Melanocortin receptor 4

Details

Name
Melanocortin receptor 4
Synonyms
  • MC4-R
Gene Name
MC4R
Organism
Humans
Amino acid sequence
>lcl|BSEQ0052043|Melanocortin receptor 4
MVNSTHRGMHTSLHLWNRSSYRLHSNASESLGKGYSDGGCYEQLFVSPEVFVTLGVISLL
ENILVIVAIAKNKNLHSPMYFFICSLAVADMLVSVSNGSETIVITLLNSTDTDAQSFTVN
IDNVIDSVICSSLLASICSLLSIAVDRYFTIFYALQYHNIMTVKRVGIIISCIWAACTVS
GILFIIYSDSSAVIICLITMFFTMLALMASLYVHMFLMARLHIKRIAVLPGTGAIRQGAN
MKGAITLTILIGVFVVCWAPFFLHLIFYISCPQNPYCVCFMSHFNLYLILIMCNSIIDPL
IYALRSQELRKTFKEIICCYPLGGLCDLSSRY
Number of residues
332
Molecular Weight
36942.325
Theoretical pI
Not Available
GO Classification
Functions
melanocortin receptor activity / melanocyte-stimulating hormone receptor activity / neuropeptide binding / peptide hormone binding / ubiquitin protein ligase binding
Processes
adenylate cyclase-activating G protein-coupled receptor signaling pathway / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / diet induced thermogenesis / energy reserve metabolic process / feeding behavior / G protein-coupled receptor signaling pathway / insulin secretion / negative regulation of feeding behavior / positive regulation of bone resorption / regulation of grooming behavior / regulation of metabolic process / response to insulin
Components
integral component of membrane / nucleus / plasma membrane
General Function
Receptor specific to the heptapeptide core common to adrenocorticotropic hormone and alpha-, beta-, and gamma-MSH. Plays a central role in energy homeostasis and somatic growth. This receptor is mediated by G proteins that stimulate adenylate cyclase (cAMP).
Specific Function
Melanocortin receptor activity
Pfam Domain Function
Transmembrane Regions
44-69 82-106 124-145 166-186 192-215 249-271 281-304
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0052044|Melanocortin receptor 4 (MC4R)
ATGGTGAACTCCACCCACCGTGGGATGCACACTTCTCTGCACCTCTGGAACCGCAGCAGT
TACAGACTGCACAGCAATGCCAGTGAGTCCCTTGGAAAAGGCTACTCTGATGGAGGGTGC
TACGAGCAACTTTTTGTCTCTCCTGAGGTGTTTGTGACTCTGGGTGTCATCAGCTTGTTG
GAGAATATCTTAGTGATTGTGGCAATAGCCAAGAACAAGAATCTGCATTCACCCATGTAC
TTTTTCATCTGCAGCTTGGCTGTGGCTGATATGCTGGTGAGCGTTTCAAATGGATCAGAA
ACCATTGTCATCACCCTATTAAACAGTACAGATACGGATGCACAGAGTTTCACAGTGAAT
ATTGATAATGTCATTGACTCGGTGATCTGTAGCTCCTTGCTTGCATCCATTTGCAGCCTG
CTTTCAATTGCAGTGGACAGGTACTTTACTATCTTCTATGCTCTCCAGTACCATAACATT
ATGACAGTTAAGCGGGTTGGGATCATCATAAGTTGTATCTGGGCAGCTTGCACGGTTTCA
GGCATTTTGTTCATCATTTACTCAGATAGTAGTGCTGTCATCATCTGCCTCATCACCATG
TTCTTCACCATGCTGGCTCTCATGGCTTCTCTCTATGTCCACATGTTCCTGATGGCCAGG
CTTCACATTAAGAGGATTGCTGTCCTCCCCGGCACTGGTGCCATCCGCCAAGGTGCCAAT
ATGAAGGGAGCGATTACCTTGACCATCCTGATTGGCGTCTTTGTTGTCTGCTGGGCCCCA
TTCTTCCTCCACTTAATATTCTACATCTCTTGTCCTCAGAATCCATATTGTGTGTGCTTC
ATGTCTCACTTTAACTTGTATCTCATACTGATCATGTGTAATTCAATCATCGATCCTCTG
ATTTATGCACTCCGGAGTCAAGAACTGAGGAAAACCTTCAAAGAGATCATCTGTTGCTAT
CCCCTGGGAGGCCTTTGTGACTTGTCTAGCAGATATTAA
Chromosome Location
18
Locus
18q21.32
External Identifiers
ResourceLink
UniProtKB IDP32245
UniProtKB Entry NameMC4R_HUMAN
HGNC IDHGNC:6932
General References
  1. Gantz I, Miwa H, Konda Y, Shimoto Y, Tashiro T, Watson SJ, DelValle J, Yamada T: Molecular cloning, expression, and gene localization of a fourth melanocortin receptor. J Biol Chem. 1993 Jul 15;268(20):15174-9. [PubMed:8392067]
