Phosphatase Subfamily MTMR1

Phosphatase Classification: FoldCC1: Superfamily CC1: Family Myotubularin: Subfamily MTMR1

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

Evolution

MTMR1 is found throughout holozoa. It consists of three members in human, MTM1, MTMR1 and MTMR2. In fruit fly and C elegans, a single copy is found. In most vertebrates from bony fish to human, MTM1 and MTMR1 are adjacent on the X chromosome (see Genomicus).

Domain Structure

MTMR1 subfamily has a PH/GRAM, phosphatase domain and coiled-coil domain. The GRAM domain is similar to PH domain in structure and is found in membrane-associated proteins. As shown in MTMR subfamily, PH/GRAM domain can bind to phosphoinositide lipids. In Monosiga, the GRAM is replaced by a C1 domain, which is also a lipid-binding domain. Coiled-coil domain has been shown to mediate the interaction between MTMR2 and MTMR5 in human. MTMR5 belongs to MTMR5 subfamily [1].

Catalytic activity and functions

Human MTM1 has phosphatase activity towards the second messenger phosphatidylinositol 3-monophosphate [PI(3)P] in vitro and in human, budding yeast, and fission yeast [2, 3]. Human MTMR1 and MTMR2 have been shown to dephosphorylate PI(3)P ([4] and [5], respectively). Although the enzymatic properties of the three human phosphatases are indistinguishable, their functions are not totally redundant. MTM1 and MTMR2 are differentially regulated in the aspects of developmental expression and subcellular localization, resulting in their use of specific cellular pools of PI(3)P [5].

Related Kinases

See PI3K.

MTMR1 subfamily and yeast 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.

References

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