phe Tyr Thr Asn Gly Asp Ser Trp 65 70 75 Gly Leu Arg Pro Ala Ser Ser Val Lys Phe Leu Gly Ser Ala Tyr 80 85 90 Thr Phe Phe Ser Leu Thr Trp His Thr Leu Leu Lys Ala Ser Gin 95 100 105 Gly Phe Ser Leu Phe Leu Gly Ser Lys Tyr Leu Glu Leu Gin Glu 110 115 120 Pro Ser Trp Ser Gly Pro Cys Pro Pro Gly Gin Leu His Cys Thr 125 130 135 Cys Gly Val Leu Leu Ser Phe Leu 140 <210> 303 <211> 1768 <212> DNA <213> Homo sapiens <400> 303 ggctggactg gaactcctgg tcccaagtga tccacccgcc tcagcctccc 50 aaggtgctgt gattataggt gtaagccacc gtgtctggcc tctgaacaac 100 tttttcagca actaaaaaag ccacaggagt tgaactgcta ggattctgac 150 tatgctgtgg tggctagtgc tcctactcct acctacatta aaatctgttt 200 tttgttctct tgtaactagc ctttaccttc ctaacacaga ggatctgtca 250 ctgtggctct ggcccaaacc tgaccttcac tctggaacga gaacagaggt 300 ttctacccac accgtcccct cgaagccggg gacagcctca ccttgctggc 350 ctctcgctgg agcagtgccc tcaccaactg tctcacgtct ggaggcactg 400 actcgggcag tgcaggtagc tgagcctctt ggtagctgcg gctttcaagg 450 757 tgggccttgc cctggccgta gaagggattg acaagcccga agatttcata 500 ggcgatggct cccactgccc aggcatcagc cttgctgtag tcaatcactg 550 ccctggggcc aggacgggcc gtggacacct gctcagaagc agtgggtgag 600 acatcacgct gcccgcccat ctaacctttt catgtcctgc acatcacctg 650 atccatgggc taatctgaac tctgtcccaa ggaacccaga gcttgagtga 700 gctgtggctc agacccagaa ggggtctgct tagaccacct ggtttatgtg 750 acaggacttg cattctcctg gaacatgagg gaacgccgga ggaaagcaaa 800 gtggcaggga aggaacttgt gccaaattat gggtcagaaa agatggaggt 850 gttgggttat cacaaggcat cgagtctcct gcattcagtg gacatgtggg 900 ggaagggctg ccgatggcgc atgacacact cgggactcac ctctggggcc 950 atcagacagc cgtttccgcc ccgatccacg taccagctgc tgaagggcaa 1000 ctgcaggccg atgctctcat cagccaggca gcagccaaaa tctgcgatca 1050 ccagccaggg gcagccgtct gggaaggagc aagcaaagtg accatttctc 1100 ctcccctcct tccctctgag aggccctcct atgtccctac taaagccacc 1150 agcaagacat agctgacagg ggctaatggc tcagtgttgg cccaggaggt 1200 cagcaaggcc tgagagctga tcagaagggc ctgctgtgcg aacacggaaa 1250 tgcctccagt aagcacaggc tgcaaaatcc ccaggcaaag gactgtgtgg 1300 ctcaatttaa atcatgttct agtaattgga gctgtcccca agaccaaagg 1350 agctagagct tggttcaaat gatctccaag ggcccttata ccccaggaga 1400 ctttgatttg aatttgaaac cccaaatcca aacctaagaa ccaggtgcat 1450 taagaatcag ttattgccgg gtgtggtggc ctgtaatgcc aacattttgg 1500 gaggccgagg cgggtagatc acctgaggtc aggagttcaa gaccagcctg 1550 gccaacatgg tgaaacccct gtctctacta aaaatacaaa aaaactagcc 1600 aggcatggtg gtgtgtgcct gtatcccagc tactcgggag gctgagacag 1650 gagaattact tgaacctggg aggtgaagga ggctgagaca ggagaatcac 1700 ttcagcctga gcaacacagc gagactctgt ctcagaaaaa ataaaaaaag 1750 aattatggtt atttgtaa 1768 <210> 304 <211> 109 <212> PRT <213> Homo sapiens <400> 304 Met Leu Trp Trp Leu Val Leu Leu Leu Leu Pro Thr Leu Lys Ser 1 5 Val Phe Cys Ser Leu 20 Asp Leu Ser Leu Trp 35 Thr Arg Thr Glu Val 50 Thr Ala Ser Pro Cys 65 Thr Val Ser Arg Leu 80 Glu Pro Leu Gly Ser 95 Arg Arg Arg Asp <210> 305 <211> 989 <212> DNA <213> Homo sapiens <400> 305 gcgggcccgc gagtccgaga cctgtcccag gagctccagc tcacgtgacc 50 tgtcactgcc tcccgccgcc tcctgcccgc gccatgaccc agccggtgcc 100 ccggctctcc gtgcccgccg cgctggccct gggctcagcc gcactgggcg 150 ccgccttcgc cactggcctc ttcctgggga ggcggtgccc cccatggcga 200 ggccggcgag agcagtgcct gcttcccccc gaggacagcc gcctgtggca 250 gtatcttctg agccgctcca tgcgggagca cccggcgctg cgaagcctga 300 ggctgctgac cctggagcag ccgcaggggg attctatgat gacctgcgag 350 caggcccagc tcttggccaa cctggcgcgg ctcatccagg ccaagaaggc 400 gctggacctg ggcaccttca cgggctactc cgccctggcc ctggccctgg 450 cgctgcccgc ggacgggcgc gtggtgacct gcgaggtgga cgcgcagccc 500 ccggagctgg gacggcccct gtggaggcag gccgaggcgg agcacaagat 550 cgacctccgg ctgaagcccg ccttggagac cctggacgag ctgctggcgg 600 cgggcgaggc cggcaccttc gacgtggccg tggtggatgc ggacaaggag 650 aactgctccg cctactacga gcgctgcctg cagctgctgc gacccggagg 700 catcctcgcc gtcctcagag tcctgtggcg cgggaaggtg ctgcaacctc 750 cgaaagggga cgtggcggcc gagtgtgtgc gaaacctaaa cgaacgcatc 800 cggcgggacg tcagggtcta catcagcctc ctgcccctgg gcgatggact 850 758 Val Thr Ser Leu Tyr Leu Pro Asn Thr Glu 25 30 Leu Trp Pro Lys Pro Asp Leu His Ser Gly 40 45 Ser Thr His Thr Val Pro Ser Lys Pro Gly 55 60 Trp Pro Leu Ala Gly Ala Val Pro Ser Pro 70 75 Glu Ala Leu Thr Arg Ala Val Gin Val Ala 85 90 Cys Gly Phe Gin Gly Gly Pro Cys Pro Gly 100 105 759 caccttggcc ttcaagatct agggctggcc cctagtgagt gggctcgagg 900 gagggttgcc tgggaacccc aggaattgac cctgagtttt aaattcgaaa 950 ataaagtggg gctgggacac aaaaaaaaaa aaaaaaaaa 989 <210> 306 <211> 262 <212> PRT <213> Homo sapiens <400> 306 Met Thr Gin Pro Val Pro Arg Leu Ser Val Pro Ala Ala Leu Ala 15 10 15 Leu Gly Ser Ala Ala Leu Gly Ala Ala Phe Ala Thr Gly Leu Phe 20 25 30 Leu Gly Arg Arg Cys Pro Pro Trp Arg Gly Arg Arg Glu Gin Cys 35 40 45 Leu Leu Pro Pro Glu Asp Ser Arg Leu Trp Gin Tyr Leu Leu Ser 50 55 60 Arg Ser Met Arg Glu His Pro Ala Leu Arg Ser Leu Arg Leu Leu 65 70 75 Thr Leu Glu Gin Pro Gin Gly Asp Ser Met Met Thr Cys Glu Gin 80 85 90 Ala Gin Leu Leu Ala Asn Leu Ala Arg Leu Ile Gin Ala Lys Lys 95 100 105 Ala Leu Asp Leu Gly Thr Phe Thr Gly Tyr Ser Ala Leu Ala Leu 110 115 120 Ala Leu Ala Leu Pro Ala Asp Gly Arg Val Val Thr Cys Glu Val 125 130 135 Asp Ala Gin Pro Pro Glu Leu Gly Arg Pro Leu Trp Arg Gin Ala 140 145 150 Glu Ala Glu His Lys Ile Asp Leu Arg Leu Lys Pro Ala Leu Glu 155 160 165 Thr Leu Asp Glu Leu Leu Ala Ala Gly Glu Ala Gly Thr Phe Asp 170 175 180 Val Ala Val Val Asp Ala Asp Lys Glu Asn Cys Ser Ala Tyr Tyr 185 190 195 Glu Arg Cys Leu Gin Leu Leu Arg Pro Gly Gly Ile Leu Ala Val 200 205 210 Leu Arg Val Leu Trp Arg Gly Lys Val Leu Gin Pro Pro Lys Gly 215 220 225 Asp Val Ala Ala Glu Cys Val Arg Asn Leu Asn Glu Arg Ile Arg 230 235 240 Arg Asp Val Arg Val Tyr Ile Ser Leu Leu Pro Leu Gly Asp Gly 245 250 255 760 Leu Thr Leu Ala Phe Lys Ile 260 <210> 307 <211> 2272 <212> DNA <213> Homo sapiens <400> 307 ccgccgccgc agccgctacc gccgctgcag ccgctttccg cggcctgggc 50 ctctcgccgt cagcatgcca cacgccttca agcccgggga cttggtgttc 100 gctaagatga agggctaccc tcactggcct gccaggatcg acgacatcgc 150 ggatggcgcc gtgaagcccc cacccaacaa gtaccccatc tttttctttg 200 gcacacacga aacagccttc ctgggaccca aggacctgtt cccctacgac 250 aaatgtaaag acaagtacgg gaagcccaac aagaggaaag gcttcaatga 300 agggctgtgg gagatccaga acaaccccca cgccagctac agcgcccctc 350 cgccagtgag ctcctccgac agcgaggccc ccgaggccaa ccccgccgac 400 ggcagtgacg ctgacgagga cgatgaggac cggggggtca tggccgtcac 450 agcggtaacc gccacagctg ccagcgacag gatggagagc gactcagact 500 cagacaagag tagcgacaac agtggcctga agaggaagac gcctgcgcta 550 aagatgtcgg tctcgaaacg agcccgaaag gcctccagcg acctggatca 600 ggccagcgtg tccccatccg aagaggagaa ctcggaaagc tcatctgagt 650 cggagaagac cagcgaccag gacttcacac ctgagaagaa agcagcggtc 700 cgggcgccac ggaggggccc tctgggggga cggaaaaaaa agaaggcgcc 750 gtcagcctcc gactccgact ccaaggccga ttcggacggg gccaagcctg 800 agccggtggc catggcgcgg tcggcgtcct cctcctcctc ttcctcctcc 850 tcctccgact ccgatgtgtc tgtgaagaag cctccgaggg gcaggaagcc 900 agcggagaag cctctcccga agccgcgagg gcggaaaccg aagcctgaac 950 ggcctccgtc cagctccagc agtgacagtg acagcgacga ggtggaccgc 1000 atcagtgagt ggaagcggcg ggacgaggcg cggaggcgcg agctggaggc 1050 ccggcggcgg cgagagcagg aggaggagct gcggcgcctg cgggagcagg 1100 agaaggagga gaaggagcgg aggcgcgagc gggccgaccg cggggaggct 1150 gagcggggca gcggcggcag cagcggggac gagctcaggg aggacgatga 1200 gcccgtcaag aagcggggac gcaagggccg gggccggggt cccccgtcct 1250 cctctgactc cgagcccgag gccgagctgg agagagaggc caagaaatca 1300 761 gcgaagaagc cgcagtcctc aagcacagag cccgccagga aacctggcca 1350 gaaggagaag agagtgcggc ccgaggagaa gcaacaagcc aagcccgtga 1400 aggtggagcg gacccggaag cggtccgagg gcttctcgat ggacaggaag 1450 gtagagaaga agaaagagcc ctccgtggag gagaagctgc agaagctgca 1500 cagtgagatc aagtttgccc taaaggtcga cagcccggac gtgaagaggt 1550 gcctgaatgc cctagaggag ctgggaaccc tgcaggtgac ctctcagatc 1600 ctccagaaga acacagacgt ggtggccacc ttgaagaaga ttcgccgtta 1650 caaagcgaac aaggacgtaa tggagaaggc agcagaagtc tatacccggc 1700 tcaagtcgcg aaggctggga ggtcctcggc tggagaagga ccaaagatcg gaaggccgag aggcggtgca gagaagctgg gaaagtgaac ccggggagga 1750 1800 gctggccggg gaggaggccc cccaggagaa ggcggaggac aagcccagca 1850 ccgatctctc agccccagtg aatggcgagg ccacatcaca gaagggggag 1900 agcgcagagg acaaggagca cgaggagggt cgggactcgg aggaggggcc 1950 aaggtgtggc tcctctgaag acctgcacga cagcgtacgg gagggtcccg 2000 acctggacag gcctgggagc gaccggcagg agcgcgagag ggcacggggg 2050 gactcggagg ccctggacga ggagagctga gccgcgggca gccaggccca 2100 gcccccgccc gagctcaggc tgcccctctc cttccccggc tcgcaggaga 2150 gcagagcaga gaactgtggg gaacgctgtg ctgtttgtat ttgttccctt 2200 gggttttttt ttcctgccta atttctgtga tttccaacca acatgaaatg 2250 actataaacg gttttttaat ga 2272 <210> 308 <211> 671 <212> PRT <213> Homo sapiens <400> 308 Met Pro His Ala Phe Lys Pro Gly Asp Leu Val Phe Ala Lys Met 15 10 15 Lys Gly Tyr Pro His Trp Pro Ala Arg Ile Asp Asp Ile Ala Asp 20 25 30 Gly Ala Val Lys Pro Pro Pro Asn Lys Tyr Pro Ile Phe Phe Phe 35 40 45 Gly Thr His Glu Thr Ala Phe Leu Gly Pro Lys Asp Leu Phe Pro 50 55 60 Tyr Asp Lys Cys Lys Asp Lys Tyr Gly Lys Pro Asn Lys Arg Lys 65 70 75 Gly Phe Asn Glu Gly Leu Trp Glu Ile Gin Asn Asn Pro His Ala 80 85 90 762 Ser Tyr Ser Ala Pro Pro Pro Val Ser Ser Ser Asp Ser Glu Ala 95 100 105 Pro Glu Ala Asn Pro Ala Asp Gly Ser Asp Ala Asp Glu Asp Asp 110 115 120 Glu Asp Arg Gly Val Met Ala Val Thr Ala Val Thr Ala Thr Ala 125 130 135 Ala Ser Asp Arg Met Glu Ser Asp Ser Asp Ser Asp Lys Ser Ser 140 145 150 Asp Asn Ser Gly Leu Lys Arg Lys Thr Pro Ala Leu Lys Met Ser 155 160 165 Val Ser Lys Arg Ala Arg Lys Ala Ser Ser Asp Leu Asp Gin Ala 170 175 180 Ser Val Ser Pro Ser Glu Glu Glu Asn Ser Glu Ser Ser Ser Glu 185 190 195 Ser Glu Lys Thr Ser Asp Gin Asp Phe Thr Pro Glu Lys Lys Ala 200 205 210 Ala Val Arg Ala Pro Arg Arg Gly Pro Leu Gly Gly Arg Lys Lys 215 220 225 Lys Lys Ala Pro Ser Ala Ser Asp Ser Asp Ser Lys Ala Asp Ser 230 235 240 Asp Gly Ala Lys Pro Glu Pro Val Ala Met Ala Arg Ser Ala Ser 245 250 255 Ser Ser Ser Ser Ser Ser Ser Ser Ser Asp Ser Asp Val Ser Val 260 265 270 Lys Lys Pro Pro Arg Gly Arg Lys Pro Ala Glu Lys Pro Leu Pro 275 280 285 Lys Pro Arg Gly Arg Lys Pro Lys Pro Glu Arg Pro Pro Ser Ser 290 295 300 Ser Ser Ser Asp Ser Asp Ser Asp Glu Val Asp Arg Ile Ser Glu 305 310 315 Trp Lys Arg Arg Asp Glu Ala Arg Arg Arg Glu Leu Glu Ala Arg 320 325 330 Arg Arg Arg Glu Gin Glu Glu Glu Leu Arg Arg Leu Arg Glu Gin 335 340 345 Glu Lys Glu Glu Lys Glu Arg Arg Arg Glu Arg Ala Asp Arg Gly 350 355 360 Glu Ala Glu Arg Gly Ser Gly Gly Ser Ser Gly Asp Glu Leu Arg 365 370 375 Glu Asp Asp Glu Pro Val Lys Lys Arg Gly Arg Lys Gly Arg Gly 380 385 390 Arg Gly Pro Pro Ser Ser Ser Asp Ser Glu Pro Glu Ala Glu Leu 395 400 405 763 Glu Arg Glu Ala Lys Lys Ser Ala Lys Lys Pro Gin Ser Ser Ser 410 415 420 Thr Glu Pro Ala Arg Lys Pro Gly Gin Lys Glu Lys Arg Val Arg 425 430 435 Pro Glu Glu Lys Gin Gin Ala Lys Pro Val Lys Val Glu Arg Thr 440 445 450 Arg Lys Arg Ser Glu Gly Phe Ser Met Asp Arg Lys Val Glu Lys 455 460 465 Lys Lys Glu Pro Ser Val Glu Glu Lys Leu Gin Lys Leu His Ser 470 475 480 Glu Ile Lys Phe Ala Leu Lys Val Asp Ser Pro Asp Val Lys Arg 485 490 495 Cys Leu Asn Ala Leu Glu Glu Leu Gly Thr Leu Gin Val Thr Ser 500 505 510 Gin Ile Leu Gin Lys Asn Thr Asp Val Val Ala Thr Leu Lys Lys 515 520 525 Ile Arg Arg Tyr Lys Ala Asn Lys Asp Val Met Glu Lys Ala Ala 530 535 540 Glu Val Tyr Thr Arg Leu Lys Ser Arg Val Leu Gly Pro Lys Ile 545 550 555 Glu Ala Val Gin Lys Val Asn Lys Ala Gly Met Glu Lys Glu Lys 560 565 570 Ala Glu Glu Lys Leu Ala Gly Glu Glu Leu Ala Gly Glu Glu Ala 575 580 585 Pro Gin Glu Lys Ala Glu Asp Lys Pro Ser Thr Asp Leu Ser Ala 590 595 600 Pro Val Asn Gly Glu Ala Thr Ser Gin Lys Gly Glu Ser Ala Glu 605 610 615 Asp Lys Glu His Glu Glu Gly Arg Asp Ser Glu Glu Gly Pro Arg 620 625 630 Cys Gly Ser Ser Glu Asp Leu His Asp Ser Val Arg Glu Gly Pro 635 640 645 Asp Leu Asp Arg Pro Gly Ser Asp Arg Gin Glu Arg Glu Arg Ala 650 655 660 Arg Gly Asp Ser Glu Ala Leu Asp Glu Glu Ser 665 670 <210> 309 <211> 3871 <212> DNA <213> Homo sapiens <400> 309 gttggttctc ctggatcttc accttaccaa ctgcagatct tgggactcat 50 764 cagcctcaat aattatatta aattaacacc atttgaaaga gaacattgtt 100 ttcatcatga atgctaataa agatgaaaga cttaaagcca gaagccaaga 150 ttttcacctt tttcctgctt tgatgatgct aagcatgacc atgttgtttc 200 ttccagtcac tggcactttg aagcaaaata ttccaagact caagctaacc 250 tacaaagact tgctgctttc aaatagctgt attccctttt tgggttcatc 300 agaaggactg gattttcaaa ctcttctctt agatgaggaa agaggcaggc 350 tgctcttggg agccaaagac cacatctttc tactcagtct ggttgactta 400 aacaaaaatt ttaagaagat ttattggcct gctgcaaagg aacgggtgga 450 attatgtaaa ttagctggga aagatgccaa tacagaatgt gcaaatttca 500 tcagagtact ggagcatttc tcagccctat atccaatatg aacaaaactc tgggtatatt acatatatgt gatcttggag gtgtggaact tctacaagga 550 600 ggatattata ttcaaactag acacacataa tttggagtct ggcagactga 650 aatgtccttt cgatcctcag cagccttttg cttcagtaat gacagatgag 700 tacctctact ctggaacagc ttctgatttc cttggcaaag atactgcatt 750 cactcgatcc cttgggccta ctcatgacca ccactacatc agaactgaca 800 tttcagagca ctactggctc aatggagcaa aatttattgg aactttcttc 850 ataccagaca cctacaatcc agatgatgat aaaatatatt tcttctttcg 900 tgaatcatct caagaaggca gtacctccga taaaaccatc ctttctcgag 950 ttggaagagt ttgtaagaat gatgtaggag gacaacgcag cctgataaac 1000 aagtggacga cttttcttaa ggccagactg atttgctcaa ttcctggaag 1050 tgatggggca gatacttact ttgatgagct tcaagatatt tatttactcc 1100 ccacaagaga tgaaagaaat cctgtagtat atggagtctt tactacaacc 1150 agctccatct tcaaaggctc tgctgtttgt gtgtatagca tggctgacat 1200 cagagcagtt tttaatggtc catatgctca taaggaaagt gcagaccatc 1250 gttgggtgca gtatgatggg agaattcctt atccacggcc tggtacatgt 1300 ccaagcaaaa cctatgaccc actgattaag tccacccgag attttccaga 1350 tgatgtcatc agtttcataa agcggcactc tgtgatgtat aagtccgtat 1400 acccagttgc aggaggacca acgttcaaga gaatcaatgt ggattacaga 1450 ctgacacaga tagtggtgga tcatgtcatt gcagaagatg gccagtacga 1500 tgtaatgttt cttggaacag acattggaac tgtcctcaaa gttgtcagca 1550 tttcaaagga aaagtggaat atggaagagg tagtgctgga ggagttgcag 1600 765 atattcaagc actcatcaat catcttgaac atggaattgt ctctgaagca 1650 gcaacaattg tacattggtt cccgagatgg attagttcag ctctccttgc 1700 acagatgcga cacttatggg aaagcttgcg cagactgttg tcttgccaga 1750 gacccctact gtgcctggga tggaaatgca tgctctcgat atgctcctac 1800 ttctaaaagg agagctagac gccaagatgt aaaatatggc gacccaatca 1850 cccagtgctg ggacatcgaa gacagcatta gtcatgaaac tgctgatgaa 1900 aaggtgattt ttggcattga atttaactca acctttctgg aatgtatacc 1950 taaatcccaa caagcaacta ttaaatggta tatccagagg tcaggggatg 2000 agcatcgaga ggagttgaag cccgatgaaa gaatcatcaa aacggaatat 2050 gggctactga ttcgaagttt gcagaagaag gattctggga tgtattactg 2100 caaagcccag atgtcattga gagcacactt gaatgaacag tcatccacac atggaaaata catagtgaag cccagagggc ctgactttga agagcatgag 2150 2200 gaggggcagg tcaaggatct attggctgag tcacggttga gatacaaaga 2250 ctacatccaa atccttagca gcccaaactt cagcctcgac cagtactgcg 2300 aacagatgtg gcacagggag aagcggagac agagaaacaa ggggggccca 2350 aagtggaagc acatgcagga aatgaagaag aaacgaaatc gaagacatca 2400 cagagacctg gatgagctcc ctagagctgt agccacgtag ttttctactt 2450 aatttaaaga aaagaattcc ttacctataa aaacattgcc ttctgttttg 2500 tatatccctt atagtaattc ataaatgctt cccatggagt tttgctaagg 2550 cacaagacaa taatctgaat aagacaatat gtgatgaata taagaaaggg 2600 caaaaaattc atttgaacca gttttccaag aacaaatctt gcacaagcaa 2650 agtataagaa ttatcctaaa aatagggggt ttacagttgt aaatgtttta 2700 tgttttgagt tttggaattt attgtcatgt aaatagttga gctaagcaag 2750 ccccgaattt gatagtgtat aaggtgcttt attccctcga atgtccatta 2800 agcatggaat ttaccatgca gttgtgctat gttcttatga acagatatat 2850 cattcctatt gagaaccagc taccttgtgg tagggaataa gaggtcagac 2900 acaaattaag acaactccca ttatcaacag gaactttctc agtgagccat 2950 tcactcctgg agaatggtat aggaatttgg agaggtgcat tatttctttc 3000 tggccactgg ggttaaattt agtgtactac aacattgatt tactgaaggg 3050 cactaatgtt tcccccagga tttctattga ctagtcagga gtaacaggtt 3100 cacagagaga agttggtgct tagttatgtg ttttttagag tatatactaa 3150 gctctacagg gacagaatgc ttaataaata ctttaataag atatgggaaa 3200 766 atattttaat aaaacaagga aaacataatg atgtataatg catcctgatg 3250 ggaaggcatg cagatgggat ttgttagaag acagaaggaa agacagccat 3300 aaattctggc tttggggaaa actcatatcc ccatgaaaag gaagaacaat 3350 cacaaataaa gtgagagtaa tgtaatggag ctcttttcac tagggtataa 3400 gtagctgcca atttgtaatt catctgttaa aaaaaatcta gattataaca 3450 aactgctagc aaaatctgag gaaacataaa ttcttctgaa gaatcatagg 3500 aagagtagac attttattta taaccaatga tatttcagta tatattttct 3550 ctcttttaaa aaatatttat catactctgt atattatttc tttttactgc 3600 ctttattctc tcctgtatat tggattttgt gattatattt gagtgaatag 3650 gagaaaacaa tatataacac acagagaatt aagaaaatga catttctggg 3700 gagtggggat aacggaaagg atatatttgt gttaaattaa tgaataacag ctctttgaca aacgagtgta tcttcactca aaattttaac accttttctc 3750 3800 attgctgagt taatctgttg taattgtagt attgtttttg taatttaaca 3850 ataaataagc ctgctacatg t 3871 <210> 310 <211> 777 <212> PRT <213> Homo sapiens <400> 310 Met Asn Ala Asn Lys Asp Glu Arg Leu Lys Ala Arg Ser Gin Asp 15 10 15 Phe His Leu Phe Pro Ala Leu Met Met Leu Ser Met Thr Met Leu 20 25 30 Phe Leu Pro Val Thr Gly Thr Leu Lys Gin Asn Ile Pro Arg Leu 35 40 45 Lys Leu Thr Tyr Lys Asp Leu Leu Leu Ser Asn Ser Cys Ile Pro 50 55 60 Phe Leu Gly Ser Ser Glu Gly Leu Asp Phe Gin Thr Leu Leu Leu 65 70 75 Asp Glu Glu Arg Gly Arg Leu Leu Leu Gly Ala Lys Asp His Ile 80 85 90 Phe Leu Leu Ser Leu Val Asp Leu Asn Lys Asn Phe Lys Lys Ile 95 100 105 Tyr Trp Pro Ala Ala Lys Glu Arg Val Glu Leu Cys Lys Leu Ala 110 115 120 Gly Lys Asp Ala Asn Thr Glu Cys Ala Asn Phe Ile Arg Val Leu 125 130 135 Gin Pro Tyr Asn Lys Thr His Ile Tyr Val Cys Gly Thr Gly Ala 140 767 145 150 Phe His Pro Ile Cys Gly Tyr Ile Asp Leu Gly Val Tyr Lys Glu 155 160 165 Asp Ile Ile Phe Lys Leu Asp Thr His Asn Leu Glu Ser Gly Arg 170 175 180 Leu Lys Cys Pro Phe Asp Pro Gin Gin Pro Phe Ala Ser Val Met 185 190 195 Thr Asp Glu Tyr Leu Tyr Ser Gly Thr Ala Ser Asp Phe Leu Gly 200 205 210 Lys Asp Thr Ala Phe Thr Arg Ser Leu Gly Pro Thr His Asp His 215 220 225 His Tyr Ile Arg Thr Asp Ile Ser Glu His Tyr Trp Leu Asn Gly 230 235 240 Ala Lys Phe Ile Gly Thr Phe Phe Ile Pro Asp Thr Tyr Asn Pro 245 250 255 Asp Asp Asp Lys Ile Tyr Phe Phe Phe Arg Glu Ser Ser Gin Glu 260 265 270 Gly Ser Thr Ser Asp Lys Thr Ile Leu Ser Arg Val Gly Arg Val 275 280 285 Cys Lys Asn Asp Val Gly Gly Gin Arg Ser Leu Ile Asn Lys Trp 290 295 300 Thr Thr Phe Leu Lys Ala Arg Leu Ile Cys Ser Ile Pro Gly Ser 305 310 315 Asp Gly Ala Asp Thr Tyr Phe Asp Glu Leu Gin Asp Ile Tyr Leu 320 325 330 Leu Pro Thr Arg Asp Glu Arg Asn Pro Val Val Tyr Gly Val Phe 335 340 345 Thr Thr Thr Ser Ser Ile Phe Lys Gly Ser Ala Val Cys Val Tyr 350 355 360 Ser Met Ala Asp Ile Arg Ala Val Phe Asn Gly Pro Tyr Ala His 365 370 375 Lys Glu Ser Ala Asp His Arg Trp Val Gin Tyr Asp Gly Arg Ile 380 385 390 Pro Tyr Pro Arg Pro Gly Thr Cys Pro Ser Lys Thr Tyr Asp Pro 395 400 405 Leu Ile Lys Ser Thr Arg Asp Phe Pro Asp Asp Val Ile Ser Phe 410 415 420 Ile Lys Arg His Ser Val Met Tyr Lys Ser Val Tyr Pro Val Ala 425 430 435 Gly Gly Pro Thr Phe Lys Arg Ile Asn Val Asp Tyr Arg Leu Thr 440 445 450 768 Gin Ile Val Val Asp His Val Ile Ala Glu Asp Gly Gin Tyr Asp 455 460 465 Val Met Phe Leu Gly Thr Asp Ile Gly Thr Val Leu Lys Val Val 470 475 480 Ser Ile Ser Lys Glu Lys Trp Asn Met Glu Glu Val Val Leu Glu 485 490 495 Glu Leu Gin Ile Phe Lys His Ser Ser Ile Ile Leu Asn Met Glu 500 505 510 Leu Ser Leu Lys Gin Gin Gin Leu Tyr Ile Gly Ser Arg Asp Gly 515 520 525 Leu Val Gin Leu Ser Leu His Arg Cys Asp Thr Tyr Gly Lys Ala 530 535 540 Cys Ala Asp Cys Cys Leu Ala Arg Asp Pro Tyr Cys Ala Trp Asp 545 550 555 Gly Asn Ala Cys Ser Arg Tyr Ala Pro Thr Ser Lys Arg Arg Ala 560 565 570 Arg Arg Gin Asp Val Lys Tyr Gly Asp Pro Ile Thr Gin Cys Trp 575 580 585 Asp Ile Glu Asp Ser Ile Ser His Glu Thr Ala Asp Glu Lys Val 590 595 600 Ile Phe Gly Ile Glu Phe Asn Ser Thr Phe Leu Glu Cys Ile Pro 605 610 615 Lys Ser Gin Gin Ala Thr Ile Lys Trp Tyr Ile Gin Arg Ser Gly 620 625 630 Asp Glu His Arg Glu Glu Leu Lys Pro Asp Glu Arg Ile Ile Lys 635 640 645 Thr Glu Tyr Gly Leu Leu Ile Arg Ser Leu Gin Lys Lys Asp Ser 650 655 660 Gly Met Tyr Tyr Cys Lys Ala Gin Glu His Thr Phe Ile His Thr 665 670 675 Ile Val Lys Leu Thr Leu Asn Val Ile Glu Asn Glu Gin Met Glu 680 685 690 Asn Thr Gin Arg Ala Glu His Glu Glu Gly Gin Val Lys Asp Leu 695 700 705 Leu Ala Glu Ser Arg Leu Arg Tyr Lys Asp Tyr Ile Gin Ile Leu 710 715 720 Ser Ser Pro Asn Phe Ser Leu Asp Gin Tyr Cys Glu Gin Met Trp 725 730 735 His Arg Glu Lys Arg Arg Gin Arg Asn Lys Gly Gly