Myotubularin-related protein 6 (MTMR6) is a catalytically active member of the myotubularin (MTM) family, which possess 3-phosphatase activity dephosphorylating phosphatidylinositol-3-phoshate and phosphatidylinositol-3,5-bisphosphate. MTMR6 forms a heteromer with enzymatically inactive MTMR9. MTMR9 increases MTMR6 binding to phospholipids and increases the 3-phosphatase activity of MTMR6 []. MTMR6 is reported to be involved in the regulation of the Ca2+-activated K+ channel KCa3.1 []and apoptosis []. The cellular localisation of MTMR6 is regulated by Rab1B in the early secretory and autophagic pathways [].
Myotubularin-related protein 7 (MTMR7) is a member of the myotubularin (MTM) family. MTMR9 is a binding partner of MTMR7, and binding of MTMR9 increases the phosphatase activity of MTMR7 []. MTMR9 and MTMR7 may be involved in regulating T-helper (Th) cells differentiation [].The myotubularin family constitutes a large group of conserved proteins, with 14 members in humans consisting of myotubularin (MTM1) and 13 myotubularin-related proteins (MTMR1-MTMR13). Orthologues have been found throughout the eukaryotic kingdom, but not in bacteria. MTM1 dephosphorylates phosphatidylinositol 3-monophosphate (PI3P) to phosphatidylinositol and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2]to phosphatidylinositol 5-monophosphate (PI5P) [, ]. The substrate phosphoinositides (PIs) are known to regulate traffic within the endosomal-lysosomal pathway []. MTMR1, MTMR2, MTMR3, MTMR4, and MTMR6 have also been shown to utilise PI(3)P as a substrate, suggesting that this activity is intrinsic to all active family members. On the other hand, six of the MTM family members encode for catalytically inactive phosphatases. Inactive myotubularin phosphatases contain substitutions in the Cys and Arg residues of the Cys-X5-Arg motif. MTM pseudophosphatases have been found to interact with MTM catalytic phosphatases []. The myotubularin family includes several members mutated in neuromuscular diseases or associated with metabolic syndrome, obesity, and cancer [].MTMR7 contains a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an active PTP domain, a SET-interaction domain, and a C-terminal coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. This entry represents the PH-GRAM domain of MTMR7.
Myotubularin-related protein 7 (MTMR7) is a member of the myotubularin (MTM) family. MTMR9 is a binding partner of MTMR7, and binding of MTMR9 increases the phosphatase activity of MTMR7 []. MTMR9 and MTMR7 may be involved in regulating T-helper (Th) cells differentiation [].The myotubularin family constitutes a large group of conserved proteins, with 14 members in humans consisting of myotubularin (MTM1) and 13 myotubularin-related proteins (MTMR1-MTMR13). Orthologues have been found throughout the eukaryotic kingdom, but not in bacteria. MTM1 dephosphorylates phosphatidylinositol 3-monophosphate (PI3P) to phosphatidylinositol and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2]to phosphatidylinositol 5-monophosphate (PI5P) [, ]. The substrate phosphoinositides (PIs) are known to regulate traffic within the endosomal-lysosomal pathway []. MTMR1, MTMR2, MTMR3, MTMR4, and MTMR6 have also been shown to utilise PI(3)P as a substrate, suggesting that this activity is intrinsic to all active family members. On the other hand, sixof the MTM family members encode for catalytically inactive phosphatases. Inactive myotubularin phosphatases contain substitutions in the Cys and Arg residues of the Cys-X5-Arg motif. MTM pseudophosphatases have been found to interact with MTM catalytic phosphatases []. The myotubularin family includes several members mutated in neuromuscular diseases or associated with metabolic syndrome, obesity, and cancer [].
Myotubularin-related protein 6 (MTMR6) is a catalytically active member of the myotubularin (MTM) family, which possess 3-phosphatase activity dephosphorylating phosphatidylinositol-3-phoshate and phosphatidylinositol-3,5-bisphosphate. MTMR6 forms a heteromer with enzymatically inactive MTMR9. MTMR9 increases MTMR6 binding to phospholipids and increases the 3-phosphatase activity of MTMR6 []. MTMR6 is reported to be involved in the regulation of the Ca2+-activated K+ channel KCa3.1 []and apoptosis []. The cellular localisation of MTMR6 is regulated by Rab1B in the early secretory and autophagic pathways [].The myotubularin family constitutes a large group of conserved proteins, with 14 members in humans consisting of myotubularin (MTM1) and 13 myotubularin-related proteins (MTMR1-MTMR13). Orthologues have been found throughout the eukaryotic kingdom, but not in bacteria. MTM1 dephosphorylates phosphatidylinositol 3-monophosphate (PI3P) to phosphatidylinositol and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2]to phosphatidylinositol 5-monophosphate (PI5P) [, ]. The substrate phosphoinositides (PIs) are known to regulate traffic within the endosomal-lysosomal pathway []. MTMR1, MTMR2, MTMR3, MTMR4, and MTMR6 have also been shown to utilise PI(3)P as a substrate, suggesting that this activity is intrinsic to all active family members. On the other hand, six of the MTM family members encode for catalytically inactive phosphatases. Inactive myotubularin phosphatases contain substitutions in the Cys and Arg residues of the Cys-X5-Arg motif. MTM pseudophosphatases have been found to interact with MTM catalytic phosphatases []. The myotubularin family includes several members mutated in neuromuscular diseases or associated with metabolic syndrome, obesity, and cancer [].MTMR6 contains an N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an active PTP domain, a SET-interaction domain, and a C-terminal coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. This entry represents the PH-GRAM domain of MTMR6.
