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Gene Review

Mc1r  -  melanocortin 1 receptor

Mus musculus

Synonyms: MC1-R, MSH-R, Melanocortin receptor 1, Melanocyte-stimulating hormone receptor, Msh-r, ...
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Disease relevance of Mc1r


High impact information on Mc1r

  • In the mouse, extension is epistatic to agouti, hence dominant mutants of the MC1R encoding constitutively active receptors are not inhibited by the agouti antagonist, and animals with dominant alleles of both loci remain darkly pigmented [6].
  • A constitutively activating C125R mutation in the MC1R was found specifically in darkly pigmented animals carrying the Alaska Silver allele (EA) [6].
  • These observations provide new insight into the regulation of energy metabolism and indicate a molecular basis for crosstalk between melanocortin-receptor signalling and immune function [7].
  • Bone morphogenetic protein (BMP) signaling controls hair pigmentation by means of cross-talk with the melanocortin receptor-1 pathway [8].
  • Via quantitative trait locus mapping followed by a candidate gene strategy using both mutant mice and pharmacological tools, we now demonstrate that the melanocortin-1 receptor (Mc1r) gene mediates kappa-opioid analgesia in female mice only [9].

Chemical compound and disease context of Mc1r


Biological context of Mc1r


Anatomical context of Mc1r


Associations of Mc1r with chemical compounds


Physical interactions of Mc1r


Regulatory relationships of Mc1r


Other interactions of Mc1r

  • Here we have addressed this aspect using a dual pharmacological and genetic approach, taking advantage of the recent characterization of more selective agonists/antagonists at MC1 and MC3-R as well as of the existence of a naturally defective MC1-R mouse strain, the recessive yellow (e/e) mouse [30].
  • These results support the hypothesis that murine hair growth and attendant melanogenesis can be regulated through coordinated changes in local expression of POMC, MC1-R, and tyrosinase genes [23].
  • Novel agouti-related-protein-based melanocortin-1 receptor antagonist [31].
  • These results suggest that the expression of the MC1-R gene, but not of the POMC gene, plays an important role in the regulation of melanocyte differentiation in mouse skin [20].
  • An MSH binding site characterized in these cells is presumably the MC5 receptor, based on the observation that this is the only other melanocortin receptor mRNA detected in these cells [32].

Analytical, diagnostic and therapeutic context of Mc1r

  • An allelism test indicated the tawny mutant gene to be a new allele at the Mc1r locus and dominant to the recessive yellow (Mc1re) [33].
  • Molecular cloning, expression, and characterization of a fifth melanocortin receptor [34].
  • MC1Re/e mice receiving MC1R+ bone marrow showed a similar course of inflammation to non-transplanted MC1Re/e. Likewise, transplantation of MC1R bone marrow into C57BL/6WT mice did not lead to any worsening of disease [3].
  • Semiquantitative RT-PCR demonstrated that monocytes and DC express MC-1R, but none of the other members of the MC-receptor family [35].
  • To better understand how Mc1r signaling affects different cutaneous phenotypes, we examined large-scale patterns of gene expression in different skin components (whole epidermal sheets, basal epidermal cells and whole skins) of neonatal (P2.5) normal and recessive yellow mice, starting with a 26K mouse cDNA microarray [36].


