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Literature summary extracted from

  • Schaletzky, J.; Dove, S.K.; Short, B.; Lorenzo, O.; Clague, M.J.; Barr, F.A.
    Phosphatidylinositol-5-phosphate activation and conserved substrate specificity of the myotubularin phosphatidylinositol 3-phosphatases (2003), Curr. Biol., 13, 504-509.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
3.1.3.64 phosphatidylinositol 3-phosphate substrate is a weak allosteric activator of MTM1 capable of binding at a regulatory site on the monomeric enzyme, no physiological activator Homo sapiens
3.1.3.64 phosphatidylinositol 5-phosphate causes MTM1 to form a heptameric ring and is a specific allosteric activator of MTM1, MTMR3 and MTMR6, activates MTM1 activity toward both phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate Homo sapiens
3.1.3.95 1-phosphatidyl-1D-myo-inositol 5-phosphate reaction product, acts as a specific allosteric activator of myotubularin MTM1, and myotubularin-related proteins MTMR3 and MTMR6 Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
3.1.3.64 cDNAs encoding MTM1 and MTMR6 are cloned and expressed in SF9 insect cells, MTM1 is also expressed in yeast Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
3.1.3.64 C336S inactive MTMR6 active site mutant Homo sapiens
3.1.3.64 C375S inactive MTM1 mutant, catalytic cysteine Homo sapiens
3.1.3.64 additional information mutation of His-469 to the amino acid found in the disease state inactivates Homo sapiens
3.1.3.64 R114A MTM1 mutant, conserved residue, decreased response to the allosteric activator phosphatidylinositol 5-phosphate Homo sapiens
3.1.3.64 R184G MTM1 mutant with reduced activity Homo sapiens
3.1.3.64 R220A inactive MTM1 mutant, conserved residue Homo sapiens
3.1.3.64 R241L inactive MTM1 mutant Homo sapiens
3.1.3.64 R421Q MTM1 mutant with reduced activity Homo sapiens
3.1.3.64 R69C a disease-causing mutation of MTM1 falling within a putative pleckstrin homology domain, decreased response to the allosteric activator phosphatidylinositol 5-phosphate due to a reduced affinity for the activator, mutant with reduced activity due to a mutation in the allosteric regulatory site Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3.1.3.64 phosphatidylinositol 3,5-bisphosphate + H2O Homo sapiens physiologically relevant substrate phosphatidylinositol 5-phosphate + phosphate product could activate enzyme by a positive feedback mechanism ?
3.1.3.64 phosphatidylinositol 3-phosphate + H2O Homo sapiens phosphoinositide metabolism phosphatidylinositol + phosphate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
3.1.3.64 Homo sapiens
-
 myotubularins MTM1 and MTMR6
-
3.1.3.95 Homo sapiens Q9Y217 isoform MTMR6
-

Purification (Commentary)

EC Number Purification (Comment) Organism
3.1.3.64 recombinant MTM1 and MTMR6 Homo sapiens

Reaction

EC Number Reaction Comment Organism Reaction ID
3.1.3.64 1-phosphatidyl-1D-myo-inositol 3-phosphate + H2O = 1-phosphatidyl-1D-myo-inositol + phosphate two-step reaction mechanism Homo sapiens
a

Source Tissue

EC Number Source Tissue Comment Organism Textmining
3.1.3.64 liver
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.1.3.64 additional information myotubularins, e.g. MTM1 and MTMR6, are a family of phosphatidylinositol 3-phosphate phosphatases Homo sapiens ?
-
 ?
3.1.3.64 phosphatidylinositol 3,5-bisphosphate + H2O MTM1 and MTMR6, in vitro Homo sapiens phosphatidylinositol 5-phosphate + phosphate product causes MTM1 to form a heptameric ring and is a specific allosteric activator of MTM1, MTMR3 and MTMR6 ?
3.1.3.64 phosphatidylinositol 3,5-bisphosphate + H2O physiologically relevant substrate Homo sapiens phosphatidylinositol 5-phosphate + phosphate product could activate enzyme by a positive feedback mechanism ?
3.1.3.64 phosphatidylinositol 3-phosphate + H2O MTM1 and MTMR6 Homo sapiens phosphatidylinositol + phosphate
-
 ?
3.1.3.64 phosphatidylinositol 3-phosphate + H2O phosphoinositide metabolism Homo sapiens phosphatidylinositol + phosphate
-
 ?
3.1.3.95 1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate + H2O
-
 Homo sapiens 1-phosphatidyl-1D-myo-inositol 5-phosphate + phosphate product causes myotubularin MTM1 to form a heptameric ring that is 12.5 nm in diameter, and it is a specific allosteric activator of myotubularin MTM1, and myotubularin-related proteins MTMR3 and MTMR6 ?
3.1.3.95 1-phosphatidyl-1D-myo-inositol 3-phosphate + H2O
-
 Homo sapiens 1-phosphatidyl-1D-myo-inositol + phosphate
-
 ?
3.1.3.95 additional information isoform MTMR6 shows similar activity with substrates 1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate and 1-phosphatidyl-1D-myo-inositol 3-phosphate Homo sapiens ?
-
 ?

Subunits

EC Number Subunits Comment Organism
3.1.3.64 monomer MTM1 and MTMR6, catalytically inactive in absence of substrate, binding of substrate and of the allosteric activator phosphatidylinositol 5-phosphate triggers oligomerization and thus activates enzyme Homo sapiens
3.1.3.64 oligomer MTM1 and MTMR6, catalytically inactive monomer in absence of substrate, binding of substrate and of the allosteric activator phosphatidylinositol 5-phosphate triggers oligomerization and thus activates enzyme Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
3.1.3.64 More myotubularins are a family of phosphatidylinositol 3-phosphate phosphatases, e.g. MTM1, MTMR6, MTMR2 and MTMR3 Homo sapiens
3.1.3.95 MTMR6
-
 Homo sapiens
3.1.3.95 myotubularin-related protein 6
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
3.1.3.64 37
-
 assay at Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
3.1.3.64 6.5
-
 MTM1 and MTMR6 Homo sapiens