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Aliases for INPP5D Gene

Aliases for INPP5D Gene

  • Inositol Polyphosphate-5-Phosphatase, 145kDa 2 3
  • SHIP 3 4 6
  • SH2 Domain-Containing Inositol 5-Phosphatase 1 3 4
  • Inositol Polyphosphate-5-Phosphatase, 145kD 2 3
  • P150Ship 3 4
  • SIP-145 3 4
  • SHIP-1 3 4
  • Hp51CN 3 4
  • SHIP1 3 4
  • Phosphatidylinositol 3,4,5-Trisphosphate 5-Phosphatase 1 3
  • Signaling Inositol Polyphosphate 5 Phosphatase SIP-145 3
  • Signaling Inositol Polyphosphate Phosphatase SHIP II 3
  • Inositol Polyphosphate-5-Phosphatase Of 145 KDa 4
  • SH2 Domain-Containing Inositol Phosphatase 1 4
  • EC 3.1.3.n1 63
  • EC 3.1.3.86 4
  • EC 3.1.3 63

External Ids for INPP5D Gene

Summaries for INPP5D Gene

Entrez Gene Summary for INPP5D Gene

  • This gene is a member of the inositol polyphosphate-5-phosphatase (INPP5) family and encodes a protein with an N-terminal SH2 domain, an inositol phosphatase domain, and two C-terminal protein interaction domains. Expression of this protein is restricted to hematopoietic cells where its movement from the cytosol to the plasma membrane is mediated by tyrosine phosphorylation. At the plasma membrane, the protein hydrolyzes the 5' phosphate from phosphatidylinositol (3,4,5)-trisphosphate and inositol-1,3,4,5-tetrakisphosphate, thereby affecting multiple signaling pathways. The protein is also partly localized to the nucleus, where it may be involved in nuclear inositol phosphate signaling processes. Overall, the protein functions as a negative regulator of myeloid cell proliferation and survival. Mutations in this gene are associated with defects and cancers of the immune system. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2014]

GeneCards Summary for INPP5D Gene

INPP5D (Inositol Polyphosphate-5-Phosphatase, 145kDa) is a Protein Coding gene. Diseases associated with INPP5D include oculocerebrorenal syndrome. Among its related pathways are Class I MHC mediated antigen processing and presentation and Hemostasis. GO annotations related to this gene include SH3 domain binding and PTB domain binding. An important paralog of this gene is SYNJ2.

UniProtKB/Swiss-Prot for INPP5D Gene

  • Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways. Acts as a negative regulator of B-cell antigen receptor signaling. Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Acts as a negative regulator of myeloid cell proliferation/survival and chemotaxis, mast cell degranulation, immune cells homeostasis, integrin alpha-IIb/beta-3 signaling in platelets and JNK signaling in B-cells. Regulates proliferation of osteoclast precursors, macrophage programming, phagocytosis and activation and is required for endotoxin tolerance. Involved in the control of cell-cell junctions, CD32a signaling in neutrophils and modulation of EGF-induced phospholipase C activity. Key regulator of neutrophil migration, by governing the formation of the leading edge and polarization required for chemotaxis. Modulates FCGR3/CD16-mediated cytotoxicity in NK cells. Mediates the activin/TGF-beta-induced apoptosis through its Smad-dependent expression. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6.

Gene Wiki entry for INPP5D Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for INPP5D Gene

Genomics for INPP5D Gene

Genomic Location for INPP5D Gene

Start:
233,059,967 bp from pter
End:
233,207,903 bp from pter
Size:
147,937 bases
Orientation:
Plus strand

Genomic View for INPP5D Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for INPP5D Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for INPP5D Gene

Regulatory Elements for INPP5D Gene

Proteins for INPP5D Gene

  • Protein details for INPP5D Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q92835-SHIP1_HUMAN
    Recommended name:
    Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1
    Protein Accession:
    Q92835
    Secondary Accessions:
    • O00145
    • Q13544
    • Q13545
    • Q6P5A4
    • Q92656
    • Q9UE80

    Protein attributes for INPP5D Gene

    Size:
    1189 amino acids
    Molecular mass:
    133292 Da
    Quaternary structure:
    • Interacts with tyrosine phosphorylated forms of SHC1, DOK1, DOK3, PTPN11/SHP-2, SLAMF1/CD150. Interacts with PTPN11 in response to IL-3. Interacts with receptors EPOR, MS4A2/FCER1B and FCER1G, FCGR2A, FCGR2B and FCGR3. Interacts with GRB2 and PLCG1. Interacts with tyrosine kinases SRC and TEC. Interacts with FCGR2A, leading to regulate gene expression during the phagocytic process. Interacts with c-Met/MET (By similarity). Interacts with MILR1 (tyrosine-phosphorylated). Can weakly interact (via NPXY motif 2) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif (By similarity).
    SequenceCaution:
    • Sequence=AAC50454.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for INPP5D Gene

