Phosphatase Subfamily MTMR1
Phosphatase Classification: FoldCC1: Superfamily CC1: Family Myotubularin: MTMR1
MTMR1 subfamily is lipid phosphatase dephosphorylates second messenger phosphatidylinositol 3-monophosphate [PI(3)P].
Evolution
MTMR1 is found throughout holozoan. 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 GRAM and phosphatase domain. GRAM domain is similar to PH domain in structure and is found in membrane-associated proteins. MTMR1 in Monosiga has a C1 domain instead of GRAM domain. C1 domain is known to bind an important secondary messenger diacylglycerol (DAG).
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, fission yeast [1, 2]. Human MTMR1 and MTMR2 has been shown to dephosphorylate PI(3)P ([3] and [4], respectively). Although the enzymatic properties of the three human phosphatases are indistinguishable, their functions are not totally redundant. Actually, MTM1 and MTMR2 are differentially regulated in the aspects of developmental expression and subcellular localization, resulting in their utilization of specific cellular pools of PI(3)P [4].
Related Kinases
See PI3K.
MTMR1 subfamily and yeast YMR1
Yeast has a single myotubularin YMR1, encoding PI(3)P phosphatase 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
- 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 |
- Blondeau F, Laporte J, Bodin S, Superti-Furga G, Payrastre B, and Mandel JL. Myotubularin, a phosphatase deficient in myotubular myopathy, acts on phosphatidylinositol 3-kinase and phosphatidylinositol 3-phosphate pathway. Hum Mol Genet. 2000 Sep 22;9(15):2223-9. DOI:10.1093/oxfordjournals.hmg.a018913 |
- Kim SA, Taylor GS, Torgersen KM, and Dixon JE. Myotubularin and MTMR2, phosphatidylinositol 3-phosphatases mutated in myotubular myopathy and type 4B Charcot-Marie-Tooth disease. J Biol Chem. 2002 Feb 8;277(6):4526-31. DOI:10.1074/jbc.M111087200 |
- Buj-Bello A, Furling D, Tronchère H, Laporte J, Lerouge T, Butler-Browne GS, and Mandel JL. Muscle-specific alternative splicing of myotubularin-related 1 gene is impaired in DM1 muscle cells. Hum Mol Genet. 2002 Sep 15;11(19):2297-307. DOI:10.1093/hmg/11.19.2297 |
