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Information on EC 3.1.3.66 - phosphatidylinositol-3,4-bisphosphate 4-phosphatase
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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
-
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 enzyme appears in 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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SYNONYM 
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
inositol-3,4-bisphosphate 4-phosphatase
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INPP4A
INPP4B
phosphatase, inositol 3,4-bisphosphate 4-
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phosphoinositide 4-phosphatase
inositol polyphosphate 4-phosphatase type II
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phosphoinositide 4-phosphatase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate + H2O = 1-phosphatidyl-1D-myo-inositol 3-phosphate + phosphate
Mg2+-independent, the 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 to Ins-3-P
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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.
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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
1-phosphatidyl-myo-inositol 3,4-bisphosphate + H2O
1-phosphatidyl-1D-myo-inositol 3-phosphate + phosphate
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?
D-myo-phosphatidylinositol-3,4-bisphosphate + H2O
D-myo-inositol 4-phosphate + phosphate
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prefered substrate
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?
phosphatidylinositol-4-phosphate + H2O
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prefered substrate
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1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate + H2O
1-phosphatidyl-1D-myo-inositol 3-phosphate + phosphate
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?
1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate + H2O
1-phosphatidyl-1D-myo-inositol 3-phosphate + phosphate
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?
1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate + H2O
1-phosphatidyl-1D-myo-inositol 3-phosphate + phosphate
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-
-
?
1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate + H2O
1-phosphatidyl-1D-myo-inositol 3-phosphate + phosphate
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-
?
1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate + H2O
1-phosphatidyl-1D-myo-inositol 3-phosphate + phosphate
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?
1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate + H2O
1-phosphatidyl-1D-myo-inositol 3-phosphate + phosphate
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?
1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate + H2O
1-phosphatidyl-1D-myo-inositol 3-phosphate + phosphate
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?
D-myo-inositol 1,3,4-trisphosphate + H2O
D-myo-inositol 3,4-bisphosphate + phosphate
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?
D-myo-inositol 1,3,4-trisphosphate + H2O
D-myo-inositol 3,4-bisphosphate + phosphate
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?
D-myo-inositol 1,3,4-trisphosphate + H2O
D-myo-inositol 3,4-bisphosphate + phosphate
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?
D-myo-inositol 1,3,4-trisphosphate + H2O
D-myo-inositol 3,4-bisphosphate + phosphate
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?
D-myo-inositol 3,4-bisphosphate + H2O
D-myo-inositol 4-phosphate + phosphate
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?
D-myo-inositol 3,4-bisphosphate + H2O
D-myo-inositol 4-phosphate + phosphate
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?
D-myo-inositol 3,4-bisphosphate + H2O
D-myo-inositol 4-phosphate + phosphate
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?
D-myo-inositol 3,4-bisphosphate + H2O
D-myo-inositol 4-phosphate + phosphate
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?
D-myo-inositol 3,4-bisphosphate + H2O
D-myo-inositol 4-phosphate + phosphate
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additional information
?
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calpain-mediated inhibition of enzyme is involved in the phosphatidylinositol 3,4-bisphosphate accumulation in thrombin-stimulated platelets
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additional information
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has no effect on phosphatidylinositol-1,3,4-triphosphate
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?
additional information
?
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inositol polyphosphate 4-phosphatase type II is a class II phosphatase that preferentially hydrolyzes the 4 position of PI(3,4)P2
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?
additional information
?
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no substrate: inositol 1,4-bisphosphate
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?
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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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?
1-phosphatidyl-myo-inositol 3,4-bisphosphate + H2O
1-phosphatidyl-1D-myo-inositol 3-phosphate + phosphate
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?
D-myo-inositol 3,4-bisphosphate + H2O
D-myo-inositol 4-phosphate + phosphate
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?
additional information
?
