Biology:Melatonin receptor 1B
From HandWiki
Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
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] Besides the brain and retina this receptor is expressed on the bone forming cells where it regulates their function in depositing bone.[3]
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.[4][5][6] MTNR1B mRNA is expressed in human islets, and immunocytochemistry confirms that it is primarily localized in beta cells in islets.[5]
Ligands
The following MT2R ligands have selectivity over MT1R:
- Compound 3d: antagonist with sub-nM affinity[7]
- Compound 18f: antagonist and compound 18g partial agonist: sub-nM affinity, >100-fold selectivity over MT1[8]
- Compound 14: antagonist[9]
- Compound 13: agonist[10]
See also
- Melatonin receptor
- Discovery and development of melatonin receptor agonists
References
- ↑ 1.0 1.1 "Entrez Gene: MTNR1B melatonin receptor 1B". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4544.
- ↑ "Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor". Proceedings of the National Academy of Sciences of the United States of America 92 (19): 8734–38. Sep 1995. doi:10.1073/pnas.92.19.8734. PMID 7568007. Bibcode: 1995PNAS...92.8734R.
- ↑ "Regulation of bone mass through pineal-derived melatonin-MT2 pathway". J Pineal Res 79A (2): 263–270. 2006. doi:10.1111/jpi.12423. PMID 28512916.
- ↑ "Gene That Regulates Glucose Levels And Increases Risk For Diabetes Identified". ScienceDaily. 2008-06-28. https://www.sciencedaily.com/releases/2008/06/080609085957.htm.; "Body Clock Linked To Diabetes And High Blood Sugar In New Genome-wide Study". ScienceDaily. 2008-12-08. https://www.sciencedaily.com/releases/2008/12/081207133817.htm.; "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. https://www.sciencedaily.com/releases/2009/01/090116073601.htm.
- ↑ 5.0 5.1 "Variants in MTNR1B influence fasting glucose levels". Nature Genetics 41 (1): 77–81. Jan 2009. doi:10.1038/ng.290. PMID 19060907.; "Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion". Nature Genetics 41 (1): 82–88. Jan 2009. doi:10.1038/ng.288. PMID 19060908.; "A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk". Nature Genetics 41 (1): 89–94. Jan 2009. doi:10.1038/ng.277. PMID 19060909. https://lirias.kuleuven.be/handle/123456789/242744.
- ↑ Maedler, Kathrin, ed (2008). "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. PMID 19088850. Bibcode: 2008PLoSO...3.3962S.
- ↑ "N-(substituted-anilinoethyl)amides: design, synthesis, and pharmacological characterization of a new class of melatonin receptor ligands". Journal of Medicinal Chemistry 50 (26): 6618–26. Dec 2007. doi:10.1021/jm700957j. PMID 18052314.
- ↑ "Design and synthesis of N-(3,3-diphenylpropenyl)alkanamides as a novel class of high-affinity MT2-selective melatonin receptor ligands". Journal of Medicinal Chemistry 49 (25): 7393–403. Dec 2006. doi:10.1021/jm060850a. PMID 17149869.
- ↑ "Design and synthesis of 3-phenyl tetrahydronaphthalenic derivatives as new selective MT2 melatoninergic ligands". Bioorganic & Medicinal Chemistry 11 (5): 753–59. Mar 2003. doi:10.1016/S0968-0896(02)00473-X. PMID 12538005.
- ↑ "Indanyl piperazines as melatonergic MT2 selective agents". Bioorganic & Medicinal Chemistry Letters 13 (6): 1199–202. Mar 2003. doi:10.1016/S0960-894X(03)00090-8. PMID 12643943.
Further reading
- "Melatonin in humans". The New England Journal of Medicine 336 (3): 186–95. Jan 1997. doi:10.1056/NEJM199701163360306. PMID 8988899.
- "Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor". Proceedings of the National Academy of Sciences of the United States of America 92 (19): 8734–8. Sep 1995. doi:10.1073/pnas.92.19.8734. PMID 7568007. Bibcode: 1995PNAS...92.8734R.
- "Cloning of a melatonin-related receptor from human pituitary". FEBS Letters 386 (2–3): 219–24. May 1996. doi:10.1016/0014-5793(96)00437-1. PMID 8647286.
- "Melatonin receptor mRNA expression in human granulosa cells". Molecular and Cellular Endocrinology 156 (1–2): 107–10. Oct 1999. doi:10.1016/S0303-7207(99)00135-5. PMID 10612428.
- "Genetic polymorphisms of human melatonin 1b receptor gene in circadian rhythm sleep disorders and controls". Neuroscience Letters 280 (1): 29–32. Feb 2000. doi:10.1016/S0304-3940(99)00981-7. PMID 10696804.
- "Cyclical regulation of GnRH gene expression in GT1-7 GnRH-secreting neurons by melatonin". Endocrinology 142 (11): 4711–20. Nov 2001. doi:10.1210/endo.142.11.8464. PMID 11606436.
- "Monitoring of ligand-independent dimerization and ligand-induced conformational changes of melatonin receptors in living cells by bioluminescence resonance energy transfer". The Journal of Biological Chemistry 277 (24): 21522–8. Jun 2002. doi:10.1074/jbc.M200729200. PMID 11940583.
- "MT(1) melatonin receptor overexpression enhances the growth suppressive effect of melatonin in human breast cancer cells". Molecular and Cellular Endocrinology 192 (1–2): 147–56. Jun 2002. doi:10.1016/S0303-7207(02)00029-1. PMID 12088876.
- "Functional activity of serotoninergic and melatoninergic systems expressed in the skin". Journal of Cellular Physiology 196 (1): 144–53. Jul 2003. doi:10.1002/jcp.10287. PMID 12767050.
- "Preferential formation of MT1/MT2 melatonin receptor heterodimers with distinct ligand interaction properties compared with MT2 homodimers". Molecular Pharmacology 66 (2): 312–21. Aug 2004. doi:10.1124/mol.104.000398. PMID 15266022.
- "Ligand binding to the human MT2 melatonin receptor: the role of residues in transmembrane domains 3, 6, and 7". Biochemical and Biophysical Research Communications 332 (3): 726–34. Jul 2005. doi:10.1016/j.bbrc.2005.05.017. PMID 15913560.
- "Positive relationship between melatonin receptor type 1B polymorphism and rheumatoid factor in rheumatoid arthritis patients in the Korean population". Journal of Pineal Research 39 (2): 201–5. Sep 2005. doi:10.1111/j.1600-079X.2005.00237.x. PMID 16098099.
- "The MT2 melatonin receptor subtype is present in human retina and decreases in Alzheimer's disease". Current Alzheimer Research 4 (1): 47–51. Feb 2007. doi:10.2174/156720507779939823. PMID 17316165.
- "Induction of metallothionein synthesis by cilostazol in mice and in human cultured neuronal cell lines". Biological & Pharmaceutical Bulletin 30 (4): 791–4. Apr 2007. doi:10.1248/bpb.30.791. PMID 17409522.
- "Melatonin receptor 1B (MTNR1B) gene polymorphism is associated with the occurrence of adolescent idiopathic scoliosis". Spine 32 (16): 1748–53. Jul 2007. doi:10.1097/BRS.0b013e3180b9f0ff. PMID 17632395.
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.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
 |  |
