MC4R_RAT
ID MC4R_RAT Reviewed; 332 AA.
AC P70596;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Melanocortin receptor 4;
DE Short=MC4-R;
GN Name=Mc4r;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RX PubMed=8794897;
RA Alvaro J.D., Tatro J.B., Quillan J.M., Fogliano M., Eisenhard M.,
RA Lerner M.R., Nestler E.J., Duman R.S.;
RT "Morphine down-regulates melanocortin-4 receptor expression in brain
RT regions that mediate opiate addiction.";
RL Mol. Pharmacol. 50:583-591(1996).
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 -!- TISSUE SPECIFICITY: Brain, enriched in the striatum, nucleus accumbens,
CC and periaqueductal gray.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U67863; AAB36517.1; -; mRNA.
DR PIR; B57055; B57055.
DR RefSeq; NP_037231.1; NM_013099.3.
DR AlphaFoldDB; P70596; -.
DR SMR; P70596; -.
DR STRING; 10116.ENSRNOP00000025223; -.
DR BindingDB; P70596; -.
DR ChEMBL; CHEMBL2700; -.
DR GuidetoPHARMACOLOGY; 285; -.
DR GlyGen; P70596; 3 sites.
DR PhosphoSitePlus; P70596; -.
DR PaxDb; P70596; -.
DR DNASU; 25635; -.
DR Ensembl; ENSRNOT00000025223; ENSRNOP00000025223; ENSRNOG00000018692.
DR GeneID; 25635; -.
DR KEGG; rno:25635; -.
DR UCSC; RGD:3057; rat.
DR CTD; 4160; -.
DR RGD; 3057; Mc4r.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01030000234510; -.
DR HOGENOM; CLU_009579_13_0_1; -.
DR InParanoid; P70596; -.
DR OMA; YCTCFMS; -.
DR OrthoDB; 869396at2759; -.
DR PhylomeDB; P70596; -.
DR TreeFam; TF332646; -.
DR Reactome; R-RNO-375276; Peptide ligand-binding receptors.
DR PRO; PR:P70596; -.
DR Proteomes; UP000002494; Chromosome 18.
DR Bgee; ENSRNOG00000018692; Expressed in heart and 4 other tissues.
DR Genevisible; P70596; RN.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0042562; F:hormone binding; IDA:RGD.
DR GO; GO:0004977; F:melanocortin receptor activity; IDA:RGD.
DR GO; GO:0004980; F:melanocyte-stimulating hormone receptor activity; ISO:RGD.
DR GO; GO:0042923; F:neuropeptide binding; ISO:RGD.
DR GO; GO:0017046; F:peptide hormone binding; IDA:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; ISO:RGD.
DR GO; GO:0002024; P:diet induced thermogenesis; IDA:RGD.
DR GO; GO:0006112; P:energy reserve metabolic process; IDA:RGD.
DR GO; GO:0007631; P:feeding behavior; IDA:RGD.
DR GO; GO:0030073; P:insulin secretion; ISO:RGD.
DR GO; GO:2000252; P:negative regulation of feeding behavior; IMP:RGD.
DR GO; GO:0045780; P:positive regulation of bone resorption; ISO:RGD.
DR GO; GO:1903998; P:regulation of eating behavior; ISO:RGD.
DR GO; GO:0060259; P:regulation of feeding behavior; IMP:RGD.
DR GO; GO:2000821; P:regulation of grooming behavior; IMP:RGD.
DR GO; GO:0019222; P:regulation of metabolic process; ISO:RGD.
DR GO; GO:0032868; P:response to insulin; ISO:RGD.
DR GO; GO:1990680; P:response to melanocyte-stimulating hormone; ISO:RGD.
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 2: Evidence at transcript level;
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_0000069726"
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; 36887 MW; E0E9BAC7E7D168E6 CRC64;
MNSTHHHGMY TSLHLWNRSS HGLHGNASES LGKGHSDGGC YEQLFVSPEV FVTLGVISLL
ENILVIVAIA KNKNLHSPMY FFICSLAVAD MLVSVSNGSE TIVITLLNST DTDAQSFTVN
IDNVIDSVIC SSLLASICSL LSIAVDRYFT IFYALQYHNI MTVRRVGIII SCIWAACTVS
GVLFIIYSDS SAVIICLITM FFTMLVLMAS LYVHMFLMAR LHIKRIAVLP GTGTIRQGAN
MKGAITLTIL IGVFVVCWAP FFLHLLFYIS CPQNPYCVCF MSHFNLYLIL IMCNAVIDPL
IYALRSQELR KTFKEIICFY PLGGICELPG RY
