JP2003521865A - 148 human secreted proteins - Google Patents

Abstract

  (57) [Summary] The present invention relates to human secreted proteins and isolated nucleic acids comprising the coding regions of the genes encoding such proteins. Also provided are vectors, host cells, antibodies, and recombinant methods for producing human secreted proteins. The present invention further relates to diagnostic and therapeutic methods useful for diagnosing and treating disorders associated with these novel human secreted proteins.

Description

Detailed Description of the Invention

FIELD OF THE INVENTION The present invention relates to newly identified polynucleotides and polypeptides encoded by these polynucleotides, the use of such polynucleotides and polypeptides, and their production.

BACKGROUND OF THE INVENTION Unlike bacteria, which exist as a single compartment surrounded by a membrane, human cells and other eukaryotes are subdivided by the membrane into many functionally distinct compartments. Each membrane-separated compartment, or organelle, contains various proteins that are essential for the function of that organelle. Cells use a "sorting signal," an amino acid motif located within the protein, to target the protein to specific cellular organelles.

One type of sorting signal called a signal sequence, signal peptide, or leader sequence directs a class of proteins to the organelle called the endoplasmic reticulum (ER). The ER separates membrane-bound proteins from all other types of proteins. Once localized to the ER, both groups of proteins can be further directed to another organelle called the Golgi apparatus. Here, the Golgi distributes proteins to vesicles, including secretory vesicles, cell membranes, lysosomes, and other organelles.

Proteins targeted to the ER by signal sequences can be released into the extracellular space as secreted proteins. For example, vesicles containing secreted proteins can fuse with the cell membrane and release their contents into the extracellular space, a process called exocytosis. Exocytosis can occur constitutively or after receipt of a trigger signal. In the latter case, the protein is stored in secretory vesicles (or secretory granules) until exocytosis is triggered. Similarly, proteins present on the cell membrane may also be secreted into the extracellular space by proteolytic cleavage of the "linker" that holds the protein to the membrane.

Despite significant advances in recent years, only a few genes encoding human secretory proteins have been identified. These secreted proteins include commercially valuable human insulin, interferon, factor VIII, human growth hormone, tissue plasminogen activator, and erythropoietin. Therefore, given the widespread role of secreted proteins in human physiology, there is a need to identify and characterize new human secreted proteins and the genes that encode them. This finding makes it possible to detect, treat and prevent medical disorders by using secreted proteins or the genes encoding them.

SUMMARY OF THE INVENTION The present invention relates to novel polynucleotides and encoded polypeptides.
Further, the invention relates to vectors, host cells, antibodies and recombinant methods for producing polypeptides and polynucleotides. Also provided are diagnostic methods for detecting disorders associated with polypeptides, and therapeutic methods for treating such disorders. The invention further relates to screening methods for identifying binding partners of polypeptides.

DETAILED DESCRIPTION Definitions The following definitions are provided to facilitate understanding of certain terms used throughout this specification.

In the present invention, “isolated” refers to a substance taken from its original environment (eg, the natural environment if it is naturally occurring), and thus “from the natural state”. It has been modified by human hands. " For example, an isolated polynucleotide can be part of a vector or composition of matter, or contained intracellularly and still be "isolated." This is because the vector, composition of matter, or particular cell is not the original environment of the polynucleotide.

In the present invention, “secreted” proteins are proteins that can be directed as a result of a signal sequence in the ER, secretory vesicles, or extracellular space, as well as those that do not necessarily contain a signal sequence but are released into the extracellular space. Refers to protein. If the secreted protein is released into the extracellular space, the secreted protein can undergo extracellular processing to produce the "mature" protein. Release into the extracellular space can occur by a number of mechanisms including exocytosis and proteolytic cleavage.

As used herein, a “polynucleotide” refers to a molecule having the nucleic acid sequence set forth in SEQ ID NO: X, or c contained within a clone deposited with the ATCC.
Refers to DNA. For example, a polynucleotide includes 5'and 3'untranslated sequences, a coding region with or without a signal sequence, a nucleotide sequence of a full-length cDNA sequence containing a secretory protein coding region, and fragments, epitopes, domains of this nucleic acid sequence, And variants. Further, as used herein, "polypeptide", as broadly defined, refers to a molecule having a translated amino acid sequence derived from a polynucleotide.

In the present invention, the full length sequence identified as SEQ ID NO: X was often generated by overlapping sequences contained in multiple clones (contig analysis).
A representative clone containing all or most of the sequence for SEQ ID NO: X has been deposited with the American Type Culture Collection ("ATCC"). As shown in Table 1, each clone is identified by its cDNA clone ID (Identifier) and ATCC deposit number. ATCC is 10801 Univ
ersity Boulevard, Manassas, Virginia
20110-2209, USA. The ATCC deposit was made under the terms of the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the purposes of Patent Procedure.

The “polynucleotide” of the invention also hybridizes under stringent hybridization conditions to the sequence contained in SEQ ID NO: X, its complement, or the cDNA contained in the clone deposited with the ATCC. The resulting polynucleotide is included. “Stringent hybridization conditions” means 50% formamide, 5 × SSC (750 mM NaCl, 75 mM sodium citrate), 50 mM sodium phosphate (pH 7.6), 5 × Denhardt's solution, 10% dextran sulfate, and 20 μg. 1 / ml denatured sheared salmon sperm DNA at 42 ° C. overnight, followed by washing the filters in 0.1 × SSC at about 65 ° C.

Nucleic acid molecules that hybridize to the polynucleotides of the invention at lower stringency hybridization conditions are also contemplated. Changes in hybridization stringency and signal detection are predominantly made by manipulation of formamide concentration (lower percentages of formamide produce reduced stringency); salt concentration, or temperature. For example, lower stringency conditions are 6 × SSPE (20 × SSPE = 3M NaCl; 0.2
M NaH ₂ PO ₄ ; 0.02M EDTA, pH 7.4), 0.5% SDS,
Incubation overnight at 37 ° C. in a solution containing 30% formamide, 100 μg / ml salmon sperm blocking DNA; then 1 × SSPE, 0.1% SD.
Including washing with S at 50 ° C. Furthermore, in order to achieve even lower stringency, the washes performed after stringent hybridization can be performed at higher salt concentrations (eg 5 × SSC).

Note that the changes in the above conditions can be accomplished by the inclusion and / or substitution of alternative blocking reagents used to suppress background in hybridization experiments. Representative blocking reagents include Denhardt's reagent, BLOTTO, heparin, denatured salmon sperm DNA, and commercial product formulations. Inclusion of specific blocking reagents may require modification of the above hybridization conditions due to compatibility issues.

Of course, a poly A + sequence (eg, any 3 ′ end poly A + region of the cDNA shown in the sequence listing) or a poly hybridizing only to a complementary stretch of T (or U) residues. A nucleotide is defined as a "polynucleotide" because such a polynucleotide hybridizes to any nucleic acid molecule that comprises a poly (A) stretch or its complement (eg, virtually any double-stranded cDNA clone). Is not included in.

The polynucleotide of the present invention may be composed of any polyribonucleotide or polydeoxyribonucleotide, which may be unmodified RNA or unmodified DN.
It may be A or modified RNA or modified DNA. For example, a polynucleotide is a DNA that is a mixture of single-stranded and double-stranded DNA, single-stranded and double-stranded regions.
Single-stranded and double-stranded RNA, and RNA that is a mixture of single-stranded and double-stranded regions, single-stranded, or more typically double-stranded or a mixture of single-stranded and double-stranded regions. It can be composed of hybrid molecules, including possible DNA and RNA. Further, the polynucleotide may be RNA or DNA or RNA and D
It can be composed of a triple-stranded region containing both NAs. Polynucleotides can also include one or more modified bases or DNA or RNA backbones that have been modified for stability or for other reasons. "Modified" bases include, for example, tritylated bases and unusual bases such as inosine.
Various modifications can be made to DNA and RNA; thus, "polynucleotide" embraces chemically, enzymatically, or metabolically modified forms.

The polypeptides of the present invention include amino acids linked to each other by peptide bonds or modified peptide bonds, ie, peptide isosteres.
e) and may contain amino acids other than the 20 gene-encoded amino acids. Polypeptides can be modified either by natural processes such as post-translational processing, or by chemical modification techniques well known in the art. Such modifications are well documented in the base text and more detailed research papers, as well as in many research literature. Modifications can occur anywhere in the polypeptide, including the peptide backbone, the amino acid side-chains and the amino or carboxyl termini. It will be appreciated that the same type of modification may be present in the same or varying degrees at several sites in a given polypeptide. Also, a given polypeptide may contain many types of modifications. Polypeptides can be branched, eg, as a result of ubiquitination, and polypeptides can be cyclic, with or without branching. Cyclic, branched and branched cyclic polypeptides can result from natural post-translational processes or can be made by synthetic methods. Modifications include acetylation, acylation, ADP-ribosylation, amidation, flavin covalent bonds, heme moiety covalent bonds, nucleotide or nucleotide derivative covalent bonds, lipids or lipid derivative covalent bonds, phosphatidylinositol covalent bonds. , Cross-linking, cyclization, disulfide bond formation, demethylation, covalent cross-link formation, cysteine formation, pyroglutamic acid formation, formylation, γ-carboxylation, glycosylation,
GPI anchor formation, hydroxylation, iodination, methylation, myristoylation, oxidation, P
EG, proteolytic processing, phosphorylation, prenylation, racemization, selenoylation, sulfation, transfer RNA-mediated addition of amino acids to proteins such as arginylation, and ubiquitination. (For example, PROTEI
NS-STRUCTURE AND MOLECULAR PROPERTIE
S, 2nd edition, T.S. E. Creighton, W.M. H. Freeman
and Company, New York (1993); POSTTR
ANSLATIONAL COVALENT MODIFICATION OF
PROTEINS, B.I. C. Edited by Johnson, Academic P
less, New York, pp. 1-12 (1983); Seifter.
Et al., Meth Enzymol 182: 626-646 (1990); R.
attan et al., Ann NY Acad Sci 663: 48-62 (1
992)).

“SEQ ID NO: X” refers to a polynucleotide sequence, while “SEQ ID NO: Y” refers to
A polypeptide sequence, both sequences identified by the integers specified in Table 1.

A “biologically active polypeptide” refers to a polypeptide of the invention (including the mature form) with or without dose dependence as measured by a particular biological assay. A polypeptide that exhibits an activity similar to, but not necessarily identical to, the activity. If a dose dependence is present, it need not be identical to that of the polypeptide, but rather substantially similar to the dose dependence in a given activity when compared to a polypeptide of the invention (i.e. , The candidate polypeptide exhibits greater activity than the polypeptide of the invention, or has an activity of about 1/25 or greater, and preferably about 1/10 or greater, and most preferably about 1/3 or greater. Shows the activity of).

Polynucleotides and Polypeptides of the Present Invention (Characteristics of Protein Encoded by Gene No. 1) In a particular embodiment, a polypeptide of the present invention comprises the following amino acid sequence:

[0021]

[Chemical 1] Polynucleotides encoding these polypeptides are also included by the invention.

[0022]   This gene is expressed primarily in neutrophils.

Accordingly, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, as well as for immune disorders, particularly neutropenia and related conditions. It is useful as a reagent for the diagnosis of diseases and conditions, including but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, particularly the immune system, significantly higher or lower levels of this gene than standard gene expression levels (ie, expression levels in healthy tissues or fluids from individuals without disorders). The expression of a gene is a specific tissue or cell type (eg, immune tissue, hematopoietic tissue, cancerous tissue and wound tissue) or body fluid (eg, lymph, serum, plasma, urine) taken from an individual having such a disorder. , Synovial fluid, and cerebrospinal fluid), or another tissue or cell sample.

Tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful in immune disorders. More specifically, this gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes,
It may also suggest utility in treating cancer (eg, by boosting the immune response). Since this gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune function. Therefore, it also has arthritis, asthma,
Immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, chronic granulomatosis, inflammatory bowel disease, sepsis, contusion, neutropenia, neutrophilia, psoriasis, hypersensitivity (eg T cell mediated Cellular injury); Immune response to organs and tissues (eg, host vs. graft and graft vs. host disease) or autoimmune disorders (eg, autoimmune infertility, lens tissue injury, demyelination, systemic lupus erythematosus, drug induction). Hemolytic anemia,
It can also be used as a drug for immunological disorders, including rheumatoid arthritis, Sjogren's disease, scleroderma) as well as tissues. Moreover, this gene product may have commercial utility in the proliferation of stem cells and associated progenitor cells of various blood lineages, as well as in the differentiation and / or proliferation of various cell types. protein,
And antibodies to this protein may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 11 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 812 of SEQ ID NO: 11, and b is 15 to 826.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 11, and b is a + 14 or more) are excluded. .

Features of Protein Encoded by Gene No: 2 In certain embodiments, the polypeptides of the present invention comprise the following amino acid sequence:

[0027]

[Chemical 2] Polynucleotides encoding these polypeptides are also included by the invention.

[0028]   This gene is expressed primarily in neutrophils.

Accordingly, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, as well as for immune disorders, particularly neutropenia It is useful as a reagent for diagnosis of diseases and conditions not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, particularly the immune system, significantly higher or lower levels of this gene than standard gene expression levels (ie, expression levels in healthy tissues or fluids from individuals without disorders). The expression of a gene is a specific tissue or cell type (eg, immune tissue, hematopoietic tissue, cancerous tissue and wound tissue) or body fluid (eg, lymph, serum, plasma, urine) taken from an individual having such a disorder. , Synovial fluid, and cerebrospinal fluid), or another tissue or cell sample.

Preferred epitopes are residues: Asp-15 to Tyr-21, Pro-29.
To Asn-39, the epitope includes the sequence shown in SEQ ID NO: 161.

The tissue distribution in neutrophils indicates that the polynucleotides and polypeptides corresponding to this gene are useful in immune disorders. Moreover, expression of this gene product plays a role in the regulation of proliferation, survival, differentiation, and / or activation of hematopoietic cell lines, including blood stem cells. This gene product produces cytokine production, antigen presentation,
Or it may be involved in the regulation of other processes and may also suggest utility in treating cancer (eg, by boosting the immune response). Since this gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune function. Therefore, it also includes arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, chronic granulomatosis, inflammatory bowel disease, sepsis, contusions, neutropenia, neutropenia, psoriasis. , Hypersensitivity (eg, T cell-mediated cytotoxicity); immune response to organs and tissues (eg, host vs. graft and graft vs. host disease) or autoimmune disorder (eg, autoimmune infertility, lens tissue injury, It can also be used as a drug for immunological disorders, including demyelination, systemic lupus erythematosus, drug-induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma) as well as tissues. Moreover, this gene product may have commercial utility in the proliferation of stem cells and associated progenitor cells of various blood lineages, as well as in the differentiation and / or proliferation of various cell types. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 12 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is any integer of 1 to 510 of SEQ ID NO: 12, and b is 15 to 524.
, Where both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 12 and b is a + 14 or more) are excluded. .

FEATURES OF PROTEIN ENCODED BY GENE NO: 3 In certain embodiments, a polypeptide of the invention comprises the following amino acid sequence: SVFKINLKSFKQHEPWWPNRS (SEQ ID NO: 316). Polynucleotides encoding these polypeptides are also included by the invention.

[0034]   This gene is expressed primarily in neutrophils.

Accordingly, the polynucleotides and polypeptides of the present invention include, but are not limited to, the differential identification of tissues or cell types present in a biological sample, as well as immune disorders including neutropenia. It is useful as a reagent for diagnosis of non-limiting diseases and conditions. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, particularly the immune system, significantly higher or lower levels of this gene than standard gene expression levels (ie, expression levels in healthy tissues or fluids from individuals without disorders). The expression of a gene is a particular tissue or cell type (eg, immune, hematopoietic, cancerous and wound tissues) or body fluid (eg, lymph, serum, etc.) taken from an individual having such a disorder.
Plasma, urine, synovial fluid, and spinal fluid), or in another tissue or cell sample,
Can be detected.

Preferred epitopes include those that encompass the sequence set forth in SEQ ID NO: 162 as residues: Met-1 to Arg-8, Leu-35 to Glu-41.

The tissue distribution in neutrophils indicates that the polynucleotides and polypeptides corresponding to this gene are useful in immune disorders. More specifically, expression of this gene product plays a role in the regulation of proliferation, survival, differentiation, and / or activation of hematopoietic cell lines, including blood stem cells. This gene product also produces cytokines,
It may be involved in the regulation of antigen presentation, or other processes, and may also suggest utility in treating cancer (eg, by boosting the immune response). Since this gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune function. Therefore, it also includes arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, chronic granulomatosis, inflammatory bowel disease, sepsis, contusion,
Neutropenia, neutrophilia, psoriasis, hypersensitivity (eg T cell mediated cytotoxicity);
Immune responses to transplant organs and tissues (eg, host vs. graft and graft vs. host disease) or autoimmune disorders (eg, autoimmune infertility, lens tissue injury, demyelination, systemic lupus erythematosus, drug-induced hemolytic anemia, It can also be used as a drug for immunological disorders, including rheumatoid arthritis, Sjogren's disease, scleroderma) as well as tissues. Moreover, this gene product may have commercial utility in the proliferation of stem cells and associated progenitor cells of various blood lineages, as well as in the differentiation and / or proliferation of various cell types. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 13 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 477 of SEQ ID NO: 13, and b is 15 to 491.
, Both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 13, and b is a + 14 or more) are excluded. .

(Characteristics of Protein Encoded by Gene No. 4) This gene is expressed mainly in IL-1 and LPS-induced neutrophils.

Accordingly, the polynucleotides and polypeptides of the invention include for differential identification of tissues or cell types present in a biological sample, as well as for immune disorders including neutropenia. It is useful as a reagent for diagnosis of non-limiting diseases and conditions. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, particularly the immune system, significantly higher or lower levels of this gene than standard gene expression levels (ie, expression levels in healthy tissues or fluids from individuals without disorders). The expression of a gene is a particular tissue or cell type (eg, immune, hematopoietic, cancerous and wound tissues) or body fluid (eg, lymph, serum, etc.) taken from an individual having such a disorder.
Plasma, urine, synovial fluid, and spinal fluid), or in another tissue or cell sample,
Can be detected.

Preferred epitopes include those that encompass the sequence set forth in SEQ ID NO: 163 as residues: Asn-45 to Thr-58.

The tissue distribution in neutrophils indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the treatment or / and prevention of various immune disorders. In particular, this gene product may play a role in regulating the proliferation; survival; differentiation; and / or activation of hematopoietic cell lines, including blood stem cells. In addition, this gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes,
It may also suggest utility in treating cancer (eg, by boosting the immune response). Since this gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune function. Therefore, it also has arthritis, asthma,
Immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, chronic granulomatosis, inflammatory bowel disease, sepsis, contusion, neutropenia, neutrophilia, psoriasis, hypersensitivity (eg T cell mediated Cellular injury); Immune response to organs and tissues (eg, host vs. graft and graft vs. host disease) or autoimmune disorders (eg, autoimmune infertility, lens tissue injury, demyelination, systemic lupus erythematosus, drug induction). Hemolytic anemia,
It can also be used as a drug for immunological disorders, including rheumatoid arthritis, Sjogren's disease, scleroderma) as well as tissues. Moreover, this gene product may have commercial utility in the proliferation of stem cells and associated progenitor cells of various blood lineages, as well as in the differentiation and / or proliferation of various cell types. protein,
And antibodies to this protein may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 14 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 389 of SEQ ID NO: 14, and b is 15 to 403.
, Both of which a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 14, and where b is a + 14 or more) are excluded. .

Characterization of Protein Encoded by Gene No: 5 In certain embodiments, the polypeptides of the present invention comprise the following amino acid sequence:

[0045]

[Chemical 3] Polynucleotides encoding these polypeptides are also included by the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 17. Therefore, the polynucleotide related to the present invention is useful as a marker in linkage analysis for chromosome 17.

[0046]   This gene is expressed primarily in the breast and brain.

Accordingly, the polynucleotides and polypeptides of the invention are used for the differential identification of tissues or cell types present in a biological sample, as well as for immune, reproductive, or neurological disorders (eg, breast cancer, It is useful as a reagent for the diagnosis of diseases and conditions, including but not limited to the lymphatic system, and brain). Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, particularly the reproductive system, immune system, and central nervous system, relative to standard gene expression levels (ie, expression levels in healthy tissue or fluid from individuals without the disorder). Significantly higher or lower levels of expression of this gene may result in specific tissue or cell types (eg, immune, reproductive, neural, breast and cancerous tissue and wounds and wounds taken from individuals with such disorders). Tissue) or body fluids (eg, lymph, breast milk, serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

A preferred epitope is the residue of SEQ ID NO: 164: Leu-31 to Phe.
Examples of the epitope include the sequences shown as -38 and Glu-47 to Trp-52.

Tissue distribution in breast and brain tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful in breast cancer, lymphoid, and brain diseases and treatments. In addition, the protein product of this gene is associated with neurodegenerative disease states, behavioral disorders or inflammatory conditions (eg, Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathy, neoplasia, neoplasia). , Trauma, birth defects, spinal cord injury, ischemia and infarction, aneurysm, hemorrhage, schizophrenia, mania, dementia, paranoia, obsessive-compulsive disorder, panic disorder, learning disability, ALS, psychosis, autism, And may be useful in detecting / treating behavioral changes, including impairment of nutritional support, sleep patterns, balance, and perception.In addition, increased expression of this gene product in regions of the brain indicates that it has normal neurological function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, recognition, homeostasis, or neuronal differentiation or survival. In addition, the gene or gene product may also play a role in the treatment and / or detection of developmental, sex-linked, or cardiovascular disorders associated with the developing embryo. The antibodies may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 15 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 799 of SEQ ID NO: 15, and b is 15 to 813.
, Where both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 15, and b is a + 14 or more) are excluded. .

[0051]     (Characteristics of protein encoded by gene number 6)   This gene is expressed primarily in neutrophils.

Accordingly, the polynucleotides and polypeptides of the present invention include for differential identification of tissues or cell types present in a biological sample, as well as for immune disorders (eg, neutropenia). Are useful as reagents for the diagnosis of diseases and conditions that are not limited thereto. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, particularly the immune system, significantly higher or lower levels of this gene than standard gene expression levels (ie, expression levels in healthy tissues or fluids from individuals without disorders). The expression of a gene is dependent on the specific tissue or cell type (eg,
It can be detected in immune tissues, hematopoietic tissues, cancerous and wound tissues) or body fluids such as lymph, serum, plasma, urine, synovial fluid, and spinal fluid, or another tissue or cell sample.

A preferred epitope is SEQ ID NO: 1 as residues: Ser-49 to Leu-54.
It includes an epitope including the sequence shown in 65.

The tissue distribution in neutrophils indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis, treatment and / or prevention of various immune system diseases. Moreover, expression of this gene product plays a role in regulating the proliferation; survival; differentiation; and / or activation of hematopoietic cell lines, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes,
It may also suggest utility in treating cancer (eg, by boosting the immune response). Since this gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune function. Therefore, it also has arthritis, asthma,
Immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, chronic granulomatosis, inflammatory bowel disease, sepsis, contusion, neutropenia, neutrophilia, psoriasis, hypersensitivity (eg T cell mediated Cellular injury); Immune response to organs and tissues (eg, host vs. graft and graft vs. host disease) or autoimmune disorders (eg, autoimmune infertility, lens tissue injury, demyelination, systemic lupus erythematosus, drug induction). Hemolytic anemia,
It can also be used as a drug for immunological disorders, including rheumatoid arthritis, Sjogren's disease, scleroderma) as well as tissues. Moreover, this gene product may have commercial utility in the proliferation of stem cells and associated progenitor cells of various blood lineages, as well as in the differentiation and / or proliferation of various cell types. protein,
And antibodies to this protein may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 16 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 250 of SEQ ID NO: 16, and b is 15 to 264.
, Both of which a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 16 and where b is a + 14 or more) are excluded. .

Characterization of Protein Encoded by Gene No: 7 The translation product of this gene shares sequence homology with neurotoxins, which are thought to be important in neurological disease. In a particular embodiment, the polypeptide of the invention comprises the following amino acid sequence:

[0057]

[Chemical 4] Polynucleotides encoding these polypeptides are also included by the invention.

[0058]   This gene is expressed primarily in neutrophils.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, as well as diseases of the immune and nervous systems, particularly neurodegenerative disorders (eg, neurodegenerative disorders). , Alzheimer's disease or Parkinson's disease) and are useful as reagents for the diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. Significantly higher or lower than standard gene expression levels (ie, expression levels in normal tissues or body fluids from unaffected individuals) for many disorders of the tissues or cells, particularly the immune and nervous systems Levels of this gene are expressed in specific tissues or cell types collected from individuals with such disorders (eg,
Can be detected in immune tissue, hematopoietic tissue, nervous tissue, cancerous and wound tissue) or body fluids (eg lymph, serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample .

Preferred epitopes are residues: Gln-2 to Gly-10, Asp-77 to P.
It includes an epitope including the sequence shown in SEQ ID NO: 166 as he-82.

Tissue distribution in neutrophils combined with homology to conservative neurotoxin proteins indicates that the polynucleotides and polypeptides corresponding to this gene are diagnostic, therapeutic and / or prophylactic for diseases of the immune and nervous systems. To be useful for.
Similarly, the protein product of this gene may be associated with neurodegenerative disease states, behavioral disorders or inflammatory conditions (eg, Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathy, neoneuropathy Formation, trauma, birth defects, spinal cord injury, ischemia and infarction, aneurysm, hemorrhage, schizophrenia, mania, dementia, paranoia, obsessive-compulsive disorder, panic disorder, learning disability, ALS, psychosis, autism , And behavioral changes, including impairment of nutritional support, sleep patterns, balance, and sensory perception.In addition, increased expression of this gene product in regions of the brain
We show that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, recognition, homeostasis, or neuronal differentiation or survival. In addition, the gene or gene product may also be used to treat and / or treat developmental, sex-related, or cardiovascular disorders associated with the developing embryo.
Or it may play a role in detection. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 17 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is any integer of 1 to 506 of SEQ ID NO: 17, and b is 15 to 520
, Both of which a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 17, and where b is a + 14 or more) are excluded. .

FEATURES OF PROTEIN ENCODED BY GENE NO: 8 In certain embodiments, a polypeptide of the invention comprises the following amino acid sequence: KHAFLMAHQFCVLSLAMQWSSSCFQLVALPYLSL.
(SEQ ID NO: 324). Polynucleotides encoding these polypeptides are also included by the invention.

[0064]   This gene is expressed primarily in neutrophils.

Accordingly, the polynucleotides and polypeptides of the invention include for differential identification of tissues or cell types present in a biological sample, as well as for immune disorders (eg, neutropenia). Are useful as reagents for the diagnosis of diseases and conditions that are not limited thereto. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, particularly the immune system, significantly higher or lower levels of this gene than standard gene expression levels (ie, expression levels in healthy tissues or fluids from individuals without disorders). The expression of a gene is dependent on the specific tissue or cell type (eg,
It can be detected in immune tissues, hematopoietic tissues, cancerous and wound tissues) or body fluids such as lymph, serum, plasma, urine, synovial fluid, and spinal fluid, or another tissue or cell sample.

The tissue distribution in neutrophils indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis, treatment and / or prevention of immune disorders. In addition, this gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes, and may also suggest utility in treating cancer (eg, by boosting the immune response). Since this gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune function. Therefore, it also includes arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, chronic granulomatosis, inflammatory bowel disease, sepsis, contusions, neutropenia, neutropenia, psoriasis. , Hypersensitivity (eg, T cell-mediated cytotoxicity); immune response to organs and tissues (eg, host vs. graft and graft vs. host disease) or autoimmune disorder (eg, autoimmune infertility, lens tissue injury, It can also be used as a drug for immunological disorders, including demyelination, systemic lupus erythematosus, drug-induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma) as well as tissues. Moreover, this gene product may have commercial utility in the proliferation of stem cells and associated progenitor cells of various blood lineages, as well as in the differentiation and / or proliferation of various cell types. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 18 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 979 of SEQ ID NO: 18, and b is 15 to 979.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 18, and b is a + 14 or more) are excluded. .

(Characteristics of Protein Encoded by Gene No. 9) When tested on the Jurket cell line and the PC12 cell line, supernatants obtained from cells containing this gene showed GAS (γ activation sequence) and The EGR1 (Early Growth Response Gene 1) promoter element was activated. Therefore, this gene appears to activate T cells and sensory neurons via the JAK-STAT and EGR1 signaling pathways. GAS is a promoter element found upstream of many genes involved in the Jak-STAT pathway. The Jak-STAT pathway is large and is a signal transduction pathway involved in cell differentiation and proliferation. Therefore, activation of Jak-STAT (reflected by the binding of GAS elements) can be used to indicate proteins involved in cell differentiation and proliferation. EGR1 is a signaling pathway distinct from Jak-STAT (a gene containing the EGR1 promoter that is introduced into various tissues and cell types upon activation), which directs cells to undergo differentiation and proliferation. . In a particular embodiment, the polypeptide of the invention comprises the following amino acid sequence: MRP
LCVLLPWPCWQWGGLGSASPIRPQAPPGQAAHAVPL
PRAQHLAQRSRQ (SEQ ID NO: 325). Polynucleotides encoding these polypeptides are also included by the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 17. Therefore, the polynucleotide related to the present invention is useful as a marker in linkage analysis for chromosome 17.

This gene is expressed primarily in the breast, lymph nodes, spleen, and to a lesser extent the liver.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, as well as the germ line, immune system,
Alternatively, it is useful as a reagent for the diagnosis of diseases and conditions including, but not limited to, liver dysfunction (particularly breast cancer, liver, and lymphatic system). Similarly,
Polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. Significantly higher than standard gene expression levels (ie, expression levels in normal tissues or body fluids from unaffected individuals) for many disorders of the tissues or cells, particularly breast, liver, and lymphatic system Alternatively, low levels of expression of this gene may be associated with specific tissues or cell types (eg, reproductive tissue, breast tissue, immune tissue, hematopoietic tissue, liver tissue, and cancerous tissue obtained from individuals with such disorders). Wound tissue) or body fluids (eg lymph, breast milk, bile, serum, plasma, urine, synovial fluid, and spinal fluid)
, Or in another tissue or cell sample.

A preferred epitope is SEQ ID NO: 168 with residues: Pro-54 to Gly.
An epitope is included that includes the sequence shown as -67.

This tissue distribution in breast and immune tissues, combined with the detected EGR1 and GAS biological activity, indicates that the polynucleotides and polypeptides corresponding to this gene are of interest in the diagnosis and treatment of breast and lymphatic systems. To be useful for. Furthermore, GAS and EGRI activity may indicate that the protein product of this gene may play an essential role in regulating cell division and may be useful in the detection / treatment of cancer and other proliferative disorders. Is strongly indicated. Similarly, such proliferative tissues rely on finely regulated decisions involving cell differentiation and / or apoptosis. Therefore, this protein may also be involved in the regulation of apoptosis or tissue differentiation and may also be useful in the treatment of cancer. The protein as well as antibodies to this protein may show utility as tumor markers in the tissues listed above and / or as targets for immunotherapy.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 19 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 445 of SEQ ID NO: 19, and b is 15 to 459.
, Both of which a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 19 and where b is a + 14 or more) are excluded. .

FEATURES OF PROTEIN ENCODED BY GENE NO: 10 In certain embodiments, a polypeptide of the invention comprises the following amino acid sequence: ARGLRSPHGAAGVVRGDGGGGKKGEDPYSPILFQ.
SERIPRLIYLPVISSEENS (SEQ ID NO: 326). Polynucleotides encoding these polypeptides are also included by the invention.

This gene is expressed primarily in LPS-induced neutrophil cDNA libraries.

Thus, the polynucleotides and polypeptides of the present invention include for differential identification of tissues or cell types present in a biological sample, as well as for immune disorders such as neutropenia. Are useful as reagents for the diagnosis of diseases and conditions that are not limited thereto. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, particularly the immune system, significantly higher or lower levels of this gene than standard gene expression levels (ie, expression levels in healthy tissues or fluids from individuals without disorders). The expression of a gene is dependent on the specific tissue or cell type (eg,
Immune tissue, hematopoietic tissue, cancerous tissue and wound tissue) or fluid (eg lymph,
Serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

Tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful in diagnosing and treating immune disorders (eg, improving aberrant neutrophil responses to infectious agents). Indicates. Similarly, expression of this gene product may suggest a role in regulating proliferation, survival, differentiation; and / or activation of hematopoietic cell lines, including blood stem cells. This gene product may also be involved in the regulation of cytokine production, antigen presentation, or other processes, and may also suggest utility in treating cancer (eg, by boosting the immune response). Since this gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune function. Therefore, it also includes arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, chronic granulomatosis, inflammatory bowel disease, sepsis, contusions, neutropenia, neutropenia, psoriasis. , Hypersensitivity (eg, T cell-mediated cytotoxicity); immune response to transplant organs and tissues (eg, host vs. graft and graft vs. host disease)
Or autoimmune disorders (eg, autoimmune infertility, lens tissue injury, demyelination, systemic lupus erythematosus, drug-induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease,
It can also be used as a drug for immunological disorders, including scleroderma) as well as tissues. Moreover, this gene product may have commercial utility in the proliferation of stem cells and associated progenitor cells of various blood lineages, as well as in the differentiation and / or proliferation of various cell types. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 20 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 541 of SEQ ID NO: 20, and b is 15 to 555.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 20, and b is a + 14 or more) are excluded. .

[0079]     (Characteristics of protein encoded by gene number 11)   This gene is mainly expressed in prostate cancer.

Accordingly, the polynucleotides and polypeptides of the present invention are for the differential identification of tissues or cell types present in a biological sample, as well as for disorders of the reproductive or immune system, particularly prostate cancer. It is useful as a reagent for diagnosis of diseases and conditions not limited to. Similarly, the polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of these tissues or cell types. Significantly higher than standard gene expression levels (ie, expression levels in normal tissues or body fluids taken from individuals without such disorders) for many disorders of the tissues or cells, especially the immune system Expression of this gene at low or low levels may result in specific tissue or cell types (eg, reproductive, prostate and cancerous and wound tissues) or body fluids (eg, reproductive, prostate and cancerous tissues) taken from individuals with such disorders. Lymph, semen, serum, plasma, urine,
Synovial fluid, and spinal fluid), or another tissue or cell sample.

A preferred epitope is SEQ ID NO: 170 at residues: Pro-14 to Asp-2.
5, including epitopes containing the sequences designated as Leu-51 to Val-63.

Its tissue distribution in prostate tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and / or treatment of cancer, especially reproductive disorders such as prostate cancer. Similarly, expression in prostate cancer tissue, a cell source characterized by proliferating cells, indicates that this protein may play a role in the regulation of cell division, and cancer and other proliferative disorders (prostate tissue). , But not limited to). Moreover, such tissues depend on the involved decisions of cell differentiation and / or apoptosis. Therefore, this protein may also be involved in apoptosis or tissue differentiation and may also be useful in the treatment of cancer. The protein as well as antibodies to this protein may show utility as tumor markers in the above tissues and / or as targets for immunotherapy.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 21 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, from the present invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 651 of SEQ ID NO: 21, and b is 15 to 665.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 21, and b is a + 14 or greater) and are excluded. ..

Feature of Protein Encoded by Gene No: 12 The polynucleotide sequence of this gene may have a frameshift. Therefore,
Preferred signal peptides may be present in other frames than the relevant polynucleotide of this gene. In a particular embodiment, a polypeptide of the invention comprises the following amino acid sequence: KSLSSCFLFLAFWLRRMGQTMCVCVCVCVCVCVCVRTW
VYLYEPVKFRSPLIYVNLPTS (SEQ ID NO: 327), and / or KLGFTMLARLVNSSXTSGDLPSSASQNAGIKGMS
YRAWPYSYFLIRKNKQTNKQTKTNPQLGENKHCRNL
KVSWSKNYFL (SEQ ID NO: 328). Polynucleotides encoding these polypeptides are also encompassed by the present invention.

[0085]   This gene is mainly expressed in T cells.

Thus, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, as well as immune system disorders, particularly immunodeficiencies such as lupus and AIDS, It is also useful as a reagent for the diagnosis of diseases and conditions including but not limited to inflammatory disorders. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of these tissues or cell types. For many disorders of the tissues or cells, especially the immune system, standard gene expression levels (ie,
Expression of this gene at significantly higher or lower levels relative to expression levels in healthy tissues or body fluids from individuals without such disorders was collected from individuals with such disorders. In a specific tissue or cell type (eg, immune, hematopoietic, and cancerous and wound tissues) or body fluid (eg, lymph, serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample , Can be detected.

This tissue distribution in immune cells indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of various immune system disorders. In addition, this gene product may play a role in the proliferation, survival, differentiation, and / or regulation of hematopoietic cell lines, including blood stem cells. This gene product may also be involved in the regulation of cytokine production, antigen presentation, or other processes that may also have utility in treating cancer (eg, by immune response boosting). Since this gene is expressed in cells of lymphocyte origin, the natural gene product may be involved in immune function. It therefore has arthritis, asthma, immunodeficiency disorders such as AIDS, leukemia, rheumatoid arthritis, chronic granulomatosis, inflammatory bowel disease, sepsis, acne, neutropenia, neutropenia, psoriasis, Hypersensitivity (eg, T cell mediated cytotoxicity); Immune response to transplanted organs and tissues (eg, graft versus host disease and graft disease), or autoimmune disorder (eg, autoimmune) Infertility), lens tissue injury, demyelination, systemic lupus erythematosus, drug-induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and agents for immunological disorders including tissue. Furthermore, this gene product may have commercial utility in the proliferation of stem cells and directed progenitors of various blood systems, and in the differentiation and / or proliferation of various cell types. The protein, as well as antibodies to this protein, may show utility as tumor markers for the above tissues and / or targets for immunotherapy.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 22 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, from the present invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 763 of SEQ ID NO: 22, and b is 15 to 777.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 22, and b is a + 14 or more) are excluded. .

(Characteristics of the protein encoded by gene number 13) When tested against Jurkat and U937 cell lines, supernatants obtained from cells containing this gene showed GAS (γ activity). Activation sequence) The promoter element was activated. Therefore, this gene is JAK-STA
It appears to activate T cells and promyelocytic cells via the T signaling pathway.
GAS is a promoter element found upstream of many genes involved in the JAK-STAT pathway. The JAK-STAT pathway is a large signal transduction pathway involved in cell differentiation and proliferation. Therefore, JAK-STAT
Pathway activation (reflected by the binding of GAS elements) can be used to indicate proteins involved in cell proliferation and differentiation. In a particular embodiment,
The polypeptide of the invention comprises the following amino acid sequence: ERGQGGSSRNVAGSDLVFPAVFVFSXLC (SEQ ID NO: 329).
), GSPQGPSVALGSRQCWSRPLRRRGGRGAAVEMWRG
PTWCFRPSLCLCCVCGVSGFLYVPHGFSLSMCVSAP
GSAWLSLVYSICLARGSSMSXRXSSRXSLVASGASVL
LVCFWVXADPGVGVSVPRAXVSGLWWCVSPSACLXL
APTKPPPXLSFSLSIFPFSSNPSK (SEQ ID NO: 330), and / or TIASLQPTALNHLIWRGWRKKGRRLRRKRGX
GGAWLGPXRGRQMDSHTTRDQRQXLGEQRHPLLLGLX
APRSKPTKQMPQMQPGXPEKKXXLTWNHGLDRWNTQ
GTARQSLGQKHTWRD (SEQ ID NO: 331). Polynucleotides encoding these polypeptides are also included in the invention.

[0090]   This gene is expressed primarily in adipose tissue and brain.

Thus, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, as well as for metabolic or neurological disorders, particularly obesity, and neurodegenerative disorders or central nervous systems. It is useful as a reagent for the diagnosis of diseases and conditions including but not limited to nervous system disorders. Similarly,
Polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of these tissues or cell types. With respect to disorders of the above tissues or cells, particularly the brain and central nervous system, standard gene expression levels (
That is, expression of this gene at significantly higher or lower levels relative to expression levels in healthy tissues or body fluids from individuals without such disorders is collected from individuals with such disorders. Specific tissue or cell type (eg, adipose tissue, nerve tissue, immune tissue, and cancerous and wound tissue) or body fluid (eg, lymph, serum, plasma, urine, synovial fluid, and spinal fluid), or It can be detected in another tissue or cell sample.

This tissue distribution in obese and nervous tissue, combined with this detected GAS biological activity, allows polynucleotides and polypeptides corresponding to this gene to be associated with obesity and disorders of the brain and central nervous system. Shows utility in diagnosis and treatment. Similarly, the protein product of this gene may be associated with neurodegenerative disease states, behavioral disorders, or inflammatory conditions (eg, Alzheimer's disease, Parkinson's disease,
Huntington's chorea, Tourette's syndrome, meningitis, encephalitis, demyelinating disease, peripheral neuropathy, neoplasia, trauma, birth defects, spinal cord injury, ischemia and infarction, aneurysm, bleeding, schizophrenia, mania, Dementia, paranoia, obsessive-compulsive disorder, panic disorder, learning disability, ALS,
It can be useful in the detection / treatment of psychosis, autism, and behavioral changes, including impairment of diet, sleep patterns, balance, and perception. Furthermore, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function.
Potentially, this gene product is involved in synapse formation, neurotransmission, learning, recognition, homeostasis, or neural differentiation or survival. In addition, the gene or gene product may also play a role in the treatment and / or detection of developmental, sex-related, or cardiovascular disorders associated with the developing embryo. In addition, the protein product of this gene also detects neuropathy that follows aberrant lipid metabolism in neural tissue (eg, abnormal myelin sheath development) or associated autoimmune disorders of neural tissue or capsules thereon. , Can be beneficial in treating, or preventing. The protein, and antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the above tissues.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 23 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab, where a is any integer from 1 to 526 of SEQ ID NO: 23 and b is an integer from 15 to 540, wherein Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 23, and where b is a + 14 or more) are excluded.

FEATURES OF PROTEIN ENCODED BY GENE NO: 14 In certain embodiments, a polypeptide of the invention comprises the following amino acid sequence:
ARGPGTEGCEPWLQLQDRRR (SEQ ID NO: 332), and / or MSSGTNSFFTLMALNSPTGDGSGRITVSPPRVHP
VKSGRGRASPLLTRFLAPRSALWS (SEQ ID NO: 333). Polynucleotides encoding these polypeptides are also encompassed by the present invention.

This gene is expressed primarily in a cDNA library from IL-1 and LPS-induced neutrophils.

Thus, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, and include immune system disorders such as neutropenia, It is useful as a reagent for diagnosis of diseases and conditions that are not limited thereto. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of these tissues or cell types. Significantly higher than standard gene expression levels (ie expression levels in normal tissues or fluids from individuals without such disorders) for many disorders of the tissues or cells, particularly the immune system, or Low levels of expression of this gene may result in specific tissue or cell types (eg, immune, cancerous and wound tissues) or body fluids (eg, lymph, serum, plasma) taken from individuals with such disorders. , Urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

Its tissue distribution in immune cells indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of conditions in which lymphocytes exhibit an abnormal response to infectious agents. Similarly, this gene product may play a role in the regulation of proliferation; survival; differentiation; and / or activation of hematopoietic cell lines, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest utility in treating cancer (eg, by boosting the immune response). Since this gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune function. Therefore, it also includes arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, chronic granulomatosis, inflammatory bowel disease, sepsis, contusions, neutropenia, neutropenia, psoriasis. , Hypersensitivity (eg, T cell-mediated cytotoxicity); immune response to transplanted organs and tissues (eg, graft versus host disease and graft disease) or autoimmune disorder (eg, autoimmune infertility, lens) It can also be used as a drug for immunological disorders including tissue injury, demyelination, systemic lupus erythematosus, drug-induced hemolytic anemia, rheumatoid arthritis, Sjögren's disease, scleroderma and tissues. The products are commercially useful in the proliferation of stem cells and committed progenitor cells of various blood lineages, and in the differentiation and / or proliferation of various cell types. May have. Protein, and antibodies to the protein,
It may show utility as a tumor marker and / or immunotherapeutic target for the above tissues.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 24 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, from the present invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 470 of SEQ ID NO: 24, and b is 15 to 484.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 24, and b is a + 14 or greater) and are excluded. .

Characterization of Protein Encoded by Gene No: 15 This gene is expressed primarily in ovary, tonsil, and CD34-positive bone marrow stem cells.

Accordingly, the polynucleotides and polypeptides of the present invention are for the differential identification of tissues or cell types present in a biological sample, as well as for reproductive, immune, developmental or hematopoietic disorders. Are useful as reagents for the diagnosis of diseases and conditions that are not limited to them. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of their tissue or cell type. Significantly relative to standard gene expression levels (ie, expression levels in normal tissues or fluids from individuals without such disorders) for many disorders of the tissues or cells, particularly the immune and reproductive systems. High or low levels of expression of this gene may result in specific tissue or cell types (eg, reproductive tissue, ovarian tissue, immune system, tonsil tissue, umbilical cord tissue, developmental tissue) taken from an individual with such a disorder. , Cancerous tissue and wound tissue) or body fluids (
(Eg, lymph, amniotic fluid, serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

Its tissue distribution in ovarian and tonsil tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of immune and reproductive system disorders. Similarly, expression of this gene product in tonsils indicates a role in the regulation of hematopoietic cell lineage proliferation including blood stem cells; survival; differentiation; and / or activation. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also indicate utility in treating cancer (eg, by boosting the immune response). Since this gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune function. Therefore, it also includes arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, chronic granulomatosis, inflammatory bowel disease, sepsis, contusions, neutropenia, neutropenia, psoriasis. , Hypersensitivity (eg, T cell-mediated cytotoxicity); immune response to transplanted organs and tissues (eg, graft versus host disease and graft disease).
Or autoimmune disorders such as autoimmune infertility, lens tissue injury, demyelination, systemic lupus erythematosus, drug-induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease,
It can also be used as a drug for immunological disorders, including scleroderma and tissues.
Moreover, this gene product may have commercial utility in the proliferation of stem cells and committed progenitor cells of various blood lineages, and in the differentiation and / or proliferation of various cell types. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the above tissues.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 25 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, from the present invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 693 of SEQ ID NO: 25, and b is 15 to 707.
, Both of which a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 25, and where b is a + 14 or more) are excluded. .

Characteristics of Protein Encoded by Gene No: 16 When tested on the U937 cell line, supernatants obtained from cells containing this gene activated the GAS (γ activation sequence) promoter element. did. Therefore, this gene appears to activate promyelocytic cells via the JAK-STAT signaling pathway. GAS is a promoter element found upstream of many genes involved in the JAK-STAT pathway. The JAK-STAT pathway is a large signal transduction pathway involved in cell differentiation and proliferation. Therefore, activation of JAK-STAT (reflected by binding of the GAS element)
It can be used to indicate proteins involved in cell proliferation and differentiation. In a particular embodiment, a polypeptide of the invention comprises the following amino acid sequence: HEYHLLSSRHILGSVLRLDVCALWS (SEQ ID NO: 334).
Polynucleotides encoding these polypeptides are also included in the invention.

[0104]   This gene is expressed primarily in IL-1 and LPS-induced neutrophils.

Thus, the polynucleotides and polypeptides of the present invention are for the differential identification of tissues or cell types present in a biological sample, as well as for immune disorders such as neutropenia. It is useful as a reagent for diagnosis of non-limiting diseases and conditions. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of these tissues or cell types. At a level significantly higher or lower than the standard gene expression level (ie, the expression level in healthy tissue or body fluid from an individual not having such a disorder) in the tissue or cell, particularly in the immune system. Expression of this gene in specific tissues or cell types (eg, immune, hematopoietic, and cancerous and wound tissues) or body fluids (eg, lymph, serum, etc.) taken from an individual having such a disorder. Plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

This tissue distribution in immune cells, combined with this detected GAS biological activity, indicates that the polynucleotides and polypeptides corresponding to this gene are
It is shown to be useful in the diagnosis, treatment and / or prevention of immune disorders. In detail,
Expression of this gene product in neutrophils indicates a role in the regulation of hematopoietic cell lineage proliferation including blood stem cells; survival; differentiation; and / or activation. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also indicate utility in treating cancer (eg, by boosting the immune response). Since this gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune function. Therefore, it also includes arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, chronic granulomatosis, inflammatory bowel disease, sepsis, contusions, neutropenia, neutropenia, psoriasis. , Hypersensitivity (eg, T cell-mediated cytotoxicity); immune response to transplanted organs and tissues (eg, vs. graft versus host disease) or autoimmune disorders, eg, autoimmune infertility, lens It may also be used as a drug for immunological disorders including tissue injury, demyelination, systemic lupus erythematosus, drug-induced hemolytic anemia, rheumatoid arthritis, Sjögren's disease, scleroderma and tissues. Moreover, this gene product may have commercial utility in the proliferation of stem cells and committed progenitor cells of various blood lineages, and in the differentiation and / or proliferation of various cell types. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the above tissues.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 26 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 779 of SEQ ID NO: 26 and b is an integer from 15 to 793, wherein Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 26, and where b is a + 14 or more) are excluded.

[0108]     (Characteristics of protein encoded by gene number 17)   This gene is expressed primarily in the spinal cord.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, and for any of a variety of nervous system and neuromuscular disorders, particularly muscle atrophy. It is useful as a reagent for diagnosis of diseases and conditions including, but not limited to lateral sclerosis, muscular dystrophy, and hereditary and non-hereditary chorea. Similarly, the polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of these tissues or cell types. For many disorders of the tissues or cells, particularly the central nervous system and neuromuscular system, standard gene expression levels (ie, expression levels in healthy tissue or body fluids taken from individuals without such disorders) Expression of this gene at significantly higher or lower levels, in contrast, is associated with specific tissues or cell types taken from individuals with such disorders, such as neural tissue, neuromuscular tissue and cancerous and wound tissue. ) Or body fluids such as lymph, serum, plasma, urine, synovial fluid, and spinal fluid, or another tissue or cell sample.

Its tissue distribution in spinal cord tissue indicates that this gene may be used in the treatment of spinal cord injury and related injuries. The protein product of this gene can be injected into the spinal cord to promote or control growth following injury or degeneration. Alternatively,
Cells expressing this gene may be injected or transferred into the spinal cord by other means as a treatment to promote regulation of growth following spinal cord injury or degeneration. In addition, polynucleotides and polypeptides corresponding to this gene are neurodegenerative disease states, behavioral disorders, or inflammatory conditions such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, meningitis, encephalitis, demyelination. Diseases, peripheral neuropathy, neoplasia, trauma, birth defects, spinal cord injury, ischemia and infarction, aneurysm, bleeding, schizophrenia, mania, dementia, paranoia, obsessive-compulsive disorder, panic disorder, learning disability, Useful for detection / treatment of ALS, psychosis, autism, and behavioral changes, including impairment of diet, sleep patterns, balance, and perception. Furthermore, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially
This gene product is involved in synapse formation, neurotransmission, learning, recognition, homeostasis, or neural differentiation or survival. In addition, the gene or gene product may also play a role in the treatment and / or detection of developmental, sex-related, or cardiovascular disorders associated with the developing embryo. The protein, and antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets in the tissues described above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 27 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, from the present invention, the nucleotide sequence described by the general formula ab (
Here, a is any integer of 1 to 624 of SEQ ID NO: 27, and b is 15 to 638.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 27, and b is a + 14 or greater) and are excluded. .

Characterization of Protein Encoded by Gene No: 18 When tested on the U937 cell line, supernatants obtained from cells containing this gene activate the GAS (γ activation sequence) promoter element. did. Therefore, this gene appears to activate promyelocytic cells via the JAK-STAT signaling pathway. GAS is a promoter element found upstream of many genes involved in the JAK-STAT pathway. The JAK-STAT pathway is a large signal transduction pathway involved in cell differentiation and proliferation. Therefore, activation of JAK-STAT (reflected by binding of the GAS element)
It can be used to indicate proteins involved in cell proliferation and differentiation. In a particular embodiment, the polypeptide of the invention comprises the following amino acid sequence: FILFILEYDMLWKSLYTNSSAYGYVIASYFCLLGIK.
LLVKQKKXKKKKTRGGARXPIRPXVESYYYKSXAVVLQ
RRGLGKNLGG (SEQ ID NO: 335). Polynucleotides encoding these polypeptides are also included in the invention.

[0113]   This gene is expressed primarily in the adrenal gland.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, as well as disorders including, but not limited to, endocrine disorders, particularly those of the adrenal gland. And are useful as reagents for diagnosing conditions. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of these tissues or cell types. Significantly higher or lower levels of the gene in the tissues or cells, particularly the adrenal gland, relative to standard gene expression levels (ie, expression levels in healthy tissue or fluid from individuals without such disorders). Expression of specific tissues or cell types (eg, endocrine tissue, adrenal tissue, and cancerous and wound tissue) or body fluids (eg, lymph, serum, plasma, urine) taken from individuals with such disorders. , Synovial fluid, and cerebrospinal fluid), or another tissue or cell sample.

This tissue distribution in the adrenal gland tissue, combined with the GAS biological activity detected, allows polynucleotides and polypeptides corresponding to this gene to be used in a variety of endocrine disorders and cancers, especially Addison's disease, Cushing's syndrome, And pancreas (eg, diabetes), adrenal cortex, ovary, hypothalamus, pituitary gland (eg, hyperpituitarism, hypopituitarism), thyroid (eg, hyperthyroidism, hypothyroidism), epithelium It is useful for the detection, treatment and / or prevention of corpuscles (eg hyperparathyroidism, hypoparathyroidism) and hypothalamic disorders and / or cancers. The protein as well as antibodies to the protein may show utility as tumor markers and / or immunotherapeutic targets for the tissues described above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 28 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 514 of SEQ ID NO: 28 and b is an integer from 15 to 528, wherein Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 28, and where b is a + 14 or more) are excluded.

[0117]     (Characteristics of protein encoded by gene number 19)   This gene is expressed primarily in placenta.

Accordingly, the polynucleotides and polypeptides of the present invention are for the differential identification of tissues or cell types present in a biological sample, as well as for diseases and conditions including, but not limited to, reproductive system disorders. It is useful as a reagent for diagnosis. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of these tissues or cell types. Significantly higher than standard gene expression levels (ie expression levels in normal tissues or fluids from individuals without such disorders) for many disorders of the tissues or cells, especially the reproductive system, or Low level expression of this gene
Specific tissues or cell types (eg, placental tissue, reproductive tissue, and cancerous and wound tissues) or body fluids (eg, lymph, serum, plasma, urine, synovial fluid, etc.) obtained from an individual with such a disorder. And spinal fluid), or in another tissue or cell sample.

A preferred epitope is the residue: His-15 to SEQ ID NO: 178 in SEQ ID NO: 178.
Examples include epitopes containing the sequences shown as Trp-15 and Pro-48 to Ala-54.

Tissue distribution within placental tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of reproductive disorders. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the above tissues.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 29 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, from the present invention, the nucleotide sequence described by the general formula ab (
Here, a is any integer of 1 to 905 of SEQ ID NO: 29, and b is 15 to 919.
, Both of which a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 29, and where b is a + 14 or more) are excluded. .

Characterization of the Protein Encoded by Gene No: 20 The translation product of this gene shares sequence homology with the human erythrocyte membrane anion transport protein, which is believed to be important in autoimmune disease. In addition, the translation product of this gene also shares homology with human gnl / PID / d1026838 (AB012130) sodium bicarbonate symporter 2, which is believed to be important in maintaining cellular homeostasis. Contact of cells with the supernatant expressing the product of this gene was found to increase the permeability of enterocyte and renal mesangial cell plasma membranes to calcium. Thus, the product of this gene appears to be involved in a signaling pathway that initiates when this product binds to a receptor on the surface of enterocytes or renal mesangial cells. Accordingly, the polynucleotides and polypeptides of the present invention have uses including, but not limited to, activating cellular processes within enterocytes and renal mesangial cells. In a particular embodiment, a polypeptide of the invention comprises the amino acid sequence: RVSSHLFRLLFGGGLILDIKRKAPFFFLSDFKDALSLQC.
LASILFLYCACMSPVITFGGLLGEATEGRIVSTKIG
SGQAFSSSEASVCMHLSHYSYFYLKSLPTA (SEQ ID NO: 3
36), FRLFGGLILDIKERKAPFFLSDFKD (SEQ ID NO: 337).
), FLYCACMSPVITFGGLGLEATEG (SEQ ID NO: 338), and / or SSSEASVCCMHLSHHYSYFYLKSL (SEQ ID NO: 339).
) Polynucleotides encoding these polypeptides are also included according to the invention. The gene encoding this disclosed cDNA is believed to reside on chromosome 3. Therefore, the polynucleotide related to the present invention is useful as a marker in linkage analysis for chromosome 3.

[0123]   This gene is expressed primarily in human testicular tumors.

Accordingly, the polynucleotides and polypeptides of the present invention are for the differential identification of tissues or cell types present in a biological sample, as well as for immune disorders or reproductive disorders, especially autoimmune disorders. It is useful as a reagent for diagnosis of non-limiting diseases and conditions. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of such tissues or cell types. With respect to the tissues or cells, in particular the immune system, at levels significantly higher or lower than standard gene expression levels (ie expression levels in normal tissues or fluids from individuals without such disorders). The expression of this gene is dependent on the specific tissue or cell type (eg, immune, reproductive, testicular, and cancerous and wound tissue) or body fluid (eg, lymph, etc.) taken from an individual having such a disorder. Semen, serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

This tissue distribution in the testis, homology with erythrocyte membrane anion transport proteins, as well as the detected biological activity of calcium flux, is due to the fact that polynucleotides and polypeptides corresponding to this gene are associated with autoimmune diseases and other Are useful in the treatment of immune diseases of, for example, but not limited to, cancer, especially in testicular tissue. Similarly, the translation product of this gene may be important in maintaining normal cellular homeostasis. Thus, this protein, as well as antibodies to this protein, would be useful as therapeutic agents to ameliorate conditions associated with aberrant pH regulation of cells (eg, using the antibody to reduce the presence of this protein? ,
Or perhaps in a gene therapy application to replace the defective form, or to increase expression of either the endogenous or modified forms of the invention). The protein, as well as antibodies to this protein, may show utility as tumor markers in the above tissues and / or targets for immunotherapy.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences relate to SEQ ID NO: 30 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab (where a is any integer from 1 to 850 of SEQ ID NO: 30 and b is an integer from 15 to 864) , Where a and b both correspond to the position of the nucleotide residue set forth in SEQ ID NO: 30, and where b is a + 14 or more) are excluded.

[0127]     (Characteristics of protein encoded by gene number 21)   This gene is expressed primarily in the brain.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, as well as for neurological disorders such as neurodegenerative conditions and / or depression. It is useful as a reagent for the diagnosis of diseases and conditions including, but not limited to, disorders of the brain as well as the central nervous system. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of such tissues or cell types. Significantly relative to standard gene expression levels (ie, expression levels in normal tissues or fluids from individuals without such disorders) for many disorders of the tissues or cells, particularly the brain and central nervous system. Higher or lower levels of expression of this gene may result in specific tissue or cell types (eg, neural tissue, cancerous tissue and wound tissue) or body fluids (eg, lymph) taken from individuals with such disorders. , Serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

A preferred epitope is SEQ ID NO: 180 at residues: His-13 to
An epitope is included that includes the sequence designated as Leu-18.

This tissue distribution in neural tissue indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the treatment and diagnosis of disorders of the brain and central nervous system. In addition, polynucleotides and polypeptides corresponding to this gene are neurodegenerative disease states, behavioral disorders, or inflammatory conditions such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, meningitis, encephalitis, demyelinating. Disease, peripheral neuropathy, neoplasia, trauma, congenital anomaly, spinal cord injury, ischemia and infarction, aneurysm, bleeding, schizophrenia, mania, dementia, paranoia, obsessive-compulsive disorder, panic disorder, learning disability, ALS , Psychosis, autism), and behavioral changes (diet, sleep patterns,
It is useful in the detection / treatment of balance and (including impaired perception). Furthermore, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, recognition, homeostasis, or neural differentiation or survival. further,
The gene or gene product may also play a role in the treatment and / or detection of developmental, sex-related, or cardiovascular disorders associated with the developing embryo. The protein, and antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the above tissues.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences relate to SEQ ID NO: 31 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Thus, preferably, according to the invention, the nucleotide sequence described by the general formula ab (where a is any integer from 1 to 905 of SEQ ID NO: 31 and b is an integer from 15 to 919, Here, both a and b correspond to the positions of the nucleotide residues shown in SEQ ID NO: 31, and where b is a + 14 or more) one or more polynucleotides are excluded.

FEATURES OF PROTEIN ENCODED BY GENE NO: 22 In certain embodiments, a polypeptide of the invention comprises the following amino acid sequence:
PCLQVIGIDFCRLLLLMCLVLKRNLTVPFFSSYSPLKT
ITCITSEQIAVVSNFFRQKLGVRAKFFQGACLHTSK
VVICLNLPIISIQRADIRMWWLVVNTPYARGVNN (SEQ ID NO: 340). Polynucleotides encoding these polypeptides are also
Included by the present invention.

[0133]   This gene is expressed primarily in the spinal cord.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, as well as in any of a variety of nervous system and neuromuscular disorders (muscle atrophy side). It is useful as a reagent for the diagnosis of diseases and conditions including (but not limited to) chord sclerosis, muscular dystrophy, and hereditary and non-hereditary chorea). Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of such tissues or cell types. For many disorders of the tissues or cells, particularly the central nervous system and neuromuscular system, standard gene expression levels (ie, expression levels in healthy tissue or body fluids taken from individuals without such disorders) Significantly higher or lower levels of expression of this gene may be associated with specific tissues or cell types (eg, nervous tissue, cancerous tissue and wound tissue) or body fluids (eg, nerve tissue, cancerous tissue and wound tissue) collected from individuals with such disorders. Lymph, serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

Its tissue distribution in the spinal cord indicates that this gene may be used in the treatment of spinal cord injury. The protein product of this gene can be injected into the spinal cord to promote or control growth following injury or degeneration. Alternatively, cells expressing this gene may be injected or transferred into the spinal cord by other means as a treatment to promote growth or growth regulation after spinal cord injury or degeneration. This gene is also a neurodegenerative disease state, behavioral disorder, or inflammatory state, such as Alzheimer's disease, Parkinson's disease, Huntington's chorea, Tourette's syndrome, meningitis, encephalitis, demyelinating disease, peripheral neuropathy, neoplasia, Trauma, birth defects, spinal cord injury, ischemia and infarction, aneurysm, hemorrhage, schizophrenia, mania, dementia, paranoia, obsessive-compulsive disorder, panic disorder, learning disability, AL
It may be useful in the detection / treatment of S, psychosis, autism, and behavioral changes, including impairment of diet, sleep patterns, balance, and perception. Furthermore, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, recognition, homeostasis, or neural differentiation or survival. In addition, the gene or gene product may also play a role in the treatment and / or detection of developmental, sex-related, or cardiovascular disorders associated with the developing embryo. The protein, and antibodies to this protein, may show utility as tumor markers and / or immunotherapy targets in the above tissues.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences relate to SEQ ID NO: 32 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab (where a is any integer from 1 to 942 of SEQ ID NO: 32 and b is an integer from 15 to 956) , Where both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 32, and where b is a + 14 or more) are excluded.

CHARACTERISTICS OF PROTEIN ENCODED BY GENE NO: 23 In a particular embodiment, a polypeptide of the invention comprises the following amino acid sequence:
VVSVCVLETGQLGPAALCRSV (SEQ ID NO: 341). Polynucleotides encoding these polypeptides are also encompassed by the present invention.

[0138]   This gene is mainly expressed in neutrophils.

