Affinage

MC1R

Melanocyte-stimulating hormone receptor · UniProt Q01726

Length
317 aa
Mass
34.7 kDa
Annotated
2026-04-28
100 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MC1R is a Gs-coupled melanocortin receptor that transduces α-MSH and ACTH signals into cAMP-dependent activation of pigmentation, DNA damage repair, antioxidant defense, and cell cycle control programs in melanocytes and other cell types. Ligand binding stimulates adenylyl cyclase to elevate cAMP, activating PKA/CREB-mediated transcription of pigmentation genes including tyrosinase and MITF, while simultaneously engaging p38 MAPK and ERK pathways to enhance nucleotide excision repair (via DDB2), suppress UV-induced reactive oxygen species, and maintain centromere integrity through MITF–CENPA interaction (PMID:8612494, PMID:22336944, PMID:21898403, PMID:34001865). Receptor function critically depends on ZDHHC13-mediated palmitoylation—enhanced by AMPK phosphorylation of ZDHHC13 at S208—which promotes MC1R surface expression and downstream signaling; common red hair color (RHC) variants (R151C, R160W, D294H and others) impair surface trafficking and/or Gs coupling and exert dominant-negative effects on wild-type receptor, leading to defective cAMP signaling, reduced UV-induced DNA repair, and elevated melanoma susceptibility (PMID:17616515, PMID:28869973, PMID:36701140, PMID:16827749). Beyond melanocytes, MC1R suppresses LPS-induced inflammatory signaling in macrophages via NF-κB and p38 inhibition, protects nigrostriatal dopaminergic neurons from toxin-induced degeneration, and guards against intestinal inflammation through expression on non-hematopoietic cells (PMID:18388300, PMID:28019657, PMID:16543288).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1996 High

    Establishing MC1R as the specific melanocortin receptor on human melanocytes answered which receptor mediates α-MSH/ACTH-driven cAMP production, tyrosinase activation, and proliferation, providing the foundational signaling framework.

    Evidence Receptor binding, cAMP, tyrosinase activity, and proliferation assays in cultured human melanocytes with ligand rank-order correlation

    PMID:8612494

    Open questions at the time
    • Downstream transcriptional targets not yet identified
    • No structural basis for ligand selectivity
    • Signaling beyond cAMP not explored
  2. 1999 Medium

    Mapping the MC1R promoter architecture identified SP-1 and E-box elements as transcriptional regulators, answering how MC1R expression itself is controlled.

    Evidence Promoter deletion/reporter assays and gel shift in cell lines

    PMID:10462496

    Open questions at the time
    • Melanocyte-specific chromatin context not addressed
    • Upstream signaling to these elements not defined
  3. 2002 Medium

    Demonstrating that MITF binds the MC1R promoter E-box and drives MC1R transcription established a positive feedback loop: MC1R→cAMP→MITF→MC1R.

    Evidence EMSA and promoter-reporter assays with MITF co-transfection in NIH/3T3 cells

    PMID:12204775

    Open questions at the time
    • Feedback loop not validated in primary melanocytes
    • Quantitative contribution of MITF vs. SP-1 unknown
  4. 2003 Medium

    Showing that RHC variants R151C and R160W have impaired cAMP/CREB signaling in heterologous cells established defective Gs coupling as the molecular basis of loss-of-function alleles linked to fair skin and melanoma risk.

    Evidence cAMP-responsive reporter and CREB phosphorylation in stably transfected HEK293 cells

    PMID:12851335

    Open questions at the time
    • Surface expression levels not quantified for these variants
    • Dominant-negative effects not yet tested
  5. 2006 High

    Two concurrent advances revealed MC1R's photoprotective roles extend beyond melanin: MC1R loss increased UV-induced CPD accumulation and impaired repair independent of pigmentation, while MC1R on non-hematopoietic cells protected against intestinal inflammation in vivo.

    Evidence Genotyped primary melanocyte CPD/apoptosis assays; MC1Re/e mouse DSS/Citrobacter colitis with bone marrow chimeras

    PMID:16543288 PMID:16827749

    Open questions at the time
    • Molecular mechanism of pigment-independent DNA repair enhancement unknown
    • Identity of protective non-hematopoietic cells in gut not defined
  6. 2007 High

    Systematic analysis of nine MC1R variants separated trafficking-defective from coupling-defective alleles and revealed dominant-negative effects of several RHC variants on wild-type MC1R, explaining heterozygous phenotypes.

