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FLASH GENE
Symbol GRK4 contributors: mct/npt - updated : 10-11-2014
HGNC name G protein-coupled receptor kinase 4
HGNC id 4543
Location 4p16.3      Physical location : 2.965.342 - 3.042.474
Synonym name
  • DNA segment,single copy,probes bj56,p363 (IT11)
  • G protein-coupled receptor kinase 2-like (Drosophila)
  • G protein-coupled receptor kinase GRK4
  • Synonym symbol(s) D4S127E, GPRKL2, IT11, GPRK2L, GPRK4, ITI1
    EC.number 2.7.11.16
    DNA
    TYPE functioning gene
    STRUCTURE 77.13 kb     16 Exon(s)
    regulatory sequence Promoter
    text structure core promoter resides in the first 1851 bp upstream of its transcription start site (Hasenkamp 2008)
    MAPPING cloned Y linked Y status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 splicing 2321 66.5 578 - Sallese, Premont, Hasenkamp (2008), Villar (2009)
  • also called GPRK4 alpha
  • phosphorylates the D3 receptor and is crucial for its signaling in proximal tubule cells
  • 5 splicing 2225 62.9 546 testis Sallese, Premont, Hasenkamp (2008)
  • also called GPRK4 beta
  • lacking exon 2
  • 15 splicing 2183 61.2 532 brain Sallese, Premont, Hasenkamp (2008), Villar (2009)
  • also called GPRK4 gamma
  • lacking exon 14
  • variation in GRK4gamma associated with HTA
  • preferentially interacts with inactive Galpha(s) and Gbeta to a greater extent than active Galpha(s) (Keever 2008)
  • phosphorylates the D3 receptor and is crucial for its signaling in proximal tubule cells
  • - splicing 1730 57.6 500 testis Sallese, Premont
  • also called GPRK4 delta
  • lacking exon 2, 14
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvesselaorta  highly Homo sapiens
    Nervousnervecranial nerve  highly
    Reproductivemale systemtestis  highly
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularsmoothvessel   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticneutrophil
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a RGS domain
  • a protein kinase domain
  • HOMOLOGY
    interspecies homolog to Drosophila G protein coupled receptor kinase 2
    ortholog to murine Gprk2l
    Homologene
    FAMILY
  • G protein coupled receptor family
  • Ser/Thr family of protein kinases
  • GPRK subfamily
  • CATEGORY enzyme , receptor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    text
  • associate with the cell membrane through palmitoylation of the cysteine residue at its C terminus
  • both DRD3 and GRK4 co-localize in lipid rafts of human renal proximal tubule cells (Villar 2009)
  • basic FUNCTION
  • inhibiting the dopamine receptor D1 (DRD1) from increasing sodium excretion
  • mediating the pressure and natriuresis relation
  • involved in renal sodium handling and blood pressure regulation (Hasenkamp 2008)
  • required for DRD3-mediated mitogenesis and activation of the MAP kinase pathway inrenal proximal tubule cells (Villar 2009)
  • via regulation of arterial AGTR1 expression and function, participates in the pathogenesis of conduit vessel abnormalities in hypertension
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interaction between DRD3 and GRK4 (Villar 2009)
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility to essential hypertension
    Variant & Polymorphism other
  • variant in isoform GRK4 gamma associated with essential hypertension
  • 65L allele is associated with stress-induced urinary sodium excretion reduction, suggesting impaired sodium handling in black normotensive adolescents
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS