Melanocortin 4 receptor

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Melanocortin 4 receptor
Identifiers
SymbolsMC4R; MGC126851; MGC138197
External IDsOMIM: 155541 MGI: 99457 HomoloGene: 4320 IUPHAR: MC4 GeneCards: MC4R Gene
RNA expression pattern
250px
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez416017202
EnsemblENSG00000166603ENSMUSG00000047259
UniProtP32245Q49NR1
RefSeq (mRNA)NM_005912NM_016977
RefSeq (protein)NP_005903NP_058673
Location (UCSC)Chr 18:
56.19 - 56.19 Mb		Chr 18:
66.98 - 66.99 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 1998, it was reported that MC4R mutations were 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 1-2.5% in people with BMIs of greater than 30, making it the most commonly known genetic defect predisposing people to obesity.[7]


Interactions

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

References

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External links

Further reading

  • Mountjoy KG, Mortrud MT, Low MJ; et al. (1995). "Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain". Mol. Endocrinol. 8 (10): 1298–308. doi:10.1210/me.8.10.1298. PMID 7854347. 
  • Gantz I, Miwa H, Konda Y; et al. (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; et al. (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; et al. (1997). "Effects of recombinant agouti-signaling protein on melanocortin action". Mol. Endocrinol. 11 (3): 274–80. doi:10.1210/me.11.3.274. PMID 9058374. 
  • Chagnon YC, Chen WJ, Pérusse L; et al. (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 Freely accessible. PMID 9392003. 
  • Yeo GS, Farooqi IS, Aminian S; et al. (1998). "A frameshift mutation in MC4R associated with dominantly inherited human obesity". Nat. Genet. 20 (2): 111–2. doi:10.1038/2404. PMID 9771698. 
  • 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. doi:10.1038/2407. PMID 9771699. 
  • Hinney A, Schmidt A, Nottebom K; et al. (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. doi:10.1210/jc.84.4.1483. PMID 10199800. 
  • Yang YK, Dickinson CJ, Zeng Q; et al. (1999). "Contribution of melanocortin receptor exoloops to Agouti-related protein binding". J. Biol. Chem. 274 (20): 14100–6. doi:10.1074/jbc.274.20.14100. PMID 10318826. 
  • Ho G, MacKenzie RG (2000). "Functional characterization of mutations in melanocortin-4 receptor associated with human obesity". J. Biol. Chem. 274 (50): 35816–22. doi:10.1074/jbc.274.50.35816. PMID 10585465. 
  • Yang YK, Fong TM, Dickinson CJ; et al. (2001). "Molecular determinants of ligand binding to the human melanocortin-4 receptor". Biochemistry. 39 (48): 14900–11. doi:10.1021/bi001684q. PMID 11101306. 
  • Mergen M, Mergen H, Ozata M; et al. (2001). "A novel melanocortin 4 receptor (MC4R) gene mutation associated with morbid obesity". J. Clin. Endocrinol. Metab. 86 (7): 3448. doi:10.1210/jc.86.7.3448. PMID 11443223. 
  • McNulty JC, Thompson DA, Bolin KA; et al. (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. doi:10.1021/bi0117192. PMID 11747427. 
  • Brocke KS, Neu-Yilik G, Gehring NH; et al. (2002). "The human intronless melanocortin 4-receptor gene is NMD insensitive". Hum. Mol. Genet. 11 (3): 331–5. doi:10.1093/hmg/11.3.331. PMID 11823452. 
  • Yang Y, Chen M, Lai Y; et al. (2002). "Molecular determinants of human melanocortin-4 receptor responsible for antagonist SHU9119 selective activity". J. Biol. Chem. 277 (23): 20328–35. doi:10.1074/jbc.M201343200. PMID 11912210. 
  • 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. doi:10.1016/S0028-3908(02)00025-4. PMID 12015205. 
  • Miraglia Del Giudice E, Cirillo G, Nigro V; et al. (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. doi:10.1038/sj.ijo.0801983. PMID 12032748. 
  • Kim CS, Lee SH, Kim RY; et al. (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. doi:10.1074/jbc.M112085200. PMID 12045190. 

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


Class A: Rhodopsin like
α1 (A, B, D) · α2 (A, B, C) · β1 · β2 · β3
Adenosine (A1, A2A, A2B, A3) · P2Y (1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14)
(all but 5-HT3) 5-HT1 (A, B, D, E, F) · 5-HT2 (A, B, C) · 5-HT (4, 5A, 6, 7)
Other
Acetylcholine (M1, M2, M3, M4, M5) · Dopamine (D1, D2, D3, D4, D5) · Histamine (H1, H2, H3, H4) · Melatonin (1A, 1B, 1C) · TAAR (1, 2, 3, 5, 6, 8, 9)
Metabolites and
signaling molecules
CysLT (1, 2) · LTB4 (1, 2) · FPRL1 · OXE · Prostaglandin (DP (1, 2), EP (1, 2, 3, 4), FP) · Prostacyclin · Thromboxane
Other
Bile acid · Cannabinoid (CB1, CB2, GPR (18, 55, 119)) · EBI2 · Estrogen · Free fatty acid (1, 2, 3, 4) · Lactate  · Lysophosphatidic acid (1, 2, 3, 4, 5, 6)  · Lysophospholipid (1, 2, 3, 4, 5, 6, 7, 8) · Niacin (1, 2) · Oxoglutarate · PAF · Sphingosine-1-phosphate (1, 2, 3, 4, 5) · Succinate
Peptide
B/W (1, 2) · FF (1, 2) · S · Y (1, 2, 4, 5) · Neuromedin (B, U (1, 2)) · Neurotensin (1, 2)
Other
Miscellaneous
GPR (1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 81, 82, 83, 84, 85, 87, 88, 92, 101, 103, 109A, 109B, 119, 120, 132, 135, 137B, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 173, 174, 176, 177, 182, 183)
Other
Class B: Secretin like
GPR (56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 155, 157)
Other
Class C: Metabotropic
glutamate / pheromone
TAS1R (1, 2, 3) · TAS2R (1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 19, 20, 30, 31, 38, 39, 40, 41, 42, 43, 45, 46, 50)
Other
Class F:
Frizzled / Smoothened
Frizzled
Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10)
Smoothened


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  1. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  2. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  3. ↑ "Entrez Gene: MC4R melanocortin 4 receptor". 
  4. ↑ Fan W, Boston BA, Kesterson RA, Hruby VJ and Cone RD. (1997). "Role of melanocortinergic neurons in feeding and the agouti obesity syndrome". Nature. 385 (6612): 165–168. doi:10.1038/385165a0. PMID 8990120. 
  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. doi:10.1016/S0092-8674(00)81865-6. PMID 9019399. 
  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. doi:10.1073/pnas.172378699. PMC 123265 Freely accessible. PMID 12172010. 
  7. ↑ Farooqi S, O'Rahilly S. (2006). "Genetics of obesity in humans". Endocrine Reviews. 27 (7): 710–718. doi:10.1210/er.2006-0040. PMID 17122358. 
  8. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
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