    Evidence Surface expression, cAMP assays, and co-expression studies in transfected cells

    PMID:17616515

    Open questions at the time
    • Structural basis for dominant-negative interaction not determined
    • Endogenous expression levels in melanocytes not measured
  7. 2007 Medium

    Demonstrating that RHC homozygous melanocytes fail to synergistically activate p38 MAPK with UV, and cannot upregulate pigmentation genes MITF and SLC45A2, connected MC1R signaling deficiency to specific pathway failures beyond cAMP alone.

    Evidence Gene expression and signaling assays in genotyped primary human melanocytes

    PMID:18006116

    Open questions at the time
    • p38 activation mechanism (direct vs. indirect) not defined
    • Other MAPK contributions not fully dissected
  8. 2010 High

    In vivo genetic dissection in mice separated MC1R's pigment-dependent from pigment-independent photoprotection, showing functional MC1R reduces p53 clones even in albino skin.

    Evidence Hairless mouse model combining MC1R and pigmentation genotypes with UVR exposure and p53 clone quantification

    PMID:20237490

    Open questions at the time
    • Specific non-pigmentary effector pathway not identified in vivo
    • Relevance to human skin architecture not directly tested
  9. 2011 Medium

    Identification of UBE3A as a transcriptional regulator of MC1R via promoter binding expanded the upstream regulatory network and linked MC1R downregulation to hypopigmentation in Ube3a knockout mice.

    Evidence ChIP showing Ube3a at Mc1r promoter, reporter assays, Ube3a−/− mouse skin pigmentation phenotype

    PMID:21733131

    Open questions at the time
    • Mechanism by which UBE3A (an E3 ligase) activates transcription unclear
    • MITF vs. UBE3A relative contributions not quantified
  10. 2012 Medium

    Showing that MC1R/α-MSH activation synergizes with UV to phosphorylate p38/p53 and regulate DDB2 in a co-culture system connected MC1R signaling to a specific nucleotide excision repair factor, explaining the DNA repair phenotype.

    Evidence Melanocyte-keratinocyte co-culture with NDP-MSH, UV, phospho-p38/p53, and DDB2 protein assays in genotyped cells

    PMID:22336944

    Open questions at the time
    • DDB2 regulation mechanism (transcriptional vs. post-translational) not fully resolved
    • Other NER factors not examined
  11. 2012 Medium

    MC1R expression in keratinocytes was shown to suppress UVA-induced ROS through PKA-dependent NoxA1 phosphorylation and NADPH oxidase inhibition, establishing a non-melanocyte antioxidant function.

    Evidence Stable MC1R-expressing HaCaT keratinocytes with ROS measurement, PKA/EGFR/ERK inhibitors

    PMID:21898403

    Open questions at the time
    • Endogenous MC1R levels in keratinocytes not quantified
    • Relevance beyond UVA not tested
  12. 2017 High

    Discovery that ZDHHC13-mediated palmitoylation is required for MC1R activation—and that pharmacological promotion of palmitoylation rescues RHC variant defects—identified a druggable post-translational regulatory switch for MC1R signaling.

    Evidence Palmitoylation biochemistry, ZDHHC13 identification, in vitro/in vivo melanoma models, pharmacological rescue

    PMID:28869973

    Open questions at the time
    • Palmitoylation sites on MC1R not fully mapped
    • Specificity of pharmacological activators for MC1R vs. other substrates unknown
  13. 2017 Medium

    MC1R's protective function was extended to dopaminergic neurons: MC1Re/e mice showed compromised nigrostriatal integrity, and a selective MC1R agonist prevented MPTP toxicity, opening a potential neuroprotective role.

    Evidence MC1Re/e mice with MPTP/6-OHDA, behavioral and neurochemical assays, pharmacological agonist rescue

    PMID:28019657

    Open questions at the time
    • Downstream signaling pathway in neurons not characterized
    • Whether cAMP/CREB mediates neuroprotection not tested
    • Single lab finding
  14. 2021 Medium

    Connecting MC1R signaling to centromere integrity through an MITF–CENPA interaction explained how MC1R loss causes UV-induced chromosomal instability, a prerequisite for melanoma transformation.

