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FLASH GENE
Symbol INPP4B contributors: mct - updated : 14-04-2017
HGNC name inositol polyphosphate-4-phosphatase, type II, 105kDa
HGNC id 6075
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • phosphatase domains are located within the C-terminus, with mostly alpha-helices
  • a CX5R (active site consensus sequence Cys-Xaa5-Arg) catalytic motif characteristic of dual-specificity phosphatases, such as PTEN
  • different AAs within the catalytic site of INPP4B are responsible for activity with lipid and protein substrates and for substrate specificity
    • HOMOLOGY
    interspecies ortholog to murine Inpp4b alpha
    homolog to rattus Inpp4b
    Homologene
    FAMILY
  • inositol-3,4-bisphosphate 4-phosphatase family
    • CATEGORY enzyme , tumor suppressor , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • removing the phosphate group at position 4 of the inositol ring from inositol 3,4-bisphosphate, 1,3,4-trisphosphate and phosphatidylinositol 3,4-bisphosphate
  • has potentially protein tyrosine phosphatase (PTP) activity 2)
  • major modulator of the osteoclast differentiation and as a gene linked to variability of bone mineral density
  • negative modulator of osteoclast differentiation
  • is an important regulator of phosphatidyl-inositol signaling in the cell
  • both PTEN and INPP4B are dual specificity phosphatases and tumor suppressors
  • regulates PI3K/Akt signaling and exerts a tumor suppressor effect, impacting the proliferative, invasive, and tumorigenic capacity of melanoma cells
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism lipid/lipoprotein
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • PTEN, INPP5J and INPP4B distinctly regulate PtdIns(3,4,5)P3 signalling downstream of PI3K and dysregulation of these phosphatases affects cancer outcomes
  • IRF2 binds INPP4B promoter and promotes INPP4B expression in Acute myeloid leukemia (AML) cells
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    associated with poor outcomes for breast, prostate, and ovarian cancer
    tumoral     --low  
    hyperactivation of the PI3K/AKT pathway caused by the decrease in INPP4B in granulosa cells promotes an ovarian environment defective in folliculogenesis and conducive to teratoma formation
    tumoral   LOH    
    in a majority of basal-like breast cancers, as well as in a significant fraction of ovarian cancers, which correlated with lower overall patient survival
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker prognostic locus for human osteoporosis
    Therapy target
    ANIMAL & CELL MODELS