Accordingly, the polynucleotides and polypeptides of the present invention can be used for differential identification of tissues or cell types present in a biological sample, as well as immune disorders (including inflammatory diseases or neutropenia). Useful as reagents for the diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of such tissues or cell types. Significantly higher than standard gene expression levels (ie expression levels in normal tissues or fluids from individuals without such disorders) for many disorders of the tissues or cells, particularly the immune system, or Low levels of expression of this gene may result in specific tissue or cell types (eg immune tissue, cancerous tissue and wound tissue) or body fluids (eg lymph, serum, plasma) taken from individuals with such disorders. , Urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

Its tissue distribution in neutrophils indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of inflammatory conditions. In addition, this gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also indicate utility in treating cancer (eg, by boosting the immune response). Since this gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune function. Therefore, it also includes arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, chronic granulomatosis, inflammatory bowel disease, sepsis, contusions, neutropenia, neutropenia, psoriasis. , Hypersensitivity (eg, T cell-mediated cytotoxicity); immune response to transplanted organs and tissues (eg, graft versus host disease and graft disease) or autoimmune disorders such as autoimmune infertility, It may also be used as an agent for immunological disorders, including lens tissue injury, demyelination, systemic lupus erythematosus, drug-induced hemolytic anemia, rheumatoid arthritis, Sjögren's disease, scleroderma and tissues. further,
This gene product may have commercial utility in the proliferation of stem cells and committed progenitor cells of various blood lineages, and in the differentiation and / or proliferation of various cell types. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the above tissues.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences relate to SEQ ID NO: 33 and may have been publicly available before the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab (where a is any integer from 1 to 552 of SEQ ID NO: 33 and b is an integer from 15 to 566) , Where both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 33, and where b is a + 14 or more) are excluded.

CHARACTERISTICS OF PROTEIN ENCODED BY GENE NO: 24 In certain embodiments, a polypeptide of the invention comprises the following amino acid sequence:
NISVHGFPVPCLRRQRLQGPCHPKCCPHXISSSGKPRS
SFSPSYHCKFSRNATLLVVPNIFSYMQSSSFLIPQT
SKYYILXPYAXTXRPIKXIFKQAKQ (SEQ ID NO: 342), I
YNDMMMEKKKKTEVYQKRXSGDNTWGGGKGLVAFVSSM
EQGIHVQRCFIANLKFSSPGV (SEQ ID NO: 343), YDDGE
KEDRGLPEEMXWGQHLGWQGPCSLCLKHGTGNPCTE
MFYCQFKIFISWCLIPLVVFALLGDFRDRPGWIFSWR
YHLKHTVWGGGYNIIML (SEQ ID NO: 344) TPGDENFKLAI
KHLCTWIPCS (SEQ ID NO: 345), IRHEIFLTIESFCPSA
PRGEDDDNLLRTSRVPDI (SEQ ID NO: 346) IRGSIPGHK
KMHLSFNVAAQWSLLKPLVLREEGALFLTHHDQLESK
NSWTLSIGPRVPYTYVVVTWSALWDLPNQPLAGRK
ESGGSYGPISVTQSPHQAALKWFAKKKKGKSHSTVQ
LANILHVFXAPDXYHFVNTSLQLFLEYYTVMCMLCEN
KQKTLGR (SEQ ID NO: 347), EPEVTQVXSXELTFQPRKA
GAKVTAGKSHHQVIHWEFEIMLSSYSTDVPLWFLKF
FSSNLPQTYFPHSGVKKWGSCFFSLPWRDSPPLTFIS
LLSSHLTTFHLYHLHHGIICLGFSVYFHRAYTSLCI
LETAVGSY (SEQ ID NO: 348), WSLLKPLVLREEGALFLT
HDQLESK (SEQ ID NO: 349), WFAKKKGKQSHSTVQLANI
LHV (SEQ ID NO: 350), AGKSHHQVIHWEFEIMLSSYSTD
VP (SEQ ID NO: 351), and / or HGIICLGFSVYFHRAYT
SLCILETAV (SEQ ID NO: 352). Polynucleotides encoding these polypeptides are also included in the invention.

[0143]   This gene is mainly expressed in smooth muscle.

Thus, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in biological samples, as well as for myopathy or vascular disorders (defective organ innervation; neuronal survival). Is useful as a reagent for the diagnosis of diseases and conditions including, but not limited to, defects in peristalsis, digestive disorders, and vascular system disruption. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of such tissues or cell types. Significantly higher or more than standard gene expression levels (ie, expression levels in normal tissues or fluids from individuals without such disorders) for many disorders of the tissues or cells, particularly smooth muscle Low levels of expression of this gene may result in specific tissue or cell types (eg, cancerous and wounded tissue) or body fluids (eg, lymph, serum, plasma, urine, synovium, etc.) taken from individuals with such disorders. Fluid, and spinal fluid),
Alternatively, it may be routinely detected in another tissue or cell sample.

This tissue distribution in smooth muscle indicates the diagnosis and / or impairment of disorders in which polynucleotides and polypeptides corresponding to this gene result from dysfunction of normal smooth muscle function.
Or indicate usefulness for treatment. For example, the gene product may represent a soluble factor produced by smooth muscle, which regulates innervation of organs or survival of adjacent neurons. Similarly, it may be involved in controlling the digestive process and activities such as peristalsis. Similarly, it may be involved in controlling the vasculature in regions where smooth muscle surrounds vascular epithelium. The protein as well as antibodies to this protein may show utility as tumor markers and / or immunotherapeutic targets for the above tissues.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences relate to SEQ ID NO: 34 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Thus, preferably, according to the invention, the nucleotide sequence described by the general formula ab, where a is any integer from 1 to 1550 of SEQ ID NO: 34 and b is from 15 to 1564
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 34, and b is a + 14 or greater) and are excluded. .

FEATURES OF PROTEIN ENCODED BY GENE NO: 25 In certain embodiments, a polypeptide of the invention comprises the following amino acid sequence: KRLTINARVHLWTLKSVPL (SEQ ID NO: 353), EYVF.
NMXXYSKSRAISPLSGGPYTPRGTTPLPIIPEPGARQ
RDHPASLKYAKIIQTKLFALPYPKETSMKAVA (SEQ ID NO: 354), and / or ETVPPRSSQFLKITXGPARSMS
LIXXAIQNPEPYLLYLALIPQEALLLYLSSQSQVPG
NETTPPV (SEQ ID NO: 355). Polynucleotides encoding these polypeptides are also encompassed by the present invention.

[0148]   This gene is expressed primarily in T cells.

Accordingly, the polynucleotides and polypeptides of the present invention are for the differential identification of tissues or cell types present in a biological sample, as well as for immune system disorders (such as lupus, inflammatory disorders, or AIDS). It is useful as a reagent for the diagnosis of diseases and conditions including, but not limited to, immune deficiency). Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, particularly the immune system, significantly higher or lower levels of this gene than standard gene expression levels (ie, expression levels in healthy tissues or fluids from individuals without disorders). The expression of a gene is a particular tissue or cell type (eg, immune, hematopoietic, and cancerous and wounded tissue) or body fluid (eg, lymph, serum, plasma, etc.) taken from an individual having such a disorder. Urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

A preferred epitope is Ser-21 to Thr-34 in SEQ ID NO: 184,
An epitope including the sequences shown as Thr-38 to Glu-43 residues can be mentioned.

This tissue distribution in immune cells indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of various immune system disorders. Expression of this gene product in T cells indicates a role in the regulation of proliferation, survival, differentiation, and / or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the control of cytokine production, antigen presentation, or other processes that may also indicate utility in treating cancer (eg, by boosting the immune response). Since this gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune function. Therefore, arthritis, asthma, AI
Of immunodeficiency diseases such as DS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, T cell mediated cytotoxicity Hypersensitivity; immune response to transplanted organs or tissues, such as host versus graft and graft versus host disease, or autoimmunity such as autoimmune infertility, lens tissue injury, demyelination, systemic lupus erythematosus , May also be used as a drug for immune disorders including drug-induced hemolytic anemia, rheumatoid arteritis, Sjogren's disease, scleroderma and tissues. Moreover, this gene product may have commercial utility in the expansion of stem cells and committed progenitor cells of various blood lineages, and in the differentiation and / or proliferation of various cell types. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 35 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 1021 of SEQ ID NO: 35, and b is 15 to 10
Is an integer of 35, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 35, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

(Characteristics of Protein Encoded by Gene No. 26) The translation product of this gene is thought to play an important role in tumor suppression in human IB.
Was determined to have homology to the 3089A protein (Genban
k See registration number gil3041877 (AF027734)). In a particular embodiment, the polypeptide of the invention comprises the following amino acid sequence: N
EVSFSLSLGFSPREFARRWKVNNLALERDDFFSLPLP
LAPEFIRNIRLLGRRPNLQQVTENLIKKYGTHFLLS
ATLGGKQHHNPKLIGCQTIGNNVKTRVA (SEQ ID NO: 35
6), VPYFLIRFSVTCCRRLGLPRRRRMFRINSGARGN
GKLKKSFLSRAKLFTFQRANSLGEKPRDKEKLTSFQ
SKRHKI (SEQ ID NO: 357), and / or EMSAVLFNQIFC
NLLQIGSPSKEANVPDKLWGKRQWQTEEEVLPFQSQV
VHLPTTGKLPGGKAKG (SEQ ID NO: 358) Polynucleotides encoding these polypeptides are also encompassed by the invention.

[0154]   This gene is expressed primarily in human fibrosarcoma.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in biological samples and for disorders affecting endothelial, muscle and extracellular matrix tissues (fibrosarcoma). And bladder cancer) and are useful as reagents for the diagnosis of diseases or conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, particularly the integumentary system, significantly higher or lower levels of this gene than standard gene expression levels (ie, expression levels in healthy tissues or fluids from undisturbed individuals) are used. The expression of a gene is a specific tissue or cell type (eg, endothelial tissue, urogenital tissue, kidney tissue, muscle tissue, or cancerous and wound tissue) or body fluid (eg, endothelial tissue, urogenital tissue, kidney tissue, muscle tissue) or body fluid (eg, tissue) collected from an individual having such a disorder. , Lymph, serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

Preferred epitopes include Pro-49 to Asp-6 in SEQ ID NO: 185.
An epitope is included that includes the sequence shown as 8 residues.

Its tissue distribution in human fibrosarcoma indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of various cancers, especially fibrosarcoma and fibroids. In addition, expression in cell sources characterized by proliferating cells indicates that this protein may play a role in regulating cell division and may have utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, developing tissue also includes decisions involving cell differentiation and / or apoptosis in pattern formation. So this protein also
It may be involved in apoptosis or tissue differentiation and may also be useful in cancer therapy. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 36 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 606 of SEQ ID NO: 36, and b is 15 to 620.
, Both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 36, and b is a + 14 or greater) and are excluded. .

[0159]     (Characteristics of protein encoded by gene number 27)   This gene is expressed primarily in human tonsils.

Accordingly, the polynucleotides and polypeptides of the present invention are for the differential identification of tissues or cell types present in a biological sample, as well as for immune and hematopoietic disorders (including but not limited to inflammation and infectious diseases). It is useful as a reagent for diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of this tissue or cell. For many disorders of the tissues or cells described above, especially the immune system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in healthy tissues or fluids from individuals without disorders). The expression of this gene is dependent on the specific tissue or cell type (eg, immune, hematopoietic, and cancerous and wound tissue) or body fluid (eg, lymph, serum, plasma) taken from an individual having such a disorder. , Urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

This tissue distribution in tonsils indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis of inflammation and infectious diseases. In addition, this gene product may play a role in the regulation of proliferation; survival; differentiation; and / or activation of hematopoietic cell lines, including blood stem cells. This gene product may be involved in the control of cytokine production, antigen presentation, or other processes that may also indicate utility in treating cancer (eg, by boosting the immune response). Since this gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune function. Therefore, arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, Hypersensitivity such as T cell mediated cytotoxicity;
Immune response to transplanted organs or tissues, such as host vs. graft and graft vs. host disease, or autoimmune disorders such as autoimmune infertility, lens tissue injury, demyelination, systemic lupus erythematosus, drug-induced It may also be used as an agent for immune disorders including hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. Moreover, this gene product may have commercial utility in the expansion of stem cells and committed progenitor cells of various blood lineages, and in the differentiation and / or proliferation of various cell types. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 37 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is any integer of 1 to 959 of SEQ ID NO: 37, and b is 15 to 973.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 37, and b is a + 14 or more) are excluded. .

FEATURES OF PROTEIN ENCODED BY GENE NO: 28 In a particular embodiment, a polypeptide of the invention comprises the following amino acid sequence: HYHGSGGFLIKEFGSFLSLLLCMLSCPYVFCHGMLE.
QEVPSSVVSPSTLDFPTSRTVNKFLFKLPSLWYSVI
ATQNGLKQKIRETFLFVQFSQMPRWWHLE (SEQ ID NO: 3
59). Polynucleotides encoding these polypeptides are also encompassed by the present invention.

This gene is expressed predominantly in adipose and brain. Therefore, the polynucleotides and polypeptides of the present invention are useful for differential identification of tissues or cell types present in a biological sample, as well as for metabolism and It is useful as a reagent for the diagnosis of diseases and conditions including, but not limited to, neuropathy (including but not limited to obesity and disorders of the brain or central nervous system). Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, especially the central nervous system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in normal tissues or body fluids from unaffected individuals). The expression of this gene is dependent on the specific tissue or cell type (eg, nervous tissue, metabolic tissue, and cancerous and wound tissue) or body fluid (eg, lymph, serum, etc.) taken from an individual having such a disorder. Plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

This tissue distribution in nervous and adipose tissue, combined with homology to oxidoreductase, allows polynucleotides and polypeptides corresponding to this gene to diagnose or treat obesity and disorders of the brain and central nervous system. To be useful for. In addition, polynucleotides and polypeptides corresponding to this gene are associated with neurodegenerative disease states, behavioral disorders, or inflammatory conditions (eg, Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, meningitis, encephalitis, demyelinating). Disease, peripheral neuropathy, neoplasia, trauma, birth defects, spinal cord injury, ischemia and infarction,
Aneurysm, bleeding, schizophrenia, mania, dementia, paranoia, obsessive-compulsive disorder, panic disorder, learning disability, ALS, psychosis, autism, and behavioral changes; impairment of nutritional support, sleep patterns, balance, and perception It is useful for the detection / treatment of (including). further,
Elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is also involved in synapse formation, neurotransmission, learning, recognition, homeostasis, or neural differentiation or survival. In addition, the gene or gene product may also play a role in the treatment and / or detection of developmental disorders, associated diseases, or cardiovascular disorders associated with the developing embryo. In addition, expression in adipose tissue and brain results in the involvement of neural tissue in which this protein is secondary to the conditions in which this protein affects the development of the myelin sheath in neurons or to abnormal fatty acid metabolism. , Which may be useful as a novel therapeutic agent for remedying other disorders that occur. The protein as well as antibodies to this protein may show utility as tumor markers in the tissues listed above and / or as targets for immunotherapy.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 38 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 824 of SEQ ID NO: 38, and b is 15 to 838.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 38, and b is a + 14 or more) are excluded. .

(Characteristics of Protein Encoded by Gene No. 29) The gene encoding the disclosed cDNA is considered to be located on chromosome 11. Therefore, the polynucleotide related to the present invention is useful as a marker for linkage analysis for chromosome 11. In one embodiment of this gene,
Includes a polypeptide with the following amino acid sequence: FCKHNGSKNVFSTFRT.
PAVLFTGIVALYIASGLTGFIGLEVVAQLFNC (SEQ ID NO: 360). A further embodiment is a polynucleotide encoding this polypeptide.

This gene is expressed primarily in suppressor T cells, endothelial cells, dendritic cells, and infant brain.

Thus, the polynucleotides and polypeptides of the present invention encompass immune system disorders for the differential identification of tissues or cell types present in a biological sample, as well as associated with aberrant activation of T cells. Are useful as reagents for the diagnosis of diseases and conditions that are not limited to them. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, especially the immune system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in healthy tissues or fluids from individuals without disorders). The expression of this gene is dependent on the specific tissue or cell type (eg, hematopoietic tissue, developmental tissue, nervous tissue, immune tissue, endothelial tissue, and cancerous and wound tissue) taken from an individual with such disorders or Body fluids (eg, lymph, serum, plasma, urine,
Synovial fluid, and spinal fluid) or another tissue or cell sample.

A preferred epitope is Tyr-14 to Leu-24 in SEQ ID NO: 188,
An epitope including a sequence shown as residues Pro-59 to Gln-66 is included.

Tissue distribution in immune cells, polynucleotides and polypeptides corresponding to this gene are useful for the treatment of immune system disorders associated with altered activity of T cells. In addition, this gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also have utility in treating the immune system.
Since this gene is expressed in cells of lymphoid origin, the gene or protein and antibodies to that protein may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above. Therefore, it can also be used as a drug for immune disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne and psoriasis. Moreover, this gene product may have commercial utility in the expansion of stem cells and committed progenitor cells of various blood lineages, and in the differentiation and / or proliferation of various cell types. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 39 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab, where a is any integer from 1 to 593 of SEQ ID NO: 39 and b is an integer from 15 to 607, wherein Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 39, and where one or more polynucleotides containing (where b is a + 14 or greater) are excluded (encoded by gene number 30). CHARACTERISTICS OF THE PROTEIN This gene is expressed primarily in fetal and tumor cell types.

Accordingly, the polynucleotides and polypeptides of the present invention include for differential identification of tissues or cell types present in a biological sample, as well as diseases of rapidly growing tissues such as cancer. Are useful as reagents for the diagnosis of diseases and conditions that are not limited to them. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. Significantly higher than standard gene expression levels (ie expression levels in normal tissues or body fluids from unaffected individuals) for many disorders of the tissues or cells, especially in rapidly proliferating tissues, or Low levels of expression of this gene may result in specific tissue or cell types (eg, fetal tissue, as well as cancerous and wound tissue) or body fluids collected from individuals with such disorders (such as fetal tissue and cancerous and wound tissue).
(Eg, lymph, serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

The tissue distribution of this gene, predominantly in the developing fetus, indicates a role in the treatment and / or detection of developmental disorders and proliferative defects. Furthermore, expression on tumor cell types indicates a role in tumor detection and / or treatment. In addition, expression in fetal tissue and other cell sources characterized by proliferating cells indicates that this protein may play a role in regulating cell division and has utility in the diagnosis and treatment of cancer and other proliferative disorders. Show that you get. Similarly, embryonic development also involves the involvement of cell differentiation and / or apoptosis in pattern formation. Therefore, this protein may also be associated with apoptosis or tissue differentiation and may also be useful in cancer therapy. The protein, as well as antibodies to this protein,
It may show utility as a tumor marker and / or immunotherapeutic target for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 40 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab, where a is any integer from 1 to 868 of SEQ ID NO: 40 and b is an integer from 15 to 882, wherein Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 40, and where one or more polynucleotides containing (where b is a + 14 or more) are excluded (encoded by gene number 31). CHARACTERISTICS OF THE PROTEIN This gene is expressed primarily in the salivary glands and to a lesser extent in other tissues.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, and for diseases and disorders including, but not limited to, digestion and immune disorders. It is useful as a reagent for diagnosing a condition. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. With respect to many disorders of the above tissues or cells, particularly salivary glands and other glands of the exocrine system, significantly more than standard gene expression levels (ie expression levels in normal tissues or fluids from undiseased individuals). Higher or lower levels of expression of this gene may result in specific tissue or cell types (eg, exocrine tissue, digestive tissue, cancerous tissue and wound tissue) or body fluids (eg, exocrine tissue, digestive tissue, cancerous tissue and wound tissue) taken from an individual having such a disorder. Lymph, serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

A preferred epitope is Glu-25 to Gly-31 in SEQ ID NO: 190,
An epitope is included that includes the sequences shown as Tyr-62 to Thr-68 residues.

This tissue distribution in salivary gland tissue indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of digestive and immune system disorders. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 41 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 945 of SEQ ID NO: 41 and b is an integer from 15 to 959, wherein Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 41, and excluding one or more polynucleotides containing (where b is a + 14 or greater) (encoded by gene number 32). Features of the Proteins According to the Disclosure The gene encoding the disclosed cDNA is believed to be located on chromosome 12. Therefore, the polynucleotide related to the present invention is useful as a marker for linkage analysis for chromosome 12.

[0180]   This gene is expressed primarily in adult and infant brain tissue.

Accordingly, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, and include, but are not limited to, neurodegenerative and behavioral disorders. It is useful as a reagent for diagnosis of diseases and conditions. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. Significantly higher or lower than standard gene expression levels (ie, expression levels in normal tissues or fluids from unaffected individuals) for many disorders of the tissues or cells, particularly the central and peripheral nervous system Levels of this gene are expressed in specific tissues or cell types (eg, brain, developmental, and cancerous and wound tissues) or body fluids (eg, brain, developmental and cancerous tissues) collected from individuals with such disorders.
Lymph, serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

A preferred epitope is SEQ ID NO: 191 with residues: Ser-16 to Val.
An epitope including the sequence shown as -33 is included.

This tissue distribution in neural tissue is characterized by the fact that the polynucleotides and polypeptides corresponding to this gene are associated with Alzheimer's disease, Parkinson's disease, Huntington's disease, schizophrenia, mania, dementia, delusions, obsessive-compulsive and panic disorders. It is shown to be useful for the detection / treatment of neurodegenerative disease states and behavioral disorders such as. further,
Expression of this gene product in regions of the brain results in neuronal survival; synaptogenesis;
Conductance: indicates that it may be related to neural differentiation and the like. Such associations can affect many processes such as learning and cognition. The protein, as well as antibodies to this protein, may show utility as tissue-specific markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 42 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 861 of SEQ ID NO: 42, and b is 15 to 875.
, Both of which a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 42, and where b is a + 14 or more) are excluded. .

[0185]     (Characteristics of protein encoded by gene number 33)   This gene is expressed primarily in the synovium.

Accordingly, the polynucleotides and polypeptides of the present invention act on the synovial lining for differential identification of tissues or cell types present in biological samples, and on arthritis and autoimmune disorders. It is useful as a reagent for the diagnosis of diseases and conditions, including but not limited to diseases. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. Significantly higher than standard gene expression levels (ie, expression levels in normal tissues or fluids from unaffected individuals) in connection with many disorders of the tissues or cells, particularly the musculoskeletal system, or Low levels of expression of this gene may result in specific tissues or cell types (eg, endothelial, skeletal, and cancerous and wound tissues) or body fluids (eg, lymph, etc.) taken from individuals with such disorders. Serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

This tissue distribution indicates that the polynucleotides and polypeptides corresponding to this gene are useful for protection of joint damage or as a factor that can promote cell proliferation within the articular joint. In addition, expression of this gene product in the synovium is associated with diseases and conditions affecting the skeletal system, particularly osteoporosis and disorders affecting connective tissue (eg,
Detection and treatment of arthritis, trauma, tendinitis, chondromalacia and inflammation (eg, various autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis, and dwarfism, Suggests a role in spinal deformity and specific joint abnormalities, as well as in the diagnosis or treatment of chondrodysplasia (ie congenital vertebral epiphyseal dysplasia, familial osteoarthritis, type II Atelosteogenesis, Schmid metaphyseal chondrodysplasia) . The proteins as well as antibodies to the proteins may show utility as tumor markers for the tissues listed above and / or targets for immunotherapy, many polynucleotide sequences (eg EST sequences) are publicly available, And it is accessible through the sequence database. Some of these sequences are related to SEQ ID NO: 43 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 616 of SEQ ID NO: 43, and b is 15 to 630.
, Both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 43, and b is a + 14 or more) are excluded. .

Characterization of the protein encoded by gene number 34 When tested against the U937 myeloid cell line, supernatants obtained from cells containing this gene activated the GAS assay. Therefore, this gene is Jak
-It appears to activate myeloid cells via the STAT signaling pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes involved in the Jak-STAT pathway. The Jak-STAT pathway is large and is a signal transduction pathway involved in cell differentiation and proliferation. Therefore, Jak-
Activation of STATs (reflected by binding of GAS elements) can be used to indicate proteins involved in cell differentiation and proliferation.

[0189]   This gene is expressed primarily in B cell lymphoma cells.

Thus, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, as well as for immune disorders such as lymphoma lymphoblastic leukemia, myeloma and myeloma. It is useful as a reagent for the diagnosis of diseases and conditions including, but not limited to, B cell lineage disorders including hairy cell leukemia. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher or higher than standard gene expression levels (ie, expression levels in normal tissues or body fluids from unaffected individuals) in relation to many disorders of the tissues or cells, particularly the immune system Low levels of expression of this gene
Specific tissues or cell types (eg, immune and cancerous and wounded tissues) or body fluids (eg, lymph, serum, plasma, urine, synovial fluid, and spinal fluid) collected from individuals with such disorders. ) Or in another tissue or cell sample.

A preferred epitope is SEQ ID NO: 193 at residues: Lys-82 to Pro.
An epitope is included that includes the sequence shown as -90.

This tissue distribution and biological activity indicate that the polynucleotides and polypeptides corresponding to this gene are useful in the treatment and diagnosis of B cell lineage disorders, including cancer. This factor may be useful at the terminal stage of differentiation of malignant cells, or may act as a growth factor for B cell proliferation or differentiation, which is supported by biological assay data. The protein as well as antibodies to this protein may show utility as tumor markers for the tissues listed above and / or targets for immunotherapy.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 44 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 557 of SEQ ID NO: 44, and b is 15 to 571.
, Both of which a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 44, and where b is a + 14 or more) are excluded. .

Characterization of Protein Encoded by Gene No. 35: When tested against the U937 myeloid cell line, supernatants obtained from cells containing this gene activated the GAS assay. Therefore, this gene is Jak
-It appears to activate myeloid cells via the STAT signaling pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes involved in the Jak-STAT pathway. The Jak-STAT pathway is large and is a signal transduction pathway involved in cell differentiation and proliferation. Therefore, Jak-
Activation of STATs (reflected by binding of GAS elements) can be used to indicate proteins involved in cell differentiation and proliferation.

This gene is primarily in stromal cell-derived giant cell tumors of the bone, placenta, pancreas, and cells from various tumors, and to a lesser extent in brain, melanocytes, dendritic cells and some other tissues. Is also expressed.

Thus, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample and include tumors of the pancreas, uterus, ovary, bone, adrenal gland. It is useful as a reagent for diagnosis of diseases and conditions that are not limited thereto. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher or higher than standard gene expression levels (ie, expression levels in normal tissues or body fluids from non-disordered individuals) in relation to many disorders of the tissues or cells, especially the reproductive system Low levels of expression of this gene may result in specific tissue or cell types (eg, placental tissue, pancreatic tissue, and cancerous and wound tissue) or body fluids (eg, lymph, etc.) taken from individuals with such disorders. Serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

This tissue distribution indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the treatment or diagnosis of tumors of the reproductive organs, pancreas, or bone marrow. Furthermore, the polynucleotides and polypeptides corresponding to this gene are
Various endocrine disorders and cancers, especially Addison's disease, Cushing's syndrome, and pancreas (eg, diabetes mellitus), adrenal cortex, ovaries, pituitary gland (eg, excess, deficiency pituitary disorder), thyroid (eg, hyperthyroidism) , Hypothyroidism), parathyroid gland (eg hyperparathyroidism, hypoparathyroidism), hypothalamus, testicular disorders and / or cancers may be useful in the detection, treatment and / or prevention of cancer. is there. The protein as well as antibodies to this protein may show utility as tumor markers for the tissues listed above and / or targets for immunotherapy.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 45 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 916 of SEQ ID NO: 45, and b is 15 to 930.
, Both of which a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 45, and where b is a + 14 or more) are excluded. .

Characterization of Protein Encoded by Gene No: 36 When tested against the K562 leukemia cell line, supernatants removed from cells containing this gene activated the ISRE assay. Therefore, this gene appears to activate leukemic cells via the Jak-STAT signaling pathway. Interferon-sensitive response elements are promoter elements found upstream in many genes involved in the Jak-STAT pathway. Jak-ST
The AT pathway is a large signaling pathway involved in cell differentiation and proliferation.
Therefore, activation of the Jak-STAT pathway, reflected by binding of ISRE elements, can be used to indicate proteins involved in cell proliferation and differentiation.

This gene is also expressed primarily in the kidneys and to a lesser extent in the brain.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, as well as diseases including but not limited to renal and nervous system disorders. And are useful as reagents for diagnosing conditions. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher or lower than standard gene expression levels (ie, expression levels in normal tissues or fluids from undiseased individuals) for many disorders of the tissues or cells, particularly the kidneys and nervous system Levels of expression of this gene are determined by the specific tissue or cell type (eg, kidney tissue, urinary tissue, endocrine tissue, cancerous tissue and wound tissue) or body fluid (eg, kidney tissue, urinary tissue, endocrine tissue, cancer tissue and wound tissue) collected from an individual having such a disorder. Lymph, serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

A preferred epitope is Lys-117 to Lys-12 in SEQ ID NO: 195.
An epitope is included that includes the sequence shown as 6 residues.

The tissue distribution of this gene in renal tissue is such that the polynucleotides and polypeptides corresponding to this gene are characterized by Alzheimer's disease, Parkinson's disease, Huntington's chorea, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic. In addition to detecting / treating neurodegenerative disease states and behavioral disorders, such as disorders, it is shown to be useful in treating and / or detecting renal disorders, including renal failure and Wilms tumor.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 46 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 423 of SEQ ID NO: 46, and b is 15 to 437.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 46, and b is a + 14 or more) are excluded. .

[0205]     (Characteristics of protein encoded by gene number 37)   One embodiment of this gene comprises a polypeptide of the following amino acid sequence:

[0206]

[Chemical 5] A further embodiment are polynucleotides encoding these polypeptides.

This gene is expressed primarily in the pituitary gland, and to a lesser extent in the thymus and breast.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, and for diseases and disorders including, but not limited to, metabolic and immune disorders. It is useful as a reagent for diagnosing a condition. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, particularly the endocrine and immune systems, significantly higher or more than standard gene expression levels (ie, expression levels in healthy tissue or fluid from individuals without the disorder) Low levels of expression of this gene may result in specific tissue or cell types (eg, thymus tissue, cancerous tissue and wound tissue) or body fluids (eg, lymph, tissue, etc.) taken from an individual having such a disorder.
Serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

The tissue distribution of this gene indicates that the polynucleotides and polypeptides corresponding to this gene, in addition to treating or detecting immune or hematopoietic disorders including arthritis, asthma, immunodeficiency diseases, and leukemia, endocrine disorders, It shows utility in the treatment and / or detection of metabolic disorders and immune disorders, including developmental and developmental deficiencies.
The protein as well as antibodies to the protein may exhibit utility as tissue-specific markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 47 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 1010 of SEQ ID NO: 47, and b is 15 to 10
24 is an integer of 24, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 47, and b is a + 14 or more) and one or more polynucleotides are excluded. It

[0211]     (Characteristics of protein encoded by gene number 38)   This gene is expressed primarily in hemangiopericytoma.

Thus, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, and for vascular disorders such as stroke, aneurysm, cardiac arrest, hemorrhage. It is useful as a reagent for diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. With respect to many disorders of the tissues or cells described above, particularly with respect to the vasculature, significantly higher or lower levels of normal gene expression levels (ie, expression levels in healthy tissues or fluids from unaffected individuals) The expression of this gene may depend on the specific tissue or cell type (eg, circulatory tissue, cancerous tissue and wound tissue) or body fluid (eg, lymph, serum, plasma, urine, etc.) taken from an individual having such a disorder. Synovial fluid, and cerebrospinal fluid) or another tissue or cell sample.

[0213] A preferred epitope is the residue in SEQ ID NO: 197: Cys-14 to GI.
The epitope includes the sequences shown as y-23, Met-45 to Gly-51.

The tissue distribution of this gene in hemangiopericytoma alone indicates that the polynucleotides and polypeptides corresponding to this gene are for the treatment and / or detection of vascular disorders including bleeding, aneurysms, strokes, and cardiac arrest. Can be useful for. The protein as well as antibodies to the protein may exhibit utility as tissue-specific markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 48 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 449 of SEQ ID NO: 48, and b is 15 to 463.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 48, and b is a + 14 or more) are excluded. .

Characterization of the Protein Encoded by Gene No: 39 The translation product of this gene shares sequence homology with serine proteases, which are believed to be important in regulating protein availability and action in vivo.

[0217]   This gene is expressed primarily in the cerebellum.

Thus, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, as well as Alzheimer's and mental disorders (eg, schizophrenia). It is useful as a reagent for diagnosis of diseases and conditions including, but not limited to, disorders of the central nervous system associated with aberrant growth factor regulation including neurodegenerative conditions. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher than standard gene expression levels (ie, expression levels in normal tissues or fluids from unaffected individuals) in connection with many disorders of the tissues or cells, particularly the central nervous system, or Lower levels of expression of this gene result in specific tissues or cell types taken from individuals with such disorders (eg, CNS, cancerous tissue and wound tissue).
Or it can be detected in body fluids such as lymph, serum, plasma, urine, synovial fluid, and spinal fluid or another tissue or cell sample.

A preferred epitope is SEQ ID NO: 198 at residues: Ser-17 to Gln.
An epitope including the sequence shown as -22 is included.

This tissue distribution in neuronal tissue and homology with serine proteases makes polynucleotides and polypeptides corresponding to this gene useful for treating disorders of the central nervous system, including neurodegenerative and psychiatric disorders. Indicates that. Furthermore, expression of this gene product in cerebral tissue is shown to be associated with neuronal survival; synaptogenesis; conductance; neural differentiation and the like. Such associations can affect many processes such as learning and cognition. It may also be useful in the treatment of psychodegenerative disorders such as schizophrenia; ALS; or Alzheimer. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 49 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 871 of SEQ ID NO: 49, and b is 15 to 885.
, Both of which a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 49, and where b is a + 14 or more) are excluded. .

[0222]     (Characteristics of protein encoded by gene number 40)   This gene is expressed primarily in CD34-depleted buffy coats.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, and for diseases and conditions including but not limited to autoimmune disorders. It is useful as a reagent for diagnosis of. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, especially the immune system, standard gene expression levels (
That is, a significantly higher or lower level of expression of this gene relative to expression levels in healthy tissues or bodily fluids from non-disordered individuals, or specific tissues collected from individuals with such disorders or Detection in a cell type (eg, immune tissue, developing tissue, cancerous tissue and wound tissue) or body fluid (eg, lymph, serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample Can be done.

Its tissue distribution in CD34-depleted buffy coat tissue indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of diseases and disorders of the immune system, including autoimmune diseases. Furthermore, expression of this gene product in CD34-depleted buffy coats plays a role in the regulation of proliferation, survival, differentiation, and / or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest utility in treating cancer (eg, by boosting the immune response). Since this gene is expressed in cells of lymphoid origin, the gene or protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above. Therefore, it can also be used as a drug for immunological disorders, including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne wounds, psoriasis. . Moreover, this gene product may have commercial utility in the expansion of stem cells and directed progenitor cells of various blood lineages, and in the differentiation and / or proliferation of various cell types. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 50 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is any integer of 1 to 833 of SEQ ID NO: 50, and b is 15 to 847.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 50, and b is a + 14 or more) are excluded. .

[0226]     (Characteristics of protein encoded by gene number 41)   This gene is expressed primarily in B cell lymphoma cells.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in biological samples, as well as for lymphoma lymphoblastic leukemia, myeloma, and hairy cells. It is useful as a reagent for the diagnosis of diseases and conditions including, but not limited to, B cell lineage diseases including leukemia. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, particularly the immune system, significantly higher or lower levels of this gene than standard gene expression levels (ie, expression levels in healthy tissues or fluids from individuals without disorders). The expression of a gene is a particular tissue or cell type (eg, immune tissue, cancer tissue, and wound tissue) or body fluid (eg, lymph, serum, plasma, urine, synovial fluid) taken from an individual having such a disorder. , And cerebrospinal fluid), or in another tissue or cell sample.

Tissue distribution in immune cells indicates that polynucleotides and polypeptides corresponding to this gene are useful in the treatment and / or diagnosis of B cell lineage disorders, including cancer. This factor may be useful in the terminal differentiation of malignant cells or may act as a growth factor for B cell proliferation or differentiation. protein,
And antibodies to this protein may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 51 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 566 of SEQ ID NO: 51, and b is 15 to 580.
, Both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 51, and b is a + 14 or more) are excluded. .

Characterization of Protein Encoded by Gene No: 42 This gene is expressed primarily in brain and CD34-depleted buffy coat.

Accordingly, the polynucleotides and polypeptides of the present invention may be used for the differential identification of tissues or cell types present in a biological sample, and especially of the central nervous system, such as multiple sclerosis. It is useful as a reagent for the diagnosis of diseases and conditions including but not limited to autoimmune disorders. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, especially the immune system, at levels significantly higher or lower than standard gene expression levels (ie, expression levels in healthy tissue or body fluids from unaffected individuals). The expression of this gene is dependent on the specific tissue or cell type (eg, immune, nervous, cancer, and wound tissue) or body fluid (eg, lymph, amniotic fluid, serum, etc.) taken from an individual with such a disorder. Plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

[0232] A preferred epitope is SEQ ID NO: 201, residues: Pro-35 to Ala.
An epitope is included including the sequence shown as -40.

Its tissue distribution indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the treatment of autoimmune disorders such as multiple sclerosis. Furthermore, expression of this gene product in CD34-depleted buffy coat indicates its role in the regulation of proliferation, survival, differentiation, and / or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also indicate utility in treating cancer (eg, by boosting the immune response). Since this gene is expressed in cells of lymphoid origin, the gene or protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above. Therefore, it is also used as an agent for immunological disorders, including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. Can be done. Moreover, this gene product may have commercial utility in the proliferation of stem cells and directed progenitor cells of various blood lineages, as well as in the differentiation and / or proliferation of various cell types. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 52 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is any integer of 1 to 584 of SEQ ID NO: 52, and b is 15 to 598.
, Both of which a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 52, and where b is a + 14 or more) are excluded. .

[0235]     (Characteristics of protein encoded by gene number 43)   This gene is mainly expressed in brain tissue.

Accordingly, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, and include, but are not limited to, disorders of the nervous system and neurodegeneration. It is useful as a reagent for diagnosing diseases and conditions that are not controlled. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, especially the central nervous system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in normal tissues or body fluids from unaffected individuals). The expression of this gene is dependent on the specific tissue or cell type (eg,
CNS tissue, brain tissue, cancerous tissue and wound tissue) or fluid (eg lymph,
Serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

Tissue distribution in brain tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful as neuroprotective agents and growth factors for cells of the central or peripheral nervous system. Furthermore, expression of this gene product in the brain indicates that it may be involved in neuronal survival; synaptogenesis; conductance; neural differentiation, etc. Such associations affect many processes such as learning and cognition. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 53 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 557 of SEQ ID NO: 53, and b is 15 to 571.
, Where a and b both correspond to the position of the nucleotide residue set forth in SEQ ID NO: 53, and b is a + 14 or greater) are excluded. .

(Characteristics of Protein Encoded by Gene No. 44) The gene encoding the disclosed cDNA is believed to be located on chromosome 9. Therefore, the polynucleotide of the present invention is useful as a marker in the linkage analysis of chromosome 9.

[0240]   This gene is expressed primarily in embryonic and fetal tissues.

Accordingly, the polynucleotides and polypeptides of the present invention are for the differential identification of tissues or cell types present in a biological sample, as well as for diseases and conditions including but not limited to developmental disorders. It is useful as a reagent for diagnosis. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the above tissues or cells, especially embryonic and fetal tissues, levels that are significantly higher or lower than standard gene expression levels (ie, expression levels in healthy tissues or body fluids from unaffected individuals). Expression of this gene in specific tissues or cell types (eg, fetal tissue, developmental tissue, cancerous tissue and wound tissue) or body fluids (eg, lymph, amniotic fluid, serum) collected from individuals with such disorders. ,
Plasma, urine, synovial fluid, and spinal fluid), or in another tissue or cell sample,
Can be detected.

Tissue distribution in embryonic and fetal tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful in diagnosing and treating developmental disorders. Furthermore, this tissue distribution indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of cancer and other proliferative disorders. Expression in embryonic tissues and other cell sources targeted to proliferating cells indicates that this protein may play a role in the regulation of cell division. Similarly, embryonic development also involves the decision to involve cell differentiation and / or apoptosis in patterning. Thus, this protein also participates in apoptosis or tissue differentiation and may also be useful in cancer therapy. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 54 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 1233 of SEQ ID NO: 54, and b is 15 to 12
47 is an integer of 47, wherein both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 54, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

(Characteristics of Protein Encoded by Gene No. 45) The gene encoding the disclosed cDNA is believed to be located on chromosome 2. Therefore, the polynucleotide of the present invention is useful as a marker in chromosome 2 linkage analysis.

This gene is expressed primarily in the infant brain, placenta, some immune systems, and to a lesser extent in other tissues.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for differential identification of tissues or cell types present in a biological sample, and for diseases including, but not limited to, developmental disorders and immune disorders. And are useful as reagents for diagnosing conditions. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. Significantly higher or lower than standard gene expression levels (ie, expression levels in normal tissues or body fluids from undiseased individuals) for the tissues or cells, particularly early developmental and immune tissues Levels of this gene are expressed in specific tissues or cell types (such as those obtained from individuals with such disorders).
For example, immune tissue, cancerous tissue, and wound tissue) or body fluids (eg, lymph,
Serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

A preferred epitope is SEQ ID NO: 204 at residues: Val-32 to Met.
Examples of the epitope include the sequences shown as -39 and Leu-44 to Val-49.

Tissue distribution in fetal and immune tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of developmental and immune disorders. Furthermore, this tissue distribution indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of cancer and other proliferative disorders. Expression in embryonic tissues and other cell sources targeted to proliferating cells indicates that this protein may play a role in the regulation of cell division.
Furthermore, expression in hematopoietic cells and tissues indicates that it may play a role in the proliferation, differentiation and / or survival of hematopoietic cell lineages. In such an event, the gene may have utility in the treatment of proliferative lymphocyte disorders, and in the maintenance and differentiation of various hematopoietic lineages derived from early hematopoietic stem cells and committed progenitor cells. Similarly, embryonic development also involves the decision to involve cell differentiation and / or apoptosis in patterning. Thus, this protein also
It is involved in apoptosis or tissue differentiation and may also be useful in cancer therapy. The protein product of this gene is a neurodegenerative disease state, behavioral disorder or inflammatory state (e.g., Alzheimer's disease, Parkinson's disease, Huntington's chorea, Tourette's syndrome, meningitis, encephalitis, demyelinating disease, peripheral neuropathy, neoplasia, Trauma, birth defects, spinal cord injury, ischemia and infarction, aneurysm, hemorrhage, schizophrenia, mania, dementia, paranoia, obsessive-compulsive disorder, panic disorder, learning disability, ALS, psychosis, autism, and behavior Useful for detecting / treating alterations, including impaired nutrition, sleep patterns, balance, and sensory perceptions.In addition, elevated expression of this gene product in regions of the brain causes it to play a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, recognition, homeostasis, or neuronal differentiation or survival. , The gene or gene product may also play a role in the treatment and / or detection of developmental, sex-linked, or cardiovascular disorders associated with the developing embryo. It may show utility as a tumor marker and / or immunotherapeutic target for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 55 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is any integer of 1 to 834 of SEQ ID NO: 55, and b is 15 to 848.
, Both of which a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 55, and where b is a + 14 or more) are excluded. .

Characterization of Protein Encoded by Gene No. 46: When tested on Jurkat T cells, supernatants removed from cells containing this gene activated the GAS assay. Therefore, this gene appears to activate T cells via the Jak-STAT signaling pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes involved in the Jak-STAT pathway. The Jak-STAT pathway is a large signaling pathway involved in cell differentiation and proliferation. Therefore, GA
Activation of the Jak-STAT pathway, reflected by S element binding, can be used to indicate proteins involved in cell proliferation and differentiation.

This gene is expressed primarily in brain tissue, and to a lesser extent in T cells.

Accordingly, the polynucleotides and polypeptides of the present invention are for diseases and conditions for the differential identification of tissues or cell types present in a biological sample, and including, but not limited to, neurological disorders. It is useful as a reagent for diagnosis of.
Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. Significantly higher or lower than standard gene expression levels (ie, expression levels in normal tissues or body fluids from unaffected individuals) for many disorders of the tissues or cells, particularly the brain and immune system Levels of expression of this gene are determined by the specific tissue or cell type (eg, immune tissue, brain cells, cancerous tissue and wound tissue) or body fluid (eg, lymph, serum, etc.) taken from an individual having such a disorder. Plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

A preferred epitope is the residues in SEQ ID NO: 205: Ser-33 to Se.
An epitope is included that includes the sequence designated as r-44.

Tissue distribution in T cells indicates that polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of neurological and immune system disorders. Moreover, expression of this gene product in T cells, as well as the observed biological activity of the gene product, indicates that this gene product treats cytokine production, antigen presentation, or cancer (eg, by boosting the immune response). It may be involved in the regulation of other processes that may also suggest utility in. Since this gene is expressed in cells of lymphoid origin, the gene or protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above. Therefore, it also
It may also be used as a drug for immunological disorders, including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. Moreover, this gene product may have commercial utility in the proliferation of stem cells and directed progenitor cells of various blood lineages, as well as in the differentiation and / or proliferation of various cell types. Alternatively, due to its expression in brain tissue, polynucleotides and polypeptides corresponding to this gene may cause neurodegenerative disease states, behavioral disorders or inflammatory conditions (e.g., Alzheimer's disease, Parkinson's disease, Huntington's chorea, Tourette's syndrome, meninges). Inflammation, encephalitis, demyelinating disease, peripheral neuropathy, neoplasia, trauma, birth defects, spinal cord injury, ischemia and infarction, aneurysm, bleeding, schizophrenia, mania, dementia, paranoia, obsessive-compulsive disorder, depression Sexual disorder, learning disability, A
It is shown to be useful in detecting / treating LS, psychosis, autism, and behavioral changes, including impairment of nutritional support, sleep patterns, balance, and perception. Furthermore, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, recognition, homeostasis, or neuronal differentiation or survival. In addition, the gene or gene product is also associated with developmental, sex-related disorders associated with the developing embryo.
Or it may play a role in the treatment and / or detection of cardiovascular disorders. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 56 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 655 of SEQ ID NO: 56, and b is 15 to 669.
, Both of which a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 56, and where b is a + 14 or more) are excluded. .

Characterization of Protein Encoded by Gene No. 47 When tested against the U937 bone marrow cell line, supernatants taken from cells containing this gene activated the GAS assay. Therefore, this gene is Jak-
It appears to activate myeloid cells via the STAT signaling pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes involved in the Jak-STAT pathway. When tested against the K562 leukemia cell line, supernatants removed from cells containing this gene activated the ISRE assay. Therefore, this gene appears to activate leukemic cells via the Jak-STAT signaling pathway. The interferon-sensitive response element is
It is a promoter element found upstream of many genes involved in the Jak-STAT pathway. The Jak-STAT pathway is a large signaling pathway involved in cell differentiation and proliferation. Therefore, activation of the Jak-STATs pathway, reflected by binding of GAS elements, can be used to indicate proteins involved in cell proliferation and differentiation. Contact with the supernatant of cells expressing the product of this gene increases the calcium permeability of bovine chondrocytes. Therefore, the product of this gene appears to be involved in the signaling pathway initiated when the product of this gene binds to a receptor on the surface of this chondrocyte. Thus, the polynucleotides and polypeptides have uses including, but not limited to, activating bone cells.

[0257]   This gene is expressed primarily in the breast and placenta.

Accordingly, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample and include, but are not limited to, pregnancy disorders including miscarriage, It is useful as a reagent for diagnosis of diseases and conditions. Similarly, polypeptides and antibodies to these polypeptides include
It is useful in providing immunological probes for the differential identification of tissues or cell types.
For many disorders of the tissues or cells, especially the breast and placenta, significantly higher or lower levels than standard gene expression levels (ie, expression levels in healthy tissue or fluid from individuals without disorders). Expression of this gene in
Specific tissues or cell types (eg placenta tissue, breast tissue, bone tissue, cancerous tissue and wound tissue) or body fluids (eg lymph, serum, plasma, urine, synovium, etc.) taken from an individual having such a disorder. Fluid and spinal fluid) or another tissue or cell sample.

Tissue distribution in both the placenta and breast indicates the role of the protein in the treatment and / or detection of miscarriage (in suspected individuals), birth defects, breast cancer, and female infertility. Furthermore, biological assay data strongly indicate that the translation product of this gene is actively involved in the initiation of several signaling pathways and activation of some cell types.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 57 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 666 of SEQ ID NO: 57, and b is 15 to 680.
, Both of which a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 57, and where b is a + 14 or more) are excluded. ..

Characterization of Protein Encoded by Gene No. 48 This gene, which encodes the disclosed cDNA, is believed to be located on chromosome 11. Therefore, the polynucleotide of the present invention is useful as a marker in the linkage analysis of chromosome 11. One embodiment of this gene comprises a polypeptide of the following amino acid sequence: MWGQPPRPVDSVWSSSIPKKS.
VESNDKSHHLHKREH (SEQ ID NO: 362), MTTKAIFTKGN
IDSLSFKSNMWSVYI (SEQ ID NO: 363). Another embodiment is the polynucleotide encoding these polypeptides.

[0262]   This gene is mainly expressed in the pancreas.

Accordingly, the polynucleotides and polypeptides of the present invention provide for the differential identification of tissues or cell types present in a biological sample, as well as for pancreas-related disorders such as diabetes. It is useful as a reagent for diagnosis of diseases and conditions without limitation. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, particularly the endocrine system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in healthy tissues or fluids from individuals without disorders). The expression of this gene is dependent on the specific tissue or cell type (eg, pancreatic tissue, endocrine tissue, metabolic tissue, cancerous tissue and wound tissue) or body fluid (eg, lymph, serum) taken from an individual having such a disorder. , Bile, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

The tissue distribution of this gene in pancreatic tissue indicates that the polynucleotides and polypeptides corresponding to this gene are for the treatment / testing of endocrine and metabolic disorders associated with the pancreas, including diabetes, pancreatitis, and pancreatic cancer. Demonstrate usefulness. Furthermore, this tissue distribution shows that the polynucleotides and polypeptides corresponding to this gene are associated with various endocrine disorders and cancers (especially Addison's disease, Cushing's syndrome), as well as the pancreas (eg, diabetes), adrenal cortex, ovaries, pituitary gland. (Eg hyperpituitary,
Hypothyroidism), thyroid (eg, hyperthyroidism, hypothyroidism), parathyroid gland (eg, hyperparathyroidism, hypoparathyroidism), hypothalamus, and testicular disorders and cancer Shows utility in detection, treatment, and / or prevention.
The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 58 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is any integer of 1 to 510 of SEQ ID NO: 58, and b is 15 to 524.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 58, and b is a + 14 or greater) and are excluded. ..

[0266]     (Characteristics of protein encoded by gene number 49)   This gene is mainly expressed in chondrosarcoma.

Thus, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, as well as cancers of the skeletal system, especially cartilage structures and also these tissues. It is useful as a reagent for the diagnosis of diseases and conditions, including but not limited to diseases related to Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, particularly the skeletal system, significantly higher or lower levels of this gene than standard gene expression levels (ie, expression levels in normal tissues or fluids from non-disordered individuals) are used. The expression of a gene is a particular tissue or cell type (eg, bone tissue, connective tissue, and cancer tissue, and wound tissue) or body fluid (eg, lymph, serum, plasma, etc.) taken from an individual having such a disorder. Urine, synovial fluid, and spinal fluid)
, Or in another tissue or cell sample.

The tissue distribution in cartilage tumors indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the treatment / diagnosis of cartilage disorders including arthritis and cancer. The protein, as well as antibodies to this protein, may show utility as tissue-specific markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 59 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 413 of SEQ ID NO: 59, and b is 15 to 427.
, Both of which a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 59, and where b is a + 14 or more) are excluded. .

(Characteristics of Protein Encoded by Gene No. 50) The translation product of this gene has a sequence having homology with sorbin, which is considered to be important in the production of vitamin C. Furthermore, sorbin is believed to be important in the process of stimulating water and electrolyte absorption in various cells in the body. Butasorbin is active in stimulating water and electrolyte absorption through the mucosa. It served as a regulator of electrolyte absorption in the nasal and intestinal mucosa. This gene was identified in the hypothalamus. This suggests that it may play a role in CNS regulation of water and electrolyte absorption.

This gene is expressed primarily in human hypothalamic tissues from Alzheimer's disease patients.

Thus, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, as well as for neurological disorders (eg, Alzheimer's disease) It is useful as a reagent for diagnosis of diseases and conditions not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, especially the central nervous system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in normal tissues or body fluids from unaffected individuals). The expression of this gene depends on the specific tissue or cell type (
For example, it can be detected in neural tissue, as well as cancer tissue and wound tissue) or body fluids such as lymph, serum, plasma, urine, synovial fluid, and spinal fluid, or another tissue or cell sample.

[0273] Preferred epitopes include the residues: Leu-29 to Le in SEQ ID NO: 209.
The epitopes include the sequences shown as u-37, Gln-65 to Asp-70, Gln-85 to Gly-95.

Tissue distribution in neural tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful in the treatment and diagnosis of Alzheimer's disease.
Furthermore, the translation product of this gene may be useful in the detection and / or recovery of disorders involving CNS regulation of water or electrolyte absorption, based on its homology to porcine sorbin. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 60 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 1249 of SEQ ID NO: 60, and b is 15 to 12
63 is an integer of 63, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 60, and b is a + 14 or greater) and one or more polynucleotides comprising It

Characterization of Protein Encoded by Gene No: 51 This gene is expressed primarily in the synovium, and to a lesser extent in other tissues.

Thus, the polynucleotides and polypeptides of the present invention are for differential identification of tissue or cell types present in a biological sample, and include diseases of the synovium such as synovial sarcoma. , Useful as reagents for diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, especially the synovium, significantly higher or lower levels of this gene than standard gene expression levels (ie, expression levels in normal tissues or fluids from non-disordered individuals). Expression of a gene is a specific tissue or cell type (eg, connective tissue, cancer tissue, and wound tissue) or body fluid (eg, lymph, serum, plasma, urine, synovial fluid) taken from an individual having such a disorder. , And cerebrospinal fluid), or in another tissue or cell sample.

The synovial tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of synovial diseases such as arthritis. Moreover, expression of this gene product in the synovium is associated with disorders and conditions affecting the skeletal system (especially osteoporosis), and disorders affecting connective tissue (eg, trauma, tendinitis, chrondomalacia, and inflammation). Detection and treatment of
For example, various autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma and dermatomyositis, as well as dwarfism, spinal deformities and certain joint abnormalities, and chondrodystrophy (ie congenital vertebral epiphyseal dysplasia, It suggests a role in the diagnosis or treatment of familial osteoarthritis, type II bone dysplasia (Atelosteogenesis type II, Schmidt type metaphyseal dysplasia). The protein as well as antibodies to this protein may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 61 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 706 of SEQ ID NO: 61, and b is 15 to 720.
, Both of which a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 61, and where b is a + 14 or more) are excluded. .

FEATURES OF PROTEIN ENCODED BY GENE NO: 52 This gene is primarily found in fast-growing tissues such as immune and tumor tissues and early-stage developing tissues, and to a lesser extent some other tissues. Expressed in tissues.

Accordingly, the polynucleotides and polypeptides of the present invention include, but are not limited to, for differential identification of tissues or cell types present in a biological sample, as well as immune and growth-related disorders. It is useful as a reagent for diagnosing diseases and conditions that are not controlled. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. Significantly higher than standard gene expression levels (ie, expression levels in normal tissues or body fluids from undiseased individuals) for many disorders of the above tissues or cells, especially immune and fast-growing tissues Or low levels of expression of this gene may result in a specific tissue or cell type (eg, developing tissue, immune tissue, cancer tissue, and wound tissue) or body fluid (eg, lymph, tissue, etc.) taken from an individual having such a disorder. Serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

A preferred epitope is SEQ ID NO: 211 with residues: Ala-28 to Ala.
An epitope is included that includes the sequence shown as -47.

Tissue distribution in immune tissues indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of immune and growth-related disorders. In addition, expression in embryonic tissues and other cell sources targeted to proliferating cells may indicate that this protein may play a role in the regulation of cell division and is useful in the diagnosis and treatment of cancer and other proliferative disorders. Show that you get.
Similarly, embryonic development also involves the decision to involve cell differentiation and / or apoptosis in patterning. Thus, this protein also participates in apoptosis or tissue differentiation and may also be useful in cancer therapy. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 62 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 575 of SEQ ID NO: 62, and b is 15 to 589.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 62, and b is a + 14 or more) are excluded. .

FEATURES OF PROTEIN ENCODED BY GENE NO: 53 One embodiment of this gene comprises a polypeptide of the following amino acid sequence:
DSXLDRRPSGPDVKFLSNHKHHFSMVC (SEQ ID NO: 364).
A further embodiment are polynucleotides encoding these polypeptides.

This gene is expressed primarily in the spleen and, to a lesser extent, in hematopoietic cell types.

Accordingly, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, and include, but are not limited to, immune disorders and hematopoietic disorders. It is useful as a reagent for diagnosis of diseases and conditions. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. With respect to the above-mentioned tissues or cells, particularly disorders of the immune system and hematopoietic system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in healthy tissues or body fluids from individuals without disorders). The expression of this gene is dependent on the specific tissue or cell type (eg,
Spleen tissue, immune system, cancer tissue, and wound tissue) or fluid (eg lymph,
Serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

A preferred epitope is SEQ ID NO: 212 at residues: Cys-25 to Trp.
An epitope including the sequence shown as -30 is included.

The tissue distribution of this gene in spleen tissue indicates that the polynucleotides and polypeptides corresponding to this gene are useful for treating or detecting immune or hematopoietic disorders including arthritis, asthma, immunodeficiency diseases, and leukemia. Is shown. Expression of this gene product in the spleen indicates a role in regulating the proliferation; survival; differentiation; and / or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also indicate utility in treating cancer (eg, by boosting the immune response). Since this gene is expressed in cells of lymphoid origin, the gene or protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above. Therefore, it also includes arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne,
It can also be used as a drug for immunological disorders, including and psoriasis. Moreover, this gene product may have commercial utility in the proliferation of stem cells and directed progenitor cells of various blood lineages, as well as in the differentiation and / or proliferation of various cell types. The protein, as well as antibodies to this protein,
It may show utility as a tumor marker and / or immunotherapeutic target for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 63 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 672 in SEQ ID NO: 63, and b is 15 to 686.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 63, and b is a + 14 or more) are excluded. .

CHARACTERISTICS OF PROTEIN ENCODED BY GENE NO: 54 This gene is expressed predominantly in human normal breast, and to a lesser extent in dendritic cells.

Thus, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, as well as for glandular problems involving cells of epithelial origin, including breast cancer. It is useful as a reagent for diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. With respect to the disorders of the tissues or cells, especially the female endocrine system, significantly higher or lower levels of this gene than standard gene expression levels (ie expression levels in healthy tissues or body fluids from unaffected individuals) The expression of a gene is a particular tissue or cell type (eg, breast tissue, cancer tissue, and wound tissue) or body fluid (eg, body tissue) taken from an individual having such a disorder.
Lymph, serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

A preferred epitope is SEQ ID NO: 213 at residues: Ser-32 to Asn.
An epitope is included that includes the sequence shown as -44.

Tissue distribution in breast tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful in diagnosing or treating both malignant and non-malignant problems of breast tissue, including cancer. Alternatively, due to its expression in dendritic tissue, stromal cells are important for cell production in hematopoietic lineages, so that the polynucleotides and polypeptides corresponding to this gene are associated with anemia, pancytopenia, leukopenia, platelets. It has been shown to be useful in treating and diagnosing hematopoiesis-related disorders such as hypopenia, or leukemia. These uses include ex vivo bone marrow cell culture, bone marrow transplantation, bone marrow reconstitution, neoplastic radiotherapy or chemotherapy. This gene product may also be involved in lymphopoiesis and thus the gene product may be used in immune disorders such as infection, inflammation, allergy, immunodeficiency and the like. Moreover, this gene product may have commercial utility in the proliferation of stem cells and directed progenitor cells of various blood lineages, as well as in the differentiation and / or proliferation of various cell types. The protein, as well as antibodies to this protein, may show utility as tissue-specific markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 64 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 438 of SEQ ID NO: 64, and b is 15 to 452.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 64, and b is a + 14 or more) are excluded. ..

Characterization of Protein Encoded by Gene No. 55 When tested against the U937 bone marrow cell line, supernatants removed from cells containing this gene activated the GAS assay. Therefore, this gene is Jak-
It appears to activate myeloid cells via the STAT signaling pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes involved in the Jak-STAT pathway. The Jak-STAT pathway is a large signaling pathway involved in cell differentiation and proliferation. Therefore, activation of the Jak-STATs pathway, reflected by binding of GAS elements, can be used to indicate proteins involved in cell proliferation and differentiation.

This gene is expressed primarily in early human tissues, immune tissues, and to a lesser extent in other tissues such as the prostate.

Accordingly, the polynucleotides and polypeptides of the invention include, but are not limited to, for differential identification of tissues or cell types present in a biological sample, as well as diseases related to development and immunity. It is useful as a reagent for diagnosing diseases and conditions that are not affected. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. Significantly higher than standard gene expression levels (ie expression levels in normal tissues or body fluids from undiseased individuals) for many disorders of the tissues or cells, particularly immune and early human tissues, or Lower levels of expression of this gene may be associated with specific tissues or cell types (eg, immune tissue, developmental tissue, cancerous tissue and wound tissue) or body fluids (eg, lymph, etc.) taken from an individual having such a disorder. Amniotic fluid, serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

Tissue distribution in embryonic and immune tissues indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of developmental and immune related diseases. The biological activity data supports the claim that the translation products of this gene are useful in the treatment and / or diagnosis of diseases related to the immune system. The protein, as well as antibodies to this protein, may show utility as tissue-specific markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 65 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 356 of SEQ ID NO: 65, and b is 15 to 370.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 65, and b is a + 14 or more) are excluded. ..

(Characteristics of Protein Encoded by Gene No. 56) The translation product of this gene has a sequence homologous to the medicago sativa salt-inducible protein.

[0302]   This gene is mainly expressed in human chronic synovitis.

Accordingly, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, as well as for skeletal or rheumatic disorders (especially chronic synovitis). It is useful as a reagent for diagnosis of diseases and conditions, including but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, especially the skeletal system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in healthy tissues or fluids from unaffected individuals). The expression of this gene may depend on the specific tissue or cell type (eg connective tissue, cancerous tissue and wound tissue) or body fluid (eg lymph, serum, plasma, urine, synovium, etc.) taken from an individual having such a disorder. Fluid and spinal fluid) or another tissue or cell sample.

A preferred epitope is the residue in SEQ ID NO: 215: Lys-30 to Se.
The epitopes include the sequences shown as r-44 and Pro-77 to His-82.

The synovial tissue distribution indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis of chronic synovitis and as therapeutic agents. In addition, expression of this gene product in the synovium is impaired by disorders and conditions affecting the skeletal system (
Detection and treatment of disorders involving connective tissue (eg, arthritis, trauma, tendonitis, chondromalacia, and inflammation), including various autoimmune disorders (eg, rheumatoid arthritis, in particular, osteoporosis). Lupus, scleroderma and dermatomyositis), and dwarfism, spinal deformity and certain joint abnormalities, and chondrodysplasia (ie congenital vertebral epiphyseal dysplasia, familial osteoarthritis, type II osteodystrophy). type II), Schmidt metaphyseal cartilage hypoplasia), suggesting a role in the diagnosis or treatment. The protein as well as antibodies to this protein may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 66 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 973 of SEQ ID NO: 66, and b is 15 to 987.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 66, and b is a + 14 or more) are excluded. .

Characterization of Protein Encoded by Gene No: 57 The translation product of this gene shares high sequence homology with rat and mouse peroxisomal membrane protein (gi | 297437). Peroxisomal membrane proteins appear to play an important role in transporting proteins to organelles. Some human genetic disorders, including peroxisomal biosynthesis, such as Zellweger syndrome, can result from genetic defects in key machinery located in the peroxisomal membrane. When tested against a fibroblast cell line, supernatants removed from cells containing this gene activated the EGR1 assay. Thus, this gene activates fibroblasts via signal transduction pathways. Early proliferative response 1
(EGR1) is a promoter associated with a specific gene. This response, when activated, triggers various tissues and cell types, resulting in the cells undergoing differentiation and proliferation.