    Evidence Chromosome stability assays and MITF–CENPA co-immunoprecipitation in melanocytes with MC1R manipulation

    PMID:34001865

    Open questions at the time
    • MITF–CENPA binding domain not mapped
    • Whether this operates in non-melanocyte contexts unknown
    • Single lab
  15. 2023 High

    Identification of AMPK-mediated phosphorylation of ZDHHC13 at S208 as a mechanism that strengthens ZDHHC13–MC1R-RHC interaction and rescues defective MC1R signaling provided a metabolic input node to MC1R regulation.

    Evidence Phosphorylation assays, co-IP, in vitro transformation and in vivo melanoma models

    PMID:36701140

    Open questions at the time
    • Physiological stimuli activating AMPK in melanocytes during UV exposure not defined
    • Whether other kinases target ZDHHC13 unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis for dominant-negative effects of RHC variants on wild-type MC1R; the precise effectors mediating pigment-independent DNA repair; and whether MC1R's neuroprotective and anti-inflammatory functions share the same downstream signaling architecture as its melanocyte functions.
  • No high-resolution structure of MC1R in active/inactive states with RHC mutations
  • Pigment-independent repair effectors beyond DDB2 not identified
  • Neuronal MC1R signaling pathway not characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3 R-HSA-73894 DNA Repair 3 R-HSA-168256 Immune System 2
Partners
ASIPMC5RMITFUBE3AZDHHC13

