Phosphatase Family Myotubularin

Phosphatase Classification: FoldCC1: Superfamily CC1: Family Myotubularin

Myotubularins are phosphoinositide phosphatase found in a broad of eukaryotes. Human genome has 15 myotubularins and 7 subfamilies. Generally, human myotubularins are dephosphorylating phosphatidylinositol 3-phosphate [PtdIns(3)P] and phosphatidylinositol 3,5-bisphosphate [PtdIns (3,5)P2], but they are not redundant and have unique functions within cells by regulating a specific pool of PI(3)P or PI(3,5)P2 [1]. For example, subcellular localization of MTMR6 is regulated by interaction with small GTPase via its PH/GRAM domain. Another feature of myotubularins is pseudophosphatases within the family. 6 out of 15 human myotubularins are catalytically inactive. Their major functions are regulating the enzymatic activity of active myotubularins, e.g. the pairs between MTMR1:MTMR5, MTMR6:MTMR9.

Subfamilies

MTMR1

MTMR1 is a lipid phosphatase that dephosphorylates the second messenger phosphatidylinositol 3-monophosphate [PI(3)P]. It is found across holozoan.

MTMR5 (SBF)

MTMR5 is a subfamily of pseudophosphatase conserved in metazoan. It regulates the active MTMR1 subfamily by protein interactions.

MTMR6

MTMR6 is a phosphoinositide phosphatase found in holozoan. Its enzymatic activity is regulated by MTMR9.

MTMR9

MTMR9 is a conserved pseudophosphatase across holozoan. It regulates active phosphatases of subfamily MTMR6.

MTMR3

MTMR3 is an inositol lipid 3-phosphatase. It is probably a protein phosphatase of receptor-regulated SMAD. It is found throughout metazoan, with a signature FYVE domain.

MTMR14

MTMR14 is an active phosphatase found in most holozoan and slime molds. Its putative substrates are phosphatidylinositol bisphophosphates PtdIns(3,5)P2 and PtdIns (3,4)P2.

YMR1

Yeast has a single myotubularin YMR1, encoding PI(3)P phosphatase [2].

Reference

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