Myotubularin-related protein 6 (MTMR6) (MTMR6)

Myotubularin-related protein 6 (MTMR6) is a member of the myotubularin family of phosphoinositide phosphatases, which are essential regulators of cellular signaling and membrane trafficking (UniProt, Q9Y217). It specifically catalyzes the dephosphorylation of phosphatidylinositol 3-phosphate (PI3P) at the D-3 position, converting it into phosphatidylinositol (PubMed, 11533054). A primary biological role of MTMR6 is the negative regulation of the calcium-activated potassium channel KCa3.1 (KCNN4) by reducing local PI3P levels required for channel activation (PubMed, 16103215). This regulation is particularly significant in T-cells, where MTMR6 acts as a brake on calcium signaling and subsequent T-cell proliferation and cytokine production (PubMed, 21613606). Consequently, MTMR6 is considered a potential therapeutic target for modulating immune responses in inflammatory and autoimmune diseases. Beyond immunology, MTMR6 has been implicated in the regulation of endosomal trafficking and cell migration, suggesting roles in cancer progression (PubMed, 21613606). While no small-molecule drugs are currently approved for MTMR6, research utilizing siRNA to target MTMR6 mRNA has demonstrated its potential in controlling immune activation and cell motility. Therapeutic challenges include achieving high selectivity over other myotubularin family members, such as MTM1 and MTMR2, which are associated with severe neuromuscular diseases when mutated (PubMed, 11533054).

Other names

MTMXPhosphatidylinositol-3-phosphatase MTMR6Myotubularin-related protein 6

MTMR6 acts as a lipid phosphatase that dephosphorylates phosphatidylinositol 3-phosphate (PI3P), thereby inhibiting the activation of the KCa3.1 potassium channel and suppressing T-cell signaling (PubMed, 16103215).