Open Access Articles- Top Results for Melanocortin 4 receptor

Melanocortin 4 receptor

SymbolsMC4R ; MGC126851; MGC138197
External IDsOMIM155541 MGI99457 HomoloGene4320 IUPHAR: 285 ChEMBL: 259 GeneCards: MC4R Gene
RNA expression pattern
File:PBB GE MC4R 221467 at tn.png
More reference expression data
RefSeq (mRNA)NM_005912NM_016977
RefSeq (protein)NP_005903NP_058673
Location (UCSC)Chr 18:
58.04 – 58.04 Mb
Chr 18:
66.86 – 66.86 Mb
PubMed search[1][2]

Melanocortin receptor 4 is a protein that in humans is encoded by the MC4R gene.[1][2][3] It encodes the MC4 protein, a G-protein coupled receptor that binds α-melanocyte stimulating hormone (α-MSH). In murine models MC4 receptors have been found to be involved in feeding behaviour, the regulation of metabolism, sexual behaviour, and male erectile function.[4][5][6]

In 2008, MC4R mutations were reported to be associated with inherited human obesity. They were found in heterozygotes, suggesting an autosomal dominant inheritance pattern. However, based on other research and observations, these mutations seem to have an incomplete penetrance and some degree of codominance. It has a prevalence of 1.0-2.5% in people with body mass indices greater than 30, making it the most commonly known genetic defect predisposing people to obesity.[7]


Melanocortin 4 receptor has been shown to interact with proopiomelanocortin.[8][9]

Clinical significance

In 2009, two very large genome-wide association studies of body mass index (BMI) confirmed the association of variants about 150 kilobases downstream of the MC4R gene with insulin resistance, obesity, and other anthropometric traits.[10][11][12][13]









See also


  1. ^ Magenis RE, Smith L, Nadeau JH, Johnson KR, Mountjoy KG, Cone RD (December 1994). "Mapping of the ACTH, MSH, and neural (MC3 and MC4) melanocortin receptors in the mouse and human". Mamm Genome 5 (8): 503–8. PMID 7949735. doi:10.1007/BF00369320. 
  2. ^ Sundaramurthy D, Campbell DA, Leek JP, Markham AF, Pieri LF (November 1998). "Assignment of the melanocortin 4 receptor (MC4R) gene to human chromosome band 18q22 by in situ hybridisation and radiation hybrid mapping". Cytogenet Cell Genet 82 (1–2): 97–8. PMID 9763669. doi:10.1159/000015074. 
  3. ^ "Entrez Gene: MC4R melanocortin 4 receptor". 
  4. ^ Fan W, Boston BA, Kesterson RA, Hruby VJ, Cone RD (1997). "Role of melanocortinergic neurons in feeding and the agouti obesity syndrome". Nature 385 (6612): 165–168. PMID 8990120. doi:10.1038/385165a0. 
