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Information on EC 3.1.3.66 - phosphatidylinositol-3,4-bisphosphate 4-phosphatase and Organism(s) Mus musculus and UniProt Accession Q9EPW0
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3.1.3.66 phosphatidylinositol-3,4-bisphosphate 4-phosphataseIUBMB Comments
Mg2+-independent. This enzyme still works when the 2,3-bis(acyloxy)propyl group is removed, i.e., it hydrolyses Ins(1,3,4)P3 to Ins(1,3)P2. It also converts Ins(3,4)P2 into Ins-3-P.
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Word Map
- 3.1.3.66
- pten
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polyphosphate-4-phosphatase
- pik3ca
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basal-like
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ptdins3,4p2
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ptdins3,4,5p3
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5-phosphatase
- medicine
- phosphatidylinositol-3,4,5-trisphosphate
- 1,3,4-trisphosphate
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
inpp4b, inpp4a, inositol polyphosphate 4-phosphatase type ii, inositol polyphosphate 4-phosphatase, inositol polyphosphate 4-phosphatase type i, pi-4-phosphatase ii, 4-ptase-1, inositol polyphosphate 4-phosphatase ii, phosphoinositide 4-phosphatase, sac1p-like phosphoinositide phosphatase, 
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topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
D-myo-inositol-3,4-bisphosphate 4-phosphohydrolase
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inositol polyphosphate 4-phosphatase
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inositol polyphosphate 4-phosphatase type II
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inositol-3,4-bisphosphate 4-phosphatase
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INPP4B
phosphatase, inositol 3,4-bisphosphate 4-
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phosphoinositide 4-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-3,4-bisphosphate 4-phosphohydrolase
Mg2+-independent. This enzyme still works when the 2,3-bis(acyloxy)propyl group is removed, i.e., it hydrolyses Ins(1,3,4)P3 to Ins(1,3)P2. It also converts Ins(3,4)P2 into Ins-3-P.
CAS REGISTRY NUMBER
COMMENTARY
122653-78-5
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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
1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate + H2O
1-phosphatidyl-1D-myo-inositol 3-phosphate + phosphate
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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 3,4-bisphosphate + H2O
1-phosphatidyl-1D-myo-inositol 3-phosphate + phosphate
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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restricted to the Purkinje cell soma and their dendrites in the molecular layer
additional information
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phosphatidylinositol 4-phosphatase type II gene expression is turned off in malignant proerythroblasts of spi-1/PU.1 transgenic mice developing erythroleukemia. Stimulation of malignant cells with erythropoetin inudces PI-4-phosphatase II transcription pointing this gene as an erythropoetin-responsive gene
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
malfunction
physiological function
physiological function
in myeloid cell-specific Inpp4a-conditional knockout mice, macrophages show increased Akt phosphorylation and reduced production of inflammatory cytokines in response to LPS or Escherichia coli in vitro. The Inpp4a knockout mice survive for a shorter time than wild type mice after i.p. infection with Escherichia coli, with less production of inflammatory cytokines. Escherichia coli clearance from blood and lung is significantly impaired in the knockout mice
physiological function
INPP4a is secreted by airway epithelial cells and extracellular INPP4A critically inhibits airway inflammation and remodeling. INPP4A is present in blood and broncho-alveolar lavage fluid and is reduced in mice with allergic airway inflammation. In mice with allergic airway inflammation as well as naive mice, antibody-mediated neutralization of extracellular INPP4A potentiates PI3K/Akt signaling and induces airway hyperresponsiveness, with prominent airway remodeling, sub-epithelial fibroblast proliferation and collagen deposition
physiological function
Raw264.7 cells that express shRNA against isoform Inpp4a show significantly increased phagocytic activity. Macrophages from Inpp4a knockout mice show similar increases in the phagocytic activity. Inpp4a is recruited to the phagosome membrane by a mechanism other than the direct interaction with Rab5. The level of PtdIns(3,4)P2 increases on the phagosome of shRNA-treated cells, while the level of PtdIns(3)P significantly decreases
malfunction
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in mouse embryonic fibroblasts lacking 4-ptase-1 (-/-MEFs), the Akt-pleckstrin homology domain is constitutively membrane-associated both in serum-starved and agonist-stimulated cells. 4-Ptase-1-deficient cells show increased Akt signalling. Loss of 4-ptase-1 results in increased cell proliferation and decreased apoptosis. Loss of function of 4-ptase-1 leads to increased and sustained growth factor-stimulated levels of pSer473/Thr308-Akt and Akt phospho-substrates
malfunction