Pro Lys Trp 740 745 750 Lys His Met Gin Glu Met Lys Lys Lys Arg Asn Arg Arg His His 755 760 765 769 Arg Asp Leu Asp Glu Leu Pro Arg Ala Val Ala Thr 770 775 <210> 311 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 311 caacgcagcc gtgataaaca agtgg 2 5 <210> 312 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 312 gcttggacat gtaccaggcc gtgg 24 <210> 313 <211> 45 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 313 ggccagactg atttgctcaa ttcctggaag tgatggggca gatac 45 <210> 314 <211> 3934 <212> DNA <213> Homo sapiens <400> 314 ccctgacctc cctgagccac actgagctgg aagccgcaga ggtcatcctg 50 gagcatgccc accgcgggga gcagacaacc tcccaggtaa gctgggagca 100 agacctgaag ctgtttcttc aggagcctgg tgtattttcc cccaccccac 150 ctcagcagtt tcagccagca gggactgatc aggtgtgtgt cctggagtgg 200 ggagcagaag gcgtggctgg caagagtggc ctggagaaag aggttcagcg 250 cttgaccagc cgagctgccc gtgactacaa gatccagaac catgggcatc 300 gggtgaggtg ggggggcaca ggtgtcatgt gcaccttctt gtctcagcaa 350 gaagagctga gagaggggat cttggagcca ttgagggtgt catggagcta 400 cagaggggag ggaaaggtat tttaaggtaa cagtgtggca caatagttaa 450 gagcacagtt tttggagcta gaccgacata ggttcaaatt ctcttctgtt 500 770 gcttcctagt tctgtagccc caggtaaggg agtgacttaa cctctctgga 550 cttcaatttc ctcatcacta aagtagggcc aataatagca cccacctcat 600 agggaagatt aaatgacata atgtatgtga tgcaactagc aaagtaccag 650 tcccatagta agtcatgccc cacagtattt ccacccaccc ctgttctctg 700 ccttcccaac caggtactgc aacgactgga gcagaggcgg cagcaggctt 750 cagagcggga ggctccaagc atagaacaga ggttacagga agtgcgagag 800 agcatccgcc gggcacaggt gagccaggtg aagggggctg cccggctggc 850 cctgctgcag ggggctggct tagatgtgga gcgctggctg aagccagcca 900 tgacccaggc ccaggatgag gtggagcagg agcggcggct cagtgaggct 950 cggctgtccc agagggacct ctctccaacc gctgaggatg ctgagctttc 1000 tgactttgag gaatgtgagg agacgggaga gctctttgag gagcctgccc 1050 cccaagccct ggccacgagg gccctcccct gccctgcaca cgtggtattt 1100 cgctatcagg cagggcgtga ggatgagctg acaatcacgg agggtgagtg 1150 gctggaggtc atagaggagg gagatgctga cgaatgggtc aaggctcgga 1200 accagcacgg cgaggtaggc tttgtccctg agcgatatct caacttcccg 1250 gacctctccc tcccagagag cagccaagac agtgacaatc cctgcggggc 1300 agagcccaca gcattcctgg cacaggccct gtacagctac accggacaga 1350 gtgcagagga gctgagcttc cctgaggggg cactcatccg tctgctgccc 1400 cgggcccaag atggagtaga tgacggcttc tggaggggag aatttggggg 1450 ccgtgttggg gtcttcccct ccctgctggt ggaagagctg cttggccccc 1500 cagggccacc tgaactctct gaccctgaac agatgctgcc gtccccttct 1550 cctcccagct tctccccacc tgcacctacc tctgtgttgg atgggccccc 1600 tgcacctgtc ctgcctgggg acaaagccct ggacttccct gggttcctgg 1650 acatgatggc acctcgactc aggccgatgc gtccaccacc tcccccgccg 1700 gctaaagccc cggatcctgg ccacccagat cccctcacct gaaggccagg 1750 gaagccttga cccccagtga tgctgctgtc cctatcttca agctgtcaga 1800 ccacaccatc aatgatccag agcaacacag ccaaaagctg gaatcgccct 1850 tatttccacc ctcacctcca agggtggaaa cttgcccctt cccatttcta 1900 gagctggaac ccactccttt ttttcccatt gttctatcat ctctaggacc 1950 ggaactacta ccttctcttc tgtcatgacc ctatctaggg tggtgaaatg 2000 cctgaaatct ctggggctgg aaaccatcca tcaaggtctc tagtagttct 2050 771 ggcccacctc tttccccacc ctggctccat gacccacccc actctggatg 2100 ccagggtcac tggggttggg ctggggagag gaacaggcct tgggaatcag 2150 gagctggagc caggatgcga agcagctgta atggtctgag cggatttatt 2200 gacaatgaat aaagggcacg aaggccaggc cagggcctgg gcctcttgtg 2250 ctaagagggc agggggccta cggtgctatt gctttagggg cccaccacgg 2300 gcaggggcct gctcccagct gccacgctct atcatatgga gcgaggtgtt 2350 ggggaaggcg gggcaggcag cctgttgcag gcaggggaag gagaagagac 2400 tgaggggctg tgacctctcc tgaggccccc agcctgagac tgtgcaactc 2450 caggtggaag tagagctggt ccctcagctg gggggcagtg ctgtccagtg 2500 gaggggaggg ctttcacgcc cacccacccc ctggccctgc cagctggtag 2550 tccatcagca caatgaagga gacttggaga agaggaagaa taacactgtt 2600 gcttcctgtt caagctgtgt ccagcttttc ccctggggct ccaggacctt 2650 ccctacctcc accaccaaac caagggattt atagcaaagg ctaagcctgc 2700 agtttactct gtgatgggaa gggggttcag gatgagatta ggagccgaaa cctcatttag ggcttaaata ggctcaggca gtttaagtag gactcacctc 2750 2800 acatactccc tgctccctgt ggtagagaca cctgagagaa aggggagggg 2850 tcaacaatga gagaccagga gtaggtccta tcagtgcccc ccagagtaga 2900 gagcaataag agcccagccc agtgcagtcc cggctgtgtt ttcctacctg 2950 gtgatcagaa gtgtctggtt tgcttggctg cccatttgcc tcttgagtgg 3000 gcagccctgg gcttgggccc ctccctccgg ccctcagtgt tggctctgca 3050 gaagctctgg ggttcccttc aagtgcacga ggggttaggc tgctgtccct 3100 gagtcctcca ttctgtactg gggggctggc taggacctgg ggctgtggcc 3150 tctcaggggg cagcctctcc atggcaggca tccctgcctt gggctgccct 3200 cccccagacc cctgaccacc ccctgggtcc tgtcccccac cagagcccca 3250 gctcctgtct gtgggggagc catcacggtg ttcgtgcagt ccatagcgct 3300 tctcaatgtg tgtcacccgg aacctgggag gggagggaac actggggttt 3350 aggaccacaa ctcagaggct gcttggccct cccctctgac cagggacatc 3400 ctgagtttgg tggctacttc cctctggcct aaggtagggg aggccttctc 3450 agattgtggg gcacattgtg tagcctgact tctgctggag ctcccagtcc 3500 aggaggaaag agccaaggcc cacttttggg atcaggtgcc tgatcactgg 3550 gccccctacc tcagcccccc tttccctgga gcacctgccc cacctgccca 3600 cagagaacac agtggtctcc cctgtccggg ggcggctttt tccttccttg 3650 772 gagcgtccct gacggacaag tggaggcctc ttgctgcggc tgcaatggat 3700 gcaaggggct gcagagccca ggtgcactgt gtgatgatgg gagggggctc 3750 cgtcctgcag gctggaggtg gcatccacac tggacagcag gaggagggga 3800 gtgagggtaa catttccatt tcccttcatg ttttgtttct tacgttcttt 3 850 cagcatgctc cttaaaaccc cagaagcccc aatttcccca agccccattt 3900 tttcttgtct ttatctaata aactcaatat taag 3934 <210> 315 <211> 370 <212> PRT <213> Homo sapiens <400> 315 Met Gin Leu Ala Lys Tyr Gin Ser His Ser Lys Ser Cys Pro Thr 15 10 15 Val Phe Pro Pro Thr Pro Val Leu Cys Leu Pro Asn Gin Val Leu 20 25 30 Gin Arg Leu Glu Gin Arg Arg Gin Gin Ala Ser Glu Arg Glu Ala 35 40 45 Pro Ser Ile Glu Gin Arg Leu Gin Glu Val Arg Glu Ser Ile Arg 50 55 60 Arg Ala Gin Val Ser Gin Val Lys Gly Ala Ala Arg Leu Ala Leu 65 70 75 Leu Gin Gly Ala Gly Leu Asp Val Glu Arg Trp Leu Lys Pro Ala 80 85 90 Met Thr Gin Ala Gin Asp Glu Val Glu Gin Glu Arg Arg Leu Ser 95 100 105 Glu Ala Arg Leu Ser Gin Arg Asp Leu Ser Pro Thr Ala Glu Asp 110 115 120 Ala Glu Leu Ser Asp Phe Glu Glu Cys Glu Glu Thr Gly Glu Leu 125 130 135 Phe Glu Glu Pro Ala Pro Gin Ala Leu Ala Thr Arg Ala Leu Pro 140 145 150 Cys Pro Ala His Val Val Phe Arg Tyr Gin Ala Gly Arg Glu Asp 155 160 165 Glu Leu Thr Ile Thr Glu Gly Glu Trp Leu Glu Val Ile Glu Glu 170 175 180 Gly Asp Ala Asp Glu Trp Val Lys Ala Arg Asn Gin His Gly Glu 185 190 195 Val Gly Phe Val Pro Glu Arg Tyr Leu Asn Phe Pro Asp Leu Ser 200 205 210 Leu Pro Glu Ser Ser Gin Asp Ser Asp Asn Pro Cys Gly Ala Glu 773 215 220 225 Pro Thr Ala Phe Leu Ala Gin Ala Leu Tyr Ser Tyr Thr Gly Gin 230 235 240 Ser Ala Glu Glu Leu Ser Phe Pro Glu Gly Ala Leu Ile Arg Leu 245 250 255 Leu Pro Arg Ala Gin Asp Gly Val Asp Asp Gly Phe Trp Arg Gly 260 265 270 Glu Phe Gly Gly Arg Val Gly Val Phe Pro Ser Leu Leu Val Glu 275 280 285 Glu Leu Leu Gly Pro Pro Gly Pro Pro Glu Leu Ser Asp Pro Glu 290 295 300 Gin Met Leu Pro Ser Pro Ser Pro Pro Ser Phe Ser Pro Pro Ala 305 310 315 Pro Thr Ser Val Leu Asp Gly Pro Pro Ala Pro Val Leu Pro Gly 320 325 330 Asp Lys Ala Leu Asp Phe Pro Gly Phe Leu Asp Met Met Ala Pro 335 340 345 Arg Leu Arg Pro Met Arg Pro Pro Pro Pro Pro Pro Ala Lys Ala 350 355 360 Pro Asp Pro Gly His Pro Asp Pro Leu Thr 365 370 <210> 316 <211> 4407 <212> DNA <213> Homo sapiens <400> 316 cacagggaga cccacagaca catatgcacg agagagacag aggaggaaag 50 agacagagac aaaggcacag cggaagaagg cagagacagg gcaggcacag 100 aagcggccca gacagagtcc tacagaggga gaggccagag aagctgcaga 150 agacacaggc agggagagac aaagatccag gaaaggaggg ctcaggagga 200 gagtttggag aagccagacc cctgggcacc tctcccaagc ccaaggacta 250 agttttctcc atttccttta acggtcctca gcccttctga aaactttgcc 300 tctgaccttg gcaggagtcc aagcccccag gctacagaga ggagctttcc 350 aaagctaggg tgtggaggac ttggtgccct agacggcctc agtccctccc 400 agctgcagta ccagtgccat gtcccagaca ggctcgcatc ccgggagggg 450 cttggcaggg cgctggctgt ggggagccca accctgcctc ctgctcccca 500 ttgtgccgct ctcctggctg gtgtggctgc ttctgctact gctggcctct 550 ctcctgccct cagcccggct ggccagcccc ctcccccggg aggaggagat 600 774 cgtgtttcca gagaagctca acggcagcgt cctgcctggc tcgggcgccc 650 ctgccaggct gttgtgccgc ttgcaggcct ttggggagac gctgctacta 700 gagctggagc aggactccgg tgtgcaggtc gaggggctga cagtgcagta 750 cctgggccag gcgcctgagc tgctgggtgg agcagagcct ggcacctacc 800 tgactggcac catcaatgga gatccggagt cggtggcatc tctgcactgg 850 gatgggggag ccctgttagg cgtgttacaa tatcgggggg ctgaactcca 900 cctccagccc ctggagggag gcacccctaa ctctgctggg ggacctgggg 950 ctcacatcct acgccggaag agtcctgcca gcggtcaagg tcccatgtgc 1000 aacgtcaagg ctcctcttgg aagccccagc cccagacccc gaagagccaa 1050 gcgctttgct tcactgagta gatttgtgga gacactggtg gtggcagatg 1100 acaagatggc cgcattccac ggtgcggggc taaagcgcta cctgctaaca 1150 gtgatggcag cagcagccaa ggccttcaag cacccaagca tccgcaatcc 1200 tgtcagcttg gtggtgactc ggctagtgat cctggggtca ggcgaggagg 1250 ggccccaagt ggggcccagt gctgcccaga ccctgcgcag cttctgtgcc 1300 tggcagcggg gcctcaacac ccctgaggac tcgggccctg accactttga 1350 cacagccatt ctgtttaccc gtcaggacct gtgtggagtc tccacttgcg 1400 acacgctggg tatggctgat gtgggcaccg tctgtgaccc ggctcggagc 1450 tgtgccattg tggaggatga tgggctccag tcagccttca ctgctgctca 1500 tgaactgggt catgtcttca acatgctcca tgacaactcc aagccatgca 1550 tcagtttgaa tgggcctttg agcacctctc gccatgtcat ggcccctgtg 1600 atggctcatg tggatcctga ggagccctgg tccccctgca gtgcccgctt 1650 catcactgac ttcctggaca atggctatgg gcactgtctc ttagacaaac 1700 cagaggctcc attgcatctg cctgtgactt tccctggcaa ggactatgat 1750 gctgaccgcc agtgccagct gaccttcggg cccgactcac gccattgtcc 1800 acagctgccg ccgccctgtg ctgccctctg gtgctctggc cacctcaatg 1850 gccatgccat gtgccagacc aaacactcgc cctgggccga tggcacaccc 1900 tgcgggcccg cacaggcctg catgggtggt cgctgcctcc acatggacca 1950 gctccaggac ttcaatattc cacaggctgg tggctggggt ccttggggac 2000 catggggtga ctgctctcgg acctgtgggg gtggtgtcca gttctcctcc 2050 cgagactgca cgaggcctgt cccccggaat ggtggcaagt actgtgaggg 2100 ccgccgtacc cgcttccgct cctgcaacac tgaggactgc ccaactggct 2150 775 cagccctgac cttccgcgag gagcagtgtg ctgcctacaa ccaccgcacc 2200 gacctcttca agagcttccc agggcccatg gactgggttc ctcgctacac 2250 aggcgtggcc ccccaggacc agtgcaaact cacctgccag gcccgggcac 2300 tgggctacta ctatgtgctg gagccacggg tggtagatgg gaccccctgt 2350 tccccggaca gctcctcggt ctgtgtccag ggccgatgca tccatgctgg 2400 ctgtgatcgc atcattggct ccaagaagaa gtttgacaag tgcatggtgt 2450 gcggagggga cggttctggt tgcagcaagc agtcaggctc cttcaggaaa 2500 ttcaggtacg gatacaacaa tgtggtcact atccccgcgg gggccaccca 2550 cattcttgtc cggcagcagg gaaaccctgg ccaccggagc atctacttgg 2600 ccctgaagct gccagatggc tcctatgccc tcaatggtga atacacgctg 2650 atgccctccc ccacagatgt ggtactgcct ggggcagtca gcttgcgcta 2700 cagcggggcc actgcagcct cagagacact gtcaggccat gggccactgg 2750 cccagccttt gacactgcaa gtcctagtgg ctggcaaccc ccaggacaca 2800 cgcctccgat acagcttctt cgtgccccgg ccgacccctt caacgccacg 2850 ccccactccc caggactggc tgcaccgaag agcacagatt ctggagatcc 2900 ttcggcggcg cctttctggg cccctgggcg caccggggcc ggcaggaaat tcggacttag aacctcacta ctgggagaaa tcccggctgc gagagagctt 2950 3000 ctgttgctgc ctcatgctaa gactcagtgg ggaggggctg tgggcgtgag 3050 acctgcccct cctctctgcc ctaatgcgca ggctggccct gccctggttt 3100 cctgccctgg gaggcagtga tgggttagtg gatggaaggg gctgacagac 3150 agccctccat ctaaactgcc ccctctgccc tgcgggtcac aggagggagg 3200 gggaaggcag ggagggcctg ggccc'cagtt gtatttattt agtatttatt 3250 cacttttatt tagcaccagg gaaggggaca aggactaggg tcctggggaa 3300 cctgacccct gacccctcat agccctcacc ctggggctag gaaatccagg 3350 gtggtggtga taggtataag tggtgtgtgt atgcgtgtgt gtgtgtgtgt 3400 gaaaatgtgt gtgtgcttat gtatgaggta caacctgttc tgctttcctc 3450 ttcctgaatt ttattttttg ggaaaagaaa agtcaagggt agggtgggcc 3500 ttcagggagt gagggattat cttttttttt ttttctttct ttctttcttt 3550 tttttttttg agacagaatc tcgctctgtc gcccaggctg gagtgcaatg 3600 gcacaatctc ggctcactgc atcctccgcc tcccgggttc aagtgattct 3650 catgcctcag cctcctgagt agctgggatt acaggctcct gccaccacgc 3700 ccagctaatt tttgttttgt tttgtttgga gacagagtct cgctattgtc 3750 776 accagggctg gaatgatttc agctcactgc aaccttcgcc acctgggttc 3800 cagcaattct cctgcctcag cctcccgagt agctgagatt ataggcacct 3850 accaccacgc ccggctaatt tttgtatttt tagtagagac ggggtttcac 3900 catgttggcc aggctggtct cgaactcctg accttaggtg atccactcgc 3950 cttcatctcc caaagtgctg ggattacagg cgtgagccac cgtgcctggc 4000 cacgcccaac taatttttgt atttttagta gagacagggt ttcaccatgt 4050 tggccaggct gctcttgaac tcctgacctc aggtaatcga cctgcctcgg 4100 cctcccaaag tgctgggatt acaggtgtga gccaccacgc ccggtacata 4150 ttttttaaat tgaattctac tatttatgtg atccttttgg agtcagacag 4200 atgtggttgc atcctaactc catgtctctg agcattagat ttctcatttg 4250 ccaataataa tacctccctt agaagtttgt tgtgaggatt aaataatgta 4300 aataaagaac tagcataaca ctcaaaaaaa aaaaaaaaaa aaaaaaaaaa 4350 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4400 aaggaaa 4407 <210> 317 <211> 837 <212> PRT <213> Homo sapiens <400> 317 Met Ser Gin Thr Gly Ser His Pro Gly Arg Gly Leu Ala Gly Arg 15 10 15 Trp Leu Trp Gly Ala Gin Pro Cys Leu Leu Leu Pro Ile Val Pro 20 25 30 Leu Ser Trp Leu Val Trp Leu Leu Leu Leu Leu Leu Ala Ser Leu 35 40 45 Leu Pro Ser Ala Arg Leu Ala Ser Pro Leu Pro Arg Glu Glu Glu 50 55 60 Ile Val Phe Pro Glu Lys Leu Asn Gly Ser Val Leu Pro Gly Ser 65 70 75 Gly Ala Pro Ala Arg Leu Leu Cys Arg Leu Gin Ala Phe Gly Glu 80 85 90 Thr Leu Leu Leu Glu Leu Glu Gin Asp Ser Gly Val Gin Val Glu 95 100 105 Gly Leu Thr Val Gin Tyr Leu Gly Gin Ala Pro Glu Leu Leu Gly 110 115 120 Gly Ala Glu Pro Gly Thr Tyr Leu Thr Gly Thr Ile Asn Gly Asp 125 130 135 Ill Pro Glu Ser Val Ala Ser Leu His Trp Asp Gly Gly Ala Leu Leu 140 145 150 Gly Val Leu Gin Tyr Arg Gly Ala Glu Leu His Leu Gin Pro Leu 155 160 165 Glu Gly Gly Thr Pro Asn Ser Ala Gly Gly Pro Gly Ala His lie 170 175 180 Leu Arg Arg Lys Ser Pro Ala Ser Gly Gin Gly Pro Met Cys Asn 185 190 195 Val Lys Ala Pro Leu Gly Ser Pro Ser Pro Arg Pro Arg Arg Ala 200 205 210 Lys Arg Phe Ala Ser Leu Ser Arg Phe Val Glu Thr Leu Val Val 215 220 225 Ala Asp Asp Lys Met Ala Ala Phe His Gly Ala Gly Leu Lys Arg 230 235 240 Tyr Leu Leu Thr Val Met Ala Ala Ala Ala Lys Ala Phe Lys His .245 250 255 Pro Ser Ile Arg Asn Pro Val Ser Leu Val Val Thr Arg Leu Val 260 265 270 Ile Leu Gly Ser Gly Glu Glu Gly Pro Gin Val Gly Pro Ser Ala 275 280 285 Ala Gin Thr Leu Arg Ser Phe Cys Ala Trp Gin Arg Gly Leu Asn 290 295 300 Thr Pro Glu Asp Ser Gly Pro Asp His Phe Asp Thr Ala Ile Leu 305 310 315 Phe Thr Arg Gin Asp Leu Cys Gly Val Ser Thr Cys Asp Thr Leu 320 325 330 Gly Met Ala Asp Val Gly Thr Val Cys Asp Pro Ala Arg Ser Cys 335 340 345 Ala Ile Val Glu Asp Asp Gly Leu Gin Ser Ala Phe Thr Ala Ala 350 355 360 His Glu Leu Gly His Val Phe Asn Met Leu His Asp Asn Ser Lys 365 370 375 Pro Cys Ile Ser Leu Asn Gly Pro Leu Ser Thr Ser Arg His Val 380 385 390 Met Ala Pro Val Met Ala His Val Asp Pro Glu Glu Pro Trp Ser 395 400 405 Pro Cys Ser Ala Arg Phe Ile Thr Asp Phe Leu Asp Asn Gly Tyr 410 415 420 Gly His Cys Leu Leu Asp Lys Pro Glu Ala Pro Leu His Leu Pro 425 430 435 Val Thr Phe Pro Gly Lys Asp Tyr Asp Ala Asp Arg Gin Cys Gin 440 445 450 778 Leu Thr Phe Gly Pro Asp Ser Arg His Cys Pro Gin Leu Pro Pro 455 460 465 Pro Cys Ala Ala Leu Trp Cys Ser Gly His Leu Asn Gly His Ala 470 475 480 Met Cys Gin Thr Lys His Ser Pro Trp Ala Asp Gly Thr Pro Cys 485 490 495 Gly Pro Ala Gin Ala Cys Met Gly Gly Arg Cys Leu His Met Asp 500 505 510 Gin Leu Gin Asp Phe Asn Ile Pro Gin Ala Gly Gly Trp Gly Pro 515 520 525 Trp Gly Pro Trp Gly Asp Cys Ser Arg Thr Cys Gly Gly Gly Val 530 535 540 Gin Phe Ser Ser Arg Asp Cys Thr Arg Pro Val Pro Arg Asn Gly 545 550 555 Gly Lys Tyr Cys Glu Gly Arg Arg Thr Arg Phe Arg Ser Cys Asn 560 565 570 Thr Glu Asp Cys Pro Thr Gly Ser Ala Leu Thr Phe Arg Glu Glu 575 580 585 Gin Cys Ala Ala Tyr Asn His Arg Thr Asp Leu Phe Lys Ser Phe 590 595 600 Pro Gly Pro Met Asp Trp Val Pro Arg Tyr Thr Gly Val Ala Pro 605 610 615 Gin Asp Gin Cys Lys Leu Thr Cys Gin Ala Arg Ala Leu Gly Tyr 620 625 630 Tyr Tyr Val Leu Glu Pro Arg Val Val Asp Gly Thr Pro Cys Ser 635 640 645 Pro Asp Ser Ser Ser Val Cys Val Gin Gly Arg Cys Ile His Ala 650 655 660 Gly Cys Asp Arg Ile Ile Gly Ser Lys Lys Lys Phe Asp Lys Cys 665 670 675 Met Val Cys Gly Gly Asp Gly Ser Gly Cys Ser Lys Gin Ser Gly 680 685 690 Ser Phe Arg Lys Phe Arg Tyr Gly Tyr Asn Asn Val Val Thr Ile 695 700 705 Pro Ala Gly Ala Thr His Ile Leu Val Arg Gin Gin Gly Asn Pro 710 715 720 Gly His Arg Ser Ile Tyr Leu Ala Leu Lys Leu Pro Asp Gly Ser 725 730 735 Tyr Ala Leu Asn Gly Glu Tyr Thr Leu Met Pro Ser Pro Thr Asp 740 745 750 Val Val Leu Pro Gly Ala Val Ser Leu Arg Tyr Ser Gly Ala Thr 755 779 760 765 Ala Ala Ser Leu Thr Leu Leu Arg Tyr Arg Pro Thr Glu Ile Leu <210> 318 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 318 ccctgaagct gccagatggc tcc 23 <210> 319 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 319 ctgtgctctt cggtgcagcc agtc 24 <210> 320 <211> 43 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 320 ccacagatgt ggtactgcct ggggcagtca gcttgcgcta cag 43 <210> 321 <211> 1197 <212> DNA <213> Homo sapiens <400> 321 cagcagtggt ctctcagtcc tctcaaagca aggaaagagt actgtgtgct 50 gagagaccat ggcaaagaat cctccagaga attgtgaaga ctgtcacatt 10 0 ctaaatgcag aagcttttaa atccaagaaa atatgtaaat cacttaagat 150 ttgtggactg gtgtttggta tcctggccct aactctaatt gtcctgtttt 200 Glu Thr Leu Ser Gly His Gly Pro Leu Ala Gin Pro 770 775 780 Gin Val Leu Val Ala Gly Asn Pro Gin Asp Thr Arg 785 790 795 Ser Phe Phe Val Pro Arg Pro Thr Pro Ser Thr Pro 800 805 810 Pro Gin Asp Trp Leu His Arg Arg Ala Gin Ile Leu 815 820 825 Arg Arg Arg Pro Trp Ala Gly Arg Lys 830 835 780 gggggagcaa gcacttctgg ccggaggtac ccaaaaaagc ctatgacatg 250 gagcacactt tctacagcaa tggagagaag aagaagattt acatggaaat 300 tgatcctgtg accagaactg aaatattcag aagcggaaat ggcactgatg 350 aaacattgga agtgcacgac tttaaaaacg gatacactgg catctacttc 400 gtgggtcttc aaaaatgttt tatcaaaact cagattaaag tgattcctga 450 attttctgaa ccagaagagg aaatagatga gaatgaagaa attaccacaa 500 ctttctttga acagtcagtg atttgggtcc cagcagaaaa gcctattgaa 550 aaccgagatt ttcttaaaaa ttccaaaatt ctggagattt gtgataacgt 600 gaccatgtat tggatcaatc ccactctaat atcagtttct gagttacaag 650 actttgagga ggagggagaa gatcttcact ttcctgccaa cgaaaaaaaa 700 gggattgaac aaaatgaaca gtgggtggtc cctcaagtga aagtagagaa 7 50 gacccgtcac gccagacaag caagtgagga agaacttcca ataaatgact 800 atactgaaaa tggaatagaa tttgatccca tgctggatga gagaggttat 850 tgttgtattt actgccgtcg aggcaaccgc tattgccgcc gcgtctgtga 900 acctttacta ggctactacc catatccata ctgctaccaa ggaggacgag 950 tcatctgtcg tgtcatcatg ccttgtaact ggtgggtggc ccgcatgctg 1000 gggagggtct aataggaggt ttgagctcaa atgcttaaac tgctggcaac 1050 atataataaa tgcatgctat tcaatgaatt tctgcctatg aggcatctgg 1100 cccctggtag ccagctctcc agaattactt gtaggtaatt cctctcttca 1150 tgttctaata aacttctaca ttatcaccaa aaaaaaaaaa aaaaaaa 1197 <210> 322 <211> 317 <212> PRT <213> Homo sapiens <400> 322 Met Ala Lys Asn Pro Pro Glu Asn Cys Glu Asp Cys His Ile Leu 15 10 15 Asn Ala Glu Ala Phe Lys Ser Lys Lys Ile Cys Lys Ser Leu Lys 20 25 30 Ile Cys Gly Leu Val Phe Gly Ile Leu Ala Leu Thr Leu Ile Val 35 40 45 Leu Phe Trp Gly Ser Lys His Phe Trp Pro Glu Val Pro Lys Lys 50 55 60 Ala Tyr Asp Met Glu His Thr Phe Tyr Ser Asn Gly Glu Lys Lys 65 70 75 Lys Ile Tyr Met Glu Ile Asp Pro Val Thr Arg Thr Glu Ile Phe 781 80 85 90 Arg Ser Gly Asn Gly Thr Asp Glu Thr Leu Glu Val His Asp Phe 95 100 105 Lys Asn Gly Tyr Thr Gly Ile Tyr Phe Val Gly Leu Gin Lys Cys 110 115 120 Phe Ile Lys Thr Gin Ile Lys Val Ile Pro Glu Phe Ser Glu Pro 125 130 135 Glu Glu Glu Ile Asp Glu Asn Glu Glu Ile Thr Thr Thr Phe Phe 140 145 150 Glu Gin Ser Val Ile Trp Val Pro Ala Glu Lys Pro Ile Glu Asn 155 160 165 Arg Asp Phe Leu Lys Asn Ser Lys Ile Leu Glu Ile Cys Asp Asn 170 175 180 Val Thr Met Tyr Trp lie Asn Pro Thr Leu lie Ser Val Ser Glu 185 190 195 Leu Gin Asp Phe Glu Glu Glu Gly Glu Asp Leu His Phe Pro Ala 200 205 210 Asn Glu Lys Lys Gly Ile Glu Gin Asn Glu Gin Trp Val Val Pro 215 220 225 Gin Val Lys Val Glu Lys Thr Arg His Ala Arg Gin Ala Ser Glu 230 235 240 Glu Glu Leu Pro Ile Asn Asp Tyr Thr Glu Asn Gly Ile Glu Phe 245 250 255 Asp Pro Met Leu Asp Glu Arg Gly Tyr Cys Cys Ile Tyr Cys Arg 260 265 270 Arg Gly Asn Arg Tyr Cys Arg Arg Val Cys Glu Pro Leu Leu Gly 275 280 285 Tyr Tyr Pro Tyr Pro Tyr Cys Tyr Gin Gly Gly Arg Val Ile Cys 290 295 300 Arg Val Ile Met Pro Cys Asn Trp Trp Val Ala Arg Met Leu Gly 305 310 315 Arg Val <210> 323 <211> 1174 <212> DNA <213> Homo sapiens <400> 323 gcggaactgg ctccggctgg cacctgagga gcggcgtgac cccgagggcc 50 cagggagctg cccggctggc ctaggcaggc agccgcacca tggccagcac 100 ggccgtgcag cttctgggct tcctgctcag cttcctgggc atggtgggca 150 cgttgatcac caccatcctg ccgcactggc ggaggacagc gcacgtgggc 2 00 782 accaacatcc tcacggccgt gtcctacctg aaagggctct ggatggagtg 250 tgtgtggcac agcacaggca tctaccagtg ccagatctac cgatccctgc 300 tggcgctgcc ccaagacctc caggctgccc gcgccctcat ggtcatctcc 3 50 tgcctgctct cgggcatagc ctgcgcctgc gccgtcatcg ggatgaagtg 400 cacgcgctgc gccaagggca cacccgccaa gaccaccttt gccatcctcg 450 gcggcaccct cttcatcctg gccggcctcc tgtgcatggt ggccgtctcc 500 tggaccacca acgacgtggt gcagaacttc tacaacccgc tgctgcccag 550 cggcatgaag tttgagattg gccaggccct gtacctgggc ttcatctcct 600 cgtccctctc gctcattggt ggcaccctgc tttgcctgtc ctgccaggac 650 gaggcaccct acaggcccta ccaggccccg cccagggcca ccacgaccac 700 tgcaaacacc gcacctgcct accagccacc agctgcctac aaagacaatc 750 gggccccctc agtgacctcg gccacgcaca gcgggtacag gctgaacgac 800 tacgtgtgag tccccacagc ctgcttctcc cctgggctgc tgtgggctgg 850 gtccccggcg ggactgtcaa tggaggcagg ggttccagca caaagtttac 900 ttctgggcaa tttttgtatc caaggaaata atgtgaatgc gaggaaatgt 950 ctttagagca cagggacaga gggggaaata agaggaggag aaagctctct 1000 ataccaaaga ctgaaaaaaa aaatcctgtc tgtttttgta tttattatat 1050 atatttatgt gggtgatttg ataacaagtt taatataaag tgacttggga 1100 gtttggtcag tggggttggt ttgtgatcca ggaataaacc ttgcggatgt 1150 ggctgtttat gaaaaaaaaa aaaa 1174 <210> 324 <211> 239 <212> PRT <213> Homo sapiens <400> 324 Met Ala Ser Thr Ala Val Gin Leu Leu Gly Phe Leu Leu Ser Phe 15 10 15 Leu Gly Met Val Gly Thr Leu Ile Thr Thr Ile Leu Pro His Trp 20 25 30 Arg Arg Thr Ala His Val Gly Thr Asn Ile Leu Thr Ala Val Ser 35 40 45 Tyr Leu Lys Gly Leu Trp Met Glu Cys Val Trp His Ser Thr Gly 50 55 60 Ile Tyr Gin Cys Gin Ile Tyr Arg Ser Leu Leu Ala Leu Pro Gin 65 70 75 Asp Leu Gin Ala Ala Arg Ala Leu Met Val Ile Ser Cys Leu Leu 783 80 85 90 Ser Gly Ile Ala Cys Ala Cys Ala Val Ile Gly Met Lys Cys Thr 95 100 105 Arg Cys Ala Lys Gly Thr Pro Ala Lys Thr Thr Phe Ala Ile Leu 110 115 120 Gly Gly Thr Leu Phe Ile Leu Ala Gly Leu Leu Cys Met Val Ala 125 130 135 Val Ser Trp Thr Thr Asn Asp Val Val Gin Asn Phe Tyr Asn Pro 140 145 150 Leu Leu Pro Ser Gly Met Lys Phe Glu Ile Gly Gin Ala Leu Tyr 155 160 165 Leu Gly Phe Ile Ser Ser Ser Leu Ser Leu Ile Gly Gly Thr Leu 170 175 180 Leu Cys Leu Ser Cys Gin Asp Glu Ala Pro Tyr Arg Pro Tyr Gin 185 190 195 Ala Pro Pro Arg Ala Thr Thr Thr Thr Ala Asn Thr Ala Pro Ala 200 205 210 Tyr Gin Pro Pro Ala Ala Tyr Lys Asp Asn Arg Ala Pro Ser Val 215 220 225 Thr Ser Ala Thr His Ser Gly Tyr Arg Leu Asn Asp Tyr Val 230 235 <210> 325 <211> 2121 <212> DNA <213> Homo sapiens <400> 325 gagctcccct ggcagcttct caggagcgcg cgcaggcggc ttagcttcac agggcgggcg accttcggca gccaggatca gcaggagggc tgtccaccac 50 100 cacatgccaa gtggtggcgt tcctcctgtc catcctgggg ctggccggct 150 gcatcgcggc caccgggatg gacatgtgga gcacccagga cctgtacgac 200 aaccccgtca cctccgtgtt ccagtacgaa gggctctgga ggagctgcgt 250 gaggcagagt tcaggcttca ccgaatgcag gccctatttc accatcctgg 300 gacttccagc catgctgcag gcagtgcgag ccctgatgat cgtaggcatc 350 gtcctgggtg ccattggcct cctggtatcc atctttgccc tgaaatgcat 400 ccgcattggc agcatggagg actctgccaa agccaacatg acactgacct 450 ccgggatcat gttcattgtc tcaggtcttt gtgcaattgc tggagtgtct 500 gtgtttgcca acatgctggt gactaacttc tggatgtcca cagctaacat 550 gtacaccggc atgggtggga tggtgcagac tgttcagacc aggtacacat 600 ttggtgcggc tctgttcgtg ggctgggtcg ctggaggcct cacactaatt 650 784 gggggtgtga tgatgtgcat cgcctgccgg ggcctggcac cagaagaaac 700 caactacaaa gccgtttctt atcatgcctc aggccacagt gttgcctaca 750 agcctggagg cttcaaggcc agcactggct ttgggtccaa caccaaaaac 800 aagaagatat acgatggagg tgcccgcaca gaggacgagg tacaatctta 850 tccttccaag cacgactatg tgtaatgctc taagacctct cagcacgggc 900 ggaagaaact cccggagagc tcacccaaaa aacaaggaga tcccatctag 950 atttcttctt gcttttgact cacagctgga agttagaaaa gcctcgattt 1000 catctttgga gaggccaaat ggtcttagcc tcagtctctg tctctaaata 1050 ttccaccata aaacagctga gttatttatg aattagaggc tatagctcac 1100 attttcaatc ctctatttct ttttttaaat ataactttct actctgatga 1150 gagaatgtgg ttttaatctc tctctcacat tttgatgatt tagacagact 1200 ccccctcttc ctcctagtca ataaacccat tgatgatcta tttcccagct 1250 tatccccaag aaaacttttg aaaggaaaga gtagacccaa agatgttatt 1300 ttctgctgtt tgaattttgt ctccccaccc ccaacttggc tagtaataaa 1350 cacttactga agaagaagca ataagagaaa gatatttgta atctctccag 1400 cccatgatct cggttttctt acactgtgat cttaaaagtt accaaaccaa 1450 agtcattttc agtttgaggc aaccaaacct ttctactgct gttgacatct 1500 tcttattaca gcaacaccat tctaggagtt tcctgagctc tccactggag 1550 tcctctttct gtcgcgggtc agaaattgtc cctagatgaa tgagaaaatt 1600 atttttttta taaaatgata atttaagtcc cactatctct taaatatagt gtgaaatagc taaaataaat ctcaccccta aatgttttag catgtggata 1650 1700 gaaggaaatg aaaaaataat tgctttgaca ttgtctatat ggtactttgt 1750 aaagtcatgc ttaagtacaa attccatgaa aagctcacac ctgtaatcct 1800 agcactttgg gaggctgagg aggaaggatc acttgagccc agaagttcga 1850 gactagcctg ggcaacatgg agaagccctg tctctacaaa atacagagag 1900 aaaaaatcag ccagtcatgg tggcatacac ctgtagtccc agcattccgg 1950 gaggctgagg tgggaggatc acttgagccc agggaggttg gggctgcagt 2000 gagccatgat cacaccactg cactccagcc aggtgacata gcgagatcct 2050 gtctaaaaaa ataaaaaata aataatggaa cacagcaagt cctaggaagt 2100 aggttaaaac taattcttta a 2121 <210> 326 <211> 261 785 <212> PRT <213> Homo sapiens <400> 326 Met Ser Thr Thr Thr Cys Gin Val Val Ala Phe Leu Leu Ser Ile 15 10 15 Leu Gly Leu Ala Gly Cys Ile Ala Ala Thr Gly Met Asp Met Trp 20 25 30 Ser Thr Gin Asp Leu Tyr Asp Asn Pro Val Thr Ser Val Phe Gin 35 40 45 Tyr Glu Gly Leu Trp Arg Ser Cys Val Arg Gin Ser Ser Gly Phe 50 55 60 Thr Glu Cys Arg Pro Tyr Phe Thr Ile Leu Gly Leu Pro Ala Met 65 70 75 Leu Gin Ala Val Arg Ala Leu Met Ile Val Gly Ile Val Leu Gly 80 85 90 Ala Ile Gly Leu Leu Val Ser Ile Phe Ala Leu Lys Cys Ile Arg 95 100 105 Ile Gly Ser Met Glu Asp Ser Ala Lys Ala Asn Met Thr Leu Thr 110 115 120 Ser Gly Ile Met Phe Ile Val Ser Gly Leu Cys Ala Ile Ala Gly 125 130 ' 135 Val Ser Val Phe Ala Asn Met Leu Val Thr Asn Phe Trp Met Ser 140 145 150 Thr Ala Asn Met Tyr Thr Gly Met Gly Gly Met Val Gin Thr Val 155 160 165 Gin Thr Arg Tyr Thr Phe Gly Ala Ala Leu Phe Val Gly Trp Val 170 175 180 Ala Gly Gly Leu Thr Leu Ile Gly Gly Val Met Met Cys Ile Ala 185 190 195 Cys Arg Gly Leu Ala Pro Glu Glu Thr Asn Tyr Lys Ala Val Ser 200 205 210 Tyr His Ala Ser Gly His Ser Val Ala Tyr Lys Pro Gly Gly Phe 215 220 225 Lys Ala Ser Thr Gly Phe Gly Ser Asn Thr Lys Asn Lys Lys Ile 230 235 240 Tyr Asp Gly Gly Ala Arg Thr Glu Asp Glu Val Gin Ser Tyr Pro 245 250 255 Ser Lys His Asp Tyr Val 260 <210> 327 <211> 2010 <212> DNA <213> Homo sapiens 786 <400> 327 ggaaaaactg ttctcttctg tggcacagag aaccctgctt caaagcagaa 50 gtagcagttc cggagtccag ctggctaaaa ctcatcccag aggataatgg 100 caacccatgc cttagaaatc gctgggctgt ttcttggtgg tgttggaatg 150 gtgggcacag tggctgtcac tgtcatgcct cagtggagag tgtcggcctt 200 cattgaaaac aacatcgtgg tttttgaaaa cttctgggaa ggactgtgga 250 tgaattgcgt gaggcaggct aacatcagga tgcagtgcaa aatctatgat 300 tccctgctgg ctctttctcc ggacctacag gcagccagag gactgatgtg 350 tgctgcttcc gtgatgtcct tcttggcttt catgatggcc atccttggca 400 tgaaatgcac caggtgcacg ggggacaatg agaaggtgaa ggctcacatt 450 ctgctgacgg ctggaatcat cttcatcatc acgggcatgg tggtgctcat 500 ccctgtgagc tgggttgcca atgccatcat cagagatttc tataactcaa 550 tagtgaatgt tgcccaaaaa cgtgagcttg gagaagctct ctacttagga 600 tggaccacgg cactggtgct gattgttgga ggagctctgt tctgctgcgt 650 tttttgttgc aacgaaaaga gcagtagcta cagatactcg ataccttccc 700 atcgcacaac ccaaaaaagt tatcacaccg gaaagaagtc accgagcgtc 750 tactccagaa gtcagtatgt gtagttgtgt atgttttttt aactttacta 800 taaagccatg caaatgacaa aaatctatat tactttctca aaatggaccc 850 caaagaaact ttgatttact gttcttaact gcctaatctt aattacagga 900 actgtgcatc agctatttat gattctataa gctatttcag cagaatgaga 950 tattaaaccc aatgctttga ttgttctaga aagtatagta atttgttttc 1000 taaggtggtt caagcatcta ctctttttat catttacttc aaaatgacat 1050 tgctaaagac tgcattattt tactactgta atttctccac gacatagcat 1100 tatgtacata gatgagtgta acatttatat ctcacataga gacatgctta 1150 tatggtttta tttaaaatga aatgccagtc cattacactg aataaataga 1200 actcaactat tgcttttcag ggaaatcatg gatagggttg aagaaggtta 1250 ctattaattg tttaaaaaca gcttagggat taatgtcctc catttataat 1300 gaagattaaa atgaaggctt taatcagcat tgtaaaggaa attgaatggc 1350 tttctgatat gctgtttttt agcctaggag ttagaaatcc taacttcttt 1400 atcctcttct cccagaggct ttttttttct tgtgtattaa attaacattt 1450 ttaaaacgca gatattttgt caaggggctt tgcattcaaa ctgcttttcc 1500 agggctatac tcagaagaaa gataaaagtg 787 tgatctaaga aaaagtgatg 1550 gttttaggaa agtgaaaata tttttgtttt tgtatttgaa gaagaatgat 1600 gcattttgac aagaaatcat atatgtatgg atatatttta ataagtattt 1650 gagtacagac tttgaggttt catcaatata aataaaagag cagaaaaata 1700 tgtcttggtt ttcatttgct taccaaaaaa acaacaacaa aaaaagttgt 1750 cctttgagaa cttcacctgc tcctatgtgg gtacctgagt caaaattgtc 1800 atttttgttc tgtgaaaaat aaatttcctt cttgtaccat ttctgtttag 1850 ttttactaaa atctgtaaat actgtatttt tctgtttatt ccaaatttga 1900 tgaaactgac aatccaattt gaaagtttgt gtcgacgtct gtctagctta 1950 aatgaatgtg ttctatttgc tttatacatt tatattaata aattgtacat 2000 ttttctaatt 2010 <210> 328 <211> 225 <212> PRT <213> Homo sapiens <400> 328 Met Ala Thr His Ala Leu Glu Ile Ala Gly Leu Phe Leu Gly Gly 10 15 Val Gly Met Val Gly Thr Val Ala Val Thr Val Met Pro Gin Trp 25 30 Arg Val Ser Ala Phe Ile Glu Asn Asn Ile Val Val Phe Glu Asn 40 45 Phe Trp Glu Gly Leu Trp Met Asn Cys Val Arg Gin Ala Asn Ile 50 55 60 Arg Met Gin Cys Lys Ile Tyr Asp Ser Leu Leu Ala Leu Ser Pro 65 70 75 Asp Leu Gin Ala Ala Arg Gly Leu Met Cys Ala Ala Ser Val Met 80 85 90 Ser Phe Leu Ala Phe Met Met Ala Ile Leu Gly Met Lys Cys Thr 95 100 105 Arg Cys Thr Gly Asp Asn Glu Lys Val Lys Ala His Ile Leu Leu 110 115 120 Thr Ala Gly Ile Ile Phe Ile Ile Thr Gly Met Val Val Leu Ile 125 130 135 Pro Val Ser Trp Val Ala Asn Ala Ile Ile Arg Asp Phe Tyr Asn 140 145 150 Ser Ile Val Asn Val Ala Gin Lys Arg Glu Leu Gly Glu Ala Leu 155 160 165 Tyr Leu Gly Trp Thr Thr Ala Leu Val Leu Ile Val Gly Gly Ala 788 170 175 180 Leu Phe Cys Cys Val Phe Cys Cys Asn Glu Lys Ser Ser Ser Tyr 185 190 195 Arg Tyr Ser Ile Pro Ser His Arg Thr Thr Gin Lys Ser Tyr His 200 205 210 Thr Gly Lys Lys Ser Pro Ser Val Tyr Ser Arg Ser Gin Tyr Val 215 220 225 <210> 329 <211> 1315 <212> DNA <213> Homo sapiens <400> 329 tcgccatggc ctctgccgga atgcagatcc tgggagtcgt cctgacactg 50 ctgggctggg tgaatggcct ggtctcctgt gccctgccca tgtggaaggt 100 gaccgctttc atcggcaaca gcatcgtggt ggcccaggtg gtgtgggagg 150 gcctgtggat gtcctgcgtg gtgcagagca ccggccagat gcagtgcaag 200 gtgtacgact cactgctggc gctgccacag gacctgcagg ctgcacgtgc 250 cctctgtgtc atcgccctcc ttgtggccct gttcggcttg ctggtctacc 300 ttgctggggc caagtgtacc acctgtgtgg aggagaagga ttccaaggcc 350 cgcctggtgc tcacctctgg gattgtcttt gtcatctcag gggtcctgac 400 gctaatcccc gtgtgctgga cggcgcatgc catcatccgg gacttctata 450 accccctggt ggctgaggcc caaaagcggg agctgggggc ctccctctac 500 ttgggctggg cggcctcagg ccttttgttg ctgggtgggg ggttgctgtg 550 ctgcacttgc ccctcggggg ggtcccaggg ccccagccat tacatggccc 600 gctactcaac atctgcccct gccatctctc gggggccctc tgagtaccct 650 accaagaatt gagccatcca acgtctgacg gaagtggcag tggaggggaa tgcccaacag tgggggctcc ctttgggatg gctggcgcta ggttcgtacc 700 750 ttttgtttct gcctcctgct atttttcttt tgactgagga tatttaaaat 800 tcatttgaaa actgagccaa ggtgttgact cagactctca cttaggctct 850 gctgtttctc acccttggat gatggagcca aagaggggat gctttgagat 900 tctggatctt gacatgccca tcttagaagc cagtcaagct atggaactaa 950 tgcggaggct gcttgctgtg ctggctttgc aacaagacag actgtcccca 1000 agagttcctg ctgctgctgg gggctgggct tccctagatg tcactggaca 1050 gctgcccccc atcctactca ggtctctgga gctcctctct tcacccctgg 1100 aaaaacaaat catctgttaa caaaggactg cccacctccg gaacttctga 1150 789 cctctgtttc ctccgtcctg ataagacgtc caccccccag ggccaggtcc 1200 cagctatgta gacccccgcc cccacctcca acactgcacc cttctgccct 12 50 gcccccctcg tctcaccccc tttacactca catttttatc aaataaagca 1300 tgttttgtta gtgca 1315 <210> 330 <211> 220 <212> PRT <213> Homo sapiens <400> 330 Met Ala Ser Ala Gly Met Gin lie Leu Gly Val Val Leu Thr Leu 15 10 15 Leu Gly Trp Val Asn Gly Leu Val Ser Cys Ala Leu Pro Met Trp 20 25 30 Lys Val Thr Ala Phe Ile Gly Asn Ser Ile Val Val Ala Gin Val 35 40 45 Val Trp Glu Gly Leu Trp Met Ser Cys Val Val Gin Ser Thr Gly 50 55 60 Gin Met Gin Cys Lys Val Tyr Asp Ser Leu Leu Ala Leu Pro Gin 65 70 75 Asp Leu Gin Ala Ala Arg Ala Leu Cys Val Ile Ala Leu Leu Val 80 85 90 Ala Leu Phe Gly Leu Leu Val Tyr Leu Ala Gly Ala Lys Cys Thr 95 100 105 Thr Cys Val Glu Glu Lys Asp Ser Lys Ala Arg Leu Val Leu Thr 110 115 120 Ser Gly Ile Val Phe Val Ile Ser Gly Val Leu Thr Leu Ile Pro 125 130 135 Val Cys Trp Thr Ala His Ala Ile Ile Arg Asp Phe Tyr Asn Pro 140 145 150 Leu Val Ala Glu Ala Gin Lys Arg Glu Leu Gly Ala Ser Leu Tyr 155 160 165 Leu Gly Trp Ala Ala Ser Gly Leu Leu Leu Leu Gly Gly Gly Leu 170 175 180 Leu Cys Cys Thr Cys Pro Ser Gly Gly Ser Gin Gly Pro Ser His 185 190 195 Tyr Met Ala Arg Tyr Ser Thr Ser Ala Pro Ala Ile Ser Arg Gly 200 205 210 Pro Ser Glu Tyr Pro Thr Lys Asn Tyr Val 215 220 <210> 331 <211> 1160 <212> DNA 790 <213> Homo sapiens <400> 331 gccaaggaga acatcatcaa agacttctct agactcaaaa ggcttccacg 50 ttctacatct tgagcatctt ctaccactcc gaattgaacc agtcttcaaa 100 gtaaaggcaa tggcatttta tcccttgcaa attgctgggc tggttcttgg 150 gttccttggc atggtgggga ctcttgccac aacccttctg cctcagtggt 200 ggagtatcag cttttgttgg cagcaacatt attgtctttg agaggctctg 250 ggaagggctc tggatgaatt gcatccgaca agccagggtc cggttgcaat 300 gcaagttcta tagctccttg ttggctctcc cgcctgccct ggaaacagcc 350 cgggccctca tgtgtgtggc tgttgctctc tccttgatcg ccctgcttat 400 tggcatctgt ggcatgaagc aggtccagtg cacaggctct aacgagaggg 450 ccaaagcata ccttctggga acttcaggag tcctcttcat cctgacgggt 500 atcttcgttc tgattccggt gagctggaca gccaatataa tcatcagaga 550 tttctacaac ccagccatcc acataggtca gaaacgagag ctgggagcag 600 cacttttcct tggctgggca agcgctgctg tcctcttcat tggagggggt 650 ctgctttgtg gattttgctg ctgcaacaga aagaagcaag ggtacagata 700 tccagtgcct ggctaccgtg tgccacacac agataagcga agaaatacga 750 caatgcttag taagacctcc accagttatg tctaatgcct ccttttggct 800 ccaagtatgg actatggtca atgttttfcta taaagtcctg ctagaaactg 850 taagtatgtg aggcaggaga acttgcttta tgtctagatt tacattgata 900 cgaaagtttc aatttgttac tggtggtagg aatgaaaatg acttacttgg 950 acattctgac ttcaggtgta ttaaatgcat tgactattgt tggacccaat 1000 cgctgctcca attttcatat tctaaattca agtataccca taatcattag 1050 caagtgtaca ctgataagaa atgatggact tctaaagttg acttattact aaattgatat ttttgaccat tctataacaa catgtattat taaaacatat 1100 1150 acctattcta 1160 <210> 332 <211> 173 <212> PRT <213> Homo sapiens <400> 332 Met Asn Cys Ile Arg Gin Ala Arg Val Arg Leu Gin Cys Lys Phe 1 5 10 15 Tyr Ser Ser Leu Leu Ala Leu Pro Pro Ala Leu Glu Thr Ala Arg 20 25 30 791 Ala Leu Met Cys Val Ala Val Ala Leu Ser Leu Ile Ala Leu Leu 35 40 45 Ile Gly Ile Cys Gly Met Lys Gin Val Gin Cys Thr Gly Ser Asn 50 55 60 Glu Arg Ala Lys Ala Tyr Leu Leu Gly Thr Ser Gly Val Leu Phe 65 70 75 Ile Leu Thr Gly Ile Phe Val Leu Ile Pro Val Ser Trp Thr Ala 80 85 90 Asn Ile Ile Ile Arg Asp Phe Tyr Asn Pro Ala Ile His Ile Gly 95 100 105 Gin Lys Arg Glu Leu Gly Ala Ala Leu Phe Leu Gly Trp Ala Ser 110 115 120 Ala Ala Val Leu Phe Ile Gly Gly Gly Leu Leu Cys Gly Phe Cys 125 130 135 Cys Cys Asn Arg Lys Lys Gin Gly Tyr Arg Tyr Pro Val Pro Gly 140 145 150 Tyr Arg Val Pro His Thr Asp Lys Arg Arg Asn Thr Thr Met Leu 155 160 165 Ser Lys Thr Ser Thr Ser Tyr Val 170 <210> 333 <211> 535 <212> DNA <213> Homo sapiens <400> 333 agtgacaatc tcagagcagc ttctacacca cagccatttc cagcatgaag 50 atcactgggg gtctccttct gctctgtaca gtggtctatt tctgtagcag 100 ctcagaagct gctagtctgt ctccaaaaaa agtggactgc agcatttaca 150 agaagtatcc agtggtggcc atcccctgcc ccatcacata cctaccagtt 200 tgtggttctg actacatcac ctatgggaat gaatgtcact tgtgtaccga 250 gagcttgaaa aaattctcca agtaatggaa tggacataga gagttcagtt gagaaaggaa tcttcacgat tgatattctc ggaagttgct atcatcatct 300 350 tcatcatccc aggctctgac tgagtttctt tcagttttac tgatgttctg 400 ggtgggggac agagccagat tcagagtaat cttgactgaa tggagaaagt 450 ttctgtgcta cccctacaaa cccatgcctc actgacagac cagcattttt 500 tttttaacac gtcaataaaa aaataatctc ccaga 535 <210> 334 <211> 85 <212> PRT <213> Homo sapiens 792 <400> 334 Met Lys Ile Thr Gly Gly Leu Leu Leu Leu Cys Thr Val Val Tyr 15 10 15 Phe Cys Ser Ser Ser Glu Ala Ala Ser Leu Ser Pro Lys Lys Val 20 25 30 Asp Cys Ser Ile Tyr Lys Lys Tyr Pro Val Val Ala Ile Pro Cys 35 40 45 Pro Ile Thr Tyr Leu Pro Val Cys Gly Ser Asp Tyr Ile Thr Tyr 50 55 60 Gly Asn Glu Cys His Leu Cys Thr Glu Ser Leu Lys Ser Asn Gly 65 70 75 Arg Val Gin Phe Leu His Asp Gly Ser Cys 80 85 <210> 335 <211> 742 <212> DNA <213> Homo sapiens <400> 335 cccgcgcccg gttctccctc gcagcacctc gaagtgcgcc cctcgccctc 50 ctgctcgcgc cccgccgcca tggctgcctc ccccgcgcgg cctgctgtcc 100 tggccctgac cgggctggcg ctgctcctgc tcctgtgctg gggcccaggt 150 ggcataagtg gaaataaact caagctgatg cttcaaaaac gagaagcacc 200 tgttccaact aagactaaag tggccgttga tgagaataaa gccaaagaat 250 tccttggcag cctgaagcgc cagaagcggc agctgtggga ccggactcgg 300 cccgaggtgc agcagtggta ccagcagttt ctctacatgg gctttgatga 350 agcgaaattt gaagatgaca tcacctattg gcttaacaga gatcgaaatg 400 gacatgaata ctatggcgat tactaccaac gtcactatga tgaagactct 450 gcaattggtc cccggagccc ctacggcttt aggcatggag ccagcgtcaa 500 ctacgatgac tactaaccat gacttgccac acgctgtaca agaagcaaat 550 agcgattctc tttgctctat ttcatgtatc ttcagcagat tcctaatgcc cttttctacc ttacactact tactttgtgt tggtttctga gatcaaaaaa 600 650 gaagagttaa aacaacacat gtaaatgcct tttgatattt catgggaatg 700 cctctcattt aaaaatagaa ataaagcatt ttgttaaaaa ga 742 <210> 336 <211> 148 <212> PRT <213> Homo sapiens <400> 336 Met Ala Ala Ser Pro Ala Arg Pro Ala Val Leu Ala Leu Thr Gly 15 10 15 793 Leu Ala Leu Leu Leu Leu Leu Cys Trp Gly Pro Gly Gly Ile Ser 20 25 30 Gly Asn Lys Leu Lys Leu Met Leu Gin Lys Arg Glu Ala Pro Val 35 40 45 Pro Thr Lys Thr Lys Val Ala Val Asp Glu Asn Lys Ala Lys Glu 50 55 60 Phe Leu Gly Ser Leu Lys Arg Gin Lys Arg Gin Leu Trp Asp Arg 65 70 75 Thr Arg Pro Glu Val Gin Gin Trp Tyr Gin Gin Phe Leu Tyr Met 80 85 90 Gly Phe Asp Glu Ala Lys Phe Glu Asp Asp Ile Thr Tyr Trp Leu 95 100 105 Asn Arg Asp Arg Asn Gly His Glu Tyr Tyr Gly Asp Tyr Tyr Gin 110 115 120 Arg His Tyr Asp Glu Asp Ser Ala Ile Gly Pro Arg Ser Pro Tyr 125 130 135 Gly Phe Arg His Gly Ala - Ser Val Asn Tyr Asp Asp Tyr 140 145 <210> 337 <211> 1310 <212> DNA <213> Homo sapiens <400> 337 cggctcgagc ccgcccggaa gtgcccgagg ggccgcgatg gagctggggg 50 agccgggcgc tcggtagcgc ggcgggcaag gcaggcgcca tgaccctgat 100 tgaaggggtg ggtgatgagg tgaccgtcct tttctcggtg cttgcctgcc 150 ttctggtgct ggcccttgcc tgggtctcaa cgcacaccgc tgagggcggg 200 gacccactgc cccagccgtc agggacccca acgccatccc agcccagcgc 250 agccatggca gctaccgaca gcatgagagg ggaggcccca ggggcagaga 300 cccccagcct gagacacaga ggtcaagctg cacagccaga gcccagcacg 350 gggttcacag gctacggctg caacaccgcc aaattcctca agccccggac atgattcaga tccccgcagg gcaggtggcc agcccctcgt agggcctggc 400 450 cccacgacac cattggctcc ttgaaaagga cccagtttcc cggccgggaa 500 cagcaggtgc gactcatcta ccaagggcag ctgctaggcg acgacaccca 550 gaccctgggc agccttcacc tccctcccaa ctgcgttctc cactgccacg 600 tgtccacgag agtcggtccc ccaaatcccc cctgcccgcc ggggtccgag 650 cccggcccct ccgggctgga aatcggcagc ctgctgctgc ccctgctgct 700 cctgctgttg ctgctgctct ggtactgcca gatccagtac cggcccttct 750 794 ttcccctgac cgccactctg ggcctggccg gcttcaccct gctcctcagt 800 ctcctggcct ttgccatgta ccgcccgtag tgcctccgcg ggcgcttggc 850 agcgtcgccg gcccctccgg accttgctcc ccgcgccgcg gcgggagctg 900 ctgcctgccc aggcccgcct ctccggcctg cctcttcccg ctgccctgga 950 gcccagccct gcgccgcaga ggactcccgg gactggcgga ggccccgccc 1000 tgcgaccgcc ggggctcggg gccacctccc ggggctgctg aacctcagcc 1050 cgcactggga gtgggctcct cggggtcggg catctgctgt cgctgcctcg 1100 gccccgggca gagccgggcc gccccggggg cccgtcttag tgttctgccg 1150 gaggacccag ccgcctccaa tccctgacag ctccttgggc tgagttgggg 12 00 acgccaggtc ggtgggaggc tggtgaaggg gagcggggag gggcagagga 1250 gttccccgga acccgtgcag attaaagtaa ctgtgaagtt ttaaaaaaaa 1300 aaaaaaaaaa 1310 <210> 338 <211> 246 <212> PRT <213> Homo sapiens <400> 338 Met Thr Leu Ile Glu Gly Val Gly Asp Glu Val Thr Val Leu Phe 15 10 15 Ser Val Leu Ala Cys Leu Leu Val Leu Ala Leu Ala Trp Val Ser 20 25 30 Thr His Thr Ala Glu Gly Gly Asp Pro Leu Pro Gin Pro Ser Gly 35 40 45 Thr Pro Thr Pro Ser Gin Pro Ser Ala Ala Met Ala Ala Thr Asp 50 55 60 Ser Met Arg Gly Glu Ala Pro Gly Ala Glu Thr Pro Ser Leu Arg 65 70 75 His Arg Gly Gin Ala Ala Gin Pro Glu Pro Ser Thr Gly Phe Thr 80 85 90 Ala Thr Pro Pro Ala Pro Asp Ser Pro Gin Glu Pro Leu Val Leu 95 100 105 Arg Leu Lys Phe Leu Asn Asp Ser Glu Gin Val Ala Arg Ala Trp 110 115 120 Pro His Asp Thr Ile Gly Ser Leu Lys Arg Thr Gin Phe Pro Gly 125 130 135 Arg Glu Gin Gin Val Arg Leu Ile Tyr Gin Gly Gin Leu Leu Gly 140 145 150 Asp Asp Thr Gin Thr Leu Gly Ser Leu His Leu Pro Pro Asn Cys 795 155 160 165 Val Leu His Cys His Val Ser Thr Arg Val Gly Pro Pro Asn Pro 170 175 180 Pro Cys Pro Pro Gly Ser Glu Pro Gly Pro Ser Gly Leu Glu Ile 185 190 195 Gly Ser Leu Leu Leu Pro Leu Leu Leu Leu Leu Leu Leu Leu Leu 200 205 210 Trp Tyr Cys Gin Ile Gin Tyr Arg Pro Phe Phe Pro Leu Thr Ala 215 . 220 225 Thr Leu,Gly Leu Ala Gly Phe Thr Leu Leu Leu Ser Leu Leu Ala 230 235 240 Phe Ala Met Tyr Arg Pro 245 <210> 339 <211> 849 <212> DNA <213> Homo sapiens <400> 339 gagattggaa acagccaggt tggagcagtg agtgagtaag gaaacctggc 50 tgccctctcc agattcccca ggctctcaga gaagatcagc agaaagtctg 100 caagacccta agaaccatca gccctcagct gcacctcctc ccctccaagg 150 atgacaaagg cgctactcat ctatttggtc agcagctttc ttgccctaaa 200 tcaggccagc ctcatcagtc gctgtgactt ggcccaggtg ctgcagctgg 250 aggacttgga tgggtttgag ggttactccc tgagtgactg gctgtgcctg 300 gcttttgtgg aaagcaagtt caacatatca aagataaatg aaaatgcgga 350 tggaagcttt gactatggcc tcttccagat caacagccac tactggtgca 400 acgattataa gagttactcg gaaaaccttt gccacgtaga ctgtcaagat 450 ctgctgaatc ccaaccttct tgcaggcatc cactgcgcaa aaaggattgt 500 gtccggagca cgggggatga acaactgggt agaatggagg ttgcactgtt 550 caggccggcc actctcctac tggctgacag gatgccgcct gagatgaaac 600 agggtgcggg ggattcttca tgcaccgtgg tttcttcttc agtcattcca ctactgcctc agactcctgt cacttcatgt cctcactcag tattttcttc 650 700 ccttcccatt tacaactaaa actgaccaga gccccaggaa taaatggttt 750 tcttggcttc ctccttactc ccatctggac ccagtcccct ggttcctgtc 800 tgttatttgt aaactgagga ccacaataaa gaaatcttta tatttatcg 849 <210> 340 <211> 148 <212> PRT <213> Homo sapiens 796 <400> 340 Met Thr Lys Ala Leu Leu Ile Tyr Leu Val Ser Ser Phe Leu Ala 15 10 15 Leu Asn Gin Ala Ser Leu Ile Ser Arg Cys Asp Leu Ala Gin Val 20 25 30 Leu Gin Leu Glu Asp Leu Asp Gly Phe Glu Gly Tyr Ser Leu Ser 35 40 45 Asp Trp Leu Cys Leu Ala Phe Val Glu Ser Lys Phe Asn Ile Ser 50 55 60 Lys Ile Asn Glu Asn Ala Asp Gly Ser Phe Asp Tyr Gly Leu Phe 65 70 75 Gin Ile Asn Ser His Tyr Trp Cys Asn Asp Tyr Lys Ser Tyr Ser 80 85 90 Glu Asn Leu Cys His Val Asp Cys Gin Asp Leu Leu Asn Pro Asn 95 100 105 Leu Leu Ala Gly Ile His Cys Ala Lys Arg Ile Val Ser Gly Ala 110 115 120 Arg Gly Met Asn Asn Trp Val Glu Trp Arg Leu His Cys Ser Gly 125 130 135 Arg Pro Leu Ser Tyr Trp Leu Thr Gly Cys Arg Leu Arg 140 145 <210> 341 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 341 ccctccaagg atgacaaagg cgc 23 <210> 342 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 342 ggtcagcagc tttcttgccc taaatcagg 2 9 <210> 343 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe 797 <400> 343 atctcaggcg gcatcctgtc agcc 24 <210> 344 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 344 gtggatgcct gcaagaaggt tggg 24 <210> 345 <211> 45 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 345 agctttcttg ccctaaatca ggccagcctc atcagtcgct gtgac 45 <210> 346 <211> 2575 <212> DNA <213> Homo sapiens <400> 346 tctgacctga ctggaagcgt ccaaagaggg acggctgtca gccctgcttg 50 actgagaacc caccagctca tcccagacac ctcatagcaa cctatttata 100 caaaggggga aagaaacacc tgagcagaat ggaatcatta tttttttccc 150 aaggagaaaa ccggggtaaa gggagggaag caattcaatt tgaagtccct 200 gtgaatgggc tttcagaagg caattaaaga aatccactca gagaggactt 250 ggggtgaaac ttgggtcctg tggttttctg attgtaagtg gaagcaggtc 300 ttgcacacgc tgttggcaaa tgtcaggacc aggttaagtg actggcagaa 350 aaacttccag gtggaacaag caacccatgt tctgctgcaa gcttgaagga 400 gcctggagcg ggagaaagct aacttgaaca tgacctgttg catttggcaa 450 gttctagcaa catgctccta aggaagcgat acaggcacag accatgcaga 500 ctccagttcc ggcgatgttg tcctgctgct caccctcccc cctgatgctg accacaccct ggatgcgtcc gcaccagact tgatgatggt gtcacagccc 550 600 aagccagcaa gcacagccct gaagccaggt accgcctgga ctttggggaa 650 tcccaggatt gggtactgga agctgaggat gagggtgaag agtacagccc 700 tctggagggc ctgccaccct ttatctcact gcgggaggat cagctgctgg 750 tggccgtggc cttaccccag gccagaagga accagagcca gggcaggaga 800 798 ggtgggagct accgcctcat caagcagcca aggaggcagg ataaggaagc 850 cccaaagagg gactgggggg ctgatgagga cggggaggtg tctgaagaag 900 aggagttgac cccgttcagc ctggacccac gtggcctcca ggaggcactc 950 agtgcccgca tccccctcca gagggctctg cccgaggtgc ggcacccact 1000 gtgtctgcag cagcaccctc aggacagcct gcccacagcc agcgtcatcc 1050 tctgtttcca tgatgaggcc tggtccactc tcctgcggac tgtacacagc 1100 atcctcgaca cagtgcccag ggccttcctg aaggagatca tcctcgtgga 1150 cgacctcagc cagcaaggac aactcaagtc tgctctcagc gaatatgtgg 1200 ccaggctgga gggggtgaag ttactcagga gcaacaagag gctgggtgcc 1250 atcagggccc ggatgctggg ggccaccaga gccaccgggg atgtgctcgt 1300 cttcatggat gcccactgcg agtgccaccc aggctggctg gagcccctcc 1350 tcagcagaat agctggtgac aggagccgag tggtatctcc ggtgatagat 1400 gtgattgact ggaagacttt ccagtattac ccctcaaagg acctgcagcg 1450 tggggtgttg gactggaagc tggatttcca ctgggaacct ttgccagagc 1500 atgtgaggaa ggccctccag tcccccataa gccccatcag gagccctgtg 1550 gtgcccggag aggtggtggc catggacaga cattacttcc aaaacactgg 1600 agcgtatgac tctcttatgt cgctgcgagg tggtgaaaac ctcgaactgt 1650 ctttcaaggc ctggctctgt ggtggctctg ttgaaatcct tccctgctct 1700 cgggtaggac acatctacca aaatcaggat tcccattccc ccctcgacca 1750 ggaggccacc ctgaggaaca gggttcgcat tgctgagacc tggctggggt 1800 cattcaaaga aaccttctac aagcatagcc cagaggcctt ctccttgagc 1850 aaggctgaga agccagactg catggaacgc ttgcagctgc aaaggagact 1900 gggttgtcgg acattccact ggtttctggc taatgtctac cctgagctgt 1950 acccatctga acccaggccc agtttctctg gaaagctcca caacactgga 2000 cttgggctct gtgcagactg ccaggcagaa ggggacatcc tgggctgtcc 2050 catggtgttg gctccttgca gtgacagccg gcagcaacag tacctgcagc 2100 acaccagcag gctgtcaggc gaaggagatt aggagcaggt cactttggca gattcttcag gcccacagca aactgcacgg cctgtgcttt aggaaggcct 2150 2200 ggccatccac cagcagcact gggacttcca ggagaatggg atgattgtcc 2250 acattctttc tgggaaatgc atggaagctg tggtgcaaga aaacaataaa 2300 gatttgtacc tgcgtccgtg tgatggaaaa gcccgccagc agtggcgatt 2350 799 tgaccagata aatgctgtgg atgaacgatg aatgtcaatg tcagaaggaa 2400 aagagaattt tggccatcaa aatccagctc caagtgaacg taaagagctt 2450 atatatttca tgaagctgat ccttttgtgt gtgtgctcct tgtgttagga 2500 gagaaaaaag ctctatgaaa gaatatagga agtttctcct tttcacacct 2550 tatttcattg actgctggct gctta 2575 <210> 347 <211> 639 <212> PRT <213> Homo sapiens <400> 347 Met Leu Leu Arg Lys Arg Tyr Arg His Arg Pro Cys Arg Leu Gin 15 10 15 Phe Leu Leu Leu Leu Leu Met Leu Gly Cys Val Leu Met Met Val 20 25 30 Ala Met Leu His Pro Pro His His Thr Leu His Gin Thr Val Thr 35 40 45 Ala Gin Ala Ser Lys His Ser Pro Glu Ala Arg Tyr Arg Leu Asp 50 55 60 Phe Gly Glu Ser Gin Asp Trp Val Leu Glu Ala Glu Asp Glu Gly 65 70 75 Glu Glu Tyr Ser Pro Leu Glu Gly Leu Pro Pro Phe Ile Ser Leu 80 85 90 Arg Glu Asp Gin Leu Leu Val Ala Val Ala Leu Pro Gin Ala Arg 95 100 105 Arg Asn Gin Ser Gin Gly Arg Arg Gly Gly Ser Tyr Arg Leu Ile 110 115 120 Lys Gin Pro Arg Arg Gin Asp Lys Glu Ala Pro Lys Arg Asp Trp 125 130 135 Gly Ala Asp Glu Asp Gly Glu Val Ser Glu Glu Glu Glu Leu Thr 140 145 150 Pro Phe Ser Leu Asp Pro Arg Gly Leu Gin Glu Ala Leu Ser Ala 155 160 165 Arg Ile Pro Leu Gin Arg Ala Leu Pro Glu Val Arg His Pro Leu 170 175 180 Cys Leu Gin Gin His Pro Gin Asp Ser Leu Pro Thr Ala Ser Val 185 190 195 Ile Leu Cys Phe His Asp Glu Ala Trp Ser Thr Leu Leu Arg Thr 200 205 210 Val His Ser Ile Leu Asp Thr Val Pro Arg Ala Phe Leu Lys Glu 215 220 225 Ile Ile Leu Val Asp Asp Leu Ser Gin Gin Gly Gin Leu Lys Ser 230 800 235 240 Ala Leu Ser Glu Tyr Val Ala Arg Leu Glu Gly Val Lys Leu Leu 245 250 255 Arg Ser Asn Lys Arg Leu Gly Ala Ile Arg Ala Arg Met Leu Gly 260 265 270 Ala Thr Arg Ala Thr Gly Asp Val Leu Val Phe Met Asp Ala His 275 280 285 Cys Glu Cys His Pro Gly Trp Leu Glu Pro Leu Leu Ser Arg Ile 290 295 300 Ala Gly Asp Arg Ser Arg Val Val Ser Pro Val Ile Asp Val Ile 305 310 315 Asp Trp Lys Thr Phe Gin Tyr Tyr Pro Ser Lys Asp Leu Gin Arg 320 325 330 Gly Val Leu Asp Trp Lys Leu Asp Phe His Trp Glu Pro Leu Pro 335 340 345 Glu His Val Arg Lys Ala Leu Gin Ser Pro Ile Ser Pro Ile Arg 350 355 360 Ser Pro Val Val Pro Gly Glu Val Val Ala Met Asp Arg His Tyr 365 370 375 Phe Gin Asn Thr Gly Ala Tyr Asp Ser Leu Met Ser Leu Arg Gly 380 385 390 Gly Glu Asn Leu Glu Leu Ser Phe Lys Ala Trp Leu Cys Gly Gly 395 400 405 Ser Val Glu Ile Leu Pro Cys Ser Arg Val Gly His Ile Tyr Gin 410 415 420 Asn Gin Asp Ser His Ser Pro Leu Asp Gin Glu Ala Thr Leu Arg 425 430 435 Asn Arg Val Arg Ile Ala Glu Thr Trp Leu Gly Ser Phe Lys Glu 440 445 450 Thr Phe Tyr Lys His Ser Pro Glu Ala Phe Ser Leu Ser Lys Ala 455 460 465 Glu Lys Pro Asp Cys Met Glu Arg Leu Gin Leu Gin Arg Arg Leu 470 475 480 Gly Cys Arg Thr Phe His Trp Phe Leu Ala Asn Val Tyr Pro Glu 485 490 495 Leu Tyr Pro Ser Glu Pro Arg Pro Ser Phe Ser Gly Lys Leu His 500 505 510 Asn Thr Gly Leu Gly Leu Cys Ala Asp Cys Gin Ala Glu Gly Asp 515 520 525 Ile Leu Gly Cys Pro Met Val Leu Ala Pro Cys Ser Asp Ser Arg 530 535 540 801 Gin Gin Gin Tyr Leu Gin His Thr Ser Arg Lys Glu Ile His Phe 545 550 555 Gly Ser Pro Ile Leu Gin His Trp Asp Gly Lys Cys Tyr Leu Arg Asp Gin Ile <210> 348 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 348 ggagaggtgg tggccatgga cag 23 <210> 349 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 349 ctgtcactgc aaggagccaa cacc 24 <210> 350 <211> 45 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 350 tatgtcgctg cgaggtggtg aaaacctcga actgtctttc aaggc 45 <210> 351 <211> 2524 <212> DNA <213> Homo sapiens <400> 351 cgccaagcat gcagtaaagg ctgaaaatct gggtcacagc tgaggaagac 50 Gin His Leu Cys Phe Ala Val Arg Gin Glu Gin Val 560 565 570 Asn Cys Thr Glu Glu Gly Leu Ala Ile His Gin Gin 575 580 585 Phe Gin Glu Asn Gly Met Ile Val His Ile Leu Ser 590 595 600 Met Glu Ala Val Val Gin Glu Asn Asn Lys Asp Leu 605 610 615 Pro Cys Asp Gly Lys Ala Arg Gin Gin Trp Arg Phe 620 625 630 Asn Ala Val Asp Glu Arg 635 802 ctcagacatg gagtccagga tgtggcctgc gctgctgctg tcccacctcc 100 tccctctctg gccactgctg ttgctgcccc tcccaccgcc tgctcagggc 150 tcttcatcct cccctcgaac cccaccagcc ccagcccgcc ccccgtgtgc 200 caggggaggc ccctcggccc cacgtcatgt gtgcgtgtgg gagcgagcac 250 ctccaccaag ccgatctcct cgggtcccaa gatcacgtcg gcaagtcctg 300 cctggcactg cacccccagc caccccatca ggctttgagg aggggccgcc 350 ctcatcccaa tacccctggg ctatcgtgtg gggtcccacc gtgtctcgag 400 aggatggagg ggaccccaac tctgccaatc ccggatttct ggactatggt 450 tttgcagccc ctcatgggct cgcaacccca caccccaact cagactccat 500 gcgaggtgat ggagatgggc ttatccttgg agaggcacct gccaccctgc 550 ggccattcct gttcgggggc cgtggggaag gtgtggaccc ccagctctat 600 gtcacaatta ccatctccat catcattgtt ctcgtggcca ctggcatcat 650 cttcaagttc tgctgggacc gcagccagaa gcgacgcaga ccctcagggc 700 agcaaggtgc cctgaggcag gaggagagcc agcagccact gacagacctg 750 tccccggctg gagtcactgt gctgggggcc ttcggggact cacctacccc 800 cacccctgac catgaggagc cccgaggggg accccggcct gggatgcccc 850 accccaaggg ggctccagcc ttccagttga accggtgagg gcaggggcaa 900 tgggatggga gggcaaagag ggaaggcaac ttaggtcttc agagctgggg 950 tgggggtgcc ctctggatgg gtagtgagga ggcaggcgtg gcctcccaca 1000 gcccctggcc ctcccaaggg ggctggacca gctcctctct gggaggcacc 1050 cttccttctc ccagtctctc aggatctgtg tcctattctc tgctgcccat 1100 aactccaact ctgccctctt tggttttttc tcatgccacc ttgtctaaga 1150 caactctgcc ctcttaacct tgattccccc tctttgtctt gaacttcccc 1200 ttctattctg gcctacccct tggttcctga ctgtgccctt tccctcttcc 1250 tctcaggatt cccctggtga atctgtgatg cccccaatgt tggggtgcag 1300 ccaagcagga ggccaagggg ccggcacagc ccccatccca ctgagggtgg 1350 ggcagctgtg gggagctggg gccacagggg ctcctggctc ctgccccttg 1400 cacaccaccc ggaacactcc ccagccccac gggcaatcct atctgctcgc 1450 cctcctgcag gtgggggcct cacatatctg tgacttcggg tccctgtccc 1500 cacccttgtg cactcacatg aaagccttgc acactcacct ccaccttcac 1550 aggccatttg cacacgctcc tgcaccctct ccccgtccat accgctccgc 1600 803 tcagctgact ctcatgttct ctcgtctcac atttgcactc tctccttccc 1650 acattctgtg ctcagctcac tcagtggtca gcgtttcctg cacactttac 1700 ctctcatgtg cgtttcccgg cctgatgttg tggtggtgtg cggcgtgctc 1750 actctctccc tcatgaacac ccacccacct cgtttccgca gcccctgcgt 1800 gctgctccag aggtgggtgg gaggtgagct gggggctcct tgggccctca 1850 tcggtcatgg tctcgtccca ttccacacca tttgtttctc tgtctcccca 1900 tcctactcca aggatgccgg catcaccctg agggctcccc cttgggaatg 1950 gggtagtgag gccccagact tcacccccag cccactgcta aaatctgttt 2000 tctgacagat gggttttggg gagtcgcctg ctgcactaca tgagaaaggg 2050 actcccattt gcccttccct ttctcctaca gtcccttttg tcttgtctgt 2100 cctggctgtc tgtgtgtgtg ccattctctg gacttcagag ccccctgagc 2150 cagtcctccc ttcccagcct ccctttgggc ctccctaact ccacctaggc 2200 tgccagggac cggagtcagc tggttcaagg ccatcgggag ctctgcctcc 2250 aagtctaccc ttcccttccc ggactccctc ctgtcccctc ctttcctccc 2300 tccttccttc cactctcctt ccttttgctt ccctgccctt tccccctcct 2350 caggttcttc cctccttctc actggttttt ccaccttcct ccttcccttc 2400 ttccctggct cctaggctgt gatatatatt tttgtattat ctctttcttc 2450 ttcttgtggt gatcatcttg aattactgtg ggatgtaagt ttcaaaattt 2500 tcaaataaag cctttgcaag ataa 2524 <210> 352 <211> 243 <212> PRT <213> Homo sapiens <400> 352 Met Arg Pro Gin Gly Pro Ala Ala Ser Pro Gin Arg Leu Arg Gly 15 10 15 Leu Leu Leu Leu Leu Leu Leu Gin Leu Pro Ala Pro Ser Ser Ala 20 25 30 Ser Glu Ile Pro Lys Gly Lys Gin Lys Ala Gin Leu Arg Gin Arg 35 40 45 Glu Val Val Asp Leu Tyr Asn Gly Met Cys Leu Gin Gly Pro Ala 50 55 60 Gly Val Pro Gly Arg Asp Gly Ser Pro Gly Ala Asn Val Ile Pro 65 70 75 Gly Thr Pro Gly Ile Pro Gly Arg Asp Gly Phe Lys Gly Glu Lys 80 85 90 804 Gly Glu Cys Leu Arg Glu Ser Phe Glu Glu Ser Trp Thr Pro Asn 95 100 105 Tyr Lys Gin Gly Lys Ile Ala Leu Arg Asn Ala Cys Cys Ser Gly Gly Ser Pro Ser Val Glu Val Ala Ile Ala Ser Thr Leu Pro Lys <210> 353 <211> 480 <212> DNA <213> Homo s< <400> 353 gttaaccagc gcagtcctcc gtgcgtcccg cccgccgctg ccctcactcc 50 cggccaggat ggcatcctgt ctggccctgc gcatggcgct gctgctggtc 100 tccggggttc tggcccctgc ggtgctcaca gacgatgttc cacaggagcc 150 cgtgcccacg ctgtggaacg agccggccga gctgccgtcg ggagaaggcc 200 ccgtggagag caccagcccc ggccgggagc ccgtggacac cggtccccca 250 gcccccaccg tcgcgccagg acccgaggac agcaccgcgc aggagcggct 300 ggaccagggc ggcgggtcgc tggggcccgg cgctatcgcg gccatcgtga 350 tcgccgccct gctggccacc tgcgtggtgc tggcgctcgt ggtcgtcgcg 400 ctgagaaagt tttctgcctc ctgaagcgaa taaaggggcc gcgcccggcc 450 gcggcgcgac tcggcaaaaa aaaaaaaaaa 480 <210> 354 <211> 121 <212> PRT Cys Ser Trp Ser Ser Leu Asn Tyr Gly Ile Asp Leu 110 115 120 Ala Glu Cys Thr Phe Thr Lys Met Arg Ser Asn Ser 125 130 135 Val Leu Phe Ser Gly Ser Leu Arg Leu Lys Cys Arg 140 145 150 Cys Gin Arg Trp Tyr Phe Thr Phe Asn Gly Ala Glu 155 160 165 Pro Leu Pro Ile Glu Ala Ile Ile Tyr Leu Asp Gin 170 175 180 Glu Met Asn Ser Thr Ile Asn Ile His Arg Thr Ser 185 190 195 Gly Leu Cys Glu Gly Ile Gly Ala Gly Leu Val Asp 200 205 210 Trp Val Gly Thr Cys Ser Asp Tyr Pro Lys Gly Asp 215 220 225 Gly Trp Asn Ser Val Ser Arg Ile Ile Ile Glu Glu 230 235 240 apiens <213> Homo sapiens <400> 354 Met Ala Ser Cys Leu 1 5 Gly Val Leu Ala Pro 20 Pro Val Pro Thr Leu 35 Glu Gly Pro Val Glu 50 Thr Gly Pro Pro Ala 65 Thr Ala Gin Glu Arg 80 Gly Ala Ile Ala Ala 95 Val Val Leu Ala Leu 110 Ser <210> 355 <211> 2134 <212> DNA <213> Homo sapiens <400> 355 ggccgttggt tggtgcgcgg ctgaagggtg tggcgcgagc agcgtcgttg 50 gttggccggc ggcgggccgg gacgggcatg gccctgctgc tgtgcctggt 100 gtgcctgacg gcggcgctgg cccacggctg tctgcactgc cacagcaact 150 tctccaagaa gttctccttc taccgccacc atgtgaactt caagtcctgg 200 tgggtgggcg acatccccgt gtcaggggcg ctgctcaccg actggagcga 2 50 cgacacgatg aaggagctgc acctggccat ccccgccaag atcacccggg 300 agaagctgga ccaagtggcg acagcagtgt accagatgat ggatcagctg 350 taccagggga agatgtactt ccccgggtat ttccccaacg agctgcgaaa 400 catcttccgg gagcaggtgc acctcatcca gaacgccatc atcgaaaggc 450 acctggcacc aggcagctgg ggaggagggc agctctccag ggagggaccc 500 agcctagcac ctgaaggatc aatgccatca ccccgcgggg acctccccta 550 agtagccccc agaggcgctg ggagtgttgc caccgccctc ccctgaagtt 600 tgctccatct cacgctgggg gtcaacctgg ggaccccttc cctccgggcc 650 atggacacac atacatgaaa accaggccgc atcgactgtc agcaccgctg 70 0 805 Ala Leu Arg Met Ala Leu Leu Leu Val Ser 10 15 Ala Val Leu Thr Asp Asp Val Pro Gin Glu 25 30 Trp Asn Glu Pro Ala Glu Leu Pro Ser Gly 40 45 Ser Thr Ser Pro Gly Arg Glu Pro Val Asp 55 60 Pro Thr Val Ala Pro Gly Pro Glu Asp Ser 70 75 Leu Asp Gin Gly Gly Gly Ser Leu Gly Pro 85 90 Ile Val Ile Ala Ala Leu Leu Ala Thr Cys 100 105 Val Val Val Ala Leu Arg Lys Phe Ser Ala 115 120 806 tggcatcttc cagtacgaga ccatctcctg caacaactgc acagactcgc 750 acgtcgcctg ctttggctat aactgcgagt agggctcagg catcacaccc 800 acccgtgcca gggccctact gtccctgggg tcccaggctc tccttggagg 850 gggctccccg ccttccacct ggctgtcatc gggtagggcg gggccgtggg 900 ttcaggggcg caccacttcc aagcctgtgt cccacaggtc ctcggcgcag 950 tggaagtcag ctgtccaggg cctcctgaac tacataaata actggcacaa 1000 gtaagtcccc tcctcaaacc aacacaggca gtgtgtgtat gtgagcacct 1050 cgtgggtgag tatgtgtggg gcacaggctg gctccctcag ctcccacgtc 1100 ctagaggggc tcccgaggag gtggaacctc aacccagctc tgcgcaggag 1150 gcggctgcag tccttttctc cctcaaaggt ctccgaccct cagctggagg 1200 cgggcatctt tcctaaaggg tccccatagg gtctggttcc accccatccc 1250 aggtctgtgg tcagagcctg ggagggttcc ctacgatggt taggggtgcc 1300 ccatggaggg gctgactgcc ccacattgcc tttcagacag gacacgagca 1350 tgaggtaagg ccgccctgac ctggacttca gggggagggg gtaaagggag 1400 agaggagggg ggctaggggg tcctctagat cagtgggggc actgcaggtg 1450 gggctctccc tatacctggg acacctgctg gatgtcacct ctgcaaccac 1500 acccatgtgg tggtttcatg aacagaccac gctcctctgc cttctcctgg 1550 cctgggacac acagagccac cccggccttg tgagtgaccc agagaaggga 1600 ggcctcggga gaaggggtgc tcgtaagcca acaccagcgt gccgcggcct 1650 gcacaccctt cggacatccc aggcacgagg gtgtcgtgga tgtggccaca 1700 cataggacca cacgtcccag ctgggaggag aggcctgggg cccccaggga 1750 gggaggcagg gggtggggga catggagagc tgaggcagcc tcgtctcccc 1800 gcagcctggt atcgccagcc ttaaggtgtc tggagccccc acacttggcc 1850 aacctgacct tggaagatgc tgctgagtgt ctcaagcagc actgacagca 1900 gctgggcctg ccccagggca acgtgggggc ggagactcag ctggacagcc 1950 cctgcctgtc actctggagc tgggctgctg ctgcctcagg accccctctc 2000 cgaccccgga cagagctgag ctggccaggg ccaggagggc gggagggagg 2050 gaatgggggt gggctgtgcg cagcatcagc gcctgggcag gtccgcagag 2100 ctgcgggatg tgattaaagt ccctgatgtt tctc 2134 <210> 356 <211> 157 <212> PRT 807 <213> Homo sapiens <400> 356 Met Ala Leu Leu Leu Cys Leu Val Cys Leu Thr Ala Ala Leu Ala 15 10 15 His Gly Cys Leu His Cys His Ser Asn Phe Ser Lys Lys Phe Ser 20 25 30 Phe Tyr Arg His His Val Asn Phe Lys Ser Trp Trp Val Gly Asp 35 40 45 Ile Pro Val Ser Gly Ala Leu Leu Thr Asp Trp Ser Asp Asp Thr 50 55 60 Met Lys Glu Leu His Leu Ala Ile Pro Ala Lys Ile Thr Arg Glu 65 70 75 Lys Leu Asp Gin Val Ala Thr Ala Val Tyr Gin Met Met Asp Gin 80 85 90 Leu Tyr Gin Gly Lys Met Tyr Phe Pro Gly Tyr Phe Pro Asn Glu 95 100 105 Leu Arg Asn Ile Phe Arg Glu Gin Val His Leu Ile Gin Asn Ala 110 115 120 Ile Ile Glu Arg His Leu Ala Pro Gly Ser Trp Gly Gly Gly Gin 125 130 135 Leu Ser Arg Glu Gly Pro Ser Leu Ala Pro Glu Gly Ser Met Pro 140 145 150 Ser Pro Arg Gly Asp Leu Pro 155 <210> 357 <211> 1536 <212> DNA <213> Homo sapiens <400> 357 agcaggagca ggagagggac aatggaagct gccccgtcca ggttcatgtt 50 cctcttattt ctcctcacgt gtgagctggc tgcagaagtt gctgcagaag 100 ttgagaaatc ctcagatggt cctggtgctg cccaggaacc cacgtggctc 150 acagatgtcc cagctgccat ggaattcatt gctgccactg aggtggctgt 200 cataggcttc ttccaggatt tagaaatacc agcagtgccc atactccata 250 gcatggtgca aaaattccca ggcgtgtcat ttgggatcag cactgattct 300 gaggttctga cacactacaa catcactggg aacaccatct gcctctttcg 350 cctggtagac aatgaacaac tgaatttaga ggacgaagac attgaaagca 400 ttgatgccac caaattgagc cgtttcattg agatcaacag cctccacatg 450 gtgacagagt acaaccctgt gactgtgatt gggttattca acagcgtaat 500 808 tcagattcat agaacatgca ctcctcctga cagataccag taatgaacaa aaggcagcca ggcctcccca agctcttcca gagtatgaag ggggaagatt 550 600 ctctttattc tggtggacag tggtatgaaa gaaaatggga aggtgatatc 650 atttttcaaa ctaaaggagt ctcaactgcc agctttggca atttaccaga 700 ctctagatga cgagtgggat acactgccca cagcagaagt ttccgtagag 750 catgtgcaaa acttttgtga tggattccta agtggaaaat tgttgaaaga 800 aaatcgtgaa tcagaaggaa agactccaaa ggtggaactc tgacttctcc 850 ttggaactac atatggccaa gtatctactt tatgcaaagt aaaaaggcac 900 aactcaaatc tcagagacac taaacaacag gatcactagg cctgccaacc 950 acacacacac gcacgtgcac acacgcacgc acgcgtgcac acacacacgc 1000 gcacacacac acacacacag agcttcattt cctgtcttaa aatctcgttt 1050 tctcttcttc cttcttttaa atttcatatc ctcactccct atccaatttc 1100 cttcttatcg tgcattcata ctctgtaagc ccatctgtaa cacacctaga 1150 tcaaggcttt aagagactca ctgtgatgcc tctatgaaag agaggcattc 1200 ctagagaaag attgttccaa tttgtcattt aatatcaagt ttgtatactg 1250 cacatgactt acacacaaca tagttcctgc tcttttaagg ttacctaagg 1300 gttgaaactc taccttcttt cataagcaca tgtccgtctc tgactcagga 1350 tcaaaaacca aaggatggtt ttaaacacct ttgtgaaatt gtctttttgc 1400 cagaagttaa aggctgtctc caagtccctg aactcagcag aaatagacca 1450 tgtgaaaact ccatgcttgg ttagcatctc caactcccta tgtaaatcaa 1500 caacctgcat aataaataaa aggcaatcat gttata 1536 <210> 358 <211> 273 <212> PRT <213> Homo sapiens <400> 358 Met Glu Ala Ala Pro Ser Arg Phe Met Phe Leu Leu Phe Leu Leu 15 10 15 Thr Cys Glu Leu Ala Ala Glu Val Ala Ala Glu Val Glu Lys Ser 20 25 30 Ser Asp Gly Pro Gly Ala Ala Gin Glu Pro Thr Trp Leu Thr Asp 35' 40 45 Val Pro Ala Ala Met Glu Phe Ile Ala Ala Thr Glu Val Ala Val 50 55 60 Ile Gly Phe Phe Gin Asp Leu Glu Ile Pro Ala Val Pro Ile Leu 65 70 75 809 His Ser Met Val Gin. Lys Phe Pro Gly Val Ser Phe Gly Ile Ser 80 85 90 Thr Asp Ser Glu Val Leu Thr His Tyr Asn Ile Thr Gly Asn Thr 95 100 105 Ile Cys Leu Phe Arg Leu Val Asp Asn Glu Gin Leu Asn Leu Glu 110 115 120 Asp Glu Asp lie Glu Ser Ile Asp Ala Thr Lys Leu Ser Arg Phe 125 130 135 Ile Glu Ile Asn Ser Leu His Met Val Thr Glu Tyr Asn Pro Val 140 145 150 Thr Val Ile Gly Leu Phe Asn Ser Val Ile Gin Ile His Leu Leu 155 160 165 Leu Ile Met Asn Lys Ala Ser Pro Glu Tyr Glu Glu Asn Met His 170 175 180 Arg Tyr Gin Lys Ala Ala Lys Leu Phe Gin Gly Lys Ile Leu Phe 185 190 195 Ile Leu Val Asp Ser Gly Met Lys Glu Asn Gly Lys Val Ile Ser 200 205 210 Phe Phe Lys Leu Lys Glu Ser Gin Leu Pro Ala Leu Ala Ile Tyr 215 220 225 Gin Thr Leu Asp Asp Glu Trp Asp Thr Leu Pro Thr Ala Glu Val 230 235 240 Ser Val Glu His Val Gin Asn Phe Cys Asp Gly Phe Leu Ser Gly 245 250 255 Lys Leu Leu Lys Glu Asn Arg Glu Ser Glu Gly Lys Thr Pro Lys 260 265 270 Val Glu Leu <210> 359 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 359 ccagcagtgc ccatactcca tagc 24 <210> 360 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 360 tgacgagtgg gatacactgc 20 810 <210> 361 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 361 gctctacgga aacttctgct gtgg 24 <210> 362 <211> 50 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 362 attcccaggc gtgtcatttg ggatcagcac tgattctgag gttctgacac 50 <210> 363 <211> 1777 <212> DNA <213> Homo sapiens <400> 363 ggagagccgc ggctgggacc ggagtgggga gcgcggcgtg gaggtgccac 50 ccggcgcggg tggcggagag atcagaagcc tcttccccaa gccgagccaa 100 cctcagcggg gacccgggct cagggacgcg gcggcggcgg cggcgactgc 150 agtggctgga cgatggcagc gtccgccgga gccggggcgg tgattgcagc 200 cccagacagc cggcgctggc tgtggtcggt gctggcggcg gcgcttgggc 250 tcttgacagc tggagtatca gccttggaag tatatacgcc aaaagaaatc 300 ttcgtggcaa atggtacaca agggaagctg acctgcaagt tcaagtctac 350 tagtacgact ggcgggttga cctcagtctc ctggagcttc cagccagagg 400 gggccgacac tactgtgtcg tttttccact actcccaagg gcaagtgtac 450 cttgggaatt atccaccatt taaagacaga atcagctggg ctggagacct 500 tgacaagaaa gatgcatcaa tcaacataga aaatatgcag tttatacaca 550 atggcaccta tatctgtgat gtcaaaaacc ctcctgacat cgttgtccag 600 cctggacaca ttaggctcta tgtcgtagaa aaagagaatt tgcctgtgtt 650 tccagtttgg gtagtggtgg gcatagttac tgctgtggtc ctaggtctca 700 ctctgctcat cagcatgatt ctggctgtcc tctatagaag gaaaaactct 750 aaacgggatt acactggctg cagtacatca gagagtttgt caccagttaa 800 gcaggctcct cggaagtccc cctccgacac tgagggtctt gtaaagagtc 850 811 tgccttctgg atctcaccag ggcccagtca tatatgcaca gttagaccac 900 tccggcggac tgcggatatc atcacagtga cgaaagaatt caagattaac aagagaatac aagtcagagt ctagaacata ctgtggtgta tcctcagcaa 950 1000 gaaacaaaac caaactggac tctcgtgcag aaaatgtagc ccattaccac 1050 atgtagcctt ggagacccag gcaaggacaa gtacacgtgt actcacagag 1100 ggagagaaag atgtgtacaa aggatatgta taaatattct atttagtcat 1150 cctgatatga ggagccagtg ttgcatgatg aaaagatggt atgattctac 1200 atatgtaccc attgtcttgc tgtttttgta ctttcttttc aggtcattta 1250 caattgggag atttcagaaa cattcctttc accatcattt agaaatggtt 1300 tgccttaatg gagacaatag cagatcctgt agtatttcca gtagacatgg 1350 ccttttaatc taagggctta agactgatta gtcttagcat ttactgtagt 1400 tggaggatgg agatgctatg atggaagcat acccagggtg gcctttagca 1450 cagtatcagt accatttatt tgtctgccgc ttttaaaaaa tacccattgg 1500 ctatgccact tgaaaacaat ttgagaagtt tttttgaagt ttttctcact 1550 aaaatatggg gcaattgtta gccttacatg ttgtgtagac ttactttaag 1600 tttgcaccct tgaaatgtgt catatcaatt tctggattca taatagcaag 1650 attagcaaag gataaatgcc gaaggtcact tcattctgga cacagttgga 1700 tcaatactga ttaagtagaa aatccaagct ttgcttgaga acttttgtaa 1750 cgtggagagt aaaaagtatc g< <210> 364 <211> 269 <212> PRT <213> Homo sapiens <400> 364 Met Ala Ala Ser Ala Gly 1 5 Ser Arg Arg Trp Leu Trp 20 Leu Thr Ala Gly Val Ser 35 Ile Phe Val Ala Asn Gly 50 Lys Ser Thr Ser Thr Thr 65 Phe Gin Pro Glu Gly Ala 80 gtttta 1777 Ala Gly Ala Val Ile Ala Ala Pro Asp 10 15 Ser Val Leu Ala Ala Ala Leu Gly Leu 25 30 Ala Leu Glu Val Tyr Thr Pro Lys Glu 40 45 Thr Gin Gly Lys Leu Thr Cys Lys Phe 55 60 Gly Gly Leu Thr Ser Val Ser Trp Ser 70 75 Asp Thr Thr Val Ser Phe Phe His Tyr 85 90 812 Ser Gin Gly Gin Val Tyr Leu Gly Asn Tyr Pro Pro Phe Lys Asp 95 100 105 Arg Ile Ser Trp Ala Gly Asp Leu Asp Lys Lys Asp Ala Ser Ile 110 115 120 Asn Ile Glu Asn Met Gin Phe Ile His Asn Gly Thr Tyr Ile Cys 125 130 135 Asp Val Lys Asn Pro Pro Asp Ile Val Val Gin Pro Gly His Ile 140 145 150 Arg Leu Tyr Val Val Glu Lys Glu Asn Leu Pro Val Phe Pro Val 155 160 165 Trp Val Val Val Gly Ile Val Thr Ala Val Val Leu Gly Leu Thr 170 175 180 Leu Leu Ile Ser Met Ile Leu Ala Val Leu Tyr Arg Arg Lys Asn 185 190 195 Ser Lys Arg Asp Tyr Thr Gly Cys Ser Thr Ser Glu Ser Leu Ser 200 205 210 Pro Val Lys Gin Ala Pro Arg Lys Ser Pro Ser Asp Thr Glu Gly 215 220 225 Leu Val Lys Ser Leu Pro Ser Gly Ser His Gin Gly Pro Val Ile 230 235 240 Tyr Ala Gin Leu Asp His Ser Gly Gly His His Ser Asp Lys Ile 245 250 255 Asn Lys Ser Glu Ser Val Val Tyr Ala Asp Ile Arg Lys Asn 260 265 <210> 365 <211> 1321 <212> DNA <213> Homo sapiens <400> 365 gccggctgtg cagagacgcc atgtaccggc tcctgtcagc agtgactgcc 50 cgggctgccg cccccggggg cttggcctca agctgcggac gacgcggggt 100 ccatcagcgc gccgggctgc cgcctctcgg ccacggctgg gtcgggggcc 150 tcgggctggg gctggggctg gcgctcgggg tgaagctggc aggtgggctg 200 aggggcgcgg ccccggcgca gtcccccgcg gcccccgacc ctgaggcgtc 250 gcctctggcc gagccgccac aggagcagtc cctcgccccg tggtctccgc 300 agaccccggc gccgccctgc tccaggtgct tcgccagagc catcgagagc 350 agccgcgacc tgctgcacag gatcaaggat gaggtgggcg caccgggcat 400 agtggttgga gtttctgtag atggaaaaga agtctggtca gaaggtttag 450 gttatgctga tgttgagaac cgtgtaccat gtaaaccaga gacagttatg 500 cgaattgcta gcatcagcaa aagtctcacc atggttgctc ttgccaaatt 550 813 gtgggaagca gggaaactgg atcttgatat tccagtacaa cattatgttc 600 ccgaattccc agaaaaagaa tatgaaggtg aaaaggtttc tgtcacaaca 650 agattactga aaaaaaggtg tttcccattt aaagaagaga aagtggaatt aagcttataa cgtcattatg agccttgaag aaaaggacat atgatgaaag 700 750 agaatgttgc atttgagcaa gaaaaagaag gcaaaagtaa tgaaaagaat 800 gattttacta aatttaaaac agagcaggag aatgaagcca aatgccggaa 850 ttcaaaacct ggcaagaaaa agaatgattt tgaacaaggc gaattatatt 900 tgagagaaaa gtttgaaaat tcaattgaat ccctaagatt atttaaaaat 950 gatcctttgt tcttcaaacc tggtagtcag tttttgtatt caacttttgg 1000 ctatacccta ctggcagcca tagtagagag agcttcagga tgtaaatatt 1050 tggactatat gcagaaaata ttccatgact tggatatgct gacgactgtg 1100 caggaagaaa acgagccagt gatttacaat agagcaaggt aaatgaatac 1150 cttctgctgt gtctagctat atcgcatctt aacactattt tattaattaa 1200 aagtcaaatt ttctttgttt ccattccaaa atcaacctgc cacattttgg 1250 gagcttttct acatgtctgt tttctcatct gtaaagtgaa ggaagtaaaa 1300 catgtttata aagtaaaaaa a 1321 <210> 366 <211> 373 <212> PRT <213> Homo sapiens <400> 366 Met Tyr Arg Leu Leu Ser Ala Val Thr Ala Arg Ala Ala Ala Pro 15 10 15 Gly Gly Leu Ala Ser Ser Cys Gly Arg Arg Gly Val His Gin Arg 20 25 30 Ala Gly Leu Pro Pro Leu Gly His Gly Trp Val Gly Gly Leu Gly 35 40 45 Leu Gly Leu Gly Leu Ala Leu Gly Val Lys Leu Ala Gly Gly Leu 50 55 60 Arg Gly Ala Ala Pro Ala Gin Ser Pro Ala Ala Pro Asp Pro Glu 65 70 75 Ala Ser Pro Leu Ala Glu Pro Pro Gin Glu Gin Ser Leu Ala Pro 80 85 90 Trp Ser Pro Gin Thr Pro Ala Pro Pro Cys Ser Arg Cys Phe Ala 95 100 105 Arg Ala Ile Glu Ser Ser Arg Asp Leu Leu His Arg Ile Lys Asp 110 115 120 814 Glu Val Gly Ala Pro Gly Ile Val Val Gly Val Ser Val Asp Gly 125 130 135 Lys Glu Val Trp Ser Glu Gly Leu Gly Tyr Ala Asp Val Glu Asn 140 145 150 Arg Val Pro Cys Lys Pro Glu Thr Val Met Arg Ile Ala Ser Ile 155 160 165 Ser Lys Ser Leu Thr Met Val Ala Leu Ala Lys Leu Trp Glu Ala 170 175 180 Gly Lys Leu Asp Leu Asp Ile Pro Val Gin His Tyr Val Pro Glu 185 190 195 Phe Pro Glu Lys Glu Tyr Glu Gly Glu Lys Val Ser Val Thr Thr 200 205 210 Arg Leu Leu Ile Ser His Leu Ser Gly Ile Arg His Tyr Glu Lys 215 220 225 Asp Ile Lys Lys Val Lys Glu Glu Lys Ala Tyr Lys Ala Leu Lys 230 235 240 Met Met Lys Glu Asn Val Ala Phe Glu Gin Glu Lys Glu Gly Lys 245 250 255 Ser Asn Glu Lys Asn Asp Phe Thr Lys Phe Lys Thr Glu Gin Glu 260 265 270 Asn Glu Ala Lys Cys Arg Asn Ser Lys Pro Gly Lys Lys Lys Asn 275 280 285 Asp Phe Glu Gin Gly Glu Leu Tyr Leu Arg Glu Lys Phe Glu Asn 290 295 300 Ser Ile Glu Ser Leu Arg Leu Phe Lys Asn Asp Pro Leu Phe Phe 305 310 315 Lys Pro Gly Ser Gin Phe Leu Tyr Ser Thr Phe Gly Tyr Thr Leu 320 325 330 Leu Ala Ala Ile Val Glu Arg Ala Ser Gly Cys Lys Tyr Leu Asp 335 340 345 Tyr Met Gin Lys Ile Phe His Asp Leu Asp Met Leu Thr Thr Val 350 355 360 Gin Glu Glu Asn Glu Pro Val Ile Tyr Asn Arg Ala Arg 365 370 <210> 367 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 367 tggaaaagaa gtctggtcag aaggtttagg 30 815 <210> 368 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 368 catttggctt cattctcctg ctctg 25 <210> 369 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 369 aaaacctcag aacaactcat tttgcacc 28 <210> 370 , <211> 41 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 370 gtctcaccat ggttgctctt gccaaattgt gggaagcagg g 41 <210> 371 <211> 1150 <212> DNA <213> Homo sapiens <400> 371 gtgacactat agaagagcta tgacgtcgca tgcacgcgta cgtaagctcg 50 gaattcggct cgaggctggt gggaagaagc cgagatggcg gcagccagcg 100 ctggggcaac ccggctgctc ctgctcttgc tgatggcggt agcagcgccc 150 agtcgagccc ggggcagcgg ctgccgggcc gggactggtg cgcgaggggc 200 tggggcggaa ggtcgagagg gcgaggcctg tggcacggtg gggctgctgc 250 tggagcactc atttgagatc gatgacagtg ccaacttccg gaagcggggc 300 tcactgctct ggaaccagca ggatggtacc ttgtccctgt cacagcggca 350 gctcagcgag gaggagcggg gccgactccg ggatgtggca gccctgaatg 400 gcctgtaccg ggtccggatc ccaaggcgac ccggggccct ggatggcctg 450 gaagctggtg gctatgtctc ctcctttgtc cctgcgtgct ccctggtgga 500 gtcgcacctg tcggaccagc tgaccctgca cgtggatgtg gccggcaacg 550 tggtgggcgt gtcggtggtg acgcaccccg ggggctgccg gggccatgag 600 816 gtggaggacg tggacctgga gctgttcaac acctcggtgc agctgcagcc 650 gcccaccaca gccccaggcc ctgagacggc ggccttcatt gagcgcctgg 700 agatggaaca ggcccagaag gccaagaacc cccaggagca gaagtccttc 750 ttcgccaaat actggatgta catcattccc gtcgtcctgt tcctcatgat 800 gtcaggagcg ccagacaccg ggggccaggg tgggggtggg ggtgggggtg 850 gtggtggggg tagtggcctt tgctgtgtgc caccctccct gtaagtctat 900 ttaaaaacat cgacgataca ttgaaatgtg tgaacgtttt gaaaagctac 950 agcttccagc agccaaaagc aactgttgtt ttggcaagac ggtcctgatg 1000 tacaagcttg attgaaattc actgctcact tgatacgtta ttcagaaacc 1050 caaggaatgg ctgtccccat cctcatgtgg ctgtgtggag ctcagctgtg 1100 ttgtgtggca gtttattaaa ctgtccccca gatcgacacg caaaaaaaaa 1150 <210> 372 <211> 269 <212> PRT <213> Homo sapiens <400> 372 Met Ala Ala Ala Ser Ala Gly Ala Thr Arg Leu Leu Leu Leu Leu 15 10 15 Leu Met Ala Val Ala Ala Pro Ser Arg Ala Arg Gly Ser Gly Cys 20 25 30 Arg Ala Gly Thr Gly Ala Arg Gly Ala Gly Ala Glu Gly Arg Glu 35 40 45 Gly Glu Ala Cys Gly Thr Val Gly Leu Leu Leu Glu His Ser Phe 50 55 60 Glu Ile Asp Asp Ser Ala Asn Phe Arg Lys Arg Gly Ser Leu Leu 65 70 75 Trp Asn Gin Gin Asp Gly Thr Leu Ser Leu Ser Gin Arg Gin Leu 80 85 90 Ser Glu Glu Glu Arg Gly Arg Leu Arg Asp Val Ala Ala Leu Asn 95 100 105 Gly Leu Tyr Arg Val Arg Ile Pro Arg Arg Pro Gly Ala Leu Asp 110 115 120 Gly Leu Glu Ala Gly Gly Tyr Val Ser Ser Phe Val Pro Ala Cys 125 130 135 Ser Leu Val Glu Ser His Leu Ser Asp Gin Leu Thr Leu His Val 140 145 150 Asp Val Ala Gly Asn Val Val Gly Val Ser Val Val Thr His Pro 155 160 165 817 Gly Gly Cys Arg Gly His Glu Val Glu Asp Val Asp Leu Glu Leu 170 175 180 Phe Asn Thr Ser Val Gin Leu Gin Pro Pro Thr Thr Ala Pro Gly 185 190 195 Pro Glu Thr Ala Ala Phe Ile Glu Arg Leu Glu Met Glu Gin Ala 200 205 210 Gin Lys Ala Lys Asn Pro Gin Glu Gin Lys Ser Phe Phe Ala Lys 215 220 225 Tyr Trp Met Tyr Ile Ile Pro Val Val Leu Phe Leu Met Met Ser 230 • 235 240 Gly Ala Pro Asp Thr Gly Gly Gin Gly Gly Gly Gly Gly Gly Gly 245 250 255 Gly Gly Gly Gly Ser Gly Leu Cys Cys Val Pro Pro Ser Leu 260 265 <210> 373 <211> 1706 <212> DNA <213> Homo sapiens <400> 373 ggagcgctgc tggaacccga gccggagccg gagccacagc ggggagggtg 50 gcctggcggc ctggagccgg acgtgtccgg ggcgtccccg cagaccgggg 100 cagcaggtcg tccgggggcc caccatgctg gtgactgcct accttgcttt 150 tgtaggcctc ctggcctcct gcctggggct ggaactgtca agatgccggg 200 ctaaaccccc tggaagggcc tgcagcaatc cctccttcct tcggtttcaa 250 ctggacttct atcaggtcta cttcctggcc ctggcagctg attggcttca 300 ggccccctac ctctataaac tctaccagca ttactacttc ctggaaggtc 350 aaattgccat cctctatgtc tgtggccttg cctctacagt cctctttggc 400 ctagtggcct cctcccttgt ggattggctg ggtcgcaaga attcttgtgt 450 cctcttctcc ctgacttact cactatgctg cttaaccaaa ctctctcaag 500 actactttgt gctgctagtg gggcgagcac ttggtgggct gtccacagcc 550 ctgctcttct cagccttcga ggcctggtat atccatgagc acgtggaacg 600 gcatgacttc cctgctgagt ggatcccagc tacctttgct cgagctgcct 650 tctggaacca tgtgctggct gtagtggcag gtgtggcagc tgaggctgta 700 gccagctgga tagggctggg gcctgtagcg ccctttgtgg ctgccatccc 750 tctcctggct ctggcagggg ccttggccct tcgaaactgg ggggagaact 800 atgaccggca gcgtgccttc tcaaggacct gtgctggagg cctgcgctgc 850 ctcctgtcgg accgccgcgt gctgctgctg ggcaccatac aagctctatt 900 818 tgagagtgtc atcttcatct ttgtcttcct ctggacacct gtgctggacc 950 cacacggggc ccctctgggc attatcttct ccagcttcat ggcagccagc 1000 ctgcttggct cttccctgta ccgtatcgcc acctccaaga ggtaccacct 1050 tcagcccatg cacctgctgt cccttgctgt gctcatcgtc gtcttctctc 1100 tcttcatgtt gactttctct accagcccag gccaggagag tccggtggag 1150 tccttcatag cctttctact tattgagttg gcttgtggat tatactttcc 1200 cagcatgagc ttcctacgga gaaaggtgat ccctgagaca gagcaggctg 1250 gtgtactcaa ctggttccgg gtacctctgc actcactggc ttgcctaggg 1300 ctccttgtcc tccatgacag tgatcgaaaa acaggcactc ggaatatgtt 1350 cagcatttgc tctgctgtca tggtgatggc tctgctggca gtggtgggac 1400 tcttcaccgt ggtaaggcat gatgctgagc tgcgggtacc ttcacctact 1450 gaggagccct atgcccctga gctgtaaccc cactccagga caagatagct 1500 gggacagact cttgaattcc agctatccgg gattgtacag atctctctgt 1550 gactgacttt gtgactgtcc tgtggtttct cctgccattg ctttgtgttt 1600 gggaggacat gatgggggtg atggactgga aagaaggtgc caaaagttcc 1650 ctctgtgtta ctcccattta gaaaataaac acttttaaat gatcaaaaaa 1700 aaaaaa 1706 <210> 374 <211> 450 <212> PRT <213> Homo sapiens <400> 374 Met Leu Val Thr Ala Tyr Leu Ala Phe Val Gly Leu Leu Ala Ser 15 10 15 Cys Leu Gly Leu Glu Leu Ser Arg Cys Arg Ala Lys Pro Pro Gly 20 25 30 Arg Ala Cys Ser Asn Pro Ser Phe Leu Arg Phe Gin Leu Asp Phe 35 40 45 Tyr Gin Val Tyr Phe Leu Ala Leu Ala Ala Asp Trp Leu Gin Ala 50 55 60 Pro Tyr Leu Tyr Lys Leu Tyr Gin His Tyr Tyr Phe Leu Glu Gly 65 70 75 Gin Ile Ala Ile Leu Tyr Val Cys Gly Leu Ala Ser Thr Val Leu 80 85 90 Phe Gly Leu Val Ala Ser Ser Leu Val Asp Trp Leu Gly Arg Lys 95 100 105 819 Asn Ser Cys Val Leu Phe Ser Leu Thr Tyr Ser Leu Cys Cys Leu 110 115 120 Thr Lys Leu Ser Gin Asp Tyr Phe Val Leu Leu Val Gly Arg Ala 125 130 135 Leu Gly Gly Leu Ser Thr Ala Leu Leu Phe Ser Ala Phe Glu Ala 140 145 150 Trp Tyr Ile His Glu His Val Glu Arg His Asp Phe Pro Ala Glu 155 160 165 Trp Ile Pro Ala Thr Phe Ala Arg Ala Ala Phe Trp Asn His Val 170 175 180 Leu Ala Val Val Ala Gly Val Ala Ala Glu Ala Val Ala Ser Trp 185 190 195 Ile Gly Leu Gly Pro Val Ala Pro Phe Val Ala Ala Ile Pro Leu 200 205 210 Leu Ala Leu Ala Gly Ala Leu Ala Leu Arg Asn Trp Gly Glu Asn 215 220 225 Tyr Asp Arg Gin Arg Ala Phe Ser Arg Thr Cys Ala Gly Gly Leu 230 235 240 Arg Cys Leu Leu Ser Asp Arg Arg Val Leu Leu Leu Gly Thr Ile 245 250 255 Gin Ala Leu Phe Glu Ser Val Ile Phe Ile Phe Val Phe Leu Trp 260 265 270 Thr Pro Val Leu Asp Pro His Gly Ala Pro Leu Gly Ile Ile Phe 275 280 285 Ser Ser Phe Met Ala Ala Ser Leu Leu Gly Ser Ser Leu Tyr Arg 290 295 300 Ile Ala Thr Ser Lys Arg Tyr His Leu Gin Pro Met His Leu Leu 305 310 315 Ser Leu Ala Val Leu Ile Val Val Phe Ser Leu Phe Met Leu Thr 320 325 330 Phe Ser Thr Ser Pro Gly Gin Glu Ser Pro Val Glu Ser Phe Ile 335 340 345 Ala Phe Leu Leu Ile Glu Leu Ala Cys Gly Leu Tyr Phe Pro Ser 350 355 360 Met Ser Phe Leu Arg Arg Lys Val Ile Pro Glu Thr Glu Gin Ala 365 370 375 Gly Val Leu Asn Trp Phe Arg Val Pro Leu His Ser Leu Ala Cys 380 385 390 Leu Gly Leu Leu Val Leu His Asp Ser Asp Arg Lys Thr Gly Thr 395 400 405 Arg Asn Met Phe Ser Ile Cys Ser Ala Val Met Val Met Ala Leu 410 415 420 820 Leu Ala Val Val Gly Leu Phe Thr Val Val Arg His Asp Ala Glu 425 430 435 Leu Arg Val Pro Ser Pro Thr Glu Glu Pro Tyr Ala Pro Glu Leu 440 445 450 <210> 375 <211> 1098 <212> DNA <213> Artificial <400> 375 gcgacgcgcg gcggggcggc gagaggaaac gcggcgccgg gccgggcccg 50 gccctggaga tggtccccgg cgccgcgggc tggtgttgtc tcgtgctctg 100 gctccccgcg tgcgtcgcgg cccacggctt ccgtatccat gattatttgt 150 actttcaagt gctgagtcct ggggacattc gatacatctt cacagccaca 200 cctgccaagg actttggtgg tatctttcac acaaggtatg agcagattca 250 ccttgtcccc gctgaacctc cagaggcctg cggggaactc agcaacggtt 300 tcttcatcca ggaccagatt gctctggtgg agaggggggg ctgctccttc 350 ctctccaaga ctcgggtggt ccaggagcac ggcgggcggg cggtgatcat 400 ctctgacaac gcagttgaca atgacagctt ctacgtggag atgatccagg 450 acagtaccca gcgcacagct gacatccccg ccctcttcct gctcggccga 500 gacggctaca tgatccgccg ctctctggaa cagcatgggc tgccatgggc 550 catcatttcc atcccagtca atgtcaccag catccccacc tttgagctgc 600 tgcaaccgcc ctggaccttc tggtagaaga gtttgtccca cattccagcc 650 ataagtgact ctgagctggg aaggggaaac ccaggaattt tgctacttgg 700 aatttggaga tagcatctgg ggacaagtgg agccaggtag aggaaaaggg 750 tttgggcgtt gctaggctga aagggaagcc acaccactgg ccttcccttc 800 cccagggccc ccaagggtgt ctcatgctac aagaagaggc aagagacagg 850 ccccagggct tctggctaga acccgaaaca aaaggagctg aaggcaggtg 900 gcctgagagc catctgtgac ctgtcacact cacctggctc cagcctcccc 950 tacccagggt ctctgcacag tgaccttcac agcagttgtt ggagtggttt 1000 aaagagctgg tgtttgggga ctcaataaac cctcactgac tttttagcaa 1050 taaagcttct catcagggtt gcaaaaaaaa aaaaaaaaaa aaaaaaaa 1098 <210> 376 <211> 188 <212> PRT <213> Homo sapiens 821 <400> 376 Met Val Pro Gly Ala Ala Gly Trp Cys Cys Leu Val Leu Trp Leu 15 10 15 Pro Ala Cys Val Ala Ala His Gly Phe Arg Ile His Asp Tyr Leu 20 25 30 Tyr Phe Gin Val Leu Ser Pro Gly Asp Ile Arg Tyr Ile Phe Thr 35 40 45 Ala Thr Pro Ala Lys Asp Phe Gly Gly Ile Phe His Thr Arg Tyr 50 55 60 Glu Gin Ile His Leu Val Pro Ala Glu Pro Pro Glu Ala Cys Gly 65 70 75 Glu Leu Ser Asn Gly Phe Phe Ile Gin Asp Gin Ile Ala Leu Val 80 85 90 Glu Arg Gly Gly Cys Ser Phe Leu Ser Lys Thr Arg Val Val Gin 95 100 105 Glu His Gly Gly Arg Ala Val Ile Ile Ser Asp Asn Ala Val Asp 110 115 120 Asn Asp Ser Phe Tyr Val Glu Met Ile Gin Asp Ser Thr Gin Arg 125 130 135 Thr Ala Asp Ile Pro Ala Leu Phe Leu Leu Gly Arg Asp Gly Tyr 140 145 150 Met Ile Arg Arg Ser Leu Glu Gin His Gly Leu Pro Trp Ala lie 155 160 165 Ile Ser Ile Pro Val Asn Val Thr Ser lie Pro Thr Phe Glu Leu 170 175 180 Leu Gin Pro Pro Trp Thr Phe Trp 185 <210> 377 <211> 496 <212> DNA <213> Artificial <220> <221> unsure <222> 396 <223> unknown base <400> 377 tctgcctcca ctgctctgtg ctgggatcat ggaacttgca ctgctgtgtg 50 ggctggtggt gatggctggt gtgattccaa tccagggcgg gatcctgaac 100 ctgaacaaga tggtcaagca agtgactggg aaaatgccca tcctctccta 150 ctggccctac ggctgtcact gcggactagg tggcagaggc caacccaaag 2 00 atgccacgga ctggtgctgc cagacccatg actgctgcta tgaccacctg 250 aagacccagg ggtgcggcat ctacaaggac aacaacaaaa gcagcataca 300 822 ttgtatggat tctatctgga aaaaaaaaaa aaaaaaaaaa <210> 378 <211> 116 <212> PRT <213> Homo sapiens <400> 378 Met Glu Leu Ala Leu Leu Cys Gly Leu Val Val Met Ala Gly Val 15 10 15 Ile Pro Ile Gin Gly Gly Ile Leu Asn Leu Asn Lys Met Val Lys 20 25 30 Gin Val Thr Gly Lys Met Pro Ile Leu Ser Tyr Trp Pro Tyr Gly 35 40 45 Cys His Cys Gly Leu Gly Gly Arg Gly Gin Pro Lys Asp Ala Thr 50 55 60 Asp Trp Cys Cys Gin Thr His Asp Cys Cys Tyr Asp His Leu Lys 65 70 75 Thr Gin