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Binding of α-MSH and ACTH to MC1R on human melanocytes stimulates cAMP formation, tyrosinase activity, and melanocyte proliferation; the order of affinity/potency (α-MSH = ACTH > β-MSH > γ-MSH) correlated with biological responses, establishing these effects are mediated specifically by MC1R activation. Receptor binding assays, cAMP measurement, tyrosinase activity assays, proliferation assays, Northern blot in cultured human melanocytes Endocrinology High 8612494
2007 Systematic functional analysis of nine common MC1R variants revealed that variants with reduced cell surface expression (V60L, D84E, R151C, I155T, R160W, R163Q) show impaired cAMP coupling, while R142H and D294H have normal surface expression but reduced G-protein coupling. D84E, R151C, I155T, R160W, and D294H variants exert dominant negative effects on wild-type MC1R surface expression and/or cAMP signaling. In vitro expression in transfected cells, cell surface expression assays, cAMP assays, co-expression studies Human molecular genetics High 17616515
2017 MC1R palmitoylation, primarily mediated by the protein-acyl transferase ZDHHC13, is essential for activating MC1R signaling; palmitoylation triggers increased pigmentation, UVB-induced G1-like cell cycle arrest, control of senescence and melanomagenesis in vitro and in vivo. Pharmacological activation of palmitoylation can rescue defects of MC1R RHC variants. Biochemical palmitoylation assays, ZDHHC13 identification, in vitro and in vivo mouse melanoma models, pharmacological rescue experiments Nature High 28869973
2023 AMPK phosphorylates ZDHHC13 at S208, which strengthens the interaction between ZDHHC13 and MC1R-RHC variants, leading to enhanced MC1R palmitoylation, increased MC1R-RHC downstream signaling, and suppression of UVB-induced melanocyte transformation and melanomagenesis. Phosphorylation assays, co-immunoprecipitation, in vitro transformation assays, in vivo mouse melanoma models Cancer research High 36701140
2002 MITF regulates human MC1R gene expression by binding to an E-box (CATGTG motif) immediately upstream of the MC1R transcriptional initiation site; co-expression of MITF induced MC1R promoter activity ~5-fold in NIH/3T3 cells. Promoter-reporter assays, electrophoretic mobility shift assay (EMSA), co-transfection Life sciences Medium 12204775
1999 Characterization of the MC1R promoter revealed GC-rich regions with SP-1 binding sites, absence of TATA/CAAT boxes, and AP-1/AP-2/E-box regulatory elements; minimal promoter activity required the region between -517 and -282, with an SP-1 site at -517 to -447 essential for activity. Promoter deletion analysis, luciferase reporter assays, gel shift assays Biochemical and biophysical research communications Medium 10462496
2007 Human melanocytes homozygous for RHC-associated MC1R variant alleles show abrogated ability of melanocortins to increase transcription of cAMP-dependent pigmentation genes (MITF, SLC45A2), impaired c-Fos activation, and reduced/absent synergistic activation of p38 MAPK by UV irradiation combined with MC1R stimulation. Primary human melanocyte cultures with defined MC1R genotypes, gene expression assays, signaling pathway analysis Peptides Medium 18006116
2006 MC1R function is an independent determinant of UVR-induced DNA damage repair in human melanocytes: melanocytes with loss-of-function MC1R variants sustained more UVR-induced apoptosis, more cyclobutane pyrimidine dimers (CPDs), and exhibited reduced CPD repair, independent of melanin content. Cultured human melanocytes with known MC1R genotypes, UVR irradiation, CPD immunoassay, apoptosis assays Pigment cell research High 16827749
2008 MC1R mediates α-MSH suppression of LPS-induced inflammatory responses in macrophages: siRNA knockdown of MC1R specifically abolished α-MSH suppression of NO generation, TNF-α production, NF-κB activation, and p38 phosphorylation in RAW264.7 macrophages, without affecting MC3R expression or function. siRNA knockdown of MC1R in RAW264.7 macrophages, LPS stimulation, NO/TNF-α/NF-κB/p38 assays Journal of leukocyte biology Medium 18388300
2006 MC1R expressed on non-haematopoietic cells plays a pivotal role in the host's response to intestinal inflammation: MC1Re/e mice (frameshift MC1R mutation) showed dramatically aggravated DSS colitis and delayed clearance of Citrobacter rodentium infection; bone marrow chimera experiments demonstrated the protective effect requires MC1R expression on non-haematopoietic cells. MC1Re/e mouse model, DSS and Citrobacter colitis models, bone marrow chimera experiments, histological analysis, myeloperoxidase activity Gut High 16543288
2010 MC1R protects against UVR by both pigmentary and non-pigmentary mechanisms in vivo: in albino skin lacking MC1R, repeated UVR led to significantly elevated p53 clones compared to albino skin with functional MC1R; in pigmented skin, fewer p53 clones occurred without functional MC1R. In vivo hairless mouse model with genetic combinations of MC1R presence/absence and pigmentation status, UVR exposure, p53 clone quantification, CPD measurement The Journal of investigative dermatology High 20237490