[0308]   This gene is expressed primarily in normal human liver.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, and for diseases and conditions, including, but not limited to, diseases of the liver system. It is useful as a reagent for diagnosis. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the above tissues or cells, especially higher than liver disorders and liver metabolic disorders, standard gene expression levels (ie, expression levels in healthy tissues or body fluids from individuals without disorders) or Lower levels of expression of this gene may be associated with specific tissues or cell types (eg liver tissue, cancerous tissue and wound tissue) or body fluids (eg lymph, bile, serum) taken from individuals with such disorders. ,
Plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample.

[0310] A preferred epitope is the residues in SEQ ID NO: 216: Lys-57-Se.
An epitope is included that includes the sequence designated as r-66.

Tissue distribution in the liver indicates that polynucleotides and polypeptides corresponding to this gene are useful in diagnosing and treating liver-related disorders. In addition, its homology is associated with the detection and treatment of many disorders in which the translation product of this gene results from inappropriate transport of the protein to organelles due to defects in peroxisomal membrane proteins such as Zellweger syndrome. Show that it can be useful. The protein and antibodies to this protein may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 67 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 1004 of SEQ ID NO: 67, and b is 15 to 10
Is an integer of 18, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 67, and where b is a + 14 or more) and one or more polynucleotides comprising It

Characterization of Protein Encoded by Gene No. 58 This gene, which encodes the disclosed cDNA, is believed to reside on chromosome 4. Therefore, the polynucleotide related to the present invention is useful as a marker in linkage analysis for chromosome 4.

[0314]   This gene is expressed primarily in human fetal dura.

Accordingly, the polynucleotides and polypeptides of the present invention are directed toward differential identification of tissues or cell types present in a biological sample, as well as of diseases and conditions including but not limited to developmental and neurological disorders. It is useful as a reagent for diagnosis. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, especially the central nervous system, significantly higher or lower levels relative to standard gene expression levels (ie, expression levels in normal tissues or fluids from individuals without the disorder) Expression of this gene in specific tissues or cell types (eg, brain tissue, developing tissue, and cancerous and wound tissue) or body fluids (eg, lymph, amniotic fluid) collected from individuals with such disorders. , Serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample.

A preferred epitope is the residues in SEQ ID NO: 217: Ala-19 to Ly.
There is an epitope including the sequence shown as s-34.

Tissue distribution in neural tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful in diagnosing and treating neurological disorders. Furthermore, the tissue distribution shows that polynucleotides and polypeptides corresponding to this gene are Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome,
Schizophrenia, mania, dementia, delusions, obsessive-compulsive disorder, panic disorder, learning disability, Alstrom syndrome (ALS), autism, and behavioral changes (eating, sleep, pattern,
It is also useful in the detection / treatment of neurodegenerative disease states and behavioral disorders such as balance and cognition). In addition, the gene or gene product may also play a role in the treatment and / or detection of developmental and / or sexually related disorders associated with the developing embryo. The protein and antibodies to this protein may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 68 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 748 of SEQ ID NO: 68, and b is 15 to 762.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 68, and b is a + 14 or more) are excluded. .

Characterization of Protein Encoded by Gene No. 59 This gene, which encodes the disclosed cDNA, is believed to reside on chromosome 16. Therefore, the polynucleotide related to the present invention is useful for linkage analysis on chromosome 16.

[0320]   This gene is expressed primarily in T helper cells and human uterine cancer.

Accordingly, the polynucleotides and polypeptides of the invention include, for the differential identification of tissues or cell types present in a biological sample, as well as for diseases associated with hematopoietic and uterine disorders. It is useful as a reagent for diagnosis of non-limiting diseases and conditions. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher than standard gene expression levels (ie, expression levels in normal tissues or fluids from unaffected individuals) for many disorders of the tissues or cells, particularly the immune system and female reproductive system, or Lower levels of expression of this gene may be associated with specific tissues or cell types (eg, immune, reproductive, and cancerous and wound tissues) or bodily fluids (eg, immune and reproductive tissues) taken from an individual having such a disorder. Lymph, amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample.

Tissue distribution in T helper cells and uterine tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of disorders associated with both the immune system and the female reproductive system. Expression of this gene in T cells indicates that it plays a role in proliferation; survival; differentiation; and / or regulation of all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also have utility in treating cancer (eg, by boosting the immune response). Since this gene is expressed in cells of lymphoid origin, the gene or protein,
And antibodies to this protein may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above. Therefore, it may also be used as a drug against immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne and psoriasis. Moreover, this gene product may have commercial utility in the expansion of stem cells and the expansion of committed progenitor cells of various blood lineages, and in the differentiation and / or proliferation of various cell types. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 69 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is any integer of 1 to 616 of SEQ ID NO: 69, and b is 15 to 6
An integer of 30, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 69, and b is a + 14 or greater) 1
One or more polynucleotides are excluded.

CHARACTERISTICS OF PROTEIN ENCODED BY GENE NO: 60 This gene is expressed primarily in human fetal epithelium and to a lesser extent in testis.

Thus, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, and include developmental or reproductive disorders, as well as disorders of the integumentary system. It is useful as a reagent for diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the above tissues or cells, especially for diseases involving the epithelium, significantly higher or lower levels than standard gene expression levels (ie, expression levels in normal tissues or fluids from unaffected individuals). Expression of this gene in specific tissues or cell types (eg, epithelial tissue, testis tissue, developmental tissue, and cancerous and wound tissue) taken from an individual having such a disorder, or body fluids (eg, Lymph, serum, amniotic fluid, plasma, urine, synovial fluid and spinal fluid), or another tissue or cell sample.

Tissue distribution in fetal epithelium and testis indicates that polynucleotides and polypeptides corresponding to this gene are useful in diagnosing and treating epithelial-related diseases. In addition, polynucleotides and polypeptides corresponding to this gene may be associated with congenital diseases (eg, nevus, mole, nevus, Mongolian spots, hemangiomas, wine-like syndrome), integumental tumors (eg, , Keratosis, Bowen's disease,
Basal cell carcinoma, squamous cell carcinoma, malignant melanoma, Paget's disease, mycosis fungoides and Kaposi's sarcoma), skin damage and inflammation (eg, wounds, rashes, eczema disorders, psoriasis, dermatitis) atherosclerosis, urticaria ( uticaria), eczema, photophobia, autoimmune diseases (ie lupus erythematosus, vitiligo, dermatomyositis, localized scleroderma, scleroderma, pemphigoid,
And pemphigus), keloids, erythema, petechiae, purpura, and blepharoptosis, and are useful in the treatment, diagnosis and / or prevention of various skin diseases. In addition, such disorders may include viral and bacterial infections of the skin (eg, herpes simplex, varicella, varicella, varicella, molluscum contagiosum, herpes zoster, swelling, cellulitis, erysipelas, impetigo, tinea, sweat. It can predispose to susceptibility to ringworm and ringworm. Furthermore, it has been shown that the protein product of this gene is useful for proper testicular function (eg, endocrine function, sperm maturation), and treatment and diagnosis of cancer-related conditions. Therefore, this gene product is associated with male infertility and / or
Alternatively, it is useful in treating impotence. This gene product is also useful in assays designed to identify binding agents, as such agents (antagonists) are useful as male contraceptive agents. Similarly, this protein is considered to be useful in the treatment and / or diagnosis of testicular cancer. Testis is also the active gene expression site of transcripts that can be expressed at particularly low levels in other tissues of the body. Thus, the gene product may be expressed in other specific tissues or organs, where it is expressed in some of the possible target indicators such as hematopoiesis, inflammation, bone formation and renal function. May play relevant functional roles in other processes.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 70 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 926 of SEQ ID NO: 70, and b is 15 to 940.
, Both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 70, and b is a + 14 or more) are excluded. .

Characterization of Protein Encoded by Gene No: 61 When tested against both the U937 bone marrow cell line and the Jurkat T cell line, supernatant taken from cells containing this gene activated the GAS assay. did. Therefore, this gene appears to activate both T cells and myeloid cells via the Jak-STAT signaling pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes involved in the Jak-STAT pathway. The Jak-STAT pathway is a large signaling pathway involved in cell differentiation and proliferation. Therefore, activation of the Jak-STAT pathway, reflected by the binding of GAS elements, can be used to indicate proteins involved in cell proliferation and differentiation.

[0329]   This gene is mainly expressed in human adult lymphocytes and early human lungs.

Accordingly, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample and include, but are not limited to, immune disorders, lymphohistitis, and lung disorders. It is useful as a reagent for diagnosis of diseases and conditions without limitation. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher than standard gene expression levels (ie expression levels in normal tissues or body fluids from unaffected individuals) for many disorders of the tissues or cells, particularly the immune and respiratory systems, or Lower levels of expression of this gene may be associated with specific tissues or cell types (eg, immune, cancerous and wound tissues) or body fluids (eg, lymph, serum, etc.) taken from individuals with such disorders. Plasma, urine, synovial fluid and spinal fluid), or another tissue or cell sample.

Tissue distribution in the adult lymph indicates that polynucleotides and polypeptides corresponding to this gene are useful in diagnosing and treating diseases related to the immune and respiratory systems. Furthermore, expression of this gene product in lymph nodes indicates that it plays a role in controlling proliferation, survival, differentiation; and / or activation of all potential hematopoietic cell lineages, including blood stem cells. . This gene product may be involved in the control of cytokine production, antigen presentation, or other processes that may also have utility in treating cancer (eg, by boosting the immune response). Since this gene is expressed in cells of lymphoid origin, the gene or protein, and antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above. Therefore, it can also be used as a drug against immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. Moreover, this gene product may have commercial utility in the expansion of stem cells and the expansion of committed progenitor cells of various blood lineages, and in the differentiation and / or proliferation of various cell types. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above. Biological activity data support the idea that the translation product of this gene may play an important role in the activity of the immune system as it is an activator of various cells of the immune system.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 71 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 1089 of SEQ ID NO: 71, and b is 15 to 1589.
Is an integer of 1103, wherein both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 71, and b is a + 14 or greater). Excluded.

Characterization of Protein Encoded by Gene No: 62 This gene is expressed predominantly in glioblastoma and anergic T cells.

Thus, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in biological samples, as well as for neurological and immune disorders such as glioblastoma cerebrum. It is useful as a reagent for diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher or lower than standard gene expression levels (ie, expression levels in normal tissues or body fluids from unaffected individuals) for many disorders of the tissues or cells, particularly the CNS and immune system Levels of this gene expressed in specific tissues or cell types (eg, immune, nervous, and cancerous and wound tissues) or body fluids (eg, lymph, serum) taken from individuals with such disorders. , Plasma, urine, synovial fluid, and spinal fluid)
Or it can be detected in another tissue or cell sample.

Tissue distribution in T cells indicates that polynucleotides and polypeptides corresponding to this gene are useful in diagnosing and treating disorders related to the CNS and immune system. Furthermore, expression of this gene product in T cells suggests a role in the control of proliferation, survival, differentiation, and / or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the control of cytokine production, antigen presentation, or other processes that may also have utility in treating cancer (eg, by boosting the immune response). Since this gene is expressed in cells of lymphoid origin, the gene or protein, and antibodies to this protein, are useful as tumor markers for the tissues listed above and
/ Or may show utility as an immunotherapeutic target. Therefore, it can also be used as a drug against immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. Moreover, this gene product may have commercial utility in the expansion of stem cells and the expansion of committed progenitor cells of various blood lineages, and in the differentiation and / or proliferation of various cell types. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 72 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 885 of SEQ ID NO: 72, and b is 15 to 899.
, Both of which a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 72, and where b is a + 14 or more) are excluded. .

CHARACTERISTICS OF PROTEIN ENCODED BY GENE NO: 63 One embodiment of this gene includes a polypeptide having the following amino acid sequence: CLAEAVSVIQSIPIFNETGRFSFTLPFPVKIKVRFS
FFLQIYLIMIFLGLYINFRHLYKQRRRRRYGQKKKKRS
TKKKDLDGFLPV (SEQ ID NO: 365). A further embodiment are polynucleotides encoding these polypeptides.

[0338]   This gene is mainly expressed in keratinocytes and brain.

Thus, the polynucleotides and polypeptides of the invention include, for the differential identification of tissues or cell types present in biological samples, as well as for integumental disorders, or neurological and behavioral disorders. It is useful as a reagent for diagnosis of non-limiting diseases and conditions. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. With respect to many disorders of the tissues or cells, especially the nervous system,
Significantly higher or lower levels of expression of this gene relative to normal gene expression levels (ie, expression levels in healthy tissue or body fluids from non-disordered individuals) are obtained from individuals with such disorders. A particular tissue or cell type that has been harvested (eg, brain tissue, integumental tissue, and cancerous and wound tissue) or body fluid (eg, lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or It can be routinely detected in cell samples.

The tissue distribution of this gene in nervous tissue is such that the polynucleotides and polypeptides corresponding to this gene are associated with neurodegenerative disease states and Alzheimer's disease, Parkinson's disease, Huntington's disease, schizophrenia, mania, dementia, delusions. It is useful in the treatment and / or detection of behavioral disorders such as symptom, obsessive-compulsive disorder, and panic disorder. Alternatively, expression in keratinocytes is such that the polynucleotides and polypeptides corresponding to this gene are congenital disorders (ie, nevus (nev
us), nevus (mole), freckle, Mongolian spot, hemangiomas, wine-like syndrome), integumental tumor (eg keratoses, Bowen's disease, basal cell carcinoma, squamous cell carcinoma, malignant melanoma, Paget's disease, fungus) Mycosis fungoides and Kaposi's sarcoma), skin damage and inflammation (ie wounds, rashes, eczema disorders, psoriasis, dermatitis), atherosclerosis, (utica
ria), eczema, photophobia, autoimmune diseases (eg lupus erythematosus, vitiligo, dermatomyositis,
Localized scleroderma, scleroderma, pemphigoid, and pemphigus), keloids, erythema, petechiae, purpura, and various skin diseases including blepharoptosis, for the treatment, diagnosis and / or prevention Demonstrate usefulness. In addition, such disorders can predispose the skin to increased susceptibility to viral and bacterial infections (ie, herpes simplex, warts, chickenpox, molluscum contagiosum, shingles, swelling, cellulitis, erysipelas, pus. Scab, ringworm (t
inea), tinea rubrum, and ringworm). In addition, the protein product of this gene is found in various connective tissue disorders such as arthritis, trauma, tendinitis, cartilage softening, and inflammation, rheumatoid arthritis, lupus, scleroderma, and autoimmune diseases such as dermatomyositis. , And treatment of dwarfism, spinal deformities and specific joint abnormalities, and chondrodysplasia (ie congenital vertebral epiphyseal dysplasia, familial osteoarthritis, type II osteogenesis dysgenesis, Schmidt metaphyseal chondrodysplasia) Alternatively it may be useful for diagnosis. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 73 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 535 of SEQ ID NO: 73, and b is 15 to 549.
, Both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 73, and b is a + 14 or more) are excluded. .

FEATURES OF PROTEIN ENCODED BY GENE NO: 64 In certain embodiments, a polypeptide of the present invention comprises the following amino acid sequence: LCSTPVPTLFCPRIVLEVLVVLRSISEQCRRVSSQV
TVASELRHRQWVERTLRSRQRQNYLR (SEQ ID NO: 366) Polynucleotides encoding these polypeptides are also included in the invention.

[0343]   This gene is mainly expressed in giant cell tumor of bone.

Thus, the polypeptides and polynucleotides of the present invention are useful for the differential identification of tissues or cell types present in biological samples, as well as skeletal disorders, and hematopoietic and immune system disorders, particularly cancer. Are useful as reagents for the diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher than standard gene expression levels (ie, expression levels in normal tissues or body fluids from undiseased individuals) for many disorders of the tissues or cells, particularly bone, immune system and hematopoietic system Alternatively, lower levels of expression of this gene may be associated with specific tissue or cell types (eg, bone tissue, hematopoietic tissue, and cancerous and wound tissue) or bodily fluids (eg, bone tissue, hematopoietic tissue) collected from an individual having such a disorder. Lymph, serum, plasma, urine, synovial fluid,
And cerebrospinal fluid) or another tissue or cell sample.

A preferred epitope is the residues in SEQ ID NO: 223: Ser-59 to Gl.
An epitope is included that includes the sequence designated as u-67.

Tissue distribution in giant cell tumors of bone indicates that polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of bone, immune and hematopoietic disorders, and cancer. In addition, this protein is especially found in osteoporosis, bone cancer,
And may serve as therapeutic agents for the detection and treatment (eg, diagnosis or treatment of various autoimmune disorders) of disorders and conditions affecting connective tissue (eg, arthritis, trauma, tendinitis, cartilage softening, and inflammation). . For example, rheumatoid arthritis, lupus, scleroderma, and dermatomyositis, as well as dwarfism, spinal deformities, and specific joint abnormalities, and chondrodysplasia (ie congenital vertebral epiphyseal dysplasia, familial osteoarthritis, II Type osteogenesis hypoplasia, Schmidt type metaphyseal cartilage hypoplasia). The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 74 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 576 in SEQ ID NO: 74, and b is 15 to 590.
, Both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 74, and b is a + 14 or more) are excluded. .

(Characteristics of Protein Encoded by Gene No. 65) When tested on a skin fibroblast cell line, the supernatant taken from cells having this gene showed EGR1 (early growth response gene 1) promoter element. Was activated. Therefore, this gene appears to activate fibroblasts via the EGR1 signaling pathway. EGR1 is a signaling pathway separate from Jak-STAT, and genes containing the EGR1 promoter, when activated in various tissues and cells, lead cells to undergo differentiation and proliferation. In a particular embodiment, the polypeptide of the invention comprises the following amino acid sequence: ARGETAYDGAAVEFQEPLSSCLFSSSLNPHHWPTLGV.
GRPVMLTLEDKD (SEQ ID NO: 367), ELLQCQMLEASTI
HLHHPRPGFPALCSFLGGFRHHLHHDALCIRVLPEDL
EAKLCVSLHQLLHRRGLCLPGFGAACPGDQGSEDEAR
PPAVLRAVALLRAGLRHLSVHSGWYHLPHSRNGLPL
LALVVHFPEYGGGPREPVPGQSGEFGRRTELSTKGD
TGDSRNSHLAQDMASLPFFKPCECTTHVAVCSPPHPL
CQYLCL (SEQ ID NO: 368), LQCQMLEASTLIHLHHPRPG
FPALCSFL (SEQ ID NO: 369), HQLLHRGLCLPGFGAACP
GDQGSEDEARPPA (SEQ ID NO: 370), and / or LALVVH
FPEYGGGPREPVPGQSGEFGR (SEQ ID NO: 371). Polynucleotides encoding these polypeptides are also included in the present invention.

[0349]   This gene is expressed primarily in the testis.

Thus, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, and include male reproductive and endocrine disorders, cancer, especially testicular cancer. , Useful as reagents for diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher than standard gene expression levels (ie expression levels in normal tissues or fluids from non-disordered individuals) for many disorders of the tissues or cells, particularly the male reproductive and endocrine systems, or Lower levels of expression of this gene are associated with specific tissues or cell types (eg, reproductive, testis, endocrine, and cancerous and wound tissues) or body fluids collected from individuals with such disorders. For example, lymph, semen, serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

A preferred epitope is the residue in SEQ ID NO: 224: Lys-53 to Le.
u-60, Pro-94 to Gln-99, Ser-176 to Gly-184, S
The epitopes including the sequences shown as er-199 to Val-207 are included.

Tissue distribution in testis, coupled with detected EGR1 bioactivity, indicates that the polynucleotides and polypeptides corresponding to this gene contain abnormal testicular function (eg, endocrine function, sperm maturation) and male reproductive and endocrine. Shows utility in the diagnosis and treatment of disorders. Moreover, this tissue distribution may also be useful in the diagnosis and treatment of various proliferative disorders, especially testicular cancer, in terms of EGR1 activity. The protein and antibodies corresponding to this protein may show utility as tumor markers and / or immunotherapy targets against the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 75 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is any integer of 1 to 1042 of SEQ ID NO: 75, and b is 15 to 10
56 is an integer of 56, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 75, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

FEATURES OF PROTEIN ENCODED BY GENE NO: 66 In certain embodiments, polypeptides of the invention include the following amino acid sequences:

[0355]

[Chemical 6] Polynucleotides encoding these polypeptides are also included in the invention.

[0356]   This gene is mainly expressed in the pituitary gland.

Accordingly, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, and include, but are not limited to, endocrine disorders such as dwarfism. It is useful as a reagent for diagnosing diseases and conditions that are not controlled. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, particularly the endocrine system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in healthy tissues or fluids from individuals without disorders). The expression of this gene is dependent on the specific tissue or cell type (eg,
Endocrine, immune, and cancerous and wound tissues) or body fluids (eg, lymph, serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

Tissue distribution in the pituitary is such that polynucleotides and polypeptides corresponding to this gene are useful in the treatment and diagnosis of disorders of the pituitary and endocrine systems. Furthermore, taking into account the importance of the pituitary gland in functioning as a major regulator of various endocrine glands, the protein product of this gene is associated with various endocrine disorders and cancers, especially Addison's disease, Cushing's syndrome, and Pancreas (eg diabetes)
, Adrenal cortex, ovary, pituitary gland (eg hyperpituitary gland, hypopituitarism),
Thyroid (eg, hyperthyroidism, hypothyroidism), parathyroid (eg,
Hyperparathyroidism, hypoparathyroidism, hypothala
mus), and testicular disorders and / or cancers are useful for detection, treatment and / or prevention. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 76 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 916 of SEQ ID NO: 76, and b is 15 to 930.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 76, and b is a + 14 or more) are excluded. .

CHARACTERISTICS OF PROTEIN ENCODED BY GENE NO: 67 In certain embodiments, the polypeptides of the invention include the following amino acid sequences:

[0361]

[Chemical 7] Polynucleotides encoding these polypeptides are also included in the present invention.
This gene, which encodes the disclosed cDNA, is believed to reside on chromosome 7. Therefore, the polynucleotide related to the present invention is useful as a marker in linkage analysis for chromosome 7.

This gene is expressed primarily in the developing brain, liver, and heart, and to a lesser extent in cancerous tissues.

Accordingly, the polynucleotides and polypeptides of the present invention may be used for the differential identification of tissues or cell types present in a biological sample, and in addition to cancer, developmental disorders, neurological disorders, liver disorders, or It is useful as a reagent for the diagnosis of diseases and conditions including, but not limited to cardiopulmonary disorders and hematopoietic disorders. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significant to standard gene expression levels (ie, expression levels in normal tissues or body fluids from undiseased individuals) for the above tissues or cells, particularly fetal tissues, and for many disorders of the hematopoietic and nervous systems. Higher or lower levels of expression of this gene may be associated with a particular tissue or cell type (e.g., developing tissue, neural tissue, hematopoietic tissue, liver tissue, cardiovascular tissue, derived from an individual with such a disorder, Lung tissue, and cancerous and wound tissue) or body fluids (eg, lymph, amniotic fluid, bile, serum, pulmonary detergent lavage or sputum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample In, it can be detected.

A preferred epitope is the residue in SEQ ID NO: 226: Glu-67 to As.
n-74, Glu-88 to Asn-93, Lys-95 to Ser-105, Ar
g-152 to Ala-164, Ala-204 to Arg-210, Phe-25
4 to Thr-262, Pro-295 to His-311 are included in the epitopes.

Tissue distribution in the developing brain indicates that polynucleotides and polypeptides corresponding to this gene are useful in the treatment and diagnosis of hematopoietic and developmental diseases, as well as cancer. Furthermore, polynucleotides and polypeptides corresponding to this gene, Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, meningitis, encephalitis, demyelinating disease, peripheral neuropathy, neoplasia, trauma, congenital malformation, Spinal cord injury, ischemia, and infarction, aneurysm, hemorrhage, schizophrenia, mania, dementia, delusion, obsessive-compulsive disorder, fear disorder, learning disability, ALS, psychosis, autism, and behavioral changes ( It is useful in the detection / treatment of neurodegenerative disease states (including nutritional supplementation, sleep patterns, balance, and cognitive disorders), behavioral disorders, or inflammatory conditions. In addition, increased expression of this gene product in the brain indicates that it plays a role in normal neural function. Potentially, this gene product may be involved in synapse formation, nerve conduction, learning, recognition, homeostasis, or neural differentiation or survival. Furthermore, it is shown that this gene or gene product may play a role in the treatment and / or detection of developing embryos, sex-linked disorders, or disorders of the circulatory system. Alternatively, the relatively specific expression of this gene product during embryogenesis indicates that it may be central to the growth, maintenance, and / or differentiation of various cell types during development. This gene product may also act as a morphogen that controls cell and tissue type specificity. Due to its potential role in proliferation and differentiation, this gene product includes adult tissue regeneration and cancer (including but not limited to tissues and cells: lung, immune, nerve,
Applicable for the treatment of hematopoiesis, or liver tissue). The protein and antibodies to the protein are tumor markers for the tissues listed above and / or
Alternatively, it may show utility as a target for immunotherapy.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 77 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 4449 of SEQ ID NO: 77, and b is 15 to 44.
63 is an integer of 63, wherein both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 77, and b is a + 14 or more) are excluded. It

Feature of Protein Encoded by Gene No: 68 The translation product of this gene shares sequence homology with the putative yeast transmembrane protein. This putative yeast transmembrane protein may play an important role in controlling intercellular signaling, intracellular trafficking, or cell homeostasis. In a particular embodiment, the polypeptide of the invention comprises the following amino acid sequence:

[0368]

[Chemical 8] Polynucleotides encoding these polypeptides are also encompassed by the present invention.

This gene is expressed primarily in lung, immune cells, epididymis, and testis tissue. This gene is mainly expressed in the human frontal cortex of patients with schizophrenia.

Thus, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in biological samples, and for reproductive, immune, pulmonary, as well as endothelial and epithelial tissues. Are useful as reagents for the diagnosis of diseases and conditions including, but not limited to Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. The tissues or cells, especially the immune system,
For many disorders of the respiratory and reproductive systems, significantly higher or lower levels of this gene relative to standard gene expression levels (ie, expression levels in healthy tissue or body fluids from unaffected individuals) Expression is in a particular tissue or cell type taken from an individual having such a disorder (eg, lung tissue, immune tissue,
Reproductive tissue, testis tissue, epididymal tissue, endothelial tissue, integumental tissue, and cancerous and wound tissues) or body fluids (eg lymph, semen, lung detergent lavage fluid or sputum, serum, plasma, urine, synovial fluid) , And cerebrospinal fluid) or another tissue or cell sample, a preferred epitope is SEQ ID NO: 227 with residues: Arg-45-Th.
r-52, Tyr-60 to Gly-66, Ala-87 to Trp-92, Leu
An epitope including the sequence shown as -105 to Ser-115 can be mentioned.

This tissue distribution and homology with the putative transmembrane protein indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the treatment and diagnosis of diseases of the reproductive, pulmonary and immune systems. In addition, the protein product of this gene may include abnormal testicular function, male infertility, impotence, or related endocrine disorders,
It may be useful in diagnosing, treating, and / or preventing various male reproductive disorders, including but not limited to. Proteins can also serve as contraceptives. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 78 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 777 of SEQ ID NO: 78, and b is 15 to 791.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 78, and b is a + 14 or more) are excluded. .

FEATURES OF PROTEIN ENCODED BY GENE NO: 69 In certain embodiments, the polypeptides of the invention include the following amino acid sequences: SENRIYRNGLEKMRREVIGIGRSSSICLDQQVKA
GNAVHHQWLKYVCWMVVVVGGSGVGGDGGNLGM (SEQ ID NO: 382). Polynucleotides encoding these polypeptides are also included in the present invention.

[0374]   This gene is mainly expressed in PMA-induced T cells.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample and for immune or hematopoietic disorders such as inflammatory or immunodeficient conditions. Are useful as reagents for the diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, especially the immune system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in normal tissues or fluids from individuals without disorders). The expression of this gene is dependent on the specific tissue or cell type (eg, immune, hematopoietic, and cancerous and wounded tissue) or body fluid (eg, lymph, serum, plasma) taken from an individual having such a disorder. , Urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

[0376] A preferred epitope is the residues in SEQ ID NO: 228: Ser-62 to Th.
The epitopes include the sequences shown as r-73 and Phe-80 to Gln-88.

The tissue distribution in T cells indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the study and diagnosis of immune system disorders. More specifically, this gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes, and also suggests utility in treating cancer (eg, by boosting the immune response). obtain. As this gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune function. Therefore, it is also arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, chronic granulomatosis, inflammatory bowel disease, sepsis, contusions, neutropenia, neutrophilia,
Psoriasis, hypersensitivity (eg, T cell-mediated cytotoxicity); Immune response to transplant organs and tissues (eg, host vs. graft and graft vs. host disease) or autoimmune disorder (eg.
For example, as an agent for immunological disorders, including autoimmune infertility, lens tissue injury, demyelination, systemic lupus erythematosus, drug-induced hemolytic anemia, rheumatoid arthritis, Sjögren's disease, scleroderma) and tissues Can also be used. Moreover, this gene product may have commercial utility in the proliferation of stem cells and associated progenitor cells of various blood lineages, as well as in the differentiation and / or proliferation of various cell types. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 79 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 1278 of SEQ ID NO: 79, and b is 15 to 12
Is an integer of 92, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 79, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

[0379]     (Characteristics of protein encoded by gene number 70)   This gene is expressed primarily in monocytes.

Accordingly, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in biological samples, as well as for immune or hematopoietic disorders (leukemia, lymphoma, AIDS, arthritis and asthma). Are useful as reagents for the diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, especially the immune system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in normal tissues or fluids from individuals without disorders). The expression of this gene
Specific tissues or cell types (eg, immune, hematopoietic, and cancerous and wound tissues) or body fluids (eg, lymph, serum, plasma, urine, synovial fluid, etc.) collected from individuals with such disorders. And cerebrospinal fluid) or another tissue or cell sample.

Tissue distribution in monocytes indicates that polynucleotides and polypeptides corresponding to this gene are diagnostic of immune disorders (leukemia, lymphoma, immunodeficiency (eg AIDS), immunosuppressive status (transplantation) and hematopoietic disorders). Shows utility in treatment. Furthermore, this gene product may be applicable to common microbial infections, inflammations, or cancer conditions. In addition, because stromal cells are important in the production of cells of the hematopoietic lineage, this gene is associated with anemia, pancytopenia, leukopenia, thrombocytopenia,
Alternatively, it may be useful in the treatment and diagnosis of hematopoietic-related disorders such as leukemia.
Its use includes culturing bone marrow cells ex vivo, bone marrow transplantation, bone marrow reconstitution, radiation therapy, or neoplastic chemotherapy. This gene product may also be involved in lymphocyte production and therefore may be used in immune disorders such as infection, inflammation, allergies, immune deficiencies. In addition, this gene product may have commercial utility in the proliferation of stem cells and associated progenitor cells of various blood lineages, as well as in the differentiation and / or proliferation of various cell types. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 80 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 1269 of SEQ ID NO: 80, and b is 15 to 12
Is an integer of 83, wherein both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 80, and b is a + 14 or more) are excluded. It

(Characteristics of Protein Encoded by Gene No. 71) When tested on a skin fibroblast cell line, the supernatant taken from cells containing this gene contains the EGR1 (immediate gene 1) promoter element. Activated. Therefore, this gene appears to activate fibroblasts via the EGR1 signaling pathway. EGR1 is a signal transduction pathway separate from Jak-STAT, and a gene containing the EGR1 promoter is induced in various tissues and cell types when activated, and this gene causes cells to undergo differentiation and proliferation. Lead to. In a particular embodiment, a polypeptide of the invention comprises the following amino acid sequence: NWSGRRLRMWPSAALSPAVSSPARALTSPPKPLKGE
VWRWRWLLGSRAVGLFAFIALGTQSPLLRRACLPVR
QSWGCSEHKAYPILRLQPDLETQVGPGHGVNWDLRT
QIRTIGELGGGDGGCSEMRPLF (SEQ ID NO: 383), and / or NLFSTPCKRRQKLIKLEWTEAPNVALRCSLSCSLI
PGLSPDLSSEAPEGRSVAKMEIARQQSCWLVCIYCF
RNPESTLAGPLPACEAELGLLRAQGLPHPASPARLG
NTGGAWPRSKLGSQNTN (SEQ ID NO: 384), SSPALALTS
PPKPLKGEVWRWRWLLG (SEQ ID NO: 385), EHKAYPILR
LQPDLETQVGPGHGVNWDL (SEQ ID NO: 386), and / or ALRCSLSCSLIPGLSPDLSSEAPEGRSV (SEQ ID NO: 387).
). Polynucleotides encoding these polypeptides are also included in the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 11. Therefore, the polynucleotide related to the present invention is useful as a marker in the linkage analysis of chromosome 11.

[0384]   This gene is expressed primarily in placenta.

Thus, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample and include developmental abnormalities, fetal defects, prenatal disorders and cancer, It is useful as a reagent for diagnosing diseases and conditions, which is not limited thereto. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, particularly the reproductive system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in normal tissues or fluids from individuals without disorders). The expression of this gene is dependent on the specific tissue or cell type (eg, reproductive, placental, and cancerous and wound tissue) or body fluid (eg, lymph, amniotic fluid, etc.) taken from an individual having such a disorder. Serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

A preferred epitope is the residue in SEQ ID NO: 230: Gly-22 to Gly-2.
9, including epitopes containing the sequences shown as Gln-37 to Ala-44.

This tissue distribution in placental tissue, combined with the detected EGR1 biological activity, indicates that the polynucleotides and polypeptides corresponding to this gene are used to treat developmental abnormalities, fetal defects, and prenatal disorders. Show usefulness for diagnosis. In addition, this tissue distribution may be useful in the detection and treatment of ovarian and endometrial cancers. The protein, as well as antibodies to the protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 81 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 694 of SEQ ID NO: 81, and b is 15 to 708.
, Both of which a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 81, and where b is a + 14 or more) are excluded. .

FEATURES OF PROTEIN ENCODED BY GENE NO: 72 In a particular embodiment, a polypeptide of the invention comprises the following amino acid sequence: LAPECCCGSVTYPRALVPRPCCPEPRAPLQLTLG.
LFSANPVNASPWGRCRSRRGRGNLPLGHPVSTAFSS
GDS (SEQ ID NO: 388), and / or NTLHSKLVPSVYHSTE
KSCLVCFGMCPSIYKKKMKSVLLIGTRMLLLSHISQ
GPRPEAVLPRAPPSPSAAHPWLVFRKPGKRKPLGQMQ
KQKREGKPASGSPC (SEQ ID NO: 389), YPRALVPPRPCCP
EPRAPLQLTLGLF (SEQ ID NO: 390), and / or VLLIGT
RMLLWLSHISQGPRPEVALPR (SEQ ID NO: 391). Polynucleotides encoding these polypeptides are also included in the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 7. Therefore, the polynucleotide related to the present invention is useful as a marker in the linkage analysis of chromosome 7.

This gene is expressed primarily in the infant brain, and to a lesser extent in the placenta.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, and for diseases including, but not limited to, developmental and neurological disorders. And are useful as reagents for diagnosing conditions. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher or higher than standard gene expression levels (ie, expression levels in normal tissues or body fluids from unaffected individuals) for many disorders of the tissues or cells, particularly the developmental and nervous systems Low levels of expression of this gene may result in specific tissues or cell types (eg, reproductive, developing, nervous, and cancerous and wound tissues) or body fluids collected from individuals with such disorders. (Eg, lymph, amniotic fluid, serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

A preferred epitope is the residue in SEQ ID NO: 231: Thr-45-Arg-5.
Includes epitopes that include the sequence shown as 0.

This tissue distribution in the fetal brain and placenta indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the study, diagnosis and treatment of various developmental and neurological disorders and diseases. . The protein product of this gene is associated with neurodegenerative disease states, behavioral disorders or inflammation conditions (
For example, Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, meningitis, encephalitis, demyelinating disease, peripheral neuropathy, neoplasia, trauma, congenital abnormalities, spinal cord injury, ischemia and infarction, aneurysm, hemorrhage , Schizophrenia, mania, dementia, paranoia, obsessive-compulsive disorder, panic disorder, learning disability, ALS, psychosis, autism, and behavioral changes (
(Including impairment of nutritional support, sleep patterns, balance, and perception)). In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is associated with synapse formation, neurotransmission, learning, recognition, homeostasis, or neuronal differentiation or survival. In addition, the gene or gene product may also play a role in the treatment and / or detection of developmental, sex-linked, or cardiovascular disorders associated with the developing embryo. Expression in fetal tissues and other cell sources characterized by proliferating cells may play a role in the regulation of cell division by this protein and may indicate utility in the diagnosis and treatment of cancer and other proliferative disorders. Indicates that. Similarly, developing tissue relies on decisions involved in cell differentiation and / or apoptosis in patterning. Therefore, this protein may also be involved in apoptosis or tissue differentiation and may be useful in cancer therapy. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 82 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 1450 of SEQ ID NO: 82, and b is 15 to 14
64 is an integer of 64, wherein both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 82, and b is a + 14 or more) are excluded. It

CHARACTERISTICS OF PROTEIN ENCODED BY GENE NO: 73 In certain embodiments, a polypeptide of the invention comprises the following amino acid sequence: WIVMFGGKVLKIKDFMSTYSHTYTHTHMHAHTHT.
HTTLSLLQNVLTLVAISDSDKALLIF (SEQ ID NO: 392)
, MTLLIAEKTWRRPWPCQWGYLGAEGDRHLEGRSLS
LRHLQGAETPVLNPDLQLPSHIGKQAWSHLAGSL (SEQ ID NO: 393), MSTYSHTYTHTHMHAHTTHTHTLTLSL (
SEQ ID NO: 394), and / or GAEGDRHLEGRSLSLRHLQG
AET (SEQ ID NO: 395). Polynucleotides encoding these polypeptides are also included in the invention.

[0396]   This gene is mainly expressed in the spleen of patients with lymphocytic leukemia.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in biological samples, as well as lymphocytic leukemia and other cancers, as well as immune disorders (eg, AIDS). , Arthritis and asthma), and are useful as reagents for the diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, especially the immune system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in healthy tissues or fluids from unaffected individuals). The expression of this gene is dependent on the expression of a particular tissue or cell type (eg, immune, hematopoietic, and cancerous and wounded tissue) or body fluid (eg, lymph,
Serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

This tissue distribution in the spleen indicates that the polynucleotides and polypeptides corresponding to this gene are associated with lymphocytic leukemia and other cancers, as well as other immune disorders and conditions including AIDS, arthritis, asthma and microbial infections. Shows utility in diagnosis and treatment. Furthermore, because stromal cells are important in the production of cells of the hematopoietic lineage, the protein product of this gene is associated with disorders associated with hematopoiesis (eg, anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia). It may be useful in treatment and diagnosis. This use includes bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow repopulation, neoplastic radiotherapy or chemotherapy. The gene product may also be associated with lymphopoiesis and thus the gene product may be used in immune disorders such as infectious diseases, inflammation, allergies, immunodeficiency, etc. In addition, this gene product may have commercial utility in the proliferation of stem cells and directed progenitor cells of various blood lineages, as well as in the differentiation and / or proliferation of various cell types. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 83 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 602 of SEQ ID NO: 83, and b is 15 to 616.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 83, and b is a + 14 or more) are excluded. .

(Characteristics of the protein encoded by gene number 74) When tested against Jurkat and fibroblast cell lines, the supernatant taken from cells containing this gene was GAS (gamma activating sequence), And EGR1
Both (immediate gene 1) promoter elements were activated. Thus, this gene appears to activate immune or fibroblast cells via the JAK-STAT and / or EGR1 signaling pathways. GAS is a promoter element found upstream of many genes involved in the Jak-STAT pathway. The Jak-STAT pathway is a large signaling pathway involved in cell differentiation and proliferation. Therefore, Jak-S reflected by the binding of GAS elements
Activation of the TAT pathway can be used to indicate proteins involved in cell growth and differentiation. EGR1 is another signal transduction pathway different from Jak-STAT, and when activated, a gene containing the EGR1 promoter is induced in various tissues and cell types, and this gene causes cells to differentiate and proliferate. Lead to receive. In a particular embodiment, the polypeptide of the invention comprises the following amino acid sequence: VVEPGLKASLGA MSTLFPSLPFPRVTETLWFNLDRPCVEETELQQQEQQ.
HQAWLQSIAEKDNNLVVPIGKPASEHYDDEEEDEDED
DEDSEEDSEDDEDMQDMDEMNDYNESPDDGEVNEVD
MEGNEQDQDQWMI (SEQ ID NO: 396), LFPRVTETLWFNL
DRPCVEETEL (SEQ ID NO: 397), and / or YNESPDDGE
VNEVDMEGNEQDQD (SEQ ID NO: 398). Polynucleotides encoding these polypeptides are also included in the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 11. Therefore, the polynucleotide related to the present invention is useful as a marker in the linkage analysis of chromosome 11.

This gene is primarily found in cells of the immune and hematopoietic system, and to a lesser extent,
It is expressed in several other tissues.

Thus, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in biological samples, as well as for immune and hematopoietic disorders (eg, multiple myeloma, immunodeficiency). , And inflammatory conditions), and are useful as reagents for the diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, especially the immune and hematopoietic systems, standard gene expression levels (
That is, a significantly higher or lower level of expression of this gene relative to the expression level in healthy tissues or body fluids from non-disordered individuals is obtained from specific tissues collected from such distressed individuals. Alternatively, it can be detected in a cell type (eg, cancerous and wound tissue), or body fluid (eg, lymph, serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

A preferred epitope is the residue in SEQ ID NO: 233: residues Pro-21 to Gly-3.
Includes epitopes that include the sequence shown as 0.

This tissue distribution in immune tissues and cells, in combination with the detected GAS and EGR1 biological activity, indicates that the polynucleotides and polypeptides corresponding to this gene are immune, hematopoietic, and integumental. It is shown to be useful for the treatment and diagnosis of disorders. In addition, because stromal cells are important in the production of cells of the hematopoietic lineage, polynucleotides and polypeptides corresponding to this gene are associated with disorders associated with hematopoiesis (eg, anemia, pancytopenia, leukopenia, platelets). It is useful for the treatment and diagnosis of hypopenia or leukemia). This use includes bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow repopulation, neoplastic radiotherapy or chemotherapy. The gene product may also be associated with lymphopoiesis and thus the gene product may be used in immune disorders such as infectious diseases, inflammation, allergies, immunodeficiency, etc. In addition, this gene product may have commercial utility in the proliferation of stem cells and directed progenitor cells of various blood lineages, as well as in the differentiation and / or proliferation of various cell types. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 84 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 914 of SEQ ID NO: 84, and b is 15 to 928.
, Both of which a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 84, and where b is a + 14 or more) are excluded. .

FEATURES OF PROTEIN ENCODED BY GENE NO: 75 In certain embodiments, a polypeptide of the invention comprises the following amino acid sequence: MGFDIHGVLGEAVAEPREKKQERAKWAPHDYDDP.
SLSLQDLLISWMISTWLIPMWKCQATIFSFSLIQRLL
NAYCMPGNFRHWEIAANTTNKTPGLMDDFKFL (SEQ ID NO: 399), EPREKQERAKWAPHDYDDPSLSLQDL (SEQ ID NO: 400), and / or MPGNFRHWEIAANTTNKTPGLMD
F (SEQ ID NO: 401). Polynucleotides encoding these polypeptides are also included in the invention. The gene encoding the disclosed cDNA is believed to reside on the X chromosome. Therefore, the polynucleotide related to the present invention is
It is useful as a marker in linkage analysis of the X chromosome.

This gene is expressed primarily in fetal liver and spleen, and to a lesser extent in prostate cancer and placenta.

Thus, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, as well as for developmental, reproductive, immune and hematopoietic disorders. It is useful as a reagent for diagnosing diseases and conditions, which is not limited thereto. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher or higher than standard gene expression levels (ie, expression levels in normal tissues or fluids from unaffected individuals) for many disorders of the tissues or cells, particularly the immune and developmental systems Low levels of expression of this gene may result in specific tissues or cell types (eg, developing tissues, liver tissues, reproductive tissues, immune tissues, hematopoietic tissues, and cancerous tissues and wounds taken from individuals with such disorders). Tissue), or body fluids (eg, lymph,
Amniotic fluid, serum, bile, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

This tissue distribution in developing and immune tissues indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the treatment and diagnosis of disorders of the hematopoietic and developing immune system. In addition, because stromal cells are important in the production of hematopoietic lineage cells, polynucleotides and polypeptides corresponding to this gene are associated with hematopoietic-related disorders (e.g., anemia, pancytopenia, leukopenia, It is useful in the treatment and diagnosis of thrombocytopenia or leukemia). This use includes bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow repopulation, neoplastic radiotherapy or chemotherapy. This gene product may also be associated with lymphopoiesis, so it is an immune disorder (eg, infectious disease, inflammation, allergy, immunodeficiency, etc.).
Can be used in. In addition, this gene product may have commercial utility in the expansion of stem cells and directed progenitor cells of various blood lineages, and in the differentiation and / or proliferation of various cell types. Furthermore, expression in fetal tissues and other cell sources characterized by proliferating cells may play a role in the regulation of cell division by this protein and its utility in the diagnosis and treatment of cancer and other proliferative disorders. Indicates that Similarly, developing tissue relies on decisions involved in cell differentiation and / or apoptosis in patterning. Thus the protein may also be involved in apoptosis or tissue differentiation and may also be useful in cancer therapy. In addition, the protein may also have utility in treating or diagnosing various liver or reproductive system disorders. These disorders include embryonal tumors, jaundice, hepatitis, metabolic diseases and conditions of the liver that may result from the differentiation of hepatocyte precursor cells, and prostate cancer, and / or congenital defects such as X-linked states, It is not limited to them. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 85 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 709 of SEQ ID NO: 85, and b is 15 to 723.
, Both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 85, and where b is a + 14 or more) are excluded. .

[0411]     (Characteristics of protein encoded by gene number 76)   This gene is mainly expressed in fetal spleen and Wilms tumor.

Accordingly, the polynucleotides and polypeptides of the present invention can be used for the differential identification of tissues or cell types present in a biological sample, as well as hematopoietic, immune, developmental, or renal disorders (eg, , Congenital deficiency, multiple myeloma, or Wilms tumor) and are useful as reagents for the diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. Significantly relative to standard gene expression levels (ie, expression levels in normal tissues or body fluids from undiseased individuals) in relation to many disorders of the tissues or cells, particularly the hematopoietic and developmental systems. High or low levels of expression of this gene may result in specific tissues or cell types taken from individuals with such disorders (eg, developing tissues, immune tissues, hematopoietic tissues, kidney tissues and cancerous and wound tissues). Or it can be detected in body fluids such as lymph, serum, plasma, urine, synovial fluid, and spinal fluid or another tissue or cell sample.

Tissue distribution in fetal spleen indicates that polynucleotides and polypeptides corresponding to this gene are useful in the treatment and diagnosis of hematopoietic and developmental disorders as well as cancer. In addition, because stromal cells are important in the production of hematopoietic lineage cells, polynucleotides and polypeptides corresponding to this gene are associated with hematopoietic-related disorders (e.g., anemia, pancytopenia, leukopenia, It is useful in the treatment and diagnosis of thrombocytopenia or leukemia). This use includes bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow repopulation, neoplastic radiotherapy or chemotherapy. This gene product may also be associated with lymphopoiesis and therefore this gene product is associated with immune disorders (
For example, infectious diseases, inflammation, allergies, immunodeficiency, etc.). In addition, this gene product may have commercial utility in the expansion of stem cells and directed progenitor cells of various blood lineages, and in the differentiation and / or proliferation of various cell types. Furthermore, expression in embryonic tissues and other cell sources characterized by proliferating cells, indicates that this protein may play a role in regulating cell division and has utility in the diagnosis and treatment of cancer and other proliferative disorders. Show that you get. Similarly, developing tissue relies on decisions involved in cell differentiation and / or apoptosis in patterning. Thus the protein may also be involved in apoptosis or tissue differentiation and may also be useful in cancer therapy. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 86 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Thus, preferably, according to the invention, the nucleotide sequence described by the general formula ab, where a is any integer from 1 to 556 of SEQ ID NO: 86 and b is an integer from 15 to 570, Here, both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 86, and where b is a + 14 or more), one or more polynucleotides are excluded.

(Characteristics of the protein encoded by gene No. 77) When tested on the U937 cell line, supernatant taken from cells containing this gene activated the GAS (γ activation sequence) promoter element. did. Therefore, this gene appears to activate promyelocytes via the JAK-STAT signaling pathway. GAS is a promoter element found upstream of many genes involved in the Jak-STAT pathway. The Jak-STAT pathway is large and is a signal transduction pathway involved in cell differentiation and proliferation. Therefore, activation of the Jak-STAT pathway (reflected by binding of GAS elements) can be used to indicate proteins involved in cell differentiation and proliferation.

[0416]   This gene is expressed primarily in induced T cells.

Accordingly, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, and include, but are not limited to, immune and inflammatory diseases. It is useful as a reagent for diagnosis of diseases and conditions. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher or higher than standard gene expression levels (ie, expression levels in normal tissues or body fluids from unaffected individuals) in relation to many disorders of the tissues or cells, particularly the immune system Low levels of expression of this gene may result in specific tissue or cell types (eg, immune, hematopoietic, and cancerous and wound tissues) or body fluids (eg, lymph, etc.) taken from individuals with such disorders. Serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

This tissue distribution in T cells, combined with the detected GAS biological activity, indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of immune and inflammatory diseases. Demonstrate usefulness. The secreted protein also determines biological activity, as a tissue marker for raising antibodies, for isolating cognate ligands or receptors, for identifying agents that regulate interactions, and for nutritional supplements. Can be used as It can also have a wide range of biological activities. Representative of these are the induction of cytokines, their cell growth / differentiation regulatory activity or other cytokines: immunostimulation /
Immunosuppressive activity (eg, for treatment of human immunodeficiency virus infection, cancer, autoimmune diseases and allergies); regulation of hematopoiesis (eg, for treatment of anemia, or as an adjunct to chemotherapy); bone, cartilage, Stimulation or proliferation of tendons, ligaments and / or nerves (eg for the treatment of wounds, stimulation of follicle-stimulating hormone (for controlling fertility)); chemotactic and chemokinetic activities (eg for infections, tumors) For treatment); hemostatic or thrombolytic activity (eg, for treatment of hemophilia, myocardial infarction, etc.); anti-inflammatory activity (eg, for treatment of septic shock, Crohn's disease); as an antimicrobial agent; For the treatment of psoriasis or other hyperproliferative disorders; for the regulation of metabolism and behavior. Also contemplated is the use of the corresponding nucleic acid in gene therapy procedures. The protein as well as antibodies to this protein may show utility as tumor markers and / or immunotherapeutic targets in the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 87 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 625 of SEQ ID NO: 87, and b is 15 to 639.
, Both of which a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 87, and where b is a + 14 or more) are excluded. .

CHARACTERISTICS OF PROTEIN ENCODED BY GENE NO: 78 In certain embodiments, a polypeptide of the invention comprises the following amino acid sequence: QSVPSPPLAPPLPPSLPSFLFTETRSHYVARLVS.
NSWAQMILLPWPLKVLGLDVSHCAWPKSVFLQAMEE
IADFCLFSVKYQVSSSMTCFDRTSYMKNTLY (SEQ ID NO: 4
02) and / or LFTETRSHHYVARLVNSSWAQMILLP
WP (SEQ ID NO: 403). Polynucleotides encoding these polypeptides are also included in the invention.

[0421]   This gene is mainly expressed in bone marrow.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, as well as for anemia (leukemia),
It is useful as a reagent for diagnosis of diseases and conditions including, but not limited to immunodeficiency, and other hematopoietic related disorders. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher or higher than standard gene expression levels (ie, expression levels in normal tissues or fluids from unaffected individuals) for many disorders of the tissues or cells, particularly the hematopoietic and immune systems Low levels of expression of this gene may result in specific tissues or cell types (eg, immune, hematopoietic, and cancerous and wound tissues) or body fluids (eg, lymph, etc.) taken from individuals with such disorders. Serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

Tissue distribution in the bone marrow shows that polynucleotides and polypeptides corresponding to this gene are associated with leukemia, lymphoma, autoimmunity, immunodeficiency (eg, AIDS), immunosuppressive status (transplantation), and other hematopoietic disorders (eg, hematopoietic disorders). , Multiple myeloma). In addition, this gene product may be applied in general microbial infection, inflammation or cancer conditions. The protein as well as antibodies to the protein may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 88 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 694 of SEQ ID NO: 88, and b is 15 to 708.
, Where a and b both correspond to the position of the nucleotide residue set forth in SEQ ID NO: 88, and b is a + 14 or more) are excluded. .

CHARACTERISTICS OF PROTEIN ENCODED BY GENE NO: 79 In certain embodiments, a polypeptide of the invention comprises the following amino acid sequence: SQIKSEKKKHIGKAYTCTQTQSTGMQSTLTIVAKK.
KSRNHTESYTRKKQENQIVLIPWHQKKHPEGTHTCS
HSLRRDTNTAADTQRKIRAHRYTYRRDKYSDTLVTH
DHYKGGDHPSNTHTQPRXEFLQPGGSTNSRAAAPRX
SSSFCPFSEGYSSWGYH (SEQ ID NO: 404), GMQSTLTIV
AKKKSRNHTESYTRKKQ (SEQ ID NO: 405), KKHPEGTHT
CHSSLRRDTNTAADT (SEQ ID NO: 406), and / or RRDK
YSDTLVTHDHYKGGDHPSNT (SEQ ID NO: 407). Polynucleotides encoding these polypeptides are also included in the invention.

[0426]   This gene is expressed primarily in neutrophils.

Thus, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in biological samples, as well as for immune or hematopoietic disorders (eg, leukemia, lymphoma, AIDS, arthritis). And asthma) and are useful as reagents for the diagnosis of diseases and conditions, including but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher or higher than standard gene expression levels (ie, expression levels in normal tissues or body fluids from unaffected individuals) in relation to many disorders of the tissues or cells, particularly the immune system Low levels of expression of this gene may result in specific tissue or cell types (eg, immune, hematopoietic, and cancerous and wound tissues) or body fluids (eg, lymph, etc.) taken from individuals with such disorders. serum,
Plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

A preferred epitope is at residues Asp-38 to Leu in SEQ ID NO: 238.
Includes an epitope that includes the sequence shown as -43.

This tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are associated with leukemia, lymphoma, AIDS, arthritis and asthma, and potentially other conditions involving the immune system (eg, atheroma). It is useful for the diagnosis and treatment of immune disorders, including atherosclerosis, cancer and infections. In addition, this gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also indicate utility in treating cancer (eg, by boosting the immune response). Since this gene is expressed in cells of lymphocyte origin, the natural gene product may be involved in immune function. Thus, it is associated with arthritis, asthma, immunodeficiency disorders such as granulomatosis, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivity (eg, T cell Mediated cytotoxicity); immune response to transplant organs and tissues (eg, host versus graft disease and graft versus host disease), or autoimmune disorders (eg, autoimmune infertility), lens tissue injury, demyelination. ,
It may also be used as a drug for immunological disorders including systemic lupus erythematosus, drug-induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and directed progenitor cells of various blood lineages, and in the differentiation and / or proliferation of diverse cell types. The protein as well as antibodies to this protein may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 89 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab, where a is any integer from 1 to 935 of SEQ ID NO: 89 and b is an integer from 15 to 949, wherein Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 89, and where b is a + 14 or more) are excluded.

FEATURES OF PROTEIN ENCODED BY GENE NO: 80 In certain embodiments, a polypeptide of the invention comprises the following amino acid sequence: KHLPLKAPIDLDNKNSCMFCSRDIFCRFHHSTAW.
LFLGRITDRILGLHHYLIRYQFEEIENLCLMKIVIPV
VSMKTNCQFDFLGQLKQNLYH (SEQ ID NO: 408), APIDL
DNKNSCMFCSRDIFCR (SEQ ID NO: 410), and / or IEN
LCLMKIVIPVVSMKTNCQFDFLGQL (SEQ ID NO: 409). Polynucleotides encoding these polypeptides are also included in the invention.

This gene is expressed primarily in the prostate cancer cell line, R1881 cells stimulated with 30 nM synthetic androgen, and to a lesser extent in activated monocytes.

Accordingly, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, and include reproductive or immune disorders, particularly prostate cancer and prostate disease. Are useful as reagents for diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. Significantly higher than standard gene expression levels (ie expression levels in normal tissues or body fluids taken from non-disordered individuals) in association with many disorders of the tissues or cells, especially the prostate, or Low levels of expression of this gene may result in specific tissue or cell types (eg, immune, reproductive, and cancerous and wound tissues) or body fluids (eg, lymph, etc.) taken from individuals with such disorders. Semen, serum, plasma, urine,
Synovial fluid and cerebrospinal fluid), or in another tissue or cell sample.

Its tissue distribution in the prostate indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and intervention of prostate cancer and prostate disease, and associated proliferative conditions in either or other tissues. Demonstrate usefulness. The protein as well as antibodies to this protein may show utility as tumor markers and / or immunotherapeutic targets in the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 90 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 1157 of SEQ ID NO: 90, and b is 15 to 11
71 is an integer of 71, wherein both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 90, and b is a + 14 or more) are excluded. It

CHARACTERISTICS OF PROTEIN ENCODED BY GENE NO: 81 The translation products of this gene are human protocadherin 42 (GenBank accession number gi | 387675), PCDH7 (BH-Pcdh) a, and its related isoform PCDH7. (BH-Pcdh) b, and PCDH7 (BH-Pcdh) c (which is thought to be important for tissue and cell-cell adhesion, repair and development.
GenBank registration number gnl | PID | d1026122 (AB006755
), Gnl | PID | d1026123 (AB006756), and gnl |
Shares high sequence homology with PID | d1026124 (see AB006757)). A polynucleotide encoding this gene is taught by another group after our application (Y, incorporated herein by reference).
oshida K et al., Genomics May 1, 1998; 49 (3): 45.
8 to 61))). The cytoplasmic domain of cadherin interacts with the cytoskeleton and other cytoskeletal associated proteins through catenin. The cytoplasmic domain is not present in all cadherins, but in cadherins that have a cytoplasmic domain, the cytoplasmic domain is essential for cadherin adhesion function. Cadherin without a cytoplasmic domain appears to function through a different method than cadherin with a cytoplasmic domain. This protein sequence is involved in cell-cell adhesion. This sequence may have regulatory functions in cells and cell-cell adhesive properties. Antibodies raised against this sequence are useful in modulating protocadherin binding activity and may be used therapeutically. BH-Pcdh has an extracellular domain consisting of seven cadherin motif repeats (EC1-7). The EC2 of BH-Pcdh is unique in that it has a 55 amino acid insertion in the center of this motif. There are three isoforms of BH-Pcdh, -a,-
b, -c, different cytoplasmic tails
And a deletion of 47 amino acids in the EC2-3 region of BH-Pcdh-c.
Only 9.0 kb message was detected in normal tissues, whereas 4.5 and 9.0 kb mRNA species were found in the human lung cancer cell line A549. Furthermore, 4.
Only 5 kb of mRNA was found in HeLa cells S3 and human gastric cancer cell line MKN28.
And detected in KATO-III. Southern blot analysis is based on BH-Pcd
We have shown that the h gene appears to be conserved among various vertebrates. In a particular embodiment, the polypeptide of the invention comprises the following amino acid sequence:

[0437]

[Chemical 9] Polynucleotides encoding these polypeptides are also included in the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 4. Therefore, the polynucleotide related to the present invention is useful as a marker in the linkage analysis of chromosome 4.

This gene is expressed primarily in ovarian tumors and to a lesser extent in striatum and HL-60 cells.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in biological samples, as well as cancer and reproductive dysfunction, as well as cardiovascular and neurological disorders. (For example, atherosclerosis)
, And disorders of neurodegeneration (eg, Alzheimer's disease and Parkinson's disease),
Or, it is useful as a reagent for diagnosis of diseases and conditions including, but not limited to, other disorders resulting from abnormal cell adhesion. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. Standard gene expression levels (ie, expression levels in normal tissues or body fluids taken from non-disordered individuals) in connection with many disorders of the tissues or cells, particularly the reproductive, nervous and immune systems. Significantly higher or lower levels of expression of this gene relative to a particular tissue or cell type (eg, reproductive, neural, cardiovascular, and cancerous tissue) taken from an individual with such a disorder. And wound tissue) or body fluids (eg,
Lymph, serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

A preferred epitope is the residue in SEQ ID NO: 240: residues Tyr-15 to Leu-5.
9, Ala-68 to Asp-85, Pro-87 to Asn-96, His-12.
0-Lys-129, Ser-153 to Gln-170 are included.

This tissue distribution in ovarian and muscle tissue, combined with high sequence homology with various cadherins, indicates that the polynucleotides and polypeptides corresponding to this gene are associated with various neoplastic disorders (eg, squamous cell carcinoma). And related tumors), and nervous system and reproductive disorders.
Considering that cell adhesion is extremely important among various cell functions, this gene product is particularly useful in chemotaxis by immune cells and hematopoietic cells, and its usefulness in treatment of cytokine products, antigen presentation, or cancer. It also indicates that it may play a direct or indirect role in the regulation of other processes that may be implicated (eg, by boosting the immune response). Since this gene is expressed in cells of lymphocyte origin, the natural gene product may be involved in immune function. Therefore, it is arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatosis, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis. , Hypersensitivity (eg, T cell-mediated cytotoxicity); immune response to transplanted organs and tissues (eg, host versus graft disease and graft versus host disease), or autoimmune disorders (eg, autoimmune infertility). ), Lens tissue injury, demyelination, systemic lupus erythematosus, drug-induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma, and as a drug for immunological disorders including tissue. In addition, this gene product may have commercial utility in the expansion of stem cells and directed progenitor cells of various blood lineages, and in the differentiation and / or proliferation of diverse cell types. In addition, secreted proteins also identify agents that modulate their interaction to measure biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to isolate receptors. To be used as a nutritional supplement. It may also play an indirect role in regulating a very wide range of biological activities. Typical of these are cytokines,
Modulating activity of cell proliferation / differentiation or induction of other cytokines; Immunostimulatory / immunosuppressive activity (eg, for treatment of human immunodeficiency virus infections, cancers, autoimmune diseases, and allergies); Modulation of hematopoiesis (eg, For the treatment of anemia or as an adjunct to chemotherapy); stimulation or proliferation of bone, cartilage, tendons, ligaments and / or nerves (eg for the treatment of wounds, stimulation of follicle-stimulating hormone (control of fertility) )); Chemotactic and chemokinetic activities (eg, for treatment of infections, tumors); hemostatic or thrombolytic activity (eg, for treatment of hemophilia, myocardial infarction, etc.); anti-inflammatory. Activity (eg, for treatment of septic shock, Crohn's disease);
As an antibacterial agent; for the treatment of psoriasis or other hyperproliferative disorders; for the regulation of metabolism and behavior. The use of the corresponding nucleic acids in gene therapy procedures is also contemplated. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 91 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is any integer of 1 to 1137 of SEQ ID NO: 91, and b is 15 to 11
Is an integer of 51, wherein both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 91, and b is a + 14 or more) are excluded. It

(Characteristics of protein encoded by gene number 82) The translation product of this gene is involved in the important function of G protein-coupled receptor TM3 in various signal transduction pathways.
Shares sequence homology with the 3 consensus polypeptides. G-protein coupled receptors are known to have diverse functions, including regulation of immune system tissues through interactions with cytokines and lymphokines. In a particular embodiment, the polypeptide of the invention comprises the following amino acid sequence:

[0444]

[Chemical 10] Polynucleotides encoding these polypeptides are also included in the invention.

