Drd4 dopamine receptor D4 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Drd4provided by RGD
Official Full Name: dopamine receptor D4provided by RGD
Primary source: RGD:2522
See related: EnsemblRapid:ENSRNOG00000017927 AllianceGenome:RGD:2522
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: D4RA
Summary: Enables dopamine binding activity; dopamine neurotransmitter receptor activity, coupled via Gi/Go; and heterocyclic compound binding activity. Involved in several processes, including learning or memory; modulation of chemical synaptic transmission; and regulation of signal transduction. Located in several cellular components, including cytoplasmic side of plasma membrane; dendrite; and perikaryon. Is active in GABA-ergic synapse; glutamatergic synapse; and synaptic membrane. Biomarker of attention deficit hyperactivity disorder and obesity. Human ortholog(s) of this gene implicated in several diseases, including Gilles de la Tourette syndrome; antisocial personality disorder; attention deficit hyperactivity disorder; conduct disorder; and substance abuse (multiple). Orthologous to human DRD4 (dopamine receptor D4). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Biased expression in Heart (RPKM 5.8), Thymus (RPKM 0.8) and 3 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 1q41

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	1	NC_086019.1 (205825937..205829124)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	1	NC_051336.1 (196396366..196400824)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	1	NC_005100.4 (214278296..214282818)

Chromosome 1 - NC_086019.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Dopamine D4 receptors in the lateral habenula regulate depression-related behaviors via a pre-synaptic mechanism in experimental Parkinson's disease.
Title: Dopamine D(4) receptors in the lateral habenula regulate depression-related behaviors via a pre-synaptic mechanism in experimental Parkinson's disease.
Theexpression level of D4 receptor was also dramatically down-regulated in the arterial endothelium of rats with streptozotocin-(STZ)-induced diabetes, and the STZ-induced impairment of acetylcholine-induced vasodilation was reversed by activation of D4 receptor.
Title: Dopamine D(4) receptor protected against hyperglycemia-induced endothelial dysfunction via PI3K /eNOS pathway.
Data provide novel evidence that the dopamine D4 receptor does not alter incentive motivation in response to cues on simple behavioural tasks.
Title: Elucidating the role of D4 receptors in mediating attributions of salience to incentive stimuli on Pavlovian conditioned approach and conditioned reinforcement paradigms.
Dopamine D4 receptor (D4R) antagonism in the prelimbic area (PL) decreases the expression of innate fear-behavior indicating that the activation of D4R in the PL is necessary for the expression of innate fear-behavior.
Title: Activation of type 4 dopaminergic receptors in the prelimbic area of medial prefrontal cortex is necessary for the expression of innate fear behavior.
Data indicate that the anterior cingulate cortex is critically involved in parsing the appropriate response when competing stimulus-outcome associations are activated, and that signalling via dopamine D4 receptors may play a particularly important role in gating the temporal and spatial summation of salient events.
Title: Activation of dopamine D4 receptors within the anterior cingulate cortex enhances the erroneous expectation of reward on a rat slot machine task.
Regulatory role of the D(4) receptor on AT(1a) receptor expression and function in VSMCs and suggest that targeting the action of the D(4) receptor may represent an effective therapeutic approach for the treatment of cardiovascular diseases.
Title: Activation of the D4 dopamine receptor attenuates proliferation and migration of vascular smooth muscle cells through downregulation of AT1a receptor expression.
Activation of DRD4 receptors suppresses the proliferation and migration of vascular smooth muscle cells, thereby inhibiting atherosclerosis via reducing the effects of insulin on artery remodeling.
Title: Dopamine D₄ receptors inhibit proliferation and migration of vascular smooth muscle cells induced by insulin via down-regulation of insulin receptor expression.
Following chronic ethanol exposure, dopamine D4 receptor activity is disrupted in the medial prefrontal cortex.
Title: Chronic alcohol disrupts dopamine receptor activity and the cognitive function of the medial prefrontal cortex.
The restoration of PFC glutamatergic transmission in stress conditions may enable D4 receptors to serve as a synaptic stabilizer in normal and pathological conditions.
Title: Restoration of glutamatergic transmission by dopamine D4 receptors in stressed animals.
D4R activation affects fast-spiking interneuron synchronization and thereby increases gamma power by an NMDA receptor-dependent mechanism.
Title: Dopamine D4 receptor activation increases hippocampal gamma oscillations by enhancing synchronization of fast-spiking interneurons.