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Inpp4a weeble mutant has a frame shift mutation in Inpp4a and is characterized by an early onset recessive cerebellar ataxia. In the Inpp4a weeble mutant, Purkinje cells are lost in a specific temporal and spatial pattern: Purkinje cells are lost at early perinatal timepoints. Prior to the appearance of climbing fibers in the developing molecular layer, the Inpp4a weeble mutant has a normal complement of Purkinje cells and they are properly positioned, degeneration and reactive gliosis are present at postnatal day 5 and progress rapidly in a defined pattern of patches. Purkinje cell loss in the Inpp4awbl mutant is due to glutamate excitotoxicity initiated by the climbing fiber, whereby Eaat4 may exert a protective effect
malfunction
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ananlysis of the role of 4-phosphatase I in the regulation of PtdIns(3,4)P2 in platelets in the weeble mouse model, the mice are viable, but lack platelet 4-phosphatase I, overview. Weeble chimeric mice have a propensity for thrombosis using a carotid artery injury model
malfunction
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lung-specific knockdown of INPP4A by siRNA induces spontaneous inflammation in mice possibly by activating the PI3K-Akt pathway. In mice with experimental asthma, further knockdown of INPP4A by siRNA leads to a severe asthma phenotype, whereas overexpression of INPP4A reverses airway hyper-responsiveness (AHR) and airway inflammation in allergic mice
malfunction
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the insertion of Tgkd 3 of the Inpp4b gene is associated with decreased expression of Inpp4b and changes in intracellular PI3 Kinase/AKT signaling in follicular granulosa cells. This is associated with several follicular defects including oocytes trapped within luteinized follicles
physiological function
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4-ptase-1 controls the activation of Akt and thereby cell proliferation, survival and tumorigenesis. In mouse embryonic fibroblasts (+/+MEFs), the Akt-pleckstrin homology domain is detected at the plasma membrane following serum stimulation
physiological function
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PtdIns(3,4)P2 is important for platelet function and stabilizes platelet aggregates, role of inositol polyphosphate 4-phosphatase 1 in regulation of PtdIns(3,4)P2 and of platelet function, overview
physiological function
INPP4B suppresses Akt and PKC signaling pathways and modulates androgen receptor transcriptional activity in normal mouse prostate. Tumor suppressor PTEN protein levels and phosphorylation of S380 are the same in Inpp4b-/- and wild-type males
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). INP4A_MOUSE
939
0
105540
Swiss-Prot
Mitochondrion (Reliability: 5)
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
full-length 4-ptase-1 cDNA subcloned into the EcoRI site of pWzl-Hygromycin vector
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
level of 4-ptase-1 protein expressed in reconstituted embryonic fibroblasts reveals a 5fold increase relative to endogenous 4-ptase-1 in +/+MEFs
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
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physiological role of PI-4-phosphatase II in the proerythroblast by controlling erythropoetin-resonsiveness through a negative regualtion of the PI3K/Akt pathway is demonstrated
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Barnache, S.; Le Scolan, E.; Kosmider, O.; Denis, N.; Moreau-Gachelin, F.
Phosphatidylinositol 4-phosphatase type II is an erythropoietin-responsive gene
Oncogene
25
1420-1423
2006
Mus musculus
Ivetac, I.; Gurung, R.; Hakim, S.; Horan, K.A.; Sheffield, D.A.; Binge, L.C.; Majerus, P.W.; Tiganis, T.; Mitchell, C.A.
Regulation of PI(3)K/Akt signalling and cellular transformation by inositol polyphosphate 4-phosphatase-1
EMBO Rep.
10
487-493
2009
Mus musculus
Sachs, A.; David, S.; Haider, N.; Nystuen, A.
Patterned neuroprotection in the Inpp4a(wbl) mutant mouse cerebellum correlates with the expression of Eaat4
PLoS ONE
4
e8270
2009
Mus musculus
Marjanovic, J.; Wilson, M.; Zhang, C.; Zou, J.; Nicholas, P.; Majerus, P.
The role of inositol polyphosphate 4-phosphatase 1 in platelet function using a weeble mouse model
Adv. Enzyme Regul.
51
101-105
2011
Mus musculus
Balakrishnan, A.; Chaillet, J.R.
Role of the inositol polyphosphate-4-phosphatase type II Inpp4b in the generation of ovarian teratomas
Dev. Biol.
373
118-129
2013
Mus musculus
Aich, J.; Mabalirajan, U.; Ahmad, T.; Agrawal, A.; Ghosh, B.
Loss-of-function of inositol polyphosphate-4-phosphatase reversibly increases the severity of allergic airway inflammation
Nat. Commun.
3
877
2012
Mus musculus
Khanna, K.; Chaudhuri, R.; Aich, J.; Pattnaik, B.; Panda, L.; Prakash, Y.S.; Mabalirajan, U.; Ghosh, B.; Agrawal, A.
Secretory inositol polyphosphate 4-phosphatase protects against airway inflammation and remodeling
Am. J. Respir. Cell Mol. Biol.
60
399-412
2018
Homo sapiens (Q96PE3), Homo sapiens, Mus musculus (Q9EPW0)
Morioka, S.; Nigorikawa, K.; Sasaki, J.; Hazeki, K.; Kasuu, Y.; Sasaki, T.; Hazeki, O.
Myeloid cell-specific inositol polyphosphate-4-phosphatase type I knockout mice impair bacteria clearance in a murine peritonitis model
Innate Immun.
22
444-451
2016
Mus musculus (Q9EPW0), Mus musculus
Zhang, M.; Suarez, E.; Vasquez, J.L.; Nathanson, L.; Peterson, L.E.; Rajapakshe, K.; Basil, P.; Weigel, N.L.; Coarfa, C.; Agoulnik, I.U.
Inositol polyphosphate 4-phosphatase type II regulation of androgen receptor activity
Oncogene
38
1121-1135
2018
Homo sapiens (O15327), Homo sapiens, Mus musculus (Q6P1Y8), Mus musculus
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