Drd4 dopamine receptor D4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Drd4provided by MGI
Official Full Name: dopamine receptor D4provided by MGI
Primary source: MGI:MGI:94926
See related: Ensembl:ENSMUSG00000025496 AllianceGenome:MGI:94926
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: D4R; Drd-4
Summary: Enables dopamine neurotransmitter receptor activity, coupled via Gi/Go. Involved in regulation of circadian rhythm and regulation of postsynaptic neurotransmitter receptor internalization. Acts upstream of or within several processes, including adenylate cyclase-inhibiting dopamine receptor signaling pathway; behavioral response to cocaine; and inhibitory postsynaptic potential. Is active in glutamatergic synapse. Is expressed in several structures, including alimentary system; central nervous system; genitourinary system; hemolymphoid system gland; and integumental system. 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 ovary adult (RPKM 6.8), testis adult (RPKM 3.5) and 4 other tissues See more
Orthologs: human all
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Genomic context

Location:: 7 F5; 7 86.6 cM

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	7	NC_000073.7 (140871931..140874868)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	7	NC_000073.6 (141291974..141296464)

Chromosome 7 - NC_000073.7 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: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Dopamine receptor D4 (DRD4) negatively regulates UCP1- and ATP-dependent thermogenesis in 3T3-L1 adipocytes and C2C12 muscle cells.
Title: Dopamine receptor D4 (DRD4) negatively regulates UCP1- and ATP-dependent thermogenesis in 3T3-L1 adipocytes and C2C12 muscle cells.
DRD4 (Dopamine D4 Receptor) Mitigate Abdominal Aortic Aneurysm via Decreasing P38 MAPK (mitogen-activated protein kinase)/NOX4 (NADPH Oxidase 4) Axis-Associated Oxidative Stress.
Title: DRD4 (Dopamine D4 Receptor) Mitigate Abdominal Aortic Aneurysm via Decreasing P38 MAPK (mitogen-activated protein kinase)/NOX4 (NADPH Oxidase 4) Axis-Associated Oxidative Stress.
Maternal care of heterozygous dopamine receptor D4 knockout mice: Differential susceptibility to early-life rearing conditions.
Title: Maternal care of heterozygous dopamine receptor D4 knockout mice: Differential susceptibility to early-life rearing conditions.
Our structure reveals a secondary binding pocket extended from the orthosteric ligand-binding pocket to a DRD4-specific crevice located between transmembrane helices 2 and 3. Additional mutagenesis studies suggest that the antagonist L745870 prevents DRD4 activation by blocking the relative movement between transmembrane helices 2 and 3
Title: Crystal structure of dopamine receptor D4 bound to the subtype selective ligand, L745870.
Male DRD4 KO mice failed to reinstate their preference after a priming dose following successful extinction. No differences in locomotor activity were observed within drug treatment conditions due to genotype, and female mice displayed reduced locomotor activity during CPP conditioning compared to male mice.
Title: Dopamine D4 receptor gene expression plays important role in extinction and reinstatement of cocaine-seeking behavior in mice.
data imply that enhanced D4 receptor-mediated dopaminergic control of corticostriatal transmission constitutes a vulnerability factor of ADHD and other neuropsychiatric disorders.
Title: Key role of the dopamine D(4) receptor in the modulation of corticostriatal glutamatergic neurotransmission.
Results indicate that the full rescue of impaired LTP in aging is achieved by the selective D4R activation.
Title: Dopamine D4 receptor activation restores CA1 LTP in hippocampal slices from aged mice.
over-suppression of NMDAR function may underlie the role of hD4.7 in attention deficit hyperactivity disorder
Title: The ADHD-linked human dopamine D4 receptor variant D4.7 induces over-suppression of NMDA receptor function in prefrontal cortex.
Synergistically acting agonists and antagonists of G protein-coupled receptors prevent photoreceptor cell degeneration
Title: Synergistically acting agonists and antagonists of G protein-coupled receptors prevent photoreceptor cell degeneration.
The G-protein coupled receptor, DRD4, requires ARR1 and ARR4 for desensitization and internalization.
Title: Dopamine receptor D4 internalization requires a beta-arrestin and a visual arrestin.

Submit: New GeneRIF Correction See all GeneRIFs (31)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (3)
Targeted (3) 1 citation

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

AW125663 (e-PCR)
- UniSTS:179672

Drd4 (e-PCR), detects polymorphism
- UniSTS:506861

Gene Ontology Provided by MGI

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	ISO Inferred from Sequence Orthology more info
enables dopamine binding	ISS Inferred from Sequence or Structural Similarity more info
enables dopamine neurotransmitter receptor activity	ISO Inferred from Sequence Orthology more info
enables dopamine neurotransmitter receptor activity, coupled via Gi/Go	IMP Inferred from Mutant Phenotype more info	PubMed
enables dopamine neurotransmitter receptor activity, coupled via Gi/Go	ISO Inferred from Sequence Orthology more info
enables dopamine neurotransmitter receptor activity, coupled via Gi/Go	ISS Inferred from Sequence or Structural Similarity 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	ISO Inferred from Sequence Orthology more info
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

