Difference between revisions of "Phosphatase Family Myotubularin"
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=== Subfamilies in other clades === | === Subfamilies in other clades === | ||
| − | + | ===== [[Phosphatase_Subfamily_YMR1|YMR1]] ===== | |
| + | The subfamily is named after the only myotubularin in budding yeast, YMR1. It encodes PI(3)P phosphatase <cite>taylor00</cite>. | ||
| − | + | ===== [[Phosphatase_Subfamily_Ank-MTM|Ank-MTM]] ===== | |
| + | The subfamily has Ank repeats at N-terminal. It is found not only in ''Dictyostelium discoideum'' but also other Dictyosteliida. | ||
| − | + | ===== [[Phosphatase_Subfamily_pats1|Pats1]] ===== | |
| + | The subfamily named after one of the two ''Dictyostelium discoideum'' myotubularins, pats1 and roco9. The subfamily is found in amoebazoa. The phosphatase domain is quite diverged from other myotubularins. It has a protein kinase domain. It is classified as [http://kinase.com/web/current/kinbase/genes/Family/LRRK/ TKL group, LRRK family in kinase.com]. | ||
=== Domains === | === Domains === | ||
Revision as of 20:38, 29 June 2015
Phosphatase Classification: Fold CC1: Superfamily CC1: Family Myotubularin
Subfamilies present in human
Human genome has 15 myotubularins and 7 subfamilies. Generally, human myotubularins dephosphorylates phosphatidylinositol 3-phosphate [PtdIns(3)P] and phosphatidylinositol 3,5-bisphosphate [PtdIns (3,5)P2], but they are not redundant and have unique functions within cells by regulating a specific pool of PI(3)P or PI(3,5)P2 [1]. For example, subcellular localization of MTMR6 is regulated by interaction with small GTPase via its PH/GRAM domain.
The myotubularin family is found throughout eukaryotes, from plants and protists of basal eukaryotes to fungi and animals. While myotubularins arose in early eukaryotes, 14 out of 15 human myotubularins probably emerged in holozoa or metazoa.
Another feature of myotubularins is a significant number of pseudophosphatases within the family. 6 out of 15 human myotubularins are catalytically inactive. Their major functions are regulating the enzymatic activity of active myotubularins, e.g. the pairs between MTMR1:MTMR5, MTMR6:MTMR9. All the interactions are mediated via coiled coils. One explanation is that MTMR1 and MTMR6 have the same ancestor, MTMR5 and MTMR9 have the same ancestor, their ancestors interacted via coiled coils. Alternatively, the coiled-coil interactions mediated MTMR1:MTMR5 and MTMR6:MTMR9 evolved, independently.
MTMR1
The MTMR1 subfamily dephosphorylates the second messenger phosphatidylinositol 3-monophosphate [PI(3)P]. It is conserved across holozoa. The pseudophosphatase MTMR5 can regulate its enzymatic activity.
MTMR3
The MTMR3 subfamily is an inositol lipid 3-phosphatase. It is probably a protein phosphatase of receptor-regulated SMAD. It is found throughout metazoa, with a signature FYVE domain.
MTMR5 (SBF): catalytically inactive
The MTMR5 subfamily is a subfamily of pseudophosphatase conserved in metazoa. It regulates the active MTMR1 subfamily by protein interactions.
MTMR6
The MTMR6 subfamily is a phosphoinositide phosphatase found in holozoa. Its enzymatic activity is regulated by MTMR9.
MTMR9: catalytically inactive
The MTMR9 subfamily is a conserved pseudophosphatase across holozoa. It regulates active phosphatases of subfamily MTMR6.
MTMR10: catalytically inactive
The MTMR10 subfamily is a conserved pseudophosphatase in metazoa. Its molecular function is unclear.
MTMR14
The MTMR14 subfamily is an active phosphatase found in most holozoa and slime molds. Its putative substrates are phosphatidylinositol bisphophosphates PtdIns(3,5)P2 and PtdIns (3,4)P2.
Subfamilies in other clades
YMR1
The subfamily is named after the only myotubularin in budding yeast, YMR1. It encodes PI(3)P phosphatase [2].
Ank-MTM
The subfamily has Ank repeats at N-terminal. It is found not only in Dictyostelium discoideum but also other Dictyosteliida.
Pats1
The subfamily named after one of the two Dictyostelium discoideum myotubularins, pats1 and roco9. The subfamily is found in amoebazoa. The phosphatase domain is quite diverged from other myotubularins. It has a protein kinase domain. It is classified as TKL group, LRRK family in kinase.com.
Domains
Myotubularins are phosphoinositide phosphatase found in a broad of eukaryotes. Myotubularins usually have multiple domains, containing PH/GRAM domain, phosphatase domain and coiled-coil domains. Some myotubularins gained and lost additional domains. Two remarkable examples are i) C1 domain was lost in vertebrate MTMR5/SBF subfamily, and ii) FYVE domain was gained in metazoa MTMR6 but lost in vertebrate MTMR6.
References
- Robinson FL and Dixon JE. Myotubularin phosphatases: policing 3-phosphoinositides. Trends Cell Biol. 2006 Aug;16(8):403-12. DOI:10.1016/j.tcb.2006.06.001 |
- 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 |
