DRD2
entrez
1813
canonical
uniprot
P14416
canonical
ensembl
ENSG00000149295
resolver
ensp
ENSP00000278597
resolver
ensp
ENSP00000354859
resolver
ensp
ENSP00000441068
resolver
ensp
ENSP00000577545
resolver
enst
ENST00000544518
resolver
genesymbol
DRD2
resolver
hgnc
HGNC:3023
resolver
uniprot
F8VUV1
resolver
uniprot
Q9NZR3
resolver
uniprot
Q9UPA9
resolver
uniprot_entry
DRD2_HUMAN
resolver
uniprot_entry
F8VUV1_HUMAN
resolver
uniprot_sec
Q9NZR3
resolver
uniprot_sec
Q9UPA9
resolver
activity_regulation
ACTIVITY REGULATION: Activated by small-molecule agonist bromocriptine (PubMed:33571431). Activated by the pan-agonist rotigotine, which activates all five dopamine receptors (PubMed:37221270). Inhibited by antipsychotic drug haloperidol; which acts as an antagonist of DRD2 (PubMed:32103023). Specifically inhibited by antipsychotic drug spiperone; which acts as a specific and potent antagonist of DRD2 (PubMed:33353947). {ECO:0000269|PubMed:32103023, ECO:0000269|PubMed:33353947, ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:37221270}.
uniprot
proteins
amino_acid_sequence
MDPLNLSWYDDDLERQNWSRPFNGSDGKADRPHYNYYATLLTLLIAVIVFGNVLVCMAVSREKALQTTTNYLIVSLAVADLLVATLVMPWVVYLEVVGEWKFSRIHCDIFVTLDVMMCTASILNLCAISIDRYTAVAMPMLYNTRYSSKRRVTVMISIVWVLSFTISCPLLFGLNNADQNECIIANPAFVVYSSIVSFYVPFIVTLLVYIKIYIVLRRRRKRVNTKRSSRAFRAHLRAPLKGNCTHPEDMKLCTVIMKSNGSFPVNRRRVEAARRAQELEMEMLSSTSPPERTRYSPIPPSHHQLTLPDPSHHGLHSTPDSPAKPEKNGHAKDHPKIAKIFEIQTMPNGKTRTSLKTMSRRKLSQQKEKKATQMLAIVLGVFIICWLPFFITHILNIHCDCNIPPVLYSAFTWLGYVNSAVNPIIYTTFNIEFRKAFLKILHC
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:21645528, PubMed:32103023, PubMed:32528175, PubMed:33353947, PubMed:33571431, PubMed:37221270, PubMed:39103320). Dopamine 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:32103023, PubMed:32528175, PubMed:33353947, PubMed:33571431, PubMed:37221270). Dopamine receptors can be classified in two categories: (1) DRD2 (together with DRD3 and DRD4) 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:32103023, PubMed:32528175, PubMed:33353947, PubMed:33571431, PubMed:37221270). In the central nervous system, DRD2 is mainly coupled to G(o)/GNAO1 (By similarity). 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 (By similarity). DRD1 and DRD2 are the most abundant dopamine receptors in the central nervous system, especially in the basal ganglia and the prefrontal cortex (PubMed:33571431). DRD2 receptor plays a key role in risky decision-making by modulating reward sensitivity and executive control; DRD2 activation in nucleus accumbens cells leading to increased risk-taking and impulsivity (By similarity). DRD2 can also couple with G(q) by forming a heteromer with the ghrelin receptor GHSR in neurons independently of ghrelin (By similarity). Following DRD2 activation by dopamine in lumbosacral defecation centers, GHSR acts as a coreceptor promoting DRD2 coupling to G(q) at the expense of G(i)/G(o), regulating defecation (By similarity). In addition to dopamine, also acts as a receptor for tryptophan-derived metabolites in intestinal epithelial cells: activation by tryptophan metabolites produced by the gut microbiota initiates a phospholipase-C-dependent signaling that promotes colonization resistance by pathogens by controlling actin cytoskeletal organization in the gut epithelium (By similarity). Positively regulates postnatal regression of retinal hyaloid vessels via suppression of VEGFR2/KDR activity, downstream of OPN5 (By similarity). Also acts as a receptor for D-lysergic (LSD) psychedelic drug (PubMed:40683247). {ECO:0000250|UniProtKB:P61168, ECO:0000250|UniProtKB:P61169, ECO:0000269|PubMed:21645528, ECO:0000269|PubMed:32103023, ECO:0000269|PubMed:32528175, ECO:0000269|PubMed:33353947, ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39103320, ECO:0000269|PubMed:40683247}.
uniprot
proteins
mass_dalton
50619
uniprot
proteins
mutagenesis
MUTAGEN 91; /note="V->A: Does not affect activation by rotigotine."; /evidence="ECO:0000269|PubMed:37221270"; MUTAGEN 110; /note="F->A,L: Enhanced-binding to antagonist haloperidol."; /evidence="ECO:0000269|PubMed:32103023"; MUTAGEN 110; /note="F->W,Y: Reduced-binding to antagonist haloperidol."; /evidence="ECO:0000269|PubMed:32103023"; MUTAGEN 126; /note="C->S: No effect on palmitoylation; no effect on localization to the plasma membrane."; /evidence="ECO:0000269|PubMed:26535572"; MUTAGEN 244; /note="C->S: No effect on palmitoylation; no effect on localization to the plasma membrane."; /evidence="ECO:0000269|PubMed:26535572"; MUTAGEN 253; /note="C->S: No effect on palmitoylation; no effect on localization to the plasma membrane."; /evidence="ECO:0000269|PubMed:26535572"; MUTAGEN 285..296; /note="SSTSPPERTRYS->AAAAPPERARYA: Decreased phosphorylation and desensitization."; /evidence="ECO:0000269|PubMed:40781549"; MUTAGEN 443; /note="Missing: Decreased palmitoylation; decreased localization to the plasma membrane; decreased stability."; /evidence="ECO:0000269|PubMed:26535572
uniprot
proteins
post_translational_modification
PTM: Palmitoylated (PubMed:7931316, PubMed:26535572). Palmitoylation which is required for proper localization to the plasma membrane and stability of the receptor could be carried on by ZDHHC4, ZDHHC3 and ZDHHC8 (PubMed:26535572). {ECO:0000269|PubMed:26535572, ECO:0000269|PubMed:7931316}.; PTM: Phosphorylation of intracellular loop 3 by GRK2 and GRK3 following prolonged stimulation by dopamine, promoting association with beta-arrestin (ARRB1 or ARRB2), leading to receptor desensitization and negative regulation of G protein-coupled receptor signaling (PubMed:33859231, PubMed:40781549). Constitutive phosphorylation (in absence of dopamine activation) by some isoforms of PKC-beta (PRKCB) inhibits G protein-coupled receptor signaling (PubMed:2953072). {ECO:0000269|PubMed:2953072, ECO:0000269|PubMed:33859231, ECO:0000269|PubMed:40781549}.
uniprot
proteins
protein_family
G protein-coupled receptor 1 family
uniprot
proteins
pubmed
10220438
uniprot
proteins
pubmed
10716258
uniprot
proteins
pubmed
10719223
uniprot
proteins
pubmed
1363862
uniprot
proteins
pubmed
15389757
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15857609
uniprot
proteins
pubmed
17264214
uniprot
proteins
pubmed
17550964
uniprot
proteins
pubmed
1835903
uniprot
proteins
pubmed
21179162
uniprot
proteins
pubmed
21184734
uniprot
proteins
pubmed
2137193
uniprot
proteins
pubmed
2138729
uniprot
proteins
pubmed
2144985
uniprot
proteins
pubmed
21645528
uniprot
proteins
pubmed
22408789
uniprot
proteins
pubmed
23493394
uniprot
proteins
pubmed
2531656
uniprot
proteins
pubmed
2532362
uniprot
proteins
pubmed
2533064
uniprot
proteins
pubmed
25979333
uniprot
proteins
pubmed
26535572
uniprot
proteins
pubmed
29466326
uniprot
proteins
pubmed
2953072
uniprot
proteins
pubmed
32103023
uniprot
proteins
pubmed
32528175
uniprot
proteins
pubmed
33353947
uniprot
proteins
pubmed
33571431
uniprot
proteins
pubmed
33859231
uniprot
proteins
pubmed
37221270
uniprot
proteins
pubmed
39103320
uniprot
proteins
pubmed
40683247
uniprot
proteins
pubmed
40781549
uniprot
proteins
pubmed
7902708
uniprot
proteins
pubmed
7931316
uniprot
proteins
pubmed
8413587
uniprot
proteins
pubmed
8471125
uniprot
proteins
sequence_length
443
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Postsynaptic cell membrane {ECO:0000250|UniProtKB:P61169}; Multi-pass membrane protein {ECO:0000269|PubMed:32528175, ECO:0000269|PubMed:33571431}. Cell membrane {ECO:0000269|PubMed:21645528, ECO:0000269|PubMed:23493394, ECO:0000269|PubMed:26535572, ECO:0000269|PubMed:8413587}; Multi-pass membrane protein {ECO:0000269|PubMed:32528175, ECO:0000269|PubMed:33571431}. Golgi apparatus membrane {ECO:0000269|PubMed:26535572}; Multi-pass membrane protein {ECO:0000269|PubMed:32528175, ECO:0000269|PubMed:33571431}. Note=Mainly active on postsynaptic membrane (By similarity). Specifically localizes to special plasma membrane microcompartments (PubMed:23493394). {ECO:0000250|UniProtKB:P61169, ECO:0000269|PubMed:23493394}.
uniprot
proteins
transmembrane_region
TRANSMEM 38..60; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:32528175, ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39103320, ECO:0000269|PubMed:40683247, ECO:0007744|PDB:6VMS, ECO:0007744|PDB:8TZQ, ECO:0007744|PDB:8U02"; TRANSMEM 71..93; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:32528175, ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39103320, ECO:0000269|PubMed:40683247, ECO:0007744|PDB:6VMS, ECO:0007744|PDB:8TZQ, ECO:0007744|PDB:8U02"; TRANSMEM 109..130; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:32528175, ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39103320, ECO:0000269|PubMed:40683247, ECO:0007744|PDB:6VMS, ECO:0007744|PDB:8TZQ, ECO:0007744|PDB:8U02"; TRANSMEM 152..172; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:32528175, ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39103320, ECO:0000269|PubMed:40683247, ECO:0007744|PDB:6VMS, ECO:0007744|PDB:8TZQ, ECO:0007744|PDB:8U02"; TRANSMEM 189..213; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:32528175, ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39103320, ECO:0000269|PubMed:40683247, ECO:0007744|PDB:6VMS, ECO:0007744|PDB:8TZQ, ECO:0007744|PDB:8U02"; TRANSMEM 374..395; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:32528175, ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39103320, ECO:0000269|PubMed:40683247, ECO:0007744|PDB:6VMS, ECO:0007744|PDB:8TZQ, ECO:0007744|PDB:8U02"; TRANSMEM 410..431; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:32528175, ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39103320, ECO:0000269|PubMed:40683247, ECO:0007744|PDB:6VMS, ECO:0007744|PDB:8TZQ, ECO:0007744|PDB:8U02
uniprot
proteins