Gly Cys Gly Ile Tyr Lys Asp Asn Asn Lys Ser Ser Ile 80 85 90 His Cys Met Asp Leu Ser Gin Arg Tyr Cys Leu Met Ala Val Phe 95 100 105 Asn Val Ile Tyr Leu Glu Asn Glu Asp Ser Glu 110 115 <210> 379 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 379 ctgcctccac tgctctgtgc tggg 24 <210> 380 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 380 cagagcagtg gatgttcccc tggg 24 ttatctcaac gctattgttt aatggctgtg tttaatgtga 350 aaatgaggac tccgaataaa aagctattac tawttnaaaa 400 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 450 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaa 496 <210> 381 823 <211> 45 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 381 ctgaacaaga tggtcaagca agtgactggg aaaatgccca tcctc 45 <210> 382 <211> 764 <212> DNA <213> Homo sapiens <400> 382 ctcgcttctt ccttctggat gggggcccag ggggcccagg agagtataaa 50 ggcgatgtgg agggtgcccg gcacaaccag acgcccagtc acaggcgaga 100 gccctgggat gcaccggcca gaggccatgc tgctgctgct cacgcttgcc 150 ctcctggggg gccccacctg ggcagggaag atgtatggcc ctggaggagg 200 caagtatttc agcaccactg aagactacga ccatgaaatc acagggctgc 250 gggtgtctgt aggtcttctc ctggtgaaaa gtgtccaggt gaaacttgga 300 gactcctggg acgtgaaact gggagcctta ggtgggaata cccaggaagt 350 caccctgcag ccaggcgaat acatcacaaa agtctttgtc gccttccaag 400 ctttcctccg gggtatggtc atgtacacca gcaaggaccg ctatttctat 450 tttgggaagc ttgatggcca gatctcctct gcctacccca gccaagaggg 500 gcaggtgctg gtgggcatct atggccagta tcaactcctt ggcatcaaga 550 gcattggctt tgaatggaat tatccactag aggagccgac cactgagcca 600 ccagttaatc tcacatactc agcaaactca cccgtgggtc gctagggtgg 650 ggtatggggc catccgagct gaggccatct gtgtggtggt ggctgatggt 700 actggagtaa ctgagtcggg acgctgaatc tgaatccacc aataaataaa 750 gcttctgcag aaaa 7 64 <210> 383 <211> 178 <212> PRT <213> Homo sapiens <400> 383 Met His Arg Pro Glu Ala Met Leu Leu Leu Leu Thr Leu Ala Leu 15 10 15 Leu Gly Gly Pro Thr Trp Ala Gly Lys Met Tyr Gly Pro Gly Gly 20 25 30 Gly Lys Tyr Phe Ser Thr Thr Glu Asp Tyr Asp His Glu Ile Thr 35 40 45 824 Gly Leu Arg Val Lys Leu Gly Asn Thr Lys Val Phe Tyr Thr Ser Gin Ile Ser Gly Ile Tyr Phe Glu Trp Val Asn Leu <210> 384 <211> 2379 <212> DNA <213> Homo s< <400> 384 gctgagcgtg tgcgcggtac ggggctctcc tgccttctgg gctccaacgc 50 agctctgtgg ctgaactggg tgctcatcac gggaactgct gggctatgga 100 atacagatgt ggcagctcag gtagccccaa attgcctgga agaatacatc 150 atgtttttcg ataagaagaa attgtaggat ccagtttttt ttttaaccgc 200 cccctcccca ccccccaaaa aaactgtaaa gatgcaaaaa cgtaatatcc 2 50 atgaagatcc tattacctag gaagattttg atgttttgct gcgaatgcgg 300 tgttgggatt tatttgttct tggagtgttc tgcgtggctg gcaaagaata 350 atgttccaaa atcggtccat ctcccaaggg gtccaatttt tcttcctggg 400 tgtcagcgag ccctgactca ctacagtgca gctgacaggg gctgtcatgc 450 aactggcccc taagccaaag caaaagacct aaggacgacc tttgaacaat 500 acaaaggatg ggtttcaatg taattaggct actgagcgga tcagctgtag 550 cactggttat agcccccact gtcttactga caatgctttc ttctgccgaa 600 cgaggatgcc ctaagggctg taggtgtgaa ggcaaaatgg tatattgtga 650 atctcagaaa ttacaggaga taccctcaag tatatctgct ggttgcttag 700 Val Ser Val Gly Leu Leu Leu Val Lys Ser Val Gin 50 55 60 Gly Asp Ser Trp Asp Val Lys Leu Gly Ala Leu Gly 65 70 75 Gin Glu Val Thr Leu Gin Pro Gly Glu Tyr Ile Thr 80 85 90 Val Ala Phe Gin Ala Phe Leu Arg Gly Met Val Met 95 100 105 Lys Asp Arg Tyr Phe Tyr Phe Gly Lys Leu Asp Gly 110 115 120 Ser Ala Tyr Pro Ser Gin Glu Gly Gin Val Leu Val 125 130 135 Gly Gin Tyr Gin Leu Leu Gly Ile Lys Ser Ile Gly 140 145 150 Asn Tyr Pro Leu Glu Glu Pro Thr Thr Glu Pro Pro 155 160 165 Thr Tyr Ser Ala Asn Ser Pro Val Gly Arg 170 175 apiens 825 gtttgtccct tcgctataac agccttcaaa aacttaagta taatcaattt 750 aaagggctca accagctcac ctggctatac cttgaccata accatatcag 800 caatattgac gaaaatgctt ttaatggaat acgcagactc aaagagctga 850 ttcttagttc caatagaatc tcctattttc ttaacaatac cttcagacct 900 gtgacaaatt tacggaactt ggatctgtcc tataatcagc tgcattctct 950 gggatctgaa cagtttcggg gcttgcggaa gctgctgagt ttacatttac 1000 ggtctaactc cctgagaacc atccctgtgc gaatattcca agactgccgc 1050 aacctggaac ttttggacct gggatataac cggatccgaa gtttagccag 1100 gaatgtcttt gctggcatga tcagactcaa agaacttcac ctggagcaca 1150 atcaattttc caagctcaac ctggcccttt ttccaaggtt ggtcagcctt 1200 cagaaccttt acttgcagtg gaataaaatc agtgtcatag gacagaccat 1250 gtcctggacc tggagctcct tacaaaggct tgatttatca ggcaatgaga 1300 tcgaagcttt cagtggaccc agtgttttcc agtgtgtccc gaatctgcag 1350 cgcctcaacc tggattccaa caagctcaca tttattggtc aagagatttt 1400 ggattcttgg atatccctca atgacatcag tcttgctggg aatatatggg 1450 aatgcagcag aaatatttgc tcccttgtaa actggctgaa aagttttaaa 1500 ggtctaaggg agaatacaat tatctgtgcc agtcccaaag agctgcaagg 1550 agtaaatgtg atcgatgcag tgaagaacta cagcatctgt ggcaaaagta 1600 ctacagagag gtttgatctg gccagggctc tcccaaagcc gacgtttaag 1650 cccaagctcc ccaggccgaa gcatgagagc aaaccccctt tgcccccgac 1700 ggtgggagcc acagagcccg gcccagagac cgatgctgac gccgagcaca 1750 tctctttcca taaaatcatc gcgggcagcg tggcgctttt cctgtccgtg 1800 ctcgtcatcc tgctggttat ctacgtgtca tggaagcggt accctgcgag 1850 catgaagcag ctgcagcagc gctccctcat gcgaaggcac aggaaaaaga 1900 aaagacagtc cctaaagcaa atgactccca gcacccagga attttatgta 1950 gattataaac ccaccaacac ggagaccagc gagatgctgc tgaatgggac 2000 gggaccctgc acctataaca aatcgggctc cagggagtgt gaggtatgaa 2050 ccattgtgat aaaaagagct cttaaaagct gggaaataag tggtgcttta 2100 ttgaactctg gtgactatca agggaacgcg atgccccccc tccccttccc 2150 tctccctctc actttggtgg caagatcctt ccttgtccgt tttagtgcat 2200 tcataatact ggtcattttc ctctcataca taatcaaccc attgaaattt 2250 826 aaataccaca atcaatgtga agcttgaact ccggtttaat ataataccta 2300 ttgtataaga ccctttactg attccattaa tgtcgcattt gttttaagat 23 50 aaaacttctt tcataggtaa aaaaaaaaa 2379 <210> 385 <211> 513 <212> PRT <213> Homo sapiens <400> 385 Met Gly Phe Asn Val Ile Arg Leu Leu Ser Gly Ser Ala Val Ala 15 10 15 Leu Val Ile Ala Pro Thr Val Leu Leu Thr Met Leu Ser Ser Ala 20 25 30 Glu Arg Gly Cys Pro Lys Gly Cys Arg Cys Glu Gly Lys Met Val 35 40 45 Tyr Cys Glu Ser Gin Lys Leu Gin Glu Ile Pro Ser Ser Ile Ser 50 55 60 Ala Gly Cys Leu Gly Leu Ser Leu Arg Tyr Asn Ser Leu Gin Lys 65 70 75 Leu Lys Tyr Asn Gin Phe Lys Gly Leu Asn Gin Leu Thr Trp Leu 80 85 90 Tyr Leu Asp His Asn His Ile Ser Asn lie Asp Glu Asn Ala Phe 95 100 105 Asn Gly Ile Arg Arg Leu Lys Glu Leu Ile Leu Ser Ser Asn Arg 110 115 120 Ile Ser Tyr Phe Leu Asn Asn Thr Phe Arg Pro Val Thr Asn Leu 125 130 135 Arg Asn Leu Asp Leu Ser Tyr Asn Gin Leu His Ser Leu Gly Ser 140 145 150 Glu Gin Phe Arg Gly Leu Arg Lys Leu Leu Ser Leu His Leu Arg 155 160 165 Ser Asn Ser Leu Arg Thr Ile Pro Val Arg Ile Phe Gin Asp Cys 170 175 180 Arg Asn Leu Glu Leu Leu Asp Leu Gly Tyr Asn Arg Ile Arg Ser 185 190 195 Leu Ala Arg Asn Val Phe Ala Gly Met Ile Arg Leu Lys Glu Leu 200 205 210 His Leu Glu His Asn Gin Phe Ser Lys Leu Asn Leu Ala Leu Phe 215 220 225 Pro Arg Leu Val Ser Leu Gin Asn Leu Tyr Leu Gin Trp Asn Lys 230 235 240 Ile Ser Val Ile Gly Gin Thr Met Ser Trp Thr Trp Ser Ser Leu 245 250 255 827 Gin Arg Leu Asp Leu Ser Gly Asn Glu Ile Glu Ala Phe Ser Gly 260 265 270 Pro Ser Val Phe Gin Cys Val Pro Asn Leu Gin Arg Leu Asn Leu 275 280 285 Asp Ser Asn Lys Leu Thr Phe Ile Gly Gin Glu Ile Leu Asp Ser 290 295 300 Trp Ile Ser Leu Asn Asp Ile Ser Leu Ala Gly Asn Ile Trp Glu 305 310 315 Cys Ser Arg Asn Ile Cys Ser Leu Val Asn Trp Leu Lys Ser Phe 320 325 330 Lys Gly Leu Arg Glu Asn Thr Ile Ile Cys Ala Ser Pro Lys Glu 335 340 345 Leu Gin Gly Val Asn Val Ile Asp Ala Val Lys Asn Tyr Ser Ile 350 355 360 Cys Gly Lys Ser Thr Thr Glu Arg Phe Asp Leu Ala Arg Ala Leu 365 370 375 Pro Lys Pro Thr Phe Lys Pro Lys Leu Pro Arg Pro Lys His Glu 380 385 390 Ser Lys Pro Pro Leu Pro Pro Thr Val Gly Ala Thr Glu Pro Gly 395 400 405 Pro Glu Thr Asp Ala Asp Ala Glu His Ile Ser Phe His Lys Ile 410 415 420 Ile Ala Gly Ser Val Ala Leu Phe Leu Ser Val Leu Val Ile Leu 425 430 435 Leu Val Ile Tyr Val Ser Trp Lys Arg Tyr Pro Ala Ser Met Lys 440 445 450 Gin Leu Gin Gin Arg Ser Leu Met Arg Arg His Arg Lys Lys Lys 455 460 465 Arg Gin Ser Leu Lys Gin Met Thr Pro Ser Thr Gin Glu Phe Tyr 470 475 480 Val Asp Tyr Lys Pro Thr Asn Thr Glu Thr Ser Glu Met Leu Leu 485 490 495 Asn Gly Thr Gly Pro Cys Thr Tyr Asn Lys Ser Gly Ser Arg Glu 500 505 510 Cys Glu Val <210> 386 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe 828 <400> 386 ctgggatctg aacagtttcg gggc 24 <210> 387 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 387 ggtccccagg acatggtctg tccc 24 <210> 388 <211> 48 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 388 gctgagttta catttacggt ctaactccct gagaaccatc cctgtgcg 48 <210> 389 <211> 1449 <212> DNA <213> Homo sapiens <400> 389 agttctgaga aagaaggaaa taaacacagg caccaaacca ctatcctaag 50 ttgactgtcc tttaaatatg tcaagatcca gacttttcag tgtcacctca 100 gcgatctcaa cgatagggat cttgtgtttg ccgctattcc agttggtgct 150 ctcggaccta ccatgcgaag aagatgaaat gtgtgtaaat tataatgacc 200 aacaccctaa tggctggtat atctggatcc tcctgctgct ggttttggtg 250 gcagctcttc tctgtggagc tgtggtcctc tgcctccagt gctggctgag 300 gagaccccga attgattctc acaggcgcac catggcagtt tttgctgttg 350 gagacttgga ctctatttat gggacagaag cagctgtgag tccaactgtt 400 ggaattcacc ttcaaactca aacccctgac ctatatcctg ttcctgctcc 450 atgttttggc cctttaggct ccccacctcc atatgaagaa attgtaaaaa 500 caacctgatt ttaggtgtgg attatcaatt taaagtatta acgacatctg 550 taattccaaa acatcaaatt taggaatagt tatttcagtt gttggaaatg 600 tccagagatc tattcatata gtctgaggaa ggacaattcg acaaaagaat 650 ggatgttgga aaaaattttg gtcatggaga tgtttaaata gtaaagtagc 700 aggcttttga tgtgtcactg ctgtatcata cttttatgct acacaaccaa 750 attaatgctt ctccactagt atccaaacag 829 gcaacaatta ggtgctggaa 800 gtagtttcca tcacatttag gactccactg cagtatacag cacaccattt 850 tctgctttaa actctttcct agcatggggt ccataaaaat tattataatt 900 taacaatagc ccaagccgag aatccaacat gtccagaacc agaaccagaa 950 agatagtatt tgaatgaagg tgaggggaga gagtaggaaa aagaaaagtt 1000 tggagttgaa gggtaaagga taaatgaaga ggaaaaggaa aagattacaa 1050 gtctcagcaa aaacaagagg ttttatgccc caacctgaag aggaagaaat 1100 tgtagataga aggtgaagga gattgctgaa gatatagagc acatataatg 1150 ccaacacggg gagaaaagaa aatttcccct tttacagtaa tgaatgtggc 1200 ctccatagtc catagtgttt ctctggagcc tcagggcttg gcatttattg 1250 cagcatcatg ctaagaacct tcggcatagg tatctgttcc catgaggact 1300 gcagaagtag caatgagaca tcttcaagtg gcattttggc agtggccatc 1350 agcaggggga cagacaaaaa catccatcac agatgacata tgatcttcag 1400 ctgacaaatt tgttgaacaa aacaataaac atcaatagat atctaaaaa : L449 <210> 390 <211> 146 <212> PRT <213> Homo sapiens <400> 390 Met Ser Arg Ser Arg Leu Phe Ser Val Thr Ser Ala Ile Ser Thr 15 10 15 Ile Gly Ile Leu Cys Leu Pro Leu Phe Gin Leu Val Leu Ser Asp 20 25 30 Leu Pro Cys Glu Glu Asp Glu Met Cys Val Asn Tyr Asn Asp Gin 35 40 45 His Pro Asn Gly Trp Tyr Ile Trp Ile Leu Leu Leu Leu Val Leu 50 55 60 Val Ala Ala Leu Leu Cys Gly Ala Val Val Leu Cys Leu Gin Cys 65 70 75 Trp Leu Arg Arg Pro Arg Ile Asp Ser His Arg Arg Thr Met Ala 80 85 90 Val Phe Ala Val Gly Asp Leu Asp Ser Ile Tyr Gly Thr Glu Ala 95 100 105 Ala Val Ser Pro Thr Val Gly Ile His Leu Gin Thr Gin Thr Pro 110 115 120 Asp Leu Tyr Pro Val Pro Ala Pro Cys Phe Gly Pro Leu Gly Ser 125 130 135 Pro Pro Pro Tyr Glu Glu Ile Val Lys Thr Thr 140 830 145 <210> 391 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 391 cttttcagtg tcacctcagc gatctc 26 <210> 392 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 392 ccaaaacatg gagcaggaac agg 23 <210> 393 <211> 47 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 393 ccagttggtg ctctcggacc taccatgcga agaagatgaa atgtgtg 47 <210> 394 <211> 2340 <212> DNA <213> Homo sapiens <400> 394 gagcggagta aaatctccac aagctgggaa caaacctcgt cccaactccc 50 acccaccggc gtttctccag ctcgatctgg aggctgcttc gccagtgtgg 100 gacgcagctg acgcccgctt attagctctc gctgcgtcgc cccggctcag 150 aagctccgtg gcggcggcga ccgtgacgag aagcccacgg ccagctcagt 200 tctcttctac tttgggagag agagaaagtc agatgcccct tttaaactcc 250 ctcttcaaaa ctcatctcct gggtgactga gttaatagag tggatacaac 300 cttgctgaag atgaagaata tacaatattg aggatatttt tttctttttt 350 ttttcaagtc ttgatttgtg gcttacctca agttaccatt tttcagtcaa 400 gtctgtttgt ttgcttcttc agaaatgttt tttacaatct caagaaaaaa 450 tatgtcccag aaattgagtt tactgttgct tgtatttgga ctcatttggg 500 gattgatgtt actgcactat acttttcaac aaccaagaca tcaaagcagt 550 831 gtcaagttac gtgagcaaat actagactta agcaaaagat atgttaaagc 600 tctagcagag gaaaataaga acacagtgga tgtcgagaac ggtgcttcta 650 tggcaggata tgcggatctg aaaagaacaa ttgctgtcct tctggatgac 700 attttgcaac gattggtgaa gctggagaac aaagttgact atattgttgt 750 gaatggctca gcagccaaca ccaccaatgg tactagtggg aatttggtgc 800 cagtaaccac aaataaaaga acgaatgtct cgggcagtat cagatagcag 850 ttgaaaatca ccttgtgctg ctccatccac tgtggattat atcctatggc 900 agaaaagctt tataattgct ggcttaggac agagcaatac tttacaataa 950 aagctctaca cattttcaag gagtatgctg gattcatgga actctaattc 1000 tgtacataaa aattttaaag ttatttgttt gctttcaggc aagtctgttc 1050 aatgctgtac tatgtcctta aagagaattt ggtaacttgg ttgatgtggt 1100 aagcagatag gtgagttttg tataaatctt ttgtgtttga gatcaagctg 1150 aaatgaaaac actgaaaaac atggattcat ttctataaca catttattta 1200 agtatataac acgttttttg gacaagtgaa gaatgtttaa tcattctgtc 1250 atttgttctc aatagatgta actgttagac tacggctatt tgaaaaaatg 1300 tgcttattgt actatatttt gttattccaa ttatgagcag agaaaggaaa 1350 tataatgttg aaaataatgt tttgaaatca tgacccaaag aatgtattga 1400 tttgcactat ccttcagaat aactgaaggt taattattgt atatttttaa 1450 aaattacact tataagagta taatcttgaa atgggtagca gccactgtcc 1500 attacctatc gtaaacattg gggcaattta ataacagcat taaaatagtt 1550 gtaaactcta atcttatact tattgaagaa taaaagatat ttttatgatg 1600 agagtaacaa taaagtattc atgatttttc acatacatga atgttcattt 1650 aaaagtttaa tcctttgagt gtctatgcta tcaggaaagc acattatttc 1700 catatttggg ttaattttgc ttttattata ttggtctagg aggaagggac 1750 tttggagaat ggaactcttg aggactttag ccaggtgtat ataataaagg 1800 tacttttgtg ctgcattaaa ttgcttggaa agtgttaaca ttatattata 1850 taagagtatc ctttatgaaa ttttgaattt gtataacaga tgcattagat 1900 attcatttta tataatggcc acttaaaata agaacattta aaatataaac 1950 tatgaagatt gactatcttt tcaggaaaaa agctgtatat agcacaggga 2000 accctaatct tgggtaattc tagtataaaa caaattatac ttttatttaa 2050 atttcccttg tagcaaatct aattgccaca tggtgcccta tatttcatag 2100 832 tatttattct ctatagtaac tgcttaagtg cagctagctt ctagatttag 2150 actatataga atttagatat tgtattgttc gtcattataa tatgctacca 22 00 catgtagcaa taattacaat attttattaa aataaatatg tgaaatattg 2250 tttcatgaaa gacagatttc caaatctctc ttctcttctc tgtactgtct 2300 acctttatgt gaagaaatta attatatgcc attgccaggt 2340 <210> 395 <211> 140 <212> PRT <213> Homo sapiens <400> 395 Met Phe Phe Thr Ile Ser Arg Lys Asn Met Ser Gin Lys Leu Ser 15 10 15 Leu Leu Leu Leu Val Phe Gly Leu Ile Trp Gly Leu Met Leu Leu 20 25 30 His Tyr Thr Phe Gin Gin Pro Arg His Gin Ser Ser Val Lys Leu 35 40 45 Arg Glu Gin Ile Leu Asp Leu Ser Lys Arg Tyr Val Lys Ala Leu 50 55 60 Ala Glu Glu Asn Lys Asn Thr Val Asp Val Glu Asn Gly Ala Ser 65 70 75 Met Ala Gly Tyr Ala Asp Leu Lys Arg Thr Ile Ala Val Leu Leu 80 85 90 Asp Asp Ile Leu Gin Arg Leu Val Lys Leu Glu Asn Lys Val Asp 95 100 105 Tyr Ile Val Val Asn Gly Ser Ala Ala Asn Thr Thr Asn Gly Thr 110 115 120 Ser Gly Asn Leu Val Pro Val Thr Thr Asn Lys Arg Thr Asn Val 125 130 135 Ser Gly Ser Ile Arg 140 <210> 396 <211> 2639 <212> DNA <213> Homo sapiens <400> 396 cgcggccggg ccgccggggt gagcgtgccg aggcggctgt ggcgcaggct 50 tccagccccc accatgccgt ggcccctgct gctgctgctg gccgtgagtg 100 gggcccagac aacccggcca tgcttccccg ggtgccaatg cgaggtggag 150 accttcggcc ttttcgacag cttcagcctg actcgggtgg attgtagcgg 200 cctgggcccc cacatcatgc cggtgcccat ccctctggac acagcccact 2 50 833 tggacctgtc ctccaaccgg ctggagatgg tgaatgagtc ggtgttggcg 300 gggccgggct acacgacgtt ggctggcctg gatctcagcc acaacctgct 350 caccagcatc tcacccactg ccttctcccg ccttcgctac ctggagtcgc 400 ttgacctcag ccacaatggc ctgacagccc tgccagccga gagcttcacc 450 agctcacccc tgagcgacgt gaaccttagc cacaaccagc tccgggaggt 500 ctcagtgtct gccttcacga cgcacagtca gggccgggca ctacacgtgg 550 acctctccca caacctcatt caccgcctcg tgccccaccc cacgagggcc 600 ggcctgcctg cgcccaccat tcagagcctg aacctggcct ggaaccggct 650 ccatgccgtg cccaacctcc gagacttgcc cctgcgctac ctgagcctgg 700 atgggaaccc tctagctgtc attggtccgg gtgccttcgc ggggctggga 750 ggccttacac acctgtctct ggccagcctg cagaggctcc ctgagctggc 800 gcccagtggc ttccgtgagc taccgggcct gcaggtcctg gacctgtcgg 850 gcaaccccaa gcttaactgg gcaggagctg aggtgttttc aggcctgagc 900 tccctgcagg agctggacct ttcgggcacc aacctggtgc ccctgcctga 950 ggcgctgctc ctccacctcc cggcactgca gagcgtcagc gtgggccagg 1000 atgtgcggtg ccggcgcctg gtgcgggagg gcacctaccc ccggaggcct 1050 ggctccagcc ccaaggtgcc cctgcactgc gtagacaccc gggaatctgc 1100 tgccaggggc cccaccatct tgtgacaaat ggtgtggccc agggccacat 1150 aacagactgc tgtcctgggc tgcctcaggt cccgagtaac ttatgttcaa 1200 tgtgccaaca ccagtgggga gcccgcaggc ctatgtggca gcgtcaccac 1250 aggagttgtg ggcctaggag aggctttgga cctgggagcc acacctagga 1300 gcaaagtctc acccctttgt ctacgttgct tccccaaacc atgagcagag 1350 ggacttcgat gccaaaccag actcgggtcc cctcctgctt cccttcccca 1400 cttatccccc aagtgccttc cctcatgcct gggccggcct gacccgcaat 1450 gggcagaggg tgggtgggac cccctgctgc agggcagagt tcaggtccac 1500 tgggctgagt gtccccttgg gcccatggcc cagtcactca ggggcgagtt 1550 tcttttctaa catagccctt tctttgccat gaggccatga ggcccgcttc 1600 atccttttct atttccctag aaccttaatg gtagaaggaa ttgcaaagaa 1650 tcaagtccac ccttctcatg tgacagatgg ggaaactgag gccttgagaa 1700 ggaaaaaggc taatctaagt tcctgcgggc agtggcatga ctggagcaca 1750 gcctcctgcc tcccagcccg gacccaatgc actttcttgt ctcctctaat 1800 aagccccacc ctccccgcct gggctcccct 834 tgctgccctt gcctgttccc 1850 cattagcaca ggagtagcag cagcaggaca ggcaagagcc tcacaagtgg 1900 gactctgggc ctctgaccag ctgtgcggca tgggctaagt cactctgccc 1950 ttcggagcct ctggaagctt agggcacatt ggttccagcc tagccagttt 2000 ctcaccctgg gttggggtcc cccagcatcc agactggaaa cctacccatt 2050 ttcccctgag catcctctag atgctgcccc aaggagttgc tgcagttctg 2100 gagcctcatc tggctgggat ctccaagggg cctcctggat tcagtcccca 2150 ctggccctga gcacgacagc ccttcttacc ctcccaggaa tgccgtgaaa 2200 ggagacaagg tctgcccgac ccatgtctat gctctacccc cagggcagca 2250 tctcagcttc cgaaccctgg gctgtttcct tagtcttcat tttataaaag 2300 ttgttgcctt tttaacggag tgtcactttc aaccggcctc ccctacccct 2350 gctggccggg gatggagaca tgtcatttgt aaaagcagaa aaaggttgca 2400 tttgttcact tttgtaatat tgtcctgggc ctgtgttggg gtgttggggg 2450 aagctgggca ccccacaggg tcagtggcca cagtgagctc catgggcatc tgtcttcccc aggggctggc cacctgccta cccacagaga gcccatcatc 2500 2550 tatctaaccg gtccttgatt taataaacac tataaaaggt ttaaaaaaaa 2600 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaa 263 9 <210> 397 <211> 353 <212> PRT <213> Homo sapiens <400> 397 Met Pro Trp Pro Leu Leu Leu Leu Leu Ala Val Ser Gly Ala Gin 15 10 15 Thr Thr Arg Pro Cys Phe Pro Gly Cys Gin Cys Glu Val Glu Thr 20 25 30 Phe Gly Leu Phe Asp Ser Phe Ser Leu Thr Arg Val Asp Cys Ser 35 40 45 Gly Leu Gly Pro His Ile Met Pro Val Pro Ile Pro Leu Asp Thr 50 55 60 Ala His Leu Asp Leu Ser Ser Asn Arg Leu Glu Met Val Asn Glu 65 70 75 Ser Val Leu Ala Gly Pro Gly Tyr Thr Thr Leu Ala Gly Leu Asp 80 85 90 Leu Ser His Asn Leu Leu Thr Ser Ile Ser Pro Thr Ala Phe Ser 95 100 105 Arg Leu Arg Tyr Leu Glu Ser Leu Asp Leu Ser 110 115 His Asn Gly Leu 120 835 Thr Ala Leu Pro Ala Glu Ser Phe Thr Ser Ser Pro Leu Ser Asp 125 130 135 Val Asn Leu Ser His Asn Gin Leu Arg Glu Val Ser Val Ser Ala 140 145 150 Phe Thr Thr His Ser Gin Gly Arg Ala Leu His Val Asp Leu Ser 155 160 165 His Asn Leu Ile His Arg Leu Val Pro His Pro Thr Arg Ala Gly 170 175 180 Leu Pro Ala Pro Thr Ile Gin Ser Leu Asn Leu Ala Trp Asn Arg 185 190 195 Leu His Ala Val Pro Asn Leu Arg Asp Leu Pro Leu Arg Tyr Leu 200 205 210 Ser Leu Asp Gly Asn Pro Leu Ala Val Ile Gly Pro Gly Ala Phe 215 220 225 Ala Gly Leu Gly Gly Leu Thr His Leu Ser Leu Ala Ser Leu Gin 230 235 240 Arg Leu Pro Glu Leu Ala Pro Ser Gly Phe Arg Glu Leu Pro Gly 245 250 255 Leu Gin Val Leu Asp Leu Ser Gly Asn Pro Lys Leu Asn Trp Ala 260 265 270 Gly Ala Glu Val Phe Ser Gly Leu Ser Ser Leu Gin Glu Leu Asp 275 280 285 Leu Ser Gly Thr Asn Leu Val Pro Leu Pro Glu Ala Leu Leu Leu 290 295 300 His Leu Pro Ala Leu Gin Ser Val Ser Val Gly Gin Asp Val Arg 305 310 315 Cys Arg Arg Leu Val Arg Glu Gly Thr Tyr Pro Arg Arg Pro Gly 320 325 330 Ser Ser Pro Lys Val Pro Leu His Cys Val Asp Thr Arg Glu Ser 335 340 345 Ala Ala Arg Gly Pro Thr Ile Leu 350 <210> 398 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 398 ccctgccagc cgagagcttc acc 23 <210> 399 <211> 23 836 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 399 ggttggtgcc cgaaaggtcc age 23 <210> 400 <211> 44 