MC4R_DANRE
ID MC4R_DANRE Reviewed; 326 AA.
AC B0V1P1; Q8JGW3;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 08-APR-2008, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=Melanocortin receptor 4;
DE Short=MC4-R;
GN Name=mc4r;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=12091460; DOI=10.1046/j.1471-4159.2002.00934.x;
RA Ringholm A., Fredriksson R., Poliakova N., Yan Y.L., Postlethwait J.H.,
RA Larhammar D., Schioth H.B.;
RT "One melanocortin 4 and two melanocortin 5 receptors from zebrafish show
RT remarkable conservation in structure and pharmacology.";
RL J. Neurochem. 82:6-18(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=12620396; DOI=10.1016/s0888-7543(02)00037-x;
RA Logan D.W., Bryson-Richardson R.J., Pagan K.E., Taylor M.S., Currie P.D.,
RA Jackson I.J.;
RT "The structure and evolution of the melanocortin and MCH receptors in fish
RT and mammals.";
RL Genomics 81:184-191(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, AND INTERACTION WITH MRAP2A AND MRAP2B.
RX PubMed=23869017; DOI=10.1126/science.1232995;
RA Sebag J.A., Zhang C., Hinkle P.M., Bradshaw A.M., Cone R.D.;
RT "Developmental control of the melanocortin-4 receptor by MRAP2 proteins in
RT zebrafish.";
RL Science 341:278-281(2013).
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:0000269|PubMed:23869017}.
CC -!- SUBUNIT: Homodimer; disulfide-linked, also forms higher order oligomers
CC (By similarity). Interacts with mrap2a; decreasing ligand-sensitivity.
CC Interacts with mrap2b; increasing ligand-sensitivity and generation of
CC cAMP. {ECO:0000250, ECO:0000269|PubMed:23869017}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AY078989; AAL85494.1; -; Genomic_DNA.
DR EMBL; AY161850; AAO24745.1; -; Genomic_DNA.
DR EMBL; CR925777; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC163219; AAI63219.1; -; mRNA.
DR EMBL; BC163227; AAI63227.1; -; mRNA.
DR RefSeq; NP_775385.1; NM_173278.1.
DR AlphaFoldDB; B0V1P1; -.
DR SMR; B0V1P1; -.
DR STRING; 7955.ENSDARP00000027547; -.
DR PaxDb; B0V1P1; -.
DR Ensembl; ENSDART00000019555; ENSDARP00000027547; ENSDARG00000015515.
DR GeneID; 286833; -.
DR KEGG; dre:286833; -.
DR CTD; 4160; -.
DR ZFIN; ZDB-GENE-021223-2; mc4r.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01030000234510; -.
DR HOGENOM; CLU_009579_13_0_1; -.
DR InParanoid; B0V1P1; -.
DR OMA; FREICCG; -.
DR OrthoDB; 869396at2759; -.
DR PhylomeDB; B0V1P1; -.
DR TreeFam; TF332646; -.
DR Reactome; R-DRE-375276; Peptide ligand-binding receptors.
DR Reactome; R-DRE-418555; G alpha (s) signalling events.
DR PRO; PR:B0V1P1; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 2.
DR Bgee; ENSDARG00000015515; Expressed in mature ovarian follicle and 13 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0004977; F:melanocortin receptor activity; IDA:UniProtKB.
DR GO; GO:0004980; F:melanocyte-stimulating hormone receptor activity; IBA:GO_Central.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:ZFIN.
DR GO; GO:0097009; P:energy homeostasis; IDA:UniProtKB.
DR GO; GO:0006112; P:energy reserve metabolic process; IDA:UniProtKB.
DR GO; GO:2000252; P:negative regulation of feeding behavior; IMP:ZFIN.
DR GO; GO:0040008; P:regulation of growth; IGI:ZFIN.
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; 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 1: Evidence at protein 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..326
FT /note="Melanocortin receptor 4"
FT /id="PRO_0000424026"
FT TOPO_DOM 1..46
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 47..67
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 68..71
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 72..92
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 93..121
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 122..142
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 143..163
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 164..184
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 185..190
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 191..211
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 212..246
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 247..267
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 268..281
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 282..302
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 303..326
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 316
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 94
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 108
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 81
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT CONFLICT 47
FT /note="I -> V (in Ref. 1; AAL85494, 2; AAO24745 and 4;
FT AAI63227/AAI63219)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 326 AA; 36435 MW; 40680015C2430C8E CRC64;
MNTSHHHGLH HSFRNHSQGA LPVGKPSHGD RGSASGCYEQ LLISTEIFLT LGLVSLLENI
LVIAAIVKNK NLHSPMYFFI CSLAVADLLV SVSNASETVV MALITGGNLT NRESIIKNMD
NVFDSMICSS LLASIWSLLA IAVDRYITIF YALRYHNIMT QRRAGTIITC IWTFCTVSGV
LFIVYSESTT VLICLISMFF TMLALMASLY VHMFLLARLH MKRIAALPGN GPIWQAANMK
GAITITILLG VFVVCWAPFF LHLILMISCP RNPYCVCFMS HFNMYLILIM CNSVIDPLIY
AFRSQEMRKT FKEICCCWYG LASLCV
