MC1R

This intronless gene encodes the receptor protein for melanocyte-stimulating hormone (MSH). The encoded protein, a seven pass transmembrane G protein coupled receptor, controls melanogenesis. Two types of melanin exist: red pheomelanin and black eumelanin. Gene mutations that lead to a loss in function are associated with increased pheomelanin production, which leads to lighter skin and hair color. Eumelanin is photoprotective but pheomelanin may contribute to UV-induced skin damage by generating free radicals upon UV radiation. Binding of MSH to its receptor activates the receptor and stimulates eumelanin synthesis. This receptor is a major determining factor in sun sensitivity and is a genetic risk factor for melanoma and non-melanoma skin cancer. Over 30 variant alleles have been identified which correlate with skin and hair color, providing evidence that this gene is an important component in determining normal human pigment variation. [provided by RefSeq, Jul 2008]

Full Name

Melanocortin 1 Receptor

Function

Receptor for MSH (alpha, beta and gamma) and ACTH (PubMed:1325670, PubMed:8463333, PubMed:1516719, PubMed:11442765, PubMed:11707265).

The activity of this receptor is mediated by G proteins which activate adenylate cyclase (PubMed:1325670, PubMed:11707265, PubMed:16463023, PubMed:19737927).

Mediates melanogenesis, the production of eumelanin (black/brown) and phaeomelanin (red/yellow), via regulation of cAMP signaling in melanocytes (PubMed:31097585).

Biological Process

Adenylate cyclase-activating G protein-coupled receptor signaling pathway Source: BHF-UCL
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Source: ProtInc
Intracellular signal transduction Source: BHF-UCL
Melanin biosynthetic process Source: Ensembl
Multicellular organism development Source: ProtInc
Negative regulation of tumor necrosis factor production Source: BHF-UCL
Pigmentation Source: BHF-UCL
Positive regulation of feeding behavior Source: Ensembl
Positive regulation of protein kinase A signaling Source: BHF-UCL
Positive regulation of protein kinase B signaling Source: BHF-UCL
Positive regulation of protein kinase C signaling Source: BHF-UCL
Positive regulation of transcription by RNA polymerase II Source: BHF-UCL
Regulation of metabolic process Source: GO_Central
Sensory perception of pain Source: Ensembl
UV-damage excision repair Source: BHF-UCL
UV protection Source: ProtInc

Cellular Location

Cell membrane

Involvement in disease

Melanoma, cutaneous malignant 5 (CMM5):
A malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but also may involve other sites.

Topology

Extracellular: 1-37
Helical: 38-63
Cytoplasmic: 64-72
Helical: 73-93
Extracellular: 94-118
Helical: 119-140
Cytoplasmic: 141-163
Helical: 164-183
Extracellular: 184-191
Helical: 192-211
Cytoplasmic: 212-240
Helical: 241-266
Extracellular: 267-279
Helical: 280-300
Cytoplasmic: 301-317