DRD4
entrez
1815
canonical
uniprot
P21917
canonical
ensembl
ENSG00000069696
resolver
ensembl
ENSG00000276825
resolver
ensp
ENSP00000176183
resolver
ensp
ENSP00000478431
resolver
enst
ENST00000176183
resolver
enst
ENST00000611962
resolver
genesymbol
DRD4
resolver
hgnc
HGNC:3025
resolver
uniprot
B0M0J7
resolver
uniprot
Q7Z7Q5
resolver
uniprot
Q8NGM5
resolver
uniprot_entry
DRD4_HUMAN
resolver
uniprot_sec
B0M0J7
resolver
uniprot_sec
Q7Z7Q5
resolver
uniprot_sec
Q8NGM5
resolver
activity_regulation
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) (PubMed:16423344, PubMed:29051383). Activated by the pan-agonist rotigotine, which activates all five dopamine receptors (PubMed:37221270). {ECO:0000269|PubMed:16423344, ECO:0000269|PubMed:29051383, ECO:0000269|PubMed:37221270}.
uniprot
proteins
amino_acid_sequence
MGNRSTADADGLLAGRGPAAGASAGASAGLAGQGAAALVGGVLLIGAVLAGNSLVCVSVATERALQTPTNSFIVSLAAADLLLALLVLPLFVYSEVQGGAWLLSPRLCDALMAMDVMLCTASIFNLCAISVDRFVAVAVPLRYNRQGGSRRQLLLIGATWLLSAAVAAPVLCGLNDVRGRDPAVCRLEDRDYVVYSSVCSFFLPCPLMLLLYWATFRGLQRWEVARRAKLHGRAPRRPSGPGPPSPTPPAPRLPQDPCGPDCAPPAPGLPRGPCGPDCAPAAPSLPQDPCGPDCAPPAPGLPPDPCGSNCAPPDAVRAAALPPQTPPQTRRRRRAKITGRERKAMRVLPVVVGAFLLCWTPFFVVHITQALCPACSVPPRLVSAVTWLGYVNSALNPVIYTVFNAEFRNVFRKALRACC
uniprot
proteins
function
FUNCTION: G protein-coupled receptor for dopamine, a catecholamine neurotransmitter hormone that functions as the brain's 'reward chemical', driving motivation, reinforcement learning and pleasure (PubMed:16423344, PubMed:1840645, PubMed:27659709, PubMed:29051383, PubMed:37221270, PubMed:7512953, PubMed:7643093, PubMed:8078498, PubMed:8413587). In addition to dopamine, also activated by epinephrine and norepinephrine, and by numerous synthetic agonists and drugs (PubMed:16423344, PubMed:1840645, PubMed:27659709, PubMed:29051383, PubMed:9003072, PubMed:9042615). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:16423344, PubMed:27659709, PubMed:29051383, PubMed:7512953, PubMed:7643093). Dopamine receptors can be classified in two categories: (1) DRD4 (together with DRD2 and DRD3) is a D2-type receptor and is coupled to G(i)/G(o) G proteins, mediating inhibition of adenylate cyclase activity, while D1-type receptors (DRD1 and DRD5) are coupled to G(s) G proteins and promote activation of adenylate cyclase activity (PubMed:16423344, PubMed:27659709, PubMed:29051383, PubMed:7512953, PubMed:7643093). D1- and D2-type dopamine receptors have antagonistic effects, particularly in the brain's striatum, where they govern voluntary movement and reward: D1-type receptors generally stimulate neural activity and promotes action, while D2-type receptors tend to inhibit neural activity and suppress movement (PubMed:16423344, PubMed:27659709, PubMed:29051383, PubMed:7512953, PubMed:7643093). DRD4 is expressed in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior (PubMed:37221270). Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity). {ECO:0000250|UniProtKB:P51436, ECO:0000269|PubMed:16423344, ECO:0000269|PubMed:1840645, ECO:0000269|PubMed:27659709, ECO:0000269|PubMed:29051383, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:7512953, ECO:0000269|PubMed:7643093, ECO:0000269|PubMed:8078498, ECO:0000269|PubMed:8413587, ECO:0000269|PubMed:9003072, ECO:0000269|PubMed:9042615}.
