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FLASH GENE
Symbol INPP5J contributors: mct/pgu - updated : 05-05-2020
HGNC name inositol polyphosphate-5-phosphatase J
HGNC id 8956
DNA
TYPE functioning gene
STRUCTURE 26.96 kb     13 Exon(s)
MAPPING cloned Y linked   status provisional
Map cen - NF2 NF2 - MTMR3 - TCN2 TCN2 - SMN1 /PIB5PA /LIMK2 - DRG1 - D22S275 /D22S1176 - ADTB1L1 - D22S1175 - YWHAH /SLC5A1 - RFPL3 - SYN3 /TIMP3 - qter
RNA
TRANSCRIPTS type messenger
text
  • exists under different isoforms which are characterized by phosphorylation at distinct positions of the inositol ring (PMID: 22728883)
    • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 - 2238 - 638 - 2014 25099196
    14 - 3529 - 939 - 2014 25099196
    15 - 2603 - 639 - 2014 25099196
    14 - 2481 - 639 - 2014 25099196
    12 - 2323 - 571 - 2014 25099196
    13 - 3348 - 1006 - 2014 25099196
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
    Endocrineparathyroid   highly
     thyroid   highly
    Nervousbrain   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two distinct regions, an anionic head group and a pair of fatty acid tails
  • SKICH domain mediating plasma membrane ruffle localization
  • binds at an interface between the transmembrane domain (TMD) and the cytoplasmic domain (CTD), and this binding site consists of a conserved non-specific phospholipid-binding region in the TMD and a specific phosphatidylinositol-binding region in the CTD
  • C-terminal growth cone-targeting domain
    • HOMOLOGY
    Homologene
    FAMILY
  • inositol-1,4,5-trisphosphate 5- phosphatase type II family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    text
  • localized at the inner leaflet of the plasma membrane
    • basic FUNCTION
  • regulator of phosphoinositide 3-kinase-dependent neurite elongation
  • INPP5J and DPYSL2 exert opposing roles in promoting axon selection and neurite elongation and the complex between these proteins serves to regulate the localization of effectors that promote neurite extension
  • negative regulator of PI3K/Akt signaling
  • can control the resting membrane potential through a specific ion-channel-receptor-ligand interaction that brings about a large conformational change, analogous to neurotransmitter activation of ion channels at synapses
  • a key signalling molecule that regulates dendritic outgrowth through activation of small GTPase signalling via interaction between FRMPD4 and ARHGEF7
  • is not involved in the regulation of KCNT1, KCNT2 by cell volume
  • role of INPP5J in regulating EHD2 plasma membrane localization
  • is a suppressor of oncogenic PI3K/AKT signaling in breast cancer
  • minor phospholipid component of cell membranes, having previously been shown to directly bind TRP channels and to play a unique role in modulating receptor function
  • putative tumour suppressor in melanoma and breast cancer
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component DPYSL22·INPP5J complex is likely to dynamically regulate both neurite outgrowth and axon polarity in the normal brain
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • tonically associated with TRPV1 (is now believed to be a TRPV1 agonist, potentiating activation by chemical and thermal stimuli)
  • ABCC8 controls KCNJ11 gating by modulating KCNJ11 interactions with INPP5J
  • interacting with DPYSL2 (its C-terminal growth cone-targeting domain facilitates its interaction with DPYSL2)
  • association between INPP5J and DPYSL2 does not require DPYSL2 phosphorylation, rather this complex significantly reduces when GSK3B is active, conditions under which PI3K/Akt signaling is not activated
  • is in addition a novel regulator of the activity of KCNT1 and KCNT2 channels
  • BASP1 myristoylation and association with INPP5J are required for the interaction of BASP1 with HDAC1, which mediates the recruitment of HDAC1 to the promoter and elicits transcriptional repression
  • feedback mechanism that replenishes Plasma membrane (PM) INPP5J during receptor-induced Ca(2+) signaling via the Ca(2+) effector ESYT1 and the PITPNM1 at ER-PM junctions
  • INPP5J-binding alters VCL structure to direct higher-order oligomerization and suggests that INPP5J and F-actin binding to VCL are mutually permissive
  • S100A1 competes with CALM1 and INPP5J for binding site on the C-terminus of the TPRV1 receptor
  • PLCB3, INPP5J interact with N-terminus region of TRPM4 channel
  • binding of INPP5J at the N-terminus of the TRPM1 receptor
  • PTEN, INPP5J and INPP4B distinctly regulate PtdIns(3,4,5)P3 signalling downstream of PI3K and dysregulation of these phosphatases affects cancer outcomes
  • KCNQ1/KCNE1 channel does not require INPP5J or PI(4)P for anterograde trafficking, but is heavily reliant on INPP5J for channel function once at the plasma membrane (PM)
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    accelerates oncogene-driven breast cancer tumor growth, but paradoxically reduces metastasis by regulating AKT1-dependent tumor cell migration
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS