D(3) dopamine receptor
Also known as: DRD3
Function
Dopamine receptor that is primarily expressed in limbic areas of the brain and is involved in the modulation of cognitive, emotional, and endocrine functions. Plays a key role in regulating neuronal signaling pathways associated with motivation, reward, and behavior. Coupled to G(i)/G(o) proteins; activation leads to inhibition of adenylate cyclase and decreased intracellular cAMP levels. Involved in the control of locomotor activity and implicated in several neuropsychiatric disorders, including schizophrenia and substance use disorders. Promotes cell proliferation through MAP kinase signaling. 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. This leads to activation of ULK1 and initiation of the autophagy cascade. Forms heterotetramers with DRD1 to potentiate beta-arrestin recruitment and mediate locomotor activity (By similarity).
Classification
- Family (Pfam)
- PF00001 7tm_1
- InterPro
- Dopamine_D3_rcpt, Dopamine_rcpt, GPCR_Rhodpsn, GPCR_Rhodpsn_7TM
- Functional cluster
- G Protein-Coupled Receptors
Experimental structures · PDB · 6
A predicted model is available from AlphaFold.
Gene Ontology · 38
- GO:0005886 plasma membrane
- GO:0045202 synapse
- GO:0001591 dopamine neurotransmitter receptor activity, coupled via Gi/Go
- GO:0004930 G protein-coupled receptor activity
- GO:0046717 acid secretion
- GO:0007191 adenylate cyclase-activating dopamine receptor signaling pathway
- GO:0007195 adenylate cyclase-inhibiting dopamine receptor signaling pathway
- GO:0050482 arachidonate secretion
- GO:0048148 behavioral response to cocaine
- GO:0032922 circadian regulation of gene expression
- GO:0042417 dopamine metabolic process
- GO:0002031 G protein-coupled receptor internalization
- GO:0007186 G protein-coupled receptor signaling pathway
- GO:0006874 intracellular calcium ion homeostasis
- GO:0007612 learning
- GO:0007611 learning or memory
- GO:0007626 locomotory behavior
- GO:0050883 musculoskeletal movement, spinal reflex action
- GO:0045776 negative regulation of blood pressure
- GO:0051481 negative regulation of cytosolic calcium ion concentration
- GO:0048715 negative regulation of oligodendrocyte differentiation
- GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
- GO:0050709 negative regulation of protein secretion
- GO:0051967 negative regulation of synaptic transmission, glutamatergic
- GO:0060158 phospholipase C-activating dopamine receptor signaling pathway
- GO:0032467 positive regulation of cytokinesis
- GO:0060161 positive regulation of dopamine receptor signaling pathway
- GO:0045840 positive regulation of mitotic nuclear division
- GO:0060134 prepulse inhibition
- GO:0014059 regulation of dopamine secretion
- GO:0051584 regulation of dopamine uptake involved in synaptic transmission
- GO:0043266 regulation of potassium ion transport
- GO:0042220 response to cocaine
- GO:0034776 response to histamine
- GO:0043278 response to morphine
- GO:0009410 response to xenobiotic stimulus
- GO:0035176 social behavior
- GO:0008542 visual learning
Disease associations
- schizophrenia MONDO:0005090
- tremor, hereditary essential, 1 MONDO:0008590
Drugs targeting this protein · 38
- LEVODOPA agonist
- DROPERIDOL antagonist
- AMOXAPINE antagonist
- ROPINIROLE HYDROCHLORIDE agonist
- PROMAZINE HYDROCHLORIDE antagonist
- BROMOCRIPTINE MESYLATE agonist
- THIORIDAZINE HYDROCHLORIDE antagonist
- HALOPERIDOL DECANOATE inverse agonist
- LOXAPINE HYDROCHLORIDE antagonist
- LOXAPINE SUCCINATE antagonist
- TRIFLUOPERAZINE HYDROCHLORIDE antagonist
- PERGOLIDE MESYLATE agonist
- ROTIGOTINE agonist
- PIMOZIDE antagonist
- CHLORPROMAZINE HYDROCHLORIDE antagonist
- LEVOMEPROMAZINE antagonist
- BLONANSERIN antagonist
- ETILEVODOPA agonist
- CARIPRAZINE HYDROCHLORIDE modulator
- PARDOPRUNOX partial agonist
- SARIZOTAN HYDROCHLORIDE agonist
- ADOPRAZINE antagonist
- ERGOLOID MESYLATES agonist
- AMISULPRIDE antagonist
- PRAMIPEXOLE DIHYDROCHLORIDE agonist
- APOMORPHINE HYDROCHLORIDE agonist
- OLANZAPINE PAMOATE antagonist
- HALOPERIDOL LACTATE inverse agonist
- ABT-925 antagonist
- MESDOPETAM antagonist
- TRAZPIROBEN antagonist
- THIORIDAZINE antagonist
- HALOPERIDOL inverse agonist
- CHLORPROMAZINE antagonist
- OLANZAPINE antagonist
- LOXAPINE antagonist
- TIAPRIDE antagonist
- CHLORPROTHIXENE antagonist
Related proteins · sequence + function similarity
- D(3) dopamine receptor 1.00
- D(3) dopamine receptor 1.00
- D(3) dopamine receptor 0.98
- D(3) dopamine receptor 0.98
- 5-hydroxytryptamine receptor 5A 0.93
- Alpha-1A adrenergic receptor 0.93
- 5-hydroxytryptamine receptor 5A 0.92
- 5-hydroxytryptamine receptor 5A 0.92
- 5-hydroxytryptamine receptor 1D 0.92
- 5-hydroxytryptamine receptor 1B 0.92
- 5-hydroxytryptamine receptor 1B 0.92
- 5-hydroxytryptamine receptor 1D 0.92
Co-cited proteins · studied together in the literature
- G protein-coupled receptor kinase 4 1 shared papers
- Paralemmin-1 1 shared papers
- D(4) dopamine receptor 1 shared papers
- Paralemmin-1 1 shared papers
- Proto-oncogene Mas 1 shared papers
- Alpha-1D adrenergic receptor 1 shared papers
- Type-1 angiotensin II receptor 1 shared papers
- Filamin-A 1 shared papers
Literature · 19 cited papers
- Striatal dopamine D2/D3 receptor regulation of human reward processing and behaviour. Nat. Commun. · 2025
- DRD3 (dopamine receptor D3) but not DRD2 activates autophagy through MTORC1 inhibition preserving protein synthesis. Autophagy · 2020
- Palmitoylation of the carboxyl-terminal tail of dopamine D4 receptor is required for surface expression, endocytosis, and signaling. Biochem. Biophys. Res. Commun. · 2016
- G Protein-Coupled Receptors Directly Bind Filamin A with High Affinity and Promote Filamin Phosphorylation. Biochemistry · 2015
- Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist. Science · 2010
- G protein-coupled receptor kinase 4 (GRK4) regulates the phosphorylation and function of the dopamine D3 receptor. J. Biol. Chem. · 2009
- A functional variant of the dopamine D3 receptor is associated with risk and age-at-onset of essential tremor. Proc. Natl. Acad. Sci. U.S.A. · 2006
- Linkage with the Ser9Gly DRD3 polymorphism in essential tremor families. Clin. Genet. · 2006
- The DNA sequence, annotation and analysis of human chromosome 3. Nature · 2006
- Paralemmin interacts with D3 dopamine receptors: implications for membrane localization and cAMP signaling. Arch. Biochem. Biophys. · 2006
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- Efficient functional coupling of the human D3 dopamine receptor to G(o) subtype of G proteins in SH-SY5Y cells. Br. J. Pharmacol. · 1999
- … and 7 more in the literature graph