Protein: Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (Q9ES52)
Organism: Mus musculus (Mouse)
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 (By similarity). Also able to hydrolyze the 5-phosphate of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P3) and inositol 1,3,4,5-tetrakisphosphate. 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
Subcellular location: Cytoplasm. Cell membrane; Peripheral membrane protein. Membrane raft. Cytoplasm, cytoskeleton. 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
Sequence: MPAMVPGWNHGNITRSKAEELLSRAGKDGSFLVRASESIPRAYALCVLFRNCVYTYRILPNEDDKFTVQASEGVPMRFFTKLDQLIDFYKKENMGLVTHLQYPVPLEEEDAIDEAEEDTVESVMSPPELPPRNIPMSAGPSEAKDLPLATENPRAPEVTRLSLSETLFQRLQSMDTSGLPEEHLKAIQDYLSTQLLLDSDFLKTGSSNLPHLKKLMSLLCKELHGEVIRTLPSLESLQRLFDQQLSPGLRPRPQVPGEASPITMVAKLSQLTSLLSSIEDKVKSLLHEGSESTNRRSLIPPVTFEVKSESLGIPQKMHLKVDVESGKLIVKKSKDGSEDKFYSHKKILQLIKSQKFLNKLVILVETEKEKILRKEYVFADSKKREGFCQLLQQMKNKHSEQPEPDMITIFIGTWNMGNAPPPKKITSWFLSKGQGKTRDDSADYIPHDIYVIGTQEDPLGEKEWLELLRHSLQEVTSMTFKTVAIHTLWNIRIVVLAKPEHENRISHICTDNVKTGIANTLGNKGAVGVSFMFNGTSLGFVNSHLTSGSEKKLRRNQNYMNILRFLALGDKKLSPFNITHRFTHLFWLGDLNYRVELPTWEAEAIIQKIKQQQYSDLLAHDQLLLERKDQKVFLHFEEEEITFAPTYRFERLTRDKYAYTKQKATGMKYNLPSWCDRVLWKSYPLVHVVCQSYGSTSDIMTSDHSPVFATFEAGVTSQFVSKNGPGTVDSQGQIEFLACYATLKTKSQTKFYLEFHSSCLESFVKSQEGENEEGSEGELVVRFGETLPKLKPIISDPEYLLDQHILISIKSSDSDESYGEGCIALRLETTEAQHPIYTPLTHHGEMTGHFRGEIKLQTSQGKMREKLYDFVKTERDESSGMKCLKNLTSHDPMRQWEPSGRVPACGVSSLNEMINPNYIGMGPFGQPLHGKSTLSPDQQLTAWSYDQLPKDSSLGPGRGEGPPTPPSQPPLSPKKFSSSTANRGPCPRVQEARPGDLGKVEALLQEDLLLTKPEMFENPLYGSVSSFPKLVPRKEQESPKMLRKEPPPCPDPGISSPSIVLPKAQEVESVKGTSKQAPVPVLGPTPRIRSFTCSSSAEGRMTSGDKSQGKPKASASSQAPVPVKRPVKPSRSEMSQQTTPIPAPRPPLPVKSPAVLQLQHSKGRDYRDNTELPHHGKHRQEEGLLGRTAMQ
InterPro domains: - IPR036691: Endonuclease/exonuclease/phosphatase superfamily (homologous_superfamily) [389-718]
- IPR036860: SH2 domain superfamily (homologous_superfamily) [3-115]
- IPR000300: Inositol polyphosphate-related phosphatase (domain) [405-721]
- IPR057509: Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1/2-like, second C2 domain (domain) [749-853]
- IPR000980: SH2 domain (domain) [6-104]
- IPR057510: Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1/2-like, first C2 domain (domain) [299-378]
Interaction partners: - SHC-transforming protein 1
- Platelet endothelial cell adhesion molecule
- Tyrosine-protein kinase Lyn
- Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
- Inositol polyphosphate-4-phosphatase type I A
- Phosphatidylinositol 3-kinase regulatory subunit alpha
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
- Type II inositol 3,4-bisphosphate 4-phosphatase
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0002376 (immune system process), GO:0023052 (signaling), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0023057 (negative regulation of signaling), GO:0008340 (determination of adult lifespan), GO:0019222 (regulation of metabolic process), GO:0006955 (immune response), GO:0051240 (positive regulation of multicellular organismal process), GO:0002684 (positive regulation of immune system process), GO:0002682 (regulation of immune system process), GO:0051241 (negative regulation of multicellular organismal process), GO:0051239 (regulation of multicellular organismal process), GO:0009892 (negative regulation of metabolic process), GO:0050793 (regulation of developmental process), GO:0002683 (negative regulation of immune system process), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0051716 (cellular response to stimulus), GO:0023051 (regulation of signaling), GO:0002252 (immune effector process), GO:0051093 (negative regulation of developmental process), GO:0051094 (positive regulation of developmental process), GO:0048523 (negative regulation of cellular process), GO:0048585 (negative regulation of response to stimulus), GO:0007154 (cell communication), GO:0007165 (signal transduction), GO:0048522 (positive regulation of cellular process), GO:0050777 (negative regulation of immune response), GO:0045597 (positive regulation of cell differentiation), GO:0009968 (negative regulation of signal transduction), GO:0010942 (positive regulation of cell death), GO:0002695 (negative regulation of leukocyte activation), GO:0010648 (negative regulation