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Melanocortin receptor 4 (MC4-R)

 MC4R_DANRE              Reviewed;         326 AA.
B0V1P1; Q8JGW3;
16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
08-APR-2008, sequence version 1.
30-AUG-2017, entry version 72.
RecName: Full=Melanocortin receptor 4;
Short=MC4-R;
Name=mc4r;
Danio rerio (Zebrafish) (Brachydanio rerio).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
Cyprinidae; Danio.
NCBI_TaxID=7955;
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=12091460; DOI=10.1046/j.1471-4159.2002.00934.x;
Ringholm A., Fredriksson R., Poliakova N., Yan Y.L.,
Postlethwait J.H., Larhammar D., Schioth H.B.;
"One melanocortin 4 and two melanocortin 5 receptors from zebrafish
show remarkable conservation in structure and pharmacology.";
J. Neurochem. 82:6-18(2002).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=12620396; DOI=10.1016/S0888-7543(02)00037-X;
Logan D.W., Bryson-Richardson R.J., Pagan K.E., Taylor M.S.,
Currie P.D., Jackson I.J.;
"The structure and evolution of the melanocortin and MCH receptors in
fish and mammals.";
Genomics 81:184-191(2003).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=Tuebingen;
PubMed=23594743; DOI=10.1038/nature12111;
Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C.,
Muffato M., Collins J.E., Humphray S., McLaren K., Matthews L.,
McLaren S., Sealy I., Caccamo M., Churcher C., Scott C., Barrett J.C.,
Koch R., Rauch G.J., White S., Chow W., Kilian B., Quintais L.T.,
Guerra-Assuncao J.A., Zhou Y., Gu Y., Yen J., Vogel J.H., Eyre T.,
Redmond S., Banerjee R., Chi J., Fu B., Langley E., Maguire S.F.,
Laird G.K., Lloyd D., Kenyon E., Donaldson S., Sehra H.,
Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
Clee C., Oliver K., Clark R., Riddle C., Eliott D., Threadgold G.,
Harden G., Ware D., Mortimer B., Kerry G., Heath P., Phillimore B.,
Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S., Pelan S.,
Griffiths G., Smith M., Glithero R., Howden P., Barker N., Stevens C.,
Harley J., Holt K., Panagiotidis G., Lovell J., Beasley H.,
Henderson C., Gordon D., Auger K., Wright D., Collins J., Raisen C.,
Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
Humphries M., Sycamore N., Barker D., Saunders D., Wallis J.,
Babbage A., Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S.,
Wray P., Ellington A., Matthews N., Ellwood M., Woodmansey R.,
Clark G., Cooper J., Tromans A., Grafham D., Skuce C., Pandian R.,
Andrews R., Harrison E., Kimberley A., Garnett J., Fosker N., Hall R.,
Garner P., Kelly D., Bird C., Palmer S., Gehring I., Berger A.,
Dooley C.M., Ersan-Urun Z., Eser C., Geiger H., Geisler M.,
Karotki L., Kirn A., Konantz J., Konantz M., Oberlander M.,
Rudolph-Geiger S., Teucke M., Osoegawa K., Zhu B., Rapp A., Widaa S.,
Langford C., Yang F., Carter N.P., Harrow J., Ning Z., Herrero J.,
Searle S.M., Enright A., Geisler R., Plasterk R.H., Lee C.,
Westerfield M., de Jong P.J., Zon L.I., Postlethwait J.H.,
Nusslein-Volhard C., Hubbard T.J., Roest Crollius H., Rogers J.,
Stemple D.L.;
"The zebrafish reference genome sequence and its relationship to the
human genome.";
Nature 496:498-503(2013).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
NIH - Zebrafish Gene Collection (ZGC) project;
Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
[5]
FUNCTION, AND INTERACTION WITH MRAP2A AND MRAP2B.
PubMed=23869017; DOI=10.1126/science.1232995;
Sebag J.A., Zhang C., Hinkle P.M., Bradshaw A.M., Cone R.D.;
"Developmental control of the melanocortin-4 receptor by MRAP2
proteins in zebrafish.";
Science 341:278-281(2013).
-!- FUNCTION: Receptor specific to the heptapeptide core common to
adrenocorticotropic hormone and alpha-, beta-, and gamma-MSH.
Plays a central role in energy homeostasis and somatic growth.
This receptor is mediated by G proteins that stimulate adenylate
cyclase (cAMP). {ECO:0000269|PubMed:23869017}.
-!- SUBUNIT: Homodimer; disulfide-linked, also forms higher order
oligomers (By similarity). Interacts with mrap2a; decreasing
ligand-sensitivity. Interacts with mrap2b; increasing ligand-
sensitivity and generation of cAMP. {ECO:0000250,
ECO:0000269|PubMed:23869017}.
-!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
-!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
{ECO:0000255|PROSITE-ProRule:PRU00521}.
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EMBL; AY078989; AAL85494.1; -; Genomic_DNA.
EMBL; AY161850; AAO24745.1; -; Genomic_DNA.
EMBL; CR925777; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC163219; AAI63219.1; -; mRNA.
EMBL; BC163227; AAI63227.1; -; mRNA.
RefSeq; NP_775385.1; NM_173278.1.
UniGene; Dr.45846; -.
ProteinModelPortal; B0V1P1; -.
SMR; B0V1P1; -.
STRING; 7955.ENSDARP00000027547; -.
PaxDb; B0V1P1; -.
Ensembl; ENSDART00000019555; ENSDARP00000027547; ENSDARG00000015515.
GeneID; 286833; -.
KEGG; dre:286833; -.
CTD; 4160; -.
ZFIN; ZDB-GENE-021223-2; mc4r.
eggNOG; KOG3656; Eukaryota.
eggNOG; ENOG410XRW9; LUCA.
GeneTree; ENSGT00770000120529; -.
HOGENOM; HOG000246927; -.
HOVERGEN; HBG108148; -.
InParanoid; B0V1P1; -.
KO; K04202; -.
OMA; MHTSLHF; -.
OrthoDB; EOG091G0BVW; -.
TreeFam; TF332646; -.
Reactome; R-DRE-375276; Peptide ligand-binding receptors.
Reactome; R-DRE-418555; G alpha (s) signalling events.
PRO; PR:B0V1P1; -.
Proteomes; UP000000437; Chromosome 2.
Bgee; ENSDARG00000015515; -.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
GO; GO:0004977; F:melanocortin receptor activity; IDA:UniProtKB.
GO; GO:0097009; P:energy homeostasis; IDA:UniProtKB.
GO; GO:0006112; P:energy reserve metabolic process; IDA:UniProtKB.
GO; GO:2000252; P:negative regulation of feeding behavior; IMP:ZFIN.
GO; GO:0030819; P:positive regulation of cAMP biosynthetic process; IDA:UniProtKB.
GO; GO:0040008; P:regulation of growth; IGI:ZFIN.
CDD; cd15353; 7tmA_MC4R; 1.
InterPro; IPR000276; GPCR_Rhodpsn.
InterPro; IPR017452; GPCR_Rhodpsn_7TM.
InterPro; IPR000155; Mcort_rcpt_4.
InterPro; IPR001908; Melancort_rcpt.
InterPro; IPR001671; Melcrt_ACTH_rcpt.
Pfam; PF00001; 7tm_1; 1.
PRINTS; PR00237; GPCRRHODOPSN.
PRINTS; PR00534; MCRFAMILY.
PRINTS; PR00535; MELNOCORTINR.
PRINTS; PR01062; MELNOCORTN4R.
SMART; SM01381; 7TM_GPCR_Srsx; 1.
PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
1: Evidence at protein level;
Cell membrane; Complete proteome; Disulfide bond;
G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane;
Palmitate; Receptor; Reference proteome; Transducer; Transmembrane;
Transmembrane helix.
CHAIN 1 326 Melanocortin receptor 4.
/FTId=PRO_0000424026.
TOPO_DOM 1 46 Extracellular. {ECO:0000255}.
TRANSMEM 47 67 Helical; Name=1. {ECO:0000255}.
TOPO_DOM 68 71 Cytoplasmic. {ECO:0000255}.
TRANSMEM 72 92 Helical; Name=2. {ECO:0000255}.
TOPO_DOM 93 121 Extracellular. {ECO:0000255}.
TRANSMEM 122 142 Helical; Name=3. {ECO:0000255}.
TOPO_DOM 143 163 Cytoplasmic. {ECO:0000255}.
TRANSMEM 164 184 Helical; Name=4. {ECO:0000255}.
TOPO_DOM 185 190 Extracellular. {ECO:0000255}.
TRANSMEM 191 211 Helical; Name=5. {ECO:0000255}.
TOPO_DOM 212 246 Cytoplasmic. {ECO:0000255}.
TRANSMEM 247 267 Helical; Name=6. {ECO:0000255}.
TOPO_DOM 268 281 Extracellular. {ECO:0000255}.
TRANSMEM 282 302 Helical; Name=7. {ECO:0000255}.
TOPO_DOM 303 326 Cytoplasmic. {ECO:0000255}.
LIPID 316 316 S-palmitoyl cysteine. {ECO:0000255}.
CARBOHYD 2 2 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 15 15 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 94 94 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 108 108 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 81 81 Interchain. {ECO:0000255|PROSITE-
ProRule:PRU00521}.
CONFLICT 47 47 I -> V (in Ref. 1; AAL85494, 2; AAO24745
and 4; AAI63227/AAI63219). {ECO:0000305}.
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


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