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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
Corresponding disease
HCL4 hair color 4
Location 16q24.3      Physical location : 89.984.286 - 89.987.384
Synonym name
  • melanocyte stimulating hormone receptor
  • melanotropin receptor
  • Synonym symbol(s) MCR1, MSHR, CMM5
    DNA
    TYPE anonymous DNA segment
    SPECIAL FEATURE arranged in tandem
    STRUCTURE 3.09 kb     1 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (TATA box)
    cytosine-phosphate-guanine/HTF
    Binding site
    text structure
  • AP1 and AP2 binding sites
  • two TATA box, several E-boxes
  • UBE3A is able to induce MC1R promoter activity
  • MAPPING cloned Y linked N status confirmed
    Physical map
    SPG7 16q24.3 spastic paraplegia 7, paraplegin (pure and complicated autosomal recessive) RPL13 16q24.3 ribosomal protein L13 CPNE7 16q24.3 copine VII DPEP1 16q24.3 dipeptidase 1 (renal) PCOLN3 16q24.3 procollagen (type III) N-endopeptidase FLJ31606 16q24.3 hypothetical protein FLJ31606 LOC388309 16 LOC388309 CDK10 16q24.3 cyclin-dependent kinase (CDC2-like) 10 MGC26885 16q24.3 hypothetical protein MGC26885 C16orf7 16q24 chromosome 16 open reading frame 7 ZFP276 16q24.3 zinc finger protein 276 homolog (mouse) FANCA 16q24.3 Fanconi anemia, complementation group A LOC197317 16q24.3 hypothetical LOC197317 Spir-2 16q24 Spir-2 protein KIAA1049 16q24.3 Spir-2 protein FLJ12547 16q24.3 hypothetical protein FLJ12547 MC1R 16q24.3 melanocortin 1 receptor (alpha melanocyte stimulating hormone receptor) TUBB4 16q24.3 tubulin, beta, 4 FLJ20186 16q24.3 hypothetical protein FLJ20186 MGC13198 16q24.3 hypothetical protein MGC13198 MGC16385 16q24.3 hypothetical protein MGC16385 AFG3L1 16q24 AFG3 ATPase family gene 3-like 1 (yeast) MGC3101 16q24.3 hypothetical protein MGC3101 GAS8 16q24.3 growth arrest-specific 8 C16orf3 16q24.3 chromosome 16 open reading frame 3 PRDM7 16q24.3 PR domain containing 7 LOC197331 16q24.3 HSA16q24 beta-tubulin 4Q pseudogene LOC388311 16 LOC388311 LOC388312 16 hypothetical gene supported by AK128780 LOC388313 16 similar to bA476I15.3 (novel protein similar to septin)
    RNA
    TRANSCRIPTS type messenger
    text
  • has an inefficient poly(A) site allowing intergenic splicing with its downstream neighbour TUBB3 (PMID: 26657157)
  • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    1 - 3115 - 317 - 2001 11707265
    65 C terminal extra Aas
    - - splicing 1270 - 385 - 2001 11707265
    65 C terminal extra Aas
    - - 954 - 317 - 2001 11707265
    - - 954 - 317 - 2001 11707265
    - - 954 - 317 - 2001 11707265
    - - 954 - 317 - 2001 11707265
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveintestinesmall intestine  highly
     liver   highly
    Endocrineadrenal glandcortex   
     pancreas   highly
    Urinarykidney   moderately
    Visualeye   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier liningretinal pigment epithelium (RPE)   Homo sapiens
    Epithelialsecretoryglandularendocrine 
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skin/Tegumentmelanocyte Homo sapiens
    cell lineage cells of melanocytic origin
    cell lines
    fluid/secretion
    at STAGE
    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