2010 α-MSH regulates intergenic splicing between MC1R and its downstream neighbor TUBB3, producing two chimeric protein isoforms localizing to plasma membrane and endoplasmic reticulum; treatment with α-MSH or activation of p38-MAPK shifts expression from MC1R to chimeric MC1R-TUBB3 isoforms in melanocytes. RT-PCR, protein localization studies, α-MSH treatment, p38-MAPK activation in cultured melanocytes Nucleic acids research Medium 21071418
2015 MC1R-TUBB3 intergenic splice isoforms (Iso1 and Iso2) show strongly reduced plasma membrane expression due to aberrant forward trafficking, reduced cAMP coupling, but unimpaired ERK activation upon αMSH binding. Heterodimerization of these isoforms with wild-type MC1R-001 decreases surface expression of binding sites. Heterologous expression in HEK293T and melanoma cells, radioligand binding, cAMP assays, ERK activation, co-immunoprecipitation, trafficking assays PloS one Medium 26657157
2012 Wild-type MC1R melanocyte strains in co-culture with keratinocytes, upon NDP-MSH treatment and UVR exposure, show synergistic activation of p38 and p53 phosphorylation and DDB2 protein regulation through p38; MC1R R/R variant melanocytes have lower basal phospho-p38, fail to show this synergism, and do not regulate DDB2 via p38. Melanocyte-keratinocyte co-culture, NDP-MSH treatment, UVR exposure, phosphorylation assays for p38 and p53, DDB2 protein expression The Journal of investigative dermatology Medium 22336944
2012 MC1R expression in keratinocytes inhibits UVA-induced ROS production via NADPH oxidase- and cAMP/PKA-dependent mechanisms: PKA-dependent NoxA1 phosphorylation was increased in MC1R-expressing keratinocytes, and inhibition of PKA restored UVA-ROS production; EGFR and ERK activity were also involved. Stable MC1R expression in HaCaT keratinocytes, ROS measurement after UVA exposure, PKA inhibition, EGFR/ERK inhibition assays Journal of cellular physiology Medium 21898403
2011 UBE3A regulates MC1R expression: UBE3A induces MC1R promoter activity, and chromatin immunoprecipitation showed Ube3a is physically associated with the Mc1r promoter; deletion of the E-box/SP1 element abolished UBE3A-induced promoter activity. Ube3a(-/-) mice show MC1R downregulation and skin hypopigmentation. Luciferase reporter assays, chromatin immunoprecipitation (ChIP), promoter deletion analysis, Ube3a knockout mouse model Pigment cell & melanoma research Medium 21733131
2017 MC1R has a protective role in nigrostriatal dopaminergic neurons: MC1Re/e mice (inactivating MC1R mutation) show compromised nigrostriatal dopaminergic neuronal integrity and increased susceptibility to 6-OHDA and MPTP toxicity; a selective MC1R agonist protected against MPTP-induced dopaminergic neurotoxicity. MC1Re/e mouse model, MPTP and 6-OHDA treatment, behavioral tests, neurochemical and neuropathological measures, pharmacological agonist treatment Annals of neurology Medium 28019657
2021 MC1R is critical for chromosome stability and centromere integrity in melanocytes: α-MSH/MC1R stimulation prevents UV radiation-induced chromosome instability. This is mediated through MITF, which directly interacts with centromere protein A (CENPA) in melanocytes. MC1R activation/loss experiments, chromosome stability assays, co-immunoprecipitation of MITF with CENPA, UV irradiation Cell death discovery Medium 34001865
2007 Human MC1R is more sensitive to exogenous ligand than mouse Mc1r in vivo; agouti signaling protein blocks human MC1R activation without generating the inverse agonist signal seen with mouse receptor; in transgenic mice, human MC1R does not elicit significant eumelanin synthesis without ligand, unlike the mouse receptor, consistent with lower receptor number in human vs. mouse melanocytes. Humanized MC1R transgenic mouse model, ligand dose-response, agouti signaling protein antagonism, pigmentation analysis Human molecular genetics Medium 17652101
2016 Dimerization of MC1R and MC5R creates a ligand-dependent signal modulation: co-immunoprecipitation confirmed heterodimerization at the plasma membrane; cotransfection of MC1R with MC5R inhibited cAMP accumulation induced by α-MSH but not by desacetyl-α-MSH, demonstrating ligand-selective inhibitory signaling through heterodimer formation. Co-immunoprecipitation, immunofluorescence co-localization, cAMP assays in CHO cells with co-transfection General and comparative endocrinology Medium 27080548
2023 MC1R signaling through cAMP-CREB/ATF-1 and ERK-NFκB pathways accelerates G1/S transition in breast cancer cells; MC1R knockdown significantly reduced cell proliferation in vitro and in vivo. MC1R knockdown, cell proliferation assays, in vivo xenograft, signaling pathway analysis (cAMP, CREB/ATF-1, ERK, NFκB) NPJ precision oncology Medium 37679505
2003 MC1R variant alleles R151C and R160W show reduced ability to stimulate cAMP and CREB phosphorylation compared to wild-type MC1R when expressed in HEK293 cells, establishing impaired G-protein signaling as the molecular basis of RHC allele loss-of-function. Stable transfection of HEK293 cells, cAMP-responsive luciferase reporter, CREB phosphorylation immunoblotting Annals of the New York Academy of Sciences Medium 12851335

