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Melatonin receptor 1B

From Wikipedia, the free encyclopedia
Protein found in humans
MTNR1B
Identifiers
AliasesMTNR1B, FGQTL2, MEL-1B-R, MT2, Melatonin receptor 1B
External IDsOMIM:600804;MGI:2181726;HomoloGene:4350;GeneCards:MTNR1B;OMA:MTNR1B - orthologs
Gene location (Human)
Chromosome 11 (human)
Chr.Chromosome 11 (human)[1]
Chromosome 11 (human)
Genomic location for MTNR1B
Genomic location for MTNR1B
Band11q14.3Start92,969,651bp[1]
End92,985,066bp[1]
Gene location (Mouse)
Chromosome 9 (mouse)
Chr.Chromosome 9 (mouse)[2]
Chromosome 9 (mouse)
Genomic location for MTNR1B
Genomic location for MTNR1B
Band9|9 A2Start15,735,824bp[2]
End15,785,852bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • gonad

  • islet of Langerhans

  • nucleus accumbens

  • placenta

  • caudate nucleus

  • renal cortex

  • endometrium

  • left testis

  • right testis

  • hypothalamus
Top expressed in
  • lip
More reference expression data
BioGPS
More reference expression data
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo /QuickGO
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 asMTNR1B, is aprotein that in humans is encoded by theMTNR1Bgene.[5][6]

Function

[edit]

This gene encodes the MT2protein, one of two high-affinity forms of a receptor formelatonin, the primary hormone secreted by thepineal gland. This gene product is anintegral membrane protein that is aG-protein coupled, 7-transmembrane receptor. It is found primarily in the retina andbrain; however, this detection requiresRT-PCR. It is thought to participate inlight-dependent functions in theretina 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

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Several studies have identified MTNR1B receptor mutations that are associated with increased averageblood sugar level and around a 20 percent elevated risk of developingtype 2 diabetes.[8][9][10] MTNR1B mRNA is expressed in human islets, andimmunocytochemistry confirms that it is primarily localized inbeta cells inislets.[9]

Ligands

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The following MT2R ligands have selectivity over MT1R:

  • Compound3d:antagonist with sub-nM affinity[11]
  • Compound18f: antagonist and compound18g partialagonist: sub-nM affinity, >100-fold selectivity over MT1[12]
  • Compound14: antagonist[13]
  • Compound13: agonist[14]

See also

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References

[edit]
  1. ^abcGRCh38: Ensembl release 89: ENSG00000134640Ensembl, May 2017
  2. ^abcGRCm38: Ensembl release 89: ENSMUSG00000050901Ensembl, 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. ^ab"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. Retrieved2009-01-18.;"Body Clock Linked To Diabetes And High Blood Sugar In New Genome-wide Study". ScienceDaily. 2008-12-08. Retrieved2009-01-18.;"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. Retrieved2009-01-18.
  9. ^abProkopenko 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

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External links

[edit]
  • "Melatonin Receptors: MT2".IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived fromthe original on 2016-03-03. Retrieved2008-12-05.

This article incorporates text from theUnited States National Library of Medicine, which is in thepublic domain.

Neurotransmitter
Adrenergic
Purinergic
Serotonin
Other
Metabolites and
signaling molecules
Eicosanoid
Other
Peptide
Neuropeptide
Other
Miscellaneous
Taste, bitter
Orphan
Other
Adhesion
Orphan
Other
Taste, sweet
Other
Frizzled
Smoothened
MT1Tooltip Melatonin receptor 1
MT2Tooltip Melatonin receptor 2
Unsorted
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