Myotubularin-related protein 8 (IPR030591)

Short name: MTMR8

Overlapping homologous superfamilies

Family relationships


Myotubularin-related protein 8 (MTMR8) is a catalytically active member of the myotubularin (MTM) family, which possess 3-phosphatase activity dephosphorylating phosphatidylinositol-3-phoshate [PI(3)P] and phosphatidylinositol-3,5-bisphosphate [PI(3,5)P]. MTMR8 dimerises with the catalytically inactive MTMR9. Complex formation increases its catalytic activity and alters the substrate specificity; the MTMR8/R9 complex prefers PI(3)P as a substrate and reduces cellular PtdIns(3)P levels [PMID: 22647598]. The MTMR8/R9 complex inhibits autophagy [PMID: 22647598]. In zebrafish, MTMR8 has been shown to cooperate with PI3K to regulate actin filament modeling, and vascular and muscle development [PMID: 19325702, PMID: 20815916].

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) [PMID: 10900271, PMID: 11001925]. The substrate phosphoinositides (PIs) are known to regulate traffic within the endosomal-lysosomal pathway [PMID: 16828287]. 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 [PMID: 16787938]. The myotubularin family includes several members mutated in neuromuscular diseases or associated with metabolic syndrome, obesity, and cancer [PMID: 22578719].

GO terms

Biological Process

GO:0046856 phosphatidylinositol dephosphorylation
GO:0010506 regulation of autophagy

Molecular Function

GO:0052629 phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity
GO:0004438 phosphatidylinositol-3-phosphatase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.