Melanocortin 5 receptor

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RefSeq (mRNA)



RefSeq (protein)



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Melanocortin receptor 5 is a protein that in humans is encoded by the MC5R gene.[1][2] It is located on the chromosome 18 in the human genome.[2] When the melanocortin 5 receptor was disrupted in transgenic mice, it induced disruption of their exocrine glands and resulted in decreased production of sebum.[3]


MC5R is necessary for normal sebum production.[3][4][5] Stimulation of MC5R promotes fatty acid oxidation in skeletal muscle[6] and lypolysis in adipocytes.[7] MC5R is essential for erythrocyte differentiation.[8] MC5R is involved in inflammation.[9][10] MC5R helps maintain thermal homeostasis.[4][11]

MC5R is expressed in the brain at different levels depending on physical activity.[12]


MC5R is heavily expressed in the preputial gland in mice (a modified sebaceous gland involved in pheromone production). MC5R deficiency in male mice decreases aggressive behavior, promotes defensive behavior and encourages other male mice to attack MC5R-deficient males through pheremonal signals.[13][14][15]


Melanocortin 2 Receptor accessory protein (MRAP) traps MC5R protein inside cells.[16]

See also


  1. Chhajlani V, Muceniece R, Wikberg JE (September 1993). "Molecular cloning of a novel human melanocortin receptor". Biochemical and Biophysical Research Communications. 195 (2): 866–73. doi:10.1006/bbrc.1993.2125. PMID 8396929.
  2. 2.0 2.1 "Entrez Gene: MC5R melanocortin 5 receptor".
  3. 3.0 3.1 Thiboutot D, Sivarajah A, Gilliland K, Cong Z, Clawson G (October 2000). "The melanocortin 5 receptor is expressed in human sebaceous glands and rat preputial cells". The Journal of Investigative Dermatology. 115 (4): 614–9. doi:10.1046/j.1523-1747.2000.00094.x. PMID 10998132.
  4. 4.0 4.1 Chen W, Kelly MA, Opitz-Araya X, Thomas RE, Low MJ, Cone RD (December 1997). "Exocrine gland dysfunction in MC5-R-deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides". Cell. 91 (6): 789–98. doi:10.1016/S0092-8674(00)80467-5. PMID 9413988.
  5. Zhang L, Li WH, Anthonavage M, Pappas A, Rossetti D, Cavender D, Seiberg M, Eisinger M (June 2011). "Melanocortin-5 receptor and sebogenesis". Eur J Pharmacol. 660 (1): 202–206. doi:10.1016/j.ejphar.2010.10.100. PMID 21215742.
  6. An JJ, Rhee Y, Kim SH, Kim DM, Han DH, Hwang JH, Jin YJ, Cha BS, Baik JH, Lee WT, Lim SK (February 2007). "Peripheral effect of alpha-melanocyte-stimulating hormone on fatty acid oxidation in skeletal muscle". The Journal of Biological Chemistry. 282 (5): 2862–70. doi:10.1074/jbc.M603454200. PMID 17127674.
  7. Møller CL, Raun K, Jacobsen ML, Pedersen TÅ, Holst B, Conde-Frieboes KW, Wulff BS (July 2011). "Characterization of murine melanocortin receptors mediating adipocyte lipolysis and examination of signalling pathways involved". Mol Cell Endocrinol. 341 (1–2): 9–17. doi:10.1016/j.mce.2011.03.010. PMID 21616121.
  8. Simamura E, Arikawa T, Ikeda T, Shimada H, Shoji H, Masuta H, Nakajima Y, Otani H, Yonekura H, Hatta T (April 2015). "Melanocortins contribute to sequential differentiation and enucleation of human erythroblasts via melanocortin receptors 1, 2 and 5". PLOS ONE. 10 (4): e0123232. doi:10.1371/journal.pone.0123232. PMC 4393082. PMID 25860801.
  9. Lee DJ, Taylor AW (October 2013). "Both MC5r and A2Ar are required for protective regulatory immunity in the spleen of post-experimental autoimmune uveitis in mice". J. Immunol. 191 (8): 4103–4111. doi:10.4049/jimmunol.1300182. PMC 3796047. PMID 24043903.
  10. Jun DJ, Na KY, Kim W, Kwak D, Kwon EJ, Yoon JH, Yea K, Lee H, Kim J, Suh PG, Ryu SH, Kim KT (April 2010). "Melanocortins induce interleukin 6 gene expression and secretion through melanocortin receptors 2 and 5 in 3T3-L1 adipocytes". J Mol Endocrinol. 44 (4): 225–236. doi:10.1677/JME-09-0161. PMC 3058511. PMID 20089716.
  11. Lute B, Jou W, Lateef DM, Goldgof M, Xiao C, Piñol RA, Kravitz AV, Miller NR, Huang YG, Girardet C, Butler AA, Gavrilova O, Reitman ML (August 2014). "Biphasic effect of melanocortin agonists on metabolic rate and body temperature". Cell Metab. 20 (2): 333–345. doi:10.1016/j.cmet.2014.05.021. PMC 4126889. PMID 24981835.
  12. Shukla C, Britton SL, Koch LG, Novak CM (July 2012). "Region-specific differences in brain melanocortin receptors in rats of the lean phenotype". NeuroReport. 23 (10): 596–600. doi:10.1097/WNR.0b013e328354f5c1. PMC 3831884. PMID 22643233.
  13. Morgan C, Thomas RE, Cone RD (January 2004). "Melanocortin-5 receptor deficiency promotes defensive behavior in male mice". Horm. Behav. 45 (1): 56–63. PMID 14733892.
  14. Morgan C, Thomas RE, Ma W, Novotny MV, Cone RD (February 2004). "Melanocortin-5 receptor deficiency reduces a pheromonal signal for aggression in male mice". Chem Senses. 29 (2): 111–115. doi:10.1093/chemse/bjh011. PMID 14977807.
  15. Morgan C, Cone RD (January 2006). "Melanocortin-5 receptor deficiency in mice blocks a novel pathway influencing pheromone-induced aggression". Behav. Genet. 36 (2): 291–300. doi:10.1007/s10519-005-9024-9. PMID 16408249.
  16. Sebag JA, Hinkle PM (August 2009). "Opposite effects of the melanocortin-2 (MC2) receptor accessory protein MRAP on MC2 and MC5 receptor dimerization and trafficking". J Biol Chem. 284 (34): 22641–22648. doi:10.1074/jbc.M109.022400. PMC 2755671. PMID 19535343.

