MSHR_HUMAN
ID MSHR_HUMAN Reviewed; 317 AA.
AC Q01726; Q66K38; Q6UR93; Q8WWX6; Q8WWX7; Q96I33; Q96RU4; Q9UBF7; Q9UN58;
AC Q9UN59; Q9UN60; Q9UN61; Q9UN62;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=Melanocyte-stimulating hormone receptor;
DE Short=MSH-R;
DE AltName: Full=Melanocortin receptor 1;
DE Short=MC1-R;
GN Name=MC1R; Synonyms=MSHR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Skin;
RX PubMed=1325670; DOI=10.1126/science.1325670;
RA Mountjoy K.G., Robbins L.S., Mortrud M., Cone R.D.;
RT "The cloning of a family of genes that encode the melanocortin receptors.";
RL Science 257:1248-1251(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX PubMed=8463333; DOI=10.1016/s0021-9258(18)53088-x;
RA Gantz I., Konda Y., Tashiro T., Shimoto Y., Miwa H., Munzert G.,
RA Watson S.J., Delvalle J., Yamada T.;
RT "Molecular cloning of a novel melanocortin receptor.";
RL J. Biol. Chem. 268:8246-8250(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=1516719; DOI=10.1016/0014-5793(92)80820-7;
RA Chhajlani V., Wikberg J.E.S.;
RT "Molecular cloning and expression of the human melanocyte stimulating
RT hormone receptor cDNA.";
RL FEBS Lett. 309:417-420(1992).
RN [4]
RP ERRATUM OF PUBMED:1516719.
RX PubMed=8706868; DOI=10.1016/0014-5793(96)81375-5;
RA Chhajlani V., Wikberg J.E.S.;
RL FEBS Lett. 390:238-238(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLN-67; GLU-84; MET-92;
RP CYS-151 AND GLN-163.
RX PubMed=10101176; DOI=10.1093/genetics/151.4.1547;
RA Rana B.K., Hewett-Emmett D., Jin L., Chang B.H., Sambuughin N., Lin M.,
RA Watkins S., Bamshad M., Jorde L.B., Ramsay M., Jenkins T., Li W.H.;
RT "High polymorphism at the human melanocortin 1 receptor locus.";
RL Genetics 151:1547-1557(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND VARIANT PRO-162.
RX PubMed=11442765; DOI=10.1046/j.0022-202x.2001.01393.x;
RA Jimenez-Cervantes C., Olivares C., Gonzalez P., Morandini R., Ghanem G.,
RA Garcia-Borron J.C.;
RT "The Pro162 variant is a loss-of-function mutation of the human
RT melanocortin 1 receptor gene.";
RL J. Invest. Dermatol. 117:156-158(2001).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11750130; DOI=10.1016/s0378-1119(01)00791-0;
RA Smith A.G., Box N.F., Marks L.H., Chen W., Smit D.J., Wyeth J.R.,
RA Huttley G.A., Easteal S., Sturm R.A.;
RT "The human melanocortin-1 receptor locus: analysis of transcription unit,
RT locus polymorphism and haplotype evolution.";
RL Gene 281:81-94(2001).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND VARIANTS THR-40 AND
RP MET-122.
RX PubMed=11707265; DOI=10.1016/s0014-5793(01)03025-3;
RA Jimenez-Cervantes C., Germer S., Gonzalez P., Sanchez J., Sanchez C.O.,
RA Garcia-Borron J.C.;
RT "Thr40 and Met122 are new partial loss-of-function natural mutations of the
RT human melanocortin 1 receptor.";
RL FEBS Lett. 508:44-48(2001).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, VARIANTS GLN-67; MET-92;
RP THR-120; PHE-147 DEL; CYS-151; ILE-157; THR-159; GLN-163 AND GLY-166, AND
RP CHARACTERIZATION OF VARIANTS GLN-67; MET-92; THR-120; PHE-147 DEL; CYS-151;
RP ILE-157; THR-159; GLN-163 AND GLY-166.
RX PubMed=16463023; DOI=10.1007/s00439-006-0141-1;
RA Nakayama K., Soemantri A., Jin F., Dashnyam B., Ohtsuka R., Duanchang P.,
RA Isa M.N., Settheetham-Ishida W., Harihara S., Ishida T.;
RT "Identification of novel functional variants of the melanocortin 1 receptor
RT gene originated from Asians.";
RL Hum. Genet. 119:322-330(2006).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Pastorino L., Cusano R., Lantieri F., Origone P., Bruno W., Barile M.,
RA Gliori S., Sturm R.A., Bianchi Scarra' G.;
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kopatz S.A., Aronstam R.S., Sharma S.V.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-60; MET-92; CYS-151;
RP THR-155; LEU-156; TRP-160; GLN-163 AND LEU-196.
