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   27-MAR-2024, entry version 194.
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   PDB; 8INR; EM; 2.73 A; R=2-325.
DR   PDB; 8IOD; EM; 2.59 A; R=2-325.
DR   PDBsum; 8INR; -.
DR   PDBsum; 8IOD; -.
DR   AlphaFoldDB; P33032; -.
DR   EMDB; EMD-35601; -.
DR   EMDB; EMD-35616; -.
DR   SMR; P33032; -.
DR   BioGRID; 110331; 1.
DR   DIP; DIP-48792N; -.
DR   IntAct; P33032; 2.
DR   STRING; 9606.ENSP00000468086; -.
DR   BindingDB; P33032; -.
DR   ChEMBL; CHEMBL4608; -.
DR   DrugBank; DB11653; Bremelanotide.
DR   DrugCentral; P33032; -.
DR   GuidetoPHARMACOLOGY; 286; -.
DR   GlyCosmos; P33032; 4 sites, No reported glycans.
DR   GlyGen; P33032; 4 sites.
DR   iPTMnet; P33032; -.
DR   PhosphoSitePlus; P33032; -.
DR   BioMuta; MC5R; -.
DR   DMDM; 729996; -.
DR   PaxDb; 9606-ENSP00000318077; -.
DR   PeptideAtlas; P33032; -.
DR   Antibodypedia; 7155; 451 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   AGR; HGNC:6933; -.
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; VYYESTY; -.
DR   OrthoDB; 4160596at2759; -.
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   SignaLink; P33032; -.
DR   SIGNOR; P33032; -.
DR   BioGRID-ORCS; 4161; 8 hits in 1135 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 primordial germ cell in gonad and 39 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IDA:HPA.
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   CDD; cd15354; 7tmA_MC5R; 1.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
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; G-PROTEIN COUPLED RECEPTOR; 1.
DR   PANTHER; PTHR22750:SF5; MELANOCORTIN RECEPTOR 5; 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   SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR   PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR   PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
DR   Genevisible; P33032; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Cell membrane; G-protein coupled receptor; Glycoprotein;
KW   Lipoprotein; 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"
FT   HELIX           40..43
FT                   /evidence="ECO:0007829|PDB:8IOD"
FT   HELIX           45..59
FT                   /evidence="ECO:0007829|PDB:8IOD"
FT   TURN            60..63
FT                   /evidence="ECO:0007829|PDB:8IOD"
FT   STRAND          64..66
FT                   /evidence="ECO:0007829|PDB:8IOD"
FT   HELIX           70..100
FT                   /evidence="ECO:0007829|PDB:8IOD"
FT   HELIX           108..145
FT                   /evidence="ECO:0007829|PDB:8IOD"
FT   STRAND          148..150
FT                   /evidence="ECO:0007829|PDB:8IOD"
FT   TURN            151..153
FT                   /evidence="ECO:0007829|PDB:8IOD"
FT   HELIX           156..179
FT                   /evidence="ECO:0007829|PDB:8IOD"
FT   HELIX           184..219
FT                   /evidence="ECO:0007829|PDB:8IOD"
FT   STRAND          220..222
FT                   /evidence="ECO:0007829|PDB:8IOD"
FT   HELIX           234..246
FT                   /evidence="ECO:0007829|PDB:8IOD"
FT   TURN            247..251
FT                   /evidence="ECO:0007829|PDB:8IOD"
FT   HELIX           253..260
FT                   /evidence="ECO:0007829|PDB:8IOD"
FT   TURN            261..263
FT                   /evidence="ECO:0007829|PDB:8IOD"
FT   HELIX           268..274
FT                   /evidence="ECO:0007829|PDB:8IOD"
FT   HELIX           277..295
FT                   /evidence="ECO:0007829|PDB:8IOD"
FT   STRAND          297..299
FT                   /evidence="ECO:0007829|PDB:8IOD"
FT   HELIX           300..311
FT                   /evidence="ECO:0007829|PDB:8IOD"
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
//