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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
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly
Digestiveliver   lowly
Endocrinepancreas   lowly
Nervousbrain   moderately
Reproductivefemale systemplacenta  moderately
Respiratorylung   moderately
Urinarykidney   lowly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectivebone  highly
Muscularstriatumskeletal highly
cell lineage
cell lines MOLT-4, HEK293, Jurkat cancer cell lines
fluid/secretion
at STAGE
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