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FLASH GENE
Symbol DRD4 contributors: mct/npt - updated : 06-02-2018
HGNC name dopamine receptor D4
HGNC id 3025
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