  1. Role of G protein-coupled receptor kinases in the homologous desensitization of the human and mouse melanocortin 1 receptors. Sánchez-Más, J., Guillo, L.A., Zanna, P., Jiménez-Cervantes, C., García-Borrón, J.C. Mol. Endocrinol. (2005) [Pubmed]
  2. Receptor biology of the melanocortins, a family of neuroimmunomodulatory peptides. Tatro, J.B. Neuroimmunomodulation (1996) [Pubmed]
  3. Crucial role of the melanocortin receptor MC1R in experimental colitis. Maaser, C., Kannengiesser, K., Specht, C., Lügering, A., Brzoska, T., Luger, T.A., Domschke, W., Kucharzik, T. Gut (2006) [Pubmed]
  4. Physiological and anatomical circuitry between Agouti-related protein and leptin signaling. Wilson, B.D., Bagnol, D., Kaelin, C.B., Ollmann, M.M., Gantz, I., Watson, S.J., Barsh, G.S. Endocrinology (1999) [Pubmed]
  5. Agouti/melanocortin interactions with leptin pathways in obesity. Zemel, M.B. Nutr. Rev. (1998) [Pubmed]
  6. A non-epistatic interaction of agouti and extension in the fox, Vulpes vulpes. Våge, D.I., Lu, D., Klungland, H., Lien, S., Adalsteinsson, S., Cone, R.D. Nat. Genet. (1997) [Pubmed]
  7. The mouse mahogany locus encodes a transmembrane form of human attractin. Gunn, T.M., Miller, K.A., He, L., Hyman, R.W., Davis, R.W., Azarani, A., Schlossman, S.F., Duke-Cohan, J.S., Barsh, G.S. Nature (1999) [Pubmed]
  8. Bone morphogenetic protein (BMP) signaling controls hair pigmentation by means of cross-talk with the melanocortin receptor-1 pathway. Sharov, A.A., Fessing, M., Atoyan, R., Sharova, T.Y., Haskell-Luevano, C., Weiner, L., Funa, K., Brissette, J.L., Gilchrest, B.A., Botchkarev, V.A. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  9. The melanocortin-1 receptor gene mediates female-specific mechanisms of analgesia in mice and humans. Mogil, J.S., Wilson, S.G., Chesler, E.J., Rankin, A.L., Nemmani, K.V., Lariviere, W.R., Groce, M.K., Wallace, M.R., Kaplan, L., Staud, R., Ness, T.J., Glover, T.L., Stankova, M., Mayorov, A., Hruby, V.J., Grisel, J.E., Fillingim, R.B. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  10. The receptor for alpha-melanotropin of mouse and human melanoma cells. Application of a potent alpha-melanotropin photoaffinity label. Solca, F., Siegrist, W., Drozdz, R., Girard, J., Eberle, A.N. J. Biol. Chem. (1989) [Pubmed]
  11. Cerulenin mimics effects of leptin on metabolic rate, food intake, and body weight independent of the melanocortin system, but unlike leptin, cerulenin fails to block neuroendocrine effects of fasting. Makimura, H., Mizuno, T.M., Yang, X.J., Silverstein, J., Beasley, J., Mobbs, C.V. Diabetes (2001) [Pubmed]
  12. Calmodulin-binding peptides interfere with melanocyte-stimulating hormone receptor activity and stimulate adenosine 3',5'-monophosphate production in M2R mouse melanoma cells. Eshel, Y., Salomon, Y. Endocrinology (1994) [Pubmed]
  13. Interaction of Agouti protein with the melanocortin 1 receptor in vitro and in vivo. Ollmann, M.M., Lamoreux, M.L., Wilson, B.D., Barsh, G.S. Genes Dev. (1998) [Pubmed]
  14. Functional variation of MC1R alleles from red-haired individuals. Healy, E., Jordan, S.A., Budd, P.S., Suffolk, R., Rees, J.L., Jackson, I.J. Hum. Mol. Genet. (2001) [Pubmed]
  15. Regulation of melanocortin 1 receptor expression at the mRNA and protein levels by its natural agonist and antagonist. Rouzaud, F., Annereau, J.P., Valencia, J.C., Costin, G.E., Hearing, V.J. FASEB J. (2003) [Pubmed]
  16. Melanocortin receptor binding determinants in the agouti protein. Kiefer, L.L., Veal, J.M., Mountjoy, K.G., Wilkison, W.O. Biochemistry (1998) [Pubmed]
  17. Agouti protein inhibits growth of B16 melanoma cells in vitro by acting through melanocortin receptors. Siegrist, W., Willard, D.H., Wilkison, W.O., Eberle, A.N. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  18. Agouti signaling protein and other factors modulating differentiation and proliferation of immortal melanoblasts. Sviderskaya, E.V., Hill, S.P., Balachandar, D., Barsh, G.S., Bennett, D.C. Dev. Dyn. (2001) [Pubmed]
  19. Alpha-melanocyte-stimulating hormone suppresses antigen-induced lymphocyte proliferation in humans independently of melanocortin 1 receptor gene status. Cooper, A., Robinson, S.J., Pickard, C., Jackson, C.L., Friedmann, P.S., Healy, E. J. Immunol. (2005) [Pubmed]
