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Symbol GRK5 contributors: mct/npt - updated : 03-05-2016
HGNC name G protein-coupled receptor kinase 5
HGNC id 4544
Location 10q26.11      Physical location : 120.967.196 - 121.215.130
Synonym name
  • FP2025
  • Synonym symbol(s) GPRK5
    TYPE functioning gene
    STRUCTURE 247.93 kb     16 Exon(s)
    MAPPING cloned Y linked N status provisional
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 - 2575 67.8 590 - 2000 10861009
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly Homo sapiens
    Lymphoid/Immunespleen   highly
    Nervousbrainbasal nucleistriatum highly Homo sapiens
    Reproductivefemale systemplacenta  highly
     male systemprostate   
    Respiratorylung   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Connectiveadiposewhite highly Homo sapiens
    cell lineage
    cell lines
    at STAGE
    physiological period pregnancy
    Text placenta
  • two distinct calmodulin-binding sites, localized to the N and C terminal regulatory regions, and DNA-binding ability of GRK5 requires both the NLS and an N-terminal calmodulin (CaM)-binding site
  • N-terminal region of GRK5 contains also a short alpha-helical region that regulates receptor phosphorylation followed by a regulator of G protein signaling homology (RH) domain, with functionally important sites in the regulator of G-protein signaling homology domain
  • a RGS domain of G protein-coupled receptor kinase 5 (GRK5) regulating plasma membrane localization and function
  • the latter involved in GRK5-calmodulin interaction
  • G protein coupled receptor family
  • CATEGORY enzyme , receptor membrane G
        plasma membrane
  • co-localizes with TUBG1, centrin, and pericentrin in centrosomes, predominantly at interphase
  • unphosphorylated enzyme preferentially localizes to synaptic membranes, whereas phosphorylated GRK5 is found in plasma membrane and cytosolic fractions
  • ADRBK1, GRK5 are abundant in the nucleus of human striatal neurons (
  • basic FUNCTION
  • mediating phosphatidylinositol 4,5-biphosphate (PIP2) dependent phosphorylation of beta adrenergic receptor 1
  • inhibition of thrombin-activated phosphoinositide hydrolysis in endothelial cells
  • nuclear HDAC kinase that plays a key role in maladaptive cardiac hypertrophy apparently independent of any action directly on GPCRs
  • GRK5/6 is a novel kinases for the single transmembrane receptor LRP6 during Wnt signaling
  • role in the regulation of G-protein coupled receptor signaling
  • positive regulator of TLR4-induced NFKBIA-NFKB pathway as well as a key modulator of LPS-induced inflammatory response
  • critically involved in neurite outgrowth, dendrite branching, and spine morphogenesis through promotion of filopodial protrusion
  • separate domains of GRK5 mediated the coupling of actin cytoskeleton dynamics and membrane remodeling and were required for its effects on neuronal morphogenesis
  • crucial for proper neuronal morphogenesis and the establishment of functional neuronal circuitry
  • NFKB regulator in TLR4 signaling pathway
  • having multiple roles in TLR signaling
  • although its localization is not dependent on microtubules, it can mediate microtubule nucleation of centrosomes
  • regulates microtubule nucleation and normal cell cycle progression
  • plays a key role in cardiac signaling regulation, and its expression is increased in heart failure
  • phosphorylates Ser-4 in nucleophosmin and regulates the sensitivity of cells to PLK1 inhibition
  • is an important regulator of adipogenesis and is crucial for the development of diet-induced obesity
  • is critically involved in the regulation of lipid homeostasis in white adipose tissue
  • ADRBK1 and GRK5 control cardiac function as well as morphogenesis during development although with different morphological outcomes
  • GRK5-mediated pathological cardiac hypertrophy involves the activation of NFATC1 because GRK5 causes enhancement of NFATC1-mediated hypertrophic gene transcription
  • acting in a kinase independent manner, is a facilitator of NFATC1 activity and part of a DNA-binding complex responsible for pathological hypertrophic gene transcription
  • GRK5 plays an important functional role in negatively regulating thrombin-induced platelet reactivity
    a component
  • GRK5 dimerization is important for its plasma membrane localization and function
    small molecule
  • calmodulin binding
  • phosphorylates TP53 at Thr-55, which promotes the degradation of TP53, leading to inhibition of TP53-dependent apoptotic response to genotoxic damage
  • RARRES1 upregulating GRK5 expression
  • bound to and phosphorylated ST13 on Ser-346 in cells
  • interaction with NFKB (NFKB plays a critical role in the regulation of GRK5 transcription in myocytes and this may translate to the significant expression changes seen in heart disease)
  • is able to interact with and phosphorylate nucleophosmin (NPM1) both in vitro and in intact cells
  • phosphorylates Ser-4 in nucleophosmin and regulates the sensitivity of cells to PLK1 inhibition
  • GRK5 and NPM1 interact directly, suggesting that the N-terminal RH domain of GRK5 interacts with the oligomerization domain of NPM1
  • GRK5 phosphorylates and promotes the nuclear export of the histone deacetylase, HDAC5
  • regulation of NFKB1 in the nucleus of cardiomyocytes by G protein-coupled receptor kinase 5 (GRK5)
  • ADRBK1 phosphorylates NTSR1 only the C-terminal Ser residues, whereas GRK5 phosphorylates Ser and Thr residues located in intracellular loop 3 and the C-terminus
  • cell & other
    inhibited by TLR4 in response to MIP2
    Other regulated by molecules that would be expected to be present in Gq-signaling cascades
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in the dysfunctional heart, and in failing myocardium may have unique significance due to its nuclear localization
    constitutional       loss of function
    deficiency linked to early Alzheimer disease (AD) (Liu 2009)
    constitutional     --low  
    impairs presynaptic M2 autoreceptor desensitization, which leads to a reduced acetylcholine release, axonal/synaptic degenerative changes, and associated amnestic, mild cognitive impairment
    constitutional     --over  
    in heart failure (HF)
  • to heart failure
  • to cardiovascular and cerebrovascular disease
  • Variant & Polymorphism other
  • polymorphism that inhibits ADRB1 signaling is protective in heart failure
  • rs10886430 variant regulates platelet cell traits and GRK5 platelet gene expression, as well as both cardiovascular and cerebrovascular disease pathologies
  • Candidate gene
    Therapy target
    finding a mechanism to maintain GRK5 activity in platelets could prove beneficial in preventing venous and arterial cardiovascular disease (CVD)
  • Grk5 deficiency in mouse leads to susceptibility to intermittent hypoxia-induced cognitive impairment
  • when fed on a high-fat diet, GRK5(-/-) mice gained significantly less weight and had decreased WAT mass than their wild type littermates, which could not be attributed to alterations in food consumption or energy expenditure