Melanokortinski 4 receptor
| edit |
| Melanokortin 4 receptor | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Identifikatori | |||||||||||
| Simboli | MC4R; MGC126851; MGC138197 | ||||||||||
| Vanjski ID | OMIM: 155541 MGI: 99457 HomoloGene: 4320 IUPHAR: MC4 GeneCards: MC4R Gene | ||||||||||
| |||||||||||
| Pregled RNK izražavanja | |||||||||||
 | |||||||||||
| podaci | |||||||||||
| Ortolozi | |||||||||||
| Vrsta | Čovek | Miš | |||||||||
| Entrez | 4160 | 17202 | |||||||||
| Ensembl | ENSG00000166603 | ENSMUSG00000047259 | |||||||||
| UniProt | P32245 | Q49NR1 | |||||||||
| RefSeq (mRNA) | NM_005912 | NM_016977 | |||||||||
| RefSeq (protein) | NP_005903 | NP_058673 | |||||||||
| Lokacija (UCSC) | Chr 18: 56.19 - 56.19 Mb | Chr 18: 66.98 - 66.99 Mb | |||||||||
| PubMed pretraga | |||||||||||
Melanokortin receptor 4 je protein koji je kod ljudi kodiran MC4R genom.[1][2][3] Ova gen kodira MC4 protein, G-protein spregnuti receptor koji vezuje α-melanocit stimulišući hormon (α-MSH). U modelima na glodarima za MC4 receptore je bilo ustanovljeno da učestvuju u ishrani, regulaciji metabolizma, seksualnom ponašanju, i muškoj erektilnoj funkciji[4][5][6]
1998 godine je bilo objavljeno da su MC4R mutacije vezane za naslednu gojaznost kod ljudi. One su nađene kod heterozigota, što sugestira autozomni dominantni nasledni trend. Međutim, na bazi drugih istraživanja i opažanja, te mutacije izgleda da imaju delimičnu penetrantnost i određeni stupanj kodominantnosti. Njihova zastupljenost od 1-2.5% kod ljudi sa BMI većim od 30, čini ih najzastupljenijim među poznatim genetskim defektima koji predispozicioniraju ljude ka gojaznosti.[7]
Za melanokortin 4 receptor je bilo pokazano da interaguje sa proopiomelanokortinom.[8][9]
2009 godine su sprovedene dve veoma velike BMI asocijacione studije koje su obuhvatale celokupni genom. One su potvrdile asocijaciju varijanti sa oko 150 kilo baza nizvodno od MC4R gena sa otpornošću na insulin, gojažnošću i drugim antropometrijskim odlikama.[10][11][12][13]
- ↑ Magenis RE, Smith L, Nadeau JH, Johnson KR, Mountjoy KG, Cone RD (Dec 1994). „Mapping of the ACTH, MSH, and neural (MC3 and MC4) melanocortin receptors in the mouse and human”. Mamm Genome 5 (8): 503–8. DOI:10.1007/BF00369320. PMID 7949735.
- ↑ Sundaramurthy D, Campbell DA, Leek JP, Markham AF, Pieri LF (Nov 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. DOI:10.1159/000015074. PMID 9763669.
- ↑ „Entrez Gene: MC4R melanocortin 4 receptor”.
- ↑ 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.
- ↑ 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.
- ↑ 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. PMID 12172010.
- ↑ 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.
- ↑ Yang, Y K; Fong T M, Dickinson C J, Mao C, Li J Y, Tota M R, Mosley R, Van Der Ploeg L H, Gantz I (December 2000). „Molecular determinants of ligand binding to the human melanocortin-4 receptor”. Biochemistry (UNITED STATES) 39 (48): 14900–11. DOI:10.1021/bi001684q. ISSN 0006-2960. PMID 11101306.
- ↑ Yang, Y K; Ollmann M M, Wilson B D, Dickinson C, Yamada T, Barsh G S, Gantz I (March 1997). „Effects of recombinant agouti-signaling protein on melanocortin action”. Mol. Endocrinol. (UNITED STATES) 11 (3): 274–80. DOI:10.1210/me.11.3.274. ISSN 0888-8809. PMID 9058374.
- ↑ Chambers JC, Elliott P, Zabaneh D, et al. (June 2008). „Common genetic variation near MC4R is associated with waist circumference and insulin resistance.”. Nat. Genet. 40 (6): 716–18. DOI:10.1038/ng.156. PMID 18454146.
- ↑ Loos RJ, Lindgren CM, Li S, Wheeler E, et al. (June 2008). „Common variants near MC4R are associated with fat mass, weight and risk of obesity.”. Nat. Genet. 40 (6): 768–75. DOI:10.1038/ng.140. PMC 2669167. PMID 18454148.
- ↑ Thorleifsson G, Walters GB, Gudbjartsson DF, 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. DOI:10.1038/ng.274. PMID 19079260.
- ↑ Willer CJ, Speliotes EK, Loos RJ, 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. DOI:10.1038/ng.287. PMC 2695662. PMID 19079261.
- 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. 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.
- „Melanocortin Receptors: MC4”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano iz originala na datum 2016-03-03.