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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.
28-MAR-2018, entry version 73.
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:0005622; C:intracellular; IEA:GOC.
GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
GO; GO:0004977; F:melanocortin receptor activity; IDA:UniProtKB.
GO; GO:0007189; P:adenylate cyclase-activating G-protein coupled receptor signaling pathway; IDA:ZFIN.
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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Pathways :
WP1004: Kit Receptor Signaling Pathway
WP1011: T Cell Receptor Signaling Pathway
WP1014: Androgen receptor signaling pathway
WP1025: B Cell Receptor Signaling Pathway
WP1045: TGF-beta Receptor Signaling Pathway
WP1046: Signaling of Hepatocyte Growth Factor Receptor
WP1067: Toll-like receptor signaling pathway
WP1112: EPO Receptor Signaling
WP1121: Kit Receptor Signaling Pathway
WP1130: T Cell Receptor Signaling Pathway
WP1133: Androgen receptor signaling pathway
WP1144: B Cell Receptor Signaling Pathway
WP1161: TGF-beta Receptor Signaling Pathway
WP1162: Signaling of Hepatocyte Growth Factor Receptor
WP1183: Toll-like receptor signaling pathway
WP1206: Signaling of Hepatocyte Growth Factor Receptor
WP1235: Signaling of Hepatocyte Growth Factor Receptor
WP1249: EPO Receptor Signaling
WP1271: Toll-like receptor signaling pathway
WP1284: EPO Receptor Signaling
WP1309: Toll-like receptor signaling pathway
WP1336: EPO Receptor Signaling
WP1341: Kit Receptor Signaling Pathway
WP1345: T Cell Receptor Signaling Pathway
WP1348: Androgen Receptor Signaling Pathway
Related Genes :
[MC4R] Melanocortin receptor 4 (MC4-R)
[MC1R MSHR] Melanocyte-stimulating hormone receptor (MSH-R) (Melanocortin receptor 1) (MC1-R)
[MRAP2 C6orf117] Melanocortin-2 receptor accessory protein 2 (MC2R accessory protein 2)
[Mrap2] Melanocortin-2 receptor accessory protein 2
[MRAP C21orf61 FALP] Melanocortin-2 receptor accessory protein (B27) (Fat cell-specific low molecular weight protein) (Fat tissue-specific low MW protein)
[MC3R] Melanocortin receptor 3 (MC3-R)
[Mc4r] Melanocortin receptor 4 (MC4-R)
[MC2R ACTHR] Adrenocorticotropic hormone receptor (ACTH receptor) (ACTH-R) (Adrenocorticotropin receptor) (Melanocortin receptor 2) (MC2-R)
[mrap2b] Melanocortin-2 receptor accessory protein 2B (zMRAP2b)
[mrap2a] Melanocortin-2 receptor accessory protein 2A (zMRAP2a)
[Mc4r] Melanocortin receptor 4 (MC4-R)
[mc4r] Melanocortin receptor 4 (MC4-R)
[MC5R] Melanocortin receptor 5 (MC5-R) (MC-2)
[Mc1r Msh-r] Melanocyte-stimulating hormone receptor (MSH-R) (Melanocortin receptor 1) (MC1-R)
[Mc3r] Melanocortin receptor 3 (MC3-R)
[Mrap Falp] Melanocortin-2 receptor accessory protein (Fat cell-specific low molecular weight protein) (Fat tissue-specific low MW protein)
[Mc3r] Melanocortin receptor 3 (MC3-R)
[MRAP FALP] Melanocortin-2 receptor accessory protein (Fat cell-specific low molecular weight protein) (Fat tissue-specific low MW protein)
[MC1R MSHR] Melanocyte-stimulating hormone receptor (MSH-R) (BDF3) (Melanocortin receptor 1) (MC1-R)
[Mc5r] Melanocortin receptor 5 (MC5-R)
[MC4R] Melanocortin receptor 4 (MC4-R)
[MC1R] Melanocyte-stimulating hormone receptor (MSH-R) (Melanocortin receptor 1) (MC1-R)
[MC4R] Melanocortin receptor 4 (MC4-R)
[Mc1r rCG_51490] Melanocyte-stimulating hormone receptor (MSH-R) (Melanocortin receptor 1)
[Mc5r] Melanocortin receptor 5 (MC5-R)
[AGRP AGRT ART] Agouti-related protein
[Agrp Agrt Art] Agouti-related protein
[POMC] Pro-opiomelanocortin (POMC) (Corticotropin-lipotropin) [Cleaved into: NPP; Melanotropin gamma (Gamma-MSH); Potential peptide; Corticotropin (Adrenocorticotropic hormone) (ACTH); Melanocyte-stimulating hormone alpha (Alpha-MSH) (Melanotropin alpha); Corticotropin-like intermediary peptide (CLIP); Lipotropin beta (Beta-LPH); Lipotropin gamma (Gamma-LPH); Melanocyte-stimulating hormone beta (Beta-MSH) (Melanotropin beta); Beta-endorphin; Met-enkephalin]
[Pomc Pomc2] Pro-opiomelanocortin (POMC) (Corticotropin-lipotropin) [Cleaved into: NPP; Melanotropin gamma (Gamma-MSH); Potential peptide; Corticotropin (Adrenocorticotropic hormone) (ACTH); Melanocyte-stimulating hormone alpha (Alpha-MSH) (Melanotropin alpha); Corticotropin-like intermediary peptide (CLIP); Lipotropin beta (Beta-LPH); Lipotropin gamma (Gamma-LPH); Melanocyte-stimulating hormone beta (Beta-MSH) (Melanotropin beta); Beta-endorphin; Met-enkephalin]
[POMC] Pro-opiomelanocortin (POMC) (Corticotropin-lipotropin) [Cleaved into: NPP; Melanotropin gamma (Gamma-MSH); Corticotropin (Adrenocorticotropic hormone) (ACTH); Melanocyte-stimulating hormone alpha (Alpha-MSH) (Melanotropin alpha); Corticotropin-like intermediary peptide (CLIP); Lipotropin beta (Beta-LPH); Lipotropin gamma (Gamma-LPH); Melanocyte-stimulating hormone beta (Beta-MSH) (Melanotropin beta); Beta-endorphin; Met-enkephalin]
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