Myotubularin-related protein 6

Definition:

Phosphatase that acts on lipids with a phosphoinositol headgroup. Dephosphorylates phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 3,5-bisphosphate (Probable). Binds with high affinity to phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) but also to phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4-phosphate (PtdIns(4)P), and phosphatidylinositol 5-phosphate (PtdIns(5)P), phosphatidic acid and phosphatidylserine. Negatively regulates ER-Golgi protein transport (By similarity). Probably in association with MTMR9, plays a role in the late stages of macropinocytosis by dephosphorylating phosphatidylinositol 3-phosphate in membrane ruffles. Acts as a negative regulator of KCNN4/KCa3.1 channel activity in CD4(+) T-cells possibly by decreasing intracellular levels of phosphatidylinositol 3-phosphate. Negatively regulates proliferation of reactivated CD4(+) T-cells. In complex with MTMR9, negatively regulates DNA damage-induced apoptosis. The formation of the MTMR6-MTMR9 complex stabilizes both MTMR6 and MTMR9 protein levels.

References:

[1]. Jun Zou, et al. MTMR9 increases MTMR6 enzyme activity, stability, and role in apoptosis. J Biol Chem. 2009 Jan 23;284(4):2064-71. [Content Brief]

[2]. Shekhar Srivastava, et al. Phosphatidylinositol-3 phosphatase myotubularin-related protein 6 negatively regulates CD4 T cells. Mol Cell Biol. 2006 Aug;26(15):5595-602. [Content Brief]

[3]. Masashi Maekawa, et al. Sequential breakdown of 3-phosphorylated phosphoinositides is essential for the completion of macropinocytosis. Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):E978-87. [Content Brief]

[4]. Jun Zou, et al. Myotubularin-related protein (MTMR) 9 determines the enzymatic activity, substrate specificity, and role in autophagy of MTMR8. Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9539-44. [Content Brief]

[5]. Shekhar Srivastava, et al. The phosphatidylinositol 3-phosphate phosphatase myotubularin- related protein 6 (MTMR6) is a negative regulator of the Ca2+-activated K+ channel KCa3.1. Mol Cell Biol. 2005 May;25(9):3630-8. [Content Brief]

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