Phosphatase Subfamily MTMR1

Phosphatase Classification: Fold CC1: 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 fish to human, MTM1 and MTMR1 are adjacent on the X chromosome (see Genomicus).

Domain Structure

MTMR1 has a PH/GRAM, phosphatase domain and coiled-coil domain. The GRAM domain is similar to the PH domain in structure and is found in membrane-associated proteins. As shown in MTMR3 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. The coiled-coil domain has been shown to mediate the interaction between MTMR2 and MTMR5 and between MTMR2 and the MTMR5 subfamily members MTMR13 and MTMR5 in human [1, 2].

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 [3, 4]. Human MTMR1 and MTMR2 have been shown to dephosphorylate PI(3)P ([5] and [6], 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 [6].

Related Kinases

See PI3K.

References

Error fetching PMID 12668758:
Error fetching PMID 15998640:
Error fetching PMID 11001925:
Error fetching PMID 10900271:
Error fetching PMID 12217958:
Error fetching PMID 11733541: