D(4) dopamine receptor

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. Agonist binding triggers signaling via G proteins that inhibit adenylyl cyclase. Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity).

Classification

Family (Pfam)

PF00001 7tm_1

InterPro

Dopamine_D4_rcpt, Dopamine_rcpt, GPCR_Rhodpsn, GPCR_Rhodpsn_7TM

Functional cluster

G Protein-Coupled Receptors

Experimental structures · PDB · 2

• 5WIU X-ray 1.96A
• 5WIV X-ray 2.14A

A predicted model is available from AlphaFold.

Gene Ontology · 39

• GO:0030425 dendrite
• GO:0098978 glutamatergic synapse
• GO:0016020 membrane
• GO:0005886 plasma membrane
• GO:0098794 postsynapse
• GO:0035240 dopamine binding
• GO:0004952 dopamine neurotransmitter receptor activity
• GO:0001591 dopamine neurotransmitter receptor activity, coupled via Gi/Go
• GO:0051379 epinephrine binding
• GO:0004993 G protein-coupled serotonin receptor activity
• GO:0042802 identical protein binding
• GO:0046872 metal ion binding
• GO:0030594 neurotransmitter receptor activity
• GO:0051380 norepinephrine binding
• GO:0015459 potassium channel regulator activity
• GO:0017124 SH3 domain binding
• GO:0007195 adenylate cyclase-inhibiting dopamine receptor signaling pathway
• GO:0007188 adenylate cyclase-modulating G protein-coupled receptor signaling pathway
• GO:0008344 adult locomotory behavior
• GO:0050482 arachidonate secretion
• GO:0001662 behavioral fear response
• GO:0048148 behavioral response to cocaine
• GO:0048149 behavioral response to ethanol
• GO:0007268 chemical synaptic transmission
• GO:0042596 fear response
• GO:0007187 G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
• GO:0060080 inhibitory postsynaptic potential
• GO:0006874 intracellular calcium ion homeostasis
• GO:0050709 negative regulation of protein secretion
• GO:0060158 phospholipase C-activating dopamine receptor signaling pathway
• GO:0051586 positive regulation of dopamine uptake involved in synaptic transmission
• GO:0043410 positive regulation of MAPK cascade
• GO:0042752 regulation of circadian rhythm
• GO:0042053 regulation of dopamine metabolic process
• GO:0099149 regulation of postsynaptic neurotransmitter receptor internalization
• GO:0001975 response to amphetamine
• GO:0034776 response to histamine
• GO:0048511 rhythmic process
• GO:0035176 social behavior

Drugs targeting this protein · 27

• 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
• SARIZOTAN HYDROCHLORIDE agonist
• ERGOLOID MESYLATES agonist
• CLOTHIAPINE antagonist
• PRAMIPEXOLE DIHYDROCHLORIDE agonist
• APOMORPHINE HYDROCHLORIDE agonist
• OLANZAPINE PAMOATE antagonist
• HALOPERIDOL LACTATE inverse agonist
• THIORIDAZINE antagonist
• HALOPERIDOL inverse agonist
• CHLORPROMAZINE antagonist
• OLANZAPINE antagonist
• LOXAPINE antagonist

Related proteins · sequence + function similarity

• D(4) dopamine receptor 0.95
• Beta-3 adrenergic receptor 0.93
• Beta-3 adrenergic receptor 0.92
• D(4) dopamine receptor 0.92
• Beta-3 adrenergic receptor 0.92
• D(4) dopamine receptor 0.91
• Beta-3 adrenergic receptor 0.91
• Beta-3 adrenergic receptor 0.91
• Beta-1 adrenergic receptor 0.91
• Beta-3 adrenergic receptor 0.90
• Beta-3 adrenergic receptor 0.90
• Beta-3 adrenergic receptor 0.90

Co-cited proteins · studied together in the literature

• D(4) dopamine receptor 1 shared papers
• Adenosine receptor A2a 1 shared papers
• Kelch-like protein 12 2 shared papers
• D(3) dopamine receptor 1 shared papers
• D(4) dopamine receptor 1 shared papers
• D(3) dopamine receptor 1 shared papers
• D(2) dopamine receptor 1 shared papers
• Delta-type opioid receptor 1 shared papers
• G protein-coupled receptor-associated sorting protein 1 1 shared papers
• D(2) dopamine receptor 1 shared papers
• Beta-2 adrenergic receptor 1 shared papers

Literature · 19 cited papers

• D4 dopamine receptor high-resolution structures enable the discovery of selective agonists. Science · 2017
• Palmitoylation of the carboxyl-terminal tail of dopamine D4 receptor is required for surface expression, endocytosis, and signaling. Biochem. Biophys. Res. Commun. · 2016
• Dopamine D2 and D4 receptor heteromerization and its allosteric receptor-receptor interactions. Biochem. Biophys. Res. Commun. · 2011
• The dopamine D(4) receptor, the ultimate disordered protein. J. Recept. Signal Transduct. · 2010
• KLHL12-mediated ubiquitination of the dopamine D4 receptor does not target the receptor for degradation. Cell. Signal. · 2010
• BTB Protein KLHL12 targets the dopamine D4 receptor for ubiquitination by a Cul3-based E3 ligase. J. Biol. Chem. · 2008
• Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature · 2006
• [35S]GTPgammaS binding at the human dopamine D4 receptor variants hD4.2, hD4.4 and hD4.7 following stimulation by dopamine, epinephrine and norepinephrine. Eur. J. Pharmacol. · 2006
• Modulation of postendocytic sorting of G protein-coupled receptors. Science · 2002
• Epinephrine and norepinephrine act as potent agonists at the recombinant human dopamine D4 receptor. J. Neurochem. · 1997
• A hypervariable segment in the human dopamine receptor D4 (DRD4) gene. Hum. Mol. Genet. · 1993
• Dopamine D4 receptor repeat: analysis of different native and mutant forms of the human and rat genes. Mol. Pharmacol. · 1994
• … and 7 more in the literature graph