RG SeattleSNPs variation discovery resource;
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-155.
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [14]
RP ASSOCIATION WITH FEMALE-SPECIFIC ANALGESIA FROM KAPPA-OPIOID RECEPTOR.
RX PubMed=12663858; DOI=10.1073/pnas.0730053100;
RA Mogil J.S., Wilson S.G., Chesler E.J., Rankin A.L., Nemmani K.V.,
RA Lariviere W.R., Groce M.K., Wallace M.R., Kaplan L., Staud R., Ness T.J.,
RA Glover T.L., Stankova M., Mayorov A., Hruby V.J., Grisel J.E.,
RA Fillingim R.B.;
RT "The melanocortin-1 receptor gene mediates female-specific mechanisms of
RT analgesia in mice and humans.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:4867-4872(2003).
RN [15]
RP FUNCTION, INTERACTION WITH MGRN1, AND MUTAGENESIS OF LYS-65; LYS-226;
RP LYS-238 AND LYS-310.
RX PubMed=19737927; DOI=10.1074/jbc.m109.028100;
RA Perez-Oliva A.B., Olivares C., Jimenez-Cervantes C., Garcia-Borron J.C.;
RT "Mahogunin ring finger-1 (MGRN1) E3 ubiquitin ligase inhibits signaling
RT from melanocortin receptor by competition with Galphas.";
RL J. Biol. Chem. 284:31714-31725(2009).
RN [16]
RP FUNCTION, INTERACTION WITH OPN3, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=31097585; DOI=10.1073/pnas.1902825116;
RA Ozdeslik R.N., Olinski L.E., Trieu M.M., Oprian D.D., Oancea E.;
RT "Human nonvisual opsin 3 regulates pigmentation of epidermal melanocytes
RT through functional interaction with melanocortin 1 receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 116:11508-11517(2019).
RN [17]
RP 3D-STRUCTURE MODELING.
RX PubMed=9640562; DOI=10.1016/s1093-3263(98)00004-7;
RA Prusis P., Schioth H.B., Muceniece R., Herzyk P., Afshar M., Hubbard R.E.,
RA Wikberg J.E.;
RT "Modeling of the three-dimensional structure of the human melanocortin 1
RT receptor, using an automated method and docking of a rigid cyclic
RT melanocyte-stimulating hormone core peptide.";
RL J. Mol. Graph. Model. 15:307-317(1997).
RN [18]
RP VARIANT HIS-294.
RX PubMed=7581459; DOI=10.1038/ng1195-328;
RA Valverde P., Healy F., Jackson I., Rees J.L., Thody A.J.;
RT "Variants of the melanocyte-stimulating hormone receptor gene are
RT associated with red hair and fair skin in humans.";
RL Nat. Genet. 11:328-330(1995).
RN [19]
RP VARIANT GLU-84.
RX PubMed=8894704; DOI=10.1093/hmg/5.10.1663;
RA Valverde P., Healy E., Sikkink S., Haldane F., Thody A.J., Carothers A.,
RA Jackson I.J., Rees J.L.;
RT "The Asp84Glu variant of the melanocortin 1 receptor (MC1R) is associated
RT with melanoma.";
RL Hum. Mol. Genet. 5:1663-1666(1996).
RN [20]
RP VARIANTS LEU-60; MET-92; CYS-151; TRP-160 AND HIS-294.
RX PubMed=9302268; DOI=10.1093/hmg/6.11.1891;
RA Box N.F., Wyeth J.R., O'Gorman L.E., Martin N.G., Sturm R.A.;
RT "Characterization of melanocyte stimulating hormone receptor variant
RT alleles in twins with red hair.";
RL Hum. Mol. Genet. 6:1891-1897(1997).
RN [21]
RP VARIANTS GLU-84 AND MET-92.
RX PubMed=8990005;
RX DOI=10.1002/(sici)1098-1004(1997)9:1<30::aid-humu5>3.0.co;2-t;
RA Koppula S.V., Robbins L.S., Lu D., Baack E., White C.R. Jr., Swanson N.A.,
RA Cone R.D.;
RT "Identification of common polymorphisms in the coding sequence of the human
RT MSH receptor (MC1R) with possible biological effects.";
RL Hum. Mutat. 9:30-36(1997).
RN [22]
RP VARIANT CYS-151.
RX PubMed=9571181; DOI=10.1006/bbrc.1998.8459;
RA Fraendberg P.-A., Doufexis M., Kapas S., Chhajlani V.;
RT "Human pigmentation phenotype: a point mutation generates nonfunctional MSH
RT receptor.";
RL Biochem. Biophys. Res. Commun. 245:490-492(1998).
RN [23]
RP VARIANT TRP-160.
RX PubMed=9665397; DOI=10.1046/j.1523-1747.1998.00252.x;
RA Smith R., Healy E., Siddiqui S., Flanagan N., Steijlen P.M., Rosdahl I.,
RA Jacques J.P., Rogers S., Turner R., Jackson I.J., Birch-MacHin M.A.,
RA Rees J.L.;
RT "Melanocortin 1 receptor variants in an Irish population.";
RL J. Invest. Dermatol. 111:119-122(1998).
RN [24]
RP CHARACTERIZATION OF VARIANTS LEU-60; HIS-142; CYS-151; TRP-160 AND HIS-294.
RX PubMed=10403794; DOI=10.1006/bbrc.1999.0935;
RA Schioeth H.B., Phillips S.R., Rudzish R., Birch-Machin M.A.,
RA Wikberg J.E.S., Rees J.L.;
RT "Loss of function mutations of the human melanocortin 1 receptor are common
RT and are associated with red hair.";
RL Biochem. Biophys. Res. Commun. 260:488-491(1999).
RN [25]
RP VARIANTS ARG-93; HIS-142 AND CYS-151, AND CHARACTERIZATION OF VARIANTS
RP ARG-93 AND CYS-151.
RX PubMed=12473109; DOI=10.1046/j.1432-1033.2002.03329.x;
RA Sanchez Mas J., Olivares Sanchez C., Ghanem G., Haycock J.,
RA Lozano Teruel J.A., Garcia-Borron J.C., Jimenez-Cervantes C.;
RT "Loss-of-function variants of the human melanocortin-1 receptor gene in
RT melanoma cells define structural determinants of receptor function.";
RL Eur. J. Biochem. 269:6133-6141(2002).
RN [26]
RP CHARACTERIZATION OF VARIANTS GLU-84; CYS-151; THR-155 AND TRP-160.
RX PubMed=15972726; DOI=10.1093/hmg/ddi219;
RA Beaumont K.A., Newton R.A., Smit D.J., Leonard J.H., Stow J.L., Sturm R.A.;
RT "Altered cell surface expression of human MC1R variant receptor alleles
RT associated with red hair and skin cancer risk.";
RL Hum. Mol. Genet. 14:2145-2154(2005).
RN [27]
RP VARIANTS CMM5 PHE-41 AND THR-128, AND VARIANTS LEU-60; MET-92; THR-155;
RP TRP-160; GLN-163; SER-281 AND HIS-294.
RX PubMed=17434924; DOI=10.1093/carcin/bgm084;
RA Fernandez L., Milne R., Bravo J., Lopez J., Aviles J., Longo M.,
RA Benitez J., Lazaro P., Ribas G.;
RT "MC1R: three novel variants identified in a malignant melanoma association
RT study in the Spanish population.";
RL Carcinogenesis 28:1659-1664(2007).
RN [28]
RP VARIANT CYS-151, AND ASSOCIATION WITH SHEP2.
RX PubMed=17952075; DOI=10.1038/ng.2007.13;
RA Sulem P., Gudbjartsson D.F., Stacey S.N., Helgason A., Rafnar T.,
RA Magnusson K.P., Manolescu A., Karason A., Palsson A., Thorleifsson G.,
RA Jakobsdottir M., Steinberg S., Palsson S., Jonasson F., Sigurgeirsson B.,
RA Thorisdottir K., Ragnarsson R., Benediktsdottir K.R., Aben K.K.,
RA Kiemeney L.A., Olafsson J.H., Gulcher J., Kong A., Thorsteinsdottir U.,
RA Stefansson K.;
RT "Genetic determinants of hair, eye and skin pigmentation in Europeans.";
RL Nat. Genet. 39:1443-1452(2007).
RN [29]
RP VARIANTS [LARGE SCALE ANALYSIS] LEU-60 AND MET-92.
RX PubMed=18987736; DOI=10.1038/nature07485;
RA Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K.,
RA Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L.,
RA Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A.,
RA Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V.,
RA Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R.,
RA Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E.,
RA Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S.,
RA Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A.,
RA DiPersio J.F., Wilson R.K.;
RT "DNA sequencing of a cytogenetically normal acute myeloid leukaemia
RT genome.";
RL Nature 456:66-72(2008).
RN [30]
RP VARIANTS CMM5 MET-38; ALA-51 AND ARG-289, CHARACTERIZATION OF VARIANTS CMM5
RP MET-38; PHE-41; ALA-51; THR-128 AND ARG-289, AND CHARACTERIZATION OF
RP VARIANT SER-281.
RX PubMed=19338054; DOI=10.1002/humu.20971;
RA Perez Oliva A.B., Fernendez L.P., DeTorre C., Herraiz C.,
RA Martinez-Escribano J.A., Benitez J., Lozano Teruel J.A.,
RA Garcia-Borron J.C., Jimenez-Cervantes C., Ribas G.;
RT "Identification and functional analysis of novel variants of the human
RT melanocortin 1 receptor found in melanoma patients.";
RL Hum. Mutat. 30:811-822(2009).
