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FLASH GENE
Symbol PLEKHO1 contributors: mct - updated : 26-06-2015
HGNC name pleckstrin homology domain containing, family O member 1
HGNC id 24310
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminal PH domain required for association with CARD11 and its inhibitory effect
  • putative C-terminal JUN leucine zipper interactive domain
  • conjugated PhosphoP
    mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies homolog to murine Plekho1 (91.4pc)
    homolog to rattus Plekho1 (89.5pc)
    Homologene
    FAMILY
  • pleckstrin-like family
  • CATEGORY regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    text
  • coexpressed with CSNK2A1
  • N-terminal PH domain and C-terminal autoinhibitory region coordinate to determine its nucleus-plasma membrane shuttling (Xi 2010)
  • nucleus/plasma membrane shuttle of PLEKHO1 is regulated by different cell stresses
  • basic FUNCTION
  • playing a role in the regulation of the actin cytoskeleton through its interactions with actin capping protein
  • involved in apoptosis
  • may function to target CK2 to the plasma membrane thereby serving as an adapter to facilitate the phosphorylation of CP by CK2
  • targeting ATM to the plasma membrane
  • inhibiting tumor cell growth by inhibiting AKT-mediated cell-survival (Tokuda 2007, Zhang 2007)
  • involved in PI3K-regulated muscle differentiation, regulation of AP-1 activity and the promotion of apoptosis induced by TNF
  • role of PLEKHO1 in cytokine signaling response and modulators IFI35 and NMI are involved via interactions
  • with CK2, inhibits the activity of actin capping protein at the barbed ends of actin filaments
  • functioning as an auxiliary factor to enhance the activation of SMURF1 (Lu 2008)
  • is a regulator of cortical actin that recruits the Arp2/3 complex at the plasma membrane essential for muscle precursor elongation and fusion (PMID;
  • functions through different ways, such as plasma membrane recruitment, transcriptional activity modulation and posttranscriptional modification regulation
  • might also function as a potential tumor suppressor
  • is a novel regulator of macrophage migration
  • is crucial during adult bone formation
  • contributes maintenance of a resting state on NFKB1 activity or prevents T cells from being activated by inadequate signaling
  • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with casein kinase 2, alpha (CSNK2A1) (Bosc 2000)
  • interacting with ATM, IFP35, JUN, JUND, NMI, PI3K
  • interacting with AKT1, AKT2, AKT3 (Tokuda 2007)
  • IFI35 and its homologue NMI are two novel PLEKHO1 interacting partners
  • interacting with SMURF1 (Lu 2008)
  • is an activator of the SMURF1 ubiquitin ligase acting to promote the ubiquitylation of SMAD5 and MAP2K1
  • PLEKHO1 mediates the SMURF1-PSMC5 interaction and delivers the ubiquitylated substrates to the proteasome
  • growth-suppressive role of PLEKHO1 was dependent on the downregulation of the cell cycle-regulated oncogene SMURF1
  • PLEKHO1 interacts with CARD11 and has an inhibitory effect on PRKCQ-CBM-NFKB1 signaling
  • plays a critical role in the regulation of macrophage homeostasis by inhibiting TRAF6-mediated AKT1 activation
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    osteoarticularbone 
    is a promising drug target for osteoporosis therapy
    ANIMAL & CELL MODELS
  • Ckip1(-/-) mice spontaneously develop a macrophage-dominated splenomegaly and myeloproliferation