| Primary Identifier | IPR030574 | Type | Family |
| Short Name | MTMR5 |
| description | Myotubularin-related protein 5 (MTMR5), also known as SET-binding factor 1 (SBF1), belongs to the myotubularin family and is a pseudophosphatase. It lacks several amino acids in the catalytic pocket which renders it catalytically inactive as a phosphatase. It interacts with MTMR2. Through this interaction, MTMR5 increases the enzymatic activity of MTMR2 and dictates its subcellular localisation []. MTMR2 and MTMR5 are highly expressed in the testis, and could have a role in spermatogenesis []. MTMR5 may also function as a guanine nucleotide exchange factor (GEF) that activates Rab28 (a Rab GTPase) []. Mutations in MTMR5/SBF1 cause Charcot-Marie-Tooth disease type 4B3 (CMT4B3), which is a disorder of the peripheral nervous system [].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 []. |
