Melanocortin 5 receptor explained

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

Physiology

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]

Pheromones

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 pheromonal signals.^{[13] [14] [15]}

MRAP

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

Evolution

Paralogues^[17]

• MC4R
• MC3R
• MC1R
• MC2R
• S1PR1
• LPAR1
• S1PR3
• GPR12
• LPAR2
• GPR3
• S1PR2
• GPR6
• GPR119
• LPAR3
• CNR1
• S1PR5
• S1PR4
• CNR2

See also

• Melanocortin receptor

Further reading

• Fathi Z, Iben LG, Parker EM . Cloning, expression, and tissue distribution of a fifth melanocortin receptor subtype . Neurochemical Research . 20 . 1 . 107–13 . January 1995 . 7739752 . 10.1007/BF00995160 . 20792213 .
• Chowdhary BP, Gustavsson I, Wikberg JE, Chhajlani V . 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 . 1994 . 7956366 . 10.1159/000133895 .
• Griffon N, Mignon V, Facchinetti P, Diaz J, Schwartz JC, Sokoloff P . Molecular cloning and characterization of the rat fifth melanocortin receptor . Biochemical and Biophysical Research Communications . 200 . 2 . 1007–14 . April 1994 . 8179577 . 10.1006/bbrc.1994.1550 .
• Gantz I, Shimoto Y, Konda Y, Miwa H, Dickinson CJ, Yamada T . Molecular cloning, expression, and characterization of a fifth melanocortin receptor . Biochemical and Biophysical Research Communications . 200 . 3 . 1214–20 . May 1994 . 8185570 . 10.1006/bbrc.1994.1580 . 2027.42/31580 . free .
• Chhajlani V . Distribution of cDNA for melanocortin receptor subtypes in human tissues . Biochemistry and Molecular Biology International . 38 . 1 . 73–80 . February 1996 . 8932521 .
• Yang YK, Ollmann MM, Wilson BD, Dickinson C, Yamada T, Barsh GS, Gantz I . Effects of recombinant agouti-signaling protein on melanocortin action . Molecular Endocrinology . 11 . 3 . 274–80 . March 1997 . 9058374 . 10.1210/mend.11.3.9898 . free .
• Frändberg PA, Xu X, Chhajlani V . Glutamine235 and arginine272 in human melanocortin 5 receptor determines its low affinity to MSH . Biochemical and Biophysical Research Communications . 236 . 2 . 489–92 . July 1997 . 9240466 . 10.1006/bbrc.1997.6994 .
• Yang YK, Thompson DA, Dickinson CJ, Wilken J, Barsh GS, Kent SB, Gantz I . Characterization of Agouti-related protein binding to melanocortin receptors . Molecular Endocrinology . 13 . 1 . 148–55 . January 1999 . 9892020 . 10.1210/me.13.1.148 .
• Hatta N, Dixon C, Ray AJ, Phillips SR, Cunliffe WJ, Dale M, Todd C, Meggit S, Birch-MacHin MA, Rees JL . Expression, candidate gene, and population studies of the melanocortin 5 receptor . The Journal of Investigative Dermatology . 116 . 4 . 564–70 . April 2001 . 11286624 . 10.1046/j.0022-202x.2001.01286.x . free .
• Bednarek MA, MacNeil T, Kalyani RN, Tang R, Van der Ploeg LH, Weinberg DH . 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 . October 2001 . 11606131 . 10.1021/jm010165y .
• Lapinsh M, Veiksina S, Uhlén S, Petrovska R, Mutule I, Mutulis F, Yahorava S, Prusis P, Wikberg JE . Proteochemometric mapping of the interaction of organic compounds with melanocortin receptor subtypes . Molecular Pharmacology . 67 . 1 . 50–9 . January 2005 . 15470082 . 10.1124/mol.104.002857 . 13536417 .
• Lohoff FW, Berrettini WH . Lack of association between variations in the melanocortin 5 receptor gene and bipolar disorder . Psychiatric Genetics . 15 . 4 . 255–8 . December 2005 . 16314755 . 10.1097/00041444-200512000-00007 . 21170090 .
• Grieco P, Cai M, Han G, Trivedi D, Campiglia P, Novellino E, Hruby VJ . 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 . June 2007 . 17482720 . 1955225 . 10.1016/j.peptides.2007.02.012 .

External links

• Web site: Melanocortin Receptors: MC₅ . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology . 2008-12-05 . 2014-07-14 . https://web.archive.org/web/20140714111153/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2356 . dead .

