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Information on EC 3.1.3.64 - phosphatidylinositol-3-phosphatase and Organism(s) Mus musculus and UniProt Accession Q9Z2C4
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3.1.3.64 phosphatidylinositol-3-phosphataseIUBMB Comments
This enzyme still works when the 2,3-bis(acyloxy)propyl group is removed, i.e., it hydrolyses Ins(1,3)P2 to Ins-1-P.
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Word Map
- 3.1.3.64
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x-linked
- phosphatases
- charcot-marie-tooth
- endosomal
- neuropathy
- autophagosome
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ptdins3,5p2
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centronuclear
- phosphatidylinositol-3-phosphate
- xlmtm
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demyelinate
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ptdins3,4,5p3
- pten
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endocytic
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ptdins5p
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beclin
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autophagy-related
- hypotonia
- ulk1
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myofibers
- dynamin
- 3-kinases
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phagophore
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sequestosome
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3,4,5-trisphosphate
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sqstm1
- 3,5-bisphosphate
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pleckstrin
- pikfyve
- pik3c3
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phosphoinositide-binding
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uvrag
- amphiphysins
- 3-phosphoinositide
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earl
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excitation-contraction
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polyphosphoinositides
- medicine
- phosphatidylinositol-3,5-bisphosphate
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Synonyms
ptdins3p, myotubularin, mtmr2, mtmr3, mtmr14, mtmr6, mtmr4, mtmr13, mtmr7, mtmr1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
D-myo-inositol 1,3-bisphosphate 3-phosphohydrolase
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inositol 1,3-bisphosphate phosphatase
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inositol-1,3-bisphosphate 3-phosphatase
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inositol-polyphosphate 3-phosphatase
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phosphatase, phosphatidylinositol 3-
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phosphatidyl-3-phosphate 3-phosphohydrolase
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phosphoinositide 3-phosphatase
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PtdIns 3-phosphatase
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
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SYSTEMATIC NAME
IUBMB Comments
1-phosphatidyl-1D-myo-inositol-3-phosphate 3-phosphohydrolase
This enzyme still works when the 2,3-bis(acyloxy)propyl group is removed, i.e., it hydrolyses Ins(1,3)P2 to Ins-1-P.
CAS REGISTRY NUMBER
COMMENTARY
122653-77-4
formerly, EC 3.1.3.65
124248-47-1
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
phosphatidylinositol 3,5-bisphosphate + H2O
phosphatidylinositol 5-phosphate + phosphate
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?
phosphatidylinositol 3-phosphate + H2O
phosphatidylinositol + phosphate
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1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate + H2O
1-phosphatidyl-1D-myo-inositol 5-phosphate + phosphate
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1-phosphatidyl-1D-myo-inositol 3-phosphate + H2O
1-phosphatidyl-1D-myo-inositol + phosphate
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phosphatidylinositol 3,5-bisphosphate + H2O
phosphatidylinositol 5-phosphate + phosphate
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phosphatidylinositol 3-phosphate + H2O
phosphatidylinositol + phosphate
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additional information
?
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MTMR1, MTMR2, MTMR3, MTMR4, MTMR6, MTMR7, MTMR8 and Jumpy (also known as MTMR14), possess an active phosphatase domain, that specifically dephosphorylates 1-phosphatidyl-1D-myo-inositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate at position 3 on inositol ring
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?
additional information
?
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MTMR6 interacts with GDP-bound Rab1B via the GRAM domain
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate + H2O
1-phosphatidyl-1D-myo-inositol 5-phosphate + phosphate
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?
1-phosphatidyl-1D-myo-inositol 3-phosphate + H2O
1-phosphatidyl-1D-myo-inositol + phosphate
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?
additional information
?
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MTMR1, MTMR2, MTMR3, MTMR4, MTMR6, MTMR7, MTMR8 and Jumpy (also known as MTMR14), possess an active phosphatase domain, that specifically dephosphorylates 1-phosphatidyl-1D-myo-inositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate at position 3 on inositol ring
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?
additional information
?
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MTMR6 interacts with GDP-bound Rab1B via the GRAM domain
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?