Submit: New GeneRIF Correction See all GeneRIFs (35)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Drd4 (e-PCR), detects polymorphism
- UniSTS:142867

UniSTS:142868 (e-PCR)
- UniSTS:142868

Drd4 (e-PCR), detects polymorphism
- UniSTS:142868

Drd4 (e-PCR), detects polymorphism
- UniSTS:508533

RH142302 (e-PCR)
- UniSTS:231549

RH94697 (e-PCR)
- UniSTS:119944

BI284462 (e-PCR)
- UniSTS:244124

D1Wox57 (e-PCR)
- UniSTS:239563

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables G protein-coupled receptor activity	IEA Inferred from Electronic Annotation more info
enables G protein-coupled serotonin receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables SH3 domain binding	IEA Inferred from Electronic Annotation more info
enables SH3 domain binding	ISO Inferred from Sequence Orthology more info
enables dopamine binding	IDA Inferred from Direct Assay more info	PubMed
enables dopamine binding	IEA Inferred from Electronic Annotation more info
enables dopamine binding	IPI Inferred from Physical Interaction more info	PubMed
enables dopamine binding	ISO Inferred from Sequence Orthology more info
enables dopamine neurotransmitter receptor activity	ISO Inferred from Sequence Orthology more info
enables dopamine neurotransmitter receptor activity, coupled via Gi/Go	IDA Inferred from Direct Assay more info	PubMed
enables dopamine neurotransmitter receptor activity, coupled via Gi/Go	IEA Inferred from Electronic Annotation more info
enables dopamine neurotransmitter receptor activity, coupled via Gi/Go	ISO Inferred from Sequence Orthology more info
enables epinephrine binding	IEA Inferred from Electronic Annotation more info
enables epinephrine binding	ISO Inferred from Sequence Orthology more info
enables heterocyclic compound binding	IDA Inferred from Direct Assay more info	PubMed
enables heterocyclic compound binding	IPI Inferred from Physical Interaction more info	PubMed
enables identical protein binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables neurotransmitter receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables norepinephrine binding	IEA Inferred from Electronic Annotation more info
enables norepinephrine binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in G protein-coupled dopamine receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	IBA Inferred from Biological aspect of Ancestor more info
involved_in adenylate cyclase-inhibiting dopamine receptor signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within adenylate cyclase-inhibiting dopamine receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in adenylate cyclase-inhibiting dopamine receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in adenylate cyclase-inhibiting dopamine receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in adenylate cyclase-modulating G protein-coupled receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in adult locomotory behavior	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within adult locomotory behavior	ISO Inferred from Sequence Orthology more info
involved_in arachidonate secretion	IEA Inferred from Electronic Annotation more info
involved_in arachidonate secretion	ISO Inferred from Sequence Orthology more info
involved_in associative learning	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in behavioral fear response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in behavioral response to cocaine	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within behavioral response to cocaine	ISO Inferred from Sequence Orthology more info
involved_in chemical synaptic transmission	IBA Inferred from Biological aspect of Ancestor more info
involved_in circadian rhythm	IEP Inferred from Expression Pattern more info	PubMed
involved_in fear response	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within fear response	ISO Inferred from Sequence Orthology more info
involved_in inhibitory postsynaptic potential	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within inhibitory postsynaptic potential	ISO Inferred from Sequence Orthology more info
involved_in intracellular calcium ion homeostasis	IEA Inferred from Electronic Annotation more info
involved_in intracellular calcium ion homeostasis	ISO Inferred from Sequence Orthology more info
involved_in modulation of inhibitory postsynaptic potential	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of protein secretion	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of protein secretion	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of synaptic transmission	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of synaptic transmission, GABAergic	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of vascular associated smooth muscle cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of vascular associated smooth muscle cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in olfactory learning	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in phospholipase C-activating dopamine receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in phospholipase C-activating dopamine receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in photoperiodism	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of positive regulation of MAP kinase activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of excitatory postsynaptic potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of penile erection	IDA Inferred from Direct Assay more info	PubMed