Further reading

  • Fathi Z, Iben LG, Parker EM (January 1995). "Cloning, expression, and tissue distribution of a fifth melanocortin receptor subtype". Neurochemical Research. 20 (1): 107–13. doi:10.1007/BF00995160. PMID 7739752.
  • Chowdhary BP, Gustavsson I, Wikberg JE, Chhajlani V (1994). "Localization of the human melanocortin-5 receptor gene (MC5R) to chromosome band 18p11.2 by fluorescence in situ hybridization". Cytogenetics and Cell Genetics. 68 (1–2): 79–81. doi:10.1159/000133895. PMID 7956366.
  • Griffon N, Mignon V, Facchinetti P, Diaz J, Schwartz JC, Sokoloff P (April 1994). "Molecular cloning and characterization of the rat fifth melanocortin receptor". Biochemical and Biophysical Research Communications. 200 (2): 1007–14. doi:10.1006/bbrc.1994.1550. PMID 8179577.
  • Gantz I, Shimoto Y, Konda Y, Miwa H, Dickinson CJ, Yamada T (May 1994). "Molecular cloning, expression, and characterization of a fifth melanocortin receptor". Biochemical and Biophysical Research Communications. 200 (3): 1214–20. doi:10.1006/bbrc.1994.1580. PMID 8185570.
  • Chhajlani V (February 1996). "Distribution of cDNA for melanocortin receptor subtypes in human tissues". Biochemistry and Molecular Biology International. 38 (1): 73–80. PMID 8932521.
  • 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". Molecular Endocrinology. 11 (3): 274–80. doi:10.1210/me.11.3.274. PMID 9058374.
  • Frändberg PA, Xu X, Chhajlani V (July 1997). "Glutamine235 and arginine272 in human melanocortin 5 receptor determines its low affinity to MSH". Biochemical and Biophysical Research Communications. 236 (2): 489–92. doi:10.1006/bbrc.1997.6994. PMID 9240466.
  • Yang YK, Thompson DA, Dickinson CJ, Wilken J, Barsh GS, Kent SB, Gantz I (January 1999). "Characterization of Agouti-related protein binding to melanocortin receptors". Molecular Endocrinology. 13 (1): 148–55. doi:10.1210/me.13.1.148. PMID 9892020.
  • Hatta N, Dixon C, Ray AJ, Phillips SR, Cunliffe WJ, Dale M, Todd C, Meggit S, Birch-MacHin MA, Rees JL (April 2001). "Expression, candidate gene, and population studies of the melanocortin 5 receptor". The Journal of Investigative Dermatology. 116 (4): 564–70. doi:10.1046/j.0022-202x.2001.01286.x. PMID 11286624.
  • Bednarek MA, MacNeil T, Kalyani RN, Tang R, Van der Ploeg LH, Weinberg DH (October 2001). "Selective, high affinity peptide antagonists of alpha-melanotropin action at human melanocortin receptor 4: their synthesis and biological evaluation in vitro". Journal of Medicinal Chemistry. 44 (22): 3665–72. doi:10.1021/jm010165y. PMID 11606131.
  • Lapinsh M, Veiksina S, Uhlén S, Petrovska R, Mutule I, Mutulis F, Yahorava S, Prusis P, Wikberg JE (January 2005). "Proteochemometric mapping of the interaction of organic compounds with melanocortin receptor subtypes". Molecular Pharmacology. 67 (1): 50–9. doi:10.1124/mol.104.002857. PMID 15470082.
  • Lohoff FW, Berrettini WH (December 2005). "Lack of association between variations in the melanocortin 5 receptor gene and bipolar disorder". Psychiatric Genetics. 15 (4): 255–8. doi:10.1097/00041444-200512000-00007. PMID 16314755.
  • Grieco P, Cai M, Han G, Trivedi D, Campiglia P, Novellino E, Hruby VJ (June 2007). "Further structure-activity studies of lactam derivatives of MT-II and SHU-9119: their activity and selectivity at human melanocortin receptors 3, 4, and 5". Peptides. 28 (6): 1191–6. doi:10.1016/j.peptides.2007.02.012. PMC 1955225. PMID 17482720.

External links

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