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FLASH GENE
Symbol INPP5D contributors: mct/npt - updated : 16-02-2016
HGNC name inositol polyphosphate-5-phosphatase, 145kDa
HGNC id 6079
Location 2q37.1      Physical location : 233.925.035 - 234.116.548
Synonym name
  • SH2 containing inositol phosphatase
  • signaling inositol polyphosphate 5 phosphatase SIP-145
  • Synonym symbol(s) SHIP, SHIP1, hp51CN, SIP-145, MGC104855, MGC142140, MGC142142, p150Ship
    EC.number 3.1.3.56, 3.1.3.n1
    DNA
    TYPE functioning gene
    STRUCTURE 147.94 kb     27 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    ALPP 2q37.1 alkaline phosphatase, placental (Regan isozyme) ALPPL2 2q37 alkaline phosphatase, placental-like 2 LOC391492 2 similar to xce ALPI 2q37.1 alkaline phosphatase, intestinal ECEL1 2q36-q37 endothelin converting enzyme-like 1 LOC389083 2 similar to enterokinase CHRND 2q37 cholinergic receptor, nicotinic, delta polypeptide CHRNG 2q37.1-q37.2 cholinergic receptor, nicotinic, gamma polypeptide TIGD1 2q36.1 tigger transposable element derived 1 EIF4EL3 2q37.3 eukaryotic translation initiation factor 4E-like 3 FLJ13612 TNRC15 2q37.1 trinucleotide repeat containing 15 KCNJ13 2q37 potassium inwardly-rectifying channel, subfamily J, member 13 LOC389084 2 similar to ASCL830 NGEF 2q37 neuronal guanine nucleotide exchange factor NEU2 2q37 sialidase 2 (cytosolic sialidase) INPP5D 2q36-q37.1 inositol polyphosphate-5-phosphatase, 145kDa APG16L 2q37.1 APG16 autophagy 16-like (S. cerevisiae) SAG 2q37.1 S-antigen; retina and pineal gland (arrestin) DGKD 2q37.1 diacylglycerol kinase, delta 130kDa USP40 2q37.1 ubiquitin specific protease 40 UGT1A12P 2q37 UDP glycosyltransferase 1 family, polypeptide A12 pseudogene UGT1A11P 2q37 UDP glycosyltransferase 1 family, polypeptide A11 pseudogene UGT1A@ 2q37 UDP glycosyltransferase 1 family, polypeptide A cluster LOC391493 2 similar to UDP-glucuronosyltransferase 1-5 precursor, microsomal (UDP-glucuronosyltransferase 1A5) (UDPGT) (UGT1*5) (UGT1-05) (UGT1.5) (UGT-1E) (UGT1E) UGT1A2P 2q37 UDP glycosyltransferase 1 family, polypeptide A2 pseudogene LOC389085 2 similar to hypothetical protein FLJ40243 LOC339766 2q37.2 hypothetical protein LOC339766 DKFZp762E1312 2q37.2 hypothetical protein DKFZp762E1312 LOC151507 2q37.2 similar to male-specific lethal 3-like 1 isoform a; drosophila MSL3-like 1 TRPM8 2q37.1 transient receptor potential cation channel, subfamily M, member 8 SPP2 2q37 secreted phosphoprotein 2, 24kDa
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    27 splicing 5294 133 1189 - 2012 21864674
    27 splicing 5291 133 1188 - 2012 21864674
    using an alternate in-frame splice site, compared to variant 1
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node   predominantly
     spleen   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  predominantly Homo sapiensAdult
    Connectivebone   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmature hematopoietic Homo sapiensAdult
    Lymphoid/ImmuneB cell
    Lymphoid/ImmuneT cell
    cell lineage
    cell lines
    fluid/secretion moderately in blood, highly in lymph
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a unique N-terminal SH2 (Src homology region 2) domain, having fast association and dissociation rates (Zhang 2009)
  • two centrally located INPP5 motif
  • three NXXY motifs
  • a sac domain
  • two C-terminal protein interaction domains, C-terminal proline rich domain (PRD) interacting with XIAP, thereby disturbing the interaction between XIAP and RIPK2 in order to decrease NFKB1 signaling
  • HOMOLOGY
    interspecies homolog to rattus Inpp5d (88.4 pc)
    homolog to murine Inpp5d (88.2 pc)
    intraspecies homolog to INPPL1
    Homologene
    FAMILY
  • inositol polyphosphate-5-phosphatase (INPP5) family
  • CATEGORY enzyme , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus,nucleolus
    text
  • is a nucleocytoplasmic shuttling protein which is actively imported into and exported out of the nucleus
