SH2 domain-containing inositol 5'-phosphatase 2 (SHIP2)

SH2 domain-containing inositol 5'-phosphatase 2 (SHIP2) is an enzyme encoded by the INPPL1 gene that specifically hydrolyzes the 5-phosphate from phosphatidylinositol-3,4,5-trisphosphate (PIP3), thus negatively regulating the PI3K/AKT signaling pathway. It contains an SH2 domain and participates in diverse biological processes, including insulin signaling, actin cytoskeleton organization, cell cycle control, cell proliferation, mitosis, endocytosis, immune cell signaling, and EGFR turnover. SHIP2 is implicated in human diseases such as cancer (notably breast cancer), metabolic diseases (including obesity and diabetes), and rare bone development syndromes (e.g., opsismodysplasia). Experimental inhibitors of SHIP2 are being developed for research purposes, but no approved therapeutic agents directly target this protein as of now. SHIP2 serves as a biomarker for certain cancers and plays a crucial role in regulating fundamental cellular and physiological processes, with its dysfunction potentially leading to pathological conditions.

Other names

Inositol polyphosphate phosphatase like 1INPPL1SHIP2INPPL-1SH2 domain-containing inositol phosphatase 2SHIP-2Inositol polyphosphate phosphatase-like protein 1Protein 51C51C proteinPhosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2

Inhibition of catalytic phosphatase activity, resulting in increased PI3K/AKT signaling and altered cellular processes (adhesion, proliferation, survival). Experimental inhibitors bind to the SHIP2 catalytic domain