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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condensed in the perinuclear region in a microtubule-dependent manner. Rab1B regulates the localization of MTMR6
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
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autophagy initiation is strictly dependent on phosphatidylinositol 3-phosphate synthesis. PI3P production is under tight control of PI3Kinase, hVps34, in complex with Beclin-1. PI3P metabolism involved in autophagy initiation is further regulated by the PI3P phosphatases Jumpy and MTMR3, and other PI3P phosphatases might be involved in this process
physiological function
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the enzyme plays central role in autophagy, overview. Regulation and cellular functions of PI3P phosphatases, protein interacting partners of active PI3P phosphatases, overview
additional information
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PI3P is a substrate for PIP5-kinase, Fab1, also named PIKfyve, an enzyme that generates phosphoinositide 1-phosphatidyl-1D-myo-inositol 3,5-diphosphate
malfunction
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MTMR2-deficient mice develop CMT4B1-like neuropathy and azoospermia. MTMR13-deficient mice manifest myelin outfoldings in peripheral nerves. Jumpy or MTMR14-/- mice display muscle weakness and fatigue similar to patients with centronuclear myopathy
malfunction
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reduction of MTMR6 accelerates the transport of vesicular stomatitis virus glycoprotein in which Rab1B is involved. Furthermore, reduction of MTMR6 or Rab1B inhibits the formation of the tubular omegasome that is induced by overexpression of DFCP1 in autophagy
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MTMR1_MOUSE
669
0
75313
Swiss-Prot
other Location (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E276X
another animal model for Charcot-Marie-Tooth type 4B1 is produced by introducing the E276X mutation in exon 9. Phosphatase activity is inactivated toward PtdIns3P and PtdIns(3,5)P2. Nerve morphology in these mice is similar to that observed in Mtmr2-null mice, although a huge variability in the number of myelin outfoldings between different mice is noted. In both mutants, Mtmr2-null and E276X, the dysmyelinating phenotype is less severe than that observed in human Charcot-Marie-Tooth type 4B1
Q426X
phosphatase activity is inactivated toward PtdIns3P and PtdIns(3,5)P2 in vitro
Q482X
phosphatase activity is inactivated toward PtdIns3P and PtdIns(3,5)P2 in vitro
additional information
additional information
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Mtmr2-null mouse are created as an animal model for Charcot-Marie-Tooth type 4B1 by removing exon 4, which encodes part of the PH-GRAM domain. Mice are viable. In both motor and sensory nerves of mutant mice, myelin outfoldings are observed starting at 3-4 weeks after birth. Semithin analysis is performed in longitudinal section of nerves. Myelin outfoldings predominantly arise at paranodal regions extending throughout the internode. At 12-15 months of age, myelin outfoldings also arise at Schmidt-Lanterman incisures, other regions enriched in Schwann cell cytoplasm. Axonal loss is observed only in Mtmr2-null mice at later stages (around 15 months) in more distal nerves. Dysmyelinating phenotype is less severe than that observed in human Charcot-Marie-Tooth type 4B1. Mtmr2-null mice have also defects in spermatogenesis, again, starting at 3-4 weeks of age
additional information
Mtmr2-null mouse are created as an animal model for Charcot-Marie-Tooth type 4B1 by removing exon 4, which encodes part of the PH-GRAM domain. Mice are viable. In both motor and sensory nerves of mutant mice, myelin outfoldings are observed starting at 3-4 weeks after birth. Semithin analysis is performed in longitudinal section of nerves. Myelin outfoldings predominantly arise at paranodal regions extending throughout the internode. At 12-15 months of age, myelin outfoldings also arise at Schmidt-Lanterman incisures, other regions enriched in Schwann cell cytoplasm. Axonal loss is observed only in Mtmr2-null mice at later stages (around 15 months) in more distal nerves. Dysmyelinating phenotype is less severe than that observed in human Charcot-Marie-Tooth type 4B1. Mtmr2-null mice have also defects in spermatogenesis, again, starting at 3-4 weeks of age
additional information
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Mtm1 deficient mice have, after birth, normal muscle fibers with nuclei located at the periphery. Starting at 4 weeks of age, these mice develop a progressive myopathy characterized by hypotrophy and an increasing number of fibers with centrally located nuclei
additional information
Mtm1 deficient mice have, after birth, normal muscle fibers with nuclei located at the periphery. Starting at 4 weeks of age, these mice develop a progressive myopathy characterized by hypotrophy and an increasing number of fibers with centrally located nuclei
additional information
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deletion of the GRAM domain (amino acids 142-617) abolishes the binding of Rab1B
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
Charcot-Marie-Tooth type 4B1 animal model created by Mtmr2 null mice
medicine
MTm1 deficient mice serve as an animal model for X-linked myotubular myopathy
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Bolis, A.; Zordan, P.; Coviello, S.; Bolino, A.
Myotubularin-related (MTMR) phospholipid phosphatase proteins in the peripheral nervous system
Mol. Neurobiol.
35
308-316
2007
Chlorocebus aethiops, Caenorhabditis elegans, Caenorhabditis elegans (Q965W9), Homo sapiens, Mus musculus, Mus musculus (Q9Z2C4), Rattus norvegicus
Vergne, I.; Deretic, V.
The role of PI3P phosphatases in the regulation of autophagy
FEBS Lett.
584
1313-1318
2010
Saccharomyces cerevisiae, Homo sapiens, Mus musculus
Mochizuki, Y.; Ohashi, R.; Kawamura, T.; Iwanari, H.; Kodama, T.; Naito, M.; Hamakubo, T.
Phosphatidylinositol 3-phosphatase myotubularin-related protein 6 (MTMR6) is regulated by small GTPase Rab1B in the early secretory and autophagic pathways
J. Biol. Chem.
288
1009-1021
2013
Mus musculus
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