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 MC1R variants, melanoma and red hair color phenotype: a meta-analysis. International journal of cancer 275 18366057
1996 Binding of melanotropic hormones to the melanocortin receptor MC1R on human melanocytes stimulates proliferation and melanogenesis. Endocrinology 259 8612494
1998 Melanocortin receptor 1 (MC1R) mutations and coat color in pigs. Genetics 234 9799269
2005 A window on the genetics of evolution: MC1R and plumage colouration in birds. Proceedings. Biological sciences 220 16087416
2004 Interactive effects of MC1R and OCA2 on melanoma risk phenotypes. Human molecular genetics 204 14709592
2000 Pleiotropic effects of the melanocortin 1 receptor (MC1R) gene on human pigmentation. Human molecular genetics 198 11030758
2017 Palmitoylation-dependent activation of MC1R prevents melanomagenesis. Nature 195 28869973
2001 Mutations in the agouti (ASIP), the extension (MC1R), and the brown (TYRP1) loci and their association to coat color phenotypes in horses (Equus caballus). Mammalian genome : official journal of the International Mammalian Genome Society 187 11353392
2004 Adaptive reptile color variation and the evolution of the Mc1r gene. Evolution; international journal of organic evolution 164 15446431
2002 Skin colour and skin cancer - MC1R, the genetic link. Melanoma research 157 12394181
2014 MC1R, the cAMP pathway, and the response to solar UV: extending the horizon beyond pigmentation. Pigment cell & melanoma research 149 24807163
2007 Receptor function, dominant negative activity and phenotype correlations for MC1R variant alleles. Human molecular genetics 137 17616515
2003 Melanocortin 1-receptor (MC1R) mutations are associated with plumage colour in chicken. Animal genetics 127 12873211
2000 The melanocortin 1 receptor (MC1R): more than just red hair. Pigment cell research 120 10885670
2002 TYRP1 and MC1R genotypes and their effects on coat color in dogs. Mammalian genome : official journal of the International Mammalian Genome Society 108 12140685
2006 Melanin content and MC1R function independently affect UVR-induced DNA damage in cultured human melanocytes. Pigment cell research 105 16827749
2016 Germline MC1R status influences somatic mutation burden in melanoma. Nature communications 104 27403562
2003 Genetic association and cellular function of MC1R variant alleles in human pigmentation. Annals of the New York Academy of Sciences 101 12851335
2010 Association of MC1R variants and host phenotypes with melanoma risk in CDKN2A mutation carriers: a GenoMEL study. Journal of the National Cancer Institute 92 20876876
2009 Interactions between HERC2, OCA2 and MC1R may influence human pigmentation phenotype. Annals of human genetics 92 19208107
2017 MC1R signaling. Intracellular partners and pathophysiological implications. Biochimica et biophysica acta. Molecular basis of disease 86 28259754
2001 A frameshift mutation in MC1R and a high frequency of somatic reversions cause black spotting in pigs. Genetics 86 11404341
2010 The association between MC1R genotype and BRAF mutation status in cutaneous melanoma: findings from an Australian population. The Journal of investigative dermatology 67 19571821
2006 Crucial role of the melanocortin receptor MC1R in experimental colitis. Gut 64 16543288
2002 Involvement of microphthalmia-associated transcription factor (MITF) in expression of human melanocortin-1 receptor (MC1R). Life sciences 64 12204775
2005 Worldwide polymorphism at the MC1R locus and normal pigmentation variation in humans. Peptides 62 15979202
2016 The MC1R Gene and Youthful Looks. Current biology : CB 61 27133870
2012 Inherited variants in the MC1R gene and survival from cutaneous melanoma: a BioGenoMEL study. Pigment cell & melanoma research 60 22325793
2021 MC1R Functions, Expression, and Implications for Targeted Therapy. The Journal of investigative dermatology 56 34362555
2007 Human melanocytes expressing MC1R variant alleles show impaired activation of multiple signaling pathways. Peptides 51 18006116
2018 Polymorphisms in MC1R and ASIP Genes are Associated with Coat Color Variation in the Arabian Camel. The Journal of heredity 50 29893870
2008 CDKN2A mutations and MC1R variants in Italian patients with single or multiple primary melanoma. Pigment cell & melanoma research 47 18983535
2008 MC1R variants associated susceptibility to basal cell carcinoma of skin: interaction with host factors and XRCC3 polymorphism. International journal of cancer 46 18067130
2005 The relation between melanocortin 1 receptor (MC1R) variation and the generation of phenotypic diversity in the cutaneous response to ultraviolet radiation. Peptides 46 15963603
