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FLASH GENE
Symbol DRD4 contributors: mct/npt - updated : 06-02-2018
HGNC name dopamine receptor D4
HGNC id 3025
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
4 - 1360 - 419 - 2017 29051383
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularvesselartery    Homo sapiens
Nervousbrain   moderately
Visualeye    
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectivebone   
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal
Text fetal eyes, lens, eye anterior segment, optic nerve, retina, retina foveal and macular, RPE and Choroid
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • seven transmembrane segments (7TM) receptor
  • HOMOLOGY
    Homologene
    FAMILY
  • G-protein coupled receptor 1 family
  • D2-like receptor family
  • CATEGORY receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • dopamine receptor D4, with high affinity for antagonist clozapine
  • stimulating the DRD4 is likely essential in maintaining the normal rhythmic production of ADCY1 from transcript to enzyme activity
  • putative involvement of SLC6A3 and DRD4 genes in the aetiology of ADHD with a main role in modulation of key dimensions of the disorder
  • regulatory role of DRD4 on AGTR1 expression and function in in the vascular smooth muscle cell (VSMC)
  • plays an essential role in cAMP regulation and gap junctional coupling in the photoreceptors, where DRD4 expression is under circadian control
  • DRD4, requires two arrestins for desensitization and internalization, and opens up the possibility that other G-protein coupled receptors may require more than one arrestin for desensitization and/or internalization
  • DRD4 is a moderator of childrearing effects on the development of disorganized attachment
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling neurotransmission
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • KLHL12 is a novel interaction partner of the DRD4 that functions as an adaptor in a CUL3-based E3 ubiquitin ligase complex to target the receptor for ubiquitination
  • inhibit proliferation and migration of vascular smooth muscle cells induced by insulin via down-regulation of insulin receptor expression
  • KLHL12, a BTB-Kelch protein, specifically interacts with the polymorphic repeats of the DRD4 and enhances its ubiquitination, which, however, has no influence on receptor degradation
  • KLHL12 strongly promotes ubiquitination of the two- and four-repeat variant but has hardly any effect on ubiquitination of the seven-repeat DRD4
  • ARRB1, ARRB2 bind constitutively to the most common DRD4 polymorphic variants and to KLHL12 and all three proteins can interact within a single macromolecular complex
  • cell & other
    REGULATION
    Other palmitoylation of the C-terminal tail of DRD4 is required for surface expression, endocytosis, and signaling
    ASSOCIATED DISORDERS
    corresponding disease(s) PTNS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    by hypermethylation, DRD4 promoter methylation was significantly higher in AD patients than in controls
    Susceptibility
  • to Gilles de la Tourette syndrome and a wide range of neuropsychiatric disorders
  • to attention deficit hyperactivity disorder (ADHD), with preferential transmission of paternal alleles
  • to dyslexia (DYX7)
  • to migraine without aura
  • to attention-deficit/hyperactivity disorder (ADHD) related to oxidative stress
  • to schizophrenia
  • to age related changes in brain glucose metabolism
  • Variant & Polymorphism repeat , other
  • association with seven repeat allele (VNTR) in exon 3 in attention deficit hyperactivity syndrome
  • exon 3 VNTR allele protecting against migraine without aura (DeSousa 2007)
  • carriers of the 7R allele appear to be less sensitive to the effects of age on brain glucose metabolism
  • male-specific association between DRD4 gene methylation and schizophrenia
  • DRD4 GG genotype, that had been exposed to high DMP levels (more than the median), and had high HNE-MA levels had a significantly increased risk for developing ADHD
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularaquired 
    may be a potential therapeutic target to reduce the effects of insulin on artery remodeling
    ANIMAL & CELL MODELS
  • Drd4 knock-out mice, when compared with wild-type and heterozygous mice, displayed a 7-9.7p100 decrease in lifespan, reduced spontaneous locomotor activity, and no lifespan increase when reared in an enriched environment
  • expression of the gene Adcy1, is downregulated in mice lacking Drd4