SHIP
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. Able also to hydrolyzes 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. Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase family. 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). 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC 3.1.3.86; Motility/polarity/chemotaxis; Phosphatase, lipid
Biological Process: apoptotic process; determination of adult lifespan; immune system process; immunoglobulin mediated immune response; intracellular signal transduction; lipid metabolic process; negative regulation of B cell activation; negative regulation of B cell proliferation; negative regulation of bone resorption; negative regulation of granulocyte differentiation; negative regulation of immune response; negative regulation of interleukin-6 production; negative regulation of monocyte differentiation; negative regulation of neutrophil differentiation; negative regulation of osteoclast differentiation; negative regulation of signal transduction; phosphatidylinositol dephosphorylation; positive regulation of apoptotic process; positive regulation of B cell differentiation; positive regulation of erythrocyte differentiation; positive regulation of lymphocyte differentiation; regulation of immune response
