Phosphatase Subfamily PTPMT1
Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily PTPMT1
Evolution
It is found in most or all animals and higher plants, but is absent from fungi, Monosiga, and lower plants. It is also found in several protists, including Dictyostelium , Leishamania, Trypanosomes, Ectocarpus, and diatoms. More surprisingly, a functional PTPMT1 is found in a eubacterium Rhodopirellula baltica [1].
Domain
PTPMT1 has a single domain: phosphatase domain. It has a mitochondria-targeting sequence on N-terminus.
Function
PTPMT1 (or PLIP) is the first member of PTP superfamily found exclusively localized to the mitochondrion [2]. It was originally discovered as an open reading frame encoding a phosphatase with sequence similarity to the tumor suppressor PTEN [3]. Like PTEN, PTPMT1 possesses very poor activity toward proteinaceous substrates [3]. In vitro, it specifically dephosphorylates phosphatidylinositol 5-phosphate (PI5P), displaying much less activity against any other phosphoinositides [3]. However, depletion of PTPMT1 in cells produces no effect on the cellular level of PI5P, suggesting that PI5P is not the endogenous substrate [2]. Later, it has been found that PTPMT1 is a mitochondrial phosphatase that converts phosphatidylglycerolphosphate (PGP) to phosphatidylglycerol, a critical step in the de novo biosynthesis of cardiolipin [4].
Acknowledgement
Thank Ji Zhang at UC San Diego for her contribution.
References
- Teh PG, Chen MJ, Engel JL, Worby CA, Manning G, Dixon JE, and Zhang J. Identification of a mammalian-type phosphatidylglycerophosphate phosphatase in the Eubacterium Rhodopirellula baltica. J Biol Chem. 2013 Feb 15;288(7):5176-85. DOI:10.1074/jbc.M112.413617 |
- Pagliarini DJ, Wiley SE, Kimple ME, Dixon JR, Kelly P, Worby CA, Casey PJ, and Dixon JE. Involvement of a mitochondrial phosphatase in the regulation of ATP production and insulin secretion in pancreatic beta cells. Mol Cell. 2005 Jul 22;19(2):197-207. DOI:10.1016/j.molcel.2005.06.008 |
- Pagliarini DJ, Worby CA, and Dixon JE. A PTEN-like phosphatase with a novel substrate specificity. J Biol Chem. 2004 Sep 10;279(37):38590-6. DOI:10.1074/jbc.M404959200 |
- Zhang J, Guan Z, Murphy AN, Wiley SE, Perkins GA, Worby CA, Engel JL, Heacock P, Nguyen OK, Wang JH, Raetz CR, Dowhan W, and Dixon JE. Mitochondrial phosphatase PTPMT1 is essential for cardiolipin biosynthesis. Cell Metab. 2011 Jun 8;13(6):690-700. DOI:10.1016/j.cmet.2011.04.007 |
