Phosphatase Family Myotubularin

Phosphatase Classification: FoldCC1: Superfamily CC1: Family Myotubularin

Myotubularins are 3-phosphatases specific for PtdIns3P and PtdIns(3,5)P2, two PIs that function within the endosomal-lysomal pathway . In yeast, there is a single myotubularin Ymr1p, and its functions appear to be redundant with those of other 3-phosphatases. In C. elegans, which has six myotubularins, several of the myotublarins have non-redundant roles in regulating PtdIns3P during endocytosis. In human, there are 14 myotublarins, and mutations in several of them lead to myotubular myopathy and Charcot-Marie-Tooth peripheral neuropathy. Interestingly, around half of myotubularins are catalytically inactive. One of their possible function is regulating active myotubularins by protein interaction. For details, see the review [1].

Subfamilies

MTMR1

MTMR1 subfamily is PI3P phosphatase conserved in holozoan. It usually has an accessory GRAM domain and a phosphatase domain. GRAM domain is found in membrane-associated proteins and is structurally similar to PH domain.

MTMR5 (SBF)

Inactive myotubularin subfamily.

YMR1

Yeast has a single myotubularin YMR1, encoding PI(3)P phosphatase [2]. It has a single phosphatase domain, - no accessary domain is detected so far. YMR1 is supposed to be the ancestor of all 14 myotubularins in human, but it is hard to determine which subfamily is orthologous to it in human.

Reference

1. Robinson FL and Dixon JE. Myotubularin phosphatases: policing 3-phosphoinositides. Trends Cell Biol. 2006 Aug;16(8):403-12. DOI:10.1016/j.tcb.2006.06.001 |
2. Taylor GS, Maehama T, and Dixon JE. Myotubularin, a protein tyrosine phosphatase mutated in myotubular myopathy, dephosphorylates the lipid second messenger, phosphatidylinositol 3-phosphate. Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):8910-5. DOI:10.1073/pnas.160255697 |