    Alternative splice isoforms for INPP5D Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for INPP5D Gene

Proteomics data for INPP5D Gene at MOPED

Post-translational modifications for INPP5D Gene

  • Tyrosine phosphorylated by the members of the SRC family after exposure to a diverse array of extracellular stimuli such as cytokines, growth factors, antibodies, chemokines, integrin ligands and hypertonic and oxidative stress. Phosphorylated upon IgG receptor FCGR2B-binding.
  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys365

Other Protein References for INPP5D Gene

Domains for INPP5D Gene

Gene Families for INPP5D Gene

HGNC:
  • SH2D :SH2 domain containing
IUPHAR :

Suggested Antigen Peptide Sequences for INPP5D Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q92835

UniProtKB/Swiss-Prot:

SHIP1_HUMAN
Domain:
  • The SH2 domain interacts with tyrosine phosphorylated forms of proteins such as SHC1 or PTPN11/SHP-2. It competes with that of GRB2 for binding to phosphorylated SHC1 to inhibit the Ras pathway. It is also required for tyrosine phosphorylation (By similarity).:
    • Q92835
  • The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain.:
    • Q92835
  • Contains 1 SH2 domain.:
    • Q92835
Family:
  • Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase family.:
    • Q92835
genes like me logo Genes that share domains with INPP5D: view

Function for INPP5D Gene

Molecular function for INPP5D Gene

GENATLAS Biochemistry: inositol 1,4,5-triphosphate-5 phosphatase (145kDa),expressed in bone marrow in B and T cells and various tissues,interacting with phosphotyrosine inhibitory motif of Fcgamma RIIB (FCGR2B) for negative regulation of the immune receptor activation in both B and mast cells,down-regulating cytokine receptor signaling in myeloid cells,inhibiting ras signaling by competing with GRB2,signal terminating reaction in the inositol signaling pathway,negative regulator of lymphocyte activation
UniProtKB/Swiss-Prot CatalyticActivity: 1-phosphatidyl-1D-myo-inositol 3,4,5-triphosphate + H(2)O = 1-phosphatidyl-1D-myo-inositol 3,4-diphosphate + phosphate.
UniProtKB/Swiss-Prot EnzymeRegulation: Activated upon translocation to the sites of synthesis of PtdIns(3,4,5)P3 in the membrane.
UniProtKB/Swiss-Prot Function: Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways. Acts as a negative regulator of B-cell antigen receptor signaling. Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Acts as a negative regulator of myeloid cell proliferation/survival and chemotaxis, mast cell degranulation, immune cells homeostasis, integrin alpha-IIb/beta-3 signaling in platelets and JNK signaling in B-cells. Regulates proliferation of osteoclast precursors, macrophage programming, phagocytosis and activation and is required for endotoxin tolerance. Involved in the control of cell-cell junctions, CD32a signaling in neutrophils and modulation of EGF-induced phospholipase C activity. Key regulator of neutrophil migration, by governing the formation of the leading edge and polarization required for chemotaxis. Modulates FCGR3/CD16-mediated cytotoxicity in NK cells. Mediates the activin/TGF-beta-induced apoptosis through its Smad-dependent expression. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6.

Enzyme Numbers (IUBMB) for INPP5D Gene

Gene Ontology (GO) - Molecular Function for INPP5D Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004445 inositol-polyphosphate 5-phosphatase activity IEA --
GO:0005515 protein binding IPI 10382761
GO:0017124 SH3 domain binding IEA --
GO:0034594 phosphatidylinositol trisphosphate phosphatase activity IEA --
GO:0051425 PTB domain binding IEA --
genes like me logo Genes that share ontologies with INPP5D: view
genes like me logo Genes that share phenotypes with INPP5D: view

Animal Models for INPP5D Gene

MGI Knock Outs for INPP5D:

miRNA for INPP5D Gene

miRTarBase miRNAs that target INPP5D

No data available for Transcription Factor Targeting and HOMER Transcription for INPP5D Gene

Localization for INPP5D Gene

Subcellular locations from UniProtKB/Swiss-Prot for INPP5D Gene

Cytoplasm. Membrane; Peripheral membrane protein. Note=Translocates to the plasma membrane when activated, translocation is probably due to different mechanisms depending on the stimulus and cell type. Partly translocated via its SH2 domain which mediates interaction with tyrosine phosphorylated receptors such as the FC-gamma-RIIB receptor (FCGR2B) or CD16/FCGR3. Tyrosine phosphorylation may also participate in membrane localization (By similarity). {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for INPP5D Gene COMPARTMENTS Subcellular localization image for INPP5D gene
Compartment Confidence
cytosol 4
plasma membrane 2
cytoskeleton 1
extracellular 1
mitochondrion 1
nucleus 1

Gene Ontology (GO) - Cellular Components for INPP5D Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with INPP5D: view

Pathways for INPP5D Gene

genes like me logo Genes that share pathways with INPP5D: view

Gene Ontology (GO) - Biological Process for INPP5D Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006644 phospholipid metabolic process TAS --
GO:0006661 phosphatidylinositol biosynthetic process TAS --
GO:0006796 phosphate-containing compound metabolic process TAS 8769125
GO:0006915 apoptotic process IEA --
GO:0007165 signal transduction TAS 8769125
genes like me logo Genes that share ontologies with INPP5D: view

Compounds for INPP5D Gene

(380) HMDB Compounds for INPP5D Gene

Compound Synonyms Cas Number PubMed IDs
Phosphate
  • NFB Orthophosphate
14265-44-2
Phosphatidylinositol-3,4,5-trisphosphate
  • Phosphatidylinositol-3,4,5-trisphosphate
Not Available
PI(16:0/16:0)
  • Phosphatidylinositol(32:0)
Not Available
PI(16:0/16:1(9Z))
  • Phosphatidylinositol(32:1)
Not Available
PI(16:0/16:2(9Z,12Z))
  • Phosphatidylinositol(16:0/16:2n4)
Not Available

(17) Novoseek inferred chemical compound relationships for INPP5D Gene

Compound -log(P) Hits PubMed IDs
inositol 92.9 116
phosphatidylinositol-3,4,5-trisphosphate 88.8 17
tyrosine 74.3 106
phosphatidylinositol 72.9 25
phosphoinositide 63.5 6
genes like me logo Genes that share compounds with INPP5D: view

Transcripts for INPP5D Gene

Unigene Clusters for INPP5D Gene

Inositol polyphosphate-5-phosphatase, 145kDa:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for INPP5D Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4a · 4b ^ 5a · 5b ^ 6 ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11 ^ 12 ^ 13a · 13b ^ 14 ^ 15 ^ 16 ^ 17 ^ 18a · 18b
SP1: - - - - -
SP2:
SP3: - - -
SP4: -
SP5:
SP6:

Relevant External Links for INPP5D Gene

GeneLoc Exon Structure for
INPP5D
ECgene alternative splicing isoforms for
INPP5D

Expression for INPP5D Gene

mRNA expression in normal human tissues for INPP5D Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for INPP5D Gene

This gene is overexpressed in Whole Blood (16.1) and Spleen (5.6).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for INPP5D Gene

SOURCE GeneReport for Unigene cluster for INPP5D Gene Hs.262886

mRNA Expression by UniProt/SwissProt for INPP5D Gene

Q92835-SHIP1_HUMAN
Tissue specificity: Specifically expressed in immune and hematopoietic cells. Expressed in bone marrow and blood cells. Levels vary considerably within this compartment. Present in at least 74% of immature CD34+ cells, whereas within the more mature population of CD33+ cells, it is present in only 10% of cells. Present in the majority of T-cells, while it is present in a minority of B-cells (at protein level).
genes like me logo Genes that share expressions with INPP5D: view

Orthologs for INPP5D Gene

This gene was present in the common ancestor of animals.

