ID   MC3R_MOUSE              Reviewed;         323 AA.
AC   P33033;
DT   01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1993, sequence version 1.
DT   04-NOV-2026, entry version 178.
DE   RecName: Full=Melanocortin receptor 3;
DE            Short=MC3-R;
GN   Name=Mc3r {ECO:0000312|MGI:MGI:96929};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=8172596; DOI=10.1042/bj2990367;
RA   Desarnaud F., Labbe O., Eggerickx D., Vassart G., Parmentier M.;
RT   "Molecular cloning, functional expression and pharmacological
RT   characterization of a mouse melanocortin receptor gene.";
RL   Biochem. J. 299:367-373(1994).
RN   [2]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=19036988; DOI=10.1523/jneurosci.3615-08.2008;
RA   Sutton G.M., Perez-Tilve D., Nogueiras R., Fang J., Kim J.K., Cone R.D.,
RA   Gimble J.M., Tschop M.H., Butler A.A.;
RT   "The melanocortin-3 receptor is required for entrainment to meal intake.";
RL   J. Neurosci. 28:12946-12955(2008).
CC   -!- FUNCTION: G protein-coupled receptor for melanocyte-stimulating
CC       hormones (alpha, beta, and gamma-MSH) and corticotropin/ACTH, which are
CC       peptide products of the POMC precursor. Upon activation, couples to
CC       G(s) protein, stimulating adenylate cyclase and the cAMP-dependent
CC       signaling pathway, which contributes to the regulation of energy
CC       homeostasis (PubMed:8172596). Required for expression of anticipatory
CC       patterns of activity and wakefulness during periods of limited nutrient
CC       availability and for the normal regulation of circadian clock activity
CC       in the brain (PubMed:19036988). Binding of the Agouti-related
CC       protein/AGPR antagonist precludes alpha-MSH-induced signaling, blocking
CC       cAMP production (By similarity). {ECO:0000250|UniProtKB:P41968,
CC       ECO:0000269|PubMed:19036988, ECO:0000269|PubMed:8172596}.
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC         Evidence={ECO:0000250|UniProtKB:P41968};
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC   -!- TISSUE SPECIFICITY: Brain. {ECO:0000269|PubMed:8172596}.
CC   -!- DISRUPTION PHENOTYPE: Knockout mice show impaired activity-based
CC       responses to restricted feeding. {ECO:0000269|PubMed:19036988}.
CC   -!- SIMILARITY: Belongs to the G protein-coupled receptor 1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR   EMBL; X74983; CAA52918.1; -; Genomic_DNA.
DR   CCDS; CCDS17127.1; -.
DR   PIR; S43850; S43850.
DR   RefSeq; NP_032587.1; NM_008561.3.
DR   AlphaFoldDB; P33033; -.
DR   SMR; P33033; -.
DR   BioGRID; 201340; 1.
DR   CORUM; P33033; -.
DR   FunCoup; P33033; 426.
DR   STRING; 10090.ENSMUSP00000047358; -.
DR   BindingDB; P33033; -.
DR   ChEMBL; CHEMBL4774; -.
DR   DrugCentral; P33033; -.
DR   GuidetoPHARMACOLOGY; 284; -.
DR   GlyCosmos; P33033; 3 sites, No reported glycans.
DR   GlyGen; P33033; 3 sites.
DR   PaxDb; 10090-ENSMUSP00000047358; -.
DR   Antibodypedia; 2935; 379 antibodies from 39 providers.
DR   DNASU; 17201; -.
DR   Ensembl; ENSMPUT00000020324; ENSMPUP00000020037; ENSMPUG00000020172.
DR   Ensembl; ENSMUST00000038532.2; ENSMUSP00000047358.2; ENSMUSG00000038537.2.
DR   GeneID; 17201; -.
DR   KEGG; mmu:17201; -.
DR   UCSC; uc008ocl.1; mouse.
DR   AGR; MGI:96929; -.
DR   CTD; 4159; -.
DR   MGI; MGI:96929; Mc3r.
DR   VEuPathDB; HostDB:ENSMUSG00000038537; -.
DR   eggNOG; KOG3656; Eukaryota.
DR   GeneTree; ENSGT01140000282542; -.
DR   HOGENOM; CLU_009579_13_0_1; -.
DR   InParanoid; P33033; -.
DR   OMA; AAIWACC; -.
