Myotubularin-related protein 4 (IPR030590)

Short name: MTMR4

Overlapping homologous superfamilies


Family relationships


Myotubularin-related protein 4 (MTMR4) is a member of the myotubularin (MTM) family. It is the only family member that possesses a FYVE domain (a zinc finger domain) at its C terminus [PMID: 11302699]. MTMR4 has dual-specificity phosphatase activity [PMID: 12925573]; some studies have shown that it can dephosphorylate PI3P or PI(3,5)P2, suggesting that MTMR4 is also a lipid phosphatase [PMID: 11302699]. MTMR4 has a unique distribution to endosomes [PMID: 16787938] and has been shown to function in early and recycling endosomes [PMID: 20736309, PMID: 20061380]. MTMR4 attenuates TGF-beta signalling by dephosphorylating intracellular signalling mediator R-Smads [PMID: 20061380]. Similarly, it acts as a negative modulator for the homeostasis of bone morphogenetic proteins (BMPs) signalling [PMID: 23150675].

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:0006470 protein dephosphorylation
GO:0007179 transforming growth factor beta receptor signaling pathway

Molecular Function

GO:0004722 protein serine/threonine phosphatase activity
GO:0004725 protein tyrosine phosphatase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

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