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 400 caaccccaag cttaactggg caggagctga ggtgttttca ggee 44 <210> 401 <211> 1571 <212> DNA <213> Homo sapiens <400> 401 gatggcgcag ccacagcttc tgtgagattc gatttctccc cagttcccct 50 gtgggtctga gaggctatat ggggaccaga gcgtcaattc agggtgagct cccaaaacaa acgttggctt gttttgacat tctggaaggg ttcccctgaa 100 150 atgtcattct ctatctattc actgcaagtg cctgctgttc caggccttac 200 ctgctgggca etaaeggegg agccaggatg gggacagaat aaaggagcca 250 cgacctgtgc caccaactcg cactcagact ctgaactcag acctgaaatc 300 ttctcttcac gggaggcttg gcagtttttc ttactcctgt ggtctccaga 350 tttcaggcct aagatgaaag cctctagtct tgccttcagc cttctctctg 400 ctgcgtttta tctcctatgg actccttcca ctggactgaa gacactcaat 450 ttgggaagct gtgtgatcgc cacaaacctt caggaaatac gaaatggatt 500 ttctgagata eggggcagtg tgcaagccaa agatggaaac attgacatca 550 gaatcttaag gaggactgag tetttgeaag acacaaagcc tgegaatega 600 tgctgcctcc tgcgccattt gctaagactc tatctggaca gggtatttaa 650 aaactaccag acccctgacc attatactct ccggaagatc agcagcctcg 700 ccaattcctt tcttaccatc aagaaggacc tccggctctc tcatgcccac 750 atgacatgcc attgtgggga ggaagcaatg aagaaataca gccagattct 800 gagtcacttt gaaaagctgg aacctcaggc agcagttgtg aaggctttgg 850 gggaactaga cattcttctg caatggatgg aggagacaga ataggaggaa 900 agtgatgctg ctgctaagaa tattcgaggt caagagctcc agtcttcaat 950 837 acctgcagag gaggcatgac cccaaaccac catctcttta ctgtactagt 1000 cttgtgctgg tcacagtgta tcttatttat gcattacttg cttccttgca 1050 tgattgtctt tatgcatccc caatcttaat tgagaccata cttgtataag 1100 atttttgtaa tatctttctg ctattggata tatttattag ttaatatatt 1150 tatttatttt ttgctattta atgtatttat ttttttactt ggacatgaaa 12 00 ctttaaaaaa attcacagat tatatttata acctgactag agcaggtgat 1250 gtatttttat acagtaaaaa aaaaaaacct tgtaaattct agaagagtgg 13 00 ctaggggggt tattcatttg tattcaacta aggacatatt tactcatgct 1350 gatgctctgt gagatatttg aaattgaacc aatgactact taggatgggt 1400 tgtggaataa gttttgatgt ggaattgcac atctacctta caattactga 1450 ccatccccag tagactcccc agtcccataa ttgtgtatct tccagccagg 1500 aatcctacac ggccagcatg tatttctaca aataaagttt tctttgcata 1550 ccaaaaaaaa aaaaaaaaaa a 1571 <210> 402 <211> 261 <212> PRT <213> Homo sapiens <400> 402 Met Arg Gin Phe Pro Lys Thr Ser Phe Asp Ile Ser Pro Glu Met 1 5 10 15 Ser Phe Ser Ile Tyr Ser Leu Gin Val Pro Ala Val Pro Gly Leu 20 25 30 Thr Cys Trp Ala Leu Thr Ala Glu Pro Gly Trp Gly Gin Asn Lys 35 40 45 Gly Ala Thr Thr Cys Ala Thr Asn Ser His Ser Asp Ser Glu Leu 50 55 60 Arg Pro Glu Ile Phe Ser Ser Arg Glu Ala Trp Gin Phe Phe Leu 65 70 75 Leu Leu Trp Ser Pro Asp Phe Arg Pro Lys Met Lys Ala Ser Ser 80 85 90 Leu Ala Phe Ser Leu Leu Ser Ala Ala Phe Tyr Leu Leu Trp Thr 95 100 105 Pro Ser Thr Gly Leu Lys Thr Leu Asn Leu Gly Ser Cys Val Ile 110 115 120 Ala Thr Asn Leu Gin Glu Ile Arg Asn Gly Phe Ser Glu Ile Arg 125 130 135 Gly Ser Val Gin Ala Lys Asp Gly Asn Ile Asp Ile Arg Ile Leu 140 145 150 838 Arg Arg Thr Glu Ser Leu Gin Asp Thr Lys Pro Ala Asn Arg Cys 155 160 165 Cys Leu Leu Arg His Leu Leu Arg Leu Tyr Leu Asp Arg Val Phe 170 175 180 Lys Asn Tyr Gin Thr Pro Asp His Tyr Thr Leu Arg Lys Ile Ser 185 190 195 Ser Leu Ala Asn Ser Phe Leu Thr Ile Lys Lys Asp Leu Arg Leu 200 205 210 Ser His Ala His Met Thr Cys His Cys Gly Glu Glu Ala Met Lys 215 220 225 Lys Tyr Ser Gin Ile Leu Ser His Phe Glu Lys Leu Glu Pro Gin 230 235 240 Ala Ala Val Val Lys Ala Leu Gly Glu Leu Asp Ile Leu Leu Gin 245 250 255 Trp Met Glu Glu Thr Glu 260 <210> 403 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 403 ctcctgtggt ctccagattt caggccta 28 <210> 404 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 404 agtcctcctt aagattctga tgtcaa 2 6 <210> 405 <211> 998 <212> DNA <213> Homo sapiens <400> 405 ccgttatcgt cttgcgctac tgctgaatgt ccgtcccgga ggaggaggag 50 aggcttttgc cgctgaccca gagatggccc cgagcgagca aattcctact 10 0 gtccggctgc gcggctaccg tggccgagct agcaaccttt cccctggatc 150 tcacaaaaac tcgactccaa atgcaaggag aagcagctct tgctcggttg 200 ggagacggtg caagagaatc tgccccctat aggggaatgg tgcgcacagc 250 839 cctagggatc attgaagagg aaggctttct aaagctttgg caaggagtga 300 cacccgccat ttacagacac gtagtgtatt ctggaggtcg aatggtcaca 350 tatgaacatc tccgagaggt tgtgtttggc aaaagtgaag atgagcatta 400 tcccctttgg aaatcagtca ttggagggat gatggctggt gttattggcc 450 agtttttagc caatccaact gacctagtga aggttcagat gcaaatggaa 500 ggaaaaagga aactggaagg aaaaccattg cgatttcgtg gtgtacatca 550 tgcatttgca aaaatcttag ctgaaggagg aatacgaggg ctttgggcag 600 gctgggtacc caatatacaa agagcagcac tggtgaatat gggagattta 650 accacttatg atacagtgaa acactacttg gtattgaata caccacttga 700 ggacaatatc atgactcacg gtttatcaag tttatgttct ggactggtag 750 cttctattct gggaacacca gccgatgtca tcaaaagcag aataatgaat 800 caaccacgag ataaacaagg aaggggactt ttgtataaat catcgactga 850 ctgcttgatt caggctgttc aaggtgaagg attcatgagt ctatataaag 900 gctttttacc atcttggctg agaatgaccc cttggtcaat ggtgttctgg 950 cttacttatg aaaaaatcag agagatgagt ggagtcagtc cattttaa 998 <210> 406 <211> 323 <212> PRT <2X3> Homo sapiens <400> 406 Met Ser Val Pro Glu Glu Glu Glu Arg Leu Leu Pro Leu Thr Gin 15 10 15 Arg Trp Pro Arg Ala Ser Lys Phe Leu Leu Ser Gly Cys Ala Ala 20 25 30 Thr Val Ala Glu Leu Ala Thr Phe Pro Leu Asp Leu Thr Lys Thr 35 40 45 Arg Leu Gin Met Gin Gly Glu Ala Ala Leu Ala Arg Leu Gly Asp 50 55 60 Gly Ala Arg Glu Ser Ala Pro Tyr Arg Gly Met Val Arg Thr Ala 65 ' 70 75 Leu Gly Ile Ile Glu Glu Glu Gly Phe Leu Lys Leu Trp Gin Gly 80 85 90 Val Thr Pro Ala Ile Tyr Arg His Val Val Tyr Ser Gly Gly Arg 95 100 105 Met Val Thr Tyr Glu His Leu Arg Glu Val Val Phe Gly Lys Ser 110 115 120 Glu Asp Glu His Tyr Pro Leu Trp Lys Ser Val Ile Gly Gly Met 840 125 130 135 Met Ala Gly Val Ile Gly Gin Phe Leu Ala Asn Pro Thr Asp Leu 140 145 150 Val Lys Val Gin Met Gin Met Glu Gly Lys Arg Lys Leu Glu Gly 155 160 165 Lys Pro Leu Arg Phe Arg Gly Val His His Ala Phe Ala Lys Ile 170 175 180 Leu Ala Glu Gly Gly Ile Arg Gly Leu Trp Ala Gly Trp Val Pro 185 190 195 Asn Ile Gin Arg Ala Ala Leu Val Asn Met Gly Asp Leu Thr Thr 200 205 210 Tyr Asp Thr Val Lys His Tyr Leu Val Leu Asn Thr Pro Leu Glu 215 220 225 Asp Asn Ile Met Thr His Gly Leu Ser Ser Leu Cys Ser Gly Leu 230 235 240 Val Ala Ser Ile Leu Gly Thr Pro Ala Asp Val Ile Lys Ser Arg 245 250 255 Ile Met Asn Gin Pro Arg Asp Lys Gin Gly Arg Gly Leu Leu Tyr 260 265 270 Lys Ser Ser Thr Asp Cys Leu Ile Gin Ala Val Gin Gly Glu Gly 275 280 285 Phe Met Ser Leu Tyr Lys Gly Phe Leu Pro Ser Trp Leu Arg Met 290 295 300 Thr Pro Trp Ser Met Val Phe Trp Leu Thr Tyr Glu Lys Ile Arg 305 310 315 Glu Met Ser Gly Val Ser Pro Phe 320 <210> 407 <211> 31 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 407 cgcggatccc gttatcgtct tgcgctactg c 31 <210> 408 <211> 34 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 408 gcggaattct taaaatggac tgactccact catc 34 841 <210> 409 <211> 1487 <212> DNA <213> Homo sapiens <400> 409 cggacgcgtg ggcgcgggac gccggcaggg ttgtggcgca gcagtctcct 50 tcctgcgcgc gcgcctgaag tcggcgtggg cgtttgagga agctgggata 100 cagcatttaa tgaaaaattt atgcttaaga agtaaaaatg gcaggcttcc 150 tagataattt tcgttggcca gaatgtgaat gtattgactg gagtgagaga 200 agaaatgctg tggcatctgt tgtcgcaggt atattgtttt ttacaggctg 250 gtggataatg attgatgcag ctgtggtgta tcctaagcca gaacagttga 300 accatgcctt tcacacatgt ggtgtatttt ccacattggc tttcttcatg 350 ataaatgctg tatccaatgc tcaggtgaga ggtgatagct atgaaagcgg 400 ctgtttagga agaacaggtg ctcgagtttg gcttttcatt ggtttcatgt 450 tgatgtttgg gtcacttatt gcttccatgt ggattctttt tggtgcatat 500 gttacccaaa atactgatgt ttatccggga ctagctgtgt tttttcaaaa 550 tgcacttata ttttttagca ctctgatcta caaatttgga agaaccgaag 600 agctatggac ctgagatcac ttcttaagtc acattttcct tttgttatat 650 tctgtttgta tagattgtac gataggtttt attaaatgtt ttatctctca ttgtttcttt gtacacattg acatttttat ccaaatggag gttctgagtt 700 750 ttgaaatagt tttatgaaat ttctttattt ttcattgcat agactgttaa 800 tatgtatata atacaagact atatgaattg gataatgagt atcagttttt 850 tattcctgag atttagaact tgatctactc cctgagccag ggttacatca 900 tcttgtcatt ttagaagtaa ccactcttgt ctctctggct gggcacggtg 950 gctcatgcct gtaatcccag cactttggga ggccgaggcg ggccgattgc 1000 ttgaggtcaa gtgtttgaga ccagcctggc caacatggcg aaaccccatc 1050 tactaaaaat acaaaaatta gccaggcatg gtggtgggtg cctgtaatcc 1100 cagctacctg ggaggctgag gcaggagaat cgcttgaacc cggggggcag 1150 aggttgcagt gagctgagtt tgcgccactg cactctagcc tgggggagaa 1200 agtgaaactc cctctcaaaa aaaagaccac tctcagtatc tctgatttct 1250 gaagatgtac aaaaaaatat agcttcatat atctggaatg agcactgagc 1300 cataaaaggt tttcagcaag ttgtaactta ttttggccta aaaatgaggt 1350 ttttttggta aagaaaaaat atttgttctt atgtattgaa gaagtgtact 1400 842 tttatataat gattttttaa atgcccaaag gactagtttg aaagcttctt 1450 ttaaaaagaa ttcctctaat atgactttat gtgagaa 1487 <210> 410 <211> 158 <212> PRT <213> Homo sapiens <400> 410 Met Ala Gly Phe Leu Asp Asn Phe Arg 1 5 Ile Asp Trp Ser Glu Arg Arg Asn Ala 20 Gly Ile Leu Phe Phe Thr Gly Trp Trp 35 Val Val Tyr Pro Lys Pro Glu Gin Leu 50 Cys Gly Val Phe Ser Thr Leu Ala Phe 65 Ser Asn Ala Gin Val Arg Gly Asp Ser 80 Gly Arg Thr Gly Ala Arg Val Trp Leu 95 Met Phe Gly Ser Leu Ile Ala Ser Met 110 Tyr Val Thr Gin Asn Thr Asp Val Tyr 125 Phe Gin Asn Ala Leu Ile Phe Phe Ser 140 Gly Arg Thr Glu Glu Leu Trp Thr 155 <210> 411 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 411 gtttgaggaa gctgggatac 2 0 <210> 412 <211> 20 <212> DNA <213> Artificial Sequence Trp Pro Glu Cys Glu Cys 10 15 Val Ala Ser Val Val Ala 25 30 Ile Met Ile Asp Ala Ala 40 45 Asn His Ala Phe His Thr 55 60 Phe Met Ile Asn Ala Val 70 75 Tyr Glu Ser Gly Cys Leu 85 90 Phe Ile Gly Phe Met Leu 100 105 Trp Ile Leu Phe Gly Ala 115 120 Pro Gly Leu Ala Val Phe 130 135 Thr Leu Ile Tyr Lys Phe 145 150 <220> <223> Synthetic oligonucleotide probe 843 <400> 412 ccaaactcga gcacctgttc 20 <210> 413 <211> 40 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 413 atggcaggct tcctagataa ttttcgttgg ccagaatgtg 40 <210> 414 <211> 1337 <212> DNA <213> Homo sapiens <400> 414 gttgatggca aacttcctca aaggaggggc agagcctgcg cagggcagga 50 gcagctggcc cactggcggc ccgcaacact ccgtctcacc ctctgggccc 100 actgcatcta gaggagggcc gtctgtgagg ccactacccc tccagcaact 150 gggaggtggg actgtcagaa gctggcccag ggtggtggtc agctgggtca 200 gggacctacg gcacctgctg gaccacctcg ccttctccat cgaagcaggg 250 aagtgggagc ctcgagccct cgggtggaag ctgaccccaa gccacccttc 300 acctggacag gatgagagtg tcaggtgtgc ttcgcctcct ggccctcatc 350 tttgccatag tcacgacatg gatgtttatt cgaagctaca tgagcttcag 400 catgaaaacc atccgtctgc cacgctggct ggcagcctcg cccaccaagg 450 agatccaggt taaaaagtac aagtgtggcc tcatcaagcc ctgcccagcc 500 aactactttg cgtttaaaat ctgcagtggg gccgccaacg tcgtgggccc 550 tactatgtgc tttgaagacc gcatgatcat gagtcctgtg aaaaacaatg 600 tgggcagagg cctaaacatc gccctggtga atggaaccac gggagctgtg 650 ctgggacaga aggcatttga catgtactct ggagatgtta tgcacctagt 700 gaaattcctt aaagaaattc cggggggtgc actggtgctg gtggcctcct 750 acgacgatcc agggaccaaa atgaacgatg aaagcaggaa actcttctct 800 gacttgggga gttcctacgc aaaacaactg ggcttccggg acagctgggt 850 cttcatagga gccaaagacc tcaggggtaa aagccccttt gagcagttct 900 taaagaacag cccagacaca aacaaatacg agggatggcc agagctgctg 950 gagatggagg gctgcatgcc cccgaagcca ttttagggtg gctgtggctc 1000 ttcctcagcc aggggcctga agaagctcct gcctgactta ggagtcagag 1050 844 cccggcaggg gctgaggagg aggagcaggg ggtgctgcgt ggaaggtgct 1100 gcaggtcctt gcacgctgtg tcgcgcctct cctcctcgga aacagaaccc 1150 tcccacagca catcctaccc ggaagaccag cctcagaggg tccttctgga 1200 accagctgtc tgtggagaga atggggtgct ttcgtcaggg actgctgacg 1250 gctggtcctg aggaaggaca aactgcccag acttgagccc aattaaattt 1300 tatttttgct ggttttgaaa aaaaaaaaaa aaaaaaa 1337 <210> 415 <211> 224 <212> PRT <213> Homo sapiens <400> 415 Met Arg Val Ser Gly Val Leu Arg Leu Leu Ala Leu Ile Phe Ala 15 10 15 Ile Val Thr Thr Trp Met Phe Ile Arg Ser Tyr Met Ser Phe Ser 20 25 30 Met Lys Thr Ile Arg Leu Pro Arg Trp Leu Ala Ala Ser Pro Thr 35 40 45 Lys Glu Ile Gin Val Lys Lys Tyr Lys Cys Gly Leu Ile Lys Pro 50 55 60 Cys Pro Ala Asn Tyr Phe Ala Phe Lys Ile Cys Ser Gly Ala Ala 65 70 75 Asn Val Val Gly Pro Thr Met Cys Phe Glu Asp Arg Met Ile Met 80 85 90 Ser Pro Val Lys Asn Asn Val Gly Arg Gly Leu Asn Ile Ala Leu 95 100 105 Val Asn Gly Thr Thr Gly Ala Val Leu Gly Gin Lys Ala Phe Asp 110 115 120 Met Tyr Ser Gly Asp Val Met His Leu Val Lys Phe Leu Lys Glu 125 130 135 Ile Pro Gly Gly Ala Leu Val Leu Val Ala Ser Tyr Asp Asp Pro 140 145 150 Gly Thr Lys Met Asn Asp Glu Ser Arg Lys Leu Phe Ser Asp Leu 155 160 165 Gly Ser Ser Tyr Ala Lys Gin Leu Gly Phe Arg Asp Ser Trp Val 170 175 180 Phe Ile Gly Ala Lys Asp Leu Arg Gly Lys Ser Pro Phe Glu Gin 185 190 195 Phe Leu Lys Asn Ser Pro Asp Thr Asn Lys Tyr Glu Gly Trp Pro 200 205 210 Glu Leu Leu Glu Met Glu Gly Cys Met Pro Pro Lys Pro Phe 215 220 845 <210> 416 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 416 gccatagtca cgacatggat g 21 <210> 417 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 417 ggatggccag agctgctg 18 <210> 418 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 418 aaagtacaag tgtggcctca tcaagc 2 6 <210> 419 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 419 tctgactcct aagtcaggca ggag 24 <210> 420 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 420 attctctcca cagacagctg gttc 24 <210> 421 <211> 46 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe 846 <400> 421 gtacaagtgt ggcctcatca agccctgccc agccaactac tttgcg 46 <210> 422 <211> 1701 <212> DNA <213> Homo sapiens <220> <221> unsure <222> 1528 <223> unknown base <400> 422 gagactgcag agggagataa agagagaggg caaagaggca gcaagagatt 50 tgtcctgggg atccagaaac ccatgatacc ctactgaaca ccgaatcccc 100 tggaagccca cagagacaga gacagcaaga gaagcagaga taaatacact 150 cacgccagga gctcgctcgc tctctctctc tctctctcac tcctccctcc 200 ctctctctct gcctgtccta gtcctctagt cctcaaattc ccagtcccct 250 gcaccccttc ctgggacact atgttgttct ccgccctcct gctggaggtg 300 atttggatcc tggctgcaga tgggggtcaa cactggacgt atgagggccc 350 acatggtcag gaccattggc cagcctctta ccctgagtgt ggaaacaatg 400 cccagtcgcc catcgatatt cagacagaca gtgtgacatt tgaccctgat 450 ttgcctgctc tgcagcccca cggatatgac cagcctggca ccgagccttt 500 ggacctgcac aacaatggcc acacagtgca actctctctg ccctctaccc 550 tgtatctggg tggacttccc cgaaaatatg tagctgccca gctccacctg 600 cactggggtc agaaaggatc cccagggggg tcagaacacc agatcaacag 650 tgaagccaca tttgcagagc tccacattgt acattatgac tctgattcct 700 atgacagctt gagtgaggct gctgagaggc ctcagggcct ggctgtcctg 750 ggcatcctaa ttgaggtggg tgagactaag aatatagctt atgaacacat 800 tctgagtcac ttgcatgaag tcaggcataa agatcagaag acctcagtgc 850 ctcccttcaa cctaagagag ctgctcccca aacagctggg gcagtacttc 900 cgctacaatg gctcgctcac aactccccct tgctaccaga gtgtgctctg 950 gacagttttt tatagaaggt cccagatttc aatggaacag ctggaaaagc 1000 ttcaggggac attgttctcc acagaagagg agccctctaa gcttctggta 1050 cagaactacc gagcccttca gcctctcaat cagcgcatgg tctttgcttc 1100 tttcatccaa gcaggatcct cgtataccac aggtgaaatg ctgagtctag 1150 gtgtaggaat cttggttggc tgtctctgcc ttctcctggc tgtttatttc 1200 847 attgctagaa agattcggaa gaagaggctg gaaaaccgaa agagtgtggt 1250 cttcacctca gcacaagcca cgactgaggc ataaattcct tctcagatac 13 00 catggatgtg gatgacttcc cttcatgcct atcaggaagc ctctaaaatg 1350 gggtgtagga tctggccaga aacactgtag gagtagtaag cagatgtcct 1400 ccttcccctg gacatctctt agagaggaat ggacccaggc tgtcattcca 1450 ggaagaactg cagagccttc agcctctcca aacatgtagg aggaaatgag 1500 gaaatcgctg tgttgttaat gcagaganca aactctgttt agttgcaggg 1550 gaagtttggg atatacccca aagtcctcta ccccctcact tttatggccc 1600 tttccctaga tatactgcgg gatctctcct taggataaag agttgctgtt 1650 gaagttgtat atttttgatc aatatatttg gaaattaaag tttctgactt 17 00 t 1701 <210> 423 <211> 337 <212> PRT <213> Homo sapiens <400> 423 Met Leu Phe Ser Ala Leu Leu Leu Glu Val Ile Trp Ile Leu Ala 1 5 10 15 Ala Asp Gly Gly Gin His Trp Thr Tyr Glu Gly Pro His Gly Gin 20 25 30 Asp His Trp Pro Ala Ser Tyr Pro Glu Cys Gly Asn Asn Ala Gin 35 40 45 Ser Pro Ile Asp Ile Gin Thr Asp Ser Val Thr Phe Asp Pro Asp 50 55 60 Leu Pro Ala Leu Gin Pro His Gly Tyr Asp Gin Pro Gly Thr Glu 65 70 75 Pro Leu Asp Leu His Asn Asn Gly His Thr Val Gin Leu Ser Leu 80 85 90 Pro Ser Thr Leu Tyr Leu Gly Gly Leu Pro Arg Lys Tyr Val Ala 95 100 105 Ala Gin Leu His Leu His Trp Gly Gin Lys Gly Ser Pro Gly Gly 110 115 120 Ser Glu His Gin Ile Asn Ser Glu Ala Thr Phe Ala Glu Leu His 125 130 135 Ile Val His Tyr Asp Ser Asp Ser Tyr Asp Ser Leu Ser Glu Ala 140 145 150 Ala Glu Arg Pro Gin Gly Leu Ala Val Leu Gly Ile Leu Ile Glu 155 160 165 Val Gly Glu Thr Lys Asn Ile Ala Tyr Glu His Ile Leu Ser His 848 170 175 180 Leu His Glu Val Arg His Lys Asp Gin Lys Thr Ser Val Pro Pro 185 190 195 Phe Asn Leu Arg Glu Leu Leu Pro Lys Gin Leu Gly Gin Tyr Phe 200 205 210 Arg Tyr Asn Gly Ser Leu Thr Thr Pro Pro Cys Tyr Gin Ser Val 215 220 225 Leu Trp Thr Val Phe Tyr Arg Arg Ser Gin Ile Ser Met Glu Gin 230 235 240 Leu Glu Lys Leu Gin Gly Thr Leu Phe Ser Thr Glu Glu Glu Pro 245 250 255 Ser Lys Leu Leu Val Gin Asn Tyr Arg Ala Leu Gin Pro Leu Asn 260 265 270 Gin Arg Met Val Phe Ala Ser Phe Ile Gin Ala Gly Ser Ser Tyr 275 280 285 Thr Thr Gly Glu Met Leu Ser Leu Gly Val Gly Ile Leu Val Gly 290 295 300 Cys Leu Cys Leu Leu Leu Ala Val Tyr Phe Ile Ala Arg Lys Ile 305 310 315 Arg Lys Lys Arg Leu Glu Asn Arg Lys Ser Val Val Phe Thr Ser 320 325 330 Ala Gin Ala Thr Thr Glu Ala 335 <210> 424 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 424 gtaaagtcgc tggccagc 18 <210> 425 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 425 cccgatctgc ctgctgta 18 <210> 426 <211> 24 <212> DNA <213> Artificial Sequence 849 <220> <223> Synthetic oligonucleotide probe <400> 426 ctgcactgta tggccattat tgtg 24 <210> 427 <211> 45 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 427 cagaaaccca tgatacccta ctgaacaccg aatcccctgg aagcc 45 <210> 428 <211> 1073 <212> DNA <213> Homo sapiens <400> 428 aatttttcac cagagtaaac ttgagaaacc aactggacct tgagtattgt 50 acattttgcc tcgtggaccc aaaggtagca atctgaaaca tgaggagtac 100 gattctactg ttttgtcttc taggatcaac tcggtcatta ccacagctca 150 aacctgcttt gggactccct cccacaaaac tggctccgga tcagggaaca 200 ctaccaaacc aacagcagtc aaatcaggtc tttccttctt taagtctgat 250 accattaaca cagatgctca cactggggcc agatctgcat ctgttaaatc 300 ctgctgcagg aatgacacct ggtacccaga cccacccatt gaccctggga 350 gggttgaatg tacaacagca actgcaccca catgtgttac caatttttgt 400 cacacaactt ggagcccagg gcactatcct aagctcagag gaattgccac 450 aaatcttcac cccaccagtc gagcctcatc aggcaggggc atccattcct taatccagat tgttcccggg gtccaggatg aggcatcctg gaagccttcc 500 550 agcaggagga gcaggtgtaa atcctgccac ccagggaacc ccagcaggcc 600 gcctcccaac tcccagtggc acagatgacg actttgcagt gaccacccct 650 gcaggcatcc aaaggagcac acatgccatc gaggaagcca ccacagaatc 700 agcaaatgga attcagtaag ctgtttcaaa ttttttcaac taagctgcct 750 cgaatttggt gatacatgtg aatctttatc attgattata ttatggaata 800 gattgagaca cattggatag tcttagaaga aattaattct taatttacct 850 gaaaatattc ttgaaatttc agaaaatatg ttctatgtag agaatcccaa 900 cttttaaaaa caataattca atggataaat ctgtctttga aatataacat 950 tatgctgcct ggatgatatg catattaaaa catatttgga aaactggaaa 1000 850 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1050 aaaaaaaaaa aaaaaaaaaa aaa 1073 <210> 429 <211> 209 <212> PRT <213> Homo sapiens <400> 429 Met Arg Ser Thr Ile Leu Leu Phe Cys Leu Leu Gly Ser Thr Arg 15 10 15 Ser Leu Pro Gin Leu Lys Pro Ala Leu Gly Leu Pro Pro Thr Lys 20 25 30 Leu Ala Pro Asp Gin Gly Thr Leu Pro Asn Gin Gin Gin Ser Asn 35 40 45 Gin Val Phe Pro Ser Leu Ser Leu Ile Pro Leu Thr Gin Met Leu 50 55 60 Thr Leu Gly Pro Asp Leu His Leu Leu Asn Pro Ala Ala Gly Met 65 70 75 Thr Pro Gly Thr Gin Thr His Pro Leu Thr Leu Gly Gly Leu Asn 80 85 90 Val Gin Gin Gin Leu His Pro His Val Leu Pro Ile Phe Val Thr 95 100 105 Gin Leu Gly Ala Gin Gly Thr Ile Leu Ser Ser Glu Glu Leu Pro 110 115 120 Gin Ile Phe Thr Ser Leu Ile Ile His Ser Leu Phe Pro Gly Gly 125 130 135 Ile Leu Pro Thr Ser Gin Ala Gly Ala Asn Pro Asp Val Gin Asp 140 145 150 Gly Ser Leu Pro Ala Gly Gly Ala Gly Val Asn Pro Ala Thr Gin 155 160 165 Gly Thr Pro Ala Gly Arg Leu Pro Thr Pro Ser Gly Thr Asp Asp 170 175 180 Asp Phe Ala Val Thr Thr Pro Ala Gly Ile Gin Arg Ser Thr His 185 190 195 Ala Ile Glu Glu Ala Thr Thr Glu Ser Ala Asn Gly Ile Gin 200 205 <210> 430 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 430 tccaggtgga ccccacttca gg 22 851 <210> 431 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide Probe <400> 431 gggaggctta taggcccaat ctgg 24 <210> 432 <211> 50 <212> DNA <213> Artificial Sequence <220> <223> Synthetic oligonucleotide probe <400> 432 ggcttcagca gcaggtgtga agtcgaagtc gcagtcacag atatcaatga 50 1