involved_in prepulse inhibition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in presynaptic modulation of chemical synaptic transmission	EXP Inferred from Experiment more info	PubMed
involved_in presynaptic modulation of chemical synaptic transmission	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of calcium-mediated signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of circadian rhythm	IEA Inferred from Electronic Annotation more info
involved_in regulation of circadian rhythm	ISO Inferred from Sequence Orthology more info
involved_in regulation of circadian rhythm	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of dopamine metabolic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of dopamine metabolic process	ISO Inferred from Sequence Orthology more info
involved_in regulation of locomotion	IEA Inferred from Electronic Annotation more info
involved_in regulation of neurotransmitter secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of postsynaptic membrane neurotransmitter receptor levels	EXP Inferred from Experiment more info	PubMed
involved_in regulation of postsynaptic membrane neurotransmitter receptor levels	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of postsynaptic membrane neurotransmitter receptor levels	IEP Inferred from Expression Pattern more info	PubMed
involved_in regulation of postsynaptic neurotransmitter receptor internalization	IEA Inferred from Electronic Annotation more info
involved_in regulation of postsynaptic neurotransmitter receptor internalization	ISO Inferred from Sequence Orthology more info
involved_in regulation of protein kinase A signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in response to amphetamine	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within response to amphetamine	ISO Inferred from Sequence Orthology more info
involved_in response to epinephrine	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to ethanol	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to histamine	IEA Inferred from Electronic Annotation more info
involved_in response to histamine	ISO Inferred from Sequence Orthology more info
involved_in response to light stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to steroid hormone	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to thyroid hormone	IEP Inferred from Expression Pattern more info	PubMed
involved_in retina development in camera-type eye	IEP Inferred from Expression Pattern more info	PubMed
involved_in short-term memory	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in synaptic transmission, dopaminergic	IEA Inferred from Electronic Annotation more info
involved_in synaptic transmission, dopaminergic	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in GABA-ergic synapse	EXP Inferred from Experiment more info	PubMed
is_active_in GABA-ergic synapse	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in axon	IDA Inferred from Direct Assay more info	PubMed
located_in axon terminus	IDA Inferred from Direct Assay more info	PubMed
located_in cell cortex	IDA Inferred from Direct Assay more info	PubMed
located_in centrosome	IEA Inferred from Electronic Annotation more info
located_in centrosome	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in dendrite	IBA Inferred from Biological aspect of Ancestor more info
located_in dendrite	IDA Inferred from Direct Assay more info	PubMed
located_in dendrite terminus	IDA Inferred from Direct Assay more info	PubMed
located_in dendritic microtubule	IDA Inferred from Direct Assay more info	PubMed
located_in dendritic shaft	IDA Inferred from Direct Assay more info	PubMed
located_in dendritic spine	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	EXP Inferred from Experiment more info	PubMed
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
is_active_in glutamatergic synapse	ISO Inferred from Sequence Orthology more info
located_in membrane	ISO Inferred from Sequence Orthology more info
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in neuronal cell body	IDA Inferred from Direct Assay more info	PubMed
located_in perikaryon	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in postsynapse	IEA Inferred from Electronic Annotation more info
is_active_in postsynaptic membrane	IDA Inferred from Direct Assay more info	PubMed
located_in presynapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in presynaptic membrane	IDA Inferred from Direct Assay more info	PubMed
located_in synapse	IDA Inferred from Direct Assay more info	PubMed
located_in terminal bouton	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: D(4) dopamine receptor

Names: d(2C) dopamine receptor; dopamine D4 receptor; dopamine receptor 4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_012944.2 → NP_037076.2 D(4) dopamine receptor

See identical proteins and their annotated locations for NP_037076.2

Status: VALIDATED

Source sequence(s)

JAXUCZ010000001

UniProtKB/Swiss-Prot

P30729, Q62610

UniProtKB/TrEMBL

A6HXT7, F1LLX2

Conserved Domains (1) summary

pfam00001
Location:50 → 368

7tm_1; 7 transmembrane receptor (rhodopsin family)

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCr8

Genomic

NC_086019.1 Reference GRCr8

Range

205825937..205829124

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006230521.4 → XP_006230583.1 D(4) dopamine receptor isoform X1

UniProtKB/Swiss-Prot

P30729, Q62610

Related

ENSRNOP00000024137.4, ENSRNOT00000024137.6

Conserved Domains (1) summary

pfam00001
Location:50 → 370

7tm_1; 7 transmembrane receptor (rhodopsin family)