P21917 · DRD4_HUMAN

  • Protein
    D(4) dopamine receptor
  • Gene
    DRD4
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Activated by dopamine, but also by epinephrine and norepinephrine, and by numerous synthetic agonists and drugs (PubMed:16423344, PubMed:27659709, PubMed:29051383, PubMed:9003072).
Agonist binding triggers signaling via G proteins that inhibit adenylyl cyclase (PubMed:16423344, PubMed:27659709, PubMed:29051383, PubMed:7512953, PubMed:7643093).
Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity).

Activity regulation

Signaling in response to agonists such as dopamine, epinephrine and norepinephrine is modulated by Na+; lower Na+ levels result in higher receptor activity (in vitro).

Features

Showing features for binding site.

141950100150200250300350400
TypeIDPosition(s)Description
Binding site80Na+ (UniProtKB | ChEBI)
Binding site115(2R,3R)-nemonapride (UniProtKB | ChEBI); antagonist
Binding site122Na+ (UniProtKB | ChEBI)
Binding site196(2R,3R)-nemonapride (UniProtKB | ChEBI); antagonist

GO annotations

AspectTerm
Cellular Componentcentrosome
Cellular Componentdendrite
Cellular Componentglutamatergic synapse
Cellular Componentmembrane
Cellular Componentplasma membrane
Cellular Componentpostsynapse
Molecular Functiondopamine binding
Molecular Functiondopamine neurotransmitter receptor activity
Molecular Functiondopamine neurotransmitter receptor activity, coupled via Gi/Go
Molecular Functionepinephrine binding
Molecular FunctionG protein-coupled serotonin receptor activity
Molecular Functionidentical protein binding
Molecular Functionmetal ion binding
Molecular Functionneurotransmitter receptor activity
Molecular Functionnorepinephrine binding
Molecular Functionpotassium channel regulator activity
Molecular Functionserotonin binding
Molecular FunctionSH3 domain binding
Biological Processadenylate cyclase-inhibiting dopamine receptor signaling pathway
Biological Processadenylate cyclase-inhibiting serotonin receptor signaling pathway
Biological Processadult locomotory behavior
Biological Processarachidonate secretion
Biological Processbehavioral fear response
Biological Processbehavioral response to cocaine
Biological Processbehavioral response to ethanol
Biological Processchemical synaptic transmission
Biological Processfear response
Biological ProcessG protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
Biological Processinhibitory postsynaptic potential
Biological Processintracellular calcium ion homeostasis
Biological Processnegative regulation of protein secretion
Biological Processphospholipase C-activating dopamine receptor signaling pathway
Biological Processpositive regulation of dopamine uptake involved in synaptic transmission
Biological Processpositive regulation of MAP kinase activity
Biological Processregulation of circadian rhythm
Biological Processregulation of dopamine metabolic process
Biological Processregulation of postsynaptic neurotransmitter receptor internalization
Biological Processresponse to amphetamine
Biological Processresponse to histamine
Biological Processrhythmic process
Biological Processsocial behavior

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    D(4) dopamine receptor
  • Alternative names
    • D(2C) dopamine receptor
    • Dopamine D4 receptor

Gene names

    • Name
      DRD4

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    P21917
  • Secondary accessions
    • B0M0J7
    • Q7Z7Q5
    • Q8NGM5

Proteomes

Organism-specific databases

Subcellular Location

Features

Showing features for topological domain, transmembrane.

Type
IDPosition(s)Description
Topological domain1-29Extracellular
Transmembrane30-50Helical; Name=1
Topological domain51-71Cytoplasmic
Transmembrane72-92Helical; Name=2
Topological domain93-110Extracellular
Transmembrane111-131Helical; Name=3
Topological domain132-152Cytoplasmic
Transmembrane153-173Helical; Name=4
Topological domain174-192Extracellular
Transmembrane193-213Helical; Name=5
Topological domain214-346Cytoplasmic
Transmembrane347-367Helical; Name=6
Topological domain368-382Extracellular
Transmembrane383-403Helical; Name=7
Topological domain404-419Cytoplasmic

Keywords

Disease & Variants

Features

Showing features for natural variant, mutagenesis.

Type
IDPosition(s)Description
Natural variantVAR_003464194in dbSNP:rs1800443
Natural variantVAR_003465265-296in allele D4.2
Natural variantVAR_081438284in allele D4.7
Mutagenesis382Increased basal level of G protein-mediated signaling.
Mutagenesis418No effect on palmitoylation.
Mutagenesis419Loss of palmitoylation.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 848 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for chain, glycosylation, disulfide bond, lipidation.

