Phosphatase Subfamily MTMR9

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Phosphatase Classification: Fold CC1: Superfamily CC1: Family Myotubularin: Subfamily MTMR9

MTMR9 is a conserved pseudophosphatase across holozoan. It regulates active phosphatases of subfamily MTMR6.

Evolution

MTMR9 is found throughout holozoan. It is usually single copy per genome.

Domain Structure

MTMR9 subfamily has three domains: 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 MTMR3 subfamily, PH/GRAM domain can bind to phosphoinositide lipids. Coiled-coil domain has been shown to mediate the interaction between MTMR9 and members of MTMR6 in human [1, 2, 3].

Catalytic activity and functions

MTMR9 is an inactive phosphatase (pseudophosphatase). MTMR9 binds to phosphatases of MTMR6 subfamily: MTMR6 [2], MTMR7 [1], MTMR8 [3]. The interactions increase the enzymatic activity of these phosphatases. The interaction between MTMR9 and members of MTMR6 subfamily is also observed in C. elegans [4].

References

  1. Mochizuki Y and Majerus PW. Characterization of myotubularin-related protein 7 and its binding partner, myotubularin-related protein 9. Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9768-73. DOI:10.1073/pnas.1333958100 | PubMed ID:12890864 | HubMed [Mochizuki03]
  2. Zou J, Chang SC, Marjanovic J, and Majerus PW. MTMR9 increases MTMR6 enzyme activity, stability, and role in apoptosis. J Biol Chem. 2009 Jan 23;284(4):2064-71. DOI:10.1074/jbc.M804292200 | PubMed ID:19038970 | HubMed [zou09]
  3. Zou J, Zhang C, Marjanovic J, Kisseleva MV, Majerus PW, and Wilson MP. Myotubularin-related protein (MTMR) 9 determines the enzymatic activity, substrate specificity, and role in autophagy of MTMR8. Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9539-44. DOI:10.1073/pnas.1207021109 | PubMed ID:22647598 | HubMed [zou12]
  4. Silhankova M, Port F, Harterink M, Basler K, and Korswagen HC. Wnt signalling requires MTM-6 and MTM-9 myotubularin lipid-phosphatase function in Wnt-producing cells. EMBO J. 2010 Dec 15;29(24):4094-105. DOI:10.1038/emboj.2010.278 | PubMed ID:21076391 | HubMed [marie10]
All Medline abstracts: PubMed | HubMed