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FLASH GENE
Symbol INPP5K contributors: mct/npt - updated : 13-04-2017
HGNC name inositol polyphosphate-5-phosphatase K
HGNC id 33882
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a 5-phosphatase domain with two highly conserved catalytic motifs
  • C-terminal SKICH motif linked to targeting of INPP5K to the ER membrane
  • HOMOLOGY
    Homologene
    FAMILY
  • inositol-1,4,5-trisphosphate 5- phosphatase type II family
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,lumen
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    text
  • primarily localized to the ER, and it can form a complex with HSPA to regulate insulin receptor signaling at actin ruffles on the plasma membrane by acting as a negative regulator of phosphatidylinositol-3-kinase (PI3K) signaling
  • basic FUNCTION
  • playing a negative role in regulating the actin cytoskeleton through hydrolyzing phosphatidyl inositol 4-5 biphosphate
  • hydrolyzes phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] to downregulate intracellular levels
  • preferentially regulates glucose transport and actin cytoskeletal rearrangement among a variety of PI(3,4,5)P3 downstream events
  • with INPP5D and INPP5E, implicated in negatively regulating insulin signalling and glucose homoeostasis in specific tissues (Ooms 2009)
  • INPPK5 and INPPL1, inhibit actin cytoskeletal reorganization by opposing PI3K/Akt signaling
  • is important for the control of the arginine vasopressin/aquaporin-2 signalling pathway and water transport in kidney collecting ducts
  • specific and prominent role of INPP5K in the regulation of insulin signaling
  • regulates MYOD1-mediated muscle differentiation
  • physiological role of PAK1-INPP5K binding in the regulation of insulin signaling in skeletal muscle
  • tumor suppressor activity of INPP5K and MYO1C, with overlapping roles in phosphoinositide (PI) 3-kinase/Akt signaling, known to be vital for the cell growth and survival
  • implicated in the regulation of insulin signaling in skeletal muscle
  • is essential for skeletal muscle structure and function
  • CELLULAR PROCESS cell organization/biogenesis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • BAG4 forms a complex with several 5-ptase family members, including INPPL1, INPP5D, INPP5K
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • PABPN1 for the control of muscle specific genes
  • markedly inhibited SLC2A4 translocation and membrane ruffle formation
  • interact with HSPA5, a master regulator of ER functions including the ER stress response
  • interacts with PAK1 and glucose-regulated protein 78 (HSPA5), both of which are necessary for the regulation of insulin signaling
  • could alter dystroglycan targeting by altering HSPA5 function
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) MDCCAID
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Inpp5k transgenic mice present defects in water metabolism characterized by a reduced plasma osmolality at baseline, a delayed urinary water excretion following a water load, and an increased acute response to vasopressin