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Protein

D(4) dopamine receptor

Gene

DRD4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins which inhibit adenylyl cyclase. Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity).By similarity

GO - Molecular functioni

  • dopamine binding Source: BHF-UCL
  • dopamine neurotransmitter receptor activity Source: BHF-UCL
  • dopamine neurotransmitter receptor activity, coupled via Gi/Go Source: BHF-UCL
  • dopamine neurotransmitter receptor activity, coupled via Gs Source: GO_Central
  • drug binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • potassium channel regulator activity Source: BHF-UCL
  • SH3 domain binding Source: BHF-UCL

GO - Biological processi

  • activation of MAPK activity Source: BHF-UCL
  • adenylate cyclase-inhibiting dopamine receptor signaling pathway Source: BHF-UCL
  • adult locomotory behavior Source: BHF-UCL
  • arachidonic acid secretion Source: BHF-UCL
  • behavioral fear response Source: BHF-UCL
  • behavioral response to cocaine Source: BHF-UCL
  • behavioral response to ethanol Source: BHF-UCL
  • cellular calcium ion homeostasis Source: BHF-UCL
  • dopamine metabolic process Source: BHF-UCL
  • dopamine receptor signaling pathway Source: BHF-UCL
  • fear response Source: BHF-UCL
  • inhibitory postsynaptic potential Source: BHF-UCL
  • negative regulation of adenylate cyclase activity Source: BHF-UCL
  • negative regulation of cAMP biosynthetic process Source: BHF-UCL
  • negative regulation of protein secretion Source: BHF-UCL
  • negative regulation of voltage-gated calcium channel activity Source: BHF-UCL
  • positive regulation of dopamine uptake involved in synaptic transmission Source: BHF-UCL
  • positive regulation of kinase activity Source: BHF-UCL
  • positive regulation of sodium:proton antiporter activity Source: BHF-UCL
  • regulation of circadian rhythm Source: UniProtKB
  • regulation of dopamine metabolic process Source: BHF-UCL
  • response to amphetamine Source: BHF-UCL
  • response to histamine Source: BHF-UCL
  • rhythmic process Source: UniProtKB-KW
  • social behavior Source: BHF-UCL
  • synaptic transmission, dopaminergic Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Biological rhythms

Enzyme and pathway databases

BioCyciZFISH:ENSG00000069696-MONOMER.
ReactomeiR-HSA-390651. Dopamine receptors.
R-HSA-418594. G alpha (i) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
D(4) dopamine receptor
Alternative name(s):
D(2C) dopamine receptor
Dopamine D4 receptor
Gene namesi
Name:DRD4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:3025. DRD4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 37ExtracellularSequence analysisAdd BLAST37
Transmembranei38 – 60Helical; Name=1Sequence analysisAdd BLAST23
Topological domaini61 – 70CytoplasmicSequence analysis10
Transmembranei71 – 93Helical; Name=2Sequence analysisAdd BLAST23
Topological domaini94 – 109ExtracellularSequence analysisAdd BLAST16
Transmembranei110 – 131Helical; Name=3Sequence analysisAdd BLAST22
Topological domaini132 – 151CytoplasmicSequence analysisAdd BLAST20
Transmembranei152 – 175Helical; Name=4Sequence analysisAdd BLAST24
Topological domaini176 – 191ExtracellularSequence analysisAdd BLAST16
Transmembranei192 – 213Helical; Name=5Sequence analysisAdd BLAST22
Topological domaini214 – 394CytoplasmicSequence analysisAdd BLAST181
Transmembranei395 – 417Helical; Name=6Sequence analysisAdd BLAST23
Topological domaini418 – 426ExtracellularSequence analysis9
Transmembranei427 – 449Helical; Name=7Sequence analysisAdd BLAST23
Topological domaini450 – 467CytoplasmicSequence analysisAdd BLAST18

GO - Cellular componenti

  • integral component of plasma membrane Source: BHF-UCL
  • membrane Source: BHF-UCL
  • plasma membrane Source: SYSCILIA_CCNET
  • postsynapse Source: GOC
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi1815.
MalaCardsiDRD4.
PharmGKBiPA27480.

Chemistry databases

ChEMBLiCHEMBL219.
DrugBankiDB00543. Amoxapine.
DB00714. Apomorphine.
DB01238. Aripiprazole.
DB06216. Asenapine.
DB01200. Bromocriptine.
DB00248. Cabergoline.
DB00477. Chlorpromazine.
DB00363. Clozapine.
DB00988. Dopamine.
DB04908. Flibanserin.
DB04946. Iloperidone.
DB01235. Levodopa.
DB00589. Lisuride.
DB00408. Loxapine.
DB01403. Methotrimeprazine.
DB00334. Olanzapine.
DB01267. Paliperidone.
DB01186. Pergolide.
DB00413. Pramipexole.
DB00420. Promazine.
DB00777. Propiomazine.
DB01224. Quetiapine.
DB00409. Remoxipride.
DB00734. Risperidone.
DB00268. Ropinirole.
DB05271. Rotigotine.
DB00246. Ziprasidone.
GuidetoPHARMACOLOGYi217.