2015 MC1R gene variants and non-melanoma skin cancer: a pooled-analysis from the M-SKIP project. British journal of cancer 45 26103569
2007 Determination of phenotype associated SNPs in the MC1R gene. Journal of forensic sciences 44 17316231
2004 Novel MC1R variants in Ligurian melanoma patients and controls. Human mutation 44 15221796
2011 Screening of TYR, OCA2, GPR143, and MC1R in patients with congenital nystagmus, macular hypoplasia, and fundus hypopigmentation indicating albinism. Molecular vision 42 21541274
2007 Cutaneous phenotype and MC1R variants as modifying factors for the development of melanoma in CDKN2A G101W mutation carriers from 4 countries. International journal of cancer 42 17397031
2008 Diminishment of alpha-MSH anti-inflammatory activity in MC1r siRNA-transfected RAW264.7 macrophages. Journal of leukocyte biology 40 18388300
2001 A polymorphism study of the human Agouti gene and its association with MC1R. Pigment cell research 40 11549109
1999 Characterization of the promoter region of the human melanocortin-1 receptor (MC1R) gene. Biochemical and biophysical research communications 40 10462496
2017 The melanoma-linked "redhead" MC1R influences dopaminergic neuron survival. Annals of neurology 39 28019657
2014 Capturing the biological impact of CDKN2A and MC1R genes as an early predisposing event in melanoma and non melanoma skin cancer. Oncotarget 37 24742402
2008 MC1R variation and melanoma risk in the Swedish population in relation to clinical and pathological parameters. Pigment cell & melanoma research 36 19077144
2007 Humanized MC1R transgenic mice reveal human specific receptor function. Human molecular genetics 35 17652101
2010 Genetic analysis of three important genes in pigmentation and melanoma susceptibility: CDKN2A, MC1R and HERC2/OCA2. Experimental dermatology 34 20629734
2010 Protection against UVR involves MC1R-mediated non-pigmentary and pigmentary mechanisms in vivo. The Journal of investigative dermatology 33 20237490
2012 MC1R variant allele effects on UVR-induced phosphorylation of p38, p53, and DDB2 repair protein responses in melanocytic cells in culture. The Journal of investigative dermatology 32 22336944
2013 Mutations in MC1R gene determine black coat color phenotype in Chinese sheep. TheScientificWorldJournal 31 24082855
2013 CDKN2A and MC1R variants influence dermoscopic and confocal features of benign melanocytic lesions in multiple melanoma patients. Experimental dermatology 30 23711066
2012 Synthesis and characterization of a melanoma-targeted fluorescence imaging probe by conjugation of a melanocortin 1 receptor (MC1R) specific ligand. Bioconjugate chemistry 30 23116461
2011 Host phenotype characteristics and MC1R in relation to early-onset basal cell carcinoma. The Journal of investigative dermatology 30 22158557
2019 Polymorphism in MC1R, TYR and ASIP genes in different colored feather chickens. 3 Biotech 29 31065503
2014 Inherited variation at MC1R and ASIP and association with melanoma-specific survival. International journal of cancer 29 25382380
2003 Identification of four novel melanocortin 1 receptor (MC1R) gene variants in a Mediterranean population. Human mutation 27 14961558
2023 Melanocortin 1 Receptor (MC1R): Pharmacological and Therapeutic Aspects. International journal of molecular sciences 26 37569558
2021 Behind the Scene: Exploiting MC1R in Skin Cancer Risk and Prevention. Genes 26 34356109
2018 Two MC1R loss-of-function alleles in cream-coloured Australian Cattle Dogs and white Huskies. Animal genetics 26 29932470
2017 Melanocortin 1 receptor (MC1R) polymorphisms' influence on size and dermoscopic features of nevi. Pigment cell & melanoma research 26 28950052
2012 MC1R expression in HaCaT keratinocytes inhibits UVA-induced ROS production via NADPH oxidase- and cAMP-dependent mechanisms. Journal of cellular physiology 26 21898403
2016 MC1R is dispensable for the proteinuria reducing and glomerular protective effect of melanocortin therapy. Scientific reports 25 27270328
2002 Holstein's milk detection in cheeses inferred from melanocortin receptor 1 (MC1R) gene polymorphism. Journal of dairy science 25 12018414
2016 The MC1R and ASIP Coat Color Loci May Impact Behavior in the Horse. The Journal of heredity 24 26884605
2015 Effect of the MC1R gene on sexual dimorphism in melanin-based colorations. Molecular ecology 23 25857339
2010 The role of MC1R gene in buffalo coat color. Science China. Life sciences 23 20596837
2009 CDKN2A and MC1R analysis in amelanotic and pigmented melanoma. Melanoma research 23 19339902
2023 EGCG, GCG, TFDG, or TSA Inhibiting Melanin Synthesis by Downregulating MC1R Expression. International journal of molecular sciences 22 37446194
2003 Exclusion of melanocortin-1 receptor (mc1r) and agouti as candidates for dominant black in dogs. The Journal of heredity 22 12692166
