LMPD Database

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LMP006557

UniProt Annotations

Entry Information
Gene Nameinositol polyphosphate-5-phosphatase D
Protein EntrySHIP1_MOUSE
UniProt IDQ9ES52
SpeciesMouse
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=6; Name=1; IsoId=Q9ES52-1; Sequence=Displayed; Name=2; IsoId=Q9ES52-2; Sequence=VSP_027981; Name=3; Synonyms=135 kDa SHIP; IsoId=Q9ES52-3; Sequence=VSP_027982; Name=4; Synonyms=SHIPdelta; IsoId=Q9ES52-4; Sequence=VSP_027981, VSP_027983, VSP_027984; Note=May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.; Name=5; Synonyms=s-SHIP; IsoId=Q9ES52-5; Sequence=VSP_027980; Name=6; Synonyms=s-SHIPD183; IsoId=Q9ES52-6; Sequence=VSP_027980, VSP_027982;
Catalytic Activity1-phosphatidyl-1D-myo-inositol 3,4,5- triphosphate + H(2)O = 1-phosphatidyl-1D-myo-inositol 3,4- diphosphate + phosphate. {ECO:0000269|PubMed:8643691, ECO:0000269|PubMed:8654924, ECO:0000269|PubMed:9341117}.
Developmental StageExpressed in late primitive-streak stage embryos (7.5 dpc), when hematopoiesis is thought to begin, and the expression is restricted to the hematopoietic lineage in embryo. In adults expression continues to be in the majority of cells from hematopoietic origin, including granulocytes, monocytes and lymphocytes, and is also found in the spermatids of the testis. {ECO:0000269|PubMed:10068665, ECO:0000269|PubMed:9531585}.
Disruption PhenotypeMice are viable and fertile. They however fail to thrive and only 40% survive by 14 weeks of age. Mortality is associated with extensive consolidation of the lungs resulting from infiltration by myeloid cells. Increased numbers of granulocyte-macrophage progenitors are observed in both the bone marrow and spleen. Absence of Inpp5d leads to steel factor-induced degranulation of mast cells. They also display increased numbers of osteoclast precursors leading to a severe osteoporosis. {ECO:0000269|PubMed:12161749, ECO:0000269|PubMed:9620849, ECO:0000269|PubMed:9857188}.
DomainThe NPXY sequence motif found in many tyrosine- phosphorylated proteins is required for the specific binding of the PID domain. {ECO:0000269|PubMed:9083021}.
DomainThe 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. {ECO:0000269|PubMed:9083021}.
Enzyme RegulationActivated upon translocation to the sites of synthesis of PtdIns(3,4,5)P3 in the membrane.
FunctionPhosphatidylinositol (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. {ECO:0000269|PubMed:11136821, ECO:0000269|PubMed:11222379, ECO:0000269|PubMed:11359765, ECO:0000269|PubMed:11896575, ECO:0000269|PubMed:12161749, ECO:0000269|PubMed:12370370, ECO:0000269|PubMed:12447389, ECO:0000269|PubMed:12882960, ECO:0000269|PubMed:14993273, ECO:0000269|PubMed:15166241, ECO:0000269|PubMed:17142780, ECO:0000269|PubMed:17173042, ECO:0000269|PubMed:8654924, ECO:0000269|PubMed:8805703, ECO:0000269|PubMed:9244303, ECO:0000269|PubMed:9620849, ECO:0000269|PubMed:9736736, ECO:0000269|PubMed:9763612, ECO:0000269|PubMed:9857188}.
InductionBy activin/TGF-beta (at protein level). Regulated by the Smad pathway. Isoform 3 is expressed during myeloid development. {ECO:0000269|PubMed:12447389}.
InteractionP23727:PIK3R1 (xeno); NbExp=2; IntAct=EBI-1452545, EBI-520244; Q8CIH5:Plcg2; NbExp=3; IntAct=EBI-300210, EBI-617954;
PtmTyrosine 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. {ECO:0000269|PubMed:10068665, ECO:0000269|PubMed:10395202, ECO:0000269|PubMed:10660611, ECO:0000269|PubMed:12370370, ECO:0000269|PubMed:17947660, ECO:0000269|PubMed:8654924, ECO:0000269|PubMed:8805618, ECO:0000269|PubMed:9099679}.
SimilarityBelongs to the inositol 1,4,5-trisphosphate 5- phosphatase family. {ECO:0000305}.
SimilarityContains 1 SH2 domain. {ECO:0000255|PROSITE- ProRule:PRU00191}.
Subcellular LocationCytoplasm. Cell 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.
Subcellular LocationIsoform 5: Cell membrane; Peripheral membrane protein. Note=Constitutively present at the cell membrane.
SubunitInteracts 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. Interacts with MILR1 (tyrosine- phosphorylated). Isoform 5 interacts with IL6ST/gp130. Can weakly interact (via NPXY motif 2) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif. {ECO:0000269|PubMed:10068665, ECO:0000269|PubMed:10395202, ECO:0000269|PubMed:10660611, ECO:0000269|PubMed:10779347, ECO:0000269|PubMed:10794720, ECO:0000269|PubMed:11016922, ECO:0000269|PubMed:11031258, ECO:0000269|PubMed:11247302, ECO:0000269|PubMed:11896575, ECO:0000269|PubMed:12370370, ECO:0000269|PubMed:12393695, ECO:0000269|PubMed:14993273, ECO:0000269|PubMed:15456754, ECO:0000269|PubMed:15492005, ECO:0000269|PubMed:16000869, ECO:0000269|PubMed:17105399, ECO:0000269|PubMed:20526344, ECO:0000269|PubMed:8643691, ECO:0000269|PubMed:8654924, ECO:0000269|PubMed:9083021, ECO:0000269|PubMed:9099679, ECO:0000269|PubMed:9110989, ECO:0000269|PubMed:9393882}.
Tissue SpecificitySpecifically expressed in immune and hematopoietic cells. Levels vary considerably within this compartment. Lost during erythropoiesis when erythroid cells become Ter119+. Increases substantially with T-cell maturation and when resting B-cells are activated. Also present in mature granulocytes, monocyte/macrophages, mast cells and platelets. Isoform 5 is the only form expressed in embryonic stem (ES) cells and is coexpressed with other isoforms in hematopoietic stem cells, and disappears with differentiation. {ECO:0000269|PubMed:10068665, ECO:0000269|PubMed:8643691, ECO:0000269|PubMed:8654924, ECO:0000269|PubMed:9531585}.