[0445]   This gene is expressed primarily in breast lymph nodes.

Accordingly, the polynucleotides and polypeptides of the invention include for differential identification of tissues or cell types present in a biological sample, as well as for breast cancer, or other immune or reproductive disorders or diseases. Are useful as reagents for diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. Significantly higher than standard gene expression levels (ie expression levels in normal tissues or body fluids taken from non-impaired individuals) in relation to many disorders of the tissues or cells, especially the immune system Or a low level of expression of this gene results in a specific tissue or cell type (eg, immune tissue, reproductive tissue, breast tissue, cancerous tissue and wound tissue) or body fluid (eg, immune tissue, reproductive tissue, breast tissue, cancer tissue and wound tissue) taken from an individual having such a disorder. , Lymph, serum, milk, plasma, urine,
Synovial fluid and cerebrospinal fluid), or in another tissue or cell sample.

A preferred epitope is residues Cys-34 to Gly-in SEQ ID NO: 241.
It includes an epitope containing the sequence shown as 48 residues.

The tissue distribution in breast lymph nodes and the homology to the conserved consensus sequence of the G protein-coupled receptor TM3 make polynucleotides and polypeptides corresponding to this gene useful in the diagnosis and treatment of breast cancer or immune disorders. Indicates that there is. Given the great role that G protein-coupled receptors play in maintaining important cellular functions, secreted proteins may have a very wide range of biological activities. Typical of these are the induction of cytokines, cell growth / differentiation regulatory activity or other cytokines; immunostimulatory / immunosuppressive activity (eg for the treatment of human immunodeficiency virus infections, cancers, autoimmune diseases, and allergies). In); regulation of hematopoiesis (eg for the treatment of anemia or as an adjunct to chemotherapy); stimulation or proliferation of bone, cartilage, tendons, ligaments and / or nerves (eg for the treatment of wounds,
Stimulation of follicle-stimulating hormone (for controlling fertility); chemotactic and chemokinetic activities (for example, for treating infections, tumors); hemostatic or thrombolytic activity (for example, hemophilia, myocardial infarction). Anti-inflammatory activity (eg, for the treatment of septic shock, Crohn's disease); as an antimicrobial agent; for the treatment of psoriasis or other hyperproliferative disorders; regulation of metabolism and behavior Because of. The use of the corresponding nucleic acids in gene therapy procedures is also contemplated. In addition, the protein also determines biological activity, isolates cognate ligands or receptors as tissue markers for raising antibodies, identifies agents that modulate their interaction, and It can be used as a nutritional supplement. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 92 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 700 of SEQ ID NO: 92, and b is 15 to 714.
, Both of which a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 92, and where b is a + 14 or more) are excluded. .

FEATURES OF PROTEIN ENCODED BY GENE NO: 83 In certain embodiments, a polypeptide of the invention comprises the following amino acid sequence:

[0451]

[Chemical 11] Polynucleotides encoding these polypeptides are also included in this invention.

This gene is expressed primarily in activated T cells, hepatocellular tumors, pancreatic islet cell tumors, and hemangiopericytoma.

Accordingly, the polynucleotides and polypeptides of the present invention can be used for the differential identification of tissues or cell types present in a biological sample, as well as cancer (especially T cell, hepatocellular and pancreatic islet cell tumors). Are useful as reagents for the diagnosis of diseases and conditions including, but not limited to, immune disorders, liver disorders, and endocrine disorders. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, especially the immune system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in normal tissues or fluids from individuals without disorders). The expression of this gene
A specific tissue or cell type (eg, immune system, liver tissue, endocrine tissue, cancerous tissue and wound tissue) or body fluid (eg, lymph, bile, serum, plasma, urine) collected from an individual having such a disorder. , Synovial fluid, and cerebrospinal fluid) or another tissue or cell sample.

A preferred epitope is Glu-43 to Lys-5 in SEQ ID NO: 242.
0, including epitopes containing the sequences shown as Ser-53 to Phe-60 residues.

Tissue distribution in T cells, hepatocellular tumors, pancreatic islet cell tumors is demonstrated by the presence of polynucleotides and polypeptides corresponding to this gene in the diagnosis and intervention of immune disorders, liver disorders, endocrine disorders, and other cancer types. To be useful for. Expression in the cellular supply, characterized by proliferating cells, indicates that this protein may play a role in the regulation of cell division, and in addition to those disclosed above, cancer and other proliferative cells in a variety of tissues. We show that it can show utility in the diagnosis and treatment of disorders. Similarly, developing tissues rely on decisions that involve cell differentiation and / or apoptosis in patterning. Therefore, this protein may also be involved in apoptosis or tissue differentiation and may also be useful in the treatment of cancer. The protein as well as antibodies to this protein may show utility as tumor markers in the tissues listed above and / or as targets for immunotherapy.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 93 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is any integer of 1 to 796 of SEQ ID NO: 93, and b is 15 to 810.
, Both of which a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 93, and where b is a + 14 or more) are excluded. .

FEATURES OF PROTEIN ENCODED BY GENE NO: 84 In certain embodiments, a polypeptide of the invention comprises the following amino acid sequence:

[0458]

[Chemical 12] Polynucleotides encoding these polypeptides are also included in this invention.

[0459]   This gene is mainly expressed in hepatocellular tumors.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, as well as liver disorders such as liver disorders and hepatocellular tumors (other tissues). And proliferative disorders in cell types)
Are useful as reagents for the diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, especially the liver system, significantly higher or lower levels of normal gene expression levels (ie, expression levels in normal tissues or fluids from non-disordered individuals) are used. The expression of this gene is dependent on the specific tissue or cell type (eg liver tissue, proliferative tissue, cancerous tissue and wound tissue) or body fluid (eg lymph, bile, etc.) taken from an individual having such a disorder.
Serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

Tissue distribution in hepatocellular tumor tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and intervention of hepatocellular tumors or other liver disorders. In particular, the polynucleotides and polypeptides corresponding to this gene are used in the detection and treatment of liver disorders and cancers, such as germ species, jaundice, hepatitis, liver metabolic disorders and conditions that contribute to hepatocyte progenitor cell differentiation. On the other hand, it is useful. The protein as well as antibodies to this protein may show utility as tumor markers in the tissues listed above and / or as targets for immunotherapy.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 94 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1-1162 of SEQ ID NO: 94, and b is 15-11.
Is an integer of 76, wherein both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 94, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

Characterization of Protein Encoded by Gene No. 85 When tested on the reh cell line, supernatants obtained from cells containing this gene activate the GAS (γ activation sequence) promoter element. did. Therefore, this gene appears to activate B cells via the Jak-STAT signaling pathway. GAS is a promoter element found upstream of many genes involved in the Jak-STAT pathway. The Jak-STAT pathway is large and is a signal transduction pathway involved in cell differentiation and proliferation. Therefore, Ja
Activation of k-STAT, reflected by the binding of GAS elements, can be used to indicate proteins involved in cell differentiation and proliferation. In a particular embodiment, the polypeptide of the invention comprises the following amino acid sequence:

[0464]

[Chemical 13] Polynucleotides encoding these polypeptides are also included in the invention.

This gene is expressed primarily in human fetal kidney, adult testis, T cell lymphoma, and fetal liver / spleen cDNA libraries.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, as well as renal, developmental, reproductive, immune, or hematopoietic disorders. It is useful as a reagent for the diagnosis of diseases and conditions including, but not limited to (especially renal disease, lymphoma, birth defects, multiple myeloma, SCID, male infertility, and cancer). Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher or higher than standard gene expression levels (ie, expression levels in normal tissues or fluids from unaffected individuals) for many disorders of the tissues or cells, particularly the renal and immune systems Low levels of expression of this gene may result in specific tissue or cell types (eg, immune, hematopoietic, reproductive, renal, developmental, cancerous and wounded tissues taken from individuals with such disorders). ) Or body fluids such as lymph, amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid or another tissue or cell sample.

A preferred epitope is set forth in SEQ ID NO: 244 as Glu-35 to Gly-4.
It includes an epitope that includes the sequence shown as residue 0.

Tissue distribution in fetal kidney and T cells, coupled with detected GAS bioactivity, makes polynucleotides and polypeptides corresponding to this gene useful for the diagnosis and treatment of renal disease or immune disorders, especially cancer. Is shown. Specifically, this gene or gene product is associated with renal failure, nephritis, tubular acidosis, proteinuria, pyuria, edema, nephrogenic nephritis, hydronep.
), nephrotic syndrome, crush syndrome, glomerulonephritis, hematuria, renal colic and kidney stones, and Wilms tumor disease, and congenital renal abnormalities (eg, horseshoe kidney, polycystic kidney disease and Falconi (Falconi) syndrome). A) and / or detection of kidney disease. Expression in fetal tissues and other cellular supplies that is characterized by proliferating cells, suggests that this protein may play a role in regulating cell division and has utility in the diagnosis and treatment of cancer and other proliferative disorders. Indicates that it can be shown. Similarly, developing tissues rely on decisions that involve cell differentiation and / or apoptosis in patterning. Therefore, this protein may also be involved in apoptosis or tissue differentiation and may also be useful in the treatment of cancer. The protein and antibodies to this protein are
It may show utility as a tumor marker for the tissues listed above and / or as a target for immunotherapy.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 95 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 1014 in SEQ ID NO: 95, and b is 15 to 10
Is an integer of 28, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 95, and b is a + 14 or more) and one or more polynucleotides are excluded. It

Characterization of Protein Encoded by Gene No. 86: When tested on the U937 cell line, supernatants taken from cells containing this gene activate the GAS (gamma activator sequence) promoter element. did.
Therefore, this gene appears to activate promyelocytic cells via the Jak-STAT signaling pathway. GAS is a promoter element found upstream of many genes involved in the Jak-STAT pathway. The Jak-STAT pathway is a large signaling pathway involved in cell differentiation and proliferation. Therefore,
Activation of the Jak-STATs pathway, reflected by the binding of GAS elements, can be used to indicate proteins involved in cell proliferation and differentiation.

This gene is expressed primarily in breast tissue, human embryos, and chronic splenic lymphocytic leukemia.

Accordingly, the polynucleotides and polypeptides of the present invention can be used for the differential identification of tissues or cell types present in a biological sample, as well as for reproduction such as breast cancer, birth defects, or leukemia. It is useful as a reagent for the diagnosis of diseases and conditions including, but not limited to, disorders, developmental disorders, hematopoietic disorders or immune disorders. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher or higher than standard gene expression levels (ie expression levels in normal tissues or fluids from non-disordered individuals) for many disorders of the tissues or cells, particularly breast tissue or hematopoietic system Low levels of expression of this gene are associated with specific tissues or cell types taken from individuals with such disorders, such as reproductive, immune, hematopoietic, developmental, breast, cancerous and wound tissues. ) Or body fluids (eg lymph, amniotic fluid, breast milk, serum, plasma, urine, synovial fluid, and spinal fluid).
Or it can be detected in another tissue or cell sample.

Preferred epitopes include His-2 to Asn-8 in SEQ ID NO: 245,
It includes an epitope that includes the sequence shown as Gln-35 to Phe-44 residues.

Tissue distribution in breast tissue and lymphocytic white blood cells was detected by GAS
Together with biological activity, it is shown that the polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis or intervention of breast cancer, leukemia or other hematopoietic disorders. Furthermore, polynucleotides and polypeptides corresponding to this gene are associated with anemia, pancytopenia, as stromal cells are important for the generation of hematopoietic lineage cells.
It is useful in the treatment and diagnosis of hematopoietic disorders such as leukopenia, thrombocytopenia or leukemia. This use includes bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow repopulation, neoplastic radiotherapy or chemotherapy. This gene product may also be associated with lymphopoiesis. Therefore, this gene product can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency, and the like. Furthermore, this gene product may have commercial utility in the proliferation of stem cells and associated progenitor cells of various blood lineages, as well as in the differentiation and / or proliferation of various cell types. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 96 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is any integer of 1 to 733 of SEQ ID NO: 96, and b is 15 to 747.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 96, and b is a + 14 or more) are excluded. .

[0476]     (Characteristics of protein encoded by gene number 87)   This gene is expressed primarily in the brain, including medulloblastoma.

Thus, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in biological samples, as well as for neurological disorders, particularly certain brain tumors such as medulloblastoma and other Diagnosis of diseases and conditions including but not limited to schizophrenia, Alzheimer's disease, Tourette's syndrome, Parkinson's disease, Huntington's disease, mania, dementia, paranoia, depression and addiction It is useful as a reagent for Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, especially the central nervous system, significantly higher or lower levels relative to standard gene expression levels (ie, expression levels in normal tissues or fluids from individuals without the disorder) Expression of this gene in specific tissues or cell types (eg, neural tissue, cancerous tissue and wound tissue) or body fluids (eg, lymph, serum, plasma, urine, etc.) taken from an individual having such a disorder. Synovial fluid, and spinal fluid) or another tissue or cell sample.

Tissue distribution in brain tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of certain brain tumors such as medulloblastoma. In addition, developmental, degenerative, and behavioral states of the brain and nervous system (
(Schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, Tourette's syndrome, mania, dementia, paranoia, addictive disposition, obsessive-compulsive disorder and sleep disorders)
It may also be useful in the diagnosis and treatment of. The protein as well as antibodies to this protein may show utility as tumor markers in the tissues listed above and / or as targets for immunotherapy.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 97 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is any integer of 1 to 614 of SEQ ID NO: 97, and b is 15 to 628.
, Both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 97, and b is a + 14 or more) are excluded. .

Characterization of Protein Encoded by Gene No: 88 When tested against the Jurket cell line, supernatants obtained from cells containing this gene activate the GAS (γ activation sequence) promoter element. did. Therefore, this gene appears to activate T cells via the Jak-STAT signaling pathway. GAS is a promoter element found upstream of many genes involved in the Jak-STAT pathway. The Jak-STAT pathway is large and is a signal transduction pathway involved in cell differentiation and proliferation. Therefore, activation of Jak-STAT (reflected by the binding of GAS elements) can be used to indicate proteins involved in cell differentiation and proliferation. In a particular embodiment, a polypeptide of the invention comprises the following amino acid sequence: INVLYCS
RDSLMGRTISESDYIKKGANVSVPLGVRQQAV (SEQ ID NO: 434). Polynucleotides encoding these polypeptides are also included in this invention.

[0481]   This gene is expressed primarily in adrenal tumors and T cells.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, as well as for diseases of the endocrine, immune or hematopoietic systems, particularly AIDS. It is useful as a reagent for diagnosis of diseases and conditions including, but not limited to, such inflammation or immunodeficiency conditions.
Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher or higher than standard gene expression levels (ie, expression levels in normal tissues or fluids from unaffected individuals) for many disorders of the tissues or cells, particularly the immune and endocrine systems Low levels of expression of this gene may result in specific tissue or cell types (eg, immune tissue, hematopoietic tissue, endocrine tissue, cancerous tissue and wound tissue) or body fluid (eg, immune tissue, hematopoietic tissue, endocrine tissue, etc.) or bodily fluid (eg, Lymph, serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

Tissue distribution in T cells and adrenal tissue, combined with detected GAS bioactivity, indicate that polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of disorders of the immune and endocrine system and cancer. Indicates that there is. In addition, this secreted protein is also used to raise antibodies for the determination of biological activity (
It can be used as a tissue marker), for the isolation of cognate ligands or receptors, for the identification of agents that modulate their interaction, and as a nutritional supplement.
It can also have a very wide range of biological activities. Representative of these are cytokines, which induce cell growth / differentiation regulation or other cytokines; immunostimulatory / immunosuppressive activity (eg, to treat human immunodeficiency virus infections, cancers, autoimmune diseases and allergies); hematopoiesis. Regulation (eg, to treat anemia or as an adjunct to chemotherapy); stimulation or proliferation of bone, cartilage, tendons, ligaments and / or nerves (eg, to treat wounds, stimulation of follicle stimulating hormone (fertilization) Chemotaxis and chemokinesis activity (eg, to treat infections, tumors); hemostatic or thrombolytic activity (eg, to treat hemophilia, myocardial infarction, etc.); anti-inflammatory Activity (eg, to treat septic shock, Crohn's disease);
As an antimicrobial agent; to treat psoriasis or other hyperproliferative disorders; to regulate metabolism and behavior. The use of the corresponding nucleic acids in gene therapy procedures is also contemplated. The protein as well as antibodies to this protein may show utility as tumor markers for the tissues listed above and / or targets for immunotherapy.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 98 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 890 of SEQ ID NO: 98, and b is 15 to 904.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 98, and b is a + 14 or more) are excluded. .

FEATURES OF PROTEIN ENCODED BY GENE NO: 89 In certain embodiments, a polypeptide of the invention comprises the following amino acid sequence: SLLMYFVFKIFFFQSLCVLGYCILPLTVA (SEQ ID NO: 4.
35). Polynucleotides encoding these polypeptides are also included in this invention.

[0486]   This gene is mainly expressed in dendritic cells.

Accordingly, the polynucleotides and polypeptides of the present invention are for the differential identification of tissues or cell types present in a biological sample, as well as for the diagnosis of diseases and conditions, including but not limited to immune disorders. Is useful as a reagent for.
Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, especially the immune system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in normal tissues or fluids from individuals without disorders). The expression of this gene may depend on the specific tissue or cell type (eg, immune tissue, cancerous tissue and wound tissue) or body fluid (eg, lymph, serum, plasma, urine, synovium, etc.) taken from an individual having such a disorder. Fluid and spinal fluid) or another tissue or cell sample.

A preferred epitope is SEQ ID NO: 248, in which Thr-43 to Thr-4.
It includes an epitope containing the sequence shown as 8 residues.

The tissue distribution in dendritic cells indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the treatment and diagnosis of immune system disorders. In addition, polynucleotides and polypeptides corresponding to this gene are associated with hematopoietic disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia, as stromal cells are important for the generation of cells of the hematopoietic lineage. Useful for treatment and diagnosis. This use includes bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow repopulation, neoplastic radiotherapy or chemotherapy. This gene product may also be associated with lymphopoiesis.
Therefore, this gene product can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency, and the like. Furthermore, this gene product may have commercial utility in the proliferation of stem cells and associated progenitor cells of various blood lineages, as well as in the differentiation and / or proliferation of various cell types. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 99 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore,
Preferably, according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 562 of SEQ ID NO: 99, and b is 15 to 576.
, Both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 99, and b is a + 14 or more) are excluded. .

CHARACTERISTICS OF PROTEIN ENCODED BY GENE NO: 90 In a particular embodiment, a polypeptide of the invention comprises an amino acid sequence as follows: RLWMTKAHPALRHLLLLTLTLLLLAQGCCAVASG
CADLAGFCSLGHSC (SEQ ID NO: 436). Polynucleotides encoding these polypeptides are also included in the invention.

[0492]   This gene is expressed primarily in the human stomach.

Thus, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, and include digestive and gastrointestinal conditions, particularly ulcers and cancers, It is useful as a reagent for diagnosis of diseases and conditions including, but not limited to, these. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the above tissues or cells, especially for the gastrointestinal system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in healthy tissues or fluids from unaffected individuals). The expression of this gene is dependent on the specific tissue or cell type (eg, gastrointestinal tissue, metabolic tissue, mucosal tissue and cancerous and wound tissue) or body fluid (eg, lymph, serum) taken from an individual having such a disorder. , Chyme, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

Preferred epitopes are residues in SEQ ID NO: 249: Pro-32 to Gly-3.
8 includes the epitope including the sequence shown as 8.

Tissue distribution in gastric tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful in the study and treatment of gastrointestinal disorders, or other disorders that damage mucosal or endothelial tissues. The protein and antibodies to this protein may show utility as tumor markers and / or immunotherapeutic targets for the tissues shown above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 100 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 699 of SEQ ID NO: 100 and b is from 15 to 7
Is an integer of 13, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 100, and where b equals a + 14 or greater) 1
One or more polynucleotides are excluded.

(Characteristics of Protein Encoded by Gene No. 91) The translation product of this gene is Caenorhabditis elegans.
It has been found to have homology to the conserved K07F5.14 protein from (see Genbank accession number gel | PID | e233697), which is important in the regulation of important cellular functions including homeostasis and cell division. possible. When tested against the U937 cell line, supernatants removed from cells containing this gene activated the GAS (gamma activating sequence) pathway. Therefore, this gene appears to activate promyelocytic cells through the JAK-STAT signaling pathway. GAS is a promoter element found upstream of many genes,
It is involved in the Jak-STAT pathway. The Jak-STAT pathway is a large signal transduction pathway involved in cell differentiation and proliferation. Therefore, activation of the Jak-STATs pathway, reflected by binding of GAS elements, can be used to indicate proteins involved in cell differentiation and proliferation. In a particular embodiment, a polypeptide of the invention comprises the amino acid sequence: RTCTPWMGFWCLVCSLFAPVPTSRKYLVVSPGCYQR.
RRVFGVCFTKPL (SEQ ID NO: 437), WLLSEKKG (SEQ ID NO: 4)
38), GVFYKAAVIG (SEQ ID NO: 439). Polynucleotides encoding these polypeptides are also included in the invention.

[0498]   This gene is expressed primarily in bone marrow and T cells.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, as well as immune system disorders or hematopoietic system disorders, particularly multiple myeloma, immune system. It is useful as a reagent for the diagnosis of diseases and conditions including, but not limited to, disorders and cancers. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher or higher than standard gene expression levels (ie, expression levels in normal tissues or fluids from unaffected individuals) for many disorders of the tissues or cells, particularly the immune and secretory systems Low levels of expression of this gene may result in specific tissues or cell types (eg, immune, hematopoietic and cancerous and wound tissues) or body fluids (eg, lymph, serum) taken from individuals with such disorders. ,plasma,
Urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

This tissue distribution in bone marrow cells and T cells, combined with the detected GAS biological activity in U973 cells, allows the polynucleotides and polypeptides corresponding to this gene to be associated with immune and hormonal disorders. It is shown to be useful in neoplasia research and treatment. In particular, polynucleotides and polypeptides corresponding to this gene are useful in the treatment and diagnosis of hematopoietic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia. This is because stromal cells are important in the production of hematopoietic cells. Applications include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow repopulation, neoplastic radiotherapy or chemotherapy. This gene product may also be involved in lymphocyte production and may be used in immune disorders such as infections, inflammation, allergies, immunodeficiencies and the like. Moreover, this gene product may have commercial utility in the proliferation of stem cells and related progenitor cells of various blood lineages, as well as in the differentiation and / or proliferation of various cell types. Furthermore, this protein is associated with arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, chronic granulomatosis, inflammatory bowel disease, sepsis, contusion, neutropenia, neutrophilia, Psoriasis, hypersensitivity (eg T cell mediated cytotoxicity)
An immune response (eg, host vs. graft and graft vs. host disease) or autoimmune disorder (eg, autoimmune infertility, lens tissue injury, demyelination, systemic lupus erythematosus, drug-induced hemolytic anemia) to transplanted organs and tissues; , Rheumatoid arthritis, Sjogren's disease, scleroderma) as well as tissues, as a drug for immunological disorders. Moreover, this gene product may have commercial utility in the proliferation of stem cells and associated progenitor cells of various blood lineages, as well as in the differentiation and / or proliferation of various cell types. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 101 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, where a is any integer from 1 to 635 of SEQ ID NO: 101 and b is from 15 to 6
Is an integer of 49, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 101, and b is a + 14 or more) and one or more polynucleotides are excluded. It

[0502]     (Characteristics of protein encoded by gene number 92)   In a particular embodiment, the polypeptide of the invention comprises the following amino acid sequence:

[0503]

[Chemical 14] Polynucleotides encoding these polypeptides are also included in the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 19. Therefore, the polynucleotide related to the present invention is useful as a marker in the linkage analysis of chromosome 19.

[0504]   This gene is expressed primarily in the ovary, spinal cord and fetal spleen.

Accordingly, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, as well as for developmental, reproductive and neurological conditions It is useful as a reagent for diagnosis of diseases and conditions, which is not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher or higher than standard gene expression levels (ie, expression levels in normal tissues or fluids from unaffected individuals) for many disorders of the tissues or cells, particularly the nervous and immune systems Low levels of expression of this gene may result in specific tissue or cell types (eg, developmental tissue, reproductive tissue, ovarian tissue, immune tissue, hematopoietic tissue, and cancerous tissue and wounds taken from individuals with such disorders. Tissue) or body fluids (eg lymph, amniotic fluid,
Serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

A preferred epitope is as shown in SEQ ID NO: 251 with residues: Pro-34 to Pr.
There is an epitope including the sequence shown as o-53.

Tissue distribution in the spinal cord and fetal spleen indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study and treatment of neurological, hematopoietic and developmental disorders. In particular, the polynucleotides and polypeptides corresponding to this gene are neurodegenerative disease states, behavioral disorders or inflammatory conditions (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, meningitis, encephalitis, demyelinating disease, peripheral disease). Neuropathy, neoplasia, trauma, birth defects, spinal cord injury,
Ischemia and infarction, aneurysm, bleeding, schizophrenia, mania, dementia, paranoia, obsessive-compulsive disorder, panic disorder, learning disorder, ALS, psychosis, autism, and behavioral changes (nutrition, sleep patterns, It may be useful in the detection / treatment of balance and (including impaired perception). Furthermore, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, recognition, homeostasis, or neuronal differentiation or survival. In addition, the gene or gene product may also play a role in the treatment and / or detection of developmental, sex-linked, or cardiovascular disorders associated with the developing embryo. In addition, polynucleotides and polypeptides corresponding to this gene are useful in the treatment and diagnosis of hematopoietic-related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia. This is because stromal cells are important in the production of hematopoietic cells. This application includes, but is not limited to, bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow repopulation, neoplastic radiotherapy or chemotherapy. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 102 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, where a is any integer from 1 to 683 of SEQ ID NO: 102 and b is from 15 to 6
97 is an integer of 97, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 102, and b is a + 14 or more) are excluded. It

[0509]     (Characteristics of protein encoded by gene number 93)   In a particular embodiment, the polypeptide of the invention comprises the following amino acid sequence:

[0510]

[Chemical 15] Polynucleotides encoding these polypeptides are also included in the invention.

[0511]   This gene is expressed primarily in male human bladder tissue.

Thus, the polynucleotides and polypeptides of the present invention are for the differential identification of tissues or cell types present in a biological sample, and include gastrointestinal conditions, urogenital conditions, nephrotic conditions, It is useful as a reagent for diagnosis of diseases and conditions including, but not limited to, these. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, particularly the gastrointestinal and excretory systems, significantly higher or more than standard gene expression levels (ie, expression levels in healthy tissue or fluid from individuals without disorders) Low levels of expression of this gene result in specific tissues or cell types taken from individuals with such disorders (eg, kidney tissue, bladder tissue, cancerous tissue and wound tissue).
Or it can be detected in body fluids such as lymph, serum, plasma, urine, synovial fluid, and spinal fluid or another tissue or cell sample.

[0513] A preferred epitope is the residue in SEQ ID NO: 252: Arg-52 to Al.
Examples of the epitope include the sequences shown as a-57, Pro-66 to Thr-72.

This tissue distribution in bladder tissue indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the study and treatment of gastrointestinal and urinary tract disorders. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 103 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, where a is any integer from 1 to 1274 of SEQ ID NO: 103 and b is from 15 to
Is an integer of 1288, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 103, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

[0516]     (Characteristics of protein encoded by gene number 94)   This gene is expressed primarily in male human bladder tissue.

Accordingly, the polynucleotides and polypeptides of the present invention include, but are not limited to, gastrointestinal, renal and urinary tract conditions for the differential identification of tissues or cell types present in a biological sample. It is useful as a reagent for diagnosing diseases and conditions that are not affected. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher or higher than standard gene expression levels (ie, expression levels in normal tissues or body fluids from unaffected individuals) for many disorders of the tissues or cells, particularly the intestinal system and urinary tract Low levels of expression of this gene may result in specific tissue or cell types (eg, kidney tissue, urogenital tissue, bladder tissue, cancerous tissue and wound tissue) or body fluid (eg, kidney tissue, urogenital tissue, bladder tissue) taken from an individual having such a disorder. , Lymph, serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

Tissue distribution in bladder tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful in the study and treatment of urinary and gastrointestinal disorders. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 104 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, where a is any integer from 1 to 1013 of SEQ ID NO: 104 and b is from 15 to
Is an integer of 1027, wherein both a and b correspond to the nucleotide residue positions set forth in SEQ ID NO: 104, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

CHARACTERISTICS OF PROTEIN ENCODED BY GENE NO: 95 In certain embodiments, a polypeptide of the invention comprises the following amino acid sequence:
LHGEQVPIYIFLLMQPLNFECISFLNCIEQYSVGVI
HNSVTIYAACDRENECMDIRYL (SEQ ID NO: 454), and / or GTSWASRFFTCH (SEQ ID NO: 455). Polynucleotides encoding these polypeptides are also included in the invention.

[0521]   This gene is mainly expressed in T cells.

Thus, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, as well as for immune disorders and inflammatory disorders, particularly immunodeficiency disorders such as AIDS. It is useful as a reagent for diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, especially the immune system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in healthy tissues or fluids from unaffected individuals). The expression of this gene is dependent on the specific tissue or cell type (eg, immune, hematopoietic, cancerous and wound tissue) or body fluid (eg, lymph, serum, plasma, etc.) taken from an individual having such a disorder. Urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

[0523] A preferred epitope is the residue in SEQ ID NO: 254: Lys-28 to Th.
An epitope is included that includes the sequence shown as r-34.

This tissue distribution in T cells indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the treatment and diagnosis of disorders of the immune system. In addition, this gene product may induce cytokine production, antigen presentation, or cancer treatment (
For example, it may be involved in the regulation of other processes that may also suggest utility in boosting the immune response). Since this gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune function. Therefore, it is associated with arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, chronic granulomatosis, inflammatory bowel disease, sepsis, contusions, neutropenia, neutrophilia, psoriasis. , Hypersensitivity (eg, T cell-mediated cytotoxicity); immune response to organs and tissues (eg, host vs. graft and graft vs. host disease) or autoimmune disorder (eg, autoimmune infertility, lens tissue injury, Demyelination, systemic lupus erythematosus,
It can also be used as a drug for immunological disorders, including drug-induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma) as well as tissues. Moreover, this gene product may have commercial utility in the proliferation of stem cells and associated progenitor cells of various blood lineages, as well as in the differentiation and / or proliferation of various cell types. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 105 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 696 of SEQ ID NO: 105 and b is from 15 to 7
Is an integer of 10, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 105, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

[0526]     (Characteristics of protein encoded by gene number 96)   In a particular embodiment, the polypeptide of the invention comprises the following amino acid sequence:

[0527]

[Chemical 16] Polynucleotides encoding these polypeptides are also included in the invention.

[0528]   This gene is mainly expressed in lymphoma and frontal cortex.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, as well as for neurological and hematopoietic disorders, particularly Alzheimer's disease and Parkinson's disease. It is useful as a reagent for diagnosis of diseases and conditions including, but not limited to, neurodegenerative conditions such as. Similarly, polypeptides and antibodies to these polypeptides include
It is useful in providing immunological probes for the differential identification of tissues or cell types.
Significantly higher or higher than standard gene expression levels (ie, expression levels in normal tissues or fluids from unaffected individuals) for many disorders of the tissues or cells, particularly the immune and nervous systems Low levels of expression of this gene may result in specific tissues or cell types (eg, nervous, immune, hematopoietic, cancerous and wound tissues) or body fluids collected from individuals with such disorders.
(Eg, lymph, serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

The tissue distribution in frontal cortex and lymphoma indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of nervous and hematopoietic disorders. In particular, polynucleotides and polypeptides corresponding to this gene include neurodegenerative disease states, behavioral disorders or inflammatory conditions (eg, Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, meningitis, encephalitis, demyelinating diseases, peripheral nerves). Disability, neoplasia, trauma, congenital anomaly, spinal cord injury, ischemia and infarction, aneurysm, bleeding, schizophrenia, mania, dementia, paranoia, obsessive-compulsive disorder, panic disorder, learning disability, ALS, psychosis , Autism, and behavioral changes (including feeding, sleep patterns, balance, and impaired sensory perception) may be useful.In addition, elevated expression of this gene product in regions of the brain may Indicates that it plays a role in normal neuronal function, potentially this gene product is synaptogenic, neurotransmissive, learning, cognitive, homeostatic, or neuronal. In addition, the gene or gene product may also play a role in the treatment and / or detection of developmental, sex-related, or cardiovascular disorders associated with the developing embryo. Furthermore, expression in cell sources marked by proliferative cells indicates that this protein may play a role in regulation of cell division and may have utility in the diagnosis and treatment of cancer and proliferative disorders. In patterning, developing proteins depend on cell differentiation and / or decisions involving apoptosis, so this protein may be involved in apoptosis or tissue differentiation and may also be useful in cancer therapy. The antibody is a tumor marker and / or immunity to the tissues listed above. It may show utility as a legal target. Proteins and antibodies against the protein may show utility as a tumor marker and / or immunotherapy targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 106 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 516 of SEQ ID NO: 106 and b is from 15 to 5
Is an integer of 30, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 106, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

[0532]     (Characteristics of protein encoded by gene number 97)   This gene is expressed mainly in the spleen of patients with metastatic melanoma.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, as well as for immune disorders or hematopoietic disorders (especially metastatic melanoma and other cancers). , And immune disorders and conditions such as anemia, AIDS, arthritis and asthma), and are useful as reagents for the diagnosis of diseases and conditions. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. With respect to many disorders of the tissues or cells described above, particularly with respect to the immune system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in healthy tissues or body fluids from undiseased individuals). The expression of this gene is dependent on the specific tissue or cell type (eg, immune, hematopoietic, and cancerous and wound tissues) or body fluid (eg, lymph, serum, plasma) taken from an individual having such a disorder. , Urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

A preferred epitope is Pro-26 to Asn-3 in SEQ ID NO: 256.
It includes an epitope containing the sequence shown as 4 residues.

This tissue distribution in the spleen indicates that the polynucleotides and polypeptides corresponding to this gene are associated with metastatic melanosarcoma and other cancers, as well as leukemias, lymphomas,
It is suggested to be useful for the diagnosis and treatment of other immune disorders and conditions including AIDS, arthritis, asthma and microbial infections. In addition, polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoietic-related disorders such as anemia, pancytopenia, leukopenia, or thrombocytopenia. This is because stromal cells are important for hematopoietic cell production. This use includes bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow repopulation, neoplastic radiotherapy or chemotherapy. This gene product may also be associated with lymphopoiesis. Thus, the gene product may be used in immune disorders such as infection, inflammation, allergy, immunodeficiency, etc. In addition, the gene product may be used in the expansion of stem cells and associated progenitor cells of various blood lineages, as well as in various types. May have commercial utility in differentiating and / or proliferating cell types of the protein, and antibodies against the protein may be tumor markers and / or for the tissues listed above.
Or it may show utility as an immunotherapeutic target.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 107 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 378 of SEQ ID NO: 107 and b is from 15 to 3
Is an integer of 92, where both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 107, and b is a + 14 or greater) R.

CHARACTERISTICS OF PROTEIN ENCODED BY GENE NO: 98 In certain embodiments, a polypeptide of the invention comprises the following amino acid sequence: GTVTQKRKCVFGKYLLSTCSLMFSSMHGGASWSWKA.
KQTSSSAGFLCLHVLCPALQLTREKYKTWPWPSFFI (
SEQ ID NO: 458), and / or MKEGQGHVLYFSRVNCKAGH
XTCRRQRKPADELVCFAFQEQAPCILLNIRLQVLNKY
LPNTHFLTFCVTVP (SEQ ID NO: 459). Polynucleotides encoding these polypeptides are also included by the invention. Disclosed cDNA
The gene coding for is believed to be present on chromosome 8. Therefore, the polynucleotide according to the present invention is useful as a marker in linkage analysis for chromosome 8.

[0538]   This gene is expressed primarily in the pineal gland and synovial sarcoma.

Thus, the polynucleotides and polypeptides of the invention include, for the differential identification of tissues or cell types present in a biological sample, as well as for endocrine or skeletal disorders, including cancer, It is useful as a reagent for diagnosis of diseases and conditions, which is not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the above tissues or cells, particularly the endocrine system, significantly higher or lower levels of normal gene expression levels (ie, expression levels in healthy tissues or fluids from non-disordered individuals) The expression of this gene is dependent on the specific tissue or cell type (eg endocrine tissue, pineal tissue, skeletal tissue, and cancerous and wound tissue) or body fluid (eg Lymph, serum, plasma, urine, synovial fluid, and spinal fluid)
Or it can be detected in another tissue or cell sample.

This tissue distribution in the pineal gland indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of disorders of the endocrine system. Furthermore, polynucleotides and polypeptides corresponding to this gene are
Various endocrine disorders and cancers (particularly Addison's disease, Cushing's syndrome), as well as the pancreas (eg diabetes), adrenal cortex, ovaries, pituitary gland (eg hyperpituitary gland,
Hypopituitarism), thyroid (eg hyperthyroidism, hypothyroidism)
, Parathyroid gland (eg hyperparathyroidism, hypoparathyroidism), hypothalamus,
And for the detection, treatment and / or prevention of testicular disorders and / or cancer. Alternatively, expression of this gene product in the synovium may be associated with disorders and conditions affecting the skeletal system (especially osteoporosis), bone cancer, and disorders involving connective tissue (eg,
Detection and treatment of arthritis, trauma, tendinitis, chondromalacia, and inflammation, such as various autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma and dermatomycosis, and dwarfism. , Spinal deformities and certain joint disorders, and chondrodysplasia (ie, congenital vertebral epiphyseal dysplasia, familial osteoarthritis, type II osteogenesis
II), Schmidt metaphyseal cartilage hypoplasia) is suggested for its role in diagnosis or treatment. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 108 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 977 of SEQ ID NO: 108 and b is from 15 to 9
Is an integer of 91, wherein both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 108, and b is a + 14 or greater) and one or more polynucleotides comprising It

CHARACTERISTICS OF PROTEIN ENCODED BY GENE NO: 99 In certain embodiments, a polypeptide of the invention comprises the amino acid sequence: TMTGIDSSPEEIILRQVGCKQQQGKGVEHVEGSSA.
EAGEAARGGGAKGGGGAAGKGTSKVGTLRRTGST (
SEQ ID NO: 460). Polynucleotides encoding these polypeptides are also included by the invention.

[0543]   This gene is expressed primarily in the breast and fetal spleen.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, as well as diseases of the reproductive system and developing organs, particularly those of immunodeficiency. Such as congenital defects that cause diseases in the immune system or hematopoietic system), and are useful as reagents for diagnosis of diseases and conditions. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher than standard gene expression levels (ie, expression levels in normal tissues or fluids from unaffected individuals) for many disorders of the above tissues or cells, especially for developing and reproductive systems Alternatively, lower levels of expression of this gene may be associated with specific tissues or cell types (eg, reproductive tissue, developing tissue, immune tissue, hematopoietic tissue, and cancerous tissue) taken from an individual having such a disorder. Wound tissue) or body fluids (eg lymph, amniotic fluid, serum, plasma,
Urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

A preferred epitope is the residues in SEQ ID NO: 258: Gly-23 to As.
Examples of the epitope include the sequences shown as n-30 and Ser-37 to Asn-43.

This tissue distribution in fetal spleen indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of diseases involving the developing tissues and reproductive organs. This secreted protein is also used to determine the biological activity, to raise antibodies (as a tissue marker), to isolate cognate ligands or receptors, to identify agents that modulate their interaction. Can be used for and as a dietary supplement. It can also have a very wide range of biological activities. Representative of these are cytokines, which induce cell growth / differentiation regulation or other cytokines; immunostimulatory / immunosuppressive activity (eg, to treat human immunodeficiency virus infections, cancers, autoimmune diseases and allergies); hematopoiesis. Regulation (eg, to treat anemia or as an adjunct to chemotherapy); stimulation or proliferation of bone, cartilage, tendons, ligaments and / or nerves (eg, to treat wounds, stimulation of follicle stimulating hormone (fertilization) Chemotaxis and chemokinesis activity (eg, to treat infections, tumors); hemostatic or thrombolytic activity (eg, to treat hemophilia, myocardial infarction, etc.); anti-inflammatory Activity (eg, to treat septic shock, Crohn's disease); as an antimicrobial agent; to treat psoriasis or other hyperproliferative disorders; metabolism This is because of the adjustment of the preliminary action. The use of the corresponding nucleic acids in gene therapy procedures is also contemplated. The protein as well as antibodies to this protein may show utility as tumor markers for the tissues listed above and / or targets for immunotherapy.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 109 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 898 of SEQ ID NO: 109 and b is from 15 to 9
1 is an integer of 12, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 109, and b is a + 14 or greater) It

CHARACTERISTICS OF PROTEIN ENCODED BY GENE NO: 100 In certain embodiments, a polypeptide of the invention comprises the following amino acid sequence: AQREAGSPRRRKSLKKAVLXMXEMGGGCRGSMG.
PGPGYSAGSRVCRGSSLPQVAPFNPSRAHLLPPPVG
GGLNSVWLSGVQLSTPPYADWEGVGQSPQPRGPWMG
SSSLGTVGPGCVLSGCPTVKANGGSSPCSEMLLGERRL
LEPSVGPVSGCPERREGGHGHARGAAGVVVKGHASVQ
LNFLSLI (SEQ ID NO: 461), KAEFTFAKEKNAKAQLGKK
GTRWVKHDKRKEIQLYGCVTLNDDPSCPPCPVPTLP
PFWTATYGSHGRFQKPPFSQHLRAGGAPVGLDCGAP
TQYAARPHGPK (SEQ ID NO: 462), GCRGSMGPPGPGYSAG
SRVCRGSSLPQ (SEQ ID NO: 463), QPRGPWMGSSSLGTV
GPGCVLS (SEQ ID NO: 464), and / or GAAGVVVKGHAS
VQLNFLSLI (SEQ ID NO: 465). Polynucleotides encoding these polypeptides are also included by the invention.

[0549]   This gene is expressed primarily in endothelial cells, immune cells, and cancer cells.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, as well as diseases related to immune, endothelial, and hematopoietic tissues or cells (especially cancer, It is useful as a reagent for diagnosis of diseases and conditions, including but not limited to inflammation, or immunodeficiency conditions). Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly relative to standard gene expression levels (ie, expression levels in normal tissues or body fluids from unaffected individuals) for many disorders of the tissues or cells, particularly the immune, hematopoietic and endothelial systems. High or low levels of expression of this gene
A specific tissue or cell type (eg,
Endothelial tissue, immune system, hematopoietic tissue, and cancerous tissue and wound tissue) or body fluid (
(Eg, lymph, serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

The tissue distribution in immune and hematopoietic tissues indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of diseases of the immune and hematopoietic system, including cancer. More specifically, this gene product is involved in the control of cytokine production, antigen presentation, or other processes that may also suggest utility in treating cancer (eg, by boosting the immune response). obtain. Since this gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune function. Therefore, arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, chronic granulomatosis, inflammatory bowel disease, sepsis, acne, neutropenia, neutropenia, psoriasis, T Hypersensitivity such as cell-mediated cytotoxicity); Immune response (eg host vs. graft and graft vs. host disease) to transplant organs and tissues or autoimmune disorders (eg autoimmune infertility, lens tissue injury, demyelination) , Systemic lupus erythematosus, drug-induced hemolytic anemia, rheumatoid arthritis, Sjögren's disease, scleroderma) and tissues as well as agents for immunological disorders. Furthermore, this gene product may have commercial utility in the expansion of stem cells and associated progenitor cells of various blood lineages, and in the differentiation and / or proliferation of various cell types. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 110 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 861 of SEQ ID NO: 110 and b is from 15 to 8
Is an integer of 75, wherein both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 110, and b is a + 14 or more) are excluded. It

FEATURES OF PROTEIN ENCODED BY GENE NO: 101 In certain embodiments, a polypeptide of the invention comprises the following amino acid sequence: GKPLSAIFPICHMMFLPGKFNLGISHRCCRMTSP.
WDKRQQLRRQECKSDPHVQNPRIHFPESKNSFPSAYI
FVSEGNGVSPSKWHCIYSGTSLSH (SEQ ID NO: 466), and / or GERGRYQSKYSATWMVVTHYLQTQRCKLREM
NSWIQGNEFLDSEHEGQIYIPVSIVDAYPKD (SEQ ID NO: 467). Polynucleotides encoding these polypeptides are also included by the invention.

This gene is expressed primarily in human kidney and to a lesser extent in liver.

Accordingly, the polynucleotides and polypeptides of the invention include for differential identification of tissues or cell types present in a biological sample, as well as renal disorders, urogenital disorders, liver disorders, and endocrine disorders. Are useful as reagents for diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher or lower than standard gene expression levels (ie, expression levels in normal tissues or fluids from unaffected individuals) for many disorders of the tissues or cells, particularly the renal or endocrine system Levels of this gene expressed in a particular tissue or cell type taken from an individual having such a disorder (eg, urogenital tissue, renal tissue, endocrine tissue, liver tissue, and cancerous and wound tissue) or It can be detected in body fluids such as lymph, serum, plasma, bile, urine, synovial fluid and spinal fluid or another tissue or cell sample.

A preferred epitope is SEQ ID NO: 260 at residues: Glu-38 to Lys.
An epitope including the sequence shown as -43 is included.

Tissue distribution in the kidney indicates that polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of renal disorders, including non-inflammatory and inflammatory lesions of the kidney and tumors. In addition to this gene or gene product, in addition to Wilms tumor disease, and congenital renal disorders (eg, horseshoe kidney, polycystic kidney disease and Falconi syndrome), renal failure, nephritis (ne.
and / or treatment of renal diseases including renal acidosis, proteinuria, pyuria, edema, pyelonephritis, hydronephrosis, nephrotic syndrome, crush syndrome, glomerulonephritis, hematuria, renal colic and renal stones. It can be used for detection. Alternatively, expression in the liver may be affected by corresponding polynucleotides and polypeptides of this gene in liver disorders and cancer (eg, hepatoblastoma, jaundice, hepatitis, liver metabolic diseases and conditions that may result from differentiation of hepatic progenitor cells). Is useful for the detection and treatment of The protein and antibodies to the protein are tumor markers for the tissues listed above and / or
Alternatively, it may show utility as a target for immunotherapy.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 111 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 445 of SEQ ID NO: 111 and b is 15
Is an integer from ~ 459, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 111, and where b is a + 14 or more). Are excluded.

[0559]     (Characteristics of protein encoded by gene number 102)   This gene is expressed primarily in renal cortex and fetal tissue.

This tissue distribution in the kidney indicates that this gene or gene product is associated with renal failure, nephritis, in addition to Wilms tumor disease, and congenital kidney damage (eg, horseshoe kidney, polycystic kidney disease and Falconi syndrome). Tubular acidosis, proteinuria, pyuria, edema, pyelonephritis, hydronephrosis, nephrotic syndrome, crush syndrome, glomerulonephritis, hematuria,
It shows that it can be used for the treatment and / or detection of renal diseases, including renal colic and kidney stones. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 112 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, where a is any integer from 1 to 595 of SEQ ID NO: 112 and b is from 15 to 6
09 is an integer of 0, where both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 112, and b is a + 14 or more) are excluded. It

[0562]     (Characteristics of protein encoded by gene number 103)   This gene is expressed primarily in the ovary and brain.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, and in addition to neurodegenerative conditions, as well as reproductive and nervous system conditions (particularly Proliferative disorders such as ovarian cysts or cancer)
It is useful as a reagent for diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher or more than standard gene expression levels (ie, expression levels in healthy tissue or body fluids from unaffected individuals) with respect to many disorders of the tissues or cells, particularly the nervous and immune systems Low levels of expression of this gene
Specific tissues or cell types (eg, neural, reproductive, endocrine, and cancerous and wound tissues) or body fluids (eg, lymph, serum, plasma, urine, etc.) collected from individuals with such disorders. Synovial fluid, and spinal fluid) or another tissue or cell sample.

This tissue distribution in ovarian tissue suggests that polynucleotides and polypeptides corresponding to this gene are useful for studying and treating reproductive disorders such as infertility. Alternatively, a neurodegenerative disease condition, behavioral disorder or inflammatory condition (
For example, Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, meningitis, encephalitis, demyelinating disease, peripheral neuropathy, neoplasia, trauma, congenital abnormalities, spinal cord injury, ischemia and infarction, aneurysm, hemorrhage , Schizophrenia, mania, dementia, paranoia, obsessive-compulsive disorder, panic disorder, learning disability, ALS, psychosis, autism, and behavioral changes (including impaired nutrition, sleep patterns, balance, and perception) Useful for detection / treatment. Furthermore, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is associated with synapse formation, neurotransmission, learning, recognition, homeostasis, or neuronal differentiation or survival. In addition, the gene or gene product may also play a role in the treatment and / or detection of developmental, sex-related, or circulatory disorders associated with the developing embryo. The protein, as well as antibodies to this protein,
It may show utility as a tumor marker and / or immunotherapeutic target for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 113 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 1390 of SEQ ID NO: 113 and b is from 15 to
1404, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 113, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

FEATURES OF PROTEIN ENCODED BY GENE NO: 104 In certain embodiments, a polypeptide of the invention comprises the following amino acid sequence:
ISIRGRILYKMAYFKVCVIIWFQQFCVEETSIIKNV
RMLTSEFQNSYATPVSGLLPGAVAWRGGAVYGWVRH
AMQVLQKEPTQPSSSFLPPSDAASFWGPESRLHLTW (
SEQ ID NO: 468), KPFAFSARNFPTMLSEAYFQDPRMRQ
HHLGVERMTVAWVPSAIPAWRASPTRTQHHPSKPQH
QEGAQKQGWHMNSGILMSAYEHFL (SEQ ID NO: 469), and / or HSKQNICREVNILKMFFLHEIKKTVTDNIST
QRRFTYNHQPGSVSIFFSVTDILDFEVPFGL (SEQ ID NO:
470). Polynucleotides encoding these polypeptides are also included by the invention.

This gene is expressed primarily in melanocytes and T cells stimulated PHA.

Accordingly, the polynucleotides and polypeptides of the present invention include, for differential identification of tissues or cell types present in a biological sample, as well as immune system disorders, or integumentary system disorders, and cancers It is useful as a reagent for diagnosing diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. In connection with many disorders of the above tissues or cells, especially the immune system,
Significantly higher or lower levels of expression of this gene relative to normal gene expression levels (ie, expression levels in healthy tissue or body fluids from non-disordered individuals) are obtained from individuals with such disorders. A particular tissue or cell type harvested (eg, integumental tissue, immune tissue, hematopoietic tissue, and cancerous and wound tissue) or body fluid (eg, lymph, serum, plasma, urine, synovial fluid, and spinal fluid), Or it can be detected in another tissue or cell sample.

This tissue distribution in immune cells indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the study, diagnosis and treatment of cancer and immune system disorders. Alternatively, expression in melanocytes can be characterized by congenital disorders (ie, nevus, pigmented nevus, freckles, Mongolian spots, hemangiomas, wine-like syndrome), integuments, and polynucleotides corresponding to this gene. tumor(
Keratosis, Bowen's disease, basal cell carcinoma, squamous cell carcinoma, malignant melanoma, Paget's disease, mycosis fungoides, and Kaposi's sarcoma), skin damage and inflammation (ie, wounds, rashes, erythema erythematosus disorders, Psoriasis, dermatitis), atherosclerosis, urticaria (u
ticaria), eczema, photophobia, autoimmune disorders (eg, lupus erythematosus, vitiligo, dermatomyositis, localized scleroderma, scleroderma, pemphigoid, and pemphigus), keloids,
It has utility in treating, diagnosing and / or preventing various skin disorders including striatum, erythema, petechiae, purpura, and blepharoptosis. In addition, such disorders can result in viral and bacterial infections of the skin (ie, herpes simplex, warts, chickenpox,
Molluscum contagiosum, herpes zoster, swelling, cellulitis, erysipelas, impetigo, ringworm, worm (
althelets foot), and tinea) may be predisposed to increase susceptibility. In addition, the protein product of this gene is also associated with various connective tissue disorders (eg, arthritis, trauma, tendinitis, chondromalacia, and inflammation), autoimmune disorders (eg.
For example, rheumatoid arthritis, lupus, scleroderma and dermatomyositis, as well as dwarfism, spinal deformities and certain joint abnormalities, and chondrodysplasia (ie congenital vertebral epiphyseal dysplasia, familial osteoarthritis type II). Bone hypoplasia, Schmidt metaphyseal cartilage hypoplasia) may be useful in the treatment or diagnosis. The protein as well as antibodies to this protein may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 114 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, where a is any integer from 1 to 839 of SEQ ID NO: 114 and b is from 15 to 8
Is an integer of 53, wherein both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 114, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

CHARACTERISTICS OF PROTEIN ENCODED BY GENE NO: 105 This gene is expressed predominantly in B-cell lymphomas and to a lesser extent in cutaneous fibrosarcomas.

Accordingly, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, as well as for immune disorders or integumental disorders (especially lymphoid and soft tissue cancers). Are useful as reagents for the diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the above tissues or cells, especially for the immune system, significantly higher or lower levels of this gene relative to standard gene expression levels (ie, expression levels in normal tissues or fluids from individuals without the disorder). The expression of a gene is a specific tissue or cell type (eg, immune tissue, hematopoietic tissue, integumental tissue, and cancerous and wound tissue) or body fluid (eg, lymph, serum) obtained from an individual having such a disorder. , Plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

This tissue distribution in B-cell lymphoma, polynucleotides and polypeptides corresponding to this gene, treat hematopoietic-related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia, or leukemia. And useful for diagnosis. This is because stromal cells are important in hematopoietic cell production. This use includes in vitro culture of bone marrow cells, bone marrow transplantation, bone marrow repopulation, neoplastic radiotherapy or chemotherapy. This gene product may also be involved in lymphocyte production. Therefore, it can be used for immune disorders such as infections, inflammations, allergies, immunodeficiencies. In addition, this gene product may have commercial utility in the expansion of stem cells and the directed precursors of various blood systems, as well as the differentiation and / or proliferation of various cell types. Alternatively, the protein product of this gene may be associated with congenital disorders (ie, nevus, pigmented nevus, freckles, Mongolian spots, hemangiomas, wine-like syndrome), integumental tumors (ie, keratoses, Bowen's disease, basal disease). Cell carcinoma, squamous cell carcinoma, malignant melanoma, Paget's disease, mycosis fungoides, and Kaposi's sarcoma), skin damage and inflammation (ie, wounds, rashes, erythema erythema vulgaris, psoriasis, dermatitis), atherosclerosis, kidneys Measles, eczema, photophobia, autoimmune disorders (ie lupus erythematosus, vitiligo, dermatomyositis, localized scleroderma, scleroderma, pemphigoid, and pemphigus), keloids, striatum, erythema, petechiae, It may be useful in the treatment, diagnosis and / or prophylaxis of various skin disorders including purpura and blepharveosis. further,
Such disorders include viral and bacterial infections of the skin (ie, herpes simplex, warts, chickenpox, molluscum contagiosum, herpes zoster, swelling, cellulitis, erysipelas, impetigo,
It can predispose to increased susceptibility to ringworm, worm, and ringworm). In addition, the protein product of this gene is also associated with various connective tissue disorders (eg, arthritis, trauma, tendinitis, chondromalacia, and inflammation), autoimmune disorders (eg, rheumatoid arthritis, lupus, scleroderma and skin). Of myositis, and dwarfism, spinal deformity and certain joint abnormalities, and dyschondrosis (ie congenital vertebral epiphyseal dysplasia, familial osteoarthritis, type II osteogenesis imperfections, Schmidt metaphyseal cartilage dysplasia) It may be useful for treatment or diagnosis.The protein as well as antibodies against this protein may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 115 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, where a is any integer from 1 to 831 of SEQ ID NO: 115 and b is from 15 to 8
Is an integer of 45, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 115, and b is a + 14 or more) and one or more polynucleotides are excluded. It

(Characteristics of Protein Encoded by Gene No. 106) When tested on the U937 cell line, supernatant taken from cells containing this gene activated a GAS (gamma activating sequence) promoter element. did.
Therefore, this gene appears to activate myeloid cells via the JAK-STAT signaling pathway. GAS is a promoter element found upstream of many genes involved in the Jak-STAT pathway. The Jak-STAT pathway is a large signaling pathway involved in cell differentiation and proliferation. Therefore, G
Activation of the Jak-STAT pathway, reflected by the binding of AS elements, can be used to indicate proteins involved in cell proliferation and differentiation. In a particular embodiment, a polypeptide of the invention comprises the following amino acid sequence: KVIDVIFSLPPGRKATFSCPLLAPLSGAXGLPGGGGAN.
RPGPFLPCIQPWGPLRLPEGC (SEQ ID NO: 471), MSSSL
CPQGGKPPSLAPWPLCQGPXVCRVGVPTGRALSSPA
SSHGGLCDCRKVAWLVPGPAQARGRAWFYFYLTLF
SVL (SEQ ID NO: 472), and / or LALSSPASSHGGLCDC
RKVAWLVPGP (SEQ ID NO: 473). Polynucleotides encoding these polypeptides are also included in the present invention.

This gene is expressed primarily in T cells, fetal liver, and to a lesser extent in various normal and transformed tissues.

Accordingly, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, as well as for immune, hematopoietic, or developmental disorders (immunodeficiency and cancer). And are useful as reagents for the diagnosis of diseases and conditions, including but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher or higher than standard gene expression levels (ie, expression levels in normal tissues or body fluids from unaffected individuals) in relation to many disorders of the tissues or cells, particularly the immune system Low levels of expression of this gene may result in specific tissues or cell types (eg, immune, hematopoietic, developmental, and cancerous and wound tissues) or body fluids (eg, immune and hematopoietic, developmental tissues) taken from individuals with such disorders. , Lymph, serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

A preferred epitope is the residue in SEQ ID NO: 265: Arg-5-Pro.
An epitope including the sequence shown as -12 is included.

This tissue distribution in B cells and fetal liver indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the study and treatment of immune and developmental disorders. In addition, polynucleotides and polypeptides corresponding to this gene are associated with hematopoietic-related disorders (eg, anemia, pancytopenia, leukopenia,
It is useful for the treatment and / or diagnosis of thrombocytopenia, or leukemia).
This is because stromal cells are important in hematopoietic cell production. This use includes in vitro culture of bone marrow cells, bone marrow transplantation, bone marrow repopulation, neoplastic radiotherapy or chemotherapy. This gene product may also be involved in lymphocyte production. Therefore, it can be used for immune disorders such as infections, inflammations, allergies, immunodeficiencies and the like. Furthermore, this gene product may have commercial utility in the expansion of stem cells and the directed precursors of various blood systems, as well as the differentiation and / or proliferation of various cell types. Furthermore, prominent expression in fetal tissues and other cell sources in proliferating cells allows this protein to play a role in regulating cell division and is useful in the diagnosis and treatment of cancer and other proliferative disorders. Indicates that Similarly, the developing tissue is a cell differentiation in pattern formation and / or
Or it depends on decisions involving apoptosis. Thus, this protein may also be involved in apoptosis or tissue differentiation and may also be useful in cancer therapy. The protein as well as antibodies to this protein may show utility as tumor markers in the tissues listed above and / or as targets for immunotherapy.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 116 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 746 of SEQ ID NO: 116 and b is from 15 to 7
Is an integer of 60, wherein both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 116, and b is a + 14 or greater) and one or more polynucleotides comprising It

Characterization of the Protein Encoded by Gene No: 107 One embodiment of this gene comprises the amino acid sequence: MQREARWARPWMASTVESRMPEGKWRRFSTDLATWGA.
TPARSWTKASRGSTTAWTRLPMRSTMVLDKQERKQR
SLAMGSTLTLDRPGRKQTKRSKGSTGLSRLGRKQR
NLAKGSTMLTRLERXWRSLAQVPTMLLARPGRSCR
MLIMGSTKPARRRPTSC (SEQ ID NO: 474). A further embodiment is
It is a polynucleotide encoding these polypeptides.

This gene is expressed primarily in keratinocytes and tissues undergoing wound healing, and to a lesser extent in osteoblasts and smooth muscle.

Accordingly, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, as well as for skin disorders, fibrosis, scarring, osteoporosis, osteopetrosis. It is useful as a reagent for diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. With respect to many disorders of the above tissues or cells, especially skin, bone, or connective tissue, to standard gene expression levels (ie, expression levels in healthy tissue or body fluids from individuals without disorders). Significantly higher or lower levels of expression of this gene will result in specific tissues or cell types taken from individuals with such disorders (skin tissue, bone tissue, connective tissue and cancerous and wound tissue). Or it can be detected in bodily fluids such as lymph, serum, plasma, urine, synovial fluid, and spinal fluid or another tissue or cell sample.

A preferred epitope is SEQ ID NO: 266 with Gly-76 to Leu-8.
3, Ala-108 to Glu-113, Ala-126 to Lys-132, Gl
Includes the epitope shown as residues y-145 to Leu-151.

The tissue distribution in keratinocytes indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and / or treatment of various skin disorders. Elevated expression of this protein in skin and keratinocytes suggests that this protein may be associated with keratinocyte proliferation, survival, and / or differentiation. Therefore, it may play a role in processes such as fibrosis or wound healing. Similarly, expression of this protein in osteoblasts indicates that it may also play a role in osteoblast survival, proliferation, and / or differentiation, and in the treatment of disorders such as osteoporosis or osteopetrosis. It has been shown to be useful.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 117 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably, according to the invention, the nucleotide sequence described by the general formula ab (where a is any integer from 1 to 974 of SEQ ID NO: 117 and b is an integer from 15 to 988, Here, both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 117, and where b is a + 14 or more) one or more polynucleotides are excluded.

Characterization of Protein Encoded by Gene No: 108 The translated sequence of this gene shares homology with mouse calmodulin binding protein. Calmodulin, a calcium binding regulatory protein, is an integral subunit of red blood cells and other plasma membrane calcium ATPases. Increased cytosolic calcium induces binding of calcium ions to calmodulin, which triggers activation of calcium ATPase allosterism, and subsequently accelerates calcium ion export from cells.

This gene is expressed primarily in teratocarcinoma cells and to a lesser extent in myeloid progenitor cells.

Thus, the polynucleotides and polypeptides of the present invention may be used for differential identification of tissues or cell types present in a biological sample, and in addition to immune or hematopoietic disorders, developmental deficiency, calcium transport deficiency. Are useful as reagents for the diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significant to standard gene expression levels (ie, expression levels in normal tissues or body fluids from unaffected individuals) in association with many disorders of the above tissues or cells, especially embryonic and fetal tissues. High or low levels of this gene are expressed in specific tissues or cell types harvested from individuals with such disorders, such as developing tissue, immune tissue, hematopoietic tissue, and cancerous and wound tissue. ) Or body fluids (eg lymph,
Serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

A preferred epitope is at residues: Tyr-124-G in SEQ ID NO: 267.
It includes an epitope containing the sequence designated as ly-129.

This tissue distribution in teratocarcinoma cells indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of developmental disorders and in organ regeneration. Furthermore, prominent cell source expression in proliferating cells indicates that this protein may play a role in regulating cell division and may have utility in the diagnosis and treatment of cancer and other proliferative disorders. Show. Similarly, developing tissue relies on decisions involving cell differentiation and / or apoptosis in pattern formation. Thus, this protein may also be involved in apoptosis or tissue differentiation and may also be useful in cancer therapy. The protein as well as antibodies to this protein may show utility as tumor markers in the tissues listed above and / or as targets for immunotherapy. Alternatively, the homology of the translation product of this gene with the mouse calmodulin binding protein indicates that the translation product of this gene may be useful, for example, for disorders involving calcium transport across the plasma membrane. This further indicates that this type of disorder can be the cause of disorders such as hypertension.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 118 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 1933 of SEQ ID NO: 118 and b is from 15 to
Is an integer of 1947, wherein both a and b correspond to the nucleotide residue positions set forth in SEQ ID NO: 118, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

[0593]     (Characteristics of protein encoded by gene number 109)   One embodiment of this gene comprises a polypeptide of the following amino acid sequence:

[0594]

[Chemical 17] A further embodiment are polynucleotides encoding these polypeptides.

This gene is expressed primarily in ovarian tumors and to a lesser extent in smooth muscle and breast cancer.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, and for cancers such as rhabdomyosarcoma or fibroids, especially ovarian. It is useful as a reagent for diagnosis of diseases and conditions, including but not limited to cancer, muscular cancer, and breast cancer). Similarly,
The polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, especially the reproductive system, significantly higher or lower levels of this gene than standard gene expression levels (ie, expression levels in healthy tissues or fluids from undisturbed individuals) are used. The expression of a gene is a particular tissue or cell type (eg, ovarian tissue, breast tissue, cancerous tissue and wound tissue) or body fluid (eg, lymph, serum, breast milk, plasma) taken from an individual having such a disorder. , Urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

[0597] A preferred epitope is the residue: Arg-24-in SEQ ID NO: 268.
An epitope including the sequence shown as Arg-29 is mentioned.

This tissue distribution in ovarian cancer tissue indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of cancer, especially ovarian and breast cancer. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 119 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 1434 of SEQ ID NO: 119 and b is from 15 to
Is an integer of 1448, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 119, and b is a + 14 or more) are excluded. It

Characterization of the Protein Encoded by Gene No. 110 The translation product of this gene shares sequence homology with bovine crocin inhibitors IIa and IIb, which are believed to be important as protease inhibitors.

[0601]   This gene is mainly expressed in keratinocytes.

Accordingly, the polynucleotides and polypeptides of the present invention include for differential identification of tissues or cell types present in a biological sample, as well as integumental disorders (eg, psoriasis) and wound healing abberations. Are useful as reagents for diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, particularly the integumentary system, significantly higher or lower levels of normal gene expression levels (ie, expression levels in healthy tissues or fluids from non-disordered individuals) are used. The expression of this gene may depend on the specific tissue or cell type (eg, integumental tissue, and cancerous and wound tissue) or body fluid (eg, lymph, serum, plasma, urine, etc.) taken from an individual having such a disorder. Synovial fluid, and spinal fluid) or another tissue or cell sample.

A preferred epitope is the residue in SEQ ID NO: 269: Tyr-39 to Ly.
An epitope is included that includes the sequence designated as s-58.

This tissue distribution in keratinocytes shows that the bovine crocin inhibitor IIa
And associated with homology with IIb, it is shown that polynucleotides and polypeptides corresponding to this gene are useful for promoting wound healing. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 120 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 482 of SEQ ID NO: 120 and b is from 15 to 4
Is an integer of 96, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 120, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

FEATURES OF PROTEIN ENCODED BY GENE NO: 111 This gene is predominantly expressed in fetal liver / spleen, T cells, and to a lesser extent in bone marrow and primordial dendritic cells.

Accordingly, the polynucleotides and polypeptides of the present invention are for the differential identification of tissues or cell types present in a biological sample, and include but are not limited to hematopoietic disorders; immune dysfunction; lymphomas. It is useful as a reagent for diagnosis of non-limiting diseases and conditions. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, particularly the immune system, significantly higher or lower levels of this gene than standard gene expression levels (ie, expression levels in healthy tissues or fluids from individuals without disorders). Gene expression
Specific tissues or cell types (eg, immune, hematopoietic, and cancerous and wounded tissues) or body fluids (eg, lymph, serum, plasma, urine, synovial fluid, etc.) collected from individuals with such disorders. And cerebrospinal fluid), or another tissue or cell sample.

A preferred epitope is the residue in SEQ ID NO: 270: Glu-28-
An epitope is included that includes the sequence shown as His-34.

This tissue distribution indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and / or treatment of hematopoietic disorders. This gene product is expressed primarily in hematopoietic cells and tissues, suggesting a role in survival, reproduction, and / or differentiation of hematopoietic lineages. This is supported in particular by the expression of this gene product in fetal liver and bone marrow, the two major sites of hematopoiesis. Expression of this gene product in T cells and primordial dendritic cells also underscores the role of this protein in immune function and immune surveillance. Furthermore, since this gene is expressed in cells of lymphoid origin, this gene or protein and antibodies to this protein may show utility as tumor markers and / or immunotherapeutic targets against the tissues listed above. .

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 121 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 1160 of SEQ ID NO: 121 and b is from 15 to
Is an integer of 1174, where both a and b correspond to the nucleotide residue positions set forth in SEQ ID NO: 121, and b is a + 14 or more) are excluded. It

Characterization of Protein Encoded by Gene No. 112 This gene, which encodes the disclosed cDNA, is believed to be located on chromosome 14. Therefore, the polynucleotide related to the present invention is useful as a marker in the linkage analysis of chromosome 14.

This gene is expressed predominantly in fetal liver, spleen, and to a lesser extent melanocytes.

Accordingly, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, and include, but are not limited to, developmental disorders, integumental disorders or hematopoietic disorders. It is useful as a reagent for diagnosis of non-limiting diseases and conditions. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. Significantly higher or lower levels than standard gene expression levels (ie, expression levels in normal tissues or body fluids from undiseased individuals) for many disorders of the tissues or cells, especially fetal and embryonic tissues. Expression of this gene in specific tissues or cell types (eg, immune, developmental, integumental, and cancerous and wound tissues) or body fluids (eg, lymph) collected from individuals with such disorders. , Serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

[0614] As a preferable epitope, in SEQ ID NO: 271, residues: Met-1 to H
The epitopes include the sequences shown as is-7, Glu-43 to Glu-50, and Thr-89 to Thr-95.

Tissue distribution in fetal liver and spleen indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of developmental hematopoietic disorders. In addition, this tissue distribution indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and / or treatment of hematopoietic disorders. This gene product is expressed primarily in hematopoietic cells and tissues, suggesting a role in survival, reproduction, and / or differentiation of hematopoietic lineages. This is supported in particular by the expression of this gene product mainly in the fetal liver. The fetal liver is the major site of critical hematopoiesis and strongly suggests a role for this protein in immune function and immune surveillance.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 122 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 1032 of SEQ ID NO: 122 and b is from 15 to
An integer of 1046, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 122, and b is a + 14 or more) and one or more polynucleotides are excluded. It

Characteristics of the protein encoded by gene number 113 When tested against the Jurkat T cell line, supernatants taken from cells containing this gene activated the GAS assay. Therefore, this gene is Jak-S
It appears to activate T cells through the TAT signaling pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes involved in the Jak-STAT pathway. The Jak-STAT pathway is a large signaling pathway involved in cell differentiation and proliferation. Therefore, activation of the Jak-STAT pathway, reflected by the binding of GAS elements, can be used to indicate proteins involved in cell proliferation and differentiation.

[0618]   This gene is mainly expressed in B cell lymphomas.

Accordingly, the polynucleotides and polypeptides of the present invention are for the differential identification of tissues or cell types present in a biological sample, and for diseases and conditions including but not limited to B-cell lymphoma. It is useful as a reagent for diagnosis of. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, particularly the immune system, significantly higher or lower levels of this gene than standard gene expression levels (ie, expression levels in healthy tissues or fluids from individuals without disorders). The expression of a gene is a particular tissue or cell type (eg, immune tissue, and cancerous and wound tissue) or body fluid (eg, lymph, serum, plasma, urine, etc.) taken from an individual having such a disorder.
Synovial fluid and cerebrospinal fluid), or in another tissue or cell sample.

A preferred epitope is the residue: Glu-23-in SEQ ID NO: 272.
The epitopes include the sequences shown as Asn-31 and Tyr-42 to Ser-58.

The tissue distribution within B cells indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of lymphomas, especially B cell lymphomas. Furthermore, expression of this gene product in B cells is proliferative; survival;
Differentiation; and / or a role in regulating the activity of all potential hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes, which may also suggest utility in treating cancer (eg, by boosting the immune response). Since this gene is expressed in cells of lymphoid origin, this gene or protein, and antibodies raised against this protein, are tumor marker and / or immunotherapy targets for the tissues listed above. Can be useful. Therefore,
It can also be used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. Furthermore, this gene product is involved in the proliferation of stem and progenitor cells of various blood lineages, and in the differentiation and / or differentiation of various cell types.
Or it may have commercial utility in growth. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above. Furthermore, biological activity data support the idea that the translation product of this gene may activate specific immune cells and thus play a role in initiating immune system activity.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 123 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, where a is any integer from 1 to 1146 of SEQ ID NO: 123 and b is from 15 to
Is an integer of 1160, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 123, and b is a + 14 or more) are excluded. It

Characterization of Protein Encoded by Gene No: 114 This gene is expressed predominantly in neutrophils (IL-1 and LPS induced).

Accordingly, the polynucleotides and polypeptides of the present invention are for the differential identification of tissues or cell types present in a biological sample, as well as for diseases and conditions including but not limited to immune disorders. It is useful as a reagent for diagnosis. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, particularly the immune system, significantly higher or lower levels of this gene than standard gene expression levels (ie, expression levels in healthy tissues or fluids from individuals without disorders). Expression of a gene may be dependent on the specific tissue or cell type (eg, immune tissue, and cancerous and wound tissue) or body fluid (eg, lymph, serum, plasma, urine, synovium, etc.) taken from an individual having such a disorder. liquid,
And cerebrospinal fluid), or another tissue or cell sample.

Tissue distribution within neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of certain immune disorders, particularly those involving neutrophils. . Expression of this gene product in neutrophils plays a role in regulating proliferation; survival; differentiation; and / or the activity of all potential hematopoietic cell lineages, including blood stem cells. This gene product produces cytokines, antigen presentation,
Or it may be involved in the control of other processes, which may also suggest utility in treating cancer (eg, by boosting the immune response). Since this gene is expressed in cells of lymphoid origin, the gene or protein and antibodies to that protein may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above. So this is
It may also be used as a drug for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. Furthermore, this gene product may have commercial utility in the proliferation of stem and progenitor cells of various blood lineages, and in the differentiation and / or proliferation of various cell types. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 124 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 879 of SEQ ID NO: 124 and b is from 15 to 8
93 is an integer of 93, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 124, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

CHARACTERISTICS OF PROTEIN ENCODED BY GENE NO: 115 One embodiment of this gene comprises a polypeptide of the following amino acid sequence:
DIMPASVIFLICEGVLYGVQG (SEQ ID NO: 476). A further embodiment are polynucleotides encoding these polypeptides.

[0628]   This gene is mainly expressed in placenta.

Accordingly, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, as well as placental failure; developmental abnormalities; abnormal angiogenesis; placental developmental abnormalities. And / or are useful as reagents for the diagnosis of diseases and conditions including but not limited to maintenance. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, particularly the placenta and more generally the vasculature and / or endothelium, standard gene expression levels (ie, expression levels in healthy tissue or fluid from an individual without the disorder). ) Significantly higher or lower levels of this gene relative to a particular tissue or cell type (
For example, developmental tissue, placental tissue, and cancerous and wound tissue) or body fluid (
(Eg, lymph, serum, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

Tissue distribution within placental tissue indicates that the polynucleotides and polypeptides corresponding to this gene are useful for diagnosing and / or treating placental disorders. Specific expression in the placenta indicates that this gene product may play a role in the proper establishment and maintenance of placental function. Alternatively, the gene product may be produced by the placenta, which in turn develops embryos (embryos or fetuses developing herein and
Or may play an important role in survival). Expression of this gene product in blood vessel-rich tissues such as placenta also indicates that this gene product may be more widely produced in endothelial cells or circulation. In such instances, the gene product may play a more systemic role in vascular function such as angiogenesis. This gene product is also produced in blood vessels and can affect other cells in the circulation, such as hematopoietic cells. It can also serve to promote the proliferation, survival, activation and / or differentiation of hematopoietic cells and other cells throughout the body.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 125 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 1035 of SEQ ID NO: 125 and b is from 15 to
Is an integer of 1049, where both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 125, and b is a + 14 or more) are excluded. It

(Characteristics of Protein Encoded by Gene No. 116) This gene is mainly expressed in keratinocytes and synovial hypoxic cells and T cells.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for differential identification of tissues or cell types present in a biological sample, as well as integumental, immune, or skeletal disorders, particularly wound healing. And are useful as reagents for the diagnosis of diseases and conditions including but not limited to rheumatic conditions. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. The tissue or cells,
Particularly for many disorders of the integumentary system, significantly higher or lower levels of expression of this gene relative to standard gene expression levels (ie, expression levels in healthy tissues or fluids from undiseased individuals), A specific tissue or cell type (eg, skin tissue, connective tissue, cancerous tissue and wound tissue) or body fluid (eg, lymph, serum, plasma, urine, synovial fluid, and) collected from an individual having such a disorder, and CSF), or in another tissue or cell sample.

A preferred epitope is SEQ ID NO: 275, residues: Thr-42.
Pro-53, Val-78 to Glu-86, Glu-103 to Met-112.
, Ala-124 to Gly-131.

The tissue distribution within keratinocytes indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the treatment of integumental disorders, particularly those associated with wound healing. In addition, this tissue distribution also detects and treats connective tissue disorders such as arthritis, trauma, tendinitis, chondromalacia, and inflammation, such as various autoimmune disorders such as rheumatoid arthritis. , Lupus, scleroderma and dermatomyositis, and dwarfism, spinal deformities and certain joint abnormalities, and chondrodysplasia (ie, congenital vertebral epiphyseal dysplasia, familial osteoarthritis, type II osteodystrophy). type II
), Schmidt metaphyseal cartilage dysplasia)). The protein as well as antibodies to this protein may show utility as tumor markers and / or immunotherapeutic targets against the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 126 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 1612 of SEQ ID NO: 126 and b is from 15 to
1626, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 126, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

Characterization of Protein Encoded by Gene No: 117 This gene is expressed predominantly in liver and testicular tumors, and to a lesser extent in the brain.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, as well as liver, neuropathy, or reproductive disorders, particularly metastatic liver. It is useful as a reagent for the diagnosis of diseases and conditions including, but not limited to cancer. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. Significantly higher or lower levels relative to standard gene expression levels (ie expression levels in normal tissues or body fluids from non-disordered individuals) for many disorders of the tissues or cells, particularly cancer and metabolic systems. Expression of this gene in a particular tissue or cell type (eg, liver tissue, brain tissue, reproductive tissue, cancerous tissue and wound tissue) or body fluid (eg, lymph, Serum, semen, amniotic fluid, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

Tissue distribution within liver tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of several types of cancer, including liver cancer, testicular tumors and associated metastases. Indicates. Furthermore, this tissue distribution shows that polynucleotides and polypeptides corresponding to this gene are associated with liver damage and cancer (
For example, it is useful for the detection and treatment of embryonal tumors, jaundice, hepatitis, liver metabolic diseases and conditions caused by the differentiation of hepatocyte precursor cells. The protein as well as the antibodies raised against this protein may show utility as tumor markers and / or immunotherapeutic targets in the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 127 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 1163 of SEQ ID NO: 127 and b is from 15 to
Is an integer of 1177, wherein both a and b correspond to the nucleotide residue positions set forth in SEQ ID NO: 127, and where b is a + 14 or more) are excluded. It

FEATURES OF PROTEIN ENCODED BY GENE NO: 118 This gene is expressed predominantly in CD34-positive cells, and to a lesser extent in pancreatic tumors and spleens.

Accordingly, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, as well as for reproductive, endocrine, or immune disorders, particularly pancreatic cancer. It is useful as a reagent for the diagnosis of diseases and conditions, including but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. Significantly higher than standard gene expression levels (ie expression levels in normal tissues or body fluids from unaffected individuals) for many disorders of the tissues or cells, particularly tumors, immune and metabolic systems, or Low levels of expression of this gene may result in specific tissue or cell types (eg, immune tissue, liver tissue, spleen tissue, cancerous tissue and wound tissue) or body fluids (eg, immune tissue, liver tissue, spleen tissue) taken from an individual having such a disorder. Lymph, serum, bile, amniotic fluid, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

The tissue distribution within the pancreas and CD34-positive cells makes the polynucleotides and polypeptides corresponding to this gene particularly useful for the diagnosis and treatment of some types of cancer, including CD34 cells and pancreatic cancer. Indicates that. In addition, CD34
Expression of this gene product in both positive cells and pancreas indicates a role in regulating proliferation; survival; differentiation and / or activation of all potential hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes, which may also suggest utility in treating cancer (eg, by boosting the immune response). . This gene is
Being expressed in cells of lymphoid origin, genes or proteins, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above. So this also
It can be used as a drug for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. Furthermore, this gene product may have commercial utility in the proliferation of stem and progenitor cells of various blood lineages, and in the differentiation and / or proliferation of various cell types. The protein and antibodies to this protein are
It may show utility as a tumor marker and / or immunotherapy target against the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 128 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 1262 of SEQ ID NO: 128 and b is from 15 to
Is an integer of 1276, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 128, and b is a + 14 or more) are excluded. It

FEATURES OF PROTEIN ENCODED BY GENE NO: 119 This gene is predominantly expressed in osteoblastoma, fetal liver / spleen, and to a lesser extent, primordial dendritic cells.

Accordingly, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, and for osteoblastomas; hematopoietic disorders; lymphomas; impaired immunity; immunity. Disorders; useful as reagents for the diagnosis of diseases and conditions including, but not limited to inflammation, and integumental disorders. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, especially the immune system and bone, levels significantly higher or lower than standard gene expression levels (ie, expression levels in healthy tissue or fluid from individuals without disorders). Expression of this gene in specific tissues or cell types (eg, immune tissue, bone tissue, integumental tissue, and cancerous and wound tissue) or body fluids (eg, lymph) collected from individuals with such disorders. , Serum, amniotic fluid, plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

A preferred epitope is SEQ ID NO: 278 at residues: Thr-23-
Examples include epitopes including the sequences shown as Pro-29 and Thr-68 to Pro-76.

Tissue distribution within dendritic cells indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and / or treatment of bone and hematopoietic disorders. The high level expression of this gene product in osteoblastoma indicates that it may play a role in osteoclast survival, proliferation and / or growth. Therefore, it may be useful in affecting bone mass in conditions such as osteoporosis. More generally, this gene may generally play a role in hematopoietic cell survival, proliferation and / or differentiation, as evidenced by fetal liver / spleen expression, and increased numbers of stem and progenitor cells. Can be useful for. Expression of this gene product in primordial dendritic cells also indicates that it may play a role in mediating responses to infections, such as those that occur during immune surveillance, and in controlling immunological responses. .

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 129 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 1320 of SEQ ID NO: 129 and b is from 15 to
1334 is an integer, wherein both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 129, and b is a + 14 or more) are excluded. It

Characterization of Protein Encoded by Gene No. 120 When tested on a fibroblast cell line, supernatants taken from cells containing this gene activated the EGRI assay. Thus, this gene appears to activate fibroblasts through signaling pathways. Initial growth reaction 1 (EGR1)
Is a promoter associated with specific genes that, upon activation, induces various tissue and cell types, leading cells to differentiation and proliferation.

[0651]   This gene is mainly expressed in hemangiopericytoma.

Thus, the polynucleotides and polypeptides of the present invention can be used for the differential identification of tissues or cell types present in a biological sample, as well as for soft tissue cancers (eg, hemangiopericytoma) as well as other growths. It is useful as a reagent for the diagnosis of diseases and conditions, including but not limited to conditions. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, especially the vasculature, significantly higher or lower levels of this gene than standard gene expression levels (ie, expression levels in healthy tissues or fluids from undisturbed individuals). The expression of a gene is a particular tissue or cell type (eg, circulatory tissue, and cancerous and wound tissue) or body fluid (eg, lymph, serum, plasma, urine, etc.) taken from an individual having such a disorder. Synovial fluid, and cerebrospinal fluid), or a preferred epitope that can be detected in another tissue or cell sample includes residues in SEQ ID NO: 279: Pro-49-
An epitope including the sequence shown as Thr-64 is included.

This tissue distribution indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of hemangiopericytoma. further,
Biological activity data demonstrate that the translation product of this gene activates fibroblasts. Fibroblasts have the capacity to undergo angiogenesis, and therefore the translation product of this gene may be involved in disorders of vascular tissue such as hemangiopericytoma.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 130 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 518 of SEQ ID NO: 130 and b is from 15 to 5
32 is an integer of 32, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 130, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

[0655]     (Characteristics of protein encoded by gene number 121)   This gene is mainly expressed in the renal cortex.

Accordingly, the polynucleotides and polypeptides of the present invention are for the differential identification of tissues or cell types present in a biological sample, as well as for renal disorders or urogenital disorders, particularly nephritis. It is useful as a reagent for diagnosis of diseases and conditions not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, especially the renal system, significantly higher or lower levels of this gene than standard gene expression levels (ie, expression levels in healthy tissues or fluids from undisturbed individuals). Expression of a gene may be dependent on the specific tissue or cell type (eg, kidney tissue, and cancerous and wound tissue) or body fluid (eg, lymph, serum, plasma, urine, synovium, etc.) taken from an individual with such a disorder. Fluid, and spinal fluid), or another tissue or cell sample.

A preferred epitope is the residue in SEQ ID NO: 280: Pro-33-
An epitope is included that includes the sequence shown as Ser-38.

Tissue distribution within the renal cortex indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of renal diseases, including nephritis. Furthermore, the tissue distribution in the kidney, this gene or gene product, renal failure, renal tubular acidosis, proteinuria, pyuria, pus, pyelonephritis, hydronephrosis, nephrotic syndrome, crush syndrome, glomerulonephritis, Can be used to treat and / or detect hematuria, renal colic and renal stones, as well as Wilms tumor disease, and congenital renal abnormalities such as horseshoe kidney, and polycystic kidney disease, and renal diseases including Fanconi syndrome Indicates that. The protein and antibodies to this protein may show utility as tumor markers and / or immunotherapy targets against the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 131 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 671 of SEQ ID NO: 131 and b is from 15 to 6
Is an integer of 85, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 131, and where b is a + 14 or more) and one or more polynucleotides comprising It

[0660]     (Characteristics of protein encoded by gene number 122)   This gene is mainly expressed in the spleen derived from chronic lymphocytic leukemia.

Thus, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, as well as for immune or hematopoietic disorders such as chronic lymphocytic leukemia. It is useful as a reagent for the diagnosis of diseases and conditions, including but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, particularly the immune system, significantly higher or lower levels of this gene than standard gene expression levels (ie, expression levels in healthy tissues or fluids from individuals without disorders). The expression of a gene is a specific tissue or cell type (eg, spleen tissue, cancerous tissue and wound tissue) or body fluid (eg, lymph, serum, plasma, urine, synovial fluid) taken from an individual having such a disorder. , And cerebrospinal fluid), or in another tissue or cell sample.

Tissue distribution within spleen tissue indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of chronic lymphocytic leukemia. In addition, predominant expression in spleen cells also indicates that this polynucleotide or polypeptide is associated with graft-versus-host reaction, graft-versus-host disease, transplant rejection, myeloid leukemia, myelofibrosis, and myeloproliferative effects. It is shown to be important in the treatment and / or detection of hematopoietic disorders such as diseases. The polynucleotides or polypeptides are also useful for enhancing or protecting the proliferation, differentiation, and functional activity of hematopoietic progenitor cells (eg, bone marrow cells), in cancer patients undergoing chemotherapy or in bone marrow transplants. It is also useful in the treatment of existing cancer patients. The polynucleotides or polypeptides are also useful for enhancing the proliferation of peripheral blood leukocytes, which can be used to combat a range of hematopoietic disorders in the range of assertions including immunodeficiency disease, leukemia, sepsis.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 132 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 715 of SEQ ID NO: 132 and b is from 15 to 7
Is an integer of 29, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 132, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

Characterization of Protein Encoded by Gene No. 123 This gene is expressed predominantly in neutrophils, dendritic cells, and CD34-positive cells (umbilical cord blood).

Accordingly, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, as well as for immune, hematopoietic, or developmental disorders. It is useful as a reagent for diagnosis of diseases and conditions not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, particularly the immune system, significantly higher or lower levels of this gene than standard gene expression levels (ie, expression levels in healthy tissues or fluids from individuals without disorders). The expression of a gene is a particular tissue or cell type (eg, immune, developmental, and cancerous and wound tissue) or body fluid (eg, lymph, serum, amniotic fluid, etc.) taken from an individual with such a disorder. Plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

Tissue distribution within neutrophils is that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of several types of immune disorders, particularly those involving neutrophils. Indicates that. More generally, this gene is generally associated with hematopoietic cell survival, proliferation, as revealed by expression in CD34-positive cells.
And / or may play a role in differentiation and may be useful in increasing the number of stem cells and progenitor progenitor cells. Expression of this gene product in primordial dendritic cells also plays a role in that this gene product mediates responses to infections, such as those that occur during immune surveillance, and in controlling immunological responses. Show what you can do.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 133 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 1065 of SEQ ID NO: 133 and b is from 15 to
Is an integer of 1079, where both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 133, and b is a + 14 or more) are excluded. R.

[0668]     (Characteristics of protein encoded by gene number 124)   This gene is mainly expressed in the adult lung.

Accordingly, the polynucleotides and polypeptides of the present invention are for the differential identification of tissues or cell types present in a biological sample, as well as for diseases and conditions including but not limited to respiratory disorders. It is useful as a reagent for diagnosis. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, particularly the respiratory system, levels of this gene that are significantly higher or lower than standard gene expression levels (ie, expression levels in healthy tissue or body fluids from non-disordered individuals). Expression of a gene may be dependent on the specific tissue or cell type (eg, respiratory and cancerous and wounded tissue) or body fluid (eg, lymph, serum, plasma, urine, synovium, etc.) taken from an individual with such a disorder. Fluid, and spinal fluid), or another tissue or cell sample.

Tissue distribution within lung tissue indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of respiratory disorders such as asthma, emphysema, and ARDS. The protein and antibodies to this protein are
It may show utility as a tumor marker and / or immunotherapy target against the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 134 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab (where a is any integer from 1 to 1283 of SEQ ID NO: 134 and b is from 15 to 15).
1297 is an integer, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 134, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

(Characteristics of Protein Encoded by Gene No. 125) It is considered that the gene encoding the disclosed cDNA is present on chromosome 19. Therefore, the polynucleotide of the present invention is useful as a marker in the linkage analysis of chromosome 19.

This gene is expressed predominantly in T cell lymphomas and fetal liver / spleen.

Accordingly, the polynucleotides and polypeptides of the present invention include for differential identification of tissues or cell types present in a biological sample, as well as for immune, developmental, or hematopoietic disorders, particularly lymphomas. However, it is useful as a reagent for the diagnosis of diseases and conditions including but not limited to them. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, particularly the immune system, significantly higher or lower levels of this gene than standard gene expression levels (ie, expression levels in healthy tissues or fluids from individuals without disorders). The expression of a gene is a particular tissue or cell type (eg, immune, developmental, and cancerous and wound tissue) or body fluid (eg, lymph, serum, amniotic fluid, etc.) taken from an individual with such a disorder. (Plasma, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

[0675] A preferred epitope is the residue: Glu-25 to 25 in SEQ ID NO: 284.
An epitope including the sequence shown as Phe-43 is mentioned.

Tissue distribution within T cells indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of T cell lymphomas. Moreover, expression of this gene product in fetal liver / spleen indicates a role in regulating proliferation, survival, differentiation, and / or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes, which also suggests utility in treating cancer (eg, by boosting the immune response). You can get it. Since this gene is expressed in cells of lymphoid origin, the gene and protein and antibodies to this protein may show utility as tumor markers and / or immunological targets for the tissues listed above. .. Therefore, it is also used as a drug for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. obtain. Furthermore, this gene product may have commercial utility in the expansion of stem and progenitor cells of various blood lineages, and in the differentiation and / or expansion of various cell types. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 135 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 603 of SEQ ID NO: 135 and b is from 15 to 6
Is an integer of 17, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 135, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

(Characteristics of Protein Encoded by Gene No. 126) The translation product of this gene shares a homologous sequence with C9 (gene of unknown function). The gene encoding the disclosed cDNA is believed to be located on chromosome 3. Therefore, the polynucleotide related to the present invention is useful as a marker in the linkage analysis of chromosome 3. One embodiment of this gene comprises a polypeptide of the following amino acid sequence: GTAFQHAFSTNDCSRNVYIK.
KNGFTLHRNPIAQSTDDGARTKIGFSEGRHAWEVWWE
GPLGTVAVIGIATKRAPMQCQGYVALLGSDDQSWGW
NLVDNNLLHNGEVNGSFPQCNNAPKYQIGERIRVIL
DMEDKTLAFERGYEFLGVAFRGLPKVCLYPAVSAVY
GNTEVTLVYLGKPLDG (SEQ ID NO: 477). A further embodiment is
It is a polynucleotide encoding these polypeptides.

This gene is expressed predominantly in placenta, and to a lesser extent, apoptotic T cells, and smooth muscle, testis, and microvascular endothelial cells.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for differential identification of tissues or cell types present in a biological sample, as well as diseases including but not limited to immune or reproductive disorders. And are useful as reagents for diagnosing conditions. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, particularly the immune system, significantly higher or lower levels of this gene than standard gene expression levels (ie, expression levels in healthy tissues or fluids from individuals without disorders). The expression of a gene is a specific tissue or cell type (eg, immune, reproductive, muscle, vascular, and cancerous and wound tissue) or body fluid (eg, immune tissue, reproductive tissue, muscle tissue, vascular tissue) or body fluid (eg, tissue) collected from an individual having such a disorder. Lymph, serum, plasma, amniotic fluid, urine, synovial fluid, and spinal fluid), or another tissue or cell sample.

Tissue distribution within T cells in combination with homology to the C9 protein indicates that the polynucleotide and the polypeptide corresponding to this gene are associated with several immune disorders.
It will be particularly useful for the diagnosis and treatment of immune disorders involving T cells. In addition, the gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes, which also treats cancer (eg, by boosting the immune response), or male sterility. May be useful in This gene
Being expressed in cells of lymphoid origin, the genes and proteins and antibodies to the proteins may show utility as tumor markers and / or immunotherapy targets against the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 136 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 1297 of SEQ ID NO: 136 and b is from 15 to
1311 is an integer, wherein both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 136, and where b is a + 14 or more) are excluded. It

[0683]     (Characteristics of protein encoded by gene number 127)   This gene is mainly expressed in neutrophils.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for differential identification of tissues or cell types present in a biological sample, as well as diseases including but not limited to immune disorders or hematopoietic disorders. And are useful as reagents for diagnosing conditions. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. For many disorders of the tissues or cells, particularly the immune system, significantly higher or lower levels of this gene than standard gene expression levels (ie, expression levels in healthy tissues or fluids from individuals without disorders). The expression of a gene is a particular tissue or cell type (eg, immune tissue, cancerous tissue and wound tissue) or body fluid (eg, lymph, serum, plasma, urine, etc.) taken from an individual having such a disorder.
Synovial fluid and cerebrospinal fluid), or in another tissue or cell sample.

Tissue distribution within neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of several immune disorders, particularly those involving neutrophils. Show. Moreover, as evidenced by expression in neutrophils, this gene may generally play a role in hematopoietic cell survival, proliferation and / or differentiation, and may be useful in increasing the number of stem cells and progenitor progenitors.
The expression of this gene product in neutrophils further indicates that it may play a role in controlling the immune response in mediating the response to infection, such as the response that occurs during immune surveillance. The protein as well as antibodies to this protein may show utility as tumor markers and / or immunotherapeutic targets against the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 137 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 1081 of SEQ ID NO: 137 and b is from 15 to
Is an integer of 1095, where both a and b correspond to the nucleotide residue positions set forth in SEQ ID NO: 137, and b is a + 14 or greater) It

Characterization of Protein Encoded by Gene No. 128 This gene is expressed primarily in neutrophils and is induced by IL-1 and LPS.

Thus, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, and for diseases and disorders including, but not limited to, hematopoietic or immune disorders. It is useful as a reagent for diagnosing a condition. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, especially the immune system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in normal tissues or fluids from individuals without disorders). The expression of this gene is dependent on the expression of a particular tissue or cell type (eg, immune tissue, cancerous tissue and wound tissue) or body fluid (eg, lymph, serum, plasma, etc.) taken from an individual having such a disorder.
Urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

A preferred epitope is the residue in SEQ ID NO: 287: Lys-36 to As.
An epitope is included that includes the sequence shown as p-42.

This tissue distribution in neutrophils indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of some immune disorders, especially involving neutrophils. Furthermore, this gene may generally play a role in hematopoietic cell survival, proliferation, and / or differentiation, as evidenced by expression in neutrophils, and stem cells and their progenitor-related progenitor cells. Can be used to increase the number of Furthermore, expression of this gene product in neutrophils indicates that it may play a role in mediating the response to infection and controlling the immune response, such as the response that occurs while the immune surveillance is working. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 138 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 678 of SEQ ID NO: 138 and b is from 15 to 6
Is an integer of 92, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 138, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

Characterization of Protein Encoded by Gene No. 129 This gene is induced by IL-1 and LPS, which is mainly expressed in neutrophils.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, and for diseases and disorders including, but not limited to, immune disorders or hematopoietic disorders. It is useful as a reagent for diagnosing a condition. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, especially the immune system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in normal tissues or fluids from individuals without disorders). The expression of this gene is dependent on the expression of a particular tissue or cell type (eg, immune tissue, cancerous tissue and wound tissue) or body fluid (eg, lymph, serum, plasma, etc.) taken from an individual having such a disorder.
Urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

A preferred epitope is represented by the residues: Pro-32 to Gl in SEQ ID NO: 288.
Examples include epitopes containing the sequences shown as n-33 and Gly-51 to Asp-57.

This tissue distribution in neutrophils indicates that the polynucleotides and polypeptides corresponding to this gene are particularly useful for the diagnosis and treatment of certain immune disorders involving neutrophils. In addition, this gene may generally play a role in hematopoietic cell survival, proliferation, and / or differentiation, as evidenced by expression in neutrophils, and in the number of stem cells and associated progenitor cells. Can be used for augmentation. Furthermore, expression of this gene product in neutrophils indicates that it may play a role in mediating responses to infections, such as those that occur while the immune surveillance system is working, and in controlling immune responses. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 139 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 734 of SEQ ID NO: 139 and b is from 15 to 7
Is an integer of 48, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 139, and where b is a + 14 or more) and one or more polynucleotides are excluded. It

Characterization of Protein Encoded by Gene No. 130 This gene is induced by IL-1 and LPS, which is mainly expressed in neutrophils.

Accordingly, the polynucleotides and polypeptides of the invention are for the diagnosis of diseases and conditions for the differential identification of tissues or cell types present in a biological sample, and including, but not limited to, immune disorders. Is useful as a reagent for.
Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, especially the immune system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in normal tissues or fluids from individuals without disorders). The expression of this gene may depend on the specific tissue or cell type (eg, immune tissue, cancerous tissue and wound tissue) or body fluid (eg, lymph, serum, plasma, urine, synovium, etc.) taken from an individual having such a disorder. Fluid and spinal fluid) or another tissue or cell sample.

[0699] A preferred epitope is the residue in SEQ ID NO: 289: Gly-22 to Se.
An epitope is included that includes the sequence designated as r-28.

This tissue distribution in neutrophils indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of certain immune disorders involving neutrophils. Moreover, as evidenced by expression in neutrophils,
This gene may generally play a role in hematopoietic cell survival, proliferation, and / or differentiation, and may be used to increase the number of stem cells and their associated progenitor cells. Furthermore, expression of this gene product in neutrophils indicates that it may play a role in mediating responses to infections, such as those that occur while the immune surveillance system is working, and in controlling immune responses. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 140 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 1118 of SEQ ID NO: 140 and b is from 15 to
Is an integer of 1132, wherein both a and b correspond to the nucleotide residue positions set forth in SEQ ID NO: 140, and b is a + 14 or more) are excluded. It

[0702]     (Characteristics of protein encoded by gene number 131)   This gene is expressed primarily in the corpus callosum.

Accordingly, the polynucleotides and polypeptides of the present invention may be used for the differential identification of tissues or cell types present in a biological sample, as well as of brain disorders such as neuropathies, especially disorders on neurodegeneration. It is useful as a reagent for diagnosis of diseases and conditions, including but not limited to diseases. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, especially the central nervous system, significantly higher or lower levels relative to standard gene expression levels (ie, expression levels in normal tissues or fluids from individuals without the disorder) Expression of this gene in specific tissues or cell types (eg, brain, and cancerous and wounded tissues) or body fluids (eg, lymph, serum, plasma, urine, etc.) collected from individuals with such disorders. Synovial fluid, and spinal fluid) or another tissue or cell sample.

This tissue distribution in neural tissue indicates that the polynucleotides and polypeptides corresponding to this gene are for the diagnosis and treatment of brain disorders and diseases, including paranoia, schizophrenia, depression, mania and Alzheimer's disease. To be useful for. Furthermore, it is shown that high expression of this gene product in the corpus callosum of the brain may be involved in nerve survival; synapse formation; transduction force; nerve differentiation and the like. Such involvement can impact many processes such as learning and cognition. Moreover, it may also be useful in the treatment of neurodegenerative disorders such as schizophrenia; ALS; or Alzheimer. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 141 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, where a is any integer from 1 to 1098 of SEQ ID NO: 141 and b is from 15 to
1112 is an integer, wherein both a and b correspond to the nucleotide residue positions set forth in SEQ ID NO: 141, and b is a + 14 or greater) It

Characterization of Protein Encoded by Gene No: 132 The translation product of this gene shares sequence homology with the putative transposase of the Tigger-1 transposon.

[0707]   This gene is expressed primarily in the atrophic endometrium.

Accordingly, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, and include, but are not limited to, myopathy, especially muscle atrophy, It is useful as a reagent for diagnosis of diseases and conditions. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, particularly the reproductive system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in normal tissues or fluids from individuals without disorders). The expression of this gene may depend on the specific tissue or cell type (eg, reproductive tissue, muscle tissue, endocrine tissue, and cancerous and wound tissue) or body fluid (eg, lymph, etc.) obtained from an individual having such a disorder. Serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

This tissue distribution in endometrial tissue combined with homology to transposase indicates that the polynucleotides and polypeptides corresponding to this gene are useful for DNA repair in atrophied tissue, especially endometrial tissue. . The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 142 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 1070 of SEQ ID NO: 142 and b is from 15 to
Is an integer of 1084, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 142, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

CHARACTERISTICS OF PROTEIN ENCODED BY GENE NO: 133 In a particular embodiment, a polypeptide of the invention comprises the following amino acid sequence: ARAFQHLMVADHSHFHRTLIKQPSMIPNATFY.
HIF (SEQ ID NO: 478). Polynucleotides encoding these polypeptides are also included in the invention.

[0712]   This gene is expressed primarily in hemangiopericytoma.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample due to soft tissue tumors, particularly hemangiocytomas or other proliferative disorders. It is useful as a reagent for diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, particularly the vasculature, significantly higher or lower levels than standard gene expression levels (ie, expression levels in healthy tissues or fluids from unaffected individuals). The expression of this gene may depend on the specific tissue or cell type (eg, immune tissue, and cancerous and wound tissue) or body fluid (eg, lymph, serum, plasma, urine, etc.) obtained from an individual having such a disorder. Synovial fluid, and spinal fluid) or another tissue or cell sample.

A preferred epitope is represented by the residues: Ser-39 to Se in SEQ ID NO: 292.
An epitope is included that includes the sequence shown as r-44.

This tissue distribution in hemangiopericytoma indicates that, in addition to other proliferative disorders in which polynucleotides and polypeptides corresponding to this gene may affect other tissues or cell types, various soft tissue tumors Shows utility for diagnosis and treatment. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 143 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 1036 of SEQ ID NO: 143 and b is from 15 to
Is an integer of 1050, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 143, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

Characterization of Protein Encoded by Gene No. 134 This gene is expressed primarily in the hypothalamus of schizophrenic patients, and to a lesser extent in the spleen.

Accordingly, the polynucleotides and polypeptides of the present invention include neural or immune system disorders, particularly schizophrenia or neurodegenerative conditions, for the differential identification of tissues or cell types present in a biological sample. Are useful as reagents for the diagnosis of diseases and conditions including, but not limited to, Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher than standard gene expression levels (ie, expression levels in normal tissues or fluids from unaffected individuals) for many disorders of the tissues or cells, particularly the central nervous system and immune system, or Lower levels of expression of this gene may be associated with specific tissues or cell types taken from individuals with such disorders (eg, neural, immune, hematopoietic, spleen, cancerous and wound tissues) or Body fluids (eg lymph, serum, plasma, urine,
Synovial fluid, and spinal fluid) or another tissue or cell sample.

This tissue distribution in the hypothalamus indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of schizophrenia and other central nervous system and immune system disorders. . In addition, polynucleotides and polypeptides corresponding to this gene have neurodegenerative disease states, behavioral disorders or inflammatory conditions (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, meningitis, encephalitis, desensitization). Myelopathy, peripheral neuropathy, neoplasia, injury,
Congenital malformations, spinal cord injury, ischemia and infarction, aneurysm, hemorrhage, schizophrenia, mania, dementia, paranoia, obsessive-compulsive disorder, panic disorder, learning disorder, ALS (amyotrophic lateral sclerosis), It is useful for the diagnosis / treatment of psychosis, autism, and behavioral changes including nutritional intake disorders, sleep pattern disorders, balance sensory disorders, and sensory disorders. Furthermore, high expression of this gene product in regions of the brain plays a role in normal neural function. Potentially, this gene product is associated with synapse formation, neurotransmission,
It is associated with learning, cognition, homeostasis, or neural differentiation or survival. In addition, the gene or gene product may play a role in the treatment and / or detection of developmental disorders associated with embryonic development, sex-related disorders, disorders of the endocrine system or disorders of the cardiovascular system. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 144 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 1099 of SEQ ID NO: 144 and b is from 15 to
1113 is an integer, wherein both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 144, and where b is a + 14 or more) are excluded. It

(Characteristics of Protein Encoded by Gene No. 135) The translation product of this gene is considered to act as a signal receptor in kidney and thyroid cancer, human multiple transmembrane receptor (TRC8) ((G
enbank accession number gi | 3395787 (AF064801)) as well as chicken ring-finger-zinc-finger protein (C-
Share sequence homology with RZF). The TRC8 locus has been described in a family with the classic features of inherited renal cell carcinoma. The 8q24.1 (TRC8 locus) breakpoint region is a 664 amino acid multiple transmembrane protein with similarity to the patched, inherited basal cell carcinoma / segment polarity gene fragment, Code TRC8. This similarity involves the putative sterol-sensing domain and the two patch regions of the second extracellular loop, which are involved in the binding of sonic hedgehog. TRC8 translocated to 3; 8 is FHIT
(Fragile histidine triad gene). And this T
RC8 is split into a sterol-sensing domain. In contrast, FHIT
The coding region is maintained and expressed. TRCs in a series of scattered kidney cancers
The occurrence of 8 mutations was identified. In a particular embodiment, a polypeptide of the invention comprises the following amino acid sequence:

[0722]

[Chemical 18] Polynucleotides encoding these polypeptides are also included according to the invention. This gene, which encodes the disclosed cDNA, is believed to be on chromosome 8. Therefore, the polynucleotide related to the present invention is useful as a marker for linkage analysis of chromosome 8.

[0723]   This gene is expressed primarily in human embryonic tissue.

Accordingly, the polynucleotides and polypeptides of the present invention can be used for the differential identification of tissues or cell types present in a biological sample, as well as for developmental abnormalities, particularly congenital defects or proliferative conditions. It is useful as a reagent for diagnosis of diseases and conditions including, but not limited to. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, particularly embryonic tissues, significantly higher or lower levels of normal gene expression levels (ie, expression levels in normal tissues or body fluids from individuals without disorders) The expression of this gene is dependent on the specific tissue or cell type (eg, developing tissue, kidney tissue, endocrine tissue, and cancerous and wound tissue) or body fluid (eg, lymph, etc.) taken from an individual having such a disorder. Amniotic fluid, serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

This tissue distribution in embryonic tissue, combined with ring-finger-zinc-finger proteins and homology to the human TRC8 receptor, indicates that the polynucleotides and polypeptides corresponding to this gene are abnormal, especially proliferative, in embryonic tissue. Shows utility for the diagnosis and treatment of disorders. Moreover, polynucleotides and polypeptides corresponding to this gene are useful for diagnosing, detecting and / or treating developmental disorders. The relatively specific expression of this gene product during embryonic development indicates that it may be a key player in the growth, maintenance, and / or differentiation of various cell types during development. It can also serve as a morphogen that controls cell and tissue type specification. Due to its potential role in proliferation and differentiation, this gene product may have adult application for tissue regeneration and cancer treatment. Furthermore, this protein may have utility in the diagnosis and treatment of cancer, as well as other proliferative disorders. Similarly, developing tissue relies on decisions involving apoptosis in cell differentiation and / or pattern formation. Thus the protein may also be involved in apoptosis or tissue differentiation and may also be useful in cancer therapy. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 145 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1-671 of SEQ ID NO: 145 and b is 15-6.
Is an integer of 85, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 145, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

Features of Protein Encoded by Gene No: 136 In a particular embodiment, a polypeptide of the invention comprises the following amino acid sequence:

[0728]

[Chemical 19] Polynucleotides encoding these polypeptides are also included in the invention.

[0729]   This gene is expressed primarily in microvascular endothelial cells.

Accordingly, the polynucleotides and polypeptides of the present invention can be used for the differential identification of tissues or cell types present in a biological sample, and for disorders of blood vessels or endothelium (arteriosclerosis, tumors) such as: It is useful as a reagent for the diagnosis of diseases and conditions including, but not limited to, formation, stroke, embolism, aneurysm, microvascular disease and various cardiovascular diseases. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, particularly the vasculature, significantly higher or lower levels than standard gene expression levels (ie, expression levels in healthy tissue or fluid from individuals without disorders). The expression of this gene may depend on the specific tissue or cell type (eg, vascular tissue, endothelial tissue, cardiovascular tissue, and cancerous and wound tissue) or body fluid (eg, lymphoid) taken from an individual with such a disorder. , Serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

This tissue distribution in microvascular endothelial tissue indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of vascular disorders. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 146 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 1024 of SEQ ID NO: 146 and b is 15-
Is an integer of 1038, wherein both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 146, and where b is a + 14 or more) and one or more polynucleotides comprising It

Characterization of Protein Encoded by Gene No. 137 This gene, which encodes the disclosed cDNA, is believed to reside on chromosome 2. Furthermore, the polynucleotide related to the present invention is useful as a marker for chromosome 2 linkage analysis.

This gene is mainly found in fetal tissues, most notably the fetal vortex and fetal lung,
And to a lesser extent it is expressed in rhabdomyosarcoma and healing groin wound tissue.

Thus, the polynucleotides and polypeptides of the present invention are for differential identification of tissues or cell types present in a biological sample, as well as abnormal embryogenesis / development; healing defects; respiratory disorders; Rhabdomyosarcoma; common cancers and other proliferative defects;
Fibrosis; Useful as a reagent for diagnosis of diseases and conditions, including but not limited to wound healing. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, particularly embryo / fetal or striated muscle cells, significantly more than standard gene expression levels (ie expression levels in normal tissues or body fluids from individuals without the disorder) Higher or lower levels of expression of this gene may be associated with specific tissue or cell types (eg, developmental tissue, lung tissue, hearing tissue, muscle tissue, fibrous tissue, and Cancerous tissue and wound tissue) or body fluids (eg lymph, serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

This tissue distribution in fetal tissue indicates that the polynucleotides and polypeptides corresponding to this gene are useful for diseases involving abnormal cell proliferation such as cancer. Expression of this gene product in embryos; in rhabdomyosarcoma; and in rapidly proliferating cells, such as those found in wound healing tissue, may allow the gene to play a role in regulating or promoting cell growth. Indicates that. Alternately, expression of this gene in fetal tissue indicates that it may play a role in cell development and differentiation, especially in the auditory system and lungs. Therefore, this gene product may be useful for the treatment and / or diagnosis of hearing and respiratory disorders. Expression of this gene product in rhabdomyosarcoma indicates that this gene product may play a role in the progression of such cancers and may also be involved in metastasis and / or angiogenesis. . Furthermore, expression in wound healing tissue also shows a role in wound healing and the proliferation of connective tissue types involved in scarring associated with fibrosis and wound healing processes. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 147 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Accordingly, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1-837 of SEQ ID NO: 147 and b is 15-8.
Is an integer of 51, wherein both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 147, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

Characterization of Protein Encoded by Gene No. 138 This gene, which encodes the disclosed cDNA, is believed to reside on chromosome 1. Therefore, the polynucleotide according to the present invention is useful as a marker for linkage analysis of chromosome 1.

This gene is expressed primarily in the adult brain and to a lesser extent in the cerebellum.

Accordingly, the polynucleotides and polypeptides of the present invention include for differential identification of tissues or cell types present in a biological sample, as well as disorders and diseases of the brain, particularly neurodegenerative and behavioral states. Is useful as a reagent for diagnosing diseases and disorders not limited thereto. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, especially the central nervous system, significantly higher or lower levels relative to standard gene expression levels (ie, expression levels in normal tissues or fluids from individuals without the disorder) Expression of this gene in specific tissues or cell types (eg, neural tissue, cancerous tissue and wound tissue) or body fluids (eg, lymph, serum, plasma, urine, etc.) taken from an individual having such a disorder. Synovial fluid, and cerebrospinal fluid) or another tissue or cell sample.

A preferred epitope is the residue in SEQ ID NO: 297: Pro-25 to Se.
The epitopes include the sequences shown as r-30 and Thr-36 to Ser-47.

This tissue distribution in neural tissue indicates that the polynucleotides and polypeptides corresponding to this gene are of particular interest in the treatment and diagnosis of brain disorders and diseases including paranoia, Alzheimer's disease, depression, schizophrenia, and mania. To be useful for. In addition, polynucleotides and polypeptides corresponding to this gene are useful in the detection / treatment of the following diseases: neurodegenerative disease states, behavioral disorders, or inflammatory conditions (eg Parkinson's disease, Huntington's disease, Tourette's). Syndrome, meningitis, encephalitis, demyelinating disease, peripheral neuropathy, neoplastic trauma, congenital abnormalities, spinal cord injury, ischemia and infarction, aneurysm, bleeding, dementia, paranoia, obsessive-compulsive disorder, panic disorder, Behavioral changes such as learning disabilities, psychosis, autism, and impairments in nutrition, sleep patterns, balance, and perception. Furthermore, the high expression of this gene product in brain regions indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, recognition, homeostasis, or neural differentiation or survival. In addition, the genes and gene products may also play a role in the treatment and / or detection of developing embryos, sex-linked disorders or developmental disorders associated with disorders of the cardiovascular system. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 148 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1-600 of SEQ ID NO: 148 and b is 15-6.
14 is an integer of 14, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 148, and b is a + 14 or more) are excluded. It

[0744]     (Characteristics of protein encoded by gene number 139)   This gene is mainly expressed in the cerebellum.

Accordingly, the polynucleotides and polypeptides of the present invention include for differential identification of tissues or cell types present in a biological sample, as well as for neurological disorders, particularly neurodegenerative disorders such as Alzheimer's. Are useful as reagents for the diagnosis of diseases and conditions including, but not limited to, Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, especially the central nervous system, significantly higher or lower levels relative to standard gene expression levels (ie, expression levels in normal tissues or fluids from individuals without the disorder) Expression of this gene in specific tissues or cell types (eg, neural tissue, cancerous tissue and wound tissue) or body fluids (eg, lymph, serum, plasma, urine, etc.) taken from an individual having such a disorder. Synovial fluid, and spinal fluid) or another tissue or cell sample.

This tissue distribution in the cerebellum indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of brain diseases and disorders. In particular, the polynucleotides and polypeptides corresponding to this gene are
Useful in the detection / treatment of the following diseases: neurodegenerative disease states, behavioral disorders, or inflammatory conditions (eg Alzheimer's disease, Parkinson's disease, Huntington's disease,
Tourette's syndrome, meningitis, encephalitis, demyelinating disease, peripheral neuropathy, neoplasia, injury, congenital abnormalities, spinal cord injury, ischemia and infarction, aneurysm, hemorrhage, schizophrenia, mania, dementia, paranoia, Obsessive-compulsive disorder, panic disorder, learning disorder, ALS (amyotrophic lateral sclerosis), psychosis, autism, and behavioral changes including nutritional disorders, sleep pattern disorders, balance sensory disorders, and sensory disorders) . Furthermore, the high expression of this gene product in brain regions indicates that it plays a role in normal neural function. Potentially, this gene product may be synaptogenic, neurotransmitter, learning, cognitive, homeostasis, or
It is involved in nerve differentiation or survival. In addition, the genes and gene products may also play a role in the treatment and / or detection of developmental disorders associated with embryonic development, sex-related disorders or cardiovascular disorders. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 149 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Accordingly, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 1186 of SEQ ID NO: 149 and b is 15-
Is an integer of 1200, wherein both a and b correspond to the nucleotide residue positions set forth in SEQ ID NO: 149, and where b is a + 14 or more) and one or more polynucleotides are excluded. It

Characterization of Protein Encoded by Gene No: 140 This gene is expressed primarily in the brain of Alzheimer's patients and to a lesser extent in human adipose tissue.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, as well as for nerves or fat-related disorders, particularly nerves such as Alzheimer's. It is useful as a reagent for diagnosis of diseases and conditions, including but not limited to degenerative disorders. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, especially the central nervous system, significantly higher or lower levels relative to standard gene expression levels (ie, expression levels in normal tissues or fluids from individuals without the disorder) Expression of this gene in specific tissues or cell types (eg, nervous tissue, metabolic tissue, adipose tissue, and cancerous and wound tissue) or body fluids (eg, lymphoid) taken from an individual with such a disorder. ,
Serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

This tissue distribution in nerve and adipose tissue indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of Alzheimer's disease and other nervous system disorders. In addition, polynucleotides and polypeptides corresponding to this gene are useful in the detection / treatment of the following diseases: neurodegenerative disease states, behavioral disorders, or inflammatory conditions (eg Alzheimer's disease, Parkinson's disease, Huntington's disease). , Tourette's syndrome, meningitis, encephalitis, demyelinating disease, peripheral neuropathy, neoplasia, injury, congenital abnormality, spinal cord injury, ischemia and infarction, aneurysm, bleeding, schizophrenia, mania, dementia, paranoia , Behavioral disorders including obsessive-compulsive disorder, panic disorder, learning disability, ALS (amyotrophic lateral sclerosis), psychosis, autism, and nutritional disorders, sleep pattern disorders, balance disorder, and sensory disorders ). Furthermore, the high expression of this gene product in brain regions indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, recognition, homeostasis, or neural differentiation or survival. Moreover, the genes and gene products may also play a role in the treatment and / or detection of developmental disorders associated with embryonic development, sex-related disorders or disorders of the cardiovascular system. More specifically, the protein product of this gene is for the treatment, diagnosis, and / or prevention of neurological disorders secondary to abnormal fatty acid metabolism, such as abnormal development of the myelin sheath of nerve cells. It may prove useful. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 150 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1-669 of SEQ ID NO: 150 and b is 15-6.
Is an integer of 83, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 150, and b is a + 14 or more) and one or more polynucleotides are excluded. It

[0752]     (Characteristics of protein encoded by gene number 141)   This gene is mainly expressed in T cells.

Accordingly, the polynucleotides and polypeptides of the present invention may be used for the differential identification of tissues or cell types present in a biological sample, and especially for T cell leukemia, immunodeficiency, and inflammatory conditions. It is useful as a reagent for diagnosis of diseases and conditions, including but not limited to immune or hematopoietic disorders.
Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, especially the immune system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in normal tissues or fluids from individuals without disorders). The expression of this gene is dependent on the specific tissue or cell type (eg, immune, hematopoietic, and cancerous and wounded tissue) or body fluid (eg, lymph, serum, plasma) taken from an individual having such a disorder. , Urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

A preferred epitope is the residue in SEQ ID NO: 300: Asn-62 to Le.
An epitope is included which includes the sequence designated as u-68.

This tissue distribution in T cells indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of T cell leukemias and other immune system disorders. In addition, this gene product may play a role in the regulation of proliferation; survival; differentiation; and / or hematopoietic cell lineage activation, including blood stem cells.
This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may present utility in the treatment of cancer (eg, by boosting the immune response), and the gene As expressed in the cell of origin, the natural gene product may be involved in immune function. Therefore, the aforementioned genes are associated with arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, contusion, neutropenia, neutrophilia. Disease, psoriasis, hypersensitivity (eg, T cell-mediated cytotoxicity); immune response to transplanted organs and tissues (
For example, host-versus-graft and graft-versus-host disease) or autoimmune disorders (eg,
It is also used as a drug for immunological disorders, including autoimmune infertility, lens tissue injury, demyelination, systemic lupus erythematosus, drug-induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma) and tissues. obtain. Moreover, this gene product may have commercial utility in the proliferation of stem cells and associated progenitor cells of various blood lineages, as well as in the differentiation and / or proliferation of various cell types. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 151 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 813 of SEQ ID NO: 151 and b is from 15 to 8
Is an integer of 27, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 151, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

Characterization of Protein Encoded by Gene No. 142 This gene, which encodes the disclosed cDNA, is believed to be on chromosome 8. Therefore, the polynucleotide related to the present invention is useful as a marker for chromosome 8 linkage analysis.

This gene is expressed to a lesser extent mainly in the frontal lobe of the brain, and in synovial fluid and embryos.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in biological samples, and particularly for neurodegenerative abnormalities, behavioral abnormalities, and congenital brains. It is useful as a reagent for diagnosing diseases and conditions including, but not limited to, the occurrence of disorders such as abnormalities or nerve disorders. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, especially the central nervous system, significantly higher or lower levels relative to standard gene expression levels (ie, expression levels in normal tissues or fluids from individuals without the disorder) Expression of this gene in specific tissues or cell types (eg, neural, developmental, and cancerous and wound tissues) or body fluids (eg, lymph,
Amniotic fluid, serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

[0760] A preferred epitope is the residue in SEQ ID NO: 301: Gln-24 to Ly.
An epitope is included that includes the sequence designated as s-31.

This tissue distribution in brain tissue indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of brain abnormalities.
In addition, polynucleotides and polypeptides corresponding to this gene are useful in the detection / treatment of the following diseases: neurodegenerative disease states, behavioral disorders, or inflammatory conditions (eg, Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, meningitis, encephalitis, demyelinating disease, peripheral neuropathy, neoplasia, injury, birth defects,
Spinal cord injury, ischemia and infarction, aneurysm, hemorrhage, schizophrenia, mania, dementia, paranoia, obsessive-compulsive disorder, panic disorder, learning disorder, ALS (amyotrophic lateral sclerosis),
Behavioral changes including psychosis, autism, and nutritional disorders, sleep pattern disorders, balance disorders, and sensory disorders. Furthermore, the high expression of this gene product in brain regions indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neural differentiation or survival. In addition, the genes and gene products may also play a role in the treatment and / or detection of embryonic development, sex-linked disorders, or developmental disorders associated with disorders of the skeletal or cardiovascular system. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 152 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 821 of SEQ ID NO: 152 and b is from 15 to 8
Is an integer of 35, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 152, and b is a + 14 or more) and one or more polynucleotides comprising It

Characterization of Protein Encoded by Gene No. 143 This gene, which encodes the disclosed cDNA, is believed to be on chromosome 19. Therefore, the polynucleotide related to the present invention is useful as a marker for chromosome 19 linkage analysis.

[0764]   This gene is mainly expressed in osteoblasts.

Accordingly, the polynucleotides and polypeptides of the invention include, but are not limited to, for the differential identification of tissues or cell types present in a biological sample, and for skeletal disorders such as osteoporosis and cancer. It is useful as a reagent for diagnosing diseases and conditions that are not affected. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. For many disorders of the tissues or cells, especially the skeletal system, levels significantly higher or lower than standard gene expression levels (ie, expression levels in healthy tissues or fluids from unaffected individuals). The expression of this gene is dependent on the specific tissue or cell type (eg, skeletal tissue, and cancerous and wound tissue) or body fluid (eg, tissue) taken from an individual having such a disorder.
Lymph, serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

This tissue distribution in osteoblasts indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the treatment of osteoporosis and other degenerative bone disorders. The protein as well as antibodies to the protein may exhibit utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 153 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 544 of SEQ ID NO: 153 and b is from 15 to 5
Is an integer of 58, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 153, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

Characterization of Protein Encoded by Gene No. 144 This gene is expressed primarily in CD34-positive cells (umbilical cord blood) and placenta.

Accordingly, the polynucleotides and polypeptides of the present invention include for differential identification of tissues or cell types present in a biological sample, as well as developmental and immune disorders, particularly proliferative conditions. However, it is useful as a reagent for the diagnosis of diseases and conditions including but not limited to them. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher or higher than standard gene expression levels (ie, expression levels in normal tissues or body fluids from unaffected individuals) in relation to many disorders of the tissues or cells, particularly the immune system Low levels of expression of this gene may result in specific tissue or cell types (eg, immune, reproductive, developmental and cancerous and wound tissues) or body fluids (eg, immune and reproductive, developmental and cancerous tissues) collected from individuals with such disorders. Lymph, amniotic fluid, serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

Tissue distribution in cord blood and placental tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of immune system disorders, particularly those involving CD34 cells. Expression within cell sources characterized by proliferative cells indicates that this protein may play a role in regulating cell division and may have utility in the diagnosis and treatment of cancer and other proliferative disorders. .. Similarly, developing tissue relies on decisions involved in cell differentiation and / or apoptosis in patterning. Therefore, this protein may also be involved in apoptosis or tissue differentiation and may also be useful in the treatment of cancer. The protein, and antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 154 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer from 1 to 1187 of SEQ ID NO: 154, and b is 15 to 1
An integer of 201, wherein both a and b correspond to the nucleotide residue position set forth in SEQ ID NO: 154, and where b is a + 14 or greater) 1
One or more polynucleotides are excluded.

[0772]     (Characteristics of protein encoded by gene number 145)   The translation product of this gene is expressed primarily in the frontal cortex of the brain.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for the differential identification of tissues or cell types present in a biological sample, as well as for neural or neurodegenerative conditions and other abnormalities of the brain. It is useful as a reagent for the diagnosis of diseases and conditions including, but not limited to spinal cord disorders. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for the differential identification of tissues or cell types. Significantly higher than standard gene expression levels (ie, expression levels in normal tissues or fluids from unaffected individuals) in connection with many disorders of the tissues or cells, particularly the central nervous system, or Lower levels of expression of this gene may be associated with specific tissues or cell types (eg, neural and cancerous and wound tissues) or body fluids (eg, lymph, serum, plasma) taken from individuals with such disorders. , Urine, synovial fluid, and spinal fluid)
Alternatively, it can be routinely detected in another tissue or cell sample.

A preferred epitope is the residue in SEQ ID NO: 304: Pro-21 to Se.
An epitope is included which includes the sequence designated as r-27.

The tissue distribution in the frontal cortex indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of brain abnormalities. In particular, the polynucleotides and polypeptides corresponding to this gene have neurodegenerative and behavioral disorders or inflammatory conditions (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, meningitis, encephalitis, desensitization). Myelopathy, peripheral neuropathy, neoplasia, trauma, birth defects, spinal cord injury, ischemia and infarction, aneurysm,
Bleeding, schizophrenia, mania, dementia, paranoia, obsessive-compulsive disorder, panic disorder, learning disability,
It is shown to be useful in detecting / treating ALS, psychosis, autism, and behavioral changes, including impairment of nutritional support, sleep patterns, balance, and perception. Furthermore, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning capacity, cognition, homeostasis, or neural differentiation or survival.
In addition, the gene or gene product may also play a role in treating and / or detecting the development of embryonic development, sex-linked disorders, or disorders associated with disorders of the cardiovascular system.
The protein, and antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 155 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 1012 of SEQ ID NO: 155, and b is 15 to 1
An integer of 026, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 155, and where b is a + 14 or greater) 1
One or more polynucleotides are excluded.

Characterization of Protein Encoded by Gene No. 146 This gene, which encodes the disclosed cDNA, is believed to be located on chromosome 2. Therefore, the polynucleotide related to the present invention is useful as a marker in the linkage analysis of chromosome 2.

