Literature summary for 3.1.3.64 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.

Search for more literature for 3.1.3.64

Activating Compound

Activating Compound	Comment	Organism	Structure
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
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

Cloned(Commentary)

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

Protein Variants

Protein Variants	Comment	Organism
C336S	inactive MTMR6 active site mutant	Homo sapiens
C375S	inactive MTM1 mutant, catalytic cysteine	Homo sapiens
additional information	mutation of His-469 to the amino acid found in the disease state inactivates	Homo sapiens
R114A	MTM1 mutant, conserved residue, decreased response to the allosteric activator phosphatidylinositol 5-phosphate	Homo sapiens
R184G	MTM1 mutant with reduced activity	Homo sapiens
R220A	inactive MTM1 mutant, conserved residue	Homo sapiens
R241L	inactive MTM1 mutant	Homo sapiens
R421Q	MTM1 mutant with reduced activity	Homo sapiens
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)

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

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	myotubularins MTM1 and MTMR6	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant MTM1 and MTMR6	Homo sapiens

Reaction

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

Source Tissue

Source Tissue	Comment	Organism	Textmining
liver	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
additional information	myotubularins, e.g. MTM1 and MTMR6, are a family of phosphatidylinositol 3-phosphate phosphatases	Homo sapiens	?	-	?
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	?
phosphatidylinositol 3,5-bisphosphate + H2O	physiologically relevant substrate	Homo sapiens	phosphatidylinositol 5-phosphate + phosphate	product could activate enzyme by a positive feedback mechanism	?
phosphatidylinositol 3-phosphate + H2O	MTM1 and MTMR6	Homo sapiens	phosphatidylinositol + phosphate	-	?
phosphatidylinositol 3-phosphate + H2O	phosphoinositide metabolism	Homo sapiens	phosphatidylinositol + phosphate	-	?

Subunits

Subunits	Comment	Organism
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
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

Synonyms	Comment	Organism
More	myotubularins are a family of phosphatidylinositol 3-phosphate phosphatases, e.g. MTM1, MTMR6, MTMR2 and MTMR3	Homo sapiens

Temperature Optimum [°C]

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

pH Optimum

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

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Release 2023.1 (January 2023)