RN [31]
RP VARIANT TRP-160.
RX PubMed=28501589; DOI=10.1016/j.clim.2017.05.009;
RA Sadovnick A.D., Traboulsee A.L., Zhao Y., Bernales C.Q., Encarnacion M.,
RA Ross J.P., Yee I.M., Criscuoli M.G., Vilarino-Gueell C.;
RT "Genetic modifiers of multiple sclerosis progression, severity and onset.";
RL Clin. Immunol. 180:100-105(2017).
CC -!- FUNCTION: Receptor for MSH (alpha, beta and gamma) and ACTH
CC (PubMed:1325670, PubMed:8463333, PubMed:1516719, PubMed:11442765,
CC PubMed:11707265). The activity of this receptor is mediated by G
CC proteins which activate adenylate cyclase (PubMed:1325670,
CC PubMed:11707265, PubMed:16463023, PubMed:19737927). Mediates
CC melanogenesis, the production of eumelanin (black/brown) and
CC phaeomelanin (red/yellow), via regulation of cAMP signaling in
CC melanocytes (PubMed:31097585). {ECO:0000269|PubMed:11442765,
CC ECO:0000269|PubMed:11707265, ECO:0000269|PubMed:1325670,
CC ECO:0000269|PubMed:1516719, ECO:0000269|PubMed:16463023,
CC ECO:0000269|PubMed:19737927, ECO:0000269|PubMed:31097585,
CC ECO:0000269|PubMed:8463333}.
CC -!- SUBUNIT: Interacts with MGRN1, but does not undergo MGRN1-mediated
CC ubiquitination; this interaction competes with GNAS-binding and thus
CC inhibits agonist-induced cAMP production (PubMed:19737927). Interacts
CC with OPN3; the interaction results in a decrease in MC1R-mediated cAMP
CC signaling and ultimately a decrease in melanin production in
CC melanocytes (PubMed:31097585). {ECO:0000269|PubMed:19737927,
CC ECO:0000269|PubMed:31097585}.
CC -!- INTERACTION:
CC Q01726; Q8TCY5: MRAP; NbExp=2; IntAct=EBI-9538513, EBI-9538727;
CC Q01726; Q9H1Y3: OPN3; NbExp=5; IntAct=EBI-9538513, EBI-21871627;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:31097585};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in melanocytes (PubMed:1325670,
CC PubMed:31097585). Expressed in corticoadrenal tissue (PubMed:1325670).
CC {ECO:0000269|PubMed:1325670, ECO:0000269|PubMed:31097585}.
CC -!- POLYMORPHISM: Genetic variants in MC1R define the skin/hair/eye
CC pigmentation variation locus 2 (SHEP2) [MIM:266300]. Hair, eye and skin
CC pigmentation are among the most visible examples of human phenotypic
CC variation, with a broad normal range that is subject to substantial
CC geographic stratification. In the case of skin, individuals tend to
CC have lighter pigmentation with increasing distance from the equator,
CC with type I skin being the most lightly pigmented and type IV the most
CC dark pigmented. By contrast, the majority of variation in human eye and
CC hair color is found among individuals of European ancestry, with most
CC other human populations fixed for brown eyes and black hair. Partial
CC loss-of-function mutations are associated with fair skin, poor tanning
CC and increased skin cancer risk.
CC -!- POLYMORPHISM: MC1R variants associated with red hair and fair skin,
CC determine female-specific increased analgesia from kappa-opioid
CC receptor agonist [MIM:613098]. {ECO:0000269|PubMed:12663858}.
CC -!- DISEASE: Melanoma, cutaneous malignant 5 (CMM5) [MIM:613099]: A
CC malignant neoplasm of melanocytes, arising de novo or from a pre-
CC existing benign nevus, which occurs most often in the skin but also may
CC involve other sites. {ECO:0000269|PubMed:17434924,
CC ECO:0000269|PubMed:19338054}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/mc1r/";
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DR EMBL; X65634; CAA46588.1; -; Genomic_DNA.
DR EMBL; X67594; CAA47865.1; -; mRNA.
DR EMBL; AF153431; AAD41349.1; -; Genomic_DNA.
DR EMBL; AF153432; AAD41350.1; -; Genomic_DNA.
DR EMBL; AF153433; AAD41351.1; -; Genomic_DNA.
DR EMBL; AF153434; AAD41352.1; -; Genomic_DNA.
DR EMBL; AF153435; AAD41353.1; -; Genomic_DNA.
DR EMBL; AF153436; AAD41354.1; -; Genomic_DNA.
