Melatoninski receptor 1B

Melatoninski receptor 1B
Identifikatori
Simboli	MTNR1B; FGQTL2; MEL-1B-R; MT2
Vanjski ID	OMIM: 600804 MGI: 2181726 HomoloGene: 4350 IUPHAR: MT2 GeneCards: MTNR1B Gene
Ontologija gena
Molekularna funkcija	• aktivnost prenosa signala; • receptorska aktivnost; • aktivnost G-protein spregnutog receptor; • aktivnost melatoninskog receptora;
Celularna komponenta	• ćelijska membrana; • integralno sa ćelijskom membranom;
Biološki proces	• G-proteinska signalizacija, spregnuta sa cikličnim nukleotidnim sekundarnim glasnikom; • sinaptička transmisija; • glukozna homeostaza; • regulacija sekrecije insulina;
Pregled RNK izražavanja
	podaci
Ortolozi

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Melatoninski receptor 1B (MTNR1B) je protein koji je kod ljudi kodiran MTNR1B genom.^[1]^[2]

Funkcija

MT₂ protein je jedan od dve forme receptora sa visokim afinitetom za melatonin, primarni hormon epifize. On je integralni membranski protein koji je G protein spregnuti receptor, 7-transmembranski receptor. On je prisutan prvenstveno u retini i mozgu. Smatra se da on učestvuje u od svetla zavisnim funkcijama u retini i da posreduje neurobiološke efekte melatonina.^[1]

Klinički značaj

Nekoliko studija je identifikovalo da su mutacije MTNR1B receptora vezane za povišeni prosečne nivoe krvnog šećera, i za oko 20 procenata povišen rizik razvoja tip 2 dijabetesa.^[3]^[4]^[5] MTNR1B iRNK je izražena u ljudskim Langerhansovim ostrvcima, i imunocitohemija potvrđuje da je prvenstveno lociran u beta ćelijama.^[4]

MT2R ligandi

Sledeći MT2R ligandi su selektivni u odnosu na MT1R:

Jedinjenje 3d: antagonist sa sub-nM afinitetom^[6]
Jedinjenje 18f: antagonist i jedinjenje 18g parcijalni agonist: sub-nM afinitet, >100-puta selektivniji u odnosu na MT1^[7]
Jedinjenje 14: antagonist^[8]
Jedinjenje 13: agonist^[9]

Reference

↑ ^1,0 ^1,1 „Entrez Gene: MTNR1B melatonin receptor 1B”.
↑ Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF (September 1995). „Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor”. Proc. Natl. Acad. Sci. U.S.A. 92 (19): 8734–8. DOI:10.1073/pnas.92.19.8734. PMC 41041. PMID 7568007.
↑ „Gene That Regulates Glucose Levels And Increases Risk For Diabetes Identified”. ScienceDaily. 28. 06. 2008.. Pristupljeno 18. 01. 2009. ; „Body Clock Linked To Diabetes And High Blood Sugar In New Genome-wide Study”. ScienceDaily. 08. 12. 2008.. Pristupljeno 18. 01. 2009. ; „Is There A Relationship Between Sleep-wake Rhythm And Diabetes? A New Gene Variant Influences Fasting Glucose Levels Via The Melatonin Metabolism”. ScienceDaily. 16. 01. 2009.. Pristupljeno 18. 01. 2009.
↑ ^4,0 ^4,1 Prokopenko I, Langenberg C, Florez JC, et al. (January 2009). „Variants in MTNR1B influence fasting glucose levels”. Nat. Genet. 41 (1): 77–81. DOI:10.1038/ng.290. PMC 2682768. PMID 19060907. ; Lyssenko V, Nagorny CL, Erdos MR, et al. (January 2009). „Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion”. Nat. Genet. 41 (1): 82–8. DOI:10.1038/ng.288. PMID 19060908. ; Bouatia-Naji N, Bonnefond A, Cavalcanti-Proença C, et al. (January 2009). „A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk”. Nat. Genet. 41 (1): 89–94. DOI:10.1038/ng.277. PMID 19060909.
↑ Staiger H, Machicao F, Schäfer SA, et al. (2008). Maedler, Kathrin. ur. „Polymorphisms within the novel type 2 diabetes risk locus MTNR1B determine beta-cell function”. PLoS ONE 3 (12): e3962. DOI:10.1371/journal.pone.0003962. PMC 2597741. PMID 19088850.
↑ Rivara S, Lodola A, Mor M, et al. (2007). „N-(substituted-anilinoethyl)amides: design, synthesis, and pharmacological characterization of a new class of melatonin receptor ligands”. J. Med. Chem. 50 (26): 6618–26. DOI:10.1021/jm700957j. PMID 18052314.
↑ Bedini A, Spadoni G, Gatti G, et al. (2006). „Design and synthesis of N-(3,3-diphenylpropenyl)alkanamides as a novel class of high-affinity MT2-selective melatonin receptor ligands”. J. Med. Chem. 49 (25): 7393–403. DOI:10.1021/jm060850a. PMID 17149869.
↑ Yous S, Durieux-Poissonnier S, Lipka-Belloli E, et al. (2003). „Design and synthesis of 3-phenyl tetrahydronaphthalenic derivatives as new selective MT2 melatoninergic ligands”. Bioorg. Med. Chem. 11 (5): 753–9. DOI:10.1016/S0968-0896(02)00473-X. PMID 12538005.
↑ Mattson RJ, Catt JD, Keavy D, et al. (2003). „Indanyl piperazines as melatonergic MT2 selective agents”. Bioorg. Med. Chem. Lett. 13 (6): 1199–202. DOI:10.1016/S0960-894X(03)00090-8. PMID 12643943.