2023 AMPK Phosphorylates ZDHHC13 to Increase MC1R Activity and Suppress Melanomagenesis. Cancer research 21 36701140
2018 Interest and Uptake of MC1R Testing for Melanoma Risk in a Diverse Primary Care Population: A Randomized Clinical Trial. JAMA dermatology 21 29801061
2016 Dimerization of melanocortin receptor 1 (MC1R) and MC5R creates a ligand-dependent signal modulation: Potential participation in physiological color change in the flounder. General and comparative endocrinology 21 27080548
2012 MC1R, ASIP, TYR, and TYRP1 gene variants in a population-based series of multiple primary melanomas. Genes, chromosomes & cancer 21 22447455
2010 Alpha-MSH regulates intergenic splicing of MC1R and TUBB3 in human melanocytes. Nucleic acids research 21 21071418
2022 MC1R and melanin-based molecular probes for theranostic of melanoma and beyond. Acta pharmacologica Sinica 20 36008707
2015 Inherited variation at MC1R and histological characteristics of primary melanoma. PloS one 20 25790105
2009 MC1R gene polymorphism affects skin color and phenotypic features related to sun sensitivity in a population of French adult women. Photochemistry and photobiology 20 19656326
2003 Defining the quantitative contribution of the melanocortin 1 receptor (MC1R) to variation in pigmentary phenotype. Annals of the New York Academy of Sciences 20 12851334
2019 Signatures of de-domestication in autochthonous pig breeds and of domestication in wild boar populations from MC1R and NR6A1 allele distribution. Animal genetics 19 30741434
2017 Mutation load in melanoma is affected by MC1R genotype. Pigment cell & melanoma research 19 28024115
2012 The melanocortin 1 receptor (MC1R) inhibits the inflammatory response in Raw 264.7 cells and atopic dermatitis (AD) mouse model. Molecular biology reports 18 23090482
2016 Fear of Pain Mediates the Association between MC1R Genotype and Dental Fear. Journal of dental research 17 27555332
2022 BMS-470539 Attenuates Oxidative Stress and Neuronal Apoptosis via MC1R/cAMP/PKA/Nurr1 Signaling Pathway in a Neonatal Hypoxic-Ischemic Rat Model. Oxidative medicine and cellular longevity 16 35140838
2017 Design of MC1R Selective γ-MSH Analogues with Canonical Amino Acids Leads to Potency and Pigmentation. Journal of medicinal chemistry 16 29094944
2013 Three novel human sporadic melanoma cell lines: signaling pathways controlled by MC1R, BRAF and β-catenins. Journal of biological regulators and homeostatic agents 16 23489693
2022 Effect of polymorphisms in the 5'-flanking sequence of MC1R on feather color in Taihang chickens. Poultry science 15 36283141
2019 MC1R variants in childhood and adolescent melanoma: a retrospective pooled analysis of a multicentre cohort. The Lancet. Child & adolescent health 15 30872112
2019 Mutations in ASIP and MC1R: dominant black and recessive black alleles segregate in native Swedish sheep populations. Animal genetics 15 31475378
2002 Molecular and pharmacological characterisation of the MSH-R alleles in Swiss cattle breeds. Journal of receptor and signal transduction research 15 12503631
2023 Genetic fine-mapping reveals single nucleotide polymorphism mutations in the MC1R regulatory region associated with duck melanism. Molecular ecology 14 36929535
2023 MC1R signaling through the cAMP-CREB/ATF-1 and ERK-NFκB pathways accelerates G1/S transition promoting breast cancer progression. NPJ precision oncology 14 37679505
2019 Synergy between MC1R and ASIP for coat color in horses (Equus caballus)1. Journal of animal science 14 30785190
2015 Functional Characterization of MC1R-TUBB3 Intergenic Splice Variants of the Human Melanocortin 1 Receptor. PloS one 14 26657157
2013 Functional melanocortin 1 receptor Mc1r is not necessary for an inflammatory response to UV radiation in adult mouse skin. Experimental dermatology 14 23489427
2011 UBE3A regulates MC1R expression: a link to hypopigmentation in Angelman syndrome. Pigment cell & melanoma research 14 21733131
2021 The protective role of MC1R in chromosome stability and centromeric integrity in melanocytes. Cell death discovery 13 34001865
2021 LINC00937 suppresses keloid fibroblast proliferation and extracellular matrix deposition by targeting the miR-28-5p/MC1R axis. Histology and histopathology 13 34486677
2020 MC1R c.310G>- and c.871G > A determine the coat color of Kumamoto sub-breed of Japanese Brown cattle. Animal science journal = Nihon chikusan Gakkaiho 13 32285552
2011 A melanocortin 1 receptor (MC1R) gene polymorphism is useful for authentication of Massese sheep dairy products. The Journal of dairy research 13 21214968
1999 The melanocyte-stimulating hormone receptor (MC1-R) gene as a tool in evolutionary studies of artiodactyles. Hereditas 13 10628296