  5. ^ Huszar D, Lynch CA, Fairchild-Huntress V, Dunmore JH, Fang Q, Berkemeier LR, Gu W, Kesterson RA, Boston BA, Cone RD, Smith FJ, Campfield LA, Burn P, Lee F (1997). "Targeted disruption of the melanocortin-4 receptor results in obesity in mice". Cell 88 (1): 131–141. PMID 9019399. doi:10.1016/S0092-8674(00)81865-6. 
  6. ^ Van der Ploeg LH, Martin WJ, Howard AD, Nargund RP, Austin CP, Guan X, Drisko J, Cashen D, Sebhat I, Patchett AA, Figueroa DJ, DiLella AG, Connolly BM, Weinberg DH, Tan CP, Palyha OC, Pong SS, MacNeil T, Rosenblum C, Vongs A, Tang R, Yu H, Sailer AW, Fong TM, Huang C, Tota MR, Chang RS, Stearns R, Tamvakopoulos C, Christ G, Drazen DL, Spar BD, Nelson RJ, MacIntyre DE (2002). "A role for the melanocortin 4 receptor in sexual function". Proc Natl Acad Sci USA 99 (17): 11381–11386. PMC 123265. PMID 12172010. doi:10.1073/pnas.172378699. 
  7. ^ Farooqi S, O'Rahilly S (2006). "Genetics of obesity in humans". Endocrine Reviews 27 (7): 710–718. PMID 17122358. doi:10.1210/er.2006-0040. 
  8. ^ Yang YK, Fong TM, Dickinson CJ, Mao C, Li JY, Tota MR, Mosley R, Van Der Ploeg LH, Gantz I (December 2000). "Molecular determinants of ligand binding to the human melanocortin-4 receptor". Biochemistry 39 (48): 14900–11. PMID 11101306. doi:10.1021/bi001684q. 
  9. ^ Yang YK, Ollmann MM, Wilson BD, Dickinson C, Yamada T, Barsh GS, Gantz I (March 1997). "Effects of recombinant agouti-signaling protein on melanocortin action". Mol. Endocrinol. 11 (3): 274–80. PMID 9058374. doi:10.1210/me.11.3.274. 
  10. ^ Chambers JC, Elliott P, Zabaneh D, Zhang W, Li Y, Froguel P, Balding D, Scott J, Kooner JS (June 2008). "Common genetic variation near MC4R is associated with waist circumference and insulin resistance". Nat. Genet. 40 (6): 716–18. PMID 18454146. doi:10.1038/ng.156. 
  11. ^ Loos RJ, Lindgren CM, Li S, Wheeler E, Zhao JH, Prokopenko I, Inouye M, Freathy RM, Attwood AP et al. (June 2008). "Common variants near MC4R are associated with fat mass, weight and risk of obesity". Nat. Genet. 40 (6): 768–75. PMC 2669167. PMID 18454148. doi:10.1038/ng.140. 
  12. ^ Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V, Sulem P, Helgadottir A, Styrkarsdottir U, Gretarsdottir S, Thorlacius S, Jonsdottir I et al. (January 2009). "Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity". Nat. Genet. 41 (1): 18–24. PMID 19079260. doi:10.1038/ng.274. 
  13. ^ Willer CJ, Speliotes EK, Loos RJ, Li S, Lindgren CM, Heid IM, Berndt SI, Elliott AL, Jackson AU et al. (January 2009). "Six new loci associated with body mass index highlight a neuronal influence on body weight regulation". Nat. Genet. 41 (1): 24–34. PMC 2695662. PMID 19079261. doi:10.1038/ng.287. 

