Melatonin receptor 1B

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Melatonin receptor 1B
Identifiers
Symbols MTNR1B ; FGQTL2; MEL-1B-R; MT2
External IDs OMIM600804 MGI2181726 HomoloGene4350 IUPHAR: MT2 ChEMBL: 1946 GeneCards: MTNR1B Gene
RNA expression pattern
PBB GE MTNR1B 208516 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4544 244701
Ensembl ENSG00000134640 ENSMUSG00000050901
UniProt P49286 Q3SXF8
RefSeq (mRNA) NM_005959 NM_145712
RefSeq (protein) NP_005950 NP_663758
Location (UCSC) Chr 11:
92.7 – 92.72 Mb
Chr 9:
15.86 – 15.87 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[edit]

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[edit]

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[edit]

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[edit]

References[edit]

  1. ^ a b "Entrez Gene: MTNR1B melatonin receptor 1B". 
  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. 
  3. ^ "Gene That Regulates Glucose Levels And Increases Risk For Diabetes Identified". ScienceDaily. 2008-06-28. Retrieved 2009-01-18. ; "Body Clock Linked To Diabetes And High Blood Sugar In New Genome-wide Study". ScienceDaily. 2008-12-08. 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. 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. ; 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). "Polymorphisms within the novel type 2 diabetes risk locus MTNR1B determine beta-cell function". In Maedler, Kathrin. 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. 

External links[edit]

  • "Melatonin Receptors: MT2". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. 

Further reading[edit]

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