DRD4_RAT
ID DRD4_RAT Reviewed; 387 AA.
AC P30729; Q62610;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=D(4) dopamine receptor;
DE AltName: Full=D(2C) dopamine receptor;
DE AltName: Full=Dopamine D4 receptor;
GN Name=Drd4;
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].
RX PubMed=1554689;
RA O'Malley K.L., Harmon S., Tang L., Todd R.D.;
RT "The rat dopamine D4 receptor: sequence, gene structure, and demonstration
RT of expression in the cardiovascular system.";
RL New Biol. 4:137-146(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=8078498;
RA Asghari V., Schoots O., van Kats S., Ohara K., Jovanovic V., Guan H.-C.,
RA Bunzow J.R., Petronis A., Van Tol H.H.M.;
RT "Dopamine D4 receptor repeat: analysis of different native and mutant forms
RT of the human and rat genes.";
RL Mol. Pharmacol. 46:364-373(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10832611; DOI=10.1007/s002100000236;
RA Gazi L., Schoeffter P., Nunn C., Croskery K., Hoyer D., Feuerbach D.;
RT "Cloning, expression, functional coupling and pharmacological
RT characterization of the rat dopamine D4 receptor.";
RL Naunyn Schmiedebergs Arch. Pharmacol. 361:555-564(2000).
RN [5]
RP INTERACTION WITH CLIC6.
RX PubMed=14499480; DOI=10.1016/s0169-328x(03)00283-3;
RA Griffon N., Jeanneteau F., Prieur F., Diaz J., Sokoloff P.;
RT "CLIC6, a member of the intracellular chloride channel family, interacts
RT with dopamine D(2)-like receptors.";
RL Brain Res. Mol. Brain Res. 117:47-57(2003).
CC -!- FUNCTION: Dopamine receptor responsible for neuronal signaling in the
CC mesolimbic system of the brain, an area of the brain that regulates
CC emotion and complex behavior. Activated by dopamine, but also by
CC epinephrine and norepinephrine, and by numerous synthetic agonists and
CC drugs (By similarity). Agonist binding triggers signaling via G
CC proteins that inhibit adenylyl cyclase (PubMed:10832611). Modulates the
CC circadian rhythm of contrast sensitivity by regulating the rhythmic
CC expression of NPAS2 in the retinal ganglion cells (By similarity).
CC {ECO:0000250|UniProtKB:P21917, ECO:0000250|UniProtKB:P51436,
CC ECO:0000269|PubMed:10832611}.
CC -!- SUBUNIT: Forms homo- and heterooligomers with DRD2. D4.7 allele
CC exhibits higher affinity for homodimers compared to DRD2 heterodimers,
CC while alleles D42. and 4.4 have similar affinities for both. The
CC interaction with DRD2 may modulate agonist-induced downstream signaling
CC (By similarity). Interacts with CLIC6 (PubMed:14499480). Interacts with
CC GPRASP1. May interact with ADORA2A. Interacts with KLHL12 (By
CC similarity). {ECO:0000250|UniProtKB:P21917,
CC ECO:0000269|PubMed:14499480}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10832611};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P21917}.
CC -!- TISSUE SPECIFICITY: Central nervous system: hypothalamus, thalamus,
CC olfactory bulb, and frontal cortex.
CC -!- PTM: Polyubiquitinated by the BCR(KLHL12) E3 ubiquitin ligase complex:
CC polyubiquitination does not lead to degradation of DRD4 protein.
CC {ECO:0000250|UniProtKB:P21917}.
CC -!- PTM: Palmitoylated. Palmitoylation of the C-terminal Cys is important
CC for normal expression at the cell membrane.
CC {ECO:0000250|UniProtKB:P21917}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; M84009; AAA96716.1; -; mRNA.
DR EMBL; U03551; AAA18588.1; -; Genomic_DNA.
DR EMBL; AC118351; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; P30729; -.
DR SMR; P30729; -.
DR DIP; DIP-59866N; -.
DR IntAct; P30729; 2.
DR STRING; 10116.ENSRNOP00000024137; -.
DR BindingDB; P30729; -.
DR ChEMBL; CHEMBL3361; -.
DR DrugCentral; P30729; -.
DR GuidetoPHARMACOLOGY; 217; -.
DR GlyGen; P30729; 1 site.
DR PhosphoSitePlus; P30729; -.
DR PaxDb; P30729; -.
DR RGD; 2522; Drd4.
DR eggNOG; KOG3656; Eukaryota.
DR InParanoid; P30729; -.
DR PhylomeDB; P30729; -.
DR Reactome; R-RNO-390651; Dopamine receptors.
DR Reactome; R-RNO-418594; G alpha (i) signalling events.
DR PRO; PR:P30729; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0043679; C:axon terminus; IDA:RGD.
DR GO; GO:0005938; C:cell cortex; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0043197; C:dendritic spine; IDA:RGD.
DR GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IDA:SynGO.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IDA:SynGO.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0043195; C:terminal bouton; IDA:RGD.
DR GO; GO:0012506; C:vesicle membrane; IDA:RGD.
DR GO; GO:0035240; F:dopamine binding; IDA:RGD.
DR GO; GO:0004952; F:dopamine neurotransmitter receptor activity; ISO:RGD.
DR GO; GO:0001591; F:dopamine neurotransmitter receptor activity, coupled via Gi/Go; IDA:RGD.
DR GO; GO:0051379; F:epinephrine binding; ISO:RGD.
DR GO; GO:0004993; F:G protein-coupled serotonin receptor activity; IBA:GO_Central.
DR GO; GO:1901363; F:heterocyclic compound binding; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR GO; GO:0051380; F:norepinephrine binding; ISO:RGD.
DR GO; GO:0017124; F:SH3 domain binding; ISO:RGD.
DR GO; GO:0007195; P:adenylate cyclase-inhibiting dopamine receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0008344; P:adult locomotory behavior; ISO:RGD.
DR GO; GO:0050482; P:arachidonic acid secretion; ISO:RGD.
DR GO; GO:0008306; P:associative learning; IMP:RGD.
DR GO; GO:0001662; P:behavioral fear response; IMP:RGD.
DR GO; GO:0048148; P:behavioral response to cocaine; ISO:RGD.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0007623; P:circadian rhythm; IEP:RGD.
DR GO; GO:0007212; P:dopamine receptor signaling pathway; IDA:RGD.
DR GO; GO:0042596; P:fear response; ISO:RGD.
DR GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; IBA:GO_Central.
DR GO; GO:0060080; P:inhibitory postsynaptic potential; ISO:RGD.
DR GO; GO:0007626; P:locomotory behavior; TAS:RGD.
DR GO; GO:0050709; P:negative regulation of protein secretion; ISO:RGD.
DR GO; GO:0050805; P:negative regulation of synaptic transmission; IDA:RGD.
DR GO; GO:1904753; P:negative regulation of vascular associated smooth muscle cell migration; IDA:RGD.
DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; IDA:RGD.
DR GO; GO:1901386; P:negative regulation of voltage-gated calcium channel activity; ISO:RGD.
DR GO; GO:0008355; P:olfactory learning; IMP:RGD.
DR GO; GO:0009648; P:photoperiodism; IEP:RGD.
DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; IMP:RGD.
DR GO; GO:0033674; P:positive regulation of kinase activity; ISO:RGD.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISO:RGD.
DR GO; GO:0060406; P:positive regulation of penile erection; IDA:RGD.
DR GO; GO:0032417; P:positive regulation of sodium:proton antiporter activity; ISO:RGD.
DR GO; GO:0050848; P:regulation of calcium-mediated signaling; IMP:RGD.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0042053; P:regulation of dopamine metabolic process; ISO:RGD.
DR GO; GO:0046928; P:regulation of neurotransmitter secretion; IMP:RGD.
DR GO; GO:0099072; P:regulation of postsynaptic membrane neurotransmitter receptor levels; IDA:SynGO.
DR GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; ISO:RGD.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IDA:SynGO.
DR GO; GO:0001975; P:response to amphetamine; ISO:RGD.
DR GO; GO:0034776; P:response to histamine; ISO:RGD.
DR GO; GO:0048545; P:response to steroid hormone; IEP:RGD.
DR GO; GO:0060041; P:retina development in camera-type eye; IEP:RGD.
DR GO; GO:0007614; P:short-term memory; IMP:RGD.
DR GO; GO:0001963; P:synaptic transmission, dopaminergic; IMP:RGD.
DR InterPro; IPR002185; Dopamine_D4_rcpt.
DR InterPro; IPR000929; Dopamine_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR PANTHER; PTHR24248:SF143; PTHR24248:SF143; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00569; DOPAMINED4R.
DR PRINTS; PR00242; DOPAMINER.
DR PRINTS; PR00237; GPCRRHODOPSN.
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 Biological rhythms; Cell membrane; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane;
KW Metal-binding; Palmitate; Receptor; Reference proteome; Sodium; Transducer;
KW Transmembrane; Transmembrane helix; Ubl conjugation.
FT CHAIN 1..387
FT /note="D(4) dopamine receptor"
FT /id="PRO_0000069403"
FT TOPO_DOM 1..34
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P21917"
FT TRANSMEM 35..57
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:P21917"
FT TOPO_DOM 58..67
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P21917"
FT TRANSMEM 68..90
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P21917"
FT TOPO_DOM 91..106
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P21917"
FT TRANSMEM 107..128
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P21917"
FT TOPO_DOM 129..146
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P21917"
FT TRANSMEM 147..170
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P21917"
FT TOPO_DOM 171..186
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P21917"
FT TRANSMEM 187..208
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P21917"
FT TOPO_DOM 209..314
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P21917"
FT TRANSMEM 315..337
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P21917"
FT TOPO_DOM 338..346
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P21917"
FT TRANSMEM 347..369
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:P21917"
FT TOPO_DOM 370..387
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P21917"
FT REGION 224..278
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 232..260
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 261..278
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 77
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /evidence="ECO:0000250|UniProtKB:P21917"
FT BINDING 119
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /evidence="ECO:0000250|UniProtKB:P21917"
FT LIPID 387
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P21917"
FT CARBOHYD 3
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 105..180
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 340..343
FT /evidence="ECO:0000250|UniProtKB:P21917"
FT CONFLICT 93..94
FT /note="Missing (in Ref. 1; AAA96716)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 387 AA; 41294 MW; 1E0A5D74524F5050 CRC64;
MGNSSATGDG GLLAGRGPES LGTGTGLGGA GAAALVGGVL LIGMVLAGNS LVCVSVASER
ILQTPTNYFI VSLAAADLLL AVLVLPLFVY SEVQGGVWLL SPRLCDTLMA MDVMLCTASI
FNLCAISVDR FVAVTVPLRY NQQGQCQLLL IAATWLLSAA VAAPVVCGLN DVPGRDPTVC
CLEDRDYVVY SSICSFFLPC PLMLLLYWAT FRGLRRWEAA RHTKLHSRAP RRPSGPGPPV
SDPTQGPLFS DCPPPSPSLR TSPTVSSRPE SDLSQSPCSP GCLLPDAALA QPPAPSSRRK
RGAKITGRER KAMRVLPVVV GAFLMCWTPF FVVHITRALC PACFVSPRLV SAVTWLGYVN
SALNPIIYTI FNAEFRSVFR KTLRLRC