External links

Further reading

  • Mountjoy KG, Mortrud MT, Low MJ, Simerly RB, Cone RD (1995). "Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain". Mol. Endocrinol. 8 (10): 1298–308. PMID 7854347. doi:10.1210/me.8.10.1298. 
  • Gantz I, Miwa H, Konda Y, Shimoto Y, Tashiro T, Watson SJ, DelValle J, Yamada T (1993). "Molecular cloning, expression, and gene localization of a fourth melanocortin receptor". J. Biol. Chem. 268 (20): 15174–9. PMID 8392067. 
  • Alvaro JD, Tatro JB, Quillan JM, Fogliano M, Eisenhard M, Lerner MR, Nestler EJ, Duman RS (1996). "Morphine down-regulates melanocortin-4 receptor expression in brain regions that mediate opiate addiction". Mol. Pharmacol. 50 (3): 583–91. PMID 8794897. 
  • Yang YK, Ollmann MM, Wilson BD, Dickinson C, Yamada T, Barsh GS, Gantz I (1997). "Effects of recombinant agouti-signaling protein on melanocortin action". Mol. Endocrinol. 11 (3): 274–80. PMID 9058374. doi:10.1210/me.11.3.274. 
  • Chagnon YC, Chen WJ, Pérusse L, Chagnon M, Nadeau A, Wilkison WO, Bouchard C (1998). "Linkage and association studies between the melanocortin receptors 4 and 5 genes and obesity-related phenotypes in the Québec Family Study". Mol. Med. 3 (10): 663–73. PMC 2230227. PMID 9392003. 
  • Yeo GS, Farooqi IS, Aminian S, Halsall DJ, Stanhope RG, O'Rahilly S (1998). "A frameshift mutation in MC4R associated with dominantly inherited human obesity". Nat. Genet. 20 (2): 111–2. PMID 9771698. doi:10.1038/2404. 
  • Vaisse C, Clement K, Guy-Grand B, Froguel P (1998). "A frameshift mutation in human MC4R is associated with a dominant form of obesity". Nat. Genet. 20 (2): 113–4. PMID 9771699. doi:10.1038/2407. 
  • Hinney A, Schmidt A, Nottebom K, Heibült O, Becker I, Ziegler A, Gerber G, Sina M, Görg T, Mayer H, Siegfried W, Fichter M, Remschmidt H, Hebebrand J (1999). "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. 84 (4): 1483–6. PMID 10199800. doi:10.1210/jc.84.4.1483. 
  • Yang YK, Dickinson CJ, Zeng Q, Li JY, Thompson DA, Gantz I (1999). "Contribution of melanocortin receptor exoloops to Agouti-related protein binding". J. Biol. Chem. 274 (20): 14100–6. PMID 10318826. doi:10.1074/jbc.274.20.14100. 
  • Ho G, MacKenzie RG (2000). "Functional characterization of mutations in melanocortin-4 receptor associated with human obesity". J. Biol. Chem. 274 (50): 35816–22. PMID 10585465. doi:10.1074/jbc.274.50.35816. 
  • Yang YK, Fong TM, Dickinson CJ, Mao C, Li JY, Tota MR, Mosley R, Van Der Ploeg LH, Gantz I (2001). "Molecular determinants of ligand binding to the human melanocortin-4 receptor". Biochemistry 39 (48): 14900–11. PMID 11101306. doi:10.1021/bi001684q. 
  • Mergen M, Mergen H, Ozata M, Oner R, Oner C (2001). "A novel melanocortin 4 receptor (MC4R) gene mutation associated with morbid obesity". J. Clin. Endocrinol. Metab. 86 (7): 3448. PMID 11443223. doi:10.1210/jc.86.7.3448. 
  • McNulty JC, Thompson DA, Bolin KA, Wilken J, Barsh GS, Millhauser GL (2002). "High-resolution NMR structure of the chemically-synthesized melanocortin receptor binding domain AGRP(87-132) of the agouti-related protein". Biochemistry 40 (51): 15520–7. PMID 11747427. doi:10.1021/bi0117192. 
  • Brocke KS, Neu-Yilik G, Gehring NH, Hentze MW, Kulozik AE (2002). "The human intronless melanocortin 4-receptor gene is NMD insensitive". Hum. Mol. Genet. 11 (3): 331–5. PMID 11823452. doi:10.1093/hmg/11.3.331. 
  • Yang Y, Chen M, Lai Y, Gantz I, Georgeson KE, Harmon CM (2002). "Molecular determinants of human melanocortin-4 receptor responsible for antagonist SHU9119 selective activity". J. Biol. Chem. 277 (23): 20328–35. PMID 11912210. doi:10.1074/jbc.M201343200. 
  • Hansen MJ, Morris MJ (2002). "Evidence for an interaction between neuropeptide Y and the melanocortin-4 receptor on feeding in the rat". Neuropharmacology 42 (6): 792–7. PMID 12015205. doi:10.1016/S0028-3908(02)00025-4. 
  • Miraglia Del Giudice E, Cirillo G, Nigro V, Santoro N, D'Urso L, Raimondo P, Cozzolino D, Scafato D, Perrone L (2002). "Low frequency of melanocortin-4 receptor (MC4R) mutations in a Mediterranean population with early-onset obesity". Int. J. Obes. Relat. Metab. Disord. 26 (5): 647–51. PMID 12032748. doi:10.1038/sj.ijo.0801983. 
  • Kim CS, Lee SH, Kim RY, Kim BJ, Li SZ, Lee IH, Lee EJ, Lim SK, Bae YS, Lee W, Baik JH (2002). "Identification of domains directing specificity of coupling to G-proteins for the melanocortin MC3 and MC4 receptors". J. Biol. Chem. 277 (35): 31310–7. PMID 12045190. doi:10.1074/jbc.M112085200. 

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

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