DR EMBL; AF153437; AAD41355.1; -; Genomic_DNA.
DR EMBL; AF326275; AAK01121.1; -; Genomic_DNA.
DR EMBL; AF263461; AAK58525.1; -; Genomic_DNA.
DR EMBL; AY046528; AAL05887.1; -; Genomic_DNA.
DR EMBL; AY046529; AAL05888.1; -; Genomic_DNA.
DR EMBL; AB241548; BAE94314.1; -; Genomic_DNA.
DR EMBL; AY363626; AAQ62976.1; -; Genomic_DNA.
DR EMBL; AY225228; AAO67713.1; -; Genomic_DNA.
DR EMBL; AF514787; AAM44861.1; -; Genomic_DNA.
DR EMBL; BC007856; AAH07856.1; -; mRNA.
DR EMBL; BC080622; AAH80622.1; -; mRNA.
DR CCDS; CCDS56011.1; -.
DR PIR; S29204; S29204.
DR RefSeq; NP_002377.4; NM_002386.3.
DR PDB; 7F4D; EM; 3.00 A; R=1-317.
DR PDB; 7F4F; EM; 2.90 A; R=1-317.
DR PDB; 7F4H; EM; 2.70 A; R=1-317.
DR PDB; 7F4I; EM; 3.10 A; R=1-317.
DR PDBsum; 7F4D; -.
DR PDBsum; 7F4F; -.
DR PDBsum; 7F4H; -.
DR PDBsum; 7F4I; -.
DR AlphaFoldDB; Q01726; -.
DR SMR; Q01726; -.
DR BioGRID; 110327; 18.
DR DIP; DIP-48789N; -.
DR IntAct; Q01726; 4.
DR STRING; 9606.ENSP00000451605; -.
DR BindingDB; Q01726; -.
DR ChEMBL; CHEMBL3795; -.
DR DrugBank; DB04931; Afamelanotide.
DR DrugBank; DB11653; Bremelanotide.
DR DrugBank; DB05479; CZEN 002.
DR DrugCentral; Q01726; -.
DR GuidetoPHARMACOLOGY; 282; -.
DR GlyGen; Q01726; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q01726; -.
DR PhosphoSitePlus; Q01726; -.
DR SwissPalm; Q01726; -.
DR BioMuta; MC1R; -.
DR DMDM; 12644376; -.
DR MassIVE; Q01726; -.
DR PaxDb; Q01726; -.
DR PeptideAtlas; Q01726; -.
DR PRIDE; Q01726; -.
DR Antibodypedia; 54873; 373 antibodies from 34 providers.
DR DNASU; 4157; -.
DR Ensembl; ENST00000555147.2; ENSP00000451605.1; ENSG00000258839.4.
DR Ensembl; ENST00000639847.1; ENSP00000492011.1; ENSG00000258839.4.
DR GeneID; 4157; -.
DR KEGG; hsa:4157; -.
DR MANE-Select; ENST00000555147.2; ENSP00000451605.1; NM_002386.4; NP_002377.4.
DR CTD; 4157; -.
DR DisGeNET; 4157; -.
DR GeneCards; MC1R; -.
DR HGNC; HGNC:6929; MC1R.
DR HPA; ENSG00000258839; Tissue enhanced (pituitary gland, testis).
DR MalaCards; MC1R; -.
DR MIM; 155555; gene.
DR MIM; 266300; phenotype.
DR MIM; 613098; phenotype.
DR MIM; 613099; phenotype.
DR neXtProt; NX_Q01726; -.
DR OpenTargets; ENSG00000258839; -.
DR Orphanet; 618; Familial melanoma.
DR Orphanet; 626; Large congenital melanocytic nevus.
DR Orphanet; 79432; Oculocutaneous albinism type 2.
DR PharmGKB; PA30673; -.
DR VEuPathDB; HostDB:ENSG00000258839; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01030000234510; -.
DR HOGENOM; CLU_009579_13_0_1; -.
DR InParanoid; Q01726; -.
DR OrthoDB; 981062at2759; -.
DR TreeFam; TF332646; -.
DR PathwayCommons; Q01726; -.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; Q01726; -.
DR SIGNOR; Q01726; -.
DR BioGRID-ORCS; 4157; 11 hits in 1068 CRISPR screens.
DR ChiTaRS; MC1R; human.
DR GeneWiki; Melanocortin_1_receptor; -.
DR GenomeRNAi; 4157; -.
DR Pharos; Q01726; Tclin.
DR PRO; PR:Q01726; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q01726; protein.
DR Bgee; ENSG00000258839; Expressed in granulocyte and 113 other tissues.
DR ExpressionAtlas; Q01726; baseline and differential.
DR Genevisible; Q01726; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; TAS:BHF-UCL.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0042562; F:hormone binding; IEA:Ensembl.