DR   OrthoDB; 5970330at2759; -.
DR   PhylomeDB; P33033; -.
DR   Reactome; R-MMU-375276; Peptide ligand-binding receptors.
DR   Reactome; R-MMU-418555; G alpha (s) signalling events.
DR   BioGRID-ORCS; 17201; 2 hits in 78 CRISPR screens.
DR   PRO; PR:P33033; -.
DR   Proteomes; UP000000589; Chromosome 2.
DR   RNAct; P33033; protein.
DR   Bgee; ENSMUSG00000038537; Expressed in epiblast cell in embryo and 23 other cell types or tissues.
DR   ExpressionAtlas; P33033; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0004978; F:corticotropin receptor activity; ISO:GO_Central.
DR   GO; GO:0004977; F:melanocortin receptor activity; ISO:GO_Central.
DR   GO; GO:0004980; F:melanocyte-stimulating hormone receptor activity; IDA:MGI.
DR   GO; GO:0042923; F:neuropeptide binding; ISO:GO_Central.
DR   GO; GO:0017046; F:peptide hormone binding; ISO:GO_Central.
DR   GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; ISO:GO_Central.
DR   GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; ISO:GO_Central.
DR   GO; GO:0032922; P:circadian regulation of gene expression; IMP:UniProtKB.
DR   GO; GO:0042309; P:homoiothermy; ISO:GO_Central.
DR   GO; GO:0045475; P:locomotor rhythm; IMP:UniProtKB.
DR   GO; GO:0008217; P:regulation of blood pressure; ISO:GO_Central.
DR   GO; GO:0060259; P:regulation of feeding behavior; IMP:UniProtKB.
DR   GO; GO:0002027; P:regulation of heart rate; ISO:GO_Central.
DR   GO; GO:0055078; P:sodium ion homeostasis; IEA:Ensembl.
DR   CDD; cd15352; 7tmA_MC3R; 1.
DR   FunFam; 1.20.1070.10:FF:000077; Melanocortin receptor 4; 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; IPR002122; Mcort_3_rcpt.
DR   InterPro; IPR001671; Melcrt_ACTH_rcpt.
DR   PANTHER; PTHR22750; G-PROTEIN COUPLED RECEPTOR; 1.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PRINTS; PR00237; GPCRRHODOPSN.
DR   PRINTS; PR00534; MCRFAMILY.
DR   PRINTS; PR00535; MELNOCORTINR.
DR   PRINTS; PR01061; MELNOCORTN3R.
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.
PE   2: Evidence at transcript level;
KW   Biological rhythms; Calcium; Cell membrane; Disulfide bond;
KW   G protein-coupled receptor; Glycoprotein; Lipoprotein; Membrane;
KW   Metal-binding; Palmitate; Receptor; Reference proteome; Transducer;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..323
FT                   /note="Melanocortin receptor 3"
FT                   /id="PRO_0000069719"
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..75
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        76..100
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        101..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..160
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        161..181
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        182..186
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        187..210
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        211..245
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        246..268
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        269..277
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        278..301
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        302..323
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   BINDING         94
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P41968"
FT   BINDING         117
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P41968"
FT   BINDING         121
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P41968"
FT   LIPID           315
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        2
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        16
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        28
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        35..276
FT                   /evidence="ECO:0000250|UniProtKB:P41968"
FT   DISULFID        268..274
FT                   /evidence="ECO:0000250|UniProtKB:P41968"
SQ   SEQUENCE   323 AA;  35806 MW;  F4B7B02FA4A87B7B CRC64;
     MNSSCCLSSV SPMLPNLSEH PAAPPASNRS GSGFCEQVFI KPEVFLALGI VSLMENILVI
     LAVVRNGNLH SPMYFFLCSL AAADMLVSLS NSLETIMIAV INSDSLTLED QFIQHMDNIF
     DSMICISLVA SICNLLAIAI DRYVTIFYAL RYHSIMTVRK ALTLIGVIWV CCGICGVMFI
     IYSESKMVIV CLITMFFAMV LLMGTLYIHM FLFARLHVQR IAVLPPAGVV APQQHSCMKG
     AVTITILLGV FIFCWAPFFL HLVLIITCPT NPYCICYTAH FNTYLVLIMC NSVIDPLIYA
     FRSLELRNTF KEILCGCNSM NLG
//