MC5R_HUMAN
ID MC5R_HUMAN Reviewed; 325 AA.
AC P33032; B0YJ34; Q502V1;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 3.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Melanocortin receptor 5;
DE Short=MC5-R;
DE AltName: Full=MC-2;
GN Name=MC5R;
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].
RC TISSUE=Placenta;
RX PubMed=8396929; DOI=10.1006/bbrc.1993.2125;
RA Chhajlani V., Muceniece R., Wikberg J.E.S.;
RT "Molecular cloning of a novel human melanocortin receptor.";
RL Biochem. Biophys. Res. Commun. 195:866-873(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8179577; DOI=10.1006/bbrc.1994.1550;
RA Griffon N., Mignon V., Facchinetti P., Diaz J., Schwartz J.-C.,
RA Sokoloff P.;
RT "Molecular cloning and characterization of the rat fifth melanocortin
RT receptor.";
RL Biochem. Biophys. Res. Commun. 200:1007-1014(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RX PubMed=7739752; DOI=10.1007/bf00995160;
RA Fathi Z., Iben L.G., Parker E.M.;
RT "Cloning, expression, and tissue distribution of a fifth melanocortin
RT receptor subtype.";
RL Neurochem. Res. 20:107-113(1995).
RN [4]
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 (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-209.
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 [8]
RP MUTAGENESIS OF GLN-235 AND ARG-272.
RX PubMed=9240466; DOI=10.1006/bbrc.1997.6994;
RA Fraendberg P.-A., Xu X., Chhajlani V.;
RT "Glutamine235 and arginine272 in human melanocortin 5 receptor determines
RT its low affinity to MSH.";
RL Biochem. Biophys. Res. Commun. 236:489-492(1997).
RN [9]
RP VARIANT LEU-209.
RX PubMed=11286624; DOI=10.1046/j.0022-202x.2001.01286.x;
RA Hatta N., Dixon C., Ray A.J., Phillips S.R., Cunliffe W.J., Dale M.,
RA Todd C., Meggit S., Birch-MacHin M.A., Rees J.L.;
RT "Expression, candidate gene, and population studies of the melanocortin 5
RT receptor.";
RL J. Invest. Dermatol. 116:564-570(2001).
CC -!- FUNCTION: Receptor for MSH (alpha, beta and gamma) and ACTH. The
CC activity of this receptor is mediated by G proteins which activate
CC adenylate cyclase. This receptor is a possible mediator of the
CC immunomodulation properties of melanocortins.
CC -!- INTERACTION:
CC P33032; Q8TCY5: MRAP; NbExp=2; IntAct=EBI-9538507, EBI-9538727;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in the brain but not in the melanoma
CC cells.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Melanocortin receptor entry;
CC URL="https://en.wikipedia.org/wiki/Melanocortin_receptor";
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DR EMBL; Z25470; CAA80962.1; -; Genomic_DNA.
DR EMBL; L27080; AAA59566.1; -; Genomic_DNA.
DR EMBL; U08353; AAB60376.1; -; Genomic_DNA.
DR EMBL; AY268429; AAP23196.1; -; Genomic_DNA.
DR EMBL; EF444993; ACA06012.1; -; Genomic_DNA.
DR EMBL; CH471113; EAX01504.1; -; Genomic_DNA.
DR EMBL; BC069153; AAH69153.1; -; mRNA.
DR EMBL; BC069545; AAH69545.1; -; mRNA.
DR EMBL; BC095531; AAH95531.1; -; mRNA.
DR CCDS; CCDS11868.1; -.
DR PIR; JC5592; JC5592.
DR PIR; JN0764; JN0764.
DR RefSeq; NP_005904.1; NM_005913.2.
DR AlphaFoldDB; P33032; -.
DR SMR; P33032; -.
DR BioGRID; 110331; 1.
DR DIP; DIP-48792N; -.
DR IntAct; P33032; 2.
DR STRING; 9606.ENSP00000318077; -.
DR BindingDB; P33032; -.
DR ChEMBL; CHEMBL4608; -.
DR DrugBank; DB11653; Bremelanotide.
DR DrugCentral; P33032; -.
DR GuidetoPHARMACOLOGY; 286; -.
DR GlyGen; P33032; 4 sites.
DR iPTMnet; P33032; -.
DR PhosphoSitePlus; P33032; -.
DR BioMuta; MC5R; -.
DR DMDM; 729996; -.
DR PaxDb; P33032; -.
DR PeptideAtlas; P33032; -.
DR PRIDE; P33032; -.
DR Antibodypedia; 7155; 428 antibodies from 37 providers.