  20. The melanocortin receptor-1 gene but not the proopiomelanocortin gene is expressed in melanoblasts and contributes their differentiation in the mouse skin. Hirobe, T., Takeuchi, S., Hotta, E. Pigment Cell Res. (2004) [Pubmed]
  21. A possible involvement of melanocortin 3 receptor in the regulation of adrenal gland function in the chicken. Takeuchi, S., Takahashi, S. Biochim. Biophys. Acta (1999) [Pubmed]
  22. Structure-activity relationships of the melanocortin tetrapeptide Ac-His-D-Phe-Arg-Trp-NH2 at the mouse melanocortin receptors. 4. Modifications at the Trp position. Holder, J.R., Xiang, Z., Bauzo, R.M., Haskell-Luevano, C. J. Med. Chem. (2002) [Pubmed]
  23. Production of POMC, CRH-R1, MC1, and MC2 receptor mRNA and expression of tyrosinase gene in relation to hair cycle and dexamethasone treatment in the C57BL/6 mouse skin. Ermak, G., Slominski, A. J. Invest. Dermatol. (1997) [Pubmed]
  24. Effects of melanocortin receptor activation and blockade on ethanol intake: a possible role for the melanocortin-4 receptor. Navarro, M., Cubero, I., Chen, A.S., Chen, H.Y., Knapp, D.J., Breese, G.R., Marsh, D.J., Thiele, T.E. Alcohol. Clin. Exp. Res. (2005) [Pubmed]
  25. Collagen metabolism is a novel target of the neuropeptide alpha-melanocyte-stimulating hormone. Böhm, M., Raghunath, M., Sunderkötter, C., Schiller, M., Ständer, S., Brzoska, T., Cauvet, T., Schiöth, H.B., Schwarz, T., Luger, T.A. J. Biol. Chem. (2004) [Pubmed]
  26. Effect of Agouti-related protein in regulation of the hypothalamic-pituitary-thyroid axis in the melanocortin 4 receptor knockout mouse. Fekete, C., Marks, D.L., Sarkar, S., Emerson, C.H., Rand, W.M., Cone, R.D., Lechan, R.M. Endocrinology (2004) [Pubmed]
  27. New Melanocortin 1 Receptor Binding Motif Based on the C-Terminal Sequence of alpha-Melanocyte-Stimulating Hormone. Schi??th, H.B., Muceniece, R., Mutule, I., Wikberg, J.E. Basic & clinical pharmacology & toxicology. (2006) [Pubmed]
  28. Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides. Getting, S.J., Schiöth, H.B., Perretti, M. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  29. A selective small molecule agonist of the melanocortin-1 receptor inhibits lipopolysaccharide-induced cytokine accumulation and leukocyte infiltration in mice. Kang, L., McIntyre, K.W., Gillooly, K.M., Yang, Y., Haycock, J., Roberts, S., Khanna, A., Herpin, T.F., Yu, G., Wu, X., Morton, G.C., Tuerdi, H., Koplowitz, B., Walker, S.G., Wardwell-Swanson, J., Macor, J.E., Lawrence, R.M., Carlson, K.E. J. Leukoc. Biol. (2006) [Pubmed]
  30. Redundancy of a functional melanocortin 1 receptor in the anti-inflammatory actions of melanocortin peptides: studies in the recessive yellow (e/e) mouse suggest an important role for melanocortin 3 receptor. Getting, S.J., Christian, H.C., Lam, C.W., Gavins, F.N., Flower, R.J., Schiöth, H.B., Perretti, M. J. Immunol. (2003) [Pubmed]
  31. Novel agouti-related-protein-based melanocortin-1 receptor antagonist. Thirumoorthy, R., Holder, J.R., Bauzo, R.M., Richards, N.G., Edison, A.S., Haskell-Luevano, C. J. Med. Chem. (2001) [Pubmed]
  32. Characterization of melanocortin receptor subtype expression in murine adipose tissues and in the 3T3-L1 cell line. Boston, B.A., Cone, R.D. Endocrinology (1996) [Pubmed]
  33. Tawny: a novel light coat color mutation found in a wild population of Mus musculus molossinus, a new allele at the melanocortin 1 receptor (Mc1r) locus. Wada, A., Okumoto, M., Tsudzuki, M. Exp. Anim. (1999) [Pubmed]
  34. Molecular cloning, expression, and characterization of a fifth melanocortin receptor. Gantz, I., Shimoto, Y., Konda, Y., Miwa, H., Dickinson, C.J., Yamada, T. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  35. Human peripheral blood-derived dendritic cells express functional melanocortin receptor MC-1R. Becher, E., Mahnke, K., Brzoska, T., Kalden, D.H., Grabbe, S., Luger, T.A. Ann. N. Y. Acad. Sci. (1999) [Pubmed]
  36. Skin layer-specific transcriptional profiles in normal and recessive yellow (Mc1re/Mc1re) mice. April, C.S., Barsh, G.S. Pigment Cell Res. (2006) [Pubmed]
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