DR GO; GO:0004977; F:melanocortin receptor activity; TAS:ProtInc.
DR GO; GO:0004980; F:melanocyte-stimulating hormone receptor activity; IPI:BHF-UCL.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; TAS:ProtInc.
DR GO; GO:0035556; P:intracellular signal transduction; ISS:BHF-UCL.
DR GO; GO:0042438; P:melanin biosynthetic process; IEA:Ensembl.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IMP:BHF-UCL.
DR GO; GO:0043473; P:pigmentation; TAS:BHF-UCL.
DR GO; GO:2000253; P:positive regulation of feeding behavior; IEA:Ensembl.
DR GO; GO:0010739; P:positive regulation of protein kinase A signaling; ISS:BHF-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISS:BHF-UCL.
DR GO; GO:0090037; P:positive regulation of protein kinase C signaling; ISS:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
DR GO; GO:0019222; P:regulation of metabolic process; IBA:GO_Central.
DR GO; GO:0019233; P:sensory perception of pain; IEA:Ensembl.
DR GO; GO:0009650; P:UV protection; TAS:ProtInc.
DR GO; GO:0070914; P:UV-damage excision repair; IDA:BHF-UCL.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR001671; Melcrt_ACTH_rcpt.
DR InterPro; IPR000761; MSH_rcpt.
DR PANTHER; PTHR22750:SF2; PTHR22750:SF2; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR00534; MCRFAMILY.
DR PRINTS; PR00536; MELNOCYTESHR.
DR SMART; SM01381; 7TM_GPCR_Srsx; 1.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Disease variant; G-protein coupled receptor;
KW Glycoprotein; Lipoprotein; Membrane; Palmitate; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..317
FT /note="Melanocyte-stimulating hormone receptor"
FT /id="PRO_0000069818"
FT TOPO_DOM 1..37
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 38..63
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 64..72
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 73..93
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 94..118
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 119..140
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 141..163
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 164..183
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 184..191
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 192..211
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 212..240
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 241..266
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 267..279
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 280..300
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 301..317
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT LIPID 315
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 29
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 38
FT /note="V -> M (in CMM5; moderate decrease in coupling to
FT the cAMP pathway; reduced cell surface expression as a
FT consequence of retention in the endoplasmic reticulum;
FT dbSNP:rs200050206)"
FT /evidence="ECO:0000269|PubMed:19338054"
FT /id="VAR_059018"
FT VARIANT 40
FT /note="I -> T (associated with fair hair and light skin;
FT partial loss-of-function; dbSNP:rs748138541)"
FT /evidence="ECO:0000269|PubMed:11707265"
FT /id="VAR_013611"
FT VARIANT 41
FT /note="S -> F (in CMM5; complete absence of functional
FT coupling to the cAMP pathway; reduced cell surface
FT expression as a consequence of retention in the endoplasmic
FT reticulum)"
FT /evidence="ECO:0000269|PubMed:17434924,
FT ECO:0000269|PubMed:19338054"
FT /id="VAR_059019"
FT VARIANT 51
FT /note="V -> A (in CMM5; moderate decrease in coupling to
FT the cAMP pathway; reduced cell surface expression as a
FT consequence of retention in the endoplasmic reticulum;
FT dbSNP:rs766080391)"
FT /evidence="ECO:0000269|PubMed:19338054"
FT /id="VAR_059020"
FT VARIANT 60
FT /note="V -> L (associated with a risk for developing
FT melanoma; unable to stimulate cAMP production as strongly
FT as the wild type receptor in response to alpha-melanocyte-
FT stimulating hormone stimulation; dbSNP:rs1805005)"
FT /evidence="ECO:0000269|PubMed:10403794,