DR DNASU; 4161; -.
DR Ensembl; ENST00000324750.5; ENSP00000318077.3; ENSG00000176136.6.
DR Ensembl; ENST00000589410.2; ENSP00000468086.2; ENSG00000176136.6.
DR GeneID; 4161; -.
DR KEGG; hsa:4161; -.
DR MANE-Select; ENST00000589410.2; ENSP00000468086.2; NM_005913.3; NP_005904.1.
DR UCSC; uc010xaf.3; human.
DR CTD; 4161; -.
DR DisGeNET; 4161; -.
DR GeneCards; MC5R; -.
DR HGNC; HGNC:6933; MC5R.
DR HPA; ENSG00000176136; Tissue enhanced (epididymis, lymphoid tissue).
DR MIM; 600042; gene.
DR neXtProt; NX_P33032; -.
DR OpenTargets; ENSG00000176136; -.
DR PharmGKB; PA30677; -.
DR VEuPathDB; HostDB:ENSG00000176136; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01030000234510; -.
DR HOGENOM; CLU_009579_13_0_1; -.
DR InParanoid; P33032; -.
DR OMA; LYCSCFM; -.
DR OrthoDB; 877700at2759; -.
DR PhylomeDB; P33032; -.
DR TreeFam; TF332646; -.
DR PathwayCommons; P33032; -.
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; P33032; -.
DR SIGNOR; P33032; -.
DR BioGRID-ORCS; 4161; 7 hits in 1057 CRISPR screens.
DR GeneWiki; Melanocortin_5_receptor; -.
DR GenomeRNAi; 4161; -.
DR Pharos; P33032; Tchem.
DR PRO; PR:P33032; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; P33032; protein.
DR Bgee; ENSG00000176136; Expressed in lower esophagus mucosa and 37 other tissues.
DR Genevisible; P33032; 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:HPA.
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; IBA:GO_Central.
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:0019222; P:regulation of metabolic process; IBA:GO_Central.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR001908; MC3-5R.
DR InterPro; IPR000621; Melancort_rcpt_5.
DR InterPro; IPR001671; Melcrt_ACTH_rcpt.
DR PANTHER; PTHR22750:SF5; PTHR22750:SF5; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR00534; MCRFAMILY.
DR PRINTS; PR00535; MELNOCORTINR.
DR PRINTS; PR01063; MELNOCORTN5R.
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 Cell membrane; G-protein coupled receptor; Glycoprotein; Lipoprotein;
KW Membrane; Palmitate; Receptor; Reference proteome; Transducer;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..325
FT /note="Melanocortin receptor 5"
FT /id="PRO_0000069728"
FT TOPO_DOM 1..37
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 38..61
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 62..73
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 74..97
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 98..114
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 115..138
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 139..155
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 156..179
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 180..186
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 187..211
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 212..239
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 240..265
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 266..273
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 274..297
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 298..325
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT LIPID 311
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000255"
FT LIPID 312
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 15
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 20
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 28
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 209
FT /note="F -> L (in dbSNP:rs2236700)"
FT /evidence="ECO:0000269|PubMed:11286624,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_013128"
FT MUTAGEN 235
FT /note="Q->K: 10% increase of binding to alpha-MSH."
FT /evidence="ECO:0000269|PubMed:9240466"
FT MUTAGEN 272
FT /note="R->C: 690% increase of binding to alpha-MSH."
FT /evidence="ECO:0000269|PubMed:9240466"
FT CONFLICT 149
FT /note="R -> A (in Ref. 2; AAA59566)"
FT /evidence="ECO:0000305"
FT CONFLICT 221..234
FT /note="ALPGASSARQRTSM -> LCPGPALRGRGPAW (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 297
FT /note="F -> Y (in Ref. 2; AAA59566)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 325 AA; 36601 MW; 8BEC17E1BDA059BB CRC64;
MNSSFHLHFL DLNLNATEGN LSGPNVKNKS SPCEDMGIAV EVFLTLGVIS LLENILVIGA
IVKNKNLHSP MYFFVCSLAV ADMLVSMSSA WETITIYLLN NKHLVIADAF VRHIDNVFDS
MICISVVASM CSLLAIAVDR YVTIFYALRY HHIMTARRSG AIIAGIWAFC TGCGIVFILY
SESTYVILCL ISMFFAMLFL LVSLYIHMFL LARTHVKRIA ALPGASSARQ RTSMQGAVTV
TMLLGVFTVC WAPFFLHLTL MLSCPQNLYC SRFMSHFNMY LILIMCNSVM DPLIYAFRSQ
EMRKTFKEII CCRGFRIACS FPRRD
