ID   MC4R_VULVU              Reviewed;         332 AA.
AC   Q0Z8I9;
DT   17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT   22-AUG-2006, sequence version 1.
DT   25-MAY-2022, entry version 51.
DE   RecName: Full=Melanocortin receptor 4;
DE            Short=MC4-R;
GN   Name=MC4R;
OS   Vulpes vulpes (Red fox).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Vulpes.
OX   NCBI_TaxID=9627;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Skorczyk A., Switonski M.;
RL   Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Receptor specific to the heptapeptide core common to
CC       adrenocorticotropic hormone and alpha-, beta-, and gamma-MSH. Plays a
CC       central role in energy homeostasis and somatic growth. This receptor is
CC       mediated by G proteins that stimulate adenylate cyclase (cAMP).
CC       {ECO:0000250|UniProtKB:P32245}.
CC   -!- SUBUNIT: Interacts with ATRNL1 (By similarity). Homodimer; disulfide-
CC       linked, also forms higher order oligomers. Interacts with MGRN1, but
CC       does not undergo MGRN1-mediated ubiquitination; this interaction
CC       competes with GNAS-binding and thus inhibits agonist-induced cAMP
CC       production. Interacts with MRAP and MRAP2; these associated factors
CC       increase ligand-sensitivity and generation of cAMP (By similarity).
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P32245};
CC       Multi-pass membrane protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR   EMBL; DQ663625; ABG48760.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q0Z8I9; -.
DR   SMR; Q0Z8I9; -.
DR   STRING; 9627.ENSVVUP00000021787; -.
DR   OMA; YCTCFMS; -.
DR   Proteomes; UP000286640; Unplaced.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0004977; F:melanocortin receptor activity; IEA:InterPro.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   InterPro; IPR001908; MC3-5R.
DR   InterPro; IPR000155; Mcort_rcpt_4.
DR   InterPro; IPR001671; Melcrt_ACTH_rcpt.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PRINTS; PR00237; GPCRRHODOPSN.
DR   PRINTS; PR00534; MCRFAMILY.
DR   PRINTS; PR00535; MELNOCORTINR.
DR   PRINTS; PR01062; MELNOCORTN4R.
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   3: Inferred from homology;
KW   Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein;
KW   Lipoprotein; Membrane; Palmitate; Receptor; Reference proteome; Transducer;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..332
FT                   /note="Melanocortin receptor 4"
FT                   /id="PRO_0000253757"
FT   TOPO_DOM        1..43
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        44..69
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        70..81
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        82..106
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        107..123
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        124..145
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        146..165
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        166..186
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        187..191
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        192..215
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        216..248
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        249..271
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        272..280
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        281..304
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        305..332
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   LIPID           318
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        2
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        17
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        26
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        84
FT                   /note="Interchain"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
SQ   SEQUENCE   332 AA;  36989 MW;  7805FB7E178DCA14 CRC64;
     MNSTLQHGMH TSLHFWNRST YGQHSNATES LGKGYPDGGC YEQLFVSPEV FVTLGVISLL
     ENILVIVAIA KNKNLHSPMY FFICSLAVAD MLVSVSNGSE TIVITLLNST DTDAQSFTVN
     IDNVIDSVIC SSLLASICSL LSIAVDRYFT IFYALQYHNI MTVRRVGIII SCIWAACTVS
     GILFIIYSDS TAVIICLITM FFTMLALMAS LYVHMFLMAR LHIKRIAVLP GTGTIRQGAN
     MKGAITLTIL IGVFVVCWAP FFLHLIFYIS CPQNPYCVCF MSHFNLYLIL IMCNSIIDPL
     IYALRSQELR KTFKEIICCY PLGGLCDLSS RY