Phosphatase Subfamily MTMR3
Phosphatase Classification: FoldCC1: Superfamily CC1: Family Myotubularin: MTMR3
MTMR1 is a lipid phosphatase that dephosphorylates the second messenger phosphatidylinositol 3-monophosphate [PI(3)P].
Evolution
MTMR1 is in metazoan. It consists of two members in human, MTMR3 and MTMR4. In fruit fly and C elegans, a single copy is found.
Domain Structure
MTMR3 subfamily has a conserved domain combination: a divergent PH/GRAM domain, an active phosphatase domain and an atypical FYVE domain. It has been shown that the FYVE domain of MTMR3 is atypical in that it neither confers endosomal localisation nor binds to the lipid PtdIns3P. Furthermore it is not required for in vitro enzyme activity of MTMR3. In contrast, the PH/GRAM domain is able to bind to phosphoinositide lipids [1].
Catalytic activity and functions
Human MTMR3 is an inositol lipid 3-phosphatase, with a so-far-unique substrate specificity. It is able to hydrolyze PtdIns3P and PtdIns(3,5)P2, both in vitro and when heterologously expressed in S. cerevisiae. Thus, MTMR3 plays critical role in the cellular production of PtdIns5P [2]. Human MTMR4 is also an inositol lipid 3-phosphatase, with amino acid sequence identity about ~47% [3].
More recently, MTMR4 has been reported to dephosphorylate receptor-regulated SMAD proteins [4, 5].
Related Kinases
See PI3K.
References
- Lorenzo O, Urbé S, and Clague MJ. Analysis of phosphoinositide binding domain properties within the myotubularin-related protein MTMR3. J Cell Sci. 2005 May 1;118(Pt 9):2005-12. DOI:10.1242/jcs.02325 |
- Walker DM, Urbé S, Dove SK, Tenza D, Raposo G, and Clague MJ. Characterization of MTMR3. an inositol lipid 3-phosphatase with novel substrate specificity. Curr Biol. 2001 Oct 16;11(20):1600-5. DOI:10.1016/s0960-9822(01)00501-2 |
- Zhao R, Qi Y, Chen J, and Zhao ZJ. FYVE-DSP2, a FYVE domain-containing dual specificity protein phosphatase that dephosphorylates phosphotidylinositol 3-phosphate. Exp Cell Res. 2001 May 1;265(2):329-38. DOI:10.1006/excr.2001.5185 |
- Yu J, Pan L, Qin X, Chen H, Xu Y, Chen Y, and Tang H. MTMR4 attenuates transforming growth factor beta (TGFbeta) signaling by dephosphorylating R-Smads in endosomes. J Biol Chem. 2010 Mar 12;285(11):8454-62. DOI:10.1074/jbc.M109.075036 |
- Yu J, He X, Chen YG, Hao Y, Yang S, Wang L, Pan L, and Tang H. Myotubularin-related protein 4 (MTMR4) attenuates BMP/Dpp signaling by dephosphorylation of Smad proteins. J Biol Chem. 2013 Jan 4;288(1):79-88. DOI:10.1074/jbc.M112.413856 |