of cell communication), GO:0002250 (adaptive immune response), GO:0035556 (intracellular signal transduction), GO:0008285 (negative regulation of cell population proliferation), GO:0034103 (regulation of tissue remodeling), GO:0009966 (regulation of signal transduction), GO:0060255 (regulation of macromolecule metabolic process), GO:0002694 (regulation of leukocyte activation), GO:1903706 (regulation of hemopoiesis), GO:0001817 (regulation of cytokine production), GO:0050867 (positive regulation of cell activation), GO:1903707 (negative regulation of hemopoiesis), GO:0002696 (positive regulation of leukocyte activation), GO:0034104 (negative regulation of tissue remodeling), GO:2000026 (regulation of multicellular organismal development), GO:0050776 (regulation of immune response), GO:0050866 (negative regulation of cell activation), GO:0042127 (regulation of cell population proliferation), GO:0010941 (regulation of cell death), GO:0010646 (regulation of cell communication), GO:0045596 (negative regulation of cell differentiation), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0045595 (regulation of cell differentiation), GO:0001818 (negative regulation of cytokine production), GO:0002443 (leukocyte mediated immunity), GO:1903708 (positive regulation of hemopoiesis), GO:0050865 (regulation of cell activation), GO:1902106 (negative regulation of leukocyte differentiation), GO:0043067 (regulation of programmed cell death), GO:0043068 (positive regulation of programmed cell death), GO:0060284 (regulation of cell development), GO:0010720 (positive regulation of cell development), GO:0032675 (regulation of interleukin-6 production), GO:0070663 (regulation of leukocyte proliferation), GO:0051250 (negative regulation of lymphocyte activation), GO:0010468 (regulation of gene expression), GO:0002449 (lymphocyte mediated immunity), GO:0045637 (regulation of myeloid cell differentiation), GO:0045639 (positive regulation of myeloid cell differentiation), GO:0051251 (positive regulation of lymphocyte activation), GO:0045638 (negative regulation of myeloid cell differentiation), GO:1902107 (positive regulation of leukocyte differentiation), GO:0032715 (negative regulation of interleukin-6 production), GO:0002460 (adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains), GO:0070664 (negative regulation of leukocyte proliferation), GO:0046851 (negative regulation of bone remodeling), GO:0046850 (regulation of bone remodeling), GO:1902105 (regulation of leukocyte differentiation), GO:0010721 (negative regulation of cell development), GO:0010629 (negative regulation of gene expression), GO:0051249 (regulation of lymphocyte activation), GO:0002762 (negative regulation of myeloid leukocyte differentiation), GO:0043065 (positive regulation of apoptotic process), GO:0042981 (regulation of apoptotic process), GO:0045619 (regulation of lymphocyte differentiation), GO:0050670 (regulation of lymphocyte proliferation), GO:0032944 (regulation of mononuclear cell proliferation), GO:0045648 (positive regulation of erythrocyte differentiation), GO:0045779 (negative regulation of bone resorption), GO:0045621 (positive regulation of lymphocyte differentiation), GO:0032945 (negative regulation of mononuclear cell proliferation), GO:0045646 (regulation of erythrocyte differentiation), GO:0019724 (B cell mediated immunity), GO:0045124 (regulation of bone resorption), GO:0050869 (negative regulation of B cell activation), GO:0050672 (negative regulation of lymphocyte proliferation), GO:0050864 (regulation of B cell activation), GO:0050871 (positive regulation of B cell activation), GO:0002761 (regulation of myeloid leukocyte differentiation), GO:0045577 (regulation of B cell differentiation), GO:0030889 (negative regulation of B cell proliferation), GO:0045671 (negative regulation of osteoclast differentiation), GO:0016064 (immunoglobulin mediated immune response), GO:0045655 (regulation of monocyte differentiation), GO:0030852 (regulation of granulocyte differentiation), GO:0030888 (regulation of B cell proliferation), GO:0045670 (regulation of osteoclast differentiation)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0005737 (cytoplasm), GO:0071944 (cell periphery), GO:0016020 (membrane), GO:0005886 (plasma membrane)