Literatura

Brzezinski A; Brzezinski, Amnon (1997). „Melatonin in humans”. N. Engl. J. Med. 336 (3): 186–95. DOI:10.1056/NEJM199701163360306. PMID 8988899.
Reppert SM, Godson C, Mahle CD, et al. (1995). „Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor”. Proc. Natl. Acad. Sci. U.S.A. 92 (19): 8734–8. DOI:10.1073/pnas.92.19.8734. PMC 41041. PMID 7568007.
Reppert SM, Weaver DR, Ebisawa T, et al. (1996). „Cloning of a melatonin-related receptor from human pituitary”. FEBS Lett. 386 (2–3): 219–24. DOI:10.1016/0014-5793(96)00437-1. PMID 8647286.
Niles LP, Wang J, Shen L, et al. (2000). „Melatonin receptor mRNA expression in human granulosa cells”. Mol. Cell. Endocrinol. 156 (1–2): 107–10. DOI:10.1016/S0303-7207(99)00135-5. PMID 10612428.
Ebisawa T, Uchiyama M, Kajimura N, et al. (2000). „Genetic polymorphisms of human melatonin 1b receptor gene in circadian rhythm sleep disorders and controls”. Neurosci. Lett. 280 (1): 29–32. DOI:10.1016/S0304-3940(99)00981-7. PMID 10696804.
Roy D, Angelini NL, Fujieda H, et al. (2001). „Cyclical regulation of GnRH gene expression in GT1-7 GnRH-secreting neurons by melatonin”. Endocrinology 142 (11): 4711–20. DOI:10.1210/en.142.11.4711. PMID 11606436.
Ayoub MA, Couturier C, Lucas-Meunier E, et al. (2002). „Monitoring of ligand-independent dimerization and ligand-induced conformational changes of melatonin receptors in living cells by bioluminescence resonance energy transfer”. J. Biol. Chem. 277 (24): 21522–8. DOI:10.1074/jbc.M200729200. PMID 11940583.
Yuan L, Collins AR, Dai J, et al. (2003). „MT(1) melatonin receptor overexpression enhances the growth suppressive effect of melatonin in human breast cancer cells”. Mol. Cell. Endocrinol. 192 (1–2): 147–56. DOI:10.1016/S0303-7207(02)00029-1. PMID 12088876.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). „Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences”. Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. DOI:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Slominski A, Pisarchik A, Zbytek B, et al. (2003). „Functional activity of serotoninergic and melatoninergic systems expressed in the skin”. J. Cell. Physiol. 196 (1): 144–53. DOI:10.1002/jcp.10287. PMID 12767050.
Ayoub MA, Levoye A, Delagrange P, Jockers R (2004). „Preferential formation of MT1/MT2 melatonin receptor heterodimers with distinct ligand interaction properties compared with MT2 homodimers”. Mol. Pharmacol. 66 (2): 312–21. DOI:10.1124/mol.104.000398. PMID 15266022.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). „The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)”. Genome Res. 14 (10B): 2121–7. DOI:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Mazna P, Berka K, Jelinkova I, et al. (2005). „Ligand binding to the human MT2 melatonin receptor: the role of residues in transmembrane domains 3, 6, and 7”. Biochem. Biophys. Res. Commun. 332 (3): 726–34. DOI:10.1016/j.bbrc.2005.05.017. PMID 15913560.
Ha E, Choe BK, Jung KH, et al. (2005). „Positive relationship between melatonin receptor type 1B polymorphism and rheumatoid factor in rheumatoid arthritis patients in the Korean population”. J. Pineal Res. 39 (2): 201–5. DOI:10.1111/j.1600-079X.2005.00237.x. PMID 16098099.
Savaskan E, Jockers R, Ayoub M, et al. (2007). „The MT2 melatonin receptor subtype is present in human retina and decreases in Alzheimer's disease”. Current Alzheimer research 4 (1): 47–51. DOI:10.2174/156720507779939823. PMID 17316165.
Suzuki S, Masui Y, Ohnuki M, et al. (2007). „Induction of metallothionein synthesis by cilostazol in mice and in human cultured neuronal cell lines”. Biol. Pharm. Bull. 30 (4): 791–4. DOI:10.1248/bpb.30.791. PMID 17409522.
Qiu XS, Tang NL, Yeung HY, et al. (2007). „Melatonin receptor 1B (MTNR1B) gene polymorphism is associated with the occurrence of adolescent idiopathic scoliosis”. Spine 32 (16): 1748–53. DOI:10.1097/BRS.0b013e3180b9f0ff. PMID 17632395.

