Phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR6 (MTMR6)

Phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR6 is a lipid phosphatase that specifically dephosphorylates the D-3 position of phosphatidylinositol 3-phosphate (PI(3)P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), producing phosphatidylinositol and phosphatidylinositol 5-phosphate, respectively. It belongs to the myotubularin-related protein family and forms a heterodimer with MTMR9, which enhances its enzymatic activity and stabilizes both proteins. MTMR6 localizes to the cytoplasm, nuclear envelope, pericentrosomal region, and peri-Golgi area in a microtubule-dependent manner, where it interacts with Rab1B via its GRAM domain to regulate early secretory and autophagic pathways. The MTMR6-MTMR9 complex negatively regulates ER-Golgi protein transport, late-stage macropinocytosis by dephosphorylating PI(3)P in membrane ruffles, KCNN4/KCa3.1 channel activity in CD4+ T-cells, proliferation of reactivated CD4+ T-cells, and DNA damage-induced apoptosis. Although no direct mutations in MTMR6 are linked to human genetic diseases, it is associated with myopathy, centronuclear, X-linked, and plays roles in 3-phosphoinositide metabolism without established therapeutic drugs or biomarkers.

Other names

Myotubularin-related protein 6Myotubularin related protein 6Phosphatidylinositol-3-phosphate phosphatasePhosphatidylinositol-3,5-bisphosphate 3-phosphatase