Notes and References

1. Chhajlani V, Muceniece R, Wikberg JE . Molecular cloning of a novel human melanocortin receptor . Biochemical and Biophysical Research Communications . 195 . 2 . 866–73 . September 1993 . 8396929 . 10.1006/bbrc.1993.2125 .
2. Web site: Entrez Gene: MC5R melanocortin 5 receptor.
3. Thiboutot D, Sivarajah A, Gilliland K, Cong Z, Clawson G . The melanocortin 5 receptor is expressed in human sebaceous glands and rat preputial cells . The Journal of Investigative Dermatology . 115 . 4 . 614–9 . October 2000 . 10998132 . 10.1046/j.1523-1747.2000.00094.x . free .
4. Chen W, Kelly MA, Opitz-Araya X, Thomas RE, Low MJ, Cone RD . Exocrine gland dysfunction in MC5-R-deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides . Cell . 91 . 6 . 789–98 . December 1997 . 9413988 . 10.1016/S0092-8674(00)80467-5 . 6251691 . free .
5. Zhang L, Li WH, Anthonavage M, Pappas A, Rossetti D, Cavender D, Seiberg M, Eisinger M . Melanocortin-5 receptor and sebogenesis. . Eur J Pharmacol . 660 . 1 . 202–206 . June 2011 . 21215742 . 10.1016/j.ejphar.2010.10.100 .
6. An JJ, Rhee Y, Kim SH, Kim DM, Han DH, Hwang JH, Jin YJ, Cha BS, Baik JH, Lee WT, Lim SK . Peripheral effect of alpha-melanocyte-stimulating hormone on fatty acid oxidation in skeletal muscle . The Journal of Biological Chemistry . 282 . 5 . 2862–70 . February 2007 . 17127674 . 10.1074/jbc.M603454200 . free .
7. Møller CL, Raun K, Jacobsen ML, Pedersen TÅ, Holst B, Conde-Frieboes KW, Wulff BS . Characterization of murine melanocortin receptors mediating adipocyte lipolysis and examination of signalling pathways involved. . Mol Cell Endocrinol . 341 . 1–2 . 9–17 . July 2011 . 21616121 . 10.1016/j.mce.2011.03.010 . 31837693 .
8. Simamura E, Arikawa T, Ikeda T, Shimada H, Shoji H, Masuta H, Nakajima Y, Otani H, Yonekura H, Hatta T . Melanocortins contribute to sequential differentiation and enucleation of human erythroblasts via melanocortin receptors 1, 2 and 5. . PLOS ONE . 10 . 4 . e0123232 . April 2015 . 25860801 . 10.1371/journal.pone.0123232 . 4393082. 2015PLoSO..1023232S . free .
9. Lee DJ, Taylor AW . 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 . October 2013 . 24043903 . 10.4049/jimmunol.1300182 . 3796047.
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 . 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 . April 2010 . 20089716 . 10.1677/JME-09-0161 . 3058511.
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 . Biphasic effect of melanocortin agonists on metabolic rate and body temperature. . Cell Metab. . 20 . 2 . 333–345 . August 2014 . 24981835 . 10.1016/j.cmet.2014.05.021 . 4126889.
12. Shukla C, Britton SL, Koch LG, Novak CM . Region-specific differences in brain melanocortin receptors in rats of the lean phenotype. . NeuroReport . 23 . 10 . 596–600 . July 2012 . 22643233 . 10.1097/WNR.0b013e328354f5c1 . 3831884.
13. Morgan C, Thomas RE, Cone RD . Melanocortin-5 receptor deficiency promotes defensive behavior in male mice. . Horm. Behav. . 45 . 1 . 56–63 . January 2004 . 14733892 . 10.1016/j.yhbeh.2003.08.004 . 32531156 .
14. Morgan C, Thomas RE, Ma W, Novotny MV, Cone RD . Melanocortin-5 receptor deficiency reduces a pheromonal signal for aggression in male mice. . Chem Senses . 29 . 2 . 111–115 . February 2004 . 14977807 . 10.1093/chemse/bjh011. free .
15. Morgan C, Cone RD . Melanocortin-5 receptor deficiency in mice blocks a novel pathway influencing pheromone-induced aggression. . Behav. Genet. . 36 . 2 . 291–300 . January 2006 . 16408249 . 10.1007/s10519-005-9024-9. 9659300 .
16. Sebag JA, Hinkle PM . 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 . August 2009 . 19535343 . 10.1074/jbc.M109.022400 . 2755671. free .
17. Web site: GeneCards®: The Human Gene Database .