Claims

WHAT WE CLAIM IS:

1. An isolated nucleic acid having at least 80% sequence identity to a nucleotide sequence that encodes a polypeptide comprising the amino acid sequence shown in Figure 32 (SEQ ID NO: 54).

2. A nucleic acid sequence of Claim 1, wherein said nucleotide sequence comprises the nucleotide sequence shown in Figure 31 (SEQ ID NO: 53).

3. A nucleic acid of Claim 1 or Claim 2, wherein said nucleotide sequence comprises die full-length coding 10 sequence of the sequence shown in Figure 31 (SEQ ID NO: 53).

4. An isolated nucleic acid which comprises the full-length coding sequence of the DNA deposited under accession number ATCC 203287. 15

5. A vector comprising a nucleic acid of any one of Claims 1 to 4.

6. A vector of Claim 5, wherein said nucleic acid is operably linked to control sequences recognised by a host cell transformed with the vector. 2 0

7. A non-human host cell comprising a vector of Claim 5 or Claim 6.

8. A non-human host cell of Claim 7, wherein said cell is a CHO cell, an E. coli all or a yeast cell.

9. A process for producing a polypeptide comprising culturing a host cell of Claim 7 or Claim 8 under 2 5 conditions suitable for expression of said polypeptide and recovering said polypeptide from the cell culture.

10. An isolated PR01295 polypeptide laving at least 80% sequence identity to the amino acid sequence shown in Figure 32 (SEQ ID NO: 54). 30

11. An isolated PR01295 polypeptide having at least 80% sequence identity to the amino acid sequence encoded by the nucleotide deposited under ATCC 203287.

12. An isolated polypeptide comprising a polypeptide sequence having at least about 80% amino acid sequence identity to the extracellular domain of a PR01295 polypeptide of SEQ ID NO: 54. 35

13. An isolated polypeptide having at least about 80% amino acid sequence identity to a PRO1295 polypeptide of SEQ ID NO: 54 lacking its associated signal peptide.

14. An isolated nucleic acid encoding a polypeptide of any one of Claims 10 to 13. 852 nKraSwr^fv 17 MAR 230*1 RECEIVED

15. IS. A chimeric molecule comprising a polypeptide according to any one of Claims 10 to 13 fused to a heterologous amino acid sequence. 5

16. A chimeric molecule of Claim 15, wherein said heterologous amino acid sequence is an epitope tag sequence.

17. A chimeric molecule of Claim IS, wherein said heterologous amino acid sequence is a Fc region of an immunoglobulin. 10

18. An antibody which specifically binds to a polypeptide according to any one of Claims 10 to 13.

19. An antibody of Claim 18, wherein said antibody is a humanised antibody. , 15

20. An antibody of Claim 18 or Claim 19, wherein said antibody is a monoclonal antibody.

21. An antibody of any one of claims 18 to 20, wherein said antibody is a chimeric antibody.

22. A pharmaceutical composition comprising a polypeptide of any one of claims 10 to 13 and a ^ ^ pharmaceuticaliy acceptable carrier, diluent or excipient.

23. A use of a polypeptide of any one of claims 10 to 13 in the manufacture of a medicament for treating tumor.

24. An isolated nucleic acid as defined in claim 1 substantially as herein described with reference to 2 5 any example thereof and with or without reference to the Figures.

25. A vector as defined in claim 5 substantially as herein described with reference to any example thereof and with or without reference to the Figures. 30

26. A non-human host cell as defined in claim 7 substantially as herein described with reference to any example thereof and with or without reference to the Figures. 35 40

27. A process for producing a polypeptide as claimed in claim 9 substantially as herein described with reference to any example thereof and with or without reference to the Figures.

28. An isolated PR01295 polypeptide as defined in claim 10 or claim 11 substantially as herein described with reference to any example thereof and with or without reference to the Figures. 853 ElLECUiAL PROPERTY QF^CE- OP N.Z 17 l.'.AR 23S1! received

29. An isolated polypeptide as defined in claim 12 or claim 13 substantially as herein described with reference to any example thereof and with or without reference to the Figures.

30. An isolated nucleic acid as claimed in claim 14 substantially as herein described with reference to any example thereof and with or without reference to the Figures.

31. A chimeric molecule as defined in claim 15 substantially as herein described with reference to any example thereof and with or without reference to the Figures.

32. An antibody as defined in claim 18 substantially as herein described with reference to any example thereof and with or without reference to the Figures.

33. A pharmaceutical composition as claimed in claim 22 substantially as herein described with reference to any example thereof and with or without reference to the Figures.

34. A use as claimed in claim 23 substantially as herein described with reference to any example thereof and with or without reference to the Figures. 854