Process	Evidence Code	Pubs
involved_in G protein-coupled dopamine receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within adenylate cyclase-inhibiting dopamine receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
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
acts_upstream_of_or_within adult locomotory behavior	IMP Inferred from Mutant Phenotype more info	PubMed
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	ISO Inferred from Sequence Orthology more info
involved_in behavioral fear response	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within behavioral response to cocaine	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in chemical synaptic transmission	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within fear response	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within inhibitory postsynaptic potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular calcium ion homeostasis	IEA Inferred from Electronic Annotation more info
involved_in modulation of inhibitory postsynaptic potential	ISO Inferred from Sequence Orthology more info
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	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of synaptic transmission, GABAergic	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of vascular associated smooth muscle cell migration	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of vascular associated smooth muscle cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of voltage-gated calcium channel activity	ISO Inferred from Sequence Orthology more info
involved_in olfactory learning	ISO Inferred from Sequence Orthology more info
involved_in phospholipase C-activating dopamine receptor signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of positive regulation of MAP kinase activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of MAP kinase activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of excitatory postsynaptic potential	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of kinase activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of penile erection	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of sodium:proton antiporter activity	ISO Inferred from Sequence Orthology more info
involved_in prepulse inhibition	ISO Inferred from Sequence Orthology more info
involved_in presynaptic modulation of chemical synaptic transmission	ISO Inferred from Sequence Orthology more info
involved_in regulation of calcium-mediated signaling	ISO Inferred from Sequence Orthology more info
involved_in regulation of circadian rhythm	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of dopamine metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of neurotransmitter secretion	ISO Inferred from Sequence Orthology more info
involved_in regulation of postsynaptic membrane neurotransmitter receptor levels	ISO Inferred from Sequence Orthology more info
involved_in regulation of postsynaptic neurotransmitter receptor internalization	EXP Inferred from Experiment more info	PubMed
involved_in regulation of postsynaptic neurotransmitter receptor internalization	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of postsynaptic neurotransmitter receptor internalization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of protein kinase A signaling	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within response to amphetamine	IMP Inferred from Mutant Phenotype 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 rhythmic process	IEA Inferred from Electronic Annotation more info
involved_in short-term memory	ISO Inferred from Sequence Orthology more info
involved_in synaptic transmission, dopaminergic	IEA Inferred from Electronic Annotation more info
involved_in synaptic transmission, dopaminergic	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
is_active_in GABA-ergic synapse	ISO Inferred from Sequence Orthology more info
located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
located_in axon	ISO Inferred from Sequence Orthology more info
located_in axon terminus	ISO Inferred from Sequence Orthology more info
located_in cell cortex	ISO Inferred from Sequence Orthology more info
located_in centrosome	IEA Inferred from Electronic Annotation more info
located_in centrosome	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytoplasmic side of plasma membrane	ISO Inferred from Sequence Orthology more info
is_active_in dendrite	IBA Inferred from Biological aspect of Ancestor more info
located_in dendrite	ISO Inferred from Sequence Orthology more info
located_in dendrite terminus	ISO Inferred from Sequence Orthology more info
located_in dendritic microtubule	ISO Inferred from Sequence Orthology more info
located_in dendritic shaft	ISO Inferred from Sequence Orthology more info
located_in dendritic spine	ISO Inferred from Sequence Orthology more info
located_in endoplasmic reticulum	ISO Inferred from Sequence Orthology more info
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
is_active_in glutamatergic synapse	IMP Inferred from Mutant Phenotype more info	PubMed
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	ISO Inferred from Sequence Orthology more info
located_in neuronal cell body	ISO Inferred from Sequence Orthology more info
located_in perikaryon	ISO Inferred from Sequence Orthology more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor 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	ISO Inferred from Sequence Orthology more info
located_in presynapse	ISO Inferred from Sequence Orthology more info
is_active_in presynaptic membrane	ISO Inferred from Sequence Orthology more info
located_in synapse	ISO Inferred from Sequence Orthology more info
located_in terminal bouton	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: D(4) dopamine receptor

Names: d(2C) dopamine 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_001412325.1 → NP_001399254.1 D(4) dopamine receptor isoform 2

Status: VALIDATED

Source sequence(s)

AC163434
NM_001412326.1 → NP_001399255.1 D(4) dopamine receptor isoform 3

Status: VALIDATED

Source sequence(s)

AC163434
NM_007878.4 → NP_031904.1 D(4) dopamine receptor isoform 1

See identical proteins and their annotated locations for NP_031904.1

Status: VALIDATED

Source sequence(s)

AC163434

Consensus CDS

CCDS22007.1

UniProtKB/Swiss-Prot

O35838, P51436, Q7TT80, Q8BXS4

Related

ENSMUSP00000026569.5, ENSMUST00000026569.6

Conserved Domains (1) summary

pfam00001
Location:48 → 368

7tm_1; 7 transmembrane receptor (rhodopsin family)