FT ECO:0000269|PubMed:17434924, ECO:0000269|PubMed:18987736,
FT ECO:0000269|PubMed:9302268, ECO:0000269|Ref.12"
FT /id="VAR_013612"
FT VARIANT 67
FT /note="R -> Q (shows a moderate and not significant
FT decrease of cAMP production to NDP-MSH stimulation; shows a
FT decreased responses to low concentrations of NDP-MSH
FT stimulation; dbSNP:rs34090186)"
FT /evidence="ECO:0000269|PubMed:10101176,
FT ECO:0000269|PubMed:16463023"
FT /id="VAR_009522"
FT VARIANT 84
FT /note="D -> E (may be associated with a risk for developing
FT melanoma; reduced expression at the cell surface;
FT dbSNP:rs1805006)"
FT /evidence="ECO:0000269|PubMed:10101176,
FT ECO:0000269|PubMed:15972726, ECO:0000269|PubMed:8894704,
FT ECO:0000269|PubMed:8990005"
FT /id="VAR_003507"
FT VARIANT 89
FT /note="G -> R (in dbSNP:rs34540312)"
FT /id="VAR_042654"
FT VARIANT 92
FT /note="V -> M (associated with a risk for developing
FT melanoma; predominantly found in type I skin; shows a
FT moderate and not significant decreased of cAMP production
FT to NDP-MSH stimulation; dbSNP:rs2228479)"
FT /evidence="ECO:0000269|PubMed:10101176,
FT ECO:0000269|PubMed:16463023, ECO:0000269|PubMed:17434924,
FT ECO:0000269|PubMed:18987736, ECO:0000269|PubMed:8990005,
FT ECO:0000269|PubMed:9302268, ECO:0000269|Ref.12"
FT /id="VAR_003508"
FT VARIANT 93
FT /note="L -> R (loss-of-function mutation abolishing agonist
FT binding)"
FT /evidence="ECO:0000269|PubMed:12473109"
FT /id="VAR_059021"
FT VARIANT 95
FT /note="T -> M (in dbSNP:rs34158934)"
FT /id="VAR_042655"
FT VARIANT 104
FT /note="G -> S (in dbSNP:rs2229617)"
FT /id="VAR_042656"
FT VARIANT 120
FT /note="I -> T (shows a moderate and not significant
FT decrease of cAMP production to NDP-MSH stimulation; shows
FT decreased responses to low concentrations of NDP-MSH
FT stimulation; dbSNP:rs33932559)"
FT /evidence="ECO:0000269|PubMed:16463023"
FT /id="VAR_042657"
FT VARIANT 122
FT /note="V -> M (associated with fair hair and light skin;
FT partial loss-of-function; dbSNP:rs201192930)"
FT /evidence="ECO:0000269|PubMed:11707265"
FT /id="VAR_013613"
FT VARIANT 128
FT /note="M -> T (in CMM5; complete absence of functional
FT coupling to the cAMP pathway; trafficked to the cell
FT surface but unable to bind agonist efficiently;
FT dbSNP:rs374235260)"
FT /evidence="ECO:0000269|PubMed:17434924,
FT ECO:0000269|PubMed:19338054"
FT /id="VAR_059022"
FT VARIANT 142
FT /note="R -> H (in dbSNP:rs11547464)"
FT /evidence="ECO:0000269|PubMed:10403794,
FT ECO:0000269|PubMed:12473109"
FT /id="VAR_059023"
FT VARIANT 147
FT /note="Missing (associated with UV induced susceptibility
FT to skin damage; unresponsive to NDP-MSH stimulation)"
FT /evidence="ECO:0000269|PubMed:16463023"
FT /id="VAR_042658"
FT VARIANT 151
FT /note="R -> C (associated with red hair and light skin of
FT type I; binds to alpha-MSH but cannot be stimulated to
FT produce cAMP; reduced expression at the cell surface;
FT dbSNP:rs1805007)"
FT /evidence="ECO:0000269|PubMed:10101176,
FT ECO:0000269|PubMed:10403794, ECO:0000269|PubMed:12473109,
FT ECO:0000269|PubMed:15972726, ECO:0000269|PubMed:16463023,
FT ECO:0000269|PubMed:17952075, ECO:0000269|PubMed:9302268,
FT ECO:0000269|PubMed:9571181, ECO:0000269|Ref.12"
FT /id="VAR_008522"
FT VARIANT 155
FT /note="I -> T (associated with a risk for developing
FT melanoma; reduced expression at the cell surface;
FT dbSNP:rs1110400)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:15972726, ECO:0000269|PubMed:17434924,
FT ECO:0000269|Ref.12"
FT /id="VAR_013614"
FT VARIANT 156
FT /note="V -> L (in dbSNP:rs3212365)"
FT /evidence="ECO:0000269|Ref.12"
FT /id="VAR_013615"
FT VARIANT 157
FT /note="T -> I (associated with UV induced susceptibility to
FT skin damage; shows a dramatically decreased cAMP production
FT to NDP-MSH stimulation; dbSNP:rs104894524)"
FT /evidence="ECO:0000269|PubMed:16463023"
FT /id="VAR_042659"
FT VARIANT 159
FT /note="P -> T (associated with UV induced susceptibility to
FT skin damage; shows a strong decreased cAMP production to
