DRD3
entrez
1814
canonical
uniprot
P35462
canonical
ensembl
ENSG00000151577
resolver
ensp
ENSP00000295881
resolver
ensp
ENSP00000373169
resolver
ensp
ENSP00000419402
resolver
ensp
ENSP00000420662
resolver
enst
ENST00000295881
resolver
genesymbol
DRD3
resolver
hgnc
HGNC:3024
resolver
uniprot
A1A4V4
resolver
uniprot
A1A4V5
resolver
uniprot
A8K8E4
resolver
uniprot
E9PCM4
resolver
uniprot
Q4VBM8
resolver
uniprot
X5D2G4
resolver
uniprot_entry
A1A4V4_HUMAN
resolver
uniprot_entry
A8K8E4_HUMAN
resolver
uniprot_entry
DRD3_HUMAN
resolver
uniprot_entry
E9PCM4_HUMAN
resolver
uniprot_entry
X5D2G4_HUMAN
resolver
uniprot_sec
A1A4V5
resolver
uniprot_sec
Q4VBM8
resolver
activity_regulation
ACTIVITY REGULATION: Specifically activated by small-molecule agonists PD128907 and pramipexole (PubMed:33548201). Specifically activated by the bitopic agonist FOB02-04A (PubMed:39237617). Activated by the pan-agonist rotigotine, which activates all five dopamine receptors (PubMed:37221270). {ECO:0000269|PubMed:33548201, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39237617}.
uniprot
proteins
amino_acid_sequence
MASLSQLSGHLNYTCGAENSTGASQARPHAYYALSYCALILAIVFGNGLVCMAVLKERALQTTTNYLVVSLAVADLLVATLVMPWVVYLEVTGGVWNFSRICCDVFVTLDVMMCTASILNLCAISIDRYTAVVMPVHYQHGTGQSSCRRVALMITAVWVLAFAVSCPLLFGFNTTGDPTVCSISNPDFVIYSSVVSFYLPFGVTVLVYARIYVVLKQRRRKRILTRQNSQCNSVRPGFPQQTLSPDPAHLELKRYYSICQDTALGGPGFQERGGELKREEKTRNSLSPTIAPKLSLEVRKLSNGRLSTSLKLGPLQPRGVPLREKKATQMVAIVLGAFIVCWLPFFLTHVLNTHCQTCHVSPELYSATTWLGYVNSALNPVIYTTFNIEFRKAFLKILSC
uniprot
proteins
disease_involvement
DISEASE: Tremor, hereditary essential 1 (ETM1) [MIM:190300]: A common movement disorder mainly characterized by postural tremor of the arms. Head, legs, trunk, voice, jaw, and facial muscles may also be involved. The condition can be aggravated by emotions, hunger, fatigue and temperature extremes, and may cause a functional disability or even incapacitation. Inheritance is autosomal dominant. {ECO:0000269|PubMed:16650084, ECO:0000269|PubMed:16809426}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry. Glycine at position 9 results in gain of function and is associated with susceptibility to essential tremor. {ECO:0000269|PubMed:16650084, ECO:0000269|PubMed:16809426}.; DISEASE: Schizophrenia (SCZD) [MIM:181500]: A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. {ECO:0000269|PubMed:1362221, ECO:0000269|PubMed:9514583}. Note=Disease susceptibility may be associated with variants affecting the gene represented in this entry. Glycine at position 9 results in gain of function and may be a risk factor for schizophrenia. {ECO:0000269|PubMed:1362221, ECO:0000269|PubMed:9514583}.
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:19520868, PubMed:33548201, PubMed:37221270, PubMed:39237617, PubMed:39984436, PubMed:8301582). 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:10578130, PubMed:33548201, PubMed:37221270, PubMed:39237617). Dopamine receptors can be classified in two categories: (1) DRD3 (together with DRD2 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:10578130, PubMed:33548201, PubMed:37221270, PubMed:39237617). 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:10578130, PubMed:33548201, PubMed:37221270, PubMed:39237617). DRD3 is primarily expressed in limbic areas of the brain and is involved in the modulation of cognitive, emotional and motor functions: plays a key role in regulating neuronal signaling pathways associated with motivation, reward and behavior (PubMed:39984436). Involved in the incentive salience of drugs: controls responses to drug-related stimuli, making it a key target for reducing addiction to substances like cocaine, morphine, and alcohol (PubMed:10432116, PubMed:39984436). Forms heterotetramers with DRD1 to potentiate beta-arrestin recruitment and mediate locomotor activity (By similarity). Also involved in autophagy regulation: receptor activation stimulates AMPK, which phosphorylates RPTOR and enhances its interaction with MTOR, thereby inhibiting mTORC1 signaling and its downstream target RPS6KB1 (PubMed:31538542). This leads to activation of ULK1 and initiation of the autophagy cascade (PubMed:31538542). {ECO:0000250|UniProtKB:P30728, ECO:0000269|PubMed:10432116, ECO:0000269|PubMed:10578130, ECO:0000269|PubMed:19520868, ECO:0000269|PubMed:31538542, ECO:0000269|PubMed:33548201, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39237617, ECO:0000269|PubMed:39984436, ECO:0000269|PubMed:8301582}.