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calpain-mediated inhibition of enzyme is involved in the phosphatidylinositol 3,4-bisphosphate accumulation in thrombin-stimulated platelets
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?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
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by using a cocktail of phosphatase inhibitors containing vanadate, molybdate, imidazole, fluoride and tartrate these inhibitors remarkably change the pattern of peroxisomal phosphoinositides
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 8
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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primary, the enzyme is expressed in nonproliferative estrogen receptor-positive cells in the normal breast, and in estrogen receptor-positive, but not negative, breast cancer cell lines
brenda
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restricted to the Purkinje cell soma and their dendrites in the molecular layer
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additional information
additional information
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present in HMEC cells. Total level of INPP4B is approximately 2-3fold higher in SUM149 cells expressing Flag-INPP4B, compared with levels in control SUM149 cells
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additional information
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INPP4B expression is evaluated by quantitative RT-PCR
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additional information
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INPP4B protein expression is frequently lost in primary human breast carcinomas, associated with high clinical grade and tumor size and loss of hormone receptors and is lost most commonly in aggressive basal-like breast carcinomas
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additional information
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no expression in MDA MB 231 cells, Hs578T cells, and BT-549cells. Colocalization of INPP4B and the proliferation marker, Ki-67, in breast lobules
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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
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additional information
highest levels of enzyme in brain, heart, skeletal muscle and spleen
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
RHD4 is selectively recruited to RabA4-blabeled membranes that are involved in polarized expansion of root hair cells. In conjunction with the phosphoinositide kinase PI-4Kb1, RHD4 regulates the accumulation of phosphatidylinositol-4-phosphate on membrane compartments at the tips of growing root hairs
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
additional information
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INPP4B is regulated by androgens at the level of transcription. INPP4B mRNA expression is induced in both LNCaP and VCaP AR-expressing prostate cancer cells. INPP4B and PTEN expression are correlated with the recurrence rate of patients with high and low expression levels of the proliferation marker Ki67
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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knocking down the expression of INPP4B in human epithelial cells, like knockdown of PTEN, results in enhanced Akt activation and anchorage-independent growth and enhanced overall motility. INPP4B knockdown results in increased migratory and invasive behavior of mammary epithelial cells. Dual knockdown of INPP4B and PTEN results in cellular senescence and causes a more prolonged phosphorylation of AKT at Thr308 than that caused by knocking down either protein alone. INPP4B knockdown in MCF-10A mammary epithelial cells results in distorted acini architecture in three-dimensional culture
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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inositol polyphosphate 4-phosphatase-II knockdown in estrogen receptor-positive breast cancer cells increased Akt activation, cell proliferation, and xenograft tumor growth
malfunction
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silenced INPP4B expression in malignant proerythroblast is associated with increased activated-Akt levels that can be alleviated by the reexpression of INPP4B. Knockdown of INPP4B in LNCaP cells enhances proliferation
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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overexpression of INPP4B in SUM149 cells in a xenograft mouse model results in reduced tumor growth. Loss of heterozygosity at the INPP4B locus in a majority of basal-like breast cancers, as well as in a significant fraction of ovarian cancers, which correlates with lower overall patient survival, suggesting that INPP4B is a tumor suppressor
physiological function
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INPP4B regulates proliferation and Akt phosphorylation in prostate cancer cells
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