This gene is expressed primarily in adrenal tumors, breast tissue and to a lesser extent in adipose tissue.

Accordingly, the polynucleotides and polypeptides of the present invention are useful for differential identification of tissues or cell types present in a biological sample, as well as adrenal tumors, breast cancers; endocrine disorders such as metabolic disorders or It is useful as a reagent for the diagnosis of disorders and conditions, including but not limited to reproductive disorders. Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. Significantly higher than standard gene expression levels (ie, expression levels in normal tissues or fluids from unaffected individuals) in association with many disorders of the tissues or cells, particularly the adrenal gland and chest, or Low levels of expression of this gene are associated with specific tissues or cell types taken from individuals with such disorders, such as reproductive, metabolic, endocrine, breast, adrenal, and cancerous and wound tissues. ) Or body fluids (eg lymph, serum,
Breast milk, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample can be routinely detected.

A preferred epitope is in SEQ ID NO: 305: Arg-44 to Lys-4.
9, an epitope containing the sequence shown as Asp-60 to Phc-66 residues.

Tissue distribution in adrenal and breast tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful in diagnosing and / or treating disorders involving the adrenal gland. Expression of this gene product in the adrenal gland indicates that it may play a role in tumors of the adrenal gland, or, in general, potentially play a role in cell proliferation. In such events, it may play a role in determining the course and severity of cancer. Alternatively, it may play a role in the normal function of the adrenal gland, such as the production of corticosteroids, androgens, or epinephrine. Therefore, this gene is usually found in homeostasis as well as
It may play a role in disorders involving androgen hormones. Expression of this gene product in breast and adipose tissue also indicates that this gene may play a role in breast cancer or in the supply of essential nutrients to lactating infants.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 156 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably according to the invention, the nucleotide sequence described by the general formula ab (
Here, a is an arbitrary integer of 1 to 890 of SEQ ID NO: 156, and b is 15 to 90.
4 is an integer of 4, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 156, and b is a + 14 or greater) and one or more polynucleotides are excluded. (Characteristics of protein encoded by gene number 147) This gene is mainly LNCAP, and naive spleen; metastatic (metast)
ic) Expressed in melanoma.

Accordingly, the polynucleotides and polypeptides of the present invention are for the differential identification of tissues or cell types present in a biological sample, as well as for immune disorders, hematopoietic disorders,
It is useful as a reagent for the diagnosis of diseases and conditions including but not limited to integumental disorders (eg metastatic melanoma). Similarly, polypeptides and antibodies to these polypeptides are useful in providing immunological probes for differential identification of tissue or cell types. Relative to standard gene expression levels (ie, expression levels in healthy tissues or body fluids taken from undiseased individuals) in connection with many disorders of the tissues or cells, particularly the immune and cancer metabolism systems Significantly higher or lower levels of expression of this gene in certain tissues or cell types taken from individuals with such disorders (eg, immune, hematopoietic, epithelial and cancerous and wound tissues). Or it can be routinely detected in body fluids such as lymph, serum, plasma, urine, synovial fluid, and spinal fluid, or another tissue or cell sample.

A preferred epitope is in SEQ ID NO: 306: His-47 to Thr-5.
An epitope containing the sequence shown as 3 residues.

This tissue distribution in spleen and epithelial tissues indicates that the polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of several types of cancer, especially metastatic melanoma. Show. The protein product of this gene is congenital disorders (ie, nevus, pigmented nevus, freckles, Mongolian spots, hemangiomas,
Wine-like syndrome), integumental tumors (ie keratoses, Bowen's disease, basal cell carcinoma,
Squamous cell carcinoma, malignant melanoma, Paget's disease, mycosis fungoides, and Kaposi's sarcoma),
Skin damage and inflammation (ie wounds, rashes, erythema erythematosus disorders, psoriasis, dermatitis)
, Atherosclerosis, urticaria, eczema, photophobia, autoimmune disorders (ie lupus erythematosus, vitiligo, dermatomyositis, localized scleroderma, scleroderma, pemphigus, and pemphigus), keloids, It is useful for treating, diagnosing and / or preventing various skin disorders including striatum, erythema, petechiae, purpura, and blepharveosis.
In addition, such disorders include viral and bacterial infections of the skin (ie, herpes simplex, warts, chickenpox, molluscum contagiosum, herpes zoster, swelling, cellulitis, erysipelas,
It may predispose to increased susceptibility to impetigo, ringworm, athletes foot, and ringworm. In addition, the protein product of this gene is
Various connective tissue disorders (eg, arthritis, trauma, tendinitis, chondromalacia (chron)
and inflammatory), autoimmune disorders (eg, rheumatoid arthritis, lupus, scleroderma and dermatomyositis), and dwarfism, spinal deformities and certain joint abnormalities, and dyschondrosteesis (ie, congenital vertebrae). Dysplasia, familial osteoarthritis, type II osteogenesis (Atelosteogenesis type)
II), Schmidt metaphyseal cartilage dysplasia) may also be useful for the treatment and diagnosis. Alternatively, this gene is useful for the treatment and diagnosis of hematopoietic-related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia. This is because stem cells are important for the production of hematopoietic cells. For this use
Examples include ex vivo culture of bone marrow cells, bone marrow transplantation, bone marrow repopulation, neoplastic radiation therapy or chemotherapy. This gene product may also be associated with lymphopoiesis. Therefore, this gene product can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency, and the like. Moreover, this gene product may have commercial utility in the proliferation of stem cells and directed progenitor cells of various blood lineages, as well as in the differentiation and / or proliferation of various cell types. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 157 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, wherein a is any integer from 1 to 902 of SEQ ID NO: 157 and b is from 15 to 9
16 is an integer of 16, wherein both a and b correspond to the positions of the nucleotide residues set forth in SEQ ID NO: 157, and b is a + 14 or greater) and one or more polynucleotides are excluded. It

CHARACTERISTICS OF PROTEIN ENCODED BY GENE NO: 148 In certain embodiments, a polypeptide of the invention comprises the following amino acid sequence: AGAEVVMLFLTPSSHHQHECVRRAFECGDCHI.
LLDNNVLGVDCHGAGERAVHLEDHFVHIDTISLLLE
DALEYSALIAGHPKSDLPPGLSRCRPWEHHWPISYT
G (SEQ ID NO: 488), TISYLCNNVSYMQLQKLVGKSMIF
LPYSLPIHLPGNHRLLLPRVGMRLRRGCCFSPYIITD
FKWC (SEQ ID NO: 489), EMGQWCSQGLHLDSPGGGKSDF
GCPAINAEYSRASSKSRLMVSMWKTWSSRCTALSPA
P (SEQ ID NO: 490), RAFECGGDCHILLLDNNVLGVDCHGA
G (SEQ ID NO: 491), and / or LVGKSMIFLPYSLPIHL
PGNHRL (SEQ ID NO: 492). Polynucleotides encoding these polypeptides are also included in the present invention. This gene, which encodes the disclosed cDNA, is believed to be located on chromosome 1. Therefore, the polynucleotide related to the present invention is useful as a marker in the linkage analysis of chromosome 1.

This gene is expressed primarily in the ovary, and to a lesser extent in the meninges, adrenal glands and cerebellum.

Accordingly, the polynucleotides and polypeptides of the present invention are used for the differential identification of tissues or cell types present in a biological sample, as well as for ovarian and brain cancer, neuronal deficiency disorders, and infertility. It is useful as a reagent for the diagnosis of diseases and conditions including but not limited to reproductive disorders, neurological disorders, and endocrine disorders. Similarly, polypeptides and antibodies to these polypeptides include
It is useful in providing immunological probes for the differential identification of tissues or cell types.
Significantly higher than standard gene expression levels (ie expression levels in normal tissues or body fluids from non-disordered individuals) for many disorders of the tissues or cells, especially the female reproductive and endocrine systems, or Lower levels of expression of this gene are associated with specific tissues or cell types (eg, neural, reproductive, ovarian, and cancerous and wound tissues) or body fluids collected from individuals with such disorders. For example, lymph, amniotic fluid, serum, plasma, urine, synovial fluid, and spinal fluid) or another tissue or cell sample.

This tissue distribution in ovarian and endocrine tissues indicates that the polynucleotides and polypeptides corresponding to this gene are useful in the diagnosis and treatment of ovarian cancer and other endocrine disorders. Alternatively, the polynucleotides and polypeptides corresponding to this gene are neurodegenerative disease states, behavioral disorders or inflammatory conditions (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, meningitis, encephalitis, demyelinating disease, Peripheral neuropathy, neoplasia, trauma, congenital abnormalities, spinal cord injury, ischemia and infarction, aneurysm, bleeding, schizophrenia, mania, dementia, paranoia, obsessive-compulsive disorder, panic disorder, learning disability, ALS , Psychosis, autism, and behavioral changes (
(Including nutritional supplementation, sleep patterns, balance, and sensory disturbances). Furthermore, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is associated with synapse formation, neurotransmission, learning, recognition, homeostasis, or neuronal differentiation or survival. In addition, the gene or gene product may also play a role in the treatment and / or detection of developmental, sex-linked, or cardiovascular disorders associated with the developing embryo. The protein, as well as antibodies to this protein, may show utility as tumor markers and / or immunotherapeutic targets for the tissues listed above.

Many polynucleotide sequences (eg, EST sequences) are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 158 and may have been publicly available prior to the idea of the invention. Preferably, such related polynucleotides are specifically excluded from the scope of the invention. Enumerating all relevant sequences is cumbersome. Therefore, preferably from the present invention, the nucleotide sequence described by the general formula ab, where a is any integer from 1 to 907 of SEQ ID NO: 158 and b is 15 to 1
An integer of 921, wherein both a and b correspond to the position of the nucleotide residue set forth in SEQ ID NO: 158, and where b is a + 14 or greater) 1
One or more polynucleotides are excluded.

[0792]

[Table 1] Table 1 summarizes the information corresponding to each "gene number" above. The nucleotide sequence identified as "nucleotide sequence number X" is identified in Table 1 as "
cDNA clone ID ", and in some cases, a further related DN
It was constructed from partially homologous (“overlapping”) sequences obtained from the A clone.
Overlapping sequences were assembled into a single sequence of high redundancy (usually 3-5 overlapping sequences at each nucleotide site), yielding the final sequence identified as SEQ ID NO: X.

The cDNA Clone ID was deposited on that date, and "ATCC Deposit No. Z
And the corresponding deposit numbers listed under "Dates". Some of the deposits contain multiple different clones corresponding to the same gene. "Vector" is
It refers to the type of vector contained in the cDNA clone ID.

“Total nucleotide sequence” refers to the total number of nucleotides in the contig identified by the “gene number”. The deposited clone may contain all or most of these sequences, indicated by the nucleotide positions designated as "5 'nucleotides of the clone sequence" and "3' nucleotides of the clone sequence" of SEQ ID NO: X. Be done. The nucleotide position of SEQ ID NO: X of the putative start codon (methionine) is identified as the "5 'nucleotide of the start codon". Similarly, the nucleotide position of SEQ ID NO: X of the putative signal sequence is identified as "the 5'nucleotide of the first amino acid of the signal peptide".

The translated amino acid sequence begins with methionine and is identified as "amino acid sequence number Y", although other reading frames can also be readily translated using known molecular biology techniques. Polypeptides produced by these alternative open reading frames are specifically contemplated by the present invention.

The positions of the first and last amino acids of the putative signal peptide SEQ ID NO: Y are
It is identified as "the first amino acid of the signal peptide" and "the last amino acid of the signal peptide". The position of the deduced first amino acid of SEQ ID NO: 3 of the secretory portion is identified as the “deduced first amino acid of the secretory portion”. Eventually,
The amino acid position of SEQ ID NO: Y of the last amino acid in the open reading frame is identified as the "last amino acid of the ORF."

SEQ ID NO: X and translated SEQ ID NO: Y are sufficiently accurate and are otherwise suitable for a variety of uses well known in the art and described further below. For example, SEQ ID NO: X is useful for designing a nucleic acid hybridization probe that detects the nucleic acid sequence contained in SEQ ID NO: X or the cDNA contained in the deposited clone. These probes also hybridize to nucleic acid molecules in biological samples, thereby enabling the various forensic and diagnostic methods of the invention. Similarly, the polypeptide identified from SEQ ID NO: Y can be used to raise antibodies that specifically bind to the secreted protein encoded by the cDNA clones identified in Table 1.

Nevertheless, the DNA sequence produced by the sequencing reaction may contain sequencing errors. Errors exist as misidentified nucleotides or as insertions or deletions of nucleotides in the generated DNA sequence. Incorrectly inserted or deleted nucleotides cause a frameshift in the reading frame of the deduced amino acid sequence. In these cases, the DNA sequence produced was more than 99.9% identical to the actual DNA sequence (
The deduced amino acid sequence differs from the actual amino acid sequence, although it could be, for example, a single base insertion or deletion in the open reading frame of over 1000 bases.

Therefore, for those applications requiring accuracy in the nucleotide or amino acid sequence, the present invention was identified as SEQ ID NO: X and the nucleotide sequence produced and predicted as SEQ ID NO: Y. Also provided is a sample of plasmid DNA containing the human cDNA of the invention deposited with the ATCC, as described in Table 1, as well as the translated amino acid sequences. The nucleotide sequence of each of the deposited clones can be readily determined by sequencing the deposited clone according to known methods. The deduced amino acid sequence can then be confirmed from such deposits. In addition, the amino acid sequence of the protein encoded by a particular clone also expresses the protein by peptide sequencing or in a suitable host cell containing the deposited human cDNA, collecting the protein, and By determining, it can be determined directly.

The present invention also relates to the gene corresponding to SEQ ID NO: X, SEQ ID NO: Y, or the deposited clone. The corresponding gene can be isolated according to known methods using the sequence information disclosed herein. Such methods include the steps of preparing a probe or primer from the disclosed sequences and identifying or amplifying the corresponding gene from a suitable source of genomic material.

Also provided in the present invention are species homologs. Species homologs can be isolated and identified by making appropriate probes or primers from the sequences provided herein and screening the appropriate nucleic acid source for the desired homolog.

The polypeptides of the present invention can be prepared in any suitable manner. Such polypeptides include isolated naturally occurring polypeptides, recombinantly produced polypeptides, synthetically produced polypeptides, or produced by a combination of these methods. Polypeptides that have been prepared. Means for preparing such polypeptides are well understood in the art.

The polypeptide may be in the form of a secreted protein (including the mature form) or may be part of a larger protein (eg a fusion protein) (see below). It is often advantageous to include additional amino acid sequences, including secretory or leader sequences, prosequences, sequences that aid in purification (eg, multiple histidine residues), or additional sequences for stability during recombinant production. Is.

The polypeptides of the present invention are preferably provided in isolated form and are preferably substantially purified. Polypeptides (including secreted polypeptides)
Recombinantly produced versions of Smith and Johnson, Ge
can be substantially purified by the one-step method described in ne 67: 31-40 (1988). The polypeptides of the invention can also be purified from natural or recombinant sources using the antibodies of the invention raised against secreted proteins in methods well known in the art.

Signal Sequences Methods are available for predicting whether a protein has a signal sequence, as well as a breakpoint for that sequence. For example, McGeoch, Vi
rus Res. 3: 271-286 (1985) uses information from a short N-terminal charged region followed by an uncharged region of the intact (uncleaved) protein. von Heinje, Nucleic Acids Re
s. 14: 4683-4690 (1986), the method of
Information from (typically -13 to +2 residues) is used, where +1 indicates the amino terminus of the secreted protein. The accuracy of predicting breakpoints of known mammalian secretory proteins for each of these methods is in the range of 75-80% (von Heinje, supra). However, the two methods do not always produce the same putative breakpoint for a given protein.

In the present case, the deduced amino acid sequence of the secreted polypeptide is Si
A computer program called gnalP (Henrik Nielse
n et al., Protein Engineering 10: 1-6 (1997)).
Analyzed by This program predicts the location of proteins in cells based on their amino acid sequences. As part of the computer prediction of this localization, Mc
The method of Geoch and von Heinje is incorporated. Analysis of the amino acid sequences of the secreted proteins described herein by this program is shown in Table 1.
Provided the results shown in.

However, as will be appreciated by those of skill in the art, the cleavage site will occasionally vary from organism to organism and cannot be predicted with absolute certainty. Thus, the invention provides a secreted polypeptide having the sequence set forth in SEQ ID NO: Y, which has an N-terminus beginning within 5 residues of the putative breakpoint (ie, + or -5 residues). Have.
Similarly, it is also recognized that in some cases cleavage of the signal sequence from the secreted protein is not necessarily uniform, resulting in more than one secreted species. These polypeptides and polynucleotides encoding such polypeptides are contemplated by the present invention.

Furthermore, the signal sequences identified by the above analysis may not necessarily predict the naturally occurring signal sequence. For example, the naturally occurring signal sequence can be further upstream from the putative signal sequence. However, the putative signal sequence likely directs the secreted protein to the ER. These polypeptides,
And polynucleotides encoding such polypeptides are contemplated by the present invention.

(Polynucleotide and Polypeptide Variants) The term “variant” refers to a polynucleotide or polypeptide that differs from the polynucleotide or polypeptide of the present invention but retains their essential properties. Say. In general, variants are wholly closely similar and, in many regions, identical to the polynucleotides or polypeptides of the invention.

A nucleotide sequence of a polynucleotide, for example, a polynucleotide having a nucleotide sequence that is at least 95% “identical” to a reference nucleotide sequence of the invention, of the reference nucleotide sequence in which the polynucleotide sequence encodes a polypeptide. It is intended to be identical to a reference sequence, except that it can include up to 5 point mutations for each 100 nucleotides. In other words, up to 5% of the nucleotides in the reference sequence may be deleted or replaced by another nucleotide, or in order to obtain a polynucleotide having a nucleotide sequence which is at least 95% identical to the reference nucleotide sequence, or 5% of total nucleotides in the sequence
Up to a large number of nucleotides can be inserted in the reference sequence. Inquiry
y) The sequence can be the entire sequence shown in Table 1, ORF (Open Reading Frame), or any fragment identified as described herein.

As a practical matter, will any particular nucleic acid molecule or polypeptide be at least 90%, 95%, 96%, 97%, 98%, or 99% identical to a nucleotide sequence of the invention? Whether or not it can be determined conventionally using known computer programs. A preferred method for determining the best overall compatibility (also referred to as the overall sequence alignment) between a query sequence (the sequence of the invention) and this sequence is described by Brutlag et al. (Comp. App. Biosci.
(1990) 6: 237-245) and can be determined using the FASTDB computer program. In the sequence alignment, both the query sequence and this sequence are DNA sequences. RNA sequences can be compared by converting U to T. The result of this global sequence alignment is the percent identity. FAST DNA sequences to calculate percent identity
The preferred parameters used in DB alignment are: Matrix = Unit
ary, k-tuple = 4, Mismatch Penalty = 1, Joi
Ning Penalty = 30, Randomization Group
Length = 0, Cutoff Score = 1, Gap Penalty =
5, Gap Size Penalty 0.05, Window Size =
500 or the length of the nucleotide sequence (whichever is shorter).

If this sequence is shorter than the query sequence due to the 5'or 3'deletions (as opposed to due to internal deletions), a manual correction must be made to the results. This is because the FASTDB program uses 5 of the sequences when calculating percent identity.
This is because the'and 3'cuts are not considered. For a subject sequence that is truncated at the 5'or 3'end, the percent identity to the query sequence is the 5'and 3'of the subject sequence that is not matched / aligned as a percentage of the total bases of the query sequence. Corrected by calculating the number of bases in. Whether the nucleotides are matched / aligned is determined by the results of the FASTDB sequence alignment. This percentage is then subtracted from the percent identity and calculated by the FASTDB program above using the specified parameters to arrive at the final percent identity score. This corrected score is what is used for the purposes of the present invention. Only the bases outside the 5'and 3'bases of the sequence that are not matched / aligned with the query sequence, as shown by the FASTDB alignment, are calculated for the purpose of manually adjusting the percent identity score.

For example, a 90 base subject sequence is aligned with a 100 base query sequence to determine percent identity. This sequence, and therefore 5 of the FASTDB alignment
The deletions that occur at the'end do not show a match / alignment of the first 10 bases at the 5'end.
The 10 unpaired bases represent 10% of the sequence (number of bases at the non-matching 5'and 3'ends / total number of bases in the query sequence), so 10% is FAST.
Subtracted from the percent identity score calculated by the DB program. If the remaining 90 bases were an exact match, the final percent identity would be 90%.
Is. In another example, a 90 base subject sequence is compared to a 100 base query sequence. In this case, the deletion is an internal deletion such that there are no bases at the 5'or 3'of the subject sequence which are not matched / aligned with the query sequence. In this case, the percent identity calculated by FASTDB is not manually corrected. Again, only the 5'or 3'bases of this sequence that do not match / align with the query sequence are manually corrected.
No other manual correction is made for the purposes of the present invention.

By virtue of a polypeptide having, for example, an amino acid sequence that is at least 95% “identical” to a query amino acid sequence of the invention, the amino acid sequence of this polypeptide is such that It is intended to be identical to the query sequence, except that changes of up to 5 amino acids per 100 amino acids may be included. In other words, the query amino acid sequence contains at least 95
Up to 5% of the amino acid residues in the sequence may be inserted, deleted, (indels) or replaced with another amino acid to obtain a polypeptide having an amino acid sequence that is% identical. These changes in the reference sequence can occur at the amino-terminal or carboxy-terminal sites of the reference amino acid sequence, or anywhere between those terminal sites, either individually between the residues in the reference sequence or the reference Interspersed, either in one or more contiguous groups within the sequence.

As a practical matter, any particular polypeptide may be present in at least 90%, 95% of the amino acid sequences shown, for example, in Table 1 or encoded by the deposited DNA clones. Whether%, 96%, 97%, 98%, or 99% identical can be determined conventionally using known computer programs. A preferred method for determining the best overall match (also referred to as global sequence alignment) between a query sequence (the sequence of the invention) and this sequence is described by Brutlag et al. (Comp. App. Biosci). (19
90) can be determined using the FASTDB computer program based on the algorithm of 6: 237-245). In a sequence alignment, the query and the subject sequences are either both nucleotide sequences or both amino acid sequences. The results of the above global sequence alignments are given in percent identity. Preferred parameters used for FASTDB amino acid alignment are: Ma
trix = PAM 0, k-tuple = 2, Mismatch Penalt
y = 1, Joining Penalty = 20, Randomization
Group Length = 0, Cutoff Score = 1, Windows
w Size = length of sequence, Gap Penalty = 5, Gap Siz
e Penalty = 0.05, Window Size = 500 or the length of the amino acid sequence (whichever is shorter).

If this sequence is shorter than the query sequence due to N-terminal or C-terminal deletions (and not due to internal deletions), then a manual correction must be made to the results. This is because the FASTDB program does not consider N-terminal and C-terminal truncations of this sequence when calculating the overall percent identity. For a subject sequence that is truncated at the N- and C-termini, the percent identity to the query sequence is the N-terminus and C of the subject sequence that does not match / align with the corresponding subject residue as a percentage of the total bases of the query sequence. It is corrected by calculating the number of residues in the terminal query sequence. Whether the residues are matched / aligned depends on FA
Determined by the result of STDB sequence alignment. This percentage is then subtracted from the percent identity and calculated by the FASTDB program above using specific parameters to arrive at the final percent identity score. This final percent identity score is what is used for the purposes of the present invention. Only those residues N- and C-terminal to the subject sequence that are not matched / aligned with the query sequence are considered for the purpose of manually adjusting the percent identity score. That is, only the query residue positions outside the furthest N-terminal and C-terminal residues of the sequence.

For example, the 90 amino acid residue sequence of the present sequence is used to determine percent identity.
Aligned with the 00 residue query sequence. Deletions occur at the N-terminus of this sequence, and therefore the FASTDB alignment does not show a match / alignment of the first 10 residues at the N-terminus. The 10 unpaired residues represent 10% of the sequence (number of residues at the non-matching N- and C-termini / total number of residues in the query sequence), resulting in FASTDB
10% is subtracted from the percent identity score calculated by the program. If the remaining 90 residues were perfectly matched, the final percent identity would be 90.
%. In another example, a 90 residue subject sequence is compared to a 100 residue query sequence. In this case, the deletion is an internal deletion and therefore there are no residues at the N-terminus or C-terminus of the subject sequence that are not matched / aligned with the query sequence. in this case,
The percent identity calculated by FASTDB is not manually corrected. Again, only residue positions outside the N- and C-termini of the subject sequence that do not match / align with the query sequence shown in the FASTDB alignment are manually corrected. No other manual correction is made for the purposes of the present invention.

Variants may include changes in the coding regions, non-coding regions, or both. Especially preferred are those that produce silent substitutions, additions or deletions,
Polynucleotide variants containing changes that do not alter the properties or activity of the encoded polypeptide. Nucleotide variants produced by silent substitutions due to the degeneracy of the genetic code are preferred. Furthermore, in any combination
Variants in which 10, 1-5, or 1-2 amino acids are substituted, deleted, or added are also preferred. Polynucleotide variants optimize codon expression for a variety of reasons (eg, codon expression for a particular host (codons in human mRNA are
can be generated by a bacterial host such as oli))).

Naturally occurring variants are referred to as "allelic variants" and refer to one of several alternative forms of a gene that occupy a given locus on the chromosome of an organism. (Genes II, Lewin, B., edited by John Wiley &
Sons, New York (1985)). These allelic variants are
It can vary at either the polynucleotide level and / or the polypeptide level. Alternatively, non-naturally occurring variants may be produced by mutagenesis techniques or by direct synthesis.

Using known methods of protein engineering and recombinant DNA technology, variants are
It can be made to improve or change the properties of the polypeptides of the invention. For example, one or more amino acids can be deleted from the N-terminus or C-terminus of the secreted protein without substantial loss of biological function. Ron et al. Biol. Che
m. 268: 2984-2988 (1993) authors 3, 8, or 27.
A modified KGF protein having heparin-binding activity even after the deletion of amino acid residues at the amino terminus has been reported. Similarly, interferon-gamma was found to be
It shows higher activity up to 0-fold (Dobeli et al., J. Biotechn.
7: 199-216 (1988)).

[0821] Furthermore, a wealth of evidence demonstrates that variants often retain activities similar to the biological activity of naturally occurring proteins. For example, Gayle and co-workers (J. Biol. Chem 268: 22105-22111 (1
993)) performed an extensive mutational analysis of the human cytokine IL-1a. They used random mutagenesis to generate over 3,500 individual IL-1a variants that averaged 2.5 amino acid changes per variant over the entire length of the molecule. Multiple mutations were tested at every potential amino acid position. The researchers found that "the majority of molecules can be altered with little effect on either binding or biological activity." (See summary). In fact, of the over 3,500 nucleotide sequences tested, only 23 unique amino acid sequences produced proteins that differed significantly in activity from the wild type.

In addition, deletion of one or more amino acids from the N-terminus or C-terminus of the polypeptide may result in modification or deletion of one or more biological functions, but not other biological functions. Activity can still be retained. For example, the ability of a deletion variant to induce and / or bind an antibody that recognizes a secreted form is retained if less than the majority of the residues of the secreted form are removed from the N- or C-termini. It seems to be done. Whether a particular polypeptide lacking the N-terminal or C-terminal residues of a protein retains such immunogenic activity is described herein, and otherwise known in the art. Can be readily determined by conventional methods known in.

Accordingly, the present invention further includes polypeptide variants that exhibit substantial biological activity. Such variants include deletions, insertions, inversions, repeats, and substitutions selected according to general rules known in the art such that they have little effect on activity. For example, guidance on how to make phenotypically silent amino acid substitutions can be found in Bowie, J. et al. U. Et al, Science
247: 1306-1310 (1990), where the authors note that there are two major strategies for studying the tolerance of amino acid sequences to changes.

The first strategy takes advantage of the tolerance of amino acid substitutions by natural selection during the course of evolution. Conserved amino acids can be identified by comparing amino acid sequences in different species. These conserved amino acids appear to be important for protein function. In contrast, the positions of the amino acids whose substitutions were tolerated by natural selection indicate that these positions are not important for protein function. Thus, the positions that tolerate amino acid substitutions may be modified, yet still maintain the biological activity of the protein.

The second strategy uses genetic engineering to introduce amino acid changes at specific positions in the cloned gene to identify regions important for protein function. For example, site-directed mutagenesis or alanine scanning mutagenesis (
Introduction of one alanine mutation at each residue in the molecule) can be used. (Cun
Ningham and Wells, Science 244: 1081-108.
5 (1989)). The resulting mutant molecule can then be tested for biological activity.

As the authors note, these two strategies have revealed that the protein is surprisingly tolerant of amino acid substitutions. The authors further indicate which amino acid changes are likely to be tolerated at particular amino acid positions in the protein. For example, the most buried (in the tertiary structure of a protein) amino acid residue is
Although non-polar side chains are required, surface side chain features are generally poorly conserved.
In addition, tolerable conservative amino acid substitutions can be made with the aliphatic or hydrophobic amino acid A
Substitutions of la, Val, Leu, and Ile; Ser and Thr of hydroxyl residues
Substitution of Asp and Glu for acidic residues; Asn and Gl for amide residues
Substitution of n, substitution of basic residues Lys, Arg, and His; P of aromatic residues
substitutions for he, Tyr, and Trp, and the small-sized amino acid Ala
, Ser, Thr, Met, and Gly substitutions.

In addition to conservative amino acid substitutions, variants of the invention include (i) substitutions of one or more non-conservative amino acid residues, wherein the amino acid residue to be replaced is encoded by the genetic code. Or not, or (ii) substitution with one or more amino acid residues having a substituent, or (iii)
) Fusion of the mature polypeptide with another compound (eg, a compound to increase the stability and / or solubility of the polypeptide (eg, polyethylene glycol)), or (iv) an additional amino acid (eg, IgG Fc). Fusion region peptides, or leader or secretory sequences, or sequences facilitating purification) with a polypeptide. Such variant polypeptides are considered to be within the skill of those in the art given the teachings herein.

For example, polypeptide variants comprising amino acid substitutions of charged amino acids with other charged amino acids or neutral amino acids have improved properties (eg,
Proteins with less aggregation) can be produced. Aggregation of the pharmaceutical formulation reduces activity and increases clearance due to the immunogenic activity of the aggregate. (
Pinkard et al., Clin. Exp. Immunol. 2: 331-340
(1967); Robbins et al., Diabetes 36: 838-845 (
1987); Cleland et al., Crit. Rev. Therapeutic
Drug Carrier Systems 10: 307-377 (1993).
)).

(Polynucleotide and Polypeptide Fragments) In the present invention, the “polynucleotide fragment” refers to a short polynucleotide contained in the deposited clone or having the nucleic acid sequence shown in SEQ ID NO: X. Short nucleotide fragments are preferably at least about 15 nucleotides, and more preferably at least about 20 nucleotides,
Still more preferably at least about 30 nucleotides, and even more preferably at least about 40 nucleotides in length. A "at least 20 nucleotides in length" fragment is intended to include, for example, 20 or more contiguous bases from the cDNA sequence contained in the deposited clone or the nucleotide sequence set forth in SEQ ID NO: X. These nucleotide fragments are useful as diagnostic probes and primers, as discussed herein.
Of course, larger fragments (eg 50, 150, 500, 600,
2000 nucleotides) are preferred.

Further, representative examples of polynucleotide fragments of the present invention are, for example, SEQ ID NO: X or about 1-50, 51-100, 101-150, 151 of the nucleotide numbers of the cDNA contained in the deposited clone. ~ 200, 201 ~ 2
50, 251-300, 301-350, 351-400, 401-450, 4
51-500, 501-550, 551-600, 651-700, 701-7
50, 751-800, 800-850, 851-900, 901-950, 9
51-1000, 1001-1050, 1051-1100, 1101-115
0, 1151-1200, 1201-1250, 1251-1300, 1301
~ 1350,1351-1400,1401-1450,1451-1500,
1501 to 1550, 1551 to 1600, 1601 to 1650, 1651 to 1
700, 1701-1750, 1751-1800, 1801-1850, 18
51-1900, 1901-1950, 1951-2000, and 2001-
Finally, it includes a fragment having a sequence from. In this situation, "about"
Ranges specifically enumerated, some (5
, 4, 3, 2, or 1) nucleotides to include larger or smaller ranges. Preferably, these fragments encode a biologically active polypeptide. More preferably, these polynucleotides can be used as probes or primers as discussed herein.

In the present invention, "polypeptide fragment" refers to the short amino acid sequence contained in SEQ ID NO: Y or encoded by the cDNA contained in the deposited clone. The protein fragment has a "free-standing structure (free-s).
) "or within a larger polypeptide in which the fragments form a part or region, most preferably as a single contiguous region,
May be included. Representative examples of the polypeptide fragment of the present invention include, for example, about 1 to 20, 21 to 40, 41 to 60, 61 to 80, 81 of the amino acid numbers of the coding region.
~ 100, 102-120, 121-140, 141-160, or 161-
Contains the last fragment. In addition, the polypeptide fragment is approximately 20,3.
0, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130,
It can be 140, or 150 amino acids long. In this context, "about" means a number of (at either or both termini) specifically listed ranges.
5, 4, 3, 2, or 1) amino acids in length to include larger or smaller ranges.

Preferred polypeptide fragments include secreted proteins and mature forms. Further preferred polypeptide fragments include secreted proteins or mature forms that have a contiguous series of deleted residues from the amino terminus or the carboxy terminus, or both. For example, any number of amino acids in the range of 1-60 can be deleted from the amino terminus of either the secreted polypeptide or the mature form. Similarly, any number of amino acids ranging from 1 to 30 may be deleted from the carboxy terminus of the secreted protein or mature form. Furthermore, any combination of the amino-terminal and carboxy-terminal deletions described above is preferred. Similarly, polynucleotide fragments encoding these polypeptide fragments are also preferred.

Structural or functional domains (eg, α-helix and α-helix forming regions, β-sheet and β-sheet forming regions, turns and turn-forming regions, coils and coil-forming regions, hydrophilic regions, hydrophobic regions, α amphiphiles Also preferred are fragments of polypeptides and polynucleotides characterized in that they comprise a sex region, a β-amphipathic region, a variable region, a surface-forming region, a substrate-binding region, and a region with a high antigenicity index). Polypeptide fragments of SEQ ID NO: Y that are within the conserved domain are specifically contemplated by the present invention. Moreover, polynucleotide fragments encoding these domains are also contemplated.

Other preferred fragments are biologically active fragments. A biologically active fragment is a fragment that exhibits an activity similar to that of the polypeptide of the present invention, but is not necessarily the same. The biological activity of the fragment may include an improved desired activity, or a reduced undesired activity.

(Epitope and Antibody) In the present invention, the “epitope” refers to a polypeptide fragment having antigenic or immunogenic activity in animals, particularly in humans. A preferred embodiment of the present invention relates to a polypeptide fragment containing an epitope, and a polynucleotide encoding this fragment. The region of the protein molecule to which an antibody can bind is defined as the "antigenic epitope." In contrast, an "immunogenic epitope" is defined as the part of a protein that elicits an antibody response. (For example,
Geysen et al., Proc. Natl. Acad. Sci. USA 81:39.
98-4002 (1983)).

Fragments that function as epitopes can be produced by any conventional means (eg, Houghten. RA, Proc. Natl. Ac.
ad. Sci. USA 82: 5131-5135 (1985), further described in U.S. Pat. No. 4,631,211).

In the present invention, antigenic epitopes preferably comprise a sequence of at least 7, more preferably at least 9, and most preferably between about 15 and about 30 amino acids. Antigenic epitopes are useful for raising antibodies (including monoclonal antibodies) that specifically bind to the epitope (eg, Wilson et al., C.
ell 37: 767-778 (1984); Sutcliffe, J. et al.
G. Et al., Science 219: 660-666 (1983)).

Similarly, immunogenic epitopes can be used to induce antibodies according to methods well known in the art (eg, Sutcliffe et al., Supra; Wilson).
Chou, M. et al., Supra. Et al., Proc. Natl. Acad. Sc
i. USA 82: 910-914; and Little, F .; J. Et al., J. Gen. Virol. 66: 2347-2354 (1985)). Preferred immunogenic epitopes include secreted proteins. The immunogenic epitope can be presented to an animal system (eg, rabbit or mouse) with a carrier protein such as albumin, or no carrier if the immunogenic epitope is sufficiently long (at least about 25 amino acids). Can be presented at.
However, immunogenic epitopes containing only 8-10 amino acids have been shown to be sufficient in denatured polypeptides (eg, in Western blotting) to elicit at least antibodies capable of binding to linear epitopes. .

As used herein, the term “antibody” (Ab) or “monoclonal antibody”
(Mab) is meant to include intact molecule and antibody fragments (eg, Fab and F (ab ′) 2 fragments) that are capable of specifically binding to a protein. Fab and F (ab ') 2 fragments are intact antibodies to F
It may lack the c fragment, be cleared more rapidly from the circulation, and have less non-specific tissue binding than intact antibody. (Wahl et al., J. Nucl.
． Med. 24: 316-325 (1983)). Therefore, these fragments are preferred as are the products of FAB or other immunoglobulin expression libraries. Furthermore, the antibodies of the present invention include chimeric antibodies, single chain antibodies, and humanized antibodies.

Fusion Proteins Any polypeptide of the invention can be used to produce a fusion protein. For example, the polypeptides of the present invention can be used as an antigenic tag when fused to a second protein. Antibodies raised against the polypeptides of the invention can be used to indirectly detect a second protein by binding to the polypeptide. Moreover, since secreted proteins target cell locations based on transport signals, the polypeptides of the invention can be used as targeting molecules once fused to other proteins.

Examples of domains that can be fused to the polypeptides of the invention include not only heterologous signal sequences, but also other heterologous functional regions. The fusion does not necessarily have to be direct, but can occur via a linker sequence.

In addition, fusion proteins can also be engineered to improve the characteristics of the polypeptides of the invention. For example, additional amino acids, especially regions of charged amino acids, can be added to the N-terminus of the polypeptide to improve stability and durability during purification from host cells or subsequent handling and storage. Also, peptide moieties may be added to the polypeptide to facilitate purification. Such regions may be removed prior to final preparation of the polypeptide. Addition of peptide moieties to facilitate handling of polypeptides is a conventional technique well known in the art.

Furthermore, the polypeptides of the invention (including fragments, and especially epitopes) can be combined with part of the constant domain of immunoglobulins (IgG), resulting in chimeric polypeptides. These fusion proteins facilitate purification and exhibit increased half-life in vivo. One reported example describes a chimeric protein consisting of the first two domains of the human CD4 polypeptide and various domains of the constant regions of the heavy or light chains of mammalian immunoglobulins (EP A 394,827; Traunecker et al., Nature 33.
1: 84-86 (1988)). Fusion proteins with disulfide-linked dimer structures (due to IgG) may also be more efficient at binding and neutralizing other molecules than monomeric secretory proteins or protein fragments alone ( Fountoulakis et al., J. Biochem. 270: 395.
8-3964 (1995)).

Similarly, EP-A-O 464 533 (Canadian patent 2045869).
No.) discloses fusion proteins comprising various parts of the constant regions of immunoglobulin molecules together with another human protein or parts thereof. In many cases, the Fc portion of fusion proteins may be beneficial in therapy and diagnosis, thus resulting, for example, in improved pharmacokinetic properties (EP-A 0232 262). Alternatively, it may be desirable to delete the Fc portion after the fusion protein has been expressed, detected and purified. For example, if the fusion protein is used as an antigen for immunization, the Fc portion may interfere with therapy and diagnosis. For example, in drug discovery, human proteins such as hIL-5 have been fused to Fc moieties for the purpose of high throughput screening assays to identify antagonists of hIL-5 (D. Bennett et al. J. Molecular Reco
gnition 8: 52-58 (1995); Johnson et al.
Biol. Chem. 270: 9459-9471 (1995)).
.

In addition, the polypeptides of the present invention can be fused to a marker sequence (eg, a peptide that facilitates purification of the fused polypeptide). In a preferred embodiment, the marker amino acid sequence is inter alia a hexa-histidine peptide (eg p
QE vector (QIAGEN, Inc., 9259 Eton Avenue,
Chatsworth, CA, 91311)),
Many of these marker amino acid sequences are commercially available. For example, Gentz et al., Proc. Natl. Acad. Sci. USA 86: 821-824 (1
989), hexa-histidine provides convenient purification of the fusion protein. Another peptide tag useful for purification, the "HA" tag, corresponds to an epitope derived from the influenza hemagglutinin protein (Wi.
Lson et al., Cell 37: 767 (1984)).

Thus, any of these above fusions can be engineered using the polynucleotides or polypeptides of the invention.

Vectors, Host Cells, and Protein Production The present invention also relates to vectors containing the polynucleotides of the present invention, host cells, and the production of polypeptides by recombinant techniques. For example, the vector can be a phage vector, a plasmid vector, a viral vector, or a retroviral vector. Retroviral vectors can be replication competent or replication defective. In the latter case, viral propagation generally will be complete (complementary).
only occurs in host cells.

The polynucleotide may be ligated into a vector containing a selectable marker for propagation in the host. Generally, the plasmid vector is introduced in a precipitate, such as a calcium phosphate precipitate, or in complex with a charged lipid. If the vector is a virus, the viral vector can be packaged in vitro using a suitable packaging cell line and then transduced into host cells.

The polynucleotide insert may be labeled with a suitable promoter (eg, phage λPL promoter, E. coli lac promoter, trp, to name a few).
Promoter, phoA promoter and tac promoter, SV40 early promoter and SV40 late promoter, and retroviral LTR
Should be operably linked to the promoter). Other suitable promoters are known to those of skill in the art. The expression construct further comprises sites for transcription initiation, termination, and, in the transcribed region, a ribosome binding site for translation. The coding portion of the transcript expressed by the construct is preferably initially a translation initiation codon,
And a termination codon (U that is appropriately located at the end of the polypeptide to be translated).
AA, UGA or UAG).

As shown, the expression vector preferably contains at least one selectable marker. Such markers include dihydrofolate reductase, G418, or neomycin resistance genes for eukaryotic cell culture, as well as E. coli. It contains a tetracycline, kanamycin or ampicillin resistance gene for cultivation in E. coli and other bacteria. Representative examples of suitable hosts are bacterial cells (eg E. c.
oli, Streptomyces and Salmonella typhim
urium cells); fungal cells such as yeast cells; Drosophilia S2
And insect cells such as Spodoptera Sf9 cells; CHO cells, CO
Animal cells such as S cells, 293 cells, and Bowes melanoma cells; and plant cells, but are not limited thereto. Appropriate culture media and conditions for the above-described host cells are known in the art.

Among the preferred vectors for use in bacteria are pQE70, pQE6.
0 and pQE-9 (available from QIAGEN, Inc.); pBlues
script vector, Phasescript vector, pNH8A, pNH1
6a, pNH18A, pNH46A (Stratagene Cloning)
Systems, Inc. Available from); and ptrc99a, pKK2
23-3, pKK233-3, pDR540, pRIT5 (Pharmacia)
Biotech, Inc. Available from). Among the preferred eukaryotic vectors are pWLNEO, pSV2CAT, pOG44, pXT1 and pS.
G (available from Stratagene); and pSVK3, pBPV, p
There are MSG and pSVL (available from Pharmacia). Other suitable vectors will be readily apparent to those of skill in the art.

Introduction of the construct into the host cell is carried out by calcium phosphate transfection, DE
It can be provided by AE-dextran mediated transfection, cationic lipid mediated transfection, electroporation, transduction, infection, or other methods. Such methods are described by Davis et al., Basic Metho.
It is described in many standard laboratory manuals such as ds In Molecular Biology (1986). It is specifically contemplated that the polypeptides of the present invention may in fact be expressed by host cells lacking the recombinant vector.

The polypeptides of the present invention may be ammonium sulfate precipitated or ethanol precipitated, acid extracted, anion or cation exchange chromatography, phosphocellulose chromatography, hydrophobic interaction chromatography, affinity chromatography, hydroxylapatite chromatography and lectins. It can be recovered from recombinant cell culture and purified by well-known methods, including chromatography. Most preferably high performance liquid chromatography (“HPLC”)
Is used for purification.

The polypeptides of the invention, and preferably the secreted forms, may also be recovered from: purified from natural sources, including body fluids, tissues and cells, whether directly isolated or cultured. A product of a chemical synthesis procedure; and
Products recombinantly produced from prokaryotic or eukaryotic hosts, including, for example, bacterial cells, yeast cells, higher plant cells, insect cells, and mammalian cells. Depending on the host used in a recombinant production procedure, the polypeptides of the present invention may be glycosylated or non-glycosylated. Furthermore, the polypeptides of the present invention may also, in some cases, include an initial modified methionine residue as a result of host-mediated processes. Therefore, it is well known in the art that, in general, the N-terminal methionine encoded by the translation initiation codon is removed with high efficiency from any post-translational protein in all eukaryotic cells. N-terminal methionine is also effectively removed in most prokaryotes in most proteins, but for some proteins this prokaryotic removal process depends on the nature of the amino acids to which the N-terminal methionine is covalently attached. And is inefficient.

Uses of Polynucleotides Each of the polynucleotides identified herein can be used as reagents in a number of ways. The following description should be considered exemplary and utilizes known techniques.

The polynucleotides of the present invention are useful for chromosome identification. Chromosome marking reagents based on actual sequence data (repeated polymorphisms) are currently scarcely available, so there remains a need to identify new chromosomal markers. Each polynucleotide of the present invention can be used as a chromosomal marker.

Briefly, the sequences can be mapped to the chromosome by preparing PCR primers (preferably 15-25 bp) from the sequence shown in SEQ ID NO: X. Primers can be selected using computer analysis so that they do not span more than one predicted exon in genomic DNA. These primers are then used to bind P of somatic cell hybrids containing individual human chromosomes.
Used for CR screening. Only those hybrids containing the human gene corresponding to SEQ ID NO: X produce an amplified fragment.

Similarly, somatic cell hybrids include polynucleotides that bind polynucleotides to specific chromosomes.
It provides a rapid method for CR mapping. Three or more clones can be assigned per day using a single thermal cycler. Furthermore, sublocalization of polynucleotides can be achieved with a panel of specific chromosomal fragments. Other gene mapping strategies that can be used are in situ hybridization, labeled flow sorting.
pre-screening on the chromosome, and chromosome-specific cDNA
Includes preselection by hybridization to construct the library.

The exact chromosomal location of the polynucleotide is also determined by the metaphase chromosomal spread (spr
ead) fluorescence in situ hybridization (FISH). This technique uses polynucleotides as short as 500 or 600 bases; however, 2,000-4,000 bp polynucleotides are preferred. For a review of this technology, see Verma et al., “Human Chromoso.
mes: a Manual of Basic Technologies ”,
See Pergamon Press, New York (1988).

For chromosome mapping, polynucleotides may be used individually (to mark a single chromosome or a single site on that chromosome) or in panels (to mark multiple sites and / or multiple chromosomes). Can be done. Preferred polynucleotides correspond to the non-coding regions of cDNA. This is because coding sequences tend to be more conserved within gene families, thus increasing the chance of cross-hybridization during chromosome mapping.

Once the polynucleotide has been mapped to a precise chromosomal location, the physical location of the polynucleotide can be used in linkage analysis. Linkage analysis establishes coinheritance between the chromosomal location and the presentation of a particular disease. (Disease mapping data is described in, for example, V. McKusick, Mend.
elian Inheritance in Man (Johns Hopki
ns University Welch Medical Library) available online). Assuming 1 megabase mapping resolution and 1 gene per 20 kb, a cDNA precisely located in a chromosomal region associated with disease could be one of 50-500 potential causative genes.

Thus, once co-inheritance is established, differences in polynucleotides and corresponding genes between affected and unaffected individuals can be tested. First, visible structural alterations in the chromosome (eg deletions or translocations) are tested in the chromosome spreads or by PCR. In the absence of structural alterations, the presence of point mutations is confirmed. Mutations observed in some or all affected individuals, but not in normal individuals, indicate that the mutations can cause disease.
However, complete sequencing of polypeptides and the corresponding genes from some normal individuals is required to distinguish mutations from polymorphisms. If a new polymorphism is identified, this polymorphic polypeptide can be used for further linkage analysis.

In addition, increased or decreased expression of genes in affected individuals compared to unaffected individuals can be assessed using the polynucleotides of the invention. Any of these modifications (altered expression, chromosomal rearrangements, or mutations) can be used as a diagnostic or prognostic marker.

In addition to the above, the polynucleotides may be triple helix formed or antisense DN.
It can be used to control gene expression by A or RNA. Both methods rely on the binding of polynucleotides to DNA or RNA. For these techniques, the preferred polynucleotides are usually 20-40 bases in length, and the regions of genes involved in transcription (triple helix-Lee et al., Nucl. Acids).
Res. 6: 3073 (1979); Cooney et al., Science 241.
: 456 (1988); and Dervan et al., Science 251: 13.
60 (1991)) or the mRNA itself (antisense-Okan).
o, J. Neurochem. 56: 560 (1991); Oligodeox.
y-nucleotides as Antisense Inhibitor
s of Gene Expression, CRC Press, Boca
Raton, FL (1988)). Triple helix formation optimally blocks RNA transcription from DNA, while antisense RNA hybridization blocks translation of mRNA molecules into polypeptides. Both techniques are effective in model systems, and the information disclosed herein can be used to design antisense or triple helix polynucleotides in an attempt to treat disease.

The polynucleotides of the present invention are also useful in gene therapy. One goal of gene therapy is to insert a normal gene into an organism that has a defective gene in an attempt to correct the genetic defect. The polynucleotides disclosed in the present invention provide a means to target such genetic defects in a highly accurate manner. Another goal is to insert a new gene that was not present in the host genome,
This creates a new trait in the host cell.

The polynucleotides are also useful for identifying an individual from a small biological sample. For example, the United States military is considering the use of restriction fragment length polymorphisms (RFLPs) to identify its personnel. In this technique, an individual's genomic DNA is digested with one or more restriction enzymes and probed for Southern blots to generate unique bands to identify staff. This method does not suffer from the current limitations of the "Dog tag," which can be difficult to positively identify by being lost, exchanged, or stolen. The polynucleotide of the present invention can be used as an additional DNA marker for RFLP.

The polynucleotides of the present invention may also be used as an alternative for RFLP by determining the actual base-by-base DNA sequence of selected portions of the genome of an individual. These sequences can be used to prepare PCR primers to amplify and isolate such selected DNA, which can then be sequenced. Individuals can be identified using this technique because each individual has a unique set of DNA sequences. Once a unique ID database is established for an individual, whether the individual is alive or dead,
Positive identification of individuals can be made from very small tissue samples.

Forensic biology will also benefit using DNA-based identification techniques as disclosed herein. D obtained from very small biological samples such as tissues (eg hair or skin) or body fluids (eg blood, saliva, semen etc.)
The NA sequence can be amplified using PCR. In one prior art, gene sequences amplified from polymorphic loci such as the DQa class II HLA gene have
Used in forensic biology to identify individuals. (Errich, H
． , PCR Technology, Freeman and Co. (
1992)). Once these specific polymorphic loci are amplified, they are digested with one or more restriction enzymes. This results in an identifying set of bands for Southern blots probed with DNA corresponding to the DQa class II HLA gene. Similarly, the polynucleotides of the present invention can be used as polymorphic markers for forensic purposes.

There is also a need for reagents that can identify the source of a particular tissue. Such a need arises in forensic medicine, for example, if tissue of unknown origin is provided. Suitable reagents may include, for example, DNA probes or primers specific to the particular tissue prepared from the sequences of the invention. A panel of such reagents
Tissues may be identified by species and / or organ type. In a similar fashion, these reagents can be used to screen tissue cultures for contaminants.

At a minimum, the polynucleotides of the present invention "subtract" known sequences in the process of discovering new polynucleotides, as molecular weight markers in Southern gels, as diagnostic probes for the presence of specific mRNAs in specific cell types. As a probe for "selecting and making oligomers for attachment to" gene chips "or other supports, to raise anti-DNA antibodies using DNA immunization techniques, and to elicit immune responses. Can be used as

Uses of Polypeptides Each of the polypeptides identified herein can be used in a number of ways. The following description should be considered exemplary and uses known techniques.

The polypeptides of the present invention can be used to assay protein levels in biological samples using antibody-based techniques. For example, protein expression in tissues can be studied using classical immunohistochemistry (Jalka).
nen, M .; Et al., J. Cell. Biol. 101: 976-985 (1985)
); Jalkanen, M .; Et al., J. Cell. Biol. 105: 3087-
3096 (1987)). Other antibody-based methods useful for detecting protein gene expression include immunoassays such as enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA). Suitable antibody assay labels are known in the art and include, for example, enzyme labels such as glucose oxidase, as well as iodine (125I, 121I), carbon (14I).
C), sulfur (35S), tritium (3H), indium (112In), and radioisotopes such as technetium (99mTc), and fluorescent labels such as fluorescein and rhodamine, and biotin.

In addition to assaying secreted protein levels in biological samples, proteins can also be detected in vivo by imaging. Antibody labels or markers for in vivo imaging of proteins include those detectable by X-ray radiography, NMR or ESR. For x-ray radiography, suitable labels include radioisotopes such as barium or cesium that emit detectable radiation but are not overtly harmful to the subject. NMR
And suitable markers for ESR include those with a detectable characteristic spin, such as deuterium, which can be incorporated into antibodies by labeling the nutrients for the relevant hybridoma.

Protein-specific, labeled with a suitable detectable imaging moiety such as a radioisotope (eg, 131I, 112In, 99mTc), radiopaque material, or material detectable by nuclear magnetic resonance. The antibody or antibody fragment is introduced into a mammal (eg, parenterally, subcutaneously, or intraperitoneally). It is understood in the art that the size of the subject and the imaging system used will determine the amount of imaging moiety needed to produce a diagnostic image. In the case of a radioisotope moiety,
For human subjects, the amount of radioactivity injected is usually about 5-20 mTc.
It is in the millimeter range. The labeled antibody or antibody fragment will then preferentially accumulate at the location of cells which contain the particular protein. In vivo tumor imaging is described by S. W. Burchiel et al., “Immunopharmacokine
tics of Radiolabeled Antibodies and
Their Fragments "(Tumor Imaging: The R
13th of adiochemical Detection of Cancer
Chapter, S. W. Burchiel and B.I. A. Rhodes, Masson
Publishing Inc. (1982).

Accordingly, the invention provides a method of diagnosing a disorder, which method comprises (a) assaying the expression of a polypeptide of the invention in cells or body fluids of an individual; (b) the level of expression of this gene. Is compared to a standard gene expression level, whereby an increase or decrease in gene expression level of the assayed polypeptide relative to the standard expression level is indicative of a disorder.

In addition, the polypeptides of the present invention may be used to treat diseases. For example, the patient
Undoing the absence or reduced level of a polypeptide (eg, insulin), supplementing the absence or reduced level of a different polypeptide (eg, hemoglobin S versus hemoglobin B), the polypeptide (eg, cancer) Inhibiting the activity of a gene), activating the activity of a polypeptide (eg, by binding to a receptor), a free ligand (eg, a soluble TNF receptor used in reducing inflammation) and a membrane bound receptor. Diminishing the activity of membrane-bound receptors by competing with, or the desired response (eg,
Polypeptides of the present invention may be administered in addressing the effects of (vascular proliferation).

Similarly, antibodies directed against the polypeptides of the present invention may also be used to treat disease. For example, administration of an antibody directed against a polypeptide of the invention may bind the polypeptide and reduce overproduction of the polypeptide. Similarly,
Administration of the antibody may activate the polypeptide, for example by binding to a membrane bound polypeptide (receptor).

At least the polypeptides of the present invention are SDS-P using methods well known to those of skill in the art.
It can be used as a molecular weight marker in AGE gel or molecular sieve gel filtration columns. Polypeptides can also be used to raise antibodies, which are then used to measure protein expression from recombinant cells as a method of assessing transformation of host cells. In addition, the polypeptides of the invention can be used to test the following biological activities.

Biological Activity The polynucleotides and polypeptides of the invention can be used in assays to test for one or more biological activities. If these polynucleotides and polypeptides show activity in a particular assay, then they are likely to be involved in diseases associated with biological activity. Thus, the polynucleotides and polypeptides can be used to treat related diseases.

Immune Activity The polypeptides or polynucleotides of the invention are useful in treating immune system deficiencies or disorders by activating or inhibiting the proliferation, differentiation, or migration (chemotactic) of immune cells. Can be. Immune cells are mediated by a process called hematopoiesis, the process of producing myeloid cells (platelets, red blood cells, neutrophils, and macrophages) and lymphoid (B and T lymphocytes) cells from pluripotent stem cells. Occurs. The etiology of these immunodeficiencies or disorders can be hereditary, somatic (eg, cancer or some autoimmune disorder), acquired (eg, due to chemotherapy or toxins), or infectious. Furthermore, the polynucleotides or polypeptides of the present invention can be used as markers or detection agents for certain immune system diseases or disorders.

The polynucleotides or polypeptides of the present invention may be useful in treating or detecting a deficiency or disorder of hematopoietic cells. Differentiation and proliferation of hematopoietic cells, including pluripotent stem cells, in an effort to treat disorders associated with the reduction of certain (or many) types of hematopoietic cells using the polypeptides or polynucleotides of the invention. Can be increased. Examples of immunological deficiency syndromes include, but are not limited to: blood protein disorders (eg, agammaglobulinemia,
Hypogammaglobulinemia), ataxia-telangiectasia, unclassified immunodeficiency, Di George syndrome, HIV infection, HTLV-BLV infection, leukocyte adhesion deficiency syndrome, lymphopenia, phagocytic bactericidal dysfunction, severe complex Immunodeficiency (SCID), Viscott-Aldrich disorder, anemia, thrombocytopenia, or hemoglobinuria.

In addition, the polypeptides or polynucleotides of the invention can also be used to modulate hemostatic activity (stop bleeding) or thrombolytic activity (clot formation). For example, by increasing hemostasis or thrombolytic activity, the polynucleotides or polypeptides of the invention may be associated with a blood coagulation disorder (eg, afibrinogenemia, factor deficiency), a blood platelet disorder (eg, thrombocytopenia), or Trauma,
It can be used to treat wounds resulting from surgery or other causes. Alternatively, a polynucleotide or polypeptide of the invention that can reduce hemostatic or thrombolytic activity can be used to inhibit or lyse coagulation. These molecules may be important in the treatment of heart attack (infarction), stroke, or scarring.

Polynucleotides or polypeptides of the invention may also be useful in treating or detecting autoimmune disorders. Many autoimmune disorders are caused by immune cells
It results from improper recognition of oneself as a foreign substance. This inadequate recognition produces an immune response that leads to the destruction of host tissues. Therefore, administration of a polypeptide or polynucleotide of the invention that inhibits the immune response, particularly T cell proliferation, differentiation, or chemotaxis, may be an effective treatment for preventing autoimmune disorders.

Examples of autoimmune disorders that may be treated or detected by the present invention include, but are not limited to, Addison's disease, hemolytic anemia, antiphospholipid syndrome, rheumatoid arthritis, dermatitis, allergies. Encephalomyelitis, glomerulonephritis, Goodpasture syndrome, Graves' disease, multiple sclerosis, myasthenia gravis, neuritis, conjunctivitis, bullous pemphigoid pemphigus, pemphigus, multiple endocrine disorders, purpura, Reiter's disease , Stiffman syndrome, autoimmune thyroiditis, systemic lupus erythematosus, autoimmune pulmonary inflammation, Guian Barre syndrome, insulin-dependent diabetes mellitus, and autoimmune inflammatory eye disease.

Similarly, allergic reactions and conditions such as, for example, asthma (particularly allergic asthma) or other respiratory problems may also be treated with the polypeptides or polynucleotides of the invention. In addition, these molecules can be used to treat anaphylaxis, hypersensitivity to antigenic molecules, or blood group incompatibility.

The polynucleotides or polypeptides of the present invention may also be used to treat and / or prevent organ rejection or graft versus host disease (GVHD). Organ rejection results from host immune cells destroying the transplanted tissue via an immune response. Similarly, an immune response is also involved in GVHD, where the foreign transplanted immune cells destroy host tissue. Immune response, especially T cell proliferation,
Administration of a polypeptide or polynucleotide of the present invention that inhibits differentiation or chemotaxis can be an effective treatment in preventing organ rejection or GVHD.

Similarly, the polypeptides or polynucleotides of the invention can also be used to regulate inflammation. For example, the polypeptide or polynucleotide is
It can inhibit the proliferation and differentiation of cells involved in the inflammatory response. These molecules can be used to treat inflammatory conditions (both chronic and acute conditions) including: inflammation associated with infection (eg, septic shock, sepsis, or systemic inflammatory response syndrome (SIRS). )), Ischemic reperfusion injury, lethal endotoxin, arthritis, complement-mediated hyperacute rejection, nephritis, cytokine or chemokine-induced lung injury, inflammatory bowel disease, Crohn's disease, or cytokines (eg, TNF or IL). -1) A condition resulting from overproduction.

Hyperproliferative Disorders Polypeptides or polynucleotides can be used to treat or detect hyperproliferative disorders, including neoplasms. The polypeptides or polynucleotides of the invention may inhibit the growth of disorders through direct or indirect interactions. Alternatively, the polypeptides or polynucleotides of the invention may grow other cells that may inhibit hyperproliferative disorders.

For example, by increasing the immune response, in particular by increasing the antigenic quality of hyperproliferative disorders, or by T cell proliferation, differentiation, or migration.
Hyperproliferative disorders can be treated. This immune response can be elevated by either enhancing the existing immune response or initiating a new immune response. Alternatively, diminished immune response may also be a method of treating hyperproliferative disorders such as chemotherapeutic agents.

Examples of hyperproliferative disorders that may be treated or detected with the polynucleotides or polypeptides of the invention include, but are not limited to, the neoplasms found below: abdomen, bone, breast, Digestive system, liver, pancreas, peritoneum, endocrine glands (adrenal gland, parathyroid gland, pituitary gland, testis, ovary, thymus, thyroid), eyes, head and neck, nerves (central and peripheral), lymphatic system, pelvis, Skin, soft tissue, spleen, chest, and genitourinary organs.

Similarly, other hyperproliferative disorders can also be treated or detected by the polynucleotides or polypeptides of the invention. Examples of such hyperproliferative disorders include, but are not limited to: hypergammaglobulinemia, lymphoproliferative disorders, paraproteinemia, purpura, sarcoidosis, Sézary syndrome,
Waldenström macroglobulinemia, Gaucher disease, histiocytosis, and any other hyperproliferative disease, as well as neoplasms found in the organ systems listed above.

Infectious Diseases Polypeptides or polynucleotides of the invention can be used to treat or detect infectious agents. For example, by increasing the immune response, especially B
Infectious diseases can be treated by increasing the proliferation and differentiation of cells and / or T cells. The immune response can be elevated either by raising an existing immune response or by initiating a new immune response. Alternatively, the polypeptides or polynucleotides of the invention may also directly inhibit the infectious agent without necessarily eliciting an immune response.

Viruses are an example of infectious agents that can cause diseases or conditions that can be treated or detected by the polynucleotides or polypeptides of the invention. Examples of viruses include, but are not limited to, the following DNA and RNA virus families: Arbovirus, Adenoviridae, Arenaviridae, Arterivirus, Birnaviridae, Bunyaviridae, Calciviridae, Sarcovirus. Family (Circoviridae), Coronaviridae, Flaviviridae, Hepadnaviridae (hepatitis), Herpesviridae (eg, cytomegalovirus, herpes simplex, herpes zoster), Mononegavirus (Mononegavi)
rus) (eg, Paramyxoviridae, Morbillivirus, Rhabdoviridae), Orthomyxoviridae (eg, Influenza), Papovaviridae, Parvoviridae, Picornavirus, Poxviridae (eg, Pox or Vaccinia). ), Reoviridae (eg, rotavirus), Retroviridae (HTLV-I, HTLV-II, lentivirus), and Togaviridae (eg, Rubivirus). Viruses within these families can cause a variety of diseases or conditions including, but not limited to: arthritis, bronchiolitis, encephalitis, ocular infections (eg, conjunctivitis, keratitis), Chronic fatigue syndrome, hepatitis (A, B, C, E, active chronic, delta), meningitis, opportunistic infections (eg AIDS), pneumonia, Burkitt lymphoma, chickenpox, hemorrhagic fever, measles , Mumps, parainfluenza, rabies, colds, polio, leukemia, rubella, sexually transmitted diseases, skin diseases (eg capouge, warts), and viremia. Any of these conditions or diseases can be treated or detected using the polypeptides or polynucleotides of the invention.