Orthologs for INPP5D Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia INPP5D 35
  • 99.46 (n)
  • 99.57 (a)
INPP5D 36
  • 98 (a)
OneToOne
cow
(Bos Taurus)
Mammalia INPP5D 35
  • 88.63 (n)
  • 90.16 (a)
INPP5D 36
  • 87 (a)
OneToOne
dog
(Canis familiaris)
Mammalia INPP5D 35
  • 87.88 (n)
  • 89.91 (a)
INPP5D 36
  • 77 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Inpp5d 35
  • 85.25 (n)
  • 88.41 (a)
Inpp5d 16
Inpp5d 36
  • 86 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia INPP5D 36
  • 80 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia INPP5D 36
  • 63 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Inpp5d 35
  • 85.38 (n)
  • 88.4 (a)
chicken
(Gallus gallus)
Aves INPP5D 35
  • 70.76 (n)
  • 69.93 (a)
INPP5D 36
  • 66 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia INPP5D 36
  • 64 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia MGC68993 35
tropical clawed frog
(Silurana tropicalis)
Amphibia inpp5d 35
  • 60.84 (n)
  • 61.18 (a)
zebrafish
(Danio rerio)
Actinopterygii inpp5d 35
  • 61.59 (n)
  • 61.99 (a)
inpp5d 36
  • 57 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Ocrl 36
  • 17 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea ocrl-1 36
  • 20 (a)
OneToMany
Species with no ortholog for INPP5D:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for INPP5D Gene

ENSEMBL:
Gene Tree for INPP5D (if available)
TreeFam:
Gene Tree for INPP5D (if available)

Paralogs for INPP5D Gene

Paralogs for INPP5D Gene

Selected SIMAP similar genes for INPP5D Gene using alignment to 9 proteins:

genes like me logo Genes that share paralogs with INPP5D: view

Variants for INPP5D Gene

Sequence variations from dbSNP and Humsavar for INPP5D Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type MAF
rs7346 -- 233,204,411(+) TTCAC(A/G)TGCTC synonymous-codon, reference
rs9247 - 233,204,655(+) TCCCG(C/T)ATCAC reference, missense
rs11036 -- 233,206,751(+) GGAAC(C/G)GCGTG utr-variant-3-prime
rs14243 -- 233,207,093(+) TCATG(A/G)TGTGC utr-variant-3-prime
rs1057258 -- 233,206,983(+) TGCCT(C/T)GTTGA utr-variant-3-prime

Structural Variations from Database of Genomic Variants (DGV) for INPP5D Gene

Variant ID Type Subtype PubMed ID
nsv876009 CNV Gain 21882294
nsv876012 CNV Gain 21882294
nsv520361 CNV Loss 19592680
esv1142800 CNV Deletion 17803354
nsv3213 CNV Insertion 18451855
esv2721651 CNV Deletion 23290073
esv2657351 CNV Deletion 23128226
nsv527354 CNV Gain 19592680
esv1209599 CNV Deletion 17803354

Relevant External Links for INPP5D Gene

HapMap Linkage Disequilibrium report
INPP5D

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for INPP5D Gene

Disorders for INPP5D Gene

(1) University of Copenhagen DISEASES for INPP5D Gene

(17) Novoseek inferred disease relationships for INPP5D Gene

Disease -log(P) Hits PubMed IDs
leukemogenesis 54.4 5
lymphoproliferative syndrome 43.3 2
erythroleukemia 30.2 1
myeloid leukemia 13.3 1
myeloproliferative disorders 13 2

Relevant External Links for INPP5D

Genetic Association Database (GAD)
INPP5D
Human Genome Epidemiology (HuGE) Navigator
INPP5D
genes like me logo Genes that share disorders with INPP5D: view

No data available for UniProtKB/Swiss-Prot for INPP5D Gene

Publications for INPP5D Gene

  1. Cloning and characterization of human SHIP, the 145-kD inositol 5- phosphatase that associates with SHC after cytokine stimulation. (PMID: 8874179) Ware M.D. … Krystal G. (Blood 1996) 2 3 4 23
  2. Multiple forms of an inositol polyphosphate 5-phosphatase form signaling complexes with Shc and Grb2. (PMID: 8723348) Kavanaugh W.M. … Williams L.T. (Curr. Biol. 1996) 3 4 23
  3. The human SHIP gene is differentially expressed in cell lineages of the bone marrow and blood. (PMID: 9058707) Geier S.J. … Rohrschneider L.R. (Blood 1997) 3 4 23
  4. CDw150 associates with src-homology 2-containing inositol phosphatase and modulates CD95-mediated apoptosis. (PMID: 10229804) Mikhalap S.V. … Sidorenko S.P. (J. Immunol. 1999) 3 4 23
  5. The phosphatidylinositol polyphosphate 5-phosphatase SHIP1 associates with the dok1 phosphoprotein in bcr-Abl transformed cells. (PMID: 10822173) Dunant N.M. … Resh M.D. (Cell. Signal. 2000) 3 4 23

Products for INPP5D Gene

  • antibodies-online peptides for INPP5D
  • antibodies-online antibodies for INPP5D
  • antibodies-online kits for INPP5D

Sources for INPP5D Gene

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