Polymorphism and mutation databases

BioMutaiDRD4.
DMDMi1345939.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000694011 – 467D(4) dopamine receptorAdd BLAST467

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi3N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi108 ↔ 185PROSITE-ProRule annotation

Post-translational modificationi

Polyubiquitinated by the BCR(KLHL12) E3 ubiquitin ligase complex: polyubiquitination does not lead to degradation of DRD4 protein.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

PeptideAtlasiP21917.
PRIDEiP21917.

PTM databases

iPTMnetiP21917.
PhosphoSitePlusiP21917.

Expressioni

Gene expression databases

BgeeiENSG00000069696.
CleanExiHS_DRD4.
GenevisibleiP21917. HS.

Organism-specific databases

HPAiCAB020697.

Interactioni

Subunit structurei

Forms homo- and heterooligomers with DRD2. D4.7 allele exhibits higher affinity for homodimers compared to DRD2 heterodimers, while alleles D42. and 4.4 have similar affinities for both. The interaction with DRD2 may modulate agonist-induced downstream signaling. Interacts with CLIC6 (By similarity) and GPRASP1. May interact with ADORA2A. Interacts with KLHL12.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself5EBI-8592297,EBI-8592297
DRD2P14416-14EBI-8592297,EBI-11686358

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • SH3 domain binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi108149. 11 interactors.
DIPiDIP-59865N.
IntActiP21917. 1 interactor.
MINTiMINT-8090293.

Chemistry databases

BindingDBiP21917.

Structurei

3D structure databases

ProteinModelPortaliP21917.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati249 – 2641; approximateAdd BLAST16
Repeati265 – 2802Add BLAST16
Repeati281 – 2963Add BLAST16
Repeati297 – 3124Add BLAST16
Repeati313 – 3285Add BLAST16
Repeati329 – 3446Add BLAST16
Repeati345 – 3607; approximateAdd BLAST16

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni249 – 3607 X 16 AA approximate tandem repeats of [PA]-A-P-G-L-P-[PQR]-[DG]-P-C-G-P-D-C-A-PAdd BLAST112

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP21917.
KOiK04147.
OrthoDBiEOG091G06VI.
PhylomeDBiP21917.
TreeFamiTF334382.

Family and domain databases

InterProiIPR002185. Dopamine_D4_rcpt.
IPR000929. Dopamine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24249:SF37. PTHR24249:SF37. 2 hits.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00569. DOPAMINED4R.
PR00242. DOPAMINER.
PR00237. GPCRRHODOPSN.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P21917-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGNRSTADAD GLLAGRGPAA GASAGASAGL AGQGAAALVG GVLLIGAVLA
60 70 80 90 100
GNSLVCVSVA TERALQTPTN SFIVSLAAAD LLLALLVLPL FVYSEVQGGA
110 120 130 140 150
WLLSPRLCDA LMAMDVMLCT ASIFNLCAIS VDRFVAVAVP LRYNRQGGSR
160 170 180 190 200
RQLLLIGATW LLSAAVAAPV LCGLNDVRGR DPAVCRLEDR DYVVYSSVCS
210 220 230 240 250
FFLPCPLMLL LYWATFRGLQ RWEVARRAKL HGRAPRRPSG PGPPSPTPPA
260 270 280 290 300
PRLPQDPCGP DCAPPAPGLP RGPCGPDCAP AAPGLPPDPC GPDCAPPAPG
310 320 330 340 350
LPQDPCGPDC APPAPGLPRG PCGPDCAPPA PGLPQDPCGP DCAPPAPGLP
360 370 380 390 400
PDPCGSNCAP PDAVRAAALP PQTPPQTRRR RRAKITGRER KAMRVLPVVV
410 420 430 440 450
GAFLLCWTPF FVVHITQALC PACSVPPRLV SAVTWLGYVN SALNPVIYTV
460
FNAEFRNVFR KALRACC
Length:467
Mass (Da):48,361
Last modified:February 1, 1996 - v2
Checksum:iB6FF2E09269A02AF
GO

Sequence cautioni

The sequence AAL58637 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti237R → F in BAC05985 (PubMed:1840645).Curated1

