P21917 · DRD4_HUMAN
- ProteinD(4) dopamine receptor
- GeneDRD4
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids419 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Binding site | 80 | Na+ (UniProtKB | ChEBI) | |||
Binding site | 115 | (2R,3R)-nemonapride (UniProtKB | ChEBI); antagonist | |||
Binding site | 122 | Na+ (UniProtKB | ChEBI) | |||
Binding site | 196 | (2R,3R)-nemonapride (UniProtKB | ChEBI); antagonist | |||
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameD(4) dopamine receptor
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP21917
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Topological domain | 1-29 | Extracellular | |||
Transmembrane | 30-50 | Helical; Name=1 | |||
Topological domain | 51-71 | Cytoplasmic | |||
Transmembrane | 72-92 | Helical; Name=2 | |||
Topological domain | 93-110 | Extracellular | |||
Transmembrane | 111-131 | Helical; Name=3 | |||
Topological domain | 132-152 | Cytoplasmic | |||
Transmembrane | 153-173 | Helical; Name=4 | |||
Topological domain | 174-192 | Extracellular | |||
Transmembrane | 193-213 | Helical; Name=5 | |||
Topological domain | 214-346 | Cytoplasmic | |||
Transmembrane | 347-367 | Helical; Name=6 | |||
Topological domain | 368-382 | Extracellular | |||
Transmembrane | 383-403 | Helical; Name=7 | |||
Topological domain | 404-419 | Cytoplasmic | |||
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Natural variant | VAR_003464 | 194 | in dbSNP:rs1800443 | ||
Natural variant | VAR_003465 | 265-296 | in allele D4.2 | ||
Natural variant | VAR_081438 | 284 | in allele D4.7 | ||
Mutagenesis | 382 | Increased basal level of G protein-mediated signaling. | |||
Mutagenesis | 418 | No effect on palmitoylation. | |||
Mutagenesis | 419 | Loss of palmitoylation. | |||
Variants
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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.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, glycosylation, disulfide bond, lipidation.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Chain | PRO_0000069401 | 1-419 | D4 dopamine receptor | ||
Glycosylation | 3 | N-linked (GlcNAc...) asparagine | |||
Disulfide bond | 108↔185 | ||||
Disulfide bond | 372↔375 | ||||
Lipidation | 419 | S-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
- PTM
Proteomic databases
PTM 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).
Interacts with CLIC6 (By similarity).
Interacts with GPRASP1 (PubMed:12142540).
May interact with ADORA2A (PubMed:20836733).
Interacts with KLHL12 (PubMed:18303015).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | IntAct | |
---|---|---|---|---|---|
BINARY | P21917 | APP P05067 | 6 | EBI-8592297, EBI-77613 | |
BINARY | P21917 | DRD4 P21917 | 5 | EBI-8592297, EBI-8592297 | |
BINARY | P21917 | GAP43 P17677 | 3 | EBI-8592297, EBI-1267511 | |
BINARY | P21917 | METAP2 P50579 | 3 | EBI-8592297, EBI-2214155 | |
BINARY | P21917 | NECAB3 Q96P71-2 | 3 | EBI-8592297, EBI-15098952 | |
BINARY | P21917 | STXBP1 P61764 | 3 | EBI-8592297, EBI-960169 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, repeat.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Region | 230-264 | Disordered | |||
Compositional bias | 238-254 | Pro residues | |||
Repeat | 249-264 | 1; approximate | |||
Region | 249-312 | 4 X 16 AA approximate tandem repeats of [PA]-A-P-G-L-P-[PQR]-[DG]-P-C-G-P-D-C-A-P | |||
Repeat | 265-280 | 2 | |||
Repeat | 281-296 | 3 | |||
Repeat | 297-312 | 4; approximate | |||
Region | 317-336 | Disordered | |||
Sequence similarities
Belongs to the G-protein coupled receptor 1 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Protein family/group databases
Sequence
- Sequence statusComplete
- Length419
- Mass (Da)43,901
- Last updated2019-04-10 v3
- MD5 Checksum85E697C2569594E0D754EED2F059C765
Sequence caution
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Sequence conflict | 237 | in Ref. 2; BAC05985 | |||
Compositional bias | 238-254 | Pro 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
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |