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Melatonin receptor 1B

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MTNR1B
Identifiers
AliasesMTNR1B, FGQTL2, MEL-1B-R, MT2, Melatonin receptor 1B
External IDsOMIM: 600804; MGI: 2181726; HomoloGene: 4350; GeneCards: MTNR1B; OMA:MTNR1B - orthologs
Orthologs
SpeciesHumanMouse
Entrez

4544

244701

Ensembl

ENSG00000134640

ENSMUSG00000050901

UniProt

P49286

Q8CIQ6
Q3SXF8

RefSeq (mRNA)

NM_005959

NM_145712

RefSeq (protein)

NP_005950

NP_663758

Location (UCSC)Chr 11: 92.97 – 92.99 MbChr 9: 15.74 – 15.79 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Melatonin receptor 1B, also known as MTNR1B, is a protein that in humans is encoded by the MTNR1B gene.[5][6]

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.[5] Besides the brain and retina this receptor is expressed on the bone forming cells where it regulates their function in depositing bone.[7]

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.[8][9][10] MTNR1B mRNA is expressed in human islets, and immunocytochemistry confirms that it is primarily localized in beta cells in islets.[9]

Ligands

The following MT2R ligands have selectivity over MT1R:

  • Compound 3d: antagonist with sub-nM affinity[11]
  • Compound 18f: antagonist and compound 18g partial agonist: sub-nM affinity, >100-fold selectivity over MT1[12]
  • Compound 14: antagonist[13]
  • Compound 13: agonist[14]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000134640 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000050901 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Entrez Gene: MTNR1B melatonin receptor 1B".
  6. ^ Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF (Sep 1995). "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. Bibcode:1995PNAS...92.8734R. doi:10.1073/pnas.92.19.8734. PMC 41041. PMID 7568007.
  7. ^ Sharan K, Lewis K, Furukawa T, Yadav VK (2006). "Regulation of bone mass through pineal-derived melatonin-MT2 pathway". J Pineal Res. 79A (2): 263–270. doi:10.1111/jpi.12423. PMC 5575491. PMID 28512916.
  8. ^ "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.
  9. ^ a b Prokopenko I, Langenberg C, Florez JC, Saxena R, Soranzo N, Thorleifsson G, et al. (Jan 2009). "Variants in MTNR1B influence fasting glucose levels". Nature Genetics. 41 (1): 77–81. doi:10.1038/ng.290. PMC 2682768. PMID 19060907.; Lyssenko V, Nagorny CL, Erdos MR, Wierup N, Jonsson A, Spégel P, et al. (Jan 2009). "Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion". Nature Genetics. 41 (1): 82–88. doi:10.1038/ng.288. PMC 3725650. PMID 19060908.; Bouatia-Naji N, Bonnefond A, Cavalcanti-Proença C, Sparsø T, Holmkvist J, Marchand M, et al. (Jan 2009). "A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk". Nature Genetics. 41 (1): 89–94. doi:10.1038/ng.277. PMID 19060909. S2CID 205347673.
  10. ^ Staiger H, Machicao F, Schäfer SA, Kirchhoff K, Kantartzis K, Guthoff M, Silbernagel G, Stefan N, Häring HU, Fritsche A (2008). Maedler K (ed.). "Polymorphisms within the novel type 2 diabetes risk locus MTNR1B determine beta-cell function". PLOS ONE. 3 (12): e3962. Bibcode:2008PLoSO...3.3962S. doi:10.1371/journal.pone.0003962. PMC 2597741. PMID 19088850.
  11. ^ Rivara S, Lodola A, Mor M, Bedini A, Spadoni G, Lucini V, Pannacci M, Fraschini F, Scaglione F, Sanchez RO, Gobbi G, Tarzia G (Dec 2007). "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. doi:10.1021/jm700957j. hdl:11576/1886829. PMID 18052314.
  12. ^ Bedini A, Spadoni G, Gatti G, Lucarini S, Tarzia G, Rivara S, Lorenzi S, Lodola A, Mor M, Lucini V, Pannacci M, Scaglione F (Dec 2006). "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. doi:10.1021/jm060850a. PMID 17149869.
  13. ^ Yous S, Durieux-Poissonnier S, Lipka-Belloli E, Guelzim H, Bochu C, Audinot V, Boutin JA, Delagrange P, Bennejean C, Renard P, Lesieur D (Mar 2003). "Design and synthesis of 3-phenyl tetrahydronaphthalenic derivatives as new selective MT2 melatoninergic ligands". Bioorganic & Medicinal Chemistry. 11 (5): 753–59. doi:10.1016/S0968-0896(02)00473-X. PMID 12538005.
  14. ^ Mattson RJ, Catt JD, Keavy D, Sloan CP, Epperson J, Gao Q, Hodges DB, Iben L, Mahle CD, Ryan E, Yocca FD (Mar 2003). "Indanyl piperazines as melatonergic MT2 selective agents". Bioorganic & Medicinal Chemistry Letters. 13 (6): 1199–202. doi:10.1016/S0960-894X(03)00090-8. PMID 12643943.

Further reading

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

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

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