Protein: Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (EC 3.1.3.86) (Inositol polyphosphate-5-phosphatase D) (EC 3.1.3.56) (Phosphatidylinositol-4,5-bisphosphate 5-phosphatase) (EC 3.1.3.36) (SH2 domain-containing inositol 5'-phosphatase 1) (SH2 domain-containing inositol phosphatase 1) (SHIP-1) (P97573)
Organism: Rattus norvegicus (Rat)
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. Also able to hydrolyze the 5-phosphate of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (By similarity). 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 (By similarity).
Subcellular location: Cytoplasm {ECO:0000250|UniProtKB:Q9ES52}. Cell membrane {ECO:0000250|UniProtKB:Q9ES52}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q9ES52}. Membrane raft {ECO:0000250|UniProtKB:Q9ES52}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:Q9ES52}. Note=Translocates to the plasma membrane when activated, translocation is probably due to different mechanisms depending on the stimulus and cell type. Translocates from the cytoplasm to membrane ruffles in a FCGR3/CD16-dependent manner. Colocalizes with FC-gamma-RIIB receptor (FCGR2B) or FCGR3/CD16 at membrane ruffles. Tyrosine phosphorylation may also participate in membrane localization. {ECO:0000250|UniProtKB:Q9ES52}.
Interaction partners:
- SHC-transforming protein 1
- Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
- Type II inositol 3,4-bisphosphate 4-phosphatase
- Phosphatidylinositol 3-kinase regulatory subunit alpha
- Inositol polyphosphate-4-phosphatase type I A
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
- phosphatidylinositol-4,5-bisphosphate 3-kinase
- Phosphatidylinositol 3-kinase regulatory subunit beta
- Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2
Sequence:
MPAMVPGWNHGNITRSKAEELLSRAGKDGSFLVRASESIPRAYALCVLFRNCVYTYRILPNEDDKFTVQASEGVPMRFFTKLDQLIEFYKKENMGLVTHLQFPVPLEEEDAIDEPEEDTESVMSPPELPPRNIPVSGGPCEAKDLPLPTENPRAPEVTRLSLSETLFQRLQSMDTSGLPEEHLKAIQDYLSTQLMLDSDFLKTGSSNLPHLKKLTSLLCKELHGEVIRTLPSLESLQRLFDQQLSPGLRPRPQVPGEANPITMVAKLSQLTSLLSSIEDKVKALLHEGSESTNRRSLIPPVTFEVKSESLGIPQKMHLKVDVESGKLIIKKSRDGSEDKFYSHKKILQLIKSQKFLNKLVILVETEKEKILRKEYVFSDSKKREGFCQLLQQMKNKHSEQSEPDMITIFIGTWNMGNAPPPKKITSWFLSKGQGKTRDDSADYIPHDIYVIGTQEDPLGEKEWLEILRHSLQEVTSMTFKTVAIHTLWNIRIVVLAKPEHENRISHICTDNVKTGIANTLGNKGAVGVSFMFNGTSLGFVNSHLTSGSEKKLRRNQNYMNILRFLALGDKKLSPFNITHRFTHLFWLGDLNYRVELPTWEAEAIIQKIKQQQYSDLLAHDQLLLERKEQEVFLHFEEEEITFAPTYRFERLTRDKYAYTKQKATGMKYNLPSWCDRVLWKSYPLVHVVCQSYGSTSDIMTSDHSPVFATFEAGVTSQFVSKNGPGAVDSQGQIEFLACYATLKTKSQTKFYLELHSSCLESFVKSQEGENEEGDEGELVVRFGETLPKLKPIISDPEYLLDQHILISIKSSDSDESYGEGCIALRLETTESQLPIYTPLTHHGEMTGHFRGEIKLQTSEGKMREKLYDFVKTERDESSGMKCLKNLTSHDPMRQWEPAGRVPACGISSLNEIINPNYIGMGPFGQPLHGKSTLSPDQQLTAWSYDQLPKDSSLGPGRGEGPPTPPSQPPLSPKKFSSSTANRGSCPRVQETRPGDLGKVEALPQEDLPLTKPEMFENPLYGSVSPFPKLVPRKEQESPKMMRKEPPPCPDPGVSSPSIMLPKAQEVENVKGTSKQAPVPVFGPTPRIRSFTCSSSAEGRMPSGDKSQGKPKAPASSQAPVPVKRPVKPSRSEMSQQTTPIPAPRPPLPVKSPAVLQLQHSKGRDYRDNTELPHHGKHRQEESLLGRTAMQ