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FLASH GENE
Symbol MC1R contributors: mct - updated : 03-02-2016
HGNC name melanocortin 1 receptor (alpha melanocyte stimulating hormone receptor)
HGNC id 6929
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • seven transmembrane segments (7TM) receptor
  • two intracellular loops, the second may be involved in GPCR recycling
  • mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies homolog to murine extension (Ext)
    homolog to C.elegans Y62E10A.4
    Homologene
    FAMILY G protein coupled receptor superfamily
    CATEGORY regulatory , signaling hormone , receptor membrane G
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule
    text melanosomes, at the cell surface
    basic FUNCTION
  • melanocortin receptor 1 or melanocyte stimulating hormone (alpha MSH) receptor, heptahelical G protein-coupled receptor
  • regulator of eumelanin and phaeomelanin production
  • regulator of pigmentation phenotype
  • sex-specific role for MC1R in acute noxious thermal responses and pain of inflammatory origin
  • DEFB103B may be a novel MC1R agonist involved in regulating melanocyte responses in humans
  • MC1R and cAMP signaling can directly inhibit melanoma growth through regulation of the G2/M checkpoint (pMID: 23908401)
  • MC1R-signaling stimulates black eumelanin production through a cAMP-dependent pathway
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    text
  • epidermal development and maintenance UV protection
  • PATHWAY
    metabolism
    signaling hormonal , signal transduction
  • activation of the MC1R/POMC signaling pathway has been implicated in the regulation of both inflammation and extracellular matrix homeostasis
  • a component
  • constitutive dimer when expressed alone and constitutive heterodimer when co-expressed with variant alleles
  • homodimerization most likely results from formation of four disulfide bonds as well as non-covalent interactions of domain-swapping type
  • MC1R-PTEN axis is a central regulator for melanocytes response to UVB exposure revealing the molecular basis underlying the association between MC1R variants and melanomagenesis
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • OCA2
  • CNR1 activation did not engage the key regulator of skin pigmentation, cyclic AMP, showing a major difference compared with the regulation of melanogenesis by POMC through MC1R
  • MC1R regulates melanoma cell migration via inhibition of SDC2 expression
  • TP53 is an important target of the downstream MC1R signaling that reduces oxidative stress and possibly malignant transformation of melanocytes
  • melanin-independent interaction between MC1R and MET signaling pathways is required for HGF-dependent melanoma and this pathway is likely involved in human melanoma
  • cell & other
    REGULATION
    activated by POMC stimulating eumelanin synthesis and enhancing repair of ultraviolet radiation (UV)-induced DNA damage
    ASSOCIATED DISORDERS
    corresponding disease(s) HCL4
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    compromises the DNA damage response (DDR) and genomic stability of melanocytes
    constitutional     --low  
    by human dermal fibroblasts contributes to excess collagen synthesis in keloid scars
    Susceptibility
  • ephelides in childhood and solar lentigines
  • red hair and fair skin
  • cutaneous malignant melanoma (germline variants confer risk for BRAF-mutant melanoma)
  • to facial pigmented spots during aging
  • Variant & Polymorphism other
  • Arg151-Cys/Arg160-TRP/ASP294HIS strong associated with melanoma
  • variants altering melanoma cell growth and adhesion to extracellular matrix
  • variant R151C, R160W, and D294H strongly associated with red hair (decreasing MC1R cell surface expression)
  • variant RHC alleles associated with red hair, poor tanning ability, and increased skin cancer risk are partial loss-of-function forms
  • genetic variations in MC1R contribute to the acquired amount of facial pigmented spots during aging, through pathways independent of the basal melanin production
  • polymorphisms being a predisposing factor of melanoma in a southern European population with a relatively low incidence of the disease
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Mc1r is down-regulated in the skin of the Ube3a(-/-) mice