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FLASH GENE
Symbol GRK6 contributors: mct - updated : 01-04-2011
HGNC name G protein-coupled receptor kinase 6
HGNC id 4545
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • putative phospholipid-binding site near the N terminus and structural elements within the kinase substrate channel that likely influence G protein-coupled receptor access and specificity
  • functionally important sites in the regulator of G-protein signaling homology domain
  • seven transmembrane domain
  • conserved DLG (asp-leu-gly) and ENIL (glu-asn-ile-leu) motifs
  • C-terminal structure would place the palmitoylation sites of GRK6 (which are not conserved among GRKs) relatively far from the predicted membrane plane and GRK6 C-terminus has a function in stabilizing the closed, receptor-bound state of GRK6
    • conjugated LipoP
    HOMOLOGY
    interspecies ortholog to murine Gprk6
    Homologene
    FAMILY
  • Ser/Thr protein kinase family
  • GRK4 subfamily
    • CATEGORY receptor membrane G kinase
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text changes in palmitoylation can regulate Plasma membrane versus cytoplasmic/nuclear localization
    basic FUNCTION
  • mediating phosphatidylinositol 4,5-biphosphate (PIP2) dependent phosphorylation of beta adrenergic receptor 1
  • key regulator of dopaminergic signaling and lymphocyte chemotaxis
  • involved in the regulation of oxytocin receptor responsiveness in human myometrial smooth muscle
  • may play a role in regulating some, but not all morphine-mediated responses
  • GRK5/6 is a novel kinases for the single transmembrane receptor LRP6 during Wnt signaling
  • exhibits lymphoid-restricted expression, and its expression in myeloma cells is regulated via direct association with the heat shock protein 90 (HSP90) chaperone
  • potent mechanism for the cytotoxicity of GRK6 inhibition in multiple myeloma (MM) tumor cells
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    ATP
    protein
    cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    inhibition of GRK6 represents a uniquely targeted novel therapeutic strategy in multiple myeloma
    ANIMAL & CELL MODELS