Melanocortin 1 receptor (MC1R) (MC1R)

The Melanocortin 1 receptor (MC1R) is a Class A G protein-coupled receptor primarily located on the plasma membrane of melanocytes (UniProt: P32245). It serves as a key regulator of mammalian skin and hair color by mediating the effects of melanocortins, specifically alpha-melanocyte-stimulating hormone (α-MSH) (NCBI Gene: 4157). Upon activation, MC1R stimulates the production of eumelanin, a photoprotective pigment, while its inhibition or loss of function results in the production of pheomelanin, which is associated with red hair, fair skin, and increased sensitivity to ultraviolet radiation (PubMed: 29438760). Beyond its role in pigmentation, MC1R is expressed in immune cells and leukocytes, where it exerts anti-inflammatory effects (PubMed: 18331458). Therapeutically, MC1R is targeted by drugs like afamelanotide to prevent phototoxicity in patients with erythropoietic protoporphyria (FDA: Scenesse). Understanding MC1R signaling is also crucial in oncology, as certain genetic variants are significant risk factors for melanoma and non-melanoma skin cancers (PubMed: 21102416).

Other names

Melanocyte-stimulating hormone receptorMSH-RMC1-RMelanocortin receptor 1

Agonism of the MC1R receptor activates the Gs-protein/adenylyl cyclase pathway, leading to increased intracellular cAMP levels, which subsequently activates microphthalmia-associated transcription factor (MITF) to promote the synthesis of eumelanin (PubMed: 29438760).