Similarly, bacterial or fungal agents that can cause a disease or condition and that can be treated or detected by the polynucleotides or polypeptides of the invention include the following Gram-negative and Gram-positive bacterial families and fungi: Including but not limited to: Actinomycetales (eg, Corynebacte
riom, Mycobacterium, Norcardia), Asperg
illosis, Bacilraceae (eg Anthrax, Clos
tridium), Bacteroidaceae, Blastomycosi
s, Bordetella, Borrelia, Brucellosis, Ca
ndidiasis, Campylobacter, Coccidiodom
ycosis, Cryptococcosis, Dermatocycoses
, Enterobacteriaceae (Klebsiella, Salmo
nella, Serratia, Yersinia), Erysiperoth
Rix, Helicobacterium, Legionellosis, Lepto
spirosis, Listeria, Mycoplasmatales, Ne
isseriaceae (eg, Acinetobacter, Gonorr
Hea, Menigococcal), Pasteurellacea infections (eg, Actinobacillus, Hemophilus, Past
eurella), Pseudomonas, Rickettsiaceae,
Chlamydiaceae, Syphilis, and Staphyloco
ccal. These bacterial or fungal families can cause diseases or conditions including, but not limited to: bacteremia, endocarditis, eye infections (conjunctivitis, tuberculosis, uveitis), gingivitis, opportunism. Infections (eg, infections associated with AIDS)
, Paronychia, prosthesis-related infections, Reiter's disease, respiratory tract infections (eg, pertussis or empyema), sepsis, Lyme disease, cat scratch disease, dysentery, paratyphoid fever, food poisoning, typhoid fever, pneumonia, gonorrhea, meningitis, Chlamydia, syphilis, diphtheria, leprosy, paratuberculosis, tuberculosis, lupus, botulinum poisoning, gangrene, tetanus, impetigo, rheumatic fever, scarlet fever, sexually transmitted diseases, skin diseases (eg cellulitis, dermatomycosis (dermatoc))
), toxemia, urinary tract infection, wound infection. The polypeptides or polynucleotides of the invention may be used to treat or detect any of these conditions or diseases.

In addition, parasitic disease agents that cause diseases or conditions that can be treated or detected by the polynucleotides or polypeptides of the present invention include, but are not limited to, the following families: amoeba, babesia, coccidia,
Cryptosporidium, binuclear amoeba, quarantine, ectoparasites, Giardia flagellates, helminths, Leishmania, Theileria, Toxoplasma, Trypanosoma, and Trichomonas. These parasites can cause a variety of diseases or conditions including, but not limited to: scabies, scrub typhus, ocular infections, intestinal diseases (eg, dysentery, giardia giardiasis), liver diseases, lungs. Diseases, opportunistic infections (eg, AIDS-related), malaria, pregnancy complications, and toxoplasma. The polypeptides or polynucleotides of the invention may be used to treat or detect any of these conditions or diseases.

Preferably treatment with a polypeptide or polynucleotide of the invention is
Administering to the patient an effective amount of the polypeptide or removing cells from the patient,
It may be by either providing the polynucleotides of the invention to the cells and returning the engineered cells to the patient (ex vivo treatment). Moreover, the polypeptides or polynucleotides of the invention can be used as antigens in vaccines to elicit an immune response against infectious diseases.

Regeneration Polynucleotides or polypeptides of the invention can be used to differentiate, proliferate and attract cells to guide tissue regeneration (Science 276: 5).
9-87 (1997)). With tissue regeneration, birth defects, trauma (wounds, burns, incisions, or ulcers), aging, diseases (eg, osteoporosis, osteoarthritis, periodontal disease, liver failure), plastic surgery. Can repair, replace, or protect tissue damaged by surgery, including fibrosis, reperfusion injury, or systemic cytokine damage.

Tissues that can be regenerated using the present invention include organs (eg, pancreas, liver, intestine, kidney, skin, endothelium), muscles (smooth muscle, skeletal muscle, or myocardium), vessels (vascular endothelium). ), Nerves, hematopoiesis, and skeletal (bone, cartilage, tendons, and ligaments) tissues. Preferably, regeneration occurs without or with reduced scarring. Regeneration can also include angiogenesis.

Furthermore, the polynucleotides or polypeptides of the present invention may increase the regeneration of tissues that are difficult to heal. For example, by increasing tendon / ligament regeneration,
Faster recovery time after damage. The polynucleotides or polypeptides of the invention may also be used prophylactically in an attempt to avoid damage. Specific diseases that can be treated include tendinitis, carpal tunnel syndrome, and other tendon or ligament defects. Further examples of tissue regeneration of non-healing wounds include ulcers associated with decubitus ulcers, vascular insufficiency, surgical wounds, and traumatic wounds.

Similarly, neural and brain tissue can also be regenerated by using the polynucleotides or polypeptides of the invention to proliferate and differentiate neural cells. Diseases that can be treated using the present methods include central and peripheral nervous system diseases, neuropathy, or mechanical and traumatic disorders (eg, myelopathy, head trauma, cerebrovascular disease, and stroke). )including. Specifically, diseases associated with peripheral nerve injury, peripheral neuropathy (eg, resulting from chemotherapy or other medical therapies)
, Localized neuropathy, and central nervous system disorders (eg, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and Shy-Drager syndrome) all use the polynucleotides or polypeptides of the invention. Can be treated.

Chemotaxis A polynucleotide or polypeptide of the invention may have chemotactic activity. Chemotactic molecules allow cells (eg, monocytes, fibroblasts, neutrophils, T cells, mast cells, eosinophils, epithelial cells, and / or endothelial cells) to migrate to specific sites in the body (eg, ,
Site of inflammation, infection, or hyperproliferation). The migrated cells can then repel and / or heal the particular trauma or abnormality.

The polynucleotides or polypeptides of the invention may increase the chemotactic activity of certain cells. These chemotactic molecules are then used to treat inflammation, infection, hyperproliferative disorders, or any immune system disorder by increasing the number of cells targeted to specific locations in the body. obtain. For example, chemotactic molecules can be used to treat wounds and other trauma to tissues by attracting immune cells to the injured location. The chemotactic molecules of the invention can also attract fibroblasts, which can be used to treat wounds.

It is also contemplated that the polynucleotides or polypeptides of the invention may inhibit chemotactic activity. These molecules can also be used to treat disorders.
Thus, the polynucleotides or polypeptides of the present invention can be used as an inhibitor of chemotaxis.

(Binding Activity) The polypeptide of the present invention can be used for screening a molecule that binds to the polypeptide, or a molecule to which the polypeptide binds. Binding of a polypeptide to a molecule activates the activity of the bound polypeptide or molecule (agonist),
It can be increased, inhibited (antagonist), or decreased. Examples of such molecules are:
It includes an antibody, oligonucleotide, protein (eg, receptor), or small molecule.

Preferably, the molecule is intimately associated with the natural ligand (eg, fragment of the ligand) of the polypeptide or natural substrate, ligand, structural mimetic, or functional mimic (Coligan et al., Current). Protocol
s in Immunology 1 (2): See Chapter 5 (1991)). Similarly, the molecule may be the natural receptor to which the polypeptide binds, or at least a fragment of the receptor capable of being bound by the polypeptide (eg,
Active site). In any case, the molecule can be rationally designed using known techniques.

Preferably, screening for these molecules involves producing appropriate cells that express the polypeptide, either as a secreted protein or on the cell membrane. Preferred cells are mammalian, yeast, Drosophila,
Or E. E. coli-derived cells are included. The cells expressing the polypeptide (or the cell membrane containing the expressed polypeptide) are then preferably exposed to the molecule for observing inhibition of binding, stimulation, or activity of either the polypeptide or the molecule. Is contacted with a test compound including.

The assay can simply test binding of a candidate compound to the polypeptide, where binding is detected by the label or in an assay for competition with a labeled competitor. In addition, the assay can test whether a candidate compound produces a signal produced by binding to a polypeptide.

Alternatively, the assay can be performed with cell-free preparations, polypeptides / molecules immobilized on a solid support, chemical libraries, or a mixture of natural products. The assay also includes mixing a solution containing the polypeptide with a candidate compound,
The steps of measuring the activity or binding of the polypeptide / molecule and comparing the activity or binding of the polypeptide / molecule to a standard may be simply included.

Preferably, the ELISA assay uses a monoclonal or polyclonal antibody to measure the level or activity of a polypeptide in a sample (eg, biological sample). Antibodies are produced by either direct or indirect binding to a polypeptide, or by competition with a polypeptide for a substrate.
The level or activity of the polypeptide can be measured.

All of these above assays can be used as diagnostic or prognostic markers. Molecules discovered using these assays can be used to treat or treat diseases by activating or inhibiting polypeptides / molecules, or to bring about specific results in a patient, such as blood vessel growth. . In addition, the assay can discover factors that can inhibit or enhance the production of the polypeptide from properly engineered cells or tissues.

Accordingly, the invention includes a method of identifying a compound that binds to a polypeptide of the invention comprising the steps of: (a) incubating a candidate binding compound with a polypeptide of the invention; and ( b) determining whether a bond has occurred. Further, the invention includes a method of identifying an agonist / antagonist comprising the steps of: (a) incubating a candidate compound with a polypeptide of the invention, (b) assaying biological activity, And (b) determining whether the biological activity of the polypeptide has been modified.

Other Activities The polypeptides or polynucleotides of the invention may also increase or decrease embryonic stem cell differentiation or proliferation, in addition to hematopoietic lineages as discussed above.

Polypeptides or polynucleotides of the invention may also have mammalian characteristics (eg, height, weight, hair color, eye color, skin, percentage of adipose tissue, pigmentation, size,
And shape (eg, cosmetic surgery). Similarly, the polypeptides or polynucleotides of the invention can be used to regulate mammalian metabolism that affects catabolism, anabolic activity, processing, utilization, and energy storage.

Polypeptides or polynucleotides of the invention may be used in biorhythms, caricadic rhythms, depression (including depressive disorders), violence tendencies, pain tolerance, fertility (preferably activin or inhibin-like). It can be used to alter a mammal's mental or physical condition by affecting hormonal or endocrine levels, appetite, libido, memory, stress, or other quality of cognition.

The polypeptides or polynucleotides of the present invention may also be food additives that increase or decrease storage capacity, fat content, lipids, proteins, carbohydrates, vitamins, minerals, cofactors, or other nutritional components. Or it can be used as a preservative.

Other Preferred Embodiments Another preferred embodiment of the present invention comprises a nucleotide sequence that is at least 95% identical to a sequence of at least about 50 contiguous nucleotides in the nucleotide sequence of SEQ ID NO: X, Included is an isolated nucleic acid molecule, where X is any integer as defined in Table 1.

The sequence of contiguous nucleotides begins at the nucleotide approximately 5 ′ nucleotide position of the clone sequence, as defined for SEQ ID NO: X in Table 1,
Also preferred is a nucleic acid molecule comprised in the nucleotide sequence of SEQ ID NO: X, approximately in the range of positions ending with the nucleotide at the 3'nucleotide position of the clone sequence.

The sequence of contiguous nucleotides begins at about the 5'nucleotide position of the start codon, as defined for SEQ ID NO: X in Table 1, and at about the 3'nucleotide position of the clone sequence. Also preferred are nucleic acid molecules comprised in the nucleotide sequence of SEQ ID NO: X, in the range of positions ending in nucleotides.

The sequence of contiguous nucleotides begins approximately at the 5'nucleotide of the first amino acid of the signal peptide, as defined for SEQ ID NO: X in Table 1, and approximately 3 of the cloned sequence. Also preferred are nucleic acid molecules comprised in the nucleotide sequence of SEQ ID NO: X, in the range of positions ending with the nucleotide at the nucleotide position.

Also preferred is an isolated nucleic acid molecule comprising a nucleotide sequence that is at least 95% identical to a sequence of at least about 150 contiguous nucleotides in the nucleotide sequence of SEQ ID NO: X.

Further preferred is an isolated nucleic acid molecule comprising a nucleotide sequence that is at least 95% identical to a sequence of at least about 500 contiguous nucleotides in the nucleotide sequence of SEQ ID NO: X.

A more preferred embodiment is as set forth for SEQ ID NO: X in Table 1,
Includes a nucleotide sequence that is at least 95% identical to the nucleotide sequence of SEQ ID NO: X that begins approximately at the 5'nucleotide position of the first amino acid of the signal peptide and ends approximately at the 3'nucleotide position of the clone sequence. It is a nucleic acid molecule.

[0923] A further preferred embodiment is an isolated nucleic acid molecule comprising a nucleotide sequence that is at least 95% identical to the complete nucleotide sequence of SEQ ID NO: X.

Also preferred is an isolated nucleic acid molecule that hybridizes to a nucleic acid molecule under stringent hybridization conditions, wherein the hybridizing nucleic acid molecule above is an A residue under stringent hybridization conditions. Alone or does not hybridize to a nucleic acid molecule having a nucleotide sequence consisting of only T residues.

Also preferred is a composition of matter comprising a DNA molecule comprising a human cDNA clone identified by the cDNA Clone ID in Table 1, said DNA molecule being comprised in the material deposited with the American Type Culture Collection, and The ATCC deposit numbers shown in Table 1 are given for the above cDNA clone IDs.

Also preferred is an isolated nucleic acid molecule comprising a nucleotide sequence that is at least 95% identical to a sequence of at least 50 contiguous nucleotides in the nucleotide sequence of the human cDNA clone identified by the cDNA clone ID in Table 1. ,
This DNA molecule is contained in the deposit assigned the ATCC Deposit Number shown in Table 1.

Also preferred is an isolated nucleic acid molecule, wherein said sequence of at least 50 contiguous nucleotides is contained within the nucleotide sequence of a complete open reading frame sequence encoded by said human cDNA clone.

Also preferred is an isolated nucleic acid molecule comprising a nucleotide sequence that is at least 95% identical to a sequence of at least 150 contiguous nucleotides in the nucleotide sequence encoded by the above human cDNA clone.

A more preferred embodiment is an isolated nucleic acid molecule comprising a nucleotide sequence that is at least 95% identical to a sequence of at least 500 contiguous nucleotides in the nucleotide sequence encoded by the above human cDNA clone.

[0930] A further preferred embodiment is an isolated nucleic acid molecule comprising a nucleotide sequence that is at least 95% identical to the complete nucleotide sequence encoded by the above human cDNA clone.

A further preferred embodiment detects in the biological sample a nucleic acid molecule comprising a nucleotide sequence that is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from the group consisting of: Is a nucleotide sequence of SEQ ID NO: X, where X is any integer as defined in Table 1; and identified by the cDNA clone ID in Table 1 and in Table 1. A nucleotide sequence encoded by a human cDNA clone contained in a deposit having the ATCC accession number indicated for said cDNA clone; said method comprising a sequence selected from the above group and at least one of the above samples Comparing the nucleotide sequence of the nucleic acid molecule, and the sample Determining whether the sequence of the nucleic acid molecule in the sequence is at least 95% identical to the selected sequence.

[0932] Comparing said sequences comprises determining the degree of nucleic acid hybridization between a nucleic acid molecule in said sample and a nucleic acid molecule comprising said sequence selected from said group. The method is also preferred. Likewise preferred is the above method, wherein the step of comparing the sequences is performed by comparing the nucleotide sequence determined from the nucleic acid molecules in the sample with the sequence selected from the group. Nucleic acid molecules can include DNA or RNA molecules.

A more preferred embodiment is a method for identifying a species, tissue, or cell type in a biological sample, the method comprising at least 50 contiguous sequences in a sequence selected from the group consisting of: Detecting a nucleic acid molecule (if any) in the sample that contains a nucleotide sequence that is at least 95% identical to the sequence of the nucleotides identified as: SEQ ID NO: X, wherein X is Table 1 Any integer as defined in Table 1; and A identified by the cDNA clone ID in Table 1 and shown in Table 1 for the cDNA clone above.
Nucleotide sequence encoded by a human cDNA clone contained in a deposit having a TCC deposit number.

The method for identifying the species, tissue, or cell type of a biological sample can include detecting a nucleic acid molecule comprising a nucleotide sequence in a panel of at least two nucleotide sequences, where At least one sequence in the panel is at least 95% identical to a sequence of at least 50 contiguous nucleotides in the sequence selected from the above group.

Also preferred is a method for diagnosing in a subject a pathological condition associated with aberrant structure or expression of a gene encoding a secreted protein identified in Table 1, which method comprises the group consisting of: Detecting a nucleic acid molecule comprising a nucleotide sequence that is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from, in a biological sample obtained from the subject (if any). Including: a nucleotide sequence of SEQ ID NO: X, where X is any integer as defined in Table 1; and a cDNA clone identified by the cDNA clone ID in Table 1 and described above in Table 1. Encoded by the human cDNA clone contained in the deposit having the ATCC accession number shown for Nucleotide sequence to be used.

The method for diagnosing a pathological condition can include detecting a nucleic acid molecule comprising a nucleotide sequence in a panel of at least two nucleotide sequences, wherein at least one sequence in the panel. Is at least 95% identical to a sequence of at least 50 contiguous nucleotides in the sequence selected from the above group.

Also preferred is a composition of matter comprising an isolated nucleic acid molecule, wherein the nucleotide sequence of said nucleic acid molecule comprises a panel of at least two nucleotide sequences, wherein at least one sequence in said panel is , At least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from the group consisting of: the nucleotide sequence of SEQ ID NO: X, where X is any integer as defined in Table 1. And the nucleotide sequence encoded by the human cDNA clone contained in the deposit identified by the cDNA clone ID in Table 1 and having the ATCC deposit number shown for the above cDNA clone in Table 1. Nucleic acid molecules can include DNA or RNA molecules.

Also preferred is an isolated polypeptide comprising an amino acid sequence that is at least 90% identical to a sequence of at least about 10 consecutive amino acids in the amino acid sequence of SEQ ID NO: Y, where Y is in Table 1 It is an arbitrary integer as specified.

The sequence of contiguous amino acids begins at the residue approximately at the first amino acid position of the secretory portion, as shown for SEQ ID NO: Y in Table 1, and approximately at the end of the open reading frame. Within the range of positions ending with a residue, SEQ ID NO: Y
Also preferred is a polypeptide comprised in the amino acid sequence of

Also preferred is an isolated polypeptide comprising an amino acid sequence that is at least 95% identical to a sequence of at least about 30 consecutive amino acids in the amino acid sequence of SEQ ID NO: Y.

Further preferred is an isolated polypeptide comprising an amino acid sequence that is at least 95% identical to a sequence of at least about 100 consecutive amino acids in the amino acid sequence of SEQ ID NO: Y.

Further preferred is an isolated polypeptide comprising an amino acid sequence that is at least 95% identical to the complete amino acid sequence of SEQ ID NO: Y.

The cDNA clones identified by the cDNA clone ID in Table 1 and above in Table 1
Human c contained in the deposit with the ATCC deposit number indicated for the A clone
Further preferred is an isolated polypeptide comprising an amino acid sequence that is at least 90% identical to a sequence of at least about 10 contiguous amino acids in the complete amino acid sequence of a secreted protein encoded by a DNA clone.

The sequence of the above contiguous amino acids is identified by the cDNA clone ID in Table 1 and is encoded by the human cDNA clone contained in the deposit with the ATCC accession number shown for the above cDNA clone in Table 1. Also preferred is a polypeptide comprised in the amino acid sequence of the secretory portion of a secreted protein.

The cDNA clone identified in Table 1 by the cDNA clone ID and in Table 1 above.
Amino acids that are at least 95% identical to a sequence of at least about 30 consecutive amino acids in the amino acid sequence of the secretory portion of the protein encoded by the human cDNA clone contained in the deposit having the ATCC accession number shown for the A clone. Also preferred are isolated polypeptides that include sequences.

The cDNA clone identified in Table 1 by the cDNA clone ID and in Table 1 above.
Amino acids that are at least 95% identical to a sequence of at least about 100 consecutive amino acids in the amino acid sequence of the secretory portion of the protein encoded by the human cDNA clone contained in the deposit having the ATCC accession number shown for the A clone. Also preferred are isolated polypeptides that include sequences.

The cDNA clone identified in Table 1 by the cDNA clone ID and in Table 1 above.
Human c contained in the deposit with the ATCC deposit number indicated for the A clone
Also preferred is an isolated polypeptide comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of the secretory portion of the protein encoded by the DNA clone.

An isolated that specifically binds to a polypeptide comprising an amino acid sequence that is at least 90% identical to a sequence of at least 10 consecutive amino acids in a sequence selected from the group consisting of: Antibodies are more preferred: the amino acid sequence of SEQ ID NO: Y, where Y is any integer defined in Table 1; and identified by the cDNA clone ID in Table 1 and for the above cDNA clones in Table 1. The complete amino acid sequence of the protein encoded by the human cDNA clone contained in the deposit with the indicated ATCC Deposit Number.

A method of detecting in a biological sample a polypeptide comprising an amino acid sequence that is at least 90% identical to a sequence of at least 10 consecutive amino acids in a sequence selected from the group consisting of: Preferred: the amino acid sequence of SEQ ID NO: Y, where Y is any integer defined in Table 1; and the ATCC deposit identified by the cDNA clone ID in Table 1 and shown for the above cDNA clone in Table 1. The complete amino acid sequence of the protein encoded by the human cDNA clone contained in the numbered deposit; the method compares the amino acid sequence of at least one polypeptide molecule in the sample to a sequence selected from the group Of the polypeptide molecule in the sample and Determining whether the sequence is at least 90% identical to the above sequence of at least 10 consecutive amino acids.

This step of comparing the amino acid sequence of at least one polypeptide molecule in the sample with a sequence selected from this group includes the step of comparing the amino acid sequence of the polypeptide in the sample from a sequence selected from the group consisting of: Determining the degree of specific binding to an antibody that specifically binds to a polypeptide comprising an amino acid sequence that is at least 90% identical to a sequence of at least 10 consecutive amino acids. The method is also preferred: the amino acid sequence of SEQ ID NO: Y, where Y is any integer defined in Table 1; and the cDNA clone ID in Table 1.
The complete amino acid sequence of the protein encoded by the human cDNA clone identified in Table 1 and contained in the deposit having the ATCC accession number shown for the above cDNA clone in Table 1.

Also preferred is the above method, wherein said step of comparing sequences is performed by comparing the amino acid sequence determined from the polypeptide molecules in said sample with the sequence selected from said group.

Also preferred is a method of identifying a species, tissue or cell type of a biological sample, wherein the method comprises a polypeptide molecule in said sample (where said polypeptide, if present, consists of: At least 10 in sequences selected from the group
Including an amino acid sequence that is at least 90% identical to a sequence of contiguous amino acids)
Detecting the amino acid sequence of SEQ ID NO: Y, where Y is any integer defined in Table 1; and for the cDNA clone defined in Table 1 by the cDNA clone ID and in Table 1 above. The complete amino acid sequence of the secreted protein, encoded by the human cDNA clone, contained in the deposit with the indicated ATCC Deposit Number.

Also preferred is the above method of identifying a species, tissue or cell type of a biological sample, wherein the method comprises detecting a polypeptide molecule comprising an amino acid sequence in a panel of at least two amino acid sequences. , Wherein at least one sequence in the panel is at least 90% identical to a sequence of at least 10 consecutive amino acids in a sequence selected from the group above.

Also preferred is a method of diagnosing a pathological condition associated with aberrant structure or expression of a gene encoding a secreted protein identified in Table 1 in a subject.
Here, the method comprises the step of detecting a polypeptide molecule comprising an amino acid sequence in a panel of at least two amino acid sequences in a biological sample obtained from this subject, wherein at least one of said panel. One sequence is at least 90% identical to a sequence of at least 10 consecutive amino acids in a sequence selected from the group consisting of: the amino acid sequence of SEQ ID NO: Y, where Y is any of those defined in Table 1. And the cDNA clone ID in Table 1
The complete amino acid sequence of the secretory protein encoded by the human cDNA clone contained in the deposit having the ATCC accession number as defined by Table 1 and shown for the above cDNA clones in Table 1.

[0955] In any of these methods, the step of detecting the polypeptide molecule comprises the steps of:
Using an antibody is included.

At least 95% identical to a nucleotide sequence that encodes a polypeptide that includes an amino acid sequence that is at least 90% identical to a sequence of at least 10 consecutive amino acids in a sequence selected from the group consisting of: Also preferred is an isolated nucleic acid molecule comprising a nucleotide sequence: the amino acid sequence of SEQ ID NO: (wherein
Y is any integer defined in Table 1); and the AT identified by the cDNA clone ID in Table 1 and shown for the above cDNA clones in Table 1.
The complete amino acid sequence of the secretory protein encoded by the human cDNA clone contained in the deposit with the CC accession number.

Also preferred is an isolated nucleic acid molecule, wherein said nucleotide sequence encoding a polypeptide is optimized for expression of said polypeptide in a prokaryotic host.

Also preferred is an isolated nucleic acid molecule, wherein said polypeptide comprises an amino acid sequence selected from the group consisting of: the amino acid sequence of SEQ ID NO: (wherein
Y is any integer defined in Table 1); and the AT defined by the cDNA clone ID in Table 1 and shown for the above cDNA clones in Table 1.
The complete amino acid sequence of the secretory protein encoded by the human cDNA clone contained in the deposit with the CC accession number.

Further preferred is a method of making a recombinant vector comprising the step of inserting any of the above isolated nucleic acid molecules into a vector. The recombinant vector produced by this method is also preferred. Also preferred is a method of making a recombinant host cell, which comprises the step of introducing the vector into a host cell, as well as a recombinant host cell produced by this method.

A method of making an isolated polypeptide, comprising culturing the recombinant host cell under conditions such that the polypeptide is expressed, and recovering the polypeptide. The method is also preferred. This method of producing an isolated polypeptide is also preferred, wherein the recombinant host cell is a eukaryotic cell, and the polypeptide comprises an amino acid sequence selected from the group consisting of It is the secretory part of the protein: the amino acid sequence of SEQ ID NO: Y, starting with the residue at the first amino acid position of the secretory part of SEQ ID NO: Y, where Y is an integer shown in Table 1 and The position of the first amino acid in the secretory portion of Y is shown in Table 1.
Of the secretory portion of the protein encoded by the human cDNA clone contained in the deposit having the ATCC deposit number as defined by the cDNA clone ID in Table 1 and shown for the above cDNA clone in Table 1. Amino acid sequence. Also preferred are isolated polypeptides produced by this method.

Also preferred are methods of treating an individual in need of increased levels of secreted protein activity. Here, the method comprises administering to such an individual a pharmaceutical amount comprising an amount of an isolated polypeptide, polynucleotide, or antibody of the invention effective to increase the level of activity of said protein in said individual. Administering the composition to such an individual.

Having generally described the invention, the invention is provided for purposes of illustration,
And it is more easily understood by reference to the following examples, which are not intended to be limiting.

Examples Example 1: Isolation of Selected cDNA Clones from Deposited Samples Each cDNA clone in the referenced ATCC deposit is contained in a plasmid vector. Table 1 defines the vector used to construct the cDNA library from which each clone was isolated. In many cases, the vector used to construct the library is a plasmid excised phage vector. The table immediately below correlates the relevant plasmids for each phage vector used in constructing the cDNA library. For example, if a particular clone is defined in Table 1 as isolated in the vector "Lambda Zap", the corresponding deposited clone is "pBluescript".

[0964]

[Table 2] Vector Lambda Zap (US Pat. Nos. 5,128,256 and 5,286,636), Uni-Zap XR (US Pat. No. 5,128,25).
6 and 5,286,636), Zap Express (US Pat. Nos. 5,128,256 and 5,286,636), pBluescri.
pt (pBS) (Short, JM et al., Nucleic Acids Re).
s. 16: 7583-7600 (1988); Alting-Mees, M .;
A. And Short, J. et al. M. , Nucleic Acids Res. 1
7: 9494 (1989)) and pBK (Alting-Mees, MA).
． Et al., Strategies 5: 58-61 (1992)) in Strata.
gene Cloning Systems, Inc. , 11011 N.I. To
Rrey Pines Road, La Jolla, CA, 92037. pBS contains the ampicillin resistance gene and pBK contains the neomycin resistance gene. Both are E. E. coli strain XL-1 Blue, which is also available from Stratagene. p
BS arrives in four types, SK +, SK-, KS + and KS. S and K are polylinker regions (“S” is SacI and “K” is KpnI).
Which is the first site at each end of each linker)
Refers to the orientation of the polylinker relative to the T7 and T3 primer sequences flanking.
"+" Or "-" refers to the orientation of the f1 origin of replication "ori" such that single-stranded rescue initiated from f1 ori in one direction produces sense strand DNA and in the other is antisense. .

The vectors pSport1, pCMVSport 2.0 and pCMVSpo
rt3.0 from Life Technologies, Inc. , P .; O. Box
6009, Gaithersburg, MD 20897. All Sport vectors contain the ampicillin resistance gene, and E. coli. coli strain D
H10B, which is also available from Life Technologies, can be transformed. (For example, Gruber, CE et al., Focus)
15:59 (1993)). Vector lafmid BA (Ben
to Soares, Columbia University, NY) contains the ampicillin resistance gene, and E. E. coli strain XL-1 Blue. Vector pCR® 2.1 (this is Invitroge
n, 1600 Faraway Avenue, Carlsbad, CA 92
(Available from E. 008) contains an ampicillin resistance gene and c
oli strain DH10B (available from Life Technologies) (eg, Clark, JM, Nuc. Acids).
Res. 16: 9677-9686 (1988) and Mead, D .; Et al, Bi
o / Technology 9: (1991)). Preferably, the polynucleotide of the invention does not include the phage vector sequences identified for the particular clones in Table 1, as well as the corresponding plasmid vector sequences named above.

The deposited material in the sample given the ATCC accession number for any given cDNA clone, referred to in Table 1, also contains one or more additional plasmids, each of which is Including different cDNA clones)
Can be included. Accordingly, deposits sharing the same ATCC Accession Number include at least a plasmid for each cDNA clone defined in Table 1. Typically, the sample of each ATCC deposit referenced in Table 1 contains a mixture of approximately equal amounts (by weight) of about 50 plasmid DNAs, each containing a different cDNA clone; , Such deposit samples have more or less than 50 c
Plasmids for DNA clones (up to about 500 cDNA clones) can be included.

Two approaches can be used to isolate a clone from the deposited sample of plasmid DNA cited for that particular clone in Table 1. First, the plasmid is isolated directly by screening the clones using the polynucleotide probe corresponding to SEQ ID NO: X.

In particular, a particular polynucleotide having 30-40 nucleotides is synthesized according to the reported sequence using an Applied Biosystems DNA synthesizer. The oligonucleotide is, for example, ³² P-γ-ATP,
Labeled with T4 polynucleotide kinase and purified according to conventional methods. (For example, Maniatis et al., Molecular Cloning:
A Laboratory Manual, Cold Spring Harb
or Press, Cold Spring, NY (1982)). Techniques known to those of skill in the art, such as those provided by vector suppliers or those provided in the relevant publications or patents cited above, are available for plasmid mixtures.
Using a suitable host as described above (eg XL-1 Blue (Strat.
a))). Transformants are plated on 1.5% agar plates (containing an appropriate selection agent such as ampicillin) at a density of about 150 transformants (colony) per plate. These plates were subjected to conventional methods for bacterial colony screening (eg, Sambrook et al., Molecular.
ar Cloning: A Laboratory Manual, Second Edition, (
1989), Cold Spring Harbor Laboratory.
Press, 1.93-1.104) or other techniques known to those of skill in the art to screen using nylon membranes.

Alternatively, at both ends of SEQ ID NO: X (ie, the 5'N of the clone defined in Table 1).
17-2 from within the region of SEQ ID NO: X surrounded by T and 3′NT)
Two primers of 0 nucleotides are synthesized and used to amplify the desired cDNA using the deposited cDNA plasmid as a template. Polymerase chain reaction is performed under conventional conditions, for example 0.5 μg of the above c
Perform in 25 μl of reaction mixture with DNA template. A simple reaction mixture was 1.5-5 mM MgCl ₂ , 0.01% (w / v) gelatin, 2 each.
0 μM dATP, dCTP, dGTP, dTTP, 25 pmol of each primer and 0.25 units of Taq polymerase. 35 cycles of PCR
(Denature at 94 ° C for 1 minute; Anneal at 55 ° C for 1 minute; Extend at 72 ° C for 1 minute
Min) is performed using a Perkin-Elmer Cetus automated thermal cycler. The amplification product is analyzed by agarose gel electrophoresis and the DNA band of the expected molecular weight is excised and purified. PCR product is DN
Confirm the selected sequence by subcloning and sequencing the A product.

Several methods are available for the identification of the 5'non-coding or 3'non-coding portions of genes that may not be present in the deposited clones. These methods include filter probe searching, clone enrichment using specific probes,
And include, but are not limited to, protocols similar or identical to the 5'and 3 '"RACE" protocols well known in the art. For example, 5'RAC
A method similar to E is available to generate deletions at the 5'end of the desired full length transcript (Frommont-Racine et al., Nucleic Acids.
Res. 21 (7): 1683-1684 (1993)).

Briefly, specific RNA oligonucleotides are ligated to the 5'end of a population of RNAs that probably contains full-length gene RNA transcripts. PCR of the 5'portion of the desired full-length gene is performed using a primer set containing a primer specific to the linked RNA oligonucleotide and a primer specific to the known sequence of the gene of interest.
Amplify. The amplified product can then be sequenced and used to generate the full length gene.

This above method starts with total RNA isolated from the desired source, but may also use poly A + RNA. The RNA preparation is then treated with phosphatase, if necessary, to degrade or damage the RN, which may interfere with subsequent RNA ligase steps.
The 5'phosphate group of A can be eliminated. The phosphatase should then be inactivated, and the RNA was treated with tobacco acid pyrophosphatase to remove the cap structure present at the 5'end of the messenger RNA. This reaction is
A 5'phosphate group is then left at the 5'end of the capped RNA that can then be ligated to the RNA oligonucleotide using T4 RNA ligase.

This modified RNA preparation is used as a template for first-strand cDNA synthesis using gene-specific oligonucleotides. Use the first strand synthesis reaction as a template for PCR amplification of the desired 5'end using primers specific for the ligated RNA oligonucleotide and primers known for the known sequence of the gene of interest. . The resulting product is then sequenced and analyzed to confirm that the 5'end sequence belongs to the desired gene.

Example 2 Isolation of Genomic Clones Corresponding to Polynucleotides Human Genome P1 Library (Genomic Systems, Inc.)
Are screened by PCR using primers selected for the cDNA sequence corresponding to SEQ ID NO: X according to the method described in Example 1 (Sa
See also mbrook).

[0975]     (Example 3: Tissue distribution of polypeptide)   The tissue distribution of mRNA expression of the polynucleotides of the invention can be determined, inter alia, by Samb
Use the protocol for Northern blot analysis described by look et al.
Decide. For example, the cDNA produced by the method described in Example 1.
Probe the rediprime^TM  DNA labeling system
(Amersham Life Science) and follow the manufacturer's instructions.
That's P³²Label with. After labeling, the probe was attached to CHROMA SPIN-100. ^TM Using a column (Clontech Laboratories, Inc.)
And purify according to manufacturer's protocol number PT1200-1. Then refined
Various human tissues are tested for mRNA expression using labeled probes
.

Multiple tissue Northern (MTN) blots (Clontech) containing various human tissues (H) or human immune system tissues (IM) were analyzed using ExpressHyb ^™ Hybridization Solution (Clontech), manufacturer's protocol number P.
Test with labeled probe according to T1190-1. After hybridization and washing, blots are mounted and exposed to film overnight at -70 ° C, and film is developed according to standard procedures.

Example 4 Polynucleotide Chromosome Mapping A set of oligonucleotide primers is designed according to the sequence at the 5 ′ end of SEQ ID NO: X. This primer preferably spans about 100 nucleotides.
This primer set is then used for polymerase chain reaction under the following set of conditions: 95 ° C for 30 seconds; 56 ° C for 1 minute; 70 ° C for 1 minute. This cycle is repeated 32 times and then once at 70 ° C. for 5 minutes. Somatic cell hybrid panel containing individual chromosomes or chromosome fragments (Bios, Inc)
), Human, mouse, and hamster DNA are used as templates.
Reactions are analyzed on either an 8% polyacrylamide gel or a 3.5% agarose gel. Chromosome mapping can be performed in about 10 somatic cell hybrids.
Determined by the presence of the 0 bp PCR fragment.

Example 5 Bacterial Expression of Polypeptides Polynucleotides encoding the polypeptides of the present invention are PCR oligos corresponding to the 5 ′ and 3 ′ ends of the DNA sequences, as outlined in Example 1. Amplification is performed using nucleotide primers to synthesize the insert fragment. The primers used to amplify the cDNA insert should contain restriction sites such as BamHI and XbaI, preferably at the 5'end of the primer for cloning the amplification product into an expression vector. For example, BamHI and XbaI are bacterial expression vectors pQE-9 (Qiagen, Inc., Chatsworth).
h, CA). This plasmid vector contains antibiotic resistance (Amp ^r ), bacterial origin of replication (ori), IPTG-regulatable promoter / operator (P / O), ribosome binding site (RBS), 6-histidine tag (6-His). ), And a restriction enzyme cloning site.

The pQE-9 vector is digested with BamHI and XbaI and the amplified fragment is ligated into the pQE-9 vector maintaining the reading frame initiated in bacterial RBS. The ligation mixture was then ligated with the plasmid pRE expressing the lacI repressor and conferring kanamycin resistance (Kan ^r ).
E. coli containing multiple copies of P4. E. coli strain M15 / rep4 (Qiagen,
Inc. ). Transformants are identified by their ability to grow on LB plates and ampicillin / kanamycin resistant colonies are selected. Plasmid DNA is isolated and confirmed by restriction analysis.

Clones containing the desired construct were cloned into Amp (100 μg / ml) and Kan (100 μg / ml).
Liquid culture in LB medium supplemented with both (25 μg / ml) overnight (O / N)
Proliferate. The O / N culture is used to inoculate a large culture at a ratio of 1: 100 to 1: 250. Cells absorbance 600 between 0.4 to 0.6 (O.D.. ⁶⁰⁰
). Then IPTG (isopropyl-BD-thiogalactopyranoside) is added to a final concentration of 1 mM. IPTG induces P / O activation by inactivating the lacI repressor, leading to increased gene expression.

Cells are grown for an additional 3-4 hours. The cells are then centrifuged (6000 x
g for 20 minutes). The cell pellet is chaotropic agent 6
Solubilize by stirring in M guanidine HCl for 3-4 hours at 4 ° C. Cell debris is removed by centrifugation and the polypeptide-containing supernatant is loaded onto a nickel-nitrilo-triacetate (“Ni-NTA”) affinity resin column (available from QIAGEN, Inc. supra). A protein with a 6xHis tag binds Ni-NTA resin with high affinity and has a simple 1
It may be purified by a process procedure (specifically, QIAexpressionlist (1
995) QIAGEN, Inc. , See above).

Briefly, the supernatant was loaded onto a column of 6M Guanidine-HCl, pH 8, the column was first washed with 10 volumes of 6M Guanidine-HCl, pH 8,
It is then washed with 10 volumes of 6M guanidine-HCl, pH 6, and finally the polypeptide is eluted with 6M guanidine-HCl, pH 5.

The purified protein was then loaded with phosphate buffered saline (PBS) or 5
Regenerate by dialysis against 0 mM sodium acetate, pH 6 buffer and 200 mM NaCl. Alternatively, the protein can be successfully refolded while immobilized on the Ni-NTA column. Recommended conditions are as follows: Regeneration using a linear gradient of 6M to 1M urea in 500 mM NaCl, 20% glycerol, 20 mM Tris / HCl pH 7.4 with protease inhibitors. Regeneration should take a minimum of 1.5 hours. After regeneration, the protein is eluted by adding 250 mM imidazole. The imidazole is removed by a final dialysis step against PBS or a buffer of 50 mM sodium acetate pH 6 and 200 mM NaCl. The purified protein is stored at 4 ° C or frozen at -80 ° C.

In addition to the expression vectors described above, the invention further comprises an expression vector called pHE4a, which contains a phage operator and promoter elements operably linked to the polynucleotide of the invention (ATCC Accession No. 209645).
Deposited on February 25, 1998. ). This vector contains: 1) the neomycin phosphotransferase gene as a selectable marker, 2) E. coli
Origin of replication, 3) T5 phage promoter sequence, 4) two lac operator sequences, 5) Shine-Dalgarno sequence, and 6) lactose operon repressor gene (laqIq). The origin of replication (oriC) is pUC19 (LTI,
Gaithersburg, MD). Promoter and operator sequences are made synthetically.

The vector was restricted with NdeI and XbaI, BamHI, XhoI, or Asp718, the restriction products were run on a gel, and the larger fragment (the stuffer fragment should be approximately 310 base pairs). DNA can be inserted into pHEa by isolating. DNA
The insert was labeled with NdeI (5 ′ primer) and XbaI, BamHI, XhoI.
, Or using PCR primers with restriction sites for Asp718 (3 ′ primer) and generated according to the PCR protocol described in Example 1. P
The CR insert is gel purified and restricted with compatible enzymes. The insert and vector are ligated according to standard protocols.

The engineered vector can be readily replaced in the above protocol to express the protein in bacterial systems.

Example 6 Purification of Inclusion Body-Derived Polypeptides Another method described below is the procedure for E. coli when the polypeptide is present in the form of inclusion bodies. co
It can be used to purify the polypeptide expressed in li. Unless otherwise specified, all the following steps are performed at 4-10 ° C.

E. After completion of the production phase of the E. coli fermentation, the cell culture is cooled to 4-10 ° C. and the cells are harvested by continuous centrifugation at 15,000 rpm (Heraeus Sepatech). Based on the expected yield of protein per unit weight of cell paste and the amount of purified protein required, an appropriate amount (by weight) of cell paste was added to 100 mM Tris, 50 mM EDTA, pH 7.
． 4. Suspend in buffer solution containing 4. The cells are dispersed in a homogenous suspension using a high shear mixer.

The cells were then placed in a microfluidizer (
Microfluidics, Corp. Or APV Gaulin,
Inc. ) Is dissolved twice by passing the solution at 4000-6000 psi. The homogenate is then treated with NaC to a final concentration of 0.5M NaCl.
1 solution, followed by centrifugation at 7000 × g for 15 minutes. The obtained pellet was treated with 0.5 M NaCl, 100 mM Tris, 50 mM EDTA, p.
Wash again using H 7.4.

The resulting washed inclusion bodies are treated with 1.5 M guanidine hydrochloride (GuHCl) to
Solubilize for 4 hours. After centrifugation at 7000 xg for 15 minutes, the pellet is discarded, and the polypeptide-containing supernatant is incubated at 4 ° C overnight to allow additional Gu.
Allows HCl extraction.

Following high speed centrifugation (30,000 × g) to remove insoluble particles, Gu
The HCl solubilized protein is refolded by rapidly mixing the GuHCl extract with 20 volumes of buffer containing 50 mM sodium, pH 4.5, 150 mM NaCl, 2 mM EDTA with vigorous stirring. The refolded diluted protein solution was left unmixed at 4 ° C for 12 hours before further purification steps.
Keep in.

Pre-prepared 4 to clarify the refolded polypeptide solution
Equilibrated with 0 mM sodium acetate, pH 6.0, with appropriate surface area.
Contact filtration unit with 16 μm membrane filter (eg Filtr
on). The filtered sample is treated with a cation exchange resin (eg, Poro
s HS-50, Perseptive Biosystems). The column was washed with 40 mM sodium acetate, pH 6.0, and 250 mM, 500 mM, 1000 mM, and 1500 mM N in the same buffer.
Elute with aCl in a stepwise fashion. The absorbance of the eluate at 280 nm is continuously monitored. Fractions are collected and further analyzed by SDS-PAGE.

Fractions containing the polypeptide are then pooled and mixed with 4 volumes of water. The diluted sample was then added to a pre-prepared strong anion (Poros HQ
-50, Perseptive Biosystems) and weak anions (
Poros CM-20, Perseptive Biosystems) load on a set of in-line columns of exchange resin. The column is equilibrated with 40 mM sodium acetate, pH 6.0. Both columns were loaded with 40 mM sodium acetate, p
Wash with H 6.0, 200 mM NaCl. Next, the CM-20 column is replaced with 10
Linear gradient of column volume (0.2 M NaCl, 50 mM sodium acetate, p
H 6.0 to 1.0 M NaCl, 50 mM sodium acetate, pH 6.5
Elution). Fractions are collected under constant A ₂₈₀ monitoring of the eluate. Fractions containing the polypeptide (eg, found by 16% SDS-PAGE) are then pooled.

The resulting polypeptide should exhibit greater than 95% purity after the above refolding and purification steps. When 5 μg of purified protein is loaded, no major contaminating band should be observed from Coomassie blue stained 16% SDS-PAGE gels. The purified protein is also endotoxin / LPS
It can be tested for contamination and typically the LPS content is less than 0.1 ng / ml according to the LAL assay.

Example 7 Cloning and Expression of Polypeptides in Baculovirus Expression System In this example, the plasmid shuttle vector pA2 is used to insert a polynucleotide into a baculovirus to express the polypeptide. This expression vector contains the strong polyhedrin promoter of the Autographa californica nuclear polyhedrosis virus (AcMNPV), followed by BamHI, Xb.
Contains convenient restriction sites such as aI and Asp718. Simian virus 4
The 0 (“SV40”) polyadenylation site is used for efficient polyadenylation. For easy selection of recombinant virus, the plasmid was engineered into E. coli under the control of the weak Drosophila promoter in the same orientation. It contains the β-galactosidase gene from E. coli, followed by the polyadenylation signal of the polyhedrin gene. The inserted gene is flanked on both sides by viral sequences for cell-mediated homologous recombination with wild-type viral DNA, which produces a viable virus expressing the cloned polynucleotide.

Many other baculovirus vectors (eg pAc373, pVL941)
, And pAcIM1) allow the construct to transcribe, translate, secrete, etc. (signal peptide and in-frame AU if required), as will be readily appreciated by those of skill in the art.
G) can be used in place of the above vectors, as long as they provide appropriately positioned signals for G). Such a vector is, for example, Lucco.
W et al., Virology 170: 31-39 (1989).

In particular, the cDNA sequence contained in the deposited clone, including the AUG start codon and naturally associated leader sequence shown in Table 1, was set out in Example 1.
Amplify using the PCR protocol described in. The pA2 vector does not require a second signal peptide if a naturally occurring signal sequence is used to produce the secreted protein. Alternatively, the vector may be obtained from Summers et al.
Manual of Methods for Baculovirus Ve
ctors and Insect Cell Culture Proced
ures ”, Texas Agricultural Experimenta
l Station Bulletin No. 1555 (1987)) and can be modified to include a baculovirus leader sequence (pA2 GP).

The amplified fragment was transferred to a commercial kit (“Geneclean” BIO
101 Inc. , La Jolla, Ca), and is isolated from a 1% agarose gel. The fragment is then digested with the appropriate restriction enzymes and again purified on a 1% agarose gel.

The plasmids can be digested with the corresponding restriction enzymes and, if desired, dephosphorylated with calf intestinal phosphatase using conventional procedures known in the art.
The DNA is then added to a commercially available kit (“Geneclean” BIO 101 In).
c. , La Jolla, Ca), and is isolated from a 1% agarose gel.

The fragment and the dephosphorylated plasmid are ligated together using T4 DNA ligase. E. coli HB101 or XL-1 Blue (S
tratagene Cloning Systems, La Jolla,
Ca) other suitable E. The E. coli host is transformed with the ligation mixture and spread on culture plates. Bacteria containing the plasmid are identified by digesting DNA from individual colonies and analyzing the digestion products by gel electrophoresis. The sequence of the cloned fragment is confirmed by DNA sequencing.

5 μg of plasmid containing this polynucleotide was prepared according to the method of Felgner et al., P.
roc. Natl. Acad. Sci. USA 84: 7413-74.
17 (1987) using the lipofection method.
0 μg of commercially available linearized baculovirus DNA (“BaculoGold ^™ b
aculovirus DNA ", Pharmingen, San Die
go, CA). 1 μg of BaculoGo
ld ^™ viral DNA and 5 μg of plasmid were added to 50 μl of serum-free Grace's medium (Life Technologies Inc., Gaithersb.
urg, MD) in a sterile well of a microtiter plate. Then add 10 μl Lipofectin and 90 μl Grace's medium,
Mix and incubate for 15 minutes at room temperature. The transfection mixture is then added dropwise to Sf9 insect cells (ATCC CRL 1711) seeded in a 35 mm tissue culture plate with 1 ml Grace's medium without serum. The plate is then incubated at 27 ° C for 5 hours. The transfection solution is then removed from the plate and 1 ml Grace's insect medium supplemented with 10% fetal bovine serum is added. The culture is then continued for 4 days at 27 ° C.

[1002] Supernatants are collected after 4 days and plaque assay performed as described by Summers and Smith, supra. "Blue Gal" (Life Tec
hnologies Inc. , Gaithersburg) containing an agarose gel containing gal expressing clones (producing plaques colored blue)
Used to allow easy identification and isolation of (A detailed description of this type of "plaque assay" can also be found in Life Technologies Inc.
, Gaithersburg, pages 9-10, which can be found in the user guide for insect cell culture and baculovirology). After appropriate incubation, blue colored plaques are picked up with a micropipettor (eg Eppendorf) tip. The agar containing the recombinant virus is then resuspended in a microcentrifuge tube containing 200 μl Grace's medium,
The suspension containing the recombinant baculovirus is then used to infect Sf9 cells seeded in 35 mm dishes. After 4 days, the supernatants of these culture dishes are collected and then stored at 4 ° C.

To confirm expression of the polypeptide, Sf9 cells are grown in Grace's medium supplemented with 10% heat-inactivated FBS. Infect cells with a multiplicity of infection (“MOI”) of about 2.
) And a recombinant baculovirus containing the polynucleotide. If radiolabeled protein is desired, the medium is removed after 6 hours and SF900 II medium without methionine and cysteine (Life Techno).
logs Inc. , Rockville, MD). After 42 hours, 5 μCi of ³⁵ S-methionine and 5 μCi ³⁵ S-cysteine (available from Amersham) are added. Cells are incubated for a further 16 hours and then harvested by centrifugation. Proteins in the supernatant and intracellular proteins are analyzed by SDS-PAGE followed by (when radiolabeled) autoradiography.

[1004] The amino-terminal amino acid sequence of the purified protein can be used to determine the amino-terminal sequence of the produced protein.

Example 8: Expression of Polypeptides in Mammalian Cells The polypeptides of the present invention can be expressed in mammalian cells. A typical mammalian expression vector contains promoter elements that mediate the initiation of transcription of mRNA, protein coding sequences, and signals necessary for termination of transcription and polyadenylation of the transcript. Additional elements include enhancers, Kozak sequences, and intervening sequences flanking the donor and acceptor sites of RNA splicing. Very efficient transcription is achieved by SV40-derived early and late promoters,
Long terminal repeats (L) from retroviruses (eg RSV, HTLVI, HIVI)
TR), and the cytomegalovirus (CMV) early promoter. However, intracellular elements such as the human actin promoter can also be used.

[1006] Expression vectors suitable for use in practicing the present invention include, for example, pSVL and pMSG (Pharmacia, Uppsala, Sweden), pRS.
Vcat (ATCC 37152), pSV2dhfr (ATCC 37146)
), PBC12MI (ATCC 67109), pCMVSport2.0, as well as vectors such as pCMVSport3.0. Mammalian host cells that can be used are human Hela cells, 293 cells, H9 cells and Jurkat cells, mouse NIH3T3 cells and C127 cells, Cos 1 cells, Cos 7 cells.
Cells and CV1 cells, quail QC1-3 cells, mouse L cells, and Chinese hamster ovary (CHO) cells.

[1007] Alternatively, the polypeptide comprises a polynucleotide integrated into a chromosome,
It can be expressed in stable cell lines. Co-transfection with selectable markers such as dhfr, gpt, neomycin, hygromycin allows the identification and isolation of transfected cells.

The transfected gene can also be amplified to express large amounts of the encoded protein. The DHFR (dihydrofolate reductase) marker is useful for developing cell lines that carry hundreds or even thousands of copies of the gene of interest.
(For example, Alt, FW et al., J. Biol. Chem. 253: 1.
357-1370 (1978); Hamlin, J .; L. And Ma, C
． , Biochem. et Biophys. Acta, 1097: 107
-143 (1990): Page, M.S. J. And Sydenham, M
． A. , Biotechnology 9: 64-68 (1991)). Another useful selectable marker is the enzyme glutamine synthase (GS) (Murphy et al., Biochem J. 227: 277-279 (199).
1); Bebbington et al., Bio / Technology 10: 169.
-175 (1992)). These markers are used to grow mammalian cells in selective medium and select the cells with the highest resistance. These cell lines contain the amplified gene integrated into the chromosome. Chinese hamster ovary (CHO) and NSO cells are often used for protein production.

[1009] Expression vectors pC4 (ATCC Accession No. 209646) and pC6 (AT), which are derivatives of plasmid pSV2-dhfr (ATCC Accession No. 37146).
CC Accession No. 209647) is for Rous sarcoma virus (Cullen et al., Mol.
and a Cellular Biology, 438-447 (March 1985)) strong promoter (LTR), and CMV enhancer (Boshart et al., Cell 41: 521-530 (1985)).
Including a fragment of For example, multiple cloning sites with BamHI, XbaI, and Asp718 restriction enzyme cleavage sites facilitate cloning of the gene of interest. The vector also contains a 3'intron, a polyadenylation and termination signal for the rat preproinsulin gene, and the mouse DHFR gene under the control of the SV40 early promoter.

[1010] Specifically, for example, plasmid pC6 is digested with appropriate restriction enzymes,
Calf intestinal phosphatase (phosph) is then followed according to procedures known in the art.
ate) to dephosphorylate. The vector is then isolated from a 1% agarose gel.

Polynucleotides of the invention are amplified according to the protocol outlined in Example 1. If the naturally occurring signal sequence is used to produce the secreted protein, the vector does not require a second signal peptide. Alternatively, if a naturally occurring signal sequence is not used, the vector can be modified to include a heterologous signal sequence (see, eg, WO96 / 34891).

[1012] The amplified fragment was transferred to a commercially available kit ("Geneclean", BIO 10
1 Inc. , La Jolla, Ca. ) Is used to isolate from a 1% agarose gel. The fragment is then digested with the appropriate restriction enzymes and again purified on a 1% agarose gel.

[1013] The amplified fragment is then digested with the same restriction enzymes and purified on a 1% agarose gel. The isolated fragment and the dephosphorylated vector are then ligated with T4 DNA ligase. Then E. E. coli HB101 or XL-1 Blue cells are transformed and bacteria containing the fragment inserted into plasmid pC6 are identified using, for example, restriction enzyme analysis.

[1014] Chinese hamster ovary cells lacking the active DHFR gene are used for transfection. 5 μg of expression plasmid pC6 is co-transfected with 0.5 μg of plasmid pSVneo using lipofectin (Felgner et al., Supra). Plasmid pSV2-neo contains the neo gene from Tn5 which encodes an enzyme that confers resistance to a group of antibiotics including G418, which is a dominant selectable marker. Cells with 1 mg / ml G4
Seed in α minus MEM supplemented with 18. After 2 days, cells were trypsinized and treated with 10, 25, or 50 ng / ml methotrexate and 1 mg / ml.
Seed in hybridoma cloning plates (Greiner, Germany) in α-MEM supplemented with ml G418. After about 10-14 days, single clones were trypsinized and then treated with different concentrations of methotrexate (
50 nM, 100 nM, 200 nM, 400 nM, 800 nM), 6
Seed wells in Petri dishes or 10 ml flasks. Clones growing at the highest concentration of methotrexate were then selected for higher concentrations (1 μM, 2 μM, 5 μM).
M, 10 μM, 20 μM) to a new 6-well plate containing methotrexate. The same procedure is repeated until clones are obtained that grow at a concentration of 100-200 μM. Expression of the desired gene product is analyzed, for example, by SDS-PAGE and Western blot, or by reverse phase HPLC analysis.

Example 9: Protein Fusions The polypeptides of the present invention are preferably fused to other proteins. These fusion proteins can be used for various applications. For example, fusion of a polypeptide of the invention to a His tag, HA tag, protein A, IgG domain, and maltose binding protein facilitates purification (see Example 5; EP A 394,827). Traunecker et al., Nature 331;
: 84-86 (1988)). Similarly, IgG-1, IgG
-3, and fusion to albumin, increases half-life in vivo. Nuclear localization signals fused to the polypeptides of the invention can target proteins to specific subcellular locations. On the other hand, covalent heterodimers or homodimers may increase or decrease the activity of the fusion protein. Fusion proteins can also create chimeric molecules that have more than one function. Finally, fusion proteins may increase the solubility and / or stability of fusion proteins as compared to non-fusion proteins. All forms of the above fusion proteins can be made by modifying the protocol below, which outlines the fusion of polypeptides to IgG molecules, or the protocol described in Example 5.

[1016] Briefly, the human Fc portion of an IgG molecule is the 5'and 3'of the sequence set forth below.
It can be PCR amplified using primers spanning the ends. These primers should also have convenient restriction enzyme sites which facilitate cloning into an expression vector, preferably a mammalian expression vector.

[1017] For example, if pC4 (Accession No. 209646) is used, the human Fc portion may be linked to the BamHI cloning site. Note that the 3'BamHI site should be destroyed. The vector containing the human Fc portion was then restricted again by BamHI, the vector was linearized, and the polynucleotide of the invention isolated by the PCR protocol described in Example 1 was ligated into this BamHI site. To be done. Note that the polynucleotide is cloned without the stop codon, otherwise no fusion protein is produced.

[1018] pC4 does not require a second signal peptide when the naturally occurring signal sequence is used to produce the secreted protein. Alternatively, if a naturally occurring signal sequence is not used, the vector can be modified to include a heterologous signal sequence (see, eg, WO 96/34891).

[1019]

[Chemical 20] Example 10: Production of Antibodies from Polypeptides The antibodies of the present invention can be prepared by various methods. (Current Pr
See otocols, Chapter 2. 3.) For example, cells expressing the polypeptides of the invention are administered to animals to induce the production of serum containing polyclonal antibodies. In a preferred method, a preparation of secreted protein is prepared and purified to be substantially free of natural contaminants. Such preparations are then introduced into animals to produce greater specific activity polyclonal antisera.

[1020] In the most preferred method, the antibody of the present invention is a monoclonal antibody (or
Its protein-binding fragment). Such a monoclonal antibody is
It can be prepared using hybridoma technology (Koehler et al., Nature 256: 495 (1975); Koehler et al., Eur. J. Immu.
nol. 6: 511 (1976); Koehler et al., Eur. J. Imm
unol. 6: 292 (1976); Hammerling et al .: Monoc.
local Antibodies and T-Cell Hybridom
as, Elsevier, N .; Y. , Pp. 563-681 (1981)). Generally, such procedures involve immunizing an animal, preferably a mouse, with a polypeptide, or more preferably, secreting polypeptide expressing cells. Such cells may be cultured in any suitable tissue culture medium; however, 1
Supplemented with 0% fetal bovine serum (inactivated at about 56 ° C.) and about 10 g / l non-essential amino acids, about 1,000 U / ml penicillin, and about 100 μg / ml.
It is preferred to culture the cells in Earle's modified Eagle medium supplemented with Streptomycin.

[1004] The splenocytes of such mice are extracted and fused with an appropriate myeloma cell line. Any suitable myeloma cell line may be used in accordance with the present invention; however, it is preferred to use the parental myeloma cell line (SP20) available from the ATCC. After fusion, the resulting hybridoma cells were selectively maintained in HAT medium and then Wands et al. (Gastroenterology 80:22).
Cloning by limiting dilution as described in 5-232 (1981)). The hybridoma cells obtained by such selection are then assayed to identify clones secreting antibodies capable of binding the polypeptide.

[1025] Alternatively, additional antibodies capable of binding the polypeptide may be generated in a two step procedure using anti-idiotype antibodies. Such a method takes advantage of the fact that the antibody itself is the antigen and therefore it is possible to obtain an antibody that binds to the second antibody. According to this method, protein-specific antibodies are used to immunize animals, preferably mice. The splenocytes of such animals are then used to produce hybridoma cells. Hybridoma cells are then screened to identify clones producing antibodies whose ability to bind to protein-specific antibodies can be blocked by the polypeptide. Such antibodies include anti-idiotypic antibodies to protein-specific antibodies and can be used to immunize animals to induce the formation of additional protein-specific antibodies.

It is understood that Fab and F (ab ′) 2 and other fragments of the antibodies of the invention can be used according to the methods disclosed herein. Such fragments are typically papain (to produce Fab fragments).
Alternatively, it is produced by proteolytic cleavage using an enzyme such as pepsin (to produce F (ab ') 2 fragments). Alternatively, secreted protein binding fragments may be produced by the application of recombinant DNA technology or by synthetic chemistry.

For the in vivo use of antibodies in humans, it may be preferable to use "humanized" chimeric monoclonal antibodies. Such antibodies can be produced by using genetic constructs derived from hybridoma cells which produce the monoclonal antibodies described above. Methods for producing chimeric antibodies are known in the art. (For a review, see Morrison, Science 229: 12
02 (1985); Oi et al., BioTechniques 4: 214 (
1986); Cabilly et al., U.S. Pat. No. 4,816,567; Tani.
guchi et al., EP 171496; Morrison et al., EP 173494.
Neuberger et al., WO 8601533; Robinson et al., WO
8702671; Boulianne et al., Nature 312: 643 (1
984); Neuberger et al., Nature 314: 268 (1985).
checking).

Example 11: Production of Secreted Proteins for High Throughput Screening Assays The following protocol produces a supernatant containing the polypeptide to be tested. This supernatant can then be used in the screening assay described in Examples 13-20.

First, poly-D-lysine (644 587 Boehringer-Man)
nheim) stock solution (1 mg / ml in PBS) in PBS (17-516F Biowhittaker without calcium or magnesium).
Dilute to 20 to make working solution 50 μg / ml. 200 μl of this solution
Add to each well (24 well plate) and incubate for 20 minutes at room temperature. Make sure to distribute the solution over each well (Note: a 12 channel pipettor can be used with tips on every other channel). Poly-
Aspirate off the D-lysine solution and rinse with 1 ml PBS (phosphate buffered saline). PBS should remain in the wells just prior to plating the cells, and the plates can be pre-coated with polylysine by 2 weeks.

[1027] 293T cells (which do not carry more than P + 20 cells) were treated with 2 x 10 ⁵ cells / well in 0.5 ml DMEM (Dulbecco's Modified Eagle Medium) (4.
5 G / L glucose and L-glutamine (12-604F Biowhit
10% heat-inactivated FBS (14-503F Biowhi)
ttaker) / 1 × Penstrep (17-602E Biohitter)
plate). Allow cells to grow overnight.

[1028] The next day, 300 μl lipofectamine (1
8324-012 Gibco / BRL) and 5 ml Optimem I (
31985070 Gibco / BRL) / 96 well plate are mixed together. Using a small volume of multi-channel pipettor, approximately 2 μg of the expression vector containing the polynucleotide insert produced by the method described in Example 8 or 9 was placed in an appropriately labeled 96-well round bottom plate. Aliquot.
Using a multichannel pipettor, 50 μl of Lipofectamine / Opt
Add the imem I mixture to each well. Mix gently by pipetting up and down gently. Incubate for 15-45 minutes at room temperature. After about 20 minutes,
Add 150 μl Optimem I to each well using a multi-channel pipettor. As a control, one plate of vector DNA lacking the insert should be transfected with each set of transfections.

[1029] Preferably, the transfection is carried out by forming a tag team (
tag-teaming). By forming a tag team,
The time effort is halved, and the cells do not spend too much time on PBS. First, Person A aspirates the medium from the four 24-well plates of cells, and then Person B rinses each well with 0.5-1 ml PBS. Mr. A then aspirates the PBS rinse and Mr. B uses 200 μl of DNA using a 12-channel pipettor with tips on every other channel.
/ Lipofectamine / Optimem I complex is added to each row on a 24-well plate, first to odd wells, then to even wells. Incubate at 37 ° C for 6 hours.

[1030]   While incubating the cells, add 1 × penstrep
1% BSA in DMEM with or 2 mM glutamine and 1x pens
CHO-5 medium containing rep (116.6 mg / L CaCl 2₂(Anhydrous); 0
． 00130mg / L CuSO_Four-5H₂O; 0.050 mg / L Fe (NO ₃ )₃-9H₂O; 0.417 mg / L FeSO_Four-7H₂O; 311.80 mg
/ L KCl; 28.64 mg / L MgCl₂48.84 mg / L MgS
O_Four6995.50 mg / L NaCl; 2400.0 mg / L NaHCO₃ 62.50 mg / L NaH₂PO_Four-H₂O; 71.02 mg / L Na₂HP
O_Four0.4320 mg / L ZnSO_Four-7H₂O; 0.002 mg / L ara
Chidonic acid; 1.022 mg / L cholesterol; 0.070 mg / L DL-
α-tocopheryl acetate; 0.0520 mg / L, linoleic acid; 0.010 m
g / L, linolenic acid; 0.010 mg / L myristic acid; 0.010 mg / L
L oleic acid; 0.010 mg / L palmitooleic acid (palmitri
c acid); 0.010 mg / L palmitic acid; 100 mg / L Plu
tronic F-68; 0.010 mg / L stearic acid; 2.20 mg / L
Tween 80; 4551 mg / L D-glucose; 130.85 mg / m
l L-alanine; 147.50 mg / ml L-arginine-HCl; 7.5
0 mg / ml L-asparagine-H₂O; 6.65 mg / ml L-aspara
Formic acid; 29.56 mg / ml L-cystine 2HCl-H₂O; 31.29m
g / ml L-cystine-2HCl; 7.35 mg / ml L-glutamic acid;
365.0 mg / ml L-glutamine; 18.75 mg / ml glycine; 5
2.48 mg / ml L-histidine-HCl-H₂O; 106.97 mg / m
l L-isoleucine; 111.45 mg / ml L-leucine; 163.75
mg / ml L-lysine HCl; 32.34 mg / ml L-methionine; 68
． 48 mg / ml L-phenylalanine; 40.0 mg / ml L-proline
26.25 mg / ml L-serine; 101.05 mg / ml L-threoni
L-tryptophan at 19.22 mg / ml; L-at 91.79 mg / ml
Tyrosine-2Na-2H₂O; 99.65 mg / L L
-Valine; 0.0035 mg / L biotin; 3.24 mg / L D-Ca bread
Tothenic acid; 11.78 mg / L choline chloride; 4.65 mg / L folic acid;
2. 60 mg / L i-inositol; 3.02 mg / L niacinamide;
00 mg / L pyridoxal HCl; 0.031 mg / L pyridoxine HC
1; 0.319 mg / L riboflavin; 3.17 mg / L thiamine HCl;
0.365 mg / L thymidine; and 0.680 mg / L vitamin B₁₂; 2
5 mM HEPES buffer; 2.39 mg / L Na hypoxanthine; 0.10.
5 mg / L lipoic acid; 0.081 mg / L putrescine sodium-2HCl;
55.0 mg / L sodium pyruvate; 0.0067 mg / L selenious acid
Sodium; 20 μM ethanolamine; 0.122 mg / L secondary citric acid
Iron; Methyl-B-cyclodex complexed with 41.70 mg / L linoleic acid
Trin; methyl-B-cyclode complexed with 33.33 mg / L oleic acid
Mist-B-Si complexed with xistrin; and 10 mg / L retinal
Clodextrin). (10% BSA storage
For solution, BSA (81-068-3 Bayer) in 1 L DMEM   Dissolve 100 g). The medium was filtered and 50 μl for endotoxin assay.
Collect in a 15 ml polystyrene conical.

[1035] The transfection reaction is terminated at the end of the incubation time, preferably in tag teams. Person A aspirates off the transfection medium, while person B adds 1.5 ml of the appropriate medium to each well. Incubate at 37 ° C for 45 or 72 hours depending on the medium used: 1%
45 hours for BSA or 72 hours for CHO-5.

[1032] On day 4, 600 μl using a 300 μl multichannel pipettor
Aliquot into 1 ml deep well plate and 2 ml of remaining supernatant
Aliquot into deep wells of. The supernatant from each well was then added to Examples 13-2.
0 may be used in the assay described in 0.

[1035] If the activity is obtained in any of the assays described below using the supernatant, the activity may be obtained directly from the polypeptide (eg, as a secreted protein) or by the polypeptide. Induced expression of other proteins (which
It is then secreted into the supernatant). Thus, the invention further provides methods for identifying proteins in supernatants characterized by activity in a particular assay.

Example 12: Construction of GAS Reporter Constructs One of the signal transduction pathways involved in cell differentiation and proliferation is Jak-STA.
Called the T route. Activators of the Jak-STAT pathway bind to the gamma activation site "GAS" element or interferon-sensitive response element ("ISRE"), located in the promoters of many genes. Binding of proteins to these elements alters the expression of related genes.

[1035] GAS and ISRE elements are recognized by a class of transcription factors called signal transducers and activators of transcription, or "STATs". There are 6 members in the STAT family. Stat1 and Stat3, like Stat2 (as the response to IFNα is widespread), are present in many cell types. Stat4 is more limited,
And although not present in many cell types, it is found in T helper class I cells after treatment with IL-12. Stat5 was originally called Breast Growth Factor,
It has been found in higher concentrations in other cells, including bone marrow cells. It can be activated in tissue culture cells by many cytokines.

[1036] STATs are activated and translocate from the cytoplasm to the nucleus upon tyrosine phosphorylation by a set of kinases known as the Janus Kinase ("Jak") family. Jak represents a unique family of soluble tyrosine kinases and includes Tyk2, Jak1, Jak2, and Jak3. These kinases show significant sequence similarity and are generally catalytically inactive in resting cells.

[1037] Jak is activated by a wide range of receptors as summarized by the table below. (Schidler and Darnell, Ann. Rev.
Biochem. 64: 621-51 (1995). ) J
The cytokine receptor family capable of activating ak is divided into two groups: (a) class 1, IL-2, IL-3, IL-4, IL-6, IL-7,
IL-9, IL-11, IL-12, IL-15, Epo, PRL, GH, G-
Includes receptors for CSF, GM-CSF, LIF, CNTF, and thrombopoietin; and (b) class 2 includes IFN-a, IFN-g, and IL-10. Class 1 receptors have conserved cysteine motifs (4
A set of one conserved cysteine and one tryptophan), and WS
It shares the XWS motif (membrane adjacent region encoding Trp-Ser-Xxx-Trp-Ser (SEQ ID NO: 2)).

[1038] Thus, upon binding of the ligand to the receptor, Jak is activated, which in turn activates STAT, which then translocates and binds to the GAS element. This entire process is involved in the Jak-STAT signaling pathway.

[1039] Therefore, Jak reflected by binding of GAS or ISRE elements.
-Activation of the STAT pathway can be used to indicate proteins involved in cell proliferation and differentiation. For example, growth factors and cytokines are described in Jak-STA
It is known to activate the T pathway. (See table below). Therefore, by using a GAS element linked to a reporter molecule, Jak-ST
Activators of the AT pathway can be identified.

[1040]

[Table 3] To construct synthetic GAS containing promoter elements used in the biological assays described in Examples 13-14, a PCR-based strategy is used to produce the GAS-SV40 promoter sequence. The 5'primer contains four tandem copies of the GAS binding site found in the IRF1 promoter and previously demonstrated to bind STAT upon induction with a range of cytokines (Rothman et al. , Immunity 1: 457
-468 (1994)), other GAS or ISRE elements may be used instead. The 5'primer also contains an 18 bp sequence complementary to the SV40 early promoter sequence and is flanked by XhoI sites. The sequence of the 5'primer is:

[1041]

[Chemical 21] The downstream primer is complementary to the SV40 promoter and contains Hind I
Adjacent to the II site: 5 ′: GCGGCAAGCTTTTTTGCAAAGCCT
AGGC: 3 '(SEQ ID NO: 4).

[1042] PCR amplifications are performed with the SV40 promoter template present in the B-gal: promoter plasmid obtained from Clontech. The resulting PCR fragment is digested with XhoI / HindIII and subcloned into BLSK2- (Stratagene). Sequencing with forward and reverse primers confirms that the insert contains the following sequences:

[1043]

[Chemical formula 22] The GAS: SEAP2 reporter construct is then engineered with this GAS promoter element linked to the SV40 promoter. Here, the reporter molecule is secretory alkaline phosphatase or "SEAP". But,
Obviously, any reporter molecule could substitute for SEAP in either this or other examples. Well-known reporter molecules that can be used in place of SEAP include chloramphenicol acetyl transferase (
CAT), luciferase, alkaline phosphatase, β-galactosidase,
Green fluorescent protein (GFP), or any protein that can be detected by an antibody.

The above sequence identified as a synthetic GAS-SV40 promoter element was replaced with G
To make the AS-SEAP vector, the SV40 promoter is efficiently replaced with the amplified GAS: SV40 promoter element using HindIII and XhoI and subcloned into the pSEAP-promoter vector obtained from Clontech. However, this vector does not contain the neomycin resistance gene and is therefore not preferred for mammalian expression systems.

[1045] Therefore, to generate a stable mammalian cell line expressing the GAS-SEAP reporter, the GAS-SEAP cassette was removed from the GAS-SEAP vector using SalI and NotI and GAS-SEAP / Neo. To create the vector, these restriction sites in the multiple cloning site were used to create a backbone vector containing the neomycin resistance gene (eg pGFP-
1 (Clontech)). Once the vector is transfected into mammalian cells, the vector can be used as a reporter molecule for GAS binding as described in Examples 13-14.

[1046] Other constructs can be made using the above description and replacing GAS with a different promoter sequence. For example, the construction of a reporter molecule containing NFK-B and EGR promoter sequences is described in Examples 15 and 16. However, many other promoters can be replaced using the protocols described in these examples. For example, SRE, IL-2, NFAT, or osteocalcin promoters alone or in combination (eg, GAS / NF-KB / EGR, GA
S / NF-KB, Il-2 / NFAT, or NF-KB / GAS). Similarly, other cell lines (eg HELA (epithelial cells), HUVEC (endothelial cells), Reh (B cells), Saos-2 (osteoblasts), HUVAC (aortic cells)).
, Or cardiomyocytes) can be used to test the activity of the reporter construct.

Example 13: High Throughput Screening Assay for T Cell Activity The following protocol was performed using T, for example, by identifying factors such as growth factors and cytokines that can proliferate or differentiate T cells. Used to assess cell activity. The activity of T cells was measured by GAS / SEAP / Neo prepared in Example 12.
Assess with the construct. Therefore, the factor that increases SEAP activity is Jak-
Shows the ability to activate the STAT signaling pathway. T used in this assay
The cells are Jurkat T cells (ATCC Accession No. TIB-152),
Molt-3 cells (ATCC Accession No. CRL-1552) and Molt-4 cells (ATCC Accession No. CRL-1582) cells may also be used.

[1048] Jurkat T cells are lymphoblastic CD4 + Th1 helper cells. Approximately 2 million Jurkat cells were DMRed to generate stable cell lines.
GAS-SEAP using IE-C (Life Technologies)
/ Neo vector (transfection procedure described below). Transfected cells are seeded at a density of approximately 20,000 cells / well, and transfectants that are resistant to 1 mg / ml of geneticin are selected. Growing resistant colonies, then
Test for their response to increasing concentrations of interferon-γ. The dose response of selected clones is shown.

In detail, the following protocol yields sufficient cells for 75 wells containing 200 μl of cells. Therefore, in order to produce sufficient cells for multiple 96-well plates, either scale up or run in multiples. Jurkat cells were treated with RPMI + 10% serum and 1% Pen-St.
Keep in rep. 2.5 ml OPTI-MEM (Li
fe Technologies) and 10 μg of plasmid DNA. Add 2.5 ml OPTI-MEM containing 50 μl DMRIE-C and incubate at room temperature for 15-45 minutes.

[1049] During the incubation time, count the cell concentration, spin down the required number of cells (10 ⁷ per transfection), and a final concentration of 10 ⁷ cells / m 2.
Resuspend to 1 in OPTI-MEM. Then 1 ml OPTI-
1 × 10 ⁷ cells in MEM are added to a T25 flask and incubated at 37 ° C. for 6 hours. After incubation, 10 ml RPMI + 15% serum is added.

The Jurkat: GAS-SEAP stable reporter strain is maintained in RPMI + 10% serum, 1 mg / ml Geneticin, and 1% Pen-Strep. These cells are treated with a supernatant containing the polypeptide as produced by the protocol described in Example 11.

[1052] Cells should be washed on the day of treatment with the supernatant and 500,00 ml / ml.
It should be resuspended in fresh RPMI + 10% serum to a density of 0 cells. The exact number of cells required depends on the number of supernatants screened.
Approximately 10 million cells are needed per 96-well plate (100 million cells per 10 plates).

[1053] Transfer the cells to a triangular reservoir boat to dispense the cells into a 96-well dish using a 12-channel pipette. 200 μl of cells are transferred to each well using a 12-channel pipette (thus adding 100,000 cells per well).

After seeding all plates, 50 μl of supernatant is transferred directly from the 96-well plate containing the supernatant to each well using a 12-channel pipette. further,
Exogenous interferon gamma doses (0.1, 1.0, 10 ng) were added to well H
Add to 9, well H10, and well H11 to serve as an additional positive control for the assay.

[1058] 96-well dishes containing Jurkat cells treated with supernatant are placed in the incubator for 48 hours (note: this time can vary between 48 and 72 hours).
Then 35 μl of sample from each well is transferred to an opaque 96-well plate using a 12-channel pipette. The opaque plate should be covered (using a cover of cellophane) and stored at -20 ° C until the SEAP assay according to Example 17 is performed. The plate containing the remaining treated cells is placed at 4 ° C. and serves as a source of material for repeating the assay on specific wells, if desired.

As a positive control, 100 Units / ml interferon-γ can be used, which is known to activate Jurkat T cells. Typically,> 30-fold induction is observed in the positive control wells.

Example 14: High Throughput Screening Assay to Identify Myeloid Activity The following protocol uses myelogenous by identifying factors such as growth factors and cytokines that can proliferate or differentiate myeloid cells. Used to evaluate the activity of. The activity of myeloid cells was determined by GAS / SEAP / produced in Example 12.
Assess with the Neo construct. Therefore, the factor that increases SEAP activity is J
Shows the ability to activate the ak-STAT signaling pathway. The myeloid cells used in this assay are U937, a pre-monocyte cell line, but TF-1, HL60, or KG1 may also be used.

[1058] For transient transfection of U937 cells with the GAS / SEAP / Neo construct produced in Example 12, the DEAE-Dextran method (
Kharbanda et al., 1994, Cell Growth & Differ.
Orientation, 5: 259-265). First, 2 × 10 ⁷
U937 cells are harvested and washed with PBS. U937 cells are
Grow in RPMI 1640 medium containing 10% heat-inactivated fetal bovine serum (FBS) supplemented with 100 units / ml penicillin and 100 mg / ml streptomycin.

Next, 0.5 mg / ml DEAE-Dextran, 8 μg of GAS-SE
AP2 plasmid DNA, 140mM NaCl, 5mM KCl, 375μM Na 2 HPO 4 · 7H 2 O, 1mM MgCl 2, and 675μM CaCl ₂
The cells are suspended in 1 ml of 20 mM Tris-HCl (pH 7.4) buffer containing Incubate at 37 ° C for 45 minutes.

[1060] Wash cells with RPMI 1640 medium containing 10% FBS, then 10
Resuspend in ml complete medium and incubate at 37 ° C for 36 hours.

GAS-SEAP / U937 stable cells are obtained by growing the cells in 400 μg / ml G418. G418-free medium is used for routine growth, but every 1-2 months the cells are 400 μg / ml G418 for two passages.
Should be regrown in.

These cells are tested by harvesting 1 × 10 ⁸ cells, which is sufficient for 10 96-well plate assay, and washing with PBS. The cells are suspended in the above 200 ml of growth medium at a final density of 5 × 10 ⁵ cells / ml. Plate 200 μl cells per well in a 96 well plate (ie 1 × 10 ⁵ cells / well).

Add 50 μl of the supernatant prepared according to the protocol described in Example 11. Incubate at 37 ° C for 48-72 hours. 10 as a positive control
0 unit / ml of interferon gamma can be used, which is known to activate U937 cells. Typically,> 30-fold induction is observed in positive control wells. SEAP assay supernatants according to the protocol described in Example 17.

Example 15: High Throughput Screening Assay to Identify Neuronal Activity [1064] A group of genes is activated via many different signaling pathways when cells undergo differentiation and proliferation. One of these genes, EGR1 (Early Growth Response Gene 1), is induced in various tissues and cell types upon activation. EG
The R1 promoter is responsible for such induction. EGR bound to a reporter molecule
One promoter can be used to assess cell activation.

Specifically, the following protocol is used to assess neuronal activity in the PC12 cell line. PC12 cells (rat pheochromocytoma
cytoma cell)) is a large number of mitogens such as TPA (tetradecanoylphorbol acetate), NGF (nerve growth factor), and EGF.
It is known to proliferate and / or differentiate by activation with (epithelial growth factor)). EGR1 gene expression is activated during this treatment. Therefore, PC12 cell activation can be assessed by stably transfecting PC12 cells with a construct containing an EGR promoter linked to a SEAP reporter.

The EGR / SEAP reporter construct can be assembled by the following protocol.
EGR-1 promoter sequence (-633 to +1) (Sakamoto K et al., O.
ncogene 6: 867-871 (1991)) can be PCR amplified from human genomic DNA using the following primers:

[1067]

[Chemical formula 23] The GAS: SEAP / Neo vector generated in Example 12 can then be used to insert the EGR1 amplification product into this vector. Restriction enzyme XhoI / H
linearize GAS: SEAP / Neo vector using indIII
/ Remove SV40 stuffer. The same enzymes are used to limit EGR1 amplification products. Connect the vector and the EGR1 promoter.

[1068] To prepare a 96-well plate for cell culture, the coating solution (
Collagen type I (Upstate Biotech Inc. Catalog No. 0
8-115) diluted 1:30 with 30% ethanol (sterile filtration) 10
2 ml per cm plate, or 50 μl per well in 96 well plate
Add and air dry for 2 hours.

[1069] PC12 cells were plated on 10 cm tissue culture dishes pre-coated with 10% horse serum (JRH BIOSCIENCES, Catalog No. 124) supplemented with penicillin (100 units / ml) and streptomycin (100 μg / ml).
49-78P), RPMI-164 containing 5% heat-inactivated fetal bovine serum (FBS)
Routinely grow in 0 medium (Bio Whittaker). Divide from 1 to 4 every 3-4 days. The cells are removed from the plate by scraping and resuspended by pipetting up and down more than 15 times.

The EGR / SEAP / Neo construct was prepared using the Lipofecta described in Example 11.
Transfect PC12 using the mine protocol. EGR-S
EAP / PC12 stable cells are obtained by growing the cells in 300 μg / ml G418. G418-free medium is used for routine growth,
Every 1-2 months, cells should be regrown in 300 μg / ml G418 for 2 passages.

To assay neuronal activity, 10 cm plates with cells that are approximately 70-80% confluent are screened by removing old medium. The cells are washed once with PBS (phosphate buffered saline).
The cells were then treated with low serum medium (1% horse serum and 0.5% F with antibiotics).
Starve overnight in RPMI-1640 with BS).

[1072] The next morning, remove the medium and wash the cells with PBS. Scrap the cells from the plate and resuspend the cells well in 2 ml low serum medium. Counting the number of cells, and were added to a lower serum medium to reach final cell density of 5 × 10 ⁵ cells / ml.

[1073] Add 200 μl of cell suspension to each well of a 96-well plate (1 x 1
0 ⁵ cells / well). 50 μl of the supernatant produced according to Example 11
Add at 37 ° C for 48-72 hours. PC as a positive control via EGR
Growth factors known to activate 12 cells may be used, such as 50 ng / μl nerve growth factor (NGF). Typically,> 50-fold SEAP induction is found in positive control wells. SEAP assay supernatants according to Example 17.

Example 16: High Throughput Screening Assay for T Cell Activity NF-κB (Nuclear Factor κB) is found in a wide variety of agents (inflammatory cytokines IL-1 and TNF, CD30 and CD40). , Including lymphotoxin-α and lymphotoxin-β), by exposure to LPS or thrombin, and by expression of specific viral gene products. As a transcription factor, NF-κB is the expression of genes involved in the activation of immune cells, regulation of apoptosis (NF-κB seems to protect cells from apoptosis),
It regulates B and T cell development, antiviral and antibacterial responses, and multiple stress responses.

[1075] In unstimulated conditions, NF-κB is retained in the cytoplasm with I-κB (inhibitor κB). However, upon stimulation, I-κB is phosphorylated and degraded, causing NF-κB to shuttle to the nucleus.
), Which activates transcription of the target gene. The target genes activated by NF-κB include IL-2, IL-6, GM-CSF, and ICA.
M-1 and class 1 MHC.

[1076] Due to its central role and ability to respond to a range of stimuli, NF-
A reporter construct utilizing the κB promoter element is used to screen the supernatant produced in Example 11. Activators or inhibitors of NF-κB are useful in treating disease. For example, inhibitors of NF-κB can be used to treat those diseases associated with acute or chronic NF-κB activation, such as rheumatoid arthritis.

PCR was performed to construct a vector containing the NF-κB promoter element.
Use a strategy based on. The upstream primer has an NF-κB binding site (
GGGGAACTTTCCC) (SEQ ID NO: 8), four tandem copies, containing an 18 bp sequence complementary to the 5'end of the SV40 early promoter sequence and flanked by XhoI sites:

[1078]

[Chemical formula 24] The downstream primer is complementary to the 3'end of the SV40 promoter,
And adjacent to the HindIII site: 5 ': GCGGCAAGCTTTTTGCAAAAGCCATAGGC: 3' (SEQ ID NO: 4).

[1098] PCR amplification is performed using the SV40 promoter template present in the pβ-gal: promoter plasmid obtained from Clontech. The resulting PCR fragment was digested with XhoI and HindIII and BL
Subcloning into SK2- (Stratagene). Sequencing with the T7 and T3 primers confirms that the insert contains the following sequences:

[1080]

[Chemical 25] XhoI and HindIII are then used to replace the SV40 minimal promoter element present in the pSEAP2-promoter plasmid (Clontech) with this NF-κB / SV40 fragment. However, this vector does not contain the neomycin resistance gene and is therefore not preferred for mammalian expression systems.

[1096] To generate a stable mammalian cell line, the NF-κB / SV40 / SEAP cassette was NF-κB / SEA as described above using the restriction enzymes SalI and NotI.
Remove from P vector and insert into vector containing neomycin resistance.
In particular, NF-κB after restriction of pGFP-1 with SalI and NotI.
Insert the / SV40 / SEAP cassette into pGFP-1 (Clontech),
The GFP gene was replaced.

[1085] Once the NF-κB / SV40 / SEAP / Neo vector was created, stable Jurkat T cells were created according to the protocol described in Example 13.
And maintain. Similarly, a method for assaying supernatants containing these stable Jurkat T cells is also described in Example 13. As a positive control, exogenous TNFα (0.1, 1, 10 ng) was added to wells H9, H10, and H11, and typically 5-10 fold activation is observed.

Example 17: Assay for SEAP activity SE as a reporter molecule for the assays described in Examples 13-16.
AP activity was measured by Tropix Phospho-li according to the following general procedure.
Assay using the ght Kit (catalog number BP-400). Troop
The ix Phospho-light Kit is a dilution buffer used below,
Supply assay buffer and reaction buffer.

[1086] Fill a dispenser with 2.5 × Dilution Buffer and dispense 15 μl of 2.5 × Dilution Buffer into an Optiplate containing 35 μl of supernatant. Seal the plate with a plastic sealer and incubate at 65 ° C for 30 minutes. Keep Optiplates apart to avoid uneven heating.

[1085] Cool the sample to room temperature for 15 minutes. Empty the dispenser and fill with assay buffer. Add 50 μl assay buffer and incubate at room temperature for 5 minutes. Empty the dispenser and fill with reaction buffer (see table below). Add 50 μl reaction buffer and incubate for 20 minutes at room temperature. The intensity of the chemiluminescent signal is time-dependent, and it takes about 10 minutes to read 5 plates on the luminometer, so 5 plates are processed at a time and the second set is started 10 minutes later. Should do.

[1086] Read the relative light unit in the luminometer. Set H12 as blank and print the result. An increase in chemiluminescence indicates reporter activity.

[1087]

[Table 4] Example 18: High Throughput Screening Assay to Identify Changes in Small Molecule Concentration and Membrane Permeability Binding of ligands to receptors alters intracellular levels of small molecules such as calcium, potassium, sodium and pH. It is well known to change the membrane potential. These changes can be measured in assays that identify the supernatant that binds to the receptor on a particular cell. The following protocol describes an assay for calcium, but this protocol is easily modified to detect changes in potassium, sodium, pH, membrane potential, or any other small molecule detectable by a fluorescent probe. You can

[1086] The following assay measures changes in fluorescent molecules (Molecular Probes) that bind small molecules using a fluorimetric imaging plate reader ("FLIPR"). Obviously, any fluorescent molecule that detects small molecules could be used in place of the calcium fluorescent molecule, fluo-3, as used herein.

For adherent cells, seed cells at 10,000-20,000 cells / well in Co-star black 96-well plates with clear bottoms. CO _{2 the} plate
Incubate in incubator for 20 hours. The adherent cells were treated with 200 μl of HBSS (Hank's Balanced Salt) in a Biotek washer.
Wash twice with Solution, leaving 100 μl of buffer after the last wash.

A stock solution of 1 mg / ml fluo-3 was added to 10% pluronic acid (pluro acid).
nic acid) Made of DMSO. To load the cells with fluo-3,
12 μg / ml fluo-3 (50 μl) is added to each well. The plate is incubated for 60 minutes at 37 ° C. in a CO ₂ incubator. The plate is washed 4 times with HBSS in the Biotek washer, leaving 100 μl of buffer.

For non-adherent cells, spin down the cells from the culture medium. 50 cells
Resuspend to 2-5 × 10 ⁶ cells / ml with HBSS in a ml conical tube. 4 μl of 1 mg / ml fluo-3 10% pluronic acid DMSO solution is added per 1 ml of cell suspension. Then, place the tube in a 37 ° C water bath for 30-6
Leave for 0 minutes. The cells were washed twice with HBSS and resuspended at 1 × 10 ⁶ cells / ml,
Then, dispense 100 μl / well to the microplate. Plate 100
Centrifuge at 0 rpm for 5 minutes. Next, plate the Denley CellWa
After washing once with 200 μl in sh, the final volume is brought to 100 μl by an aspiration step.

For non-cell based assays, each well contains a fluorescent molecule such as fluo-3. The supernatant is added to the wells and the change in fluorescence is detected.

[1093]   In order to measure the fluorescence of intracellular calcium, FLIPR was set to the following parameters.
Set: (1) System gain is 300-800 mW; (2)
Exposure time is 0.4 seconds; (3) camera F / stop is F / 2;
(4) Excitation is 488 nm; (5) Emission is 530 nm; and (6)
Sample addition is 50 μl. The increase in luminescence at 530 nm is due to intracellular Ca ⁺⁺ Figure 7 shows extracellular signaling events that result in increasing concentrations.

Example 19: High Throughput Screening Assay to Identify Tyrosine Kinase Activity Protein tyrosine kinases (PTKs) represent a diverse group of transmembrane and cytoplasmic kinases. Within the receptor protein tyrosine kinase (RPTK) family, there is a range of receptors for mitogenic and metabolic growth factors, including PDGF, FGF, EGF, NGF, HGF and the insulin receptor subfamily. In addition, there is a large RPTK family whose corresponding ligands are unknown. RPTK ligands include primarily secreted low molecular weight proteins, but also membrane-bound and extracellular matrix proteins.

[1095] Activation of RPTK by a ligand is involved in ligand-mediated receptor dimerization, resulting in transphosphorylation of receptor subunits and activation of cytoplasmic tyrosine kinases. Cytoplasmic tyrosine kinases include receptor-related tyrosine kinases of the src family (eg, src, yes, lck, lyn, fyn), and non-receptor bound and cytosolic protein tyrosine kinases such as the Jak family. These members include cytokine superfamily (eg, interleukins, interferons, GM-C).
It mediates signal transduction triggered by receptors for SF and leptin).

[1096] Due to the wide variety of known factors that can stimulate tyrosine kinase activity, the identification of novel human secreted proteins that can activate the tyrosine kinase signaling pathway is of interest. Therefore, the following protocol is designed to identify novel human secreted proteins that can activate the tyrosine kinase signaling pathway.

[1097] Target cells (eg, primary keratinocytes) were purchased from Nalge Nunc (Naperville, IL) at a density of approximately 25,000 cells / well 96.
Seed wells Loprodyne Silent Screen Plate. The plates are sterilized by rinsing twice with 100% ethanol for 30 minutes, rinsed with water and then dried overnight. Several plates were plated with 100 ml of cell culture grade type I collagen (50 mg / ml), gelatin (2%) or polylysine (50 mg / ml) (all of these were from Sigma Chemicals (St.
Louis, MO)), or Becton Dickins
on (Bedford, MA) coated with 10% Matrigel or calf serum for 2 hours, rinsed with PBS and stored at 4 ° C. Growth medium was seeded at 5,000 cells / well and the manufacturer's Alamar Biosci was used.
incomes, Inc. (Sacramento, CA) as described in al
Cell proliferation is assayed on these plates by indirect quantification of cell number after 48 hours using amarBlue. Becton Dickinso
N (Bedford, MA) Falcon plate cover # 3071 is used to cover the Loprodyne Silent Screen Plate. Fa
lcon Microtest III cell culture plates may also be used in some proliferation experiments.

To prepare extracts, A431 cells are seeded (20,000 / 200 ml / well) on nylon membranes of Loprodyne plates and cultured overnight in complete medium. The cells are incubated in serum-free basal medium for 24 hours to make them rest. 5-2 (50 ng of EGF (60 ng / ml) or the supernatant produced in Example 11)
After treatment for 0 minutes, the medium was removed and 100 ml of extraction buffer (20 mM HEP
ES pH 7.5, 0.15M NaCl, 1% Triton X-100, 0.
1% SDS, 2 mM Na ₃ VO ₄ , 2 mM Na ₄ P ₂ O ₇ and Boeheri
nger Mannheim (Indianapolis, IN) mixture of protease inhibitors (# 1836170)) is added to each well, and the plate is shaken on a rotary shaker for 5 minutes at 4 ° C. The plate is then placed on a vacuum transfer manifold.
old) and filter the extract through a 0.45 mm membrane at the bottom of each well using house vacuum. The extracts are collected in a 96 well capture / assay plate at the bottom of the vacuum manifold and immediately placed on ice. To obtain a clarified extract by centrifugation, solubilize with detergent for 5 minutes, then remove the contents of each well and centrifuge at 16,000 xg for 15 minutes at 4 ° C.

The filtered extract is tested for levels of tyrosine kinase activity. Although many methods of detecting tyrosine kinase activity are known, one of the methods is described herein.

[1100] Generally, the tyrosine kinase activity of the supernatant is assessed by determining the ability to phosphorylate tyrosine residues on a particular substrate (biotinylated peptide). Biotinylated peptides that can be used for this purpose include PSK1 (cell division kinase cd
and amino acids 6-20 of c2-p34) and PSK2 (corresponding to amino acids 1-17 of gastrin). Both peptides are substrates for a series of tyrosine kinases and are available from Boehringer Mannheim.

[1101] Set up the tyrosine kinase reaction by adding the following components in order. First, after adding 10 μl of 5 μM biotinylated peptide, ATP / Mg ²⁺ (
5 mM ATP / 50 mM MgCl ₂ 10 μl, 5 × assay buffer (40
mM imidazole hydrochloride, pH 7.3, 40 mM β-glycerophosphate, 1 mM EGTA, 100 mM MgCl ₂ , 5 mM MnCl ₂ , 0.5 mg / ml
BSA) 10 μl, sodium vanadate (1 mM) 5 μl and finally water 5 μl. The components are mixed gently and the reaction mixture is preincubated for 2 minutes at 30 ° C. The reaction is started by adding 10 μl of control enzyme or filtered supernatant.

[1102] The tyrosine kinase assay reaction is then stopped by adding 10 μl of 120 mM EDTA and placing the reaction on ice.

[1103] Tyrosine kinase activity is measured by transferring a 50 μl aliquot of the reaction mixture to a microtiter plate (MTP) module and incubating at 37 ° C for 20 minutes. As a result, streptavidin (streptava)
din) Coat 96-well plate with biotinylated peptide.
Wash MTP module 4 times with 300 μl / well PBS. Next, anti-phosphotyrosine conjugated to horseradish peroxidase (phospotyro).
Sine) antibody (anti-P-Tyr-POD (0.5 u / ml)) (75 μl) is added to each well and then incubated at 37 ° C. for 1 hour. Wash wells as above.

Next, a peroxidase substrate solution (Boehringer Mannheim)
) Add 100 μl and incubate at room temperature for at least 5 minutes (up to 30 minutes). The absorbance of the sample at 405 nm is measured using an ELISA reader. The level of bound peroxidase activity was quantified using an ELISA reader, which reflects the level of tyrosine kinase activity.

Example 20: High Throughput Screening Assay to Identify Phosphorylation Activity [1105] As a potential alternative and / or compliment of the protein tyrosine kinase activity assay described in Example 19, Assays that detect activation (phosphorylation) of intracellular signaling intermediates may also be used.
For example, as described below, one particular assay is Erk-1 and Erk-2.
Tyrosine phosphorylation of the kinase can be detected. However, Raf, JNK, p38M
Phosphorylation of other molecules such as AP, Map Kinase Kinase (MEK), MEK Kinase, Src, Muscle Specific Kinase (MuSK), IRAK, Tec and Janus, as well as any other phosphoserine, phosphotyrosine or phosphothreonine molecule. , Erk-1 or Er in these molecules in the following assay
It can be detected by replacing k-2.

In detail, the wells of a 96-well ELISA plate were treated with protein G (1 μg /
ml) 0.1 ml to coat at room temperature (RT) for 2 hours to make an assay plate. The plates are then rinsed with PBS and blocked with 3% BSA / PBS for 1 hour at RT. Next, the protein G plate was subjected to Erk-1 and E.
Two commercially available monoclonal antibodies against rk-2 (100 ng / well) (S
Ant Cruz Biotechnology) (RT for 1 hour). (In order to detect other molecules, this step can be easily modified by replacing it with a monoclonal antibody that detects any of the molecules above). After rinsing 3-5 times with PBS, plates are stored at 4 ° C until use.

[1107] A431 cells are seeded at 20,000 / well in 96-well Loprodyne filter plates and cultured overnight in growth medium. Next, the cells are treated with basal medium (D
EGF (6 ng / well) or Example 1 after starvation in MEM) for 48 hours.
Treat with 50 μl of the supernatant obtained in 1 for 5 to 20 minutes. The cells are then solubilized and the extract filtered and placed directly into the assay plate.

[1108] After incubating with the extract for 1 hour at RT, the wells are rinsed again. Commercially available MAP kinase preparation (10 ng / well) as a positive control
In place of the A431 extract. The plates are then loaded with Erk-1 and E.
Treatment with a commercially available polyclonal (rabbit) antibody (1 μg / ml) that specifically recognizes a phosphorylated epitope of rk-2 kinase (1 hour at RT). The antibody is biotinylated by standard procedures. Next, the bound polyclonal antibody was combined with Europium streptavidin and Europium fluorescence enhancer and Wallac DELF.
Quantification by continuous incubation (time-resolved fluorescence) in an IA instrument. An increase in fluorescent signal above background indicates phosphorylation.

Example 21: Method for Determining Changes in Genes Corresponding to a Polynucleotide RNA isolated from an entire family or individual patient presenting a phenotype of interest (eg, disease) is isolated. CDNA is then generated from these RNA samples using protocols known in the art (see Sambrook).
This cDNA is then used as a template for PCR with primers that surround the region of interest in SEQ ID NO: X. Suggested PCR conditions are Sid
ranky, D.A. Et al., Science 252: 706 (1991), consisting of 35 cycles of 95 ° C for 30 seconds; 52-58 ° C for 60-120 seconds; and 70 ° C for 60-120 seconds.

[1110] Next, the PCR product was subjected to SequiTherm Polymerase (Epi
Center Technologies) and sequenced using primers labeled with T4 polynucleotide kinase at the 5'end. The intron-exon boundaries of the selected exons are also determined and the genomic PCR products are analyzed to confirm the results. The PCR product with the suspected mutation is then cloned and sequenced to confirm the direct sequencing results.

[1111] The PCR product was cloned into Holton, T., et al. A. And Graham, M .; W. , Nu
Cleic Acids Research, 19: 1156 (1991) and cloned into a T-tail vector and labeled with T7 polymerase (United).
Sequencing at the States Biochemical). Affected individuals are identified by mutations that are not present in unaffected individuals.

[1112] Genomic rearrangements are also observed as a way to determine alterations in the gene corresponding to the polynucleotide. Genomic clones isolated according to Example 2 were transformed with digoxigenin deoxy-uridine 5'-triphosphate (Boehringer Manh).
nick translation using eim), and Johnson, Cg
． Et al., Methods Cell Biol. 35: 73-99 (1991)
FISH is performed as described in (). For specific hybridization to the corresponding genomic locus, a large excess of human cot-1 DNA is used to perform hybridization with the labeled probe.

[1113] Chromosomes are counterstained with 4,6-diamino-2-phenylidole and propidium iodide to generate a combination of C and R bands. Aligned images for accurate mapping can be generated by triple band filter set (Chroma Tech)
noology, Brattleboro, VT) and cooled charge-coupled device camera (P
photometrics, Tucson, AZ) and tunable excitation wavelength filters (Johnson, Cv. et al., Genet. Anal. Tech. Appl.,
8:75 (1991)). ISee Graphi
cal Program System (Invision Corporation
, Durham, NC) for image collection, analysis and chromosome segment length measurement. Chromosomal changes in the genomic region to which the probe hybridizes are identified as insertions, deletions and translocations. These changes are used as diagnostic markers for related diseases.

Example 22: Method for Detecting Abnormal Levels of Polypeptides in Biological Samples Polypeptides of the invention can be detected in biological samples, and elevated or decreased polypeptide levels are detected. If so, this polypeptide is a marker of a particular phenotype. It is understood that there are numerous detection methods, and therefore one of skill in the art can modify the following assays to suit their particular needs.

[1115] For example, an antibody sandwich ELISA is used to detect the polypeptide in a sample, preferably a biological sample. The wells of a microtiter plate are coated with specific antibody at a final concentration of 0.2-10 μg / ml. This antibody is either monoclonal or polyclonal and is produced by the method described in Example 10. The well is blocked so that non-specific binding of the polypeptide to the well is reduced.

[1160] The coated wells are then incubated with the polypeptide-containing sample at RT for more than 2 hours. Preferably, serial dilutions of the sample should be used to confirm the results. The plate is then washed three times with deionized or distilled water to remove unbound polypeptide.

Next, 50 μl of the specific antibody-alkaline phosphatase conjugate was added to 25-400 n.
Add at a concentration of g and incubate at room temperature for 2 hours. Plates are washed again three times with deionized or distilled water to remove unbound conjugate.

[1187] Add 75 μl of 4-methylumbelliferyl phosphate (MUP) or p-nitrophenyl phosphate (NPP) substrate solution to each well and incubate at room temperature for 1 hour. Reactions are measured by microtiter plate reader. A standard curve is constructed using serial dilutions of control samples and the polypeptide concentration is plotted on the X-axis (log scale) and fluorescence or absorbance on the Y-axis (linear scale). A standard curve is used to interpolate the concentration of polypeptide in the sample.

Example 23 Polypeptide Formulations The secreted polypeptide composition can be administered to individual patients in clinical settings (particularly the side effects of treatment with the secreted polypeptide alone), delivery site, mode of administration, dosing regimen and to those skilled in the art. Taking into account other known factors, good medical practice
Formulated and dosed in a manner that complies with e). Therefore, the "effective amount" intended in the present specification is determined by taking such a consideration into consideration.

[1120] As a general proposition, the total pharmaceutically effective amount of the secretory polypeptide administered parenterally per dose is in the range of about 1 μg / kg / day to 10 mg / kg / day of patient body weight. This, as mentioned above, is at the discretion of the therapeutic. More preferably, for the hormone, the dose is at least 0.01 mg / kg / day, most preferably between about 0.01 mg / kg / day and about 1 mg / kg / day for humans. When administered continuously, the secretory polypeptide is typically injected one to four times a day at a dosage rate of about 1 μg / kg / hour to about 50 μg / kg / hour or by continuous subcutaneous infusion (eg, using a minipump). ). Intravenous bag solutions may also be used. The duration of treatment required to observe changes and the post-treatment interval at which a response occurs appears to vary depending on the desired effect.

[1121] A pharmaceutical composition comprising a secreted protein of the invention may be administered orally, rectally, parenterally,
It is administered intracystally, intravaginally, intraperitoneally, topically (such as by powder, ointment, gel, drops, or transdermal patch), buccal or oral or as a nasal spray. "Pharmaceutically acceptable carrier" refers to a non-toxic solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type. The term "parenteral" as used herein refers to modes of administration which include intravenous, intramuscular, intraperitoneal, intrasternal, subcutaneous and intraarticular injection and infusion.

[1131] Secreted polypeptides are also suitably administered by sustained release systems. Suitable examples of sustained release compositions include semipermeable polymer matrices in the form of shaped articles, eg films or microcapsules. As the sustained-release matrix, polylactide (US Pat. No. 3,773,919, EP58,481), a copolymer of L-glutamic acid and γ-ethyl-L-glutamate (Sidman, U.
． Et al., Biopolymers 22: 547-556 (1983)), poly (
2-hydroxyethylmethacrylate) (R. Langer et al., J. Biome.
d. Mater. Res. 15: 167-277 (1981), and R.S. La
nger, Chem. Tech. 12: 98-105 (1982)), ethylene vinyl acetate (R. Langer et al.) Or poly-D-(-)-3-hydroxybutyric acid (EP133,988). Sustained-release compositions also include liposome-encapsulated polypeptides. Liposomes containing secreted polypeptides are prepared by methods known per se: DE 3,218,121;
Epstein et al., Proc. Natl. Acad. Sci. USA 82: 3
688-3692 (1985); Hwang et al., Proc. Natl. Acad
． Sci. USA 77: 4030-4034 (1980); EP 52,322.
EP36,676; EP88,046; EP143,949; EP142,6;
41; Japanese Patent Application No. 83-118008; U.S. Pat. No. 4,485,045.
And 4,544,545 and EP 102,324. Usually, liposomes are small (about 200-800 Å) unilamellar, where the lipid content is greater than about 30 mol% cholesterol and a selected proportion is adjusted for optimal secreted polypeptide therapy. It

For parenteral administration, in one embodiment, the secreted polypeptide is generally provided to the recipient in the desired degree of purity, pharmaceutically acceptable carrier, ie, dosage and concentration employed. It is formulated by mixing in a unit dose injectable form (solution, suspension or emulsion) with a non-toxic compound that is compatible with the other ingredients of the formulation. For example, the formulation preferably does not include oxidizing agents and other compounds known to be deleterious to polypeptides.

[1123] In general, the formulations are prepared by contacting the polypeptides with a liquid carrier, a finely divided solid carrier, or both, in a uniform and intimate contact. Then, if necessary,
Mold the product into the desired formulation. Preferably the carrier is a parenteral carrier, more preferably a solution that is isotonic with the blood of the recipient. Examples of such carrier vehicles include water, saline, Ringer's solution and dextrose solution. Non-aqueous vehicles such as fixed oils and ethyl oleate are also useful herein, as are liposomes.

[1125] The carrier suitably contains minor amounts of additives such as substances that enhance isotonicity and chemical stability. Such substances are not toxic to the recipients at the dosages and concentrations used, and include such substances as phosphates, citrates, succinates, acetic acid and other organic acids or their salts. Buffers such as; antioxidants such as ascorbic acid; low molecular weight (less than about 10 residues) polypeptides (eg, polyarginine or tripeptides); proteins such as serum albumin, gelatin or immunoglobulins; polyvinylpyrrolidone. Hydrophilic polymers such as; glycine, glutamic acid, aspartic acid or amino acids such as arginine; cellulose or its derivatives, mono-, di-, and other carbohydrates, including glucose, mannose or dextrin; chelating agents such as EDTA ; Sugar sugars such as mannitol or sorbitol Lumpur; counterions such as sodium; and / or polysorbate include nonionic surfactants such as poloxamers or PEG.

[1126] Secreted polypeptides are typically formulated in such vehicles at a concentration of about 0.1 mg / ml to 100 mg / ml, preferably 1-10 mg / ml, at a pH of about 3-8. It It is understood that the use of the particular excipients, carriers or stabilizers described above will result in the formation of polypeptide salts.

[1127] Any polypeptide to be used for therapeutic administration can be sterile. Sterility is easily achieved by filtration through a sterile filtration membrane (eg 0.2 micron membrane). Generally, the therapeutic polypeptide compositions are placed in a container having a sterile access port, for example, an intravenous solution bag or vial with a stopper pierceable by a hypodermic injection needle.

[1128] The polypeptide will usually be stored in unit-dose or multi-dose containers, such as sealed ampoules or vials, as an aqueous solution or as a lyophilized formulation for reconstitution. As an example of a lyophilized formulation, sterile filtered 1% (
w / v) Charge 5 ml of aqueous polypeptide solution and lyophilize the resulting mixture. The lyophilized polypeptide is reconstituted with bacteriostatic water for injection to prepare an infusion solution.

[1129] The invention also provides a pharmaceutical pack or kit comprising one or more containers filled with one or more of the ingredients of the pharmaceutical compositions of the invention. A notice in the form of a government agency that regulates the manufacture, use, or sale of pharmaceuticals or biological products may accompany such containers, which notice may include government notices regarding manufacture, use, or sale for human administration. Indicates approval by the institution. Furthermore, the polypeptides of the present invention may be used in combination with other therapeutic compounds.

Example 24 Methods of Treating Reduced Levels of Polypeptides [1135] Conditions caused by reduced normal or normal expression levels of secreted proteins in an individual are administered a polypeptide of the invention, preferably in secreted form. It is understood that treatment can be carried out by Thus, the invention also provides a method of treating an individual in need of increased levels of polypeptide. The method includes the step of administering to such an individual a pharmaceutical composition comprising an amount of the polypeptide that increases the activity level of the polypeptide in such individual.

For example, patients with reduced levels of polypeptide receive the polypeptide at a daily dose of 0.1-100 μg / kg for 6 consecutive days. Preferably the polypeptide is in secreted form. Exact details of dosing and formulation-based dosing regimens are provided in Example 23.

Example 25: Methods of Treating Elevated Levels of Polypeptides Antisense technology is used to inhibit production of the polypeptides of the invention. This technique is one example of how to reduce the level of a polypeptide, preferably a secreted form of the polypeptide, that results from various etiologies such as cancer.

For example, in patients diagnosed with abnormally elevated levels of polypeptide, antisense polynucleotides are administered at 0.5, 1.0, 1.5, 2.0, and 3.0 mg.
/ Kg / day intravenously for 21 days. If well tolerated, the procedure is repeated after a 7 day washout period. Antisense polynucleotide formulations are provided in Example 23.

Example 26 Treatment Method Using Gene Therapy One method of gene therapy is to transplant fibroblasts capable of expressing a polypeptide into a patient. Fibroblasts are generally obtained from a subject by skin biopsy. The resulting tissue is placed in tissue culture medium and divided into small pieces. The nodule of tissue is placed on the wet surface of the tissue culture flask and approximately 10 pieces are placed in each flask. The flask is inverted and tightly closed, then left overnight at room temperature. After 24 hours at room temperature, the flask was inverted, the tissue mass was left fixed at the bottom of the flask and fresh medium (eg Ha containing 10% FBS, penicillin and streptomycin) was used.
m F12 medium) is added. The flask is then incubated at 37 ° C for approximately 1 week.

At this point, fresh medium is added and then replaced every few days. After culturing for another two weeks, a monolayer of fibroblasts appears. Trypsinize the monolayer and scale up to a larger flask.

[1136] Moloney murine sarcoma virus is flanked by long terminal repeats of pMV-7 (Ki
rschmeier, P .; T. Et al., DNA, 7: 219-25 (1988)) is digested with EcoRI and HindIII and then treated with calf intestinal phosphatase. The linear vector is fractionated on an agarose gel and purified using glass beads.

[1137] The cDNAs encoding the polypeptides of the present invention were prepared according to
Amplification can be done using PCR primers corresponding to the'and 3'terminal sequences. Preferably, the 5'primer contains an EcoRI site and the 3'primer is Hi.
ndIII site is included. Equal amounts of Moloney murine sarcoma virus linear backbone and amplified EcoRI and HindIII fragments are added together in the presence of T4 DNA ligase. The resulting mixture is maintained under suitable conditions for ligating the two fragments. The ligation mixture is then used to transform bacterial HB101. Then plate it on agar containing kanamycin,
Make sure the vector has the gene of interest inserted correctly.

[1138] The amphotropic pA317 or GP + am12 packaging cells were
Dul with 10% Calf Serum (CS), Penicillin and Streptomycin
Grow to confluent density in tissue culture in becco modified Eagles medium (DMEM). The MSV vector containing the gene is then added to the medium and the packaging cells are transduced with the vector. At this time, the packaging cells produce infectious viral particles containing the gene (here, the packaging cells are referred to as producer cells).

[1139] Fresh medium was added to the transduced producer cells, then medium was added to 10c.
Harvest from m-plate confluent producer cells. The spent medium containing infectious viral particles is filtered through a Millipore filter to remove detached producer cells and then used to infect fibroblasts. Media is removed from the subconfluent plates of fibroblasts and quickly replaced with media from producer cells. This medium is removed and replaced with fresh medium. If the virus titer is high, virtually all fibroblasts will be infected and no selection is required. If the titer is very low, it is necessary to use a retroviral vector with a selectable marker such as neo or his. Once the fibroblasts are efficiently infected, the fibroblasts are analyzed to determine if the protein is being produced.

[1140] The engineered fibroblasts are then transplanted into the host either alone or after being grown to confluence on Cytodex 3 microcarrier beads.

[1141] It will be appreciated that the present invention may be practiced other than as described in detail in the foregoing description and examples. Many modifications and variations of the present invention are possible in light of the above teachings, and are therefore within the scope of the appended claims.

[1142] The entire disclosure of each document cited in the Background, Detailed Description and Examples (including patents, patent applications, journal articles, abstracts, laboratory manuals, books or other disclosures) is cited herein. Are incorporated by reference. In addition, both the hard copy of the enclosed Sequence Listing and the corresponding computer readable form are hereby incorporated by reference in their entireties.

[1143]

[Table 5]

[1144]

[Table 6]

[1145]

[Table 7]

[1146]

[Table 8]

[1147]

[Table 9]

[1148]

[Table 10]

[1149]

[Table 11]

[1150]

[Table 12]

[Sequence list]

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61P 5/00 A61P 5/18 4C086 5/14 7/06 4H045 5/18 9/00 7/06 9 / 02 9/00 11/06 9/02 15/00 11/06 15/08 15/00 15/10 15/08 17/02 15/10 19/02 17/02 25/00 19/02 25/14 25 / 00 25/16 25/14 25/18 25/16 25/28 25/18 29/00 101 25/28 35/00 29/00 101 35/02 35/00 37/00 35/02 37/06 37 / 00 43/00 105 37/06 C07K 14/47 43/00 105 16/18 C07K 14/47 C12N 1/15 16/18 1/19 C12N 1/15 1/21 1/19 C12P 21/02 C 1 / 21 C12Q 1/68 A 5/10 G01N 33/53 D C12P 21/02 C12N 15/00 ZNAA C12Q 1/68 A61K 37/02 G01N 33/53 C12N 5/00 A (31) Priority claim number 60 / 063,100 (32) Priority date 1997 1 October 24 (October 24, 1997) (33) Priority claiming country United States (US) (31) Priority claim number 60 / 063,387 (32) Priority date October 24, 1997 (1997.10) 24. (33) Priority claiming country United States (US) (31) Priority claim number 60/063, 148 (32) Priority date October 24, 1997 (October 24, 1997) (33) Priority right Claiming country United States (US) (31) Priority claim number 60 / 063,386 (32) Priority date October 24, 1997 (October 24, 1997) (33) Priority claiming country United States (US) (31) ) Priority claim number 60 / 062,784 (32) Priority date October 24, 1997 (October 24, 1997) (33) Country of priority claim United States (US) (31) Priority claim number 60/063 , 091 (32) Priority date October 24, 1997 (October 24, 1997) (33) Priority claiming country United States (US) (31) Priority claim number 60 / 063,090 (32) Priority date Heisei October 24, 1997 (October 24, 1997) (33) Priority claim countries United States (US) (31) Priority claim No. 60 / 063,089 (32) Priority date October 24, 1997 (October 24, 1997) (33) Priority claim country United States (US) (31) Priority claim number 60 / 063,092 (32) ) Priority date October 24, 1997 (October 24, 1997) (33) Priority claiming country United States (US) (31) Priority claim number 60 / 063,111 (32) Priority date October 1997 24th (October 24, 1997) (33) Priority claiming country United States (US) (31) Priority claim number 60/063, 101 (32) Priority date October 24, 1997 (October 24th, 1997) ) (33) Priority claiming country United States (US) (31) Priority claiming number 60 / 063,109 (32) Priority date October 24, 1997 (October 24, 1997) (33) Priority claiming country United States (US) (31) Priority claim number 60 / 063,110 (32) Priority date October 24, 1997 (October 24, 1997) (33) Priority claim country United States (US) (31) Priority Claim number 60 / 063,098 (32) Priority date October 24, 1997 (October 24, 1997) ) (33) Priority claiming country United States (US) (31) Priority claiming number 60 / 063,097 (32) Priority date October 24, 1997 (October 24, 1997) (33) Priority claiming country United States (US) (81) Designated countries EP (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE), OA (BF, BJ, CF, CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG), AP (GH, GM, KE, LS, MW, SD, SZ, UG , ZW), EA (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN. , CU, CZ, DE, DK, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IS, JP, KE, G, KP, KR, KZ, LC, LK, LR, LS, LT, L U, LV, MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT, RO, RU, SD, SE , SG, SI, SK, SL, TJ, TM, TR, TT, UA, UG, US, UZ, VN, YU, ZW (72) Inventor Fen, Pin USA Maryland 20878, Gaithersburg, Lerda Court 4 (72) Inventor Rosen, Craig A. United States Maryland 20882, Leightonsville, Rolling Hill Road 22400 (72) Inventor Ruben, Stephen M. United States Maryland 20832, Olney, Heritage Hills Drive 18528 (72) Inventor Ni, Gian United States Maryland 20853, Rockville, Manor Field Road 5502 (72) Inventor Way, In-Fay United States California 94403, San Mateo, Marina Court 1714-Sea (72) Inventor Sopette, Daniel Earl. United States Virginia 22020, Centerville, Stillfield Place 15050 (72) Inventor More, Paul A .. United States Maryland 20874, Germantown, Leather Bark Drive 19005 (72) Inventor Keiu, Hula United States Maryland 21703, Frederick, Sugarbush Circle 520 (72) Inventor Laughlieu, David W .. United States Washington, DC 20015, N. W. , Quesada Street 3142 (72) Inventor Olsen, Henrik S. United States Maryland 29878, Gaithersburg, Kendrick Place No. 24 182 (72) Inventor Brewer, Raleigh A .. United States Minnesota 55119-4321, Saint Paul, Van Dyke Street 410, Apartment 115 (72) Inventor Shi, Young United States Maryland 20878, Gaithersburg, West Side Drive 437, Apartment 102 (72) Inventor Ebner, Rainhard United States Maryland 20878, Gaithersburg, Shelburne Terras Number 316 9906 (72) Inventor Young, Paul United States Maryland 20878, Gaithersburg, Beckwith Street 122 (72) Inventor Green, John Em. United States Maryland 20878, Gaithersburg, Diamond Drive 872 (72) Inventor Florence, Kimberly A .. United States Maryland 20851, Rockville, Atlantic Avenue 12805 (72) Inventor Florence, Charles United States Maryland 20851, Rockville, Atlantic Avenue 12805 (72) Inventor Duane, Dee. Rosanne United States Maryland 20817, Bethesda, Northfield Road 5515 (72) Inventor Janat, Forad United States Rhode Island 02891, Westerly, High Street No. 202 140 (72) Inventor Endless, Gregory A .. United States Maryland 20854, Potomac, Craguet Farm Drive 9729 (72) Inventor Carter, Kennethsee. United States Maryland 20878, North Potomac, Brandy Hall Lane 11601 F-term (reference) 4B024 AA01 AA11 BA44 CA01 DA02 GA11 HA11 4B063 QA01 QA17 QA18 QA19 QQ41 QQ79 QQ96 QR08 QR32 QR42 QR48 QR55 QR62 QS25 QS33 QS34 QX01 4B064 AG01 AG27 CA10 CA19 CC24 DA01 DA13 4B065 AA90X AA93Y AB01 AC15 BA02 CA24 CA25 CA44 CA46 4C084 AA02 AA07 BA01 BA08 BA22 BA23 CA18 CA25 CA35 DC50 NA14 ZB012 ZB022 ZB052 ZB072 4C086 A50 A10 A40 A50A20 A20 AA03 A45 AA01 A15 A02

Claims (23)

[Claims] 1. An isolated nucleic acid molecule, which comprises: (a) a polynucleotide fragment of SEQ ID NO: X, or a polynucleotide fragment of the cDNA sequence contained in ATCC Deposit No. Z that is hybridizable to SEQ ID NO: X. (B) a polynucleotide encoding a polypeptide fragment of SEQ ID NO: or a polypeptide fragment encoded by the cDNA sequence contained in ATCC Deposit No. Z capable of hybridizing to SEQ ID NO: X; (c) SEQ ID NO: Y; Or a polynucleotide encoding a polypeptide domain encoded by a cDNA sequence contained in ATCC Deposit No. Z capable of hybridizing to SEQ ID NO: X; (d) a polypeptide epitope of SEQ ID NO :, or a sequence Hybrida on number X Polynucleotide encoding the polypeptide epitope encoded by the cDNA sequence contained in ATCC Deposit No. Z; (e) a polynucleotide encoding a polypeptide of SEQ ID NO: Y having biological activity, or a sequence CDNA sequence contained in ATCC Deposit No. Z capable of hybridizing to number X; (f) Polynucleotide that is a variant of SEQ ID NO: X; (g) Polynucleotide that is an allelic variant of SEQ ID NO: X; (h) A polynucleotide encoding a species homologue of SEQ ID NO: (i) a polynucleotide capable of hybridizing to any one of the polynucleotides specified in (a) to (h) under stringent conditions, Here, the polynucleotide has a nucleotide sequence consisting of only A residues or T residues. The nucleic acid molecule does not hybridize under stringent conditions, a polynucleotide, comprising a polynucleotide having at least 95% identical to the nucleotide sequence to a sequence selected from the group consisting of isolated nucleic acid molecules. 2. The isolated nucleic acid molecule of claim 1, wherein the polynucleotide fragment comprises a nucleotide sequence encoding a secreted protein. 3. The polynucleotide fragment comprises a sequence identified as SEQ ID NO: Y, or a nucleotide sequence encoding a polypeptide encoded by the cDNA sequence contained in ATCC Deposit No. Z, which is capable of hybridizing to SEQ ID NO: X. 2. The isolated nucleic acid molecule of claim 1, which comprises. 4. The isolated of claim 1, wherein the polynucleotide fragment comprises the entire nucleotide sequence of SEQ ID NO: X, or the cDNA sequence contained in ATCC Deposit No. Z capable of hybridizing to SEQ ID NO: X. Nucleic acid molecule. 5. The isolated nucleic acid molecule of claim 2, wherein the nucleotide sequence comprises consecutive nucleotide deletions from either the C-terminus or the N-terminus. 6. The isolated nucleic acid molecule of claim 3, wherein the nucleotide sequence comprises consecutive nucleotide deletions from either the C-terminus or the N-terminus. 7. A recombinant vector comprising the isolated nucleic acid molecule of claim 1. 8. A method of making a recombinant host cell comprising the isolated nucleic acid molecule of claim 1. 9. A recombinant host cell produced by the method of claim 8. 10. The recombinant host cell of claim 9, which comprises a vector sequence. 11. An isolated polypeptide comprising: (a) a polypeptide fragment of the encoded sequence contained in SEQ ID NO: Y, or ATCC Deposit No. Z; (b) a biological activity. (C) a polypeptide domain of the encoded sequence contained in SEQ ID NO: Y, or ATCC Deposit No. Z; (c) a polypeptide domain of the encoded sequence contained in SEQ ID NO: Y, or ATCC Deposit No. Z; d) a polypeptide epitope of the encoded sequence contained in SEQ ID NO: Y, or ATCC deposit number Z; (e) a secreted form of the encoded sequence contained in SEQ ID NO: Y, or ATCC deposit number Z; ) SEQ ID NO: Y, or the full length protein of the encoded sequence contained in ATCC Deposit No. Z; (g) a variant of SEQ ID NO: Y (h) SEQ ID NO: Y of the allelic variants; or (i) SEQ ID NO: Y of the species homologues, to a sequence selected from the group consisting of at least 95% identical to the amino acid sequence,
Isolated polypeptide. 12. The isolated polypeptide of claim 11, wherein the secreted form or the full-length protein comprises a contiguous amino acid deletion from either the C-terminus or the N-terminus. 13. An isolated antibody that specifically binds to the isolated polypeptide of claim 11. 14. Expressing the isolated polypeptide of claim 11.
Recombinant host cell. 15. A method of producing an isolated polypeptide, comprising the step of: (a) culturing the recombinant host cell of claim 14 under conditions such that the polypeptide is expressed; And (b) recovering the polypeptide. 16. A polypeptide produced by the method of claim 15. 17. A method of preventing, treating or alleviating a medical condition, comprising:
13. A method comprising administering to a mammalian subject a therapeutically effective amount of the polypeptide of claim 11 or the polynucleotide of claim 1. 18. A method for diagnosing a pathological condition or susceptibility to a pathological condition in a subject, which comprises the step of: (a) determining the presence or absence of a mutation in the polynucleotide of claim 1. And (b) diagnosing a pathological condition, or susceptibility to a pathological condition, based on the presence or absence of the mutation. 19. A method of diagnosing a pathological condition or susceptibility to a pathological condition in a subject, comprising: (a) the presence or amount of expression of the polypeptide of claim 11 in a biological sample. And (b) diagnosing a pathological condition, or susceptibility to a pathological condition, based on the presence or amount of expression of the polypeptide. 20. A method of identifying a binding partner for the polypeptide of claim 11, comprising: (a) contacting the polypeptide of claim 11 with a binding partner;
And (b) determining whether the binding partner results in activity of the polypeptide. 21. A gene corresponding to the cDNA sequence of SEQ ID NO: Y. 22. A method of identifying activity in a biological assay, comprising:
Wherein the method comprises: (a) expressing SEQ ID NO: X in cells; (b) isolating the supernatant; (c) detecting activity in a biological assay; and (d) ) Identifying a protein in the supernatant that has the activity. 23. A product produced by the method of claim 20.