Type
IDPosition(s)Description
ChainPRO_00000694011-419D4 dopamine receptor
Glycosylation3N-linked (GlcNAc...) asparagine
Disulfide bond108↔185
Disulfide bond372↔375
Lipidation419S-palmitoyl cysteine

Post-translational modification

Polyubiquitinated by the BCR(KLHL12) E3 ubiquitin ligase complex: polyubiquitination does not lead to degradation of DRD4 protein.
Palmitoylated. Palmitoylation of the C-terminal Cys is important for normal expression at the cell membrane.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Highly expressed in retina. Detected at much lower levels in brain, in amygdala, thalamus, hypothalamus, cerebellum and pituitary.

Gene expression databases

    • ENSG00000069696Expressed in male germ line stem cell (sensu Vertebrata) in testis and 92 other cell types or tissues

Organism-specific databases

Interaction

Subunit

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 (PubMed:21184734).
Interacts with CLIC6 (By similarity).
Interacts with GPRASP1 (PubMed:12142540).
May interact with ADORA2A (PubMed:20836733).
Interacts with KLHL12 (PubMed:18303015).

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntAct
BINARY P21917APP P050676EBI-8592297, EBI-77613
BINARY P21917DRD4 P219175EBI-8592297, EBI-8592297
BINARY P21917GAP43 P176773EBI-8592297, EBI-1267511
BINARY P21917METAP2 P505793EBI-8592297, EBI-2214155
BINARY P21917NECAB3 Q96P71-23EBI-8592297, EBI-15098952
BINARY P21917STXBP1 P617643EBI-8592297, EBI-960169

Protein-protein interaction databases

Chemistry

Miscellaneous

Family & Domains

Features

Showing features for region, compositional bias, repeat.

Type
IDPosition(s)Description
Region230-264Disordered
Compositional bias238-254Pro residues
Repeat249-2641; approximate
Region249-3124 X 16 AA approximate tandem repeats of [PA]-A-P-G-L-P-[PQR]-[DG]-P-C-G-P-D-C-A-P
Repeat265-2802
Repeat281-2963
Repeat297-3124; approximate
Region317-336Disordered

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Keywords

Phylogenomic databases

Family and domain databases

Protein family/group databases

Sequence

  • Sequence status
    Complete
  • Length
    419
  • Mass (Da)
    43,901
  • Last updated
    2019-04-10 v3
  • MD5 Checksum
    85E697C2569594E0D754EED2F059C765
MGNRSTADADGLLAGRGPAAGASAGASAGLAGQGAAALVGGVLLIGAVLAGNSLVCVSVATERALQTPTNSFIVSLAAADLLLALLVLPLFVYSEVQGGAWLLSPRLCDALMAMDVMLCTASIFNLCAISVDRFVAVAVPLRYNRQGGSRRQLLLIGATWLLSAAVAAPVLCGLNDVRGRDPAVCRLEDRDYVVYSSVCSFFLPCPLMLLLYWATFRGLQRWEVARRAKLHGRAPRRPSGPGPPSPTPPAPRLPQDPCGPDCAPPAPGLPRGPCGPDCAPAAPSLPQDPCGPDCAPPAPGLPPDPCGSNCAPPDAVRAAALPPQTPPQTRRRRRAKITGRERKAMRVLPVVVGAFLLCWTPFFVVHITQALCPACSVPPRLVSAVTWLGYVNSALNPVIYTVFNAEFRNVFRKALRACC

Sequence caution

The sequence AAL58637.1 differs from that shown. Reason: Erroneous gene model prediction

Features

Showing features for sequence conflict, compositional bias.

Type
IDPosition(s)Description
Sequence conflict237in Ref. 2; BAC05985
Compositional bias238-254Pro residues

Polymorphism

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 D4.4. The polymorphic repeat sequence has little influence on DRD4-binding profiles and might not be essential for G protein interaction.

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
L12398
EMBL· GenBank· DDBJ
AAB59386.1
EMBL· GenBank· DDBJ
mRNA
L12397
EMBL· GenBank· DDBJ
AAL58637.1
EMBL· GenBank· DDBJ
Genomic DNA Sequence problems.
AB065765
EMBL· GenBank· DDBJ
BAC05985.1
EMBL· GenBank· DDBJ
Genomic DNA
EU432112
EMBL· GenBank· DDBJ
ABY87911.1
EMBL· GenBank· DDBJ
mRNA
AP006284
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
CH471158
EMBL· GenBank· DDBJ
EAX02369.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

Disclaimer

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