Mc1r pigmentation pathway implicated in melanoma risk. Alpha-melanocyte stimulating hormone (α-MSH) serves as a ligand of Mc1r. Agouti protein antagonizes this interaction. Binding of MSH to Mc1r stimulates adenylate cyclase to generate cAMP. cAMP is one of the key mediators of a series of events that leads to the conversion of pheomelanin to a photoprotective eumelanin during melanogenesis. The tyrosinase (Tyr) and the tyrosine-related protein kinase 1 (Tyrp-1) are the key enzymes that regulate this process. The variants of the MC1R, TYR, and TYRP-1, presumably lead to pigmentation differences, photosensitivity, and predisposition to cutaneous melanoma.