Melanocyte-stimulating hormone receptor

NameMelanocyte-stimulating hormone receptor
Synonyms
  • MC1-R
  • Melanocortin receptor 1
  • MSH-R
  • MSHR
Gene NameMC1R
OrganismHuman
Amino acid sequence
>lcl|BSEQ0011751|Melanocyte-stimulating hormone receptor
MAVQGSQRRLLGSLNSTPTAIPQLGLAANQTGARCLEVSISDGLFLSLGLVSLVENALVV
ATIAKNRNLHSPMYCFICCLALSDLLVSGSNVLETAVILLLEAGALVARAAVLQQLDNVI
DVITCSSMLSSLCFLGAIAVDRYISIFYALRYHSIVTLPRARRAVAAIWVASVVFSTLFI
AYYDHVAVLLCLVVFFLAMLVLMAVLYVHMLARACQHAQGIARLHKRQRPVHQGFGLKGA
VTLTILLGIFFLCWGPFFLHLTLIVLCPEHPTCGCIFKNFNLFLALIICNAIIDPLIYAF
HSQELRRTLKEVLTCSW
Number of residues317
Molecular Weight34705.04
Theoretical pI8.44
GO Classification
Functions
  • melanocyte-stimulating hormone receptor activity
  • melanocortin receptor activity
  • ubiquitin protein ligase binding
  • hormone binding
  • G-protein coupled peptide receptor activity
Processes
  • negative regulation of tumor necrosis factor production
  • pigmentation
  • positive regulation of feeding behavior
  • positive regulation of transcription from RNA polymerase II promoter
  • positive regulation of protein kinase A signaling
  • UV protection
  • multicellular organismal development
  • UV-damage excision repair
  • intracellular signal transduction
  • G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
  • sensory perception of pain
  • positive regulation of cAMP biosynthetic process
  • positive regulation of protein kinase C signaling
  • melanin biosynthetic process
  • positive regulation of protein kinase B signaling
Components
  • intracellular
  • plasma membrane
  • integral component of plasma membrane
General FunctionUbiquitin protein ligase binding
Specific FunctionReceptor 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 Regions38-63 73-93 119-140 164-183 192-211 241-266 280-300
GenBank Protein IDNot Available
UniProtKB IDQ01726
UniProtKB Entry NameMSHR_HUMAN
Cellular LocationCell 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
GenBank Gene IDX65634
GeneCard IDNot Available
GenAtlas IDMC1R
HGNC IDHGNC:6929
Chromosome Location16
Locus16q24.3
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. 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. 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. 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. 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. 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. 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. 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. 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. 16463023
  10. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 17952075
  25. Ley TJ, Mardis ER, Ding L, Fulton B, McLellan MD, Chen K, Dooling D, Dunford-Shore BH, McGrath S, Hickenbotham M, Cook L, Abbott R, Larson DE, Koboldt DC, Pohl C, Smith S, Hawkins A, Abbott S, Locke D, Hillier LW, Miner T, Fulton L, Magrini V, Wylie T, Glasscock J, Conyers J, Sander N, Shi X, Osborne JR, Minx P, Gordon D, Chinwalla A, Zhao Y, Ries RE, Payton JE, Westervelt P, Tomasson MH, Watson M, Baty J, Ivanovich J, Heath S, Shannon WD, Nagarajan R, Walter MJ, Link DC, Graubert TA, DiPersio JF, Wilson RK: DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature. 2008 Nov 6;456(7218):66-72. doi: 10.1038/nature07485. 18987736
  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. 19338054