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quantitative real-time reverse-transcription PCR analysis, inositol polyphosphate 4-phosphatase-II , INPP4B, functions as a tumor suppressor by negatively regulating normal and malignant mammary epithelial cell proliferation through regulation of the PI3K/Akt signaling pathway, and that loss of INPP4B protein is a marker of aggressive basal-like breast carcinomas
physiological function
cells expressing wild-type, but not catalytically inactive inositol polyphosphate 4-phosphatase show impaired phosphatidylinositol-3,4-bisphosphate responses induced by chenomkine SDF-1 and reduced migration in Transwell chamber assays. Phosphatidylinositol-3,4-bisphosphate depletion in primary chronic lymphocytic leukemia cells significantly impairs their migration capacity. Phosphatidylinositol-3,4-bisphosphate depletion reduces both overall motility and migration directionality in the presence of a stable chemokine gradient
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 asthma patients. Cultured airway epithelial cells secrete enzymatically active INPP4A in extracellular vesicles and in a free form. Extracellular vesicles-mediated INPP4A is transferred from epithelial cells to fibroblasts. Inhibition of this transfer increases fibroblast proliferation
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
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
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
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
104000
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x * 104000, SDS-PAGE, enzyme forms a complex with phosphatidylinositiol 3-kinase
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
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x * 104000, SDS-PAGE, enzyme forms a complex with phosphatidylinositiol 3-kinase
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
G449S
rhd4-2 mutant containing a mutation in motif VII of the SAC phosphatase domain, reduces the phosphatidylinositol-4-phosphate phosphatase activity to residual levels
additional information
additional information
rhd4-1 mutant, mutation results in root hairs that are shorter and randomly form bulges along their length. Stochastic loss and recovery of the RabA4b compartment in the tips of growing root hairs, altered subcellular distribution of phosphatidylinositol-4-phosphate within the root hair cell. EYFPRHD4 is capable of rescuing the rhd4-1 mutant phenotype
additional information
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rhd4-1 mutant, mutation results in root hairs that are shorter and randomly form bulges along their length. Stochastic loss and recovery of the RabA4b compartment in the tips of growing root hairs, altered subcellular distribution of phosphatidylinositol-4-phosphate within the root hair cell. EYFPRHD4 is capable of rescuing the rhd4-1 mutant phenotype
additional information
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C2-domain deletion mutant, loss of enzyme activity, no localization to endosomes, no TAPP1 PH domain membrane recruitment
additional information
a nonsynonymous single nucleotide polymorphism +110832A/G (Thr/Ala) present within a PEST sequence (peptide sequence rich in proline, glutamic acid, serine and threonine), shows a significant association with atopic asthma. INPP4A alpha3 protein variant from platelets of individuals with AA genotype is found to be more susceptible to degradation, whereas the protein from individuals with GG genotype is less susceptible. Also, the basal levels of INPP4A protein in platelets from individuals with AA genotypes is found to be lower, suggesting poor stability in vivo as well
additional information
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a nonsynonymous single nucleotide polymorphism +110832A/G (Thr/Ala) present within a PEST sequence (peptide sequence rich in proline, glutamic acid, serine and threonine), shows a significant association with atopic asthma. INPP4A alpha3 protein variant from platelets of individuals with AA genotype is found to be more susceptible to degradation, whereas the protein from individuals with GG genotype is less susceptible. Also, the basal levels of INPP4A protein in platelets from individuals with AA genotypes is found to be lower, suggesting poor stability in vivo as well
additional information
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rescue construct pLXSN/Flag-INPP4BR harbors two silent mutations at Ser687 to render it resistant to shRNA-INPP4B-1 knockdown. The catalytic-dead pLXSN/Flag-INPP4BR construct harbors a Cys842Ala mutation to abolish phosphatase activity as well as two silent mutations at Ser687 to avoid knockdown
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
full-length 4-ptase-1 cDNA subcloned into the EcoRI site of pWzl-Hygromycin vector
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pLXSN-Flag-INPP4B expressed in 293T cells or in SUM149 cells subcutaneously injected into nude mice
