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 [].
Members of the golgin subfamily A were identified as Golgi auto-antigens []. They might be involved in maintaining cis-Golgi structure []. One of the members of this family, member 2 or GM130, is a specific interacting partner of the small GTPase Rab1b []and plays a key role in the disassembly and reassembly of the Golgi apparatus during mitosis. GM130 is also involved in vesicle tethering and fusion at the cis-cisternae to facilitate transit between transport vesicles and the stacked cisternae. It interacts with GRASPs proteins, which mediate the stacking of Golgi cisternae []. Additionally, GM130 was localised to the spindle poles and regulates microtubule organization [].Structurally, GM130 is comprised of six coiled-coil regions in the middle, a Golgi-targeting domain at the C terminus, and a p115-interacting motif at the N terminus []. This entry represents the conserved domain found in the Golgin subfamily A members. This domain is comprised of coiled-coil in GM130 (GOLGA2) and related proteins [].
Members of the golgin subfamily A were identified as Golgi auto-antigens []. They might be involved in maintaining cis-Golgi structure []. One of the members of this family, member 2 or GM130, is a specific interacting partner of the small GTPase Rab1b []and plays a key role in the disassembly and reassembly of the Golgi apparatus during mitosis. GM130 is also involved in vesicle tethering and fusion at the cis-cisternae to facilitate transit between transport vesicles and the stacked cisternae. It interacts with GRASPs proteins, which mediate the stacking of Golgi cisternae []. Additionally, GM130 was localised to the spindle poles and regulates microtubule organization [].Structurally, GM130 is comprised of six coiled-coil regions in the middle, a Golgi-targeting domain at the C terminus, and a p115-interacting motif at the N terminus [].
Members of the golgin subfamily A were identified as Golgi auto-antigens []. They might be involved in maintaining cis-Golgi structure []. One of the members of this family, member 2 or GM130, is a specific interacting partner of the small GTPase Rab1b []and plays a key role in the disassembly and reassembly of the Golgi apparatus during mitosis. GM130 is also involved in vesicle tethering and fusion at the cis-cisternae to facilitate transit between transport vesicles and the stacked cisternae. It interacts with GRASPs proteins, which mediate the stacking of Golgi cisternae []. Additionally, GM130 was localised to the spindle poles and regulates microtubule organization [].Structurally, GM130 is comprised of six coiled-coil regions in the middle, a Golgi-targeting domain at the C terminus, and a p115-interacting motif at the N terminus []. This entry represents the C-terminal motif of the golgin subfamily A member 2 protein (or GM130) that is bound by the GRASP65 PDZ1 and PDZ2 domains [, ]. These interactions are required for their association and localisation of GRASP65 to the cis-cisternae.
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.