FT NDP-MSH stimulation; dbSNP:rs104894523)"
FT /evidence="ECO:0000269|PubMed:16463023"
FT /id="VAR_042660"
FT VARIANT 160
FT /note="R -> W (associated with a risk for developing
FT melanoma; unable to stimulate cAMP production as strongly
FT as the wild type receptor in response to alpha-melanocyte-
FT stimulating hormone stimulation; reduced expression at the
FT cell surface.; dbSNP:rs1805008)"
FT /evidence="ECO:0000269|PubMed:10403794,
FT ECO:0000269|PubMed:15972726, ECO:0000269|PubMed:17434924,
FT ECO:0000269|PubMed:9302268, ECO:0000269|PubMed:9665397,
FT ECO:0000269|Ref.12"
FT /id="VAR_008523"
FT VARIANT 162
FT /note="R -> P"
FT /evidence="ECO:0000269|PubMed:11442765"
FT /id="VAR_013632"
FT VARIANT 163
FT /note="R -> Q (associated with a risk for developing
FT melanoma; shows a moderate and not significant decrease of
FT cAMP production to NDP-MSH stimulation; shows a not
FT significant decrease in cAMP production at any
FT concentrations of NDP-MSH stimulation; dbSNP:rs885479)"
FT /evidence="ECO:0000269|PubMed:10101176,
FT ECO:0000269|PubMed:16463023, ECO:0000269|PubMed:17434924,
FT ECO:0000269|Ref.12"
FT /id="VAR_009523"
FT VARIANT 166
FT /note="A -> G (shows a moderate and not significant
FT decrease of cAMP production to NDP-MSH stimulation; shows a
FT not significant decrease in cAMP production at any
FT concentrations of NDP-MSH stimulation; dbSNP:rs35040147)"
FT /evidence="ECO:0000269|PubMed:16463023"
FT /id="VAR_042661"
FT VARIANT 171
FT /note="A -> S (in dbSNP:rs35784916)"
FT /id="VAR_042662"
FT VARIANT 196
FT /note="F -> L (in dbSNP:rs3212366)"
FT /evidence="ECO:0000269|Ref.12"
FT /id="VAR_013616"
FT VARIANT 281
FT /note="N -> S (does not affect receptor surface expression,
FT agonist binding and agonist-induced signaling;
FT dbSNP:rs141177570)"
FT /evidence="ECO:0000269|PubMed:17434924,
FT ECO:0000269|PubMed:19338054"
FT /id="VAR_059024"
FT VARIANT 289
FT /note="C -> R (in CMM5; complete absence of functional
FT coupling to the cAMP pathway; trafficked to the cell
FT surface but unable to bind agonist efficiently;
FT dbSNP:rs369542041)"
FT /evidence="ECO:0000269|PubMed:19338054"
FT /id="VAR_059025"
FT VARIANT 294
FT /note="D -> H (associated with a risk for developing
FT melanoma; unable to stimulate cAMP production as strongly
FT as the wild type receptor in response to alpha-melanocyte-
FT stimulating hormone stimulation; dbSNP:rs1805009)"
FT /evidence="ECO:0000269|PubMed:10403794,
FT ECO:0000269|PubMed:17434924, ECO:0000269|PubMed:7581459,
FT ECO:0000269|PubMed:9302268"
FT /id="VAR_008524"
FT MUTAGEN 65
FT /note="K->R: Only minor effect on internalization rate and
FT protein half-life; when associated with R-226; R-238 and R-
FT 310."
FT /evidence="ECO:0000269|PubMed:19737927"
FT MUTAGEN 226
FT /note="K->R: Only minor effect on internalization rate and
FT protein half-life; when associated with R-65; R-238 and R-
FT 310."
FT /evidence="ECO:0000269|PubMed:19737927"
FT MUTAGEN 238
FT /note="K->R: Only minor effect on internalization rate and
FT protein half-life; when associated with R-65; R-226 and R-
FT 310."
FT /evidence="ECO:0000269|PubMed:19737927"
FT MUTAGEN 310
FT /note="K->R: Only minor effect on internalization rate and
FT protein half-life; when associated with R-65; R-226 and R-
FT 238."
FT /evidence="ECO:0000269|PubMed:19737927"
FT CONFLICT 90
FT /note="S -> T (in Ref. 1 and 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 164
FT /note="A -> R (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 222
FT /note="A -> T (in Ref. 10; AAQ62976)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 317 AA; 34706 MW; CB67405A562C29B2 CRC64;
MAVQGSQRRL LGSLNSTPTA IPQLGLAANQ TGARCLEVSI SDGLFLSLGL VSLVENALVV
ATIAKNRNLH SPMYCFICCL ALSDLLVSGS NVLETAVILL LEAGALVARA AVLQQLDNVI
DVITCSSMLS SLCFLGAIAV DRYISIFYAL RYHSIVTLPR ARRAVAAIWV ASVVFSTLFI
AYYDHVAVLL CLVVFFLAML VLMAVLYVHM LARACQHAQG IARLHKRQRP VHQGFGLKGA
VTLTILLGIF FLCWGPFFLH LTLIVLCPEH PTCGCIFKNF NLFLALIICN AIIDPLIYAF
HSQELRRTLK EVLTCSW