Spoljašnje veze

„Melatonin Receptors: MT₂”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano iz originala na datum 2016-03-03.

Povezano

Melatoninski receptor

[entrez-1] 1,0 ^1,1 „Entrez Gene: MTNR1B melatonin receptor 1B”.

[pmid7568007-2] Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF (September 1995). „Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor”. Proc. Natl. Acad. Sci. U.S.A. 92 (19): 8734–8. DOI:10.1073/pnas.92.19.8734. PMC 41041. PMID 7568007.

[SN-3] „Gene That Regulates Glucose Levels And Increases Risk For Diabetes Identified”. ScienceDaily. 28. 06. 2008.. Pristupljeno 18. 01. 2009. ; „Body Clock Linked To Diabetes And High Blood Sugar In New Genome-wide Study”. ScienceDaily. 08. 12. 2008.. Pristupljeno 18. 01. 2009. ; „Is There A Relationship Between Sleep-wake Rhythm And Diabetes? A New Gene Variant Influences Fasting Glucose Levels Via The Melatonin Metabolism”. ScienceDaily. 16. 01. 2009.. Pristupljeno 18. 01. 2009.

[Nat_Genet_2009-4] 4,0 ^4,1 Prokopenko I, Langenberg C, Florez JC, et al. (January 2009). „Variants in MTNR1B influence fasting glucose levels”. Nat. Genet. 41 (1): 77–81. DOI:10.1038/ng.290. PMC 2682768. PMID 19060907. ; Lyssenko V, Nagorny CL, Erdos MR, et al. (January 2009). „Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion”. Nat. Genet. 41 (1): 82–8. DOI:10.1038/ng.288. PMID 19060908. ; Bouatia-Naji N, Bonnefond A, Cavalcanti-Proença C, et al. (January 2009). „A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk”. Nat. Genet. 41 (1): 89–94. DOI:10.1038/ng.277. PMID 19060909.

[pmid19088850-5] Staiger H, Machicao F, Schäfer SA, et al. (2008). Maedler, Kathrin. ur. „Polymorphisms within the novel type 2 diabetes risk locus MTNR1B determine beta-cell function”. PLoS ONE 3 (12): e3962. DOI:10.1371/journal.pone.0003962. PMC 2597741. PMID 19088850.

[6] Rivara S, Lodola A, Mor M, et al. (2007). „N-(substituted-anilinoethyl)amides: design, synthesis, and pharmacological characterization of a new class of melatonin receptor ligands”. J. Med. Chem. 50 (26): 6618–26. DOI:10.1021/jm700957j. PMID 18052314.

[7] Bedini A, Spadoni G, Gatti G, et al. (2006). „Design and synthesis of N-(3,3-diphenylpropenyl)alkanamides as a novel class of high-affinity MT2-selective melatonin receptor ligands”. J. Med. Chem. 49 (25): 7393–403. DOI:10.1021/jm060850a. PMID 17149869.

[8] Yous S, Durieux-Poissonnier S, Lipka-Belloli E, et al. (2003). „Design and synthesis of 3-phenyl tetrahydronaphthalenic derivatives as new selective MT2 melatoninergic ligands”. Bioorg. Med. Chem. 11 (5): 753–9. DOI:10.1016/S0968-0896(02)00473-X. PMID 12538005.

[9] Mattson RJ, Catt JD, Keavy D, et al. (2003). „Indanyl piperazines as melatonergic MT2 selective agents”. Bioorg. Med. Chem. Lett. 13 (6): 1199–202. DOI:10.1016/S0960-894X(03)00090-8. PMID 12643943.

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