  • INPP5D nuclear puncta partially colocalize with CASP8AP2, a component of nuclear bodies
  • also colocalizes in nucleolar cavities with components of the ubiquitin-proteasome pathway
  • basic FUNCTION
  • acting as a negative regulator of lymphocyte activation and of myeliod cell proliferation and survival
  • inhibiting ras signaling by competing with GRB2
  • down-regulating cytokine receptor signaling in myeloid cells
  • acts by hydrolysing the 5-phosphates from PtdIns(3,4,5)P(3) and Ins(1,3,4,5)P(4), thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathway (Gloire 2007)
  • not only acts as a negative player in T-cell lines proliferation, but also regulates critical pathways, such as NF-kappaB (nuclear factor kappaB) activation, and also appears to remarkably inhibit T-cell apoptosis (Gloire 2007)
  • plays a major role in inhibiting proliferation of myeloid cells
  • involved in the signal terminating reaction in the inositol signaling pathway
  • playing a major role in controlling PtdIns(3,4,5) P3 levels in response to thrombin or collagen activation
  • with INPP5E and INPP5K, implicated in negatively regulating insulin signalling and glucose homoeostasis in specific tissues (Ooms 2009)
  • regulate macrophage phagocytosis, and also controls haemopoietic cell proliferation (Ooms 2009)
  • its inactivation could play a central role in the deregulation of Akt pathway and tumorigenesis, perhaps in conjunction with PTEN inactivation (Lo 2009)
  • cannot bind to ubiquitin, which is consistent with the fact that does not contain such a UIM domain (De Schutter 2009)
  • negative regulator of signaling processes in hematopoietic cells
  • plays likely a role for nuclear phosphoinositide and/or nuclear inositol phosphate signaling
  • INPP5D, DOK1 and DOK2 play central roles in CD4-mediated inhibitory signaling
  • its presence at focal adhesions and lamellipodia could suggest a role in cell adhesion and migration
  • is an adhesion molecule that control NK cell cytotoxicity and interferon-gamma production against a wide range of cancer and infected cells
  • INPP5D control of natural killer cells functions through nectin and nectin-like proteins
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism other
    signaling signal transduction
  • phosphate (inositol) metabolic process
  • intracellular signaling cascade
  • a component
  • BAG4 forms a complex with several 5-ptase family members, including INPPL1, INPP5D, INPP5K
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with phosphotyrosine inhibitory motif of Fcgamma RIIB (FCGR2B) for negative regulation of the immune receptor activation in both B and mast cells
  • mediates its regulatory function after relocalization from the cytoplasm to the plasma membrane where it converts its substrate PI(3,4,5)P(3) to PI(3,4)P(2) thereby terminating PI3-kinase mediated signaling
  • like INPP5D, UBASH3B functions as a negative regulator of FCER1A signaling in mast cells
  • decreases NOD2-induced NFKB1 activation in macrophages
  • ARRB2 associates with phosphorylated TIGIT for further recruitment of INPP5D (SH2-containing inositol phosphatase 1) through the ITT-like motif
  • coupling of SLAMF7 to INPP5D required SRC kinases, which phosphorylated SLAMF7
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    in most primary ALL and in the T-ALL cell line Jurkat, which harbored a bi-allelic null mutation and a frame-shift deletion (Lo 2009)
    Susceptibility
  • to late-onset Alzheimer disease (LOAD)
  • Variant & Polymorphism SNP
  • SNP rs35349669 of INPP5D was significantly associated with susceptibility to late-onset Alzheimer disease (LOAD)
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    inhibition of INPP5D and INPPL1 may have broad clinical application in the treatment of multiple tumor types
    ANIMAL & CELL MODELS
  • inflamed intestinal tissues and intestinal macrophages from Ship-null mice produced higher levels of Il1b and Il18 than intestinal tissues from control mice