Melanocyte-stimulating hormone receptor

Details

Name
Melanocyte-stimulating hormone receptor
Synonyms
  • MC1-R
  • Melanocortin receptor 1
  • MSH-R
  • MSHR
Gene Name
MC1R
Organism
Humans
Amino acid sequence
>lcl|BSEQ0011751|Melanocyte-stimulating hormone receptor
MAVQGSQRRLLGSLNSTPTAIPQLGLAANQTGARCLEVSISDGLFLSLGLVSLVENALVV
ATIAKNRNLHSPMYCFICCLALSDLLVSGSNVLETAVILLLEAGALVARAAVLQQLDNVI
DVITCSSMLSSLCFLGAIAVDRYISIFYALRYHSIVTLPRARRAVAAIWVASVVFSTLFI
AYYDHVAVLLCLVVFFLAMLVLMAVLYVHMLARACQHAQGIARLHKRQRPVHQGFGLKGA
VTLTILLGIFFLCWGPFFLHLTLIVLCPEHPTCGCIFKNFNLFLALIICNAIIDPLIYAF
HSQELRRTLKEVLTCSW
Number of residues
317
Molecular Weight
34705.04
Theoretical pI
8.44
GO Classification
Functions
G-protein coupled peptide receptor activity / hormone binding / melanocortin receptor activity / melanocyte-stimulating hormone receptor activity / ubiquitin protein ligase binding
Processes
G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / intracellular signal transduction / melanin biosynthetic process / multicellular organismal development / negative regulation of tumor necrosis factor production / pigmentation / positive regulation of cAMP biosynthetic process / positive regulation of feeding behavior / positive regulation of protein kinase A signaling / positive regulation of protein kinase B signaling / positive regulation of protein kinase C signaling / positive regulation of transcription from RNA polymerase II promoter / sensory perception of pain / UV protection / UV-damage excision repair
Components
integral component of plasma membrane / intracellular / plasma membrane
General Function
Ubiquitin protein ligase binding
Specific Function
Receptor for MSH (alpha, beta and gamma) and ACTH. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.
Pfam Domain Function
Transmembrane Regions
38-63 73-93 119-140 164-183 192-211 241-266 280-300
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0011752|Melanocyte-stimulating hormone receptor (MC1R)
ATGGCTGTGCAGGGATCCCAGAGAAGACTTCTGGGCTCCCTCAACTCCACCCCCACAGCC
ATCCCCCAGCTGGGGCTGGCTGCCAACCAGACAGGAGCCCGGTGCCTGGAGGTGTCCATC
TCTGACGGGCTCTTCCTCAGCCTGGGGCTGGTGAGCTTGGTGGAGAACGCGCTGGTGGTG
GCCACCATCGCCAAGAACCGGAACCTGCACTCACCCATGTACTGCTTCATCTGCTGCCTG
GCCTTGTCGGACCTGCTGGTGAGCGGGAGCAACGTGCTGGAGACGGCCGTCATCCTCCTG
CTGGAGGCCGGTGCACTGGTGGCCCGGGCTGCGGTGCTGCAGCAGCTGGACAATGTCATT
GACGTGATCACCTGCAGCTCCATGCTGTCCAGCCTCTGCTTCCTGGGCGCCATCGCCGTG
GACCGCTACATCTCCATCTTCTACGCACTGCGCTACCACAGCATCGTGACCCTGCCGCGG
GCGCGGCGAGCCGTTGCGGCCATCTGGGTGGCCAGTGTCGTCTTCAGCACGCTCTTCATC
GCCTACTACGACCACGTGGCCGTCCTGCTGTGCCTCGTGGTCTTCTTCCTGGCTATGCTG
GTGCTCATGGCCGTGCTGTACGTCCACATGCTGGCCCGGGCCTGCCAGCACGCCCAGGGC
ATCGCCCGGCTCCACAAGAGGCAGCGCCCGGTCCACCAGGGCTTTGGCCTTAAAGGCGCT
GTCACCCTCACCATCCTGCTGGGCATTTTCTTCCTCTGCTGGGGCCCCTTCTTCCTGCAT
CTCACACTCATCGTCCTCTGCCCCGAGCACCCCACGTGCGGCTGCATCTTCAAGAACTTC
AACCTCTTTCTCGCCCTCATCATCTGCAATGCCATCATCGACCCCCTCATCTACGCCTTC
CACAGCCAGGAGCTCCGCAGGACGCTCAAGGAGGTGCTGACATGCTCCTGGTGA
Chromosome Location
16
Locus
16q24.3
External Identifiers
ResourceLink
UniProtKB IDQ01726
UniProtKB Entry NameMSHR_HUMAN
GenBank Gene IDX65634
GenAtlas IDMC1R
HGNC IDHGNC:6929
General References
  1. Mountjoy KG, Robbins LS, Mortrud MT, Cone RD: The cloning of a family of genes that encode the melanocortin receptors. Science. 1992 Aug 28;257(5074):1248-51. [PubMed:1325670]
  2. Gantz I, Konda Y, Tashiro T, Shimoto Y, Miwa H, Munzert G, Watson SJ, DelValle J, Yamada T: Molecular cloning of a novel melanocortin receptor. J Biol Chem. 1993 Apr 15;268(11):8246-50. [PubMed:8463333]
  3. Chhajlani V, Wikberg JE: Molecular cloning and expression of the human melanocyte stimulating hormone receptor cDNA. FEBS Lett. 1992 Sep 14;309(3):417-20. [PubMed:1516719]
  4. Chhajlani V, Wikberg JE: Molecular cloning and expression of the human melanocyte stimulating hormone receptor cDNA (FEBS 11553). FEBS Lett. 1996 Jul 22;390(2):238. [PubMed:8706868]
  5. Rana BK, Hewett-Emmett D, Jin L, Chang BH, Sambuughin N, Lin M, Watkins S, Bamshad M, Jorde LB, Ramsay M, Jenkins T, Li WH: High polymorphism at the human melanocortin 1 receptor locus. Genetics. 1999 Apr;151(4):1547-57. [PubMed:10101176]
  6. Jimenez-Cervantes C, Olivares C, Gonzalez P, Morandini R, Ghanem G, Garcia-Borron JC: The Pro162 variant is a loss-of-function mutation of the human melanocortin 1 receptor gene. J Invest Dermatol. 2001 Jul;117(1):156-8. [PubMed:11442765]
  7. Smith AG, Box NF, Marks LH, Chen W, Smit DJ, Wyeth JR, Huttley GA, Easteal S, Sturm RA: The human melanocortin-1 receptor locus: analysis of transcription unit, locus polymorphism and haplotype evolution. Gene. 2001 Dec 27;281(1-2):81-94. [PubMed:11750130]
  8. Jimenez-Cervantes C, Germer S, Gonzalez P, Sanchez J, Sanchez CO, Garcia-Borron JC: Thr40 and Met122 are new partial loss-of-function natural mutations of the human melanocortin 1 receptor. FEBS Lett. 2001 Nov 9;508(1):44-8. [PubMed:11707265]
  9. Nakayama K, Soemantri A, Jin F, Dashnyam B, Ohtsuka R, Duanchang P, Isa MN, Settheetham-Ishida W, Harihara S, Ishida T: Identification of novel functional variants of the melanocortin 1 receptor gene originated from Asians. Hum Genet. 2006 Apr;119(3):322-30. Epub 2006 Feb 4. [PubMed:16463023]
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  11. Mogil JS, Wilson SG, Chesler EJ, Rankin AL, Nemmani KV, Lariviere WR, Groce MK, Wallace MR, Kaplan L, Staud R, Ness TJ, Glover TL, Stankova M, Mayorov A, Hruby VJ, Grisel JE, Fillingim RB: The melanocortin-1 receptor gene mediates female-specific mechanisms of analgesia in mice and humans. Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4867-72. Epub 2003 Mar 27. [PubMed:12663858]
  12. Perez-Oliva AB, Olivares C, Jimenez-Cervantes C, Garcia-Borron JC: Mahogunin ring finger-1 (MGRN1) E3 ubiquitin ligase inhibits signaling from melanocortin receptor by competition with Galphas. J Biol Chem. 2009 Nov 13;284(46):31714-25. doi: 10.1074/jbc.M109.028100. Epub 2009 Sep 8. [PubMed:19737927]
  13. Prusis P, Schioth HB, Muceniece R, Herzyk P, Afshar M, Hubbard RE, Wikberg JE: Modeling of the three-dimensional structure of the human melanocortin 1 receptor, using an automated method and docking of a rigid cyclic melanocyte-stimulating hormone core peptide. J Mol Graph Model. 1997 Oct;15(5):307-17, 334. [PubMed:9640562]
  14. Valverde P, Healy E, Jackson I, Rees JL, Thody AJ: Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans. Nat Genet. 1995 Nov;11(3):328-30. [PubMed:7581459]
  15. Valverde P, Healy E, Sikkink S, Haldane F, Thody AJ, Carothers A, Jackson IJ, Rees JL: The Asp84Glu variant of the melanocortin 1 receptor (MC1R) is associated with melanoma. Hum Mol Genet. 1996 Oct;5(10):1663-6. [PubMed:8894704]
  16. Box NF, Wyeth JR, O'Gorman LE, Martin NG, Sturm RA: Characterization of melanocyte stimulating hormone receptor variant alleles in twins with red hair. Hum Mol Genet. 1997 Oct;6(11):1891-7. [PubMed:9302268]
  17. Koppula SV, Robbins LS, Lu D, Baack E, White CR Jr, Swanson NA, Cone RD: Identification of common polymorphisms in the coding sequence of the human MSH receptor (MCIR) with possible biological effects. Hum Mutat. 1997;9(1):30-6. [PubMed:8990005]
  18. Frandberg PA, Doufexis M, Kapas S, Chhajlani V: Human pigmentation phenotype: a point mutation generates nonfunctional MSH receptor. Biochem Biophys Res Commun. 1998 Apr 17;245(2):490-2. [PubMed:9571181]
  19. Smith R, Healy E, Siddiqui S, Flanagan N, Steijlen PM, Rosdahl I, Jacques JP, Rogers S, Turner R, Jackson IJ, Birch-Machin MA, Rees JL: Melanocortin 1 receptor variants in an Irish population. J Invest Dermatol. 1998 Jul;111(1):119-22. [PubMed:9665397]
  20. Schioth HB, Phillips SR, Rudzish R, Birch-Machin MA, Wikberg JE, Rees JL: Loss of function mutations of the human melanocortin 1 receptor are common and are associated with red hair. Biochem Biophys Res Commun. 1999 Jul 5;260(2):488-91. [PubMed:10403794]
  21. Sanchez Mas J, Olivares Sanchez C, Ghanem G, Haycock J, Lozano Teruel JA, Garcia-Borron JC, Jimenez-Cervantes C: Loss-of-function variants of the human melanocortin-1 receptor gene in melanoma cells define structural determinants of receptor function. Eur J Biochem. 2002 Dec;269(24):6133-41. [PubMed:12473109]
  22. Beaumont KA, Newton RA, Smit DJ, Leonard JH, Stow JL, Sturm RA: Altered cell surface expression of human MC1R variant receptor alleles associated with red hair and skin cancer risk. Hum Mol Genet. 2005 Aug 1;14(15):2145-54. Epub 2005 Jun 22. [PubMed:15972726]
  23. Fernandez L, Milne R, Bravo J, Lopez J, Aviles J, Longo M, Benitez J, Lazaro P, Ribas G: MC1R: three novel variants identified in a malignant melanoma association study in the Spanish population. Carcinogenesis. 2007 Aug;28(8):1659-64. Epub 2007 Apr 13. [PubMed:17434924]
  24. Sulem P, Gudbjartsson DF, Stacey SN, Helgason A, Rafnar T, Magnusson KP, Manolescu A, Karason A, Palsson A, Thorleifsson G, Jakobsdottir M, Steinberg S, Palsson S, Jonasson F, Sigurgeirsson B, Thorisdottir K, Ragnarsson R, Benediktsdottir KR, Aben KK, Kiemeney LA, Olafsson JH, Gulcher J, Kong A, Thorsteinsdottir U, Stefansson K: Genetic determinants of hair, eye and skin pigmentation in Europeans. Nat Genet. 2007 Dec;39(12):1443-52. Epub 2007 Oct 21. [PubMed:17952075]
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  26. Perez Oliva AB, Fernendez LP, Detorre C, Herraiz C, Martinez-Escribano JA, Benitez J, Lozano Teruel JA, Garcia-Borron JC, Jimenez-Cervantes C, Ribas G: Identification and functional analysis of novel variants of the human melanocortin 1 receptor found in melanoma patients. Hum Mutat. 2009 May;30(5):811-22. doi: 10.1002/humu.20971. [PubMed:19338054]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB04931Afamelanotideapproved, investigationalyesagonistDetails
DB05479CZEN 002investigationalunknownDetails
DB11653Bremelanotideapproved, investigationalunknownagonistDetails