UniProt functional annotation for Q01726



	UniProt functional annotation for Q01726

UniProt code: Q01726.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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). {ECO:0000269|PubMed:11442765, ECO:0000269|PubMed:11707265, ECO:0000269|PubMed:1325670, ECO:0000269|PubMed:1516719, ECO:0000269|PubMed:16463023, ECO:0000269|PubMed:19737927, ECO:0000269|PubMed:31097585, ECO:0000269|PubMed:8463333}.

Subunit: Interacts with MGRN1, but does not undergo MGRN1-mediated ubiquitination; this interaction competes with GNAS-binding and thus inhibits agonist-induced cAMP production (PubMed:19737927). Interacts with OPN3; the interaction results in a decrease in MC1R-mediated cAMP signaling and ultimately a decrease in melanin production in melanocytes (PubMed:31097585). {ECO:0000269|PubMed:19737927, ECO:0000269|PubMed:31097585}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:31097585}; Multi-pass membrane protein {ECO:0000255}.

Tissue specificity: Expressed in melanocytes (PubMed:1325670, PubMed:31097585). Expressed in corticoadrenal tissue (PubMed:1325670). {ECO:0000269|PubMed:1325670, ECO:0000269|PubMed:31097585}.

Polymorphism: Genetic variants in MC1R define the skin/hair/eye pigmentation variation locus 2 (SHEP2) [MIM:266300]. Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator, with type I skin being the most lightly pigmented and type IV the most dark pigmented. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair. Partial loss-of-function mutations are associated with fair skin, poor tanning and increased skin cancer risk.

Polymorphism: MC1R variants associated with red hair and fair skin, determine female-specific increased analgesia from kappa-opioid receptor agonist [MIM:613098]. {ECO:0000269|PubMed:12663858}.

Disease: Melanoma, cutaneous malignant 5 (CMM5) [MIM:613099]: 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. {ECO:0000269|PubMed:17434924, ECO:0000269|PubMed:19338054}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

Similarity: Belongs to the G-protein coupled receptor 1 family. {ECO:0000255|PROSITE-ProRule:PRU00521}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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). {ECO:0000269\|PubMed:11442765, ECO:0000269\|PubMed:11707265, ECO:0000269\|PubMed:1325670, ECO:0000269\|PubMed:1516719, ECO:0000269\|PubMed:16463023, ECO:0000269\|PubMed:19737927, ECO:0000269\|PubMed:31097585, ECO:0000269\|PubMed:8463333}.


Subunit:		Interacts with MGRN1, but does not undergo MGRN1-mediated ubiquitination; this interaction competes with GNAS-binding and thus inhibits agonist-induced cAMP production (PubMed:19737927). Interacts with OPN3; the interaction results in a decrease in MC1R-mediated cAMP signaling and ultimately a decrease in melanin production in melanocytes (PubMed:31097585). {ECO:0000269\|PubMed:19737927, ECO:0000269\|PubMed:31097585}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:31097585}; Multi-pass membrane protein {ECO:0000255}.
Tissue specificity:		Expressed in melanocytes (PubMed:1325670, PubMed:31097585). Expressed in corticoadrenal tissue (PubMed:1325670). {ECO:0000269\|PubMed:1325670, ECO:0000269\|PubMed:31097585}.
Polymorphism:		Genetic variants in MC1R define the skin/hair/eye pigmentation variation locus 2 (SHEP2) [MIM:266300]. Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator, with type I skin being the most lightly pigmented and type IV the most dark pigmented. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair. Partial loss-of-function mutations are associated with fair skin, poor tanning and increased skin cancer risk.
Polymorphism:		MC1R variants associated with red hair and fair skin, determine female-specific increased analgesia from kappa-opioid receptor agonist [MIM:613098]. {ECO:0000269\|PubMed:12663858}.
Disease:		Melanoma, cutaneous malignant 5 (CMM5) [MIM:613099]: 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. {ECO:0000269\|PubMed:17434924, ECO:0000269\|PubMed:19338054}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
Similarity:		Belongs to the G-protein coupled receptor 1 family. {ECO:0000255\|PROSITE-ProRule:PRU00521}.