SHIP-2 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. Plays a central role in regulation of PI3K-dependent insulin signaling, although the precise molecular mechanisms and signaling pathways remain unclear. While overexpression reduces both insulin-stimulated MAP kinase and Akt activation, its absence does not affect insulin signaling or GLUT4 trafficking. Confers resistance to dietary obesity. May act by regulating AKT2, but not AKT1, phosphorylation at the plasma membrane. Part of a signaling pathway that regulates actin cytoskeleton remodeling. Required for the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation. Participates in regulation of cortical and submembraneous actin by hydrolyzing PtdIns(3,4,5)P3 thereby regulating membrane ruffling. Regulates cell adhesion and cell spreading. Required for HGF-mediated lamellipodium formation, cell scattering and spreading. Acts as a negative regulator of EPHA2 receptor endocytosis by inhibiting via PI3K-dependent Rac1 activation. Acts as a regulator of neuritogenesis by regulating PtdIns(3,4,5)P3 level and is required to form an initial protrusive pattern, and later, maintain proper neurite outgrowth. Acts as a negative regulator of the FC-gamma-RIIA receptor (FCGR2A). Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Involved in EGF signaling pathway. Upon stimulation by EGF, it is recruited by EGFR and dephosphorylates PtdIns(3,4,5)P3. Plays a negative role in regulating the PI3K-PKB pathway, possibly by inhibiting PKB activity. Down-regulates Fc-gamma-R-mediated phagocytosis in macrophages independently of INPP5D/SHIP1. In macrophages, down-regulates NF-kappa-B-dependent gene transcription by regulating macrophage colony-stimulating factor (M-CSF)-induced signaling. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6. Involved in endochondral ossification. Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase family. Widely expressed, most prominently in skeletal muscle, heart and brain. Present in platelets. Expressed in transformed myeloid cells and in primary macrophages, but not in peripheral blood monocytes. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: Carbohydrate Metabolism - inositol phosphate; EC; Motility/polarity/chemotaxis; Phosphatase, lipid
Chromosomal Location of Human Ortholog: 1q32
Cellular Component:  cytoplasm; cytoskeleton; cytosol; filopodium; Golgi apparatus; lamellipodium; membrane; plasma membrane
Molecular Function:  actin binding; hydrolase activity; inositol-polyphosphate 5-phosphatase activity; phosphatidylinositol-3,4,5-trisphosphate binding; protein binding; SH2 domain binding; SH3 domain binding
Biological Process:  actin filament organization; brain development; cell adhesion; cellular lipid metabolic process; endochondral ossification; endocytosis; glucose metabolic process; immune system process; inositol trisphosphate metabolic process; negative regulation of cell proliferation; negative regulation of DNA replication; negative regulation of gene expression; negative regulation of insulin receptor signaling pathway; negative regulation of insulin-like growth factor receptor signaling pathway; negative regulation of MAP kinase activity; negative regulation of neuron projection development; negative regulation of platelet-derived growth factor receptor signaling pathway; phosphatidylinositol biosynthetic process; phosphatidylinositol dephosphorylation; post-embryonic development; response to drug; response to insulin; ruffle assembly
Reference #:  Q9WVR3 (UniProtKB)
Alt. Names/Synonyms: inositol polyphosphate phosphatase-like 1; Inositol polyphosphate phosphatase-like protein 1; INPPL-1; Inppl1; Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2; Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2; SH2 domain-containing inositol phosphatase 2; SH2 domain-containing inositol-5'-phosphatase 2; SH2-containing inositol phosphatase 2; SHIP-2; Ship2
Gene Symbols: Inppl1
Molecular weight: 139,143 Da
Basal Isoelectric point: 6.06  Predict pI for various phosphorylation states
CST Pathways:  B Cell Receptor Signaling  |  Insulin Receptor Signaling
Select Structure to View Below


Protein Structure Not Found.

Cross-references to other databases:  STRING  |  Reactome  |  BioGPS  |  Pfam  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene