Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
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.n1
    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
    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
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node   predominantly
     spleen   moderately
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  predominantly Homo sapiensAdult
    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
  • 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
    interspecies homolog to rattus Inpp5d (88.4 pc)
    homolog to murine Inpp5d (88.2 pc)
    intraspecies homolog to INPPL1
  • inositol polyphosphate-5-phosphatase (INPP5) family
  • CATEGORY enzyme , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
  • 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
    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
    small molecule
  • 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
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    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)
  • 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
    Therapy target
    inhibition of INPP5D and INPPL1 may have broad clinical application in the treatment of multiple tumor types
  • inflamed intestinal tissues and intestinal macrophages from Ship-null mice produced higher levels of Il1b and Il18 than intestinal tissues from control mice