uniprot
proteins
mass_dalton
43901
uniprot
proteins
mutagenesis
MUTAGEN 67..71; /note="TPTNS->APANA: In ST0 mutant; decreased ubiquitination and degradation; when associated with A-215, A-239, 245-A--A-247, A-284, A-308, 325-A--A-329 and A-338."; /evidence="ECO:0000269|PubMed:29101232"; MUTAGEN 91; /note="F->A: Strongly reduced activation by rotigotine."; /evidence="ECO:0000269|PubMed:37221270"; MUTAGEN 215; /note="T->A: In ST0 mutant; decreased ubiquitination and degradation; when associated with 67-A--A-71, A-239, 245-A--A-247, A-284, A-308, 325-A--A-329 and A-338."; /evidence="ECO:0000269|PubMed:29101232"; MUTAGEN 229; /note="K->R: In K0 mutant; decreased ubiquitination and degradation; when associated with R-336, R-343 and R-413."; /evidence="ECO:0000269|PubMed:29101232"; MUTAGEN 239; /note="S->A: In ST0 mutant; decreased ubiquitination and degradation; when associated with 67-A--A-71, A-215, 245-A--A-247, A-284, A-308, 325-A--A-329 and A-338."; /evidence="ECO:0000269|PubMed:29101232"; MUTAGEN 245..247; /note="SPT->APA: In ST0 mutant; decreased ubiquitination and degradation; when associated with 67-A--A-71, A-215, A-239, A-284, A-308, 325-A--A-329 and A-338."; /evidence="ECO:0000269|PubMed:29101232"; MUTAGEN 284; /note="S->A: In ST0 mutant; decreased ubiquitination and degradation; when associated with 67-A--A-71, A-215, A-239, 245-A--A-247, A-308, 325-A--A-329 and A-338."; /evidence="ECO:0000269|PubMed:29101232"; MUTAGEN 308; /note="S->A: In ST0 mutant; decreased ubiquitination and degradation; when associated with 67-A--A-71, A-215, A-239, 245-A--A-247, A-284, 325-A--A-329 and A-338."; /evidence="ECO:0000269|PubMed:29101232"; MUTAGEN 325..329; /note="TPPQT->APPQA: In ST0 mutant; decreased ubiquitination and degradation; when associated with 67-A--A-71, A-215, A-239, 245-A--A-247, A-284, A-308, 325-A--A-329 and A-338."; /evidence="ECO:0000269|PubMed:29101232"; MUTAGEN 336; /note="K->R: In K0 mutant; decreased ubiquitination and degradation; when associated with R-229, R-343 and R-413."; /evidence="ECO:0000269|PubMed:29101232"; MUTAGEN 338; /note="T->A: In ST0 mutant; decreased ubiquitination and degradation; when associated with 67-A--A-71, A-215, A-239, 245-A--A-247, A-284, A-308 and 325-A--A-329."; /evidence="ECO:0000269|PubMed:29101232"; MUTAGEN 343; /note="K->R: In K0 mutant; decreased ubiquitination and degradation; when associated with R-229, R-336 and R-413."; /evidence="ECO:0000269|PubMed:29101232"; MUTAGEN 382; /note="V->Y: Increased basal level of G protein-mediated signaling."; /evidence="ECO:0000269|PubMed:29051383"; MUTAGEN 413; /note="K->R: In K0 mutant; decreased ubiquitination and degradation; when associated with R-229, R-336 and R-343."; /evidence="ECO:0000269|PubMed:29101232"; MUTAGEN 418; /note="C->G: No effect on palmitoylation."; /evidence="ECO:0000269|PubMed:27659709"; MUTAGEN 419; /note="C->G: Loss of palmitoylation."; /evidence="ECO:0000269|PubMed:27659709
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated via both ester and isopeptide bonds; leading to its degradation (PubMed:20100572). Polyubiquitinated by the BCR(KLHL12) E3 ubiquitin ligase complex: polyubiquitination does not lead to degradation of DRD4 protein (PubMed:18303015, PubMed:20100572). {ECO:0000269|PubMed:18303015, ECO:0000269|PubMed:20100572}.; PTM: Palmitoylated. Palmitoylation of the C-terminal Cys is important for normal expression at the cell membrane. {ECO:0000269|PubMed:27659709}.
uniprot
proteins
protein_family
G protein-coupled receptor 1 family
uniprot
proteins
pubmed
12142540
uniprot
proteins
pubmed
1319557
uniprot
proteins
pubmed
1358063
uniprot
proteins
pubmed
16423344
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
18303015
uniprot
proteins
pubmed
1840645
uniprot
proteins
pubmed
20100572
uniprot
proteins
pubmed
20836733
uniprot
proteins
pubmed
21184734
uniprot
proteins
pubmed
27659709
uniprot
proteins
pubmed
29051383
uniprot
proteins
pubmed
29101232
uniprot
proteins
pubmed
37221270
uniprot
proteins
pubmed
7512953
uniprot
proteins
pubmed
7643093
uniprot
proteins
pubmed
7726213
uniprot
proteins
pubmed
7769992
uniprot
proteins
pubmed
8078498
uniprot
proteins
pubmed
8353495
uniprot
proteins
pubmed
8413587
uniprot
proteins
pubmed
9003072
uniprot
proteins
pubmed
9042615
uniprot
proteins
sequence_length
419
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1319557, ECO:0000269|PubMed:16423344, ECO:0000269|PubMed:1840645, ECO:0000269|PubMed:20100572, ECO:0000269|PubMed:27659709, ECO:0000269|PubMed:29051383, ECO:0000269|PubMed:7512953, ECO:0000269|PubMed:7643093, ECO:0000269|PubMed:8078498, ECO:0000269|PubMed:8413587, ECO:0000269|PubMed:9003072}; Multi-pass membrane protein {ECO:0000269|PubMed:20100572, ECO:0000269|PubMed:29051383}.
uniprot
proteins
transmembrane_region
TRANSMEM 30..50; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:29051383, ECO:0000269|PubMed:37221270, ECO:0007744|PDB:8IRU"; TRANSMEM 72..92; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:29051383, ECO:0000269|PubMed:37221270, ECO:0007744|PDB:8IRU"; TRANSMEM 111..131; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:29051383, ECO:0000269|PubMed:37221270, ECO:0007744|PDB:8IRU"; TRANSMEM 153..173; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:29051383, ECO:0000269|PubMed:37221270, ECO:0007744|PDB:8IRU"; TRANSMEM 193..213; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:29051383, ECO:0000269|PubMed:37221270, ECO:0007744|PDB:8IRU"; TRANSMEM 347..367; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:29051383, ECO:0000269|PubMed:37221270, ECO:0007744|PDB:8IRU"; TRANSMEM 383..403; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:29051383, ECO:0000269|PubMed:37221270, ECO:0007744|PDB:8IRU
uniprot
proteins