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wild-type RHD4 and the mutant rhd4-2 N-terminal catalytic domains expressed from Escherichia coli Rosetta cells or BL21 cells as GST fusion proteins. EYFP-wild-type fusion protein transformed into Arabidopsis under control of the native RHD4 promoter
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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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optimal induction of INPP4B by an androgen receptor required the expression of the transcriptional coactivator NCoR
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
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calpain-mediated inhibition of enzyme is involved in the phosphatidylinositol 3,4-bisphosphate accumulation in thrombin-stimulated platelets
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
medicine
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decreased expression of INPP4B correlates with poor outcome in both breast cancer and ovarian cancer patients, whereby the PI3K pathway is likely to play a major role in driving this subset of cancers. Loss of INPP4B expression may provide a marker for selecting patients who will respond to PI3K drugs
medicine
colorectal carcinoma cell lines HCT-116, SW-620, DLD-1, and WiDr express significantly lower levels of INPP4B protein than the normal colonic epithelial cell lines CCD-841 CoTr and FHC. INPP4B mRNA expression in the colorectal carcinoma cell lines is significantly lower than in the normal colonic epithelial cells. Normal colonic mucosa displays uniform and strong-to-moderate INPP4B immunoreactivity, whereas 60.7% and 76.5% of the primary and metastatic colorectal carcinoma tissue samples exhibit reduced INPP4B expression, respectively
medicine
in acute myeloid leukemia, isoform IPNPP4B is significantly overexpressed, in association with reduced responses to chemotherapy, early relapse, and poor overall survival, independent of other risk factors. Ectopic overexpression of INPP4B confers leukemic resistance to cytosine arabinoside, daunorubicin, and etoposide. Expression of phosphatase inert variant C842A fails to abrogate resistance of acute myeloid leukemiacells to chemotherapy in vitro or in vivo. Targeted suppression of endogenously overexpressed INPP4B by RNAi sensitizes acute myeloid leukemia cell lines and primary acute myeloid leukemia to chemotherapy
medicine
in prostate cancer cell lines INPP4B regulates androgen recetor transcriptional activity and the oncogenic signaling pathways Akt and PKC. In prostate cancer patient cohorts, a positive correlation between INPP4B expression and both androgen receptor mRNA levels and transcriptional output exists
medicine
in Triple-negative breast cancer cells, which lack expression of estrogen receptor, progesterone receptor, and amplification of HER2/Neu, silencing isoform INPP4B decreases basal phospho-Akt (pAkt) and cellular proliferation, and in most cases sensitizes cells to phosphatidylinositol-3-kinase PI3K-alpha and PI3K-beta isoform-specific inhibitors. Overexpression of INPP4B desensitizes cells to PI3K inhibitors in a phosphatase activity-dependent manner
medicine
inositol polyphosphate 4-phosphatase type II is a direct target of microRNA-590-3p. Enforced expression of microRNA-590-3p leads to repression of inositol polyphosphate 4-phosphatase type II messenger RNA and protein expression, as well as upregulation of p-Akt, p-FoxO3a, and cyclin D1 and downregulation of p21 expression in prostate cancer cell lines. Overexpression of inositol polyphosphate 4-phosphatase type II can reduce microRNA-590-3p-induced cell proliferation and invasion as well as tumor growth, and decrease microRNA-590-3p-mediated upregulation of cyclin D1 and downregulation of p21 expression in prostate cancer cells
medicine
INPP4B is low expressed in osteosarcoma tissues and in osteosarcoma cell lines. INPP4B overexpression significantly decreases cell viability and induces apoptosis in SaOS2 and U2OS cells. Combination of INPP4B overexpression and poly-ADP ribose polymerase inhibitor rucaparib declines Myc, cyclin E1 and cyclin D1 expressions, enhances Bad, Bax, and cleaves caspase3 expressions, and blocks PI3K/AKT signal pathway in SaOS2 and U2OS cells. Combination of INPP4B overexpression and rucaparib inhibits tumor formation in vivo
medicine
INPP4B manipulates cadherin switch in certain pancreatic ductal adenocarcinoma cell lines through a phosphorylated AKT-inactivation. The knockdown of INPP4B in AsPC-1 cells results in a more invasive phenotype, and overexpression of INPP4B in PANC-1 leads to partial reversion of mesenchymal status and impediment of in vitro invasion but not migration. E-cadherin is enriched in the early and sorting endosomes containing INPP4B which enables its recycling rather than degradation. INPP4B acts as an tumor suppressor in pancreatic ductal adenocarcinomas which attenuates AKT activation and participates in preservation of E-cadherin in endocytic pool and cellular membrane
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Howell, S.; Barnaby, R.J.; Rowe, T.; Ragan, C.I.; Gee, N.S.
Evidence for at least four different inositol bisphosphatases in bovine brain
Eur. J. Biochem.
183
169-172
1989
Bos taurus
brenda
Munday, A.D.; Norris, F.A.; Caldwell, K.K.; Brown, S.; Majerus, P.W.; Mitchell, C.A.
The inositol polyphosphate 4-phosphatase forms a complex with phosphatidylinositol 3-kinase in human platelet cytosol
Proc. Natl. Acad. Sci. USA
96
3640-3645
1999
Homo sapiens
brenda
Norris, F.A.; Auethavekiat, V.; Majerus, P.W.
The isolation and characterization of cDNA encoding human and rat brain inositol polyphosphate 4-phosphatase
J. Biol. Chem.
270
16128-16133
1995
Rattus norvegicus (Q62784), Homo sapiens (Q96PE3), Homo sapiens
brenda
Norris, F.A.; Atkins, R.C.; Majerus, P.W.
The cDNA cloning and characterization of inositol polyphosphate 4-phosphatase type II. Evidence for conserved alternative splicing in the 4-phosphatase family
J. Biol. Chem.
272
23859-23864
1997
Homo sapiens (Q96PE3), Homo sapiens, Rattus norvegicus (Q9QWG5)
brenda
Norris, F.A.; Atkins, R.C.; Majerus, P.W.
Inositol polyphosphate 4-phosphatase is inactivated by calpain-mediated proteolysis in stimulated human platelets
J. Biol. Chem.
272
10987-10989
1997
Homo sapiens
brenda
Ivetac, I.; Munday, A.D.; Kisseleva, M.V.; Zhang, X.M.; Luff, S.; Tiganis, T.; Whisstock, J.C.; Rowe, T.; Majerus, P.W.; Mitchell, C.A.
The type Ialpha inositol polyphosphate 4-phosphatase generates and terminates phosphoinositide 3-kinase signals on endosomes and the plasma membrane
Mol. Biol. Cell
16
2218-2233
2005
Homo sapiens
brenda
Sharma, M.; Batra, J.; Mabalirajan, U.; Sharma, S.; Nagarkatti, R.; Aich, J.; Sharma, S.K.; Niphadkar, P.V.; Ghosh, B.
A genetic variation in inositol polyphosphate 4 phosphatase A enhances susceptibility to asthma
Am. J. Respir. Crit. Care Med.
177
712-719
2008
Homo sapiens (Q96PE3), Homo sapiens
brenda
Jeynov, B.; Lay, D.; Schmidt, F.; Tahirovic, S.; Just, W.W.
Phosphoinositide synthesis and degradation in isolated rat liver peroxisomes
FEBS Lett.
580
5917-5924
2006
Rattus norvegicus
brenda
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
brenda
Thole, J.M.; Vermeer, J.E.; Zhang, Y.; Gadella, T.W.; Nielsen, E.
Root hair defective4 encodes a phosphatidylinositol-4-phosphate phosphatase required for proper root hair development in Arabidopsis thaliana
Plant Cell
20
381-395
2008
Arabidopsis thaliana (Q9C5G5), Arabidopsis thaliana
brenda
Gewinner, C.; Wang, Z.C.; Richardson, A.; Teruya-Feldstein, J.; Etemadmoghadam, D.; Bowtell, D.; Barretina, J.; Lin, W.M.; Rameh, L.; Salmena, L.; Pandolfi, P.P.; Cantley, L.C.
Evidence that inositol polyphosphate 4-phosphatase type II is a tumor suppressor that inhibits PI3K signaling
Cancer Cell
16
115-125
2009
Homo sapiens
brenda
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
brenda
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
brenda
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
brenda
Hodgson, M.C.; Shao, L.J.; Frolov, A.; Li, R.; Peterson, L.E.; Ayala, G.; Ittmann, M.M.; Weigel, N.L.; Agoulnik, I.U.
Decreased expression and androgen regulation of the tumor suppressor gene INPP4B in prostate cancer
Cancer Res.
71
572-582
2011
Homo sapiens
brenda
Fedele, C.G.; Ooms, L.M.; Ho, M.; Vieusseux, J.; OToole, S.A.; Millar, E.K.; Lopez-Knowles, E.; Sriratana, A.; Gurung, R.; Baglietto, L.; Giles, G.G.; Bailey, C.G.; Rasko, J.E.; Shields, B.J.; Price, J.T.; Majerus, P.W.; Sutherland, R.L.; Tiganis, T.; McLean, C.A.; Mitchell, C.A.
Inositol polyphosphate 4-phosphatase II regulates PI3K/Akt signaling and is lost in human basal-like breast cancers
Proc. Natl. Acad. Sci. USA
107
22231-22236
2010
Homo sapiens
brenda
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
brenda
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
brenda
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)
brenda
Sung, J.Y.; Na, K.; Kim, H.S.
Down-regulation of inositol polyphosphate 4-phosphatase type II expression in colorectal carcinoma
Anticancer Res.
37
5525-5531
2017
Homo sapiens (O15327), Homo sapiens
brenda
Rijal, S.; Fleming, S.; Cummings, N.; Rynkiewicz, N.K.; Ooms, L.M.; Nguyen, N.Y.; Teh, T.C.; Avery, S.; McManus, J.F.; Papenfuss, A.T.; McLean, C.; Guthridge, M.A.; Mitchell, C.A.; Wei, A.H.
Inositol polyphosphate 4-phosphatase II (INPP4B) is associated with chemoresistance and poor outcome in AML
Blood
125
2815-2824
2015
Homo sapiens (O15327), Homo sapiens
brenda
Zhang, B.; Wang, W.; Li, C.; Liu, R.
Inositol polyphosphate-4-phosphatase type II plays critical roles in the modulation of cadherin-mediated adhesion dynamics of pancreatic ductal adenocarcinomas
Cell Adh. Migr.
12
548-563
2018
Homo sapiens (O15327), Homo sapiens
brenda
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
brenda
Li, D.; Yang, J.; Ma, H.; Sun, C.; Feng, R.
Inositol polyphosphate-4-phosphatase type II and rucaparib treatment inhibit the growth of osteosarcoma cells dependent on phosphoinositide 3-kinase/protein kinase B pathway
J. Cell. Biochem.
119
9899-9909
2018
Homo sapiens (O15327), Homo sapiens
brenda
Li, H.; Wu, X.; Hou, S.; Malek, M.; Kielkowska, A.; Noh, E.; Makondo, K.J.; Du, Q.; Wilkins, J.A.; Johnston, J.B.; Gibson, S.B.; Lin, F.; Marshall, A.J.
Phosphatidylinositol-3,4-bisphosphate and its binding protein lamellipodin regulate chemotaxis of malignant B lymphocytes
J. Immunol.
196
586-595
2016
Homo sapiens (O15327)
brenda
Reed, D.E.; Shokat, K.M.
INPP4B and PTEN loss leads to PI-3,4-P2 accumulation and inhibition of PI3K in TNBC
Mol. Cancer Res.
15
765-775
2017
Homo sapiens (O15327), Homo sapiens
brenda
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
brenda
Nigorikawa, K.; Hazeki, K.; Sasaki, J.; Omori, Y.; Miyake, M.; Morioka, S.; Guo, Y.; Sasaki, T.; Hazeki, O.
Inositol polyphosphate-4-phosphatase type I negatively regulates phagocytosis via dephosphorylation of phagosomal PtdIns(3,4)P2
PLoS ONE
10
e0142091
2015
Mus musculus (Q9