Polymorphismi

The number of repeats of 16 amino acids in the third cytoplasmic loop is highly polymorphic and varies among different alleles. Alleles corresponding in size to a 2 (D4.2), 3 (D4.3), 4 (D4.4), 5 (D4.5), 6 (D4.6), 7 (D4.7) and 9 (D4.9) repeats have been described. The sequence shown is that of allele D4.7. The polymorphic repeat sequence has little influence on DRD4-binding profiles and might not be essential for G protein interaction.2 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_003464194V → G in Afro-Caribbeans. 1 PublicationCorresponds to variant rs1800443dbSNPEnsembl.1
Natural variantiVAR_003465265 – 344Missing in allele D4.2. Add BLAST80
Natural variantiVAR_003466281 – 328Missing in allele D4.4. Add BLAST48
Natural variantiVAR_055914281A → P.Corresponds to variant rs3889692dbSNPEnsembl.1
Natural variantiVAR_003467329P → A in allele D4.4. 1
Natural variantiVAR_003468332G → S in allele D4.4. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L12398 mRNA. Translation: AAB59386.1.
L12397 Genomic DNA. Translation: AAL58637.1. Sequence problems.
AB065765 Genomic DNA. Translation: BAC05985.1.
EU432112 mRNA. Translation: ABY87911.1.
AP006284 Genomic DNA. No translation available.
CH471158 Genomic DNA. Translation: EAX02369.1.
PIRiS15079. DYHUD4.
S24195.
RefSeqiNP_000788.2. NM_000797.3.
UniGeneiHs.99922.

Genome annotation databases

EnsembliENST00000176183; ENSP00000176183; ENSG00000069696.
GeneIDi1815.
KEGGihsa:1815.
UCSCiuc001lqp.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L12398 mRNA. Translation: AAB59386.1.
L12397 Genomic DNA. Translation: AAL58637.1. Sequence problems.
AB065765 Genomic DNA. Translation: BAC05985.1.
EU432112 mRNA. Translation: ABY87911.1.
AP006284 Genomic DNA. No translation available.
CH471158 Genomic DNA. Translation: EAX02369.1.
PIRiS15079. DYHUD4.
S24195.
RefSeqiNP_000788.2. NM_000797.3.
UniGeneiHs.99922.

3D structure databases

ProteinModelPortaliP21917.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108149. 11 interactors.
DIPiDIP-59865N.
IntActiP21917. 1 interactor.
MINTiMINT-8090293.

Chemistry databases

BindingDBiP21917.
ChEMBLiCHEMBL219.
DrugBankiDB00543. Amoxapine.
DB00714. Apomorphine.
DB01238. Aripiprazole.
DB06216. Asenapine.
DB01200. Bromocriptine.
DB00248. Cabergoline.
DB00477. Chlorpromazine.
DB00363. Clozapine.
DB00988. Dopamine.
DB04908. Flibanserin.
DB04946. Iloperidone.
DB01235. Levodopa.
DB00589. Lisuride.
DB00408. Loxapine.
DB01403. Methotrimeprazine.
DB00334. Olanzapine.
DB01267. Paliperidone.
DB01186. Pergolide.
DB00413. Pramipexole.
DB00420. Promazine.
DB00777. Propiomazine.
DB01224. Quetiapine.
DB00409. Remoxipride.
DB00734. Risperidone.
DB00268. Ropinirole.
DB05271. Rotigotine.
DB00246. Ziprasidone.
GuidetoPHARMACOLOGYi217.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP21917.
PhosphoSitePlusiP21917.

Polymorphism and mutation databases

BioMutaiDRD4.
DMDMi1345939.

Proteomic databases

PeptideAtlasiP21917.
PRIDEiP21917.

Protocols and materials databases

DNASUi1815.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000176183; ENSP00000176183; ENSG00000069696.
GeneIDi1815.
KEGGihsa:1815.
UCSCiuc001lqp.3. human.

Organism-specific databases

CTDi1815.
DisGeNETi1815.
GeneCardsiDRD4.
HGNCiHGNC:3025. DRD4.
HPAiCAB020697.
MalaCardsiDRD4.
MIMi126452. gene.
neXtProtiNX_P21917.
PharmGKBiPA27480.
GenAtlasiSearch...

Phylogenomic databases

HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP21917.
KOiK04147.
OrthoDBiEOG091G06VI.
PhylomeDBiP21917.
TreeFamiTF334382.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000069696-MONOMER.
ReactomeiR-HSA-390651. Dopamine receptors.
R-HSA-418594. G alpha (i) signalling events.

Miscellaneous databases

ChiTaRSiDRD4. human.
GeneWikiiDopamine_receptor_D4.
GenomeRNAii1815.
PROiP21917.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000069696.
CleanExiHS_DRD4.
GenevisibleiP21917. HS.

Family and domain databases

InterProiIPR002185. Dopamine_D4_rcpt.
IPR000929. Dopamine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24249:SF37. PTHR24249:SF37. 2 hits.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00569. DOPAMINED4R.
PR00242. DOPAMINER.
PR00237. GPCRRHODOPSN.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDRD4_HUMAN
AccessioniPrimary (citable) accession number: P21917
Secondary accession number(s): B0M0J7, Q7Z7Q5, Q8NGM5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: February 1, 1996
Last modified: November 2, 2016
This is version 165 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.