uniprot
proteins
mass_dalton
44195
uniprot
proteins
mutagenesis
MUTAGEN 29; /note="H->F,K,R: Reduced affinity for bitopic agonist FOB02-04A."; /evidence="ECO:0000269|PubMed:39237617"; MUTAGEN 86; /note="V->A: Does not affect activation by rotigotine."; /evidence="ECO:0000269|PubMed:37221270"; MUTAGEN 94; /note="Missing: Abolished activation by bitopic agonist FOB02-04A."; /evidence="ECO:0000269|PubMed:39237617"; MUTAGEN 114; /note="C->A: Reduced affinity for PD128907 and pramipexole."; /evidence="ECO:0000269|PubMed:33548201"; MUTAGEN 115; /note="T->A: Reduced affinity for pramipexole without affecting affinity for PD128907."; /evidence="ECO:0000269|PubMed:33548201"; MUTAGEN 192; /note="S->A: Strongly reduced affinity for PD128907; slightly reduced affinity for pramipexole."; /evidence="ECO:0000269|PubMed:33548201"; MUTAGEN 342; /note="W->A: Reduced activation by dopamine."; /evidence="ECO:0000269|PubMed:33548201"; MUTAGEN 349; /note="H->A: Strongly reduced affinity for PD128907 and pramipexole."; /evidence="ECO:0000269|PubMed:33548201
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by GRK4 (GRK4-alpha and GRK4-gamma). {ECO:0000269|PubMed:19520868}.; PTM: Palmitoylated. {ECO:0000269|PubMed:27659709}.
uniprot
proteins
protein_family
G protein-coupled receptor 1 family
uniprot
proteins
pubmed
10391209
uniprot
proteins
pubmed
10432116
uniprot
proteins
pubmed
10578130
uniprot
proteins
pubmed
1362221
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16386234
uniprot
proteins
pubmed
16641997
uniprot
proteins
pubmed
16650084
uniprot
proteins
pubmed
16809426
uniprot
proteins
pubmed
19520868
uniprot
proteins
pubmed
21097933
uniprot
proteins
pubmed
2129115
uniprot
proteins
pubmed
26460884
uniprot
proteins
pubmed
27659709
uniprot
proteins
pubmed
31538542
uniprot
proteins
pubmed
33548201
uniprot
proteins
pubmed
37221270
uniprot
proteins
pubmed
39237617
uniprot
proteins
pubmed
39984436
uniprot
proteins
pubmed
7961889
uniprot
proteins
pubmed
8301582
uniprot
proteins
pubmed
8413587
uniprot
proteins
pubmed
8415635
uniprot
proteins
pubmed
9034004
uniprot
proteins
pubmed
9514583
uniprot
proteins
sequence_length
400
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19520868, ECO:0000269|PubMed:8413587}; Multi-pass membrane protein {ECO:0000269|PubMed:21097933, ECO:0000269|PubMed:37221270}. Note=Both membrane-bound and scattered in the cytoplasm during basal conditions (PubMed:19520868). Receptor stimulation results in the rapid internalization and sequestration of the receptors at the perinuclear area (5 and 15 minutes), followed by the dispersal of the receptors to the membrane (30 minutes) (PubMed:19520868). DRD3 and GRK4 co-localize in lipid rafts of renal proximal tubule cells (PubMed:19520868). {ECO:0000269|PubMed:19520868}.
uniprot
proteins
transmembrane_region
TRANSMEM 33..55; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:21097933, ECO:0000269|PubMed:33548201, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39237617, ECO:0007744|PDB:8IRT, ECO:0007744|PDB:9F33, ECO:0007744|PDB:9F34"; TRANSMEM 66..88; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:21097933, ECO:0000269|PubMed:33548201, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39237617, ECO:0007744|PDB:8IRT, ECO:0007744|PDB:9F33, ECO:0007744|PDB:9F34"; TRANSMEM 105..126; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:21097933, ECO:0000269|PubMed:33548201, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39237617, ECO:0007744|PDB:8IRT, ECO:0007744|PDB:9F33, ECO:0007744|PDB:9F34"; TRANSMEM 150..170; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:21097933, ECO:0000269|PubMed:33548201, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39237617, ECO:0007744|PDB:8IRT, ECO:0007744|PDB:9F33, ECO:0007744|PDB:9F34"; TRANSMEM 188..209; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:21097933, ECO:0000269|PubMed:33548201, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39237617, ECO:0007744|PDB:8IRT, ECO:0007744|PDB:9F33, ECO:0007744|PDB:9F34"; TRANSMEM 330..351; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:21097933, ECO:0000269|PubMed:33548201, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39237617, ECO:0007744|PDB:8IRT, ECO:0007744|PDB:9F33, ECO:0007744|PDB:9F34"; TRANSMEM 367..386; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:21097933, ECO:0000269|PubMed:33548201, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39237617, ECO:0007744|PDB:8IRT, ECO:0007744|PDB:9F33, ECO:0007744|PDB:9F34
uniprot
proteins