Phosphatase Subfamily MTMR10
Phosphatase Classification: Fold CC1: Superfamily CC1: Family Myotubularin: Subfamily MTMR10
MTMR10 is a metazoan pseudophosphatase that interacts with active myotubularins.
Evolution
MTMR10 is found in most metazoa. Humans have 3 genes: MTMR10, MTMR11, MTMR12, and most invertebrates have one.
Domain Structure
MTMR10 subfamily has three domains: GRAM, phosphatase domain and coiled-coil domain. The GRAM domain is similar in structure to the PH domain and is found in membrane-associated proteins.
Two of the three sponge MTMR10s have a Death domain and a DUF3584 domain flanking the phosphatase domains. Death domains bind each other forming oligomers. DUF3584 is close to AAA+ superfamily. They do not have a GRAM or coiled-coil domain. The third sponge member is a fragment copy of one of the other two.
Catalytic activity and functions
MTMR10 and MTM12 interact with MTMR2 [1], and MTMR12 also with MTM1 [2], both of the MTMR1 subfamily. In human, mouse and zebrafish, loss of MTMR12 destabilizes MTM1[3], and in zebrafish, gives a similar disease phenotype to loss of MTM1. Similar interactions between other subfamilies of active and inactive myotubularins are seen, usually mediated by the coiled-coil interaction domains.
References
- Hein MY, Hubner NC, Poser I, Cox J, Nagaraj N, Toyoda Y, Gak IA, Weisswange I, Mansfeld J, Buchholz F, Hyman AA, and Mann M. A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell. 2015 Oct 22;163(3):712-23. DOI:10.1016/j.cell.2015.09.053 |
- Nandurkar HH, Layton M, Laporte J, Selan C, Corcoran L, Caldwell KK, Mochizuki Y, Majerus PW, and Mitchell CA. Identification of myotubularin as the lipid phosphatase catalytic subunit associated with the 3-phosphatase adapter protein, 3-PAP. Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8660-5. DOI:10.1073/pnas.1033097100 |
- Gupta VA, Hnia K, Smith LL, Gundry SR, McIntire JE, Shimazu J, Bass JR, Talbot EA, Amoasii L, Goldman NE, Laporte J, and Beggs AH. Loss of catalytically inactive lipid phosphatase myotubularin-related protein 12 impairs myotubularin stability and promotes centronuclear myopathy in zebrafish. PLoS Genet. 2013 Jun;9(6):e1003583. DOI:10.1371/journal.pgen.1003583 |
