{PDOC51339}
{PS51339; PPASE_MYOTUBULARIN}
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* Myotubularin phosphatase domain *
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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 beta
sheet  flanked  by  thirteen  alpha helices (see <PDB:1LW3>) [3]. 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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: November 2007 / First entry.

[ 1] Denu J.M., Dixon J.E.
     "Protein tyrosine phosphatases: mechanisms of catalysis and
     regulation."
     Curr. Opin. Chem. Biol. 2:633-641(1998).
     PubMed=9818190
[ 2] Robinson F.L., Dixon J.E.
     "Myotubularin phosphatases: policing 3-phosphoinositides."
     Trends Cell Biol. 16:403-412(2006).
     PubMed=16828287; DOI=10.1016/j.tcb.2006.06.001
[ 3] Begley M.J., Taylor G.S., Kim S.A., Veine D.M., Dixon J.E.,
     Stuckey J.A.
     "Crystal structure of a phosphoinositide phosphatase, MTMR2: insights
     into myotubular myopathy and Charcot-Marie-Tooth syndrome."
     Mol. Cell 12:1391-1402(2003).
     PubMed=14690594

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