Melatonin receptor 1B

Melatonin receptor 1B
Identifiers
Symbols	MTNR1B; FGQTL2; MEL-1B-R; MT2
External IDs	OMIM: 600804 MGI: 2181726 HomoloGene: 4350 GeneCards: MTNR1B Gene
Gene Ontology Molecular function • receptor activity • G-protein coupled receptor activity • melatonin receptor activity Cellular component • plasma membrane • plasma membrane • integral to plasma membrane Biological process • G-protein signaling, coupled to cyclic nucleotide second messenger • synaptic transmission • glucose homeostasis • regulation of insulin secretion Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4544	244701
Ensembl	ENSG00000134640	ENSMUSG00000050901
UniProt	P49286	P70329
RefSeq (mRNA)	NM_005959	NM_145712.2
RefSeq (protein)	NP_005950	NP_663758.2
Location (UCSC)	Chr 11: 92.7 – 92.72 Mb	Chr 9: 15.67 – 15.68 Mb
PubMed search	[1]	[2]

Melatonin receptor 1B, also known as MTNR1B, is a protein that in humans is encoded by the MTNR1B gene.^[1][2]

Function

This gene encodes the MT₂ protein, one of two high-affinity forms of a receptor for melatonin, the primary hormone secreted by the pineal gland. This gene product is an integral membrane protein that is a G-protein coupled, 7-transmembrane receptor. It is found primarily in the retina and brain; however, this detection requires RT-PCR. It is thought to participate in light-dependent functions in the retina and may be involved in the neurobiological effects of melatonin.^[1]

Clinical significance

Several studies have identified MTNR1B receptor mutations that are associated with increased average blood sugar level and around a 20 percent elevated risk of developing type 2 diabetes.^[3][4][5] MTNR1B mRNA is expressed in human islets, and immunocytochemistry confirms that it is primarily localized in beta cells in islets.^[4]

MT2R Ligands

The following MT2R ligands have selectivity over MT1R:

• Compound 3d: antagonist with sub-nM affinity^[6]
• Compound 18f: antagonist and compound 18g partial agonist: sub-nM affinity, >100-fold selectivity over MT1^[7]
• Compound 14: antagonist^[8]
• Compound 13: agonist^[9]

See also

• Melatonin receptor
• Discovery and development of melatonin receptor agonists

References

1. ^ ^{a b} "Entrez Gene: MTNR1B melatonin receptor 1B". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4544. 
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. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=7568007. 
3. ^ "Gene That Regulates Glucose Levels And Increases Risk For Diabetes Identified". ScienceDaily. 2008-06-28. http://www.sciencedaily.com/releases/2008/06/080609085957.htm. Retrieved 2009-01-18. ; "Body Clock Linked To Diabetes And High Blood Sugar In New Genome-wide Study". ScienceDaily. 2008-12-08. http://www.sciencedaily.com/releases/2008/12/081207133817.htm. Retrieved 2009-01-18. ; "Is There A Relationship Between Sleep-wake Rhythm And Diabetes? A New Gene Variant Influences Fasting Glucose Levels Via The Melatonin Metabolism". ScienceDaily. 2009-01-16. http://www.sciencedaily.com/releases/2009/01/090116073601.htm. Retrieved 2009-01-18. 
4. ^ ^{a b} 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2682768. ; 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. 
5. ^ Staiger H, Machicao F, Schäfer SA, et al. (2008). Maedler, Kathrin. ed. "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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2597741. 
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. http://linkinghub.elsevier.com/retrieve/pii/S096808960200473X. 
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. http://linkinghub.elsevier.com/retrieve/pii/S0960894X03000908. 

External links

• "Melatonin Receptors: MT₂". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2361. 

Further reading

• 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=41041. 
• 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928. 
• 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. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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