MC1R

Protein identityUniProt · HPA

UniProt accession

Q01726

Gene

MC1R

Ensembl

ENSG00000258839

Chromosome

16

Canonical length

317 aa

Protein class

Disease related genes, FDA approved drug targets, G-protein coupled receptors, Human disease related genes, Predicted membrane proteins

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

317 residues, UniProt reviewed canonical sequence.

>Q01726|MC1R
     1  MAVQGSQRRL LGSLNSTPTA IPQLGLAANQ TGARCLEVSI SDGLFLSLGL VSLVENALVV
    61  ATIAKNRNLH SPMYCFICCL ALSDLLVSGS NVLETAVILL LEAGALVARA AVLQQLDNVI
   121  DVITCSSMLS SLCFLGAIAV DRYISIFYAL RYHSIVTLPR ARRAVAAIWV ASVVFSTLFI
   181  AYYDHVAVLL CLVVFFLAML VLMAVLYVHM LARACQHAQG IARLHKRQRP VHQGFGLKGA
   241  VTLTILLGIF FLCWGPFFLH LTLIVLCPEH PTCGCIFKNF NLFLALIICN AIIDPLIYAF
   301  HSQELRRTLK EVLTCSW

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MC1R can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

7

Mean surface accessibility (rSASA)

0.31

Highest tissue expression

31 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MC1R.

Disease | AllUniProt

Conditions MC1R is implicated in, by any mechanism.

• Melanoma, cutaneous malignant 5 (CMM5) MIM:613099

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 819 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Tyrosinase-positive oculocutaneous albinism
• Skin and Hair Hypopigmentation
• SKIN/HAIR/EYE PIGMENTATION, VARIATION IN, 2

Disease | ImmuneIEDB

Conditions an epitope on MC1R was assayed in.

• skin melanoma T cell
• alopecia areata T cell
• melanoma T cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.97

gnomAD pLI

0

gnomAD missense Z

-2.34

DepMap mean gene effect

0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adenylate cyclase-activating G protein-coupled receptor signaling pathway
• G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
• intracellular signal transduction
• melanin biosynthetic process
• negative regulation of tumor necrosis factor production
• phospholipase C-activating G protein-coupled receptor signaling pathway
• pigmentation
• positive regulation of cAMP/PKA signal transduction
• positive regulation of feeding behavior
• positive regulation of melanin biosynthetic process
• positive regulation of transcription by RNA polymerase II
• sensory perception of pain
• UV protection
• UV-damage excision repair

Molecular functions

• corticotropin receptor activity
• G protein-coupled peptide receptor activity
• hormone binding
• melanocortin receptor activity
• melanocyte-stimulating hormone receptor activity
• ubiquitin protein ligase binding

Cellular components

• cytoplasm
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• G protein-coupled receptor, rhodopsin-like
• Melanocortin/ACTH receptor
• GPCR, rhodopsin-like, 7TM
• 7 transmembrane receptor (rhodopsin family)
• Melanocyte-stimulating hormone receptor

KeywordsUniProt

• Calcium
• Cell membrane
• Disulfide bond
• G-protein coupled receptor
• Glycoprotein
• Lipoprotein
• Membrane
• Metal-binding
• Palmitate
• Receptor
• Transducer
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of MC1R in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• GNB1
• MGRN1
• OPN3
• MRAP2
• MRAP