|PROSITE documentation PDOC51339|
Myotubularin phosphatases are members of the protein tyrosine phosphatase (PTP) superfamily. The PTP domain is found in a diverse group of enzymes that catalyze phosphoester hydrolysis using a cysteine nucleophile and an arginine residue that binds to oxygen atoms of the phosphate. These two catalytically essential residues are found in a Cys-x(5)-Arg motif, which is a hallmark of PTP domains (see <PDOC00323>). The PTP superfamily of enzymes includes tyrosine-specific, dual specificity, low molecular weight, and Cdc25 phosphatases. All of these enzymes utilize phosphoproteins as substrates. Unlike these members of PTPs, enzymes that contain the tensin (see <PDOC51181>) and myotubularin PTP domain utilize the phosphoinositide as its physiologic substrate. Myotubularins are 3-phosphatases specific for membrane-embedded PtdIns3P and PtdIns(3,5)P2, two PIs that function within the endosomal-lysosomal pathway [1,2].
The myotubularin phosphatase domain consists of a central seven stranded β sheet flanked by thirteen α helices (see <PDB:1LW3>) . Although its core structure is similar to that of other PTP superfamily members, the myotubularin phosphatase domain is much larger. It contains an extra C-terminal region, which could be implicated in protein-protein interactions. The active site motif forms a P-loop at the base of a substrate binding pocket that is characteristic of PTP domains. This pocket is significantly deeper than that of other PTP pockets, which could explain the difference in substrate specificity.
The profile we developed covers the whole myotubularin phosphatase domain.Last update:
November 2007 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Denu J.M., Dixon J.E.|
|Title||Protein tyrosine phosphatases: mechanisms of catalysis and regulation.|
|Source||Curr. Opin. Chem. Biol. 2:633-641(1998).|
|2||Authors||Robinson F.L., Dixon J.E.|
|Title||Myotubularin phosphatases: policing 3-phosphoinositides.|
|Source||Trends Cell Biol. 16:403-412(2006).|
|3||Authors||Begley M.J., Taylor G.S., Kim S.A., Veine D.M., Dixon J.E., Stuckey J.A.|
|Title||Crystal structure of a phosphoinositide phosphatase, MTMR2: insights into myotubular myopathy and Charcot-Marie-Tooth syndrome.|
|Source||Mol. Cell 12:1391-1402(2003).|