  2. Mountjoy KG, Mortrud MT, Low MJ, Simerly RB, Cone RD: Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Mol Endocrinol. 1994 Oct;8(10):1298-308. [PubMed:7854347]
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039]
  4. 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. [PubMed:15489334]
  5. Chan LF, Webb TR, Chung TT, Meimaridou E, Cooray SN, Guasti L, Chapple JP, Egertova M, Elphick MR, Cheetham ME, Metherell LA, Clark AJ: MRAP and MRAP2 are bidirectional regulators of the melanocortin receptor family. Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6146-51. doi: 10.1073/pnas.0809918106. Epub 2009 Mar 27. [PubMed:19329486]
  6. 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]
  7. Chapman KL, Findlay JB: The melanocortin 4 receptor: oligomer formation, interaction sites and functional significance. Biochim Biophys Acta. 2013 Feb;1828(2):535-42. doi: 10.1016/j.bbamem.2012.10.011. Epub 2012 Oct 23. [PubMed:23088915]
  8. Hinney A, Schmidt A, Nottebom K, Heibult O, Becker I, Ziegler A, Gerber G, Sina M, Gorg T, Mayer H, Siegfried W, Fichter M, Remschmidt H, Hebebrand J: Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans. J Clin Endocrinol Metab. 1999 Apr;84(4):1483-6. [PubMed:10199800]
  9. Mergen M, Mergen H, Ozata M, Oner R, Oner C: A novel melanocortin 4 receptor (MC4R) gene mutation associated with morbid obesity. J Clin Endocrinol Metab. 2001 Jul;86(7):3448. [PubMed:11443223]
  10. Dubern B, Clement K, Pelloux V, Froguel P, Girardet JP, Guy-Grand B, Tounian P: Mutational analysis of melanocortin-4 receptor, agouti-related protein, and alpha-melanocyte-stimulating hormone genes in severely obese children. J Pediatr. 2001 Aug;139(2):204-9. [PubMed:11487744]
  11. Yeo GS, Lank EJ, Farooqi IS, Keogh J, Challis BG, O'Rahilly S: Mutations in the human melanocortin-4 receptor gene associated with severe familial obesity disrupts receptor function through multiple molecular mechanisms. Hum Mol Genet. 2003 Mar 1;12(5):561-74. [PubMed:12588803]
  12. Donohoue PA, Tao YX, Collins M, Yeo GS, O'Rahilly S, Segaloff DL: Deletion of codons 88-92 of the melanocortin-4 receptor gene: a novel deleterious mutation in an obese female. J Clin Endocrinol Metab. 2003 Dec;88(12):5841-5. [PubMed:14671178]
  13. Farooqi IS, Keogh JM, Yeo GS, Lank EJ, Cheetham T, O'Rahilly S: Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med. 2003 Mar 20;348(12):1085-95. [PubMed:12646665]
  14. Valli-Jaakola K, Lipsanen-Nyman M, Oksanen L, Hollenberg AN, Kontula K, Bjorbaek C, Schalin-Jantti C: Identification and characterization of melanocortin-4 receptor gene mutations in morbidly obese finnish children and adults. J Clin Endocrinol Metab. 2004 Feb;89(2):940-5. [PubMed:14764818]
  15. Larsen LH, Echwald SM, Sorensen TI, Andersen T, Wulff BS, Pedersen O: Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity. J Clin Endocrinol Metab. 2005 Jan;90(1):219-24. Epub 2004 Oct 14. [PubMed:15486053]
  16. Delhanty PJ, Bouw E, Huisman M, Vervenne RM, Themmen AP, van der Lely AJ, van den Akker EL: Functional characterization of a new human melanocortin-4 receptor homozygous mutation (N72K) that is associated with early-onset obesity. Mol Biol Rep. 2014 Dec;41(12):7967-72. doi: 10.1007/s11033-014-3691-7. Epub 2014 Aug 28. [PubMed:25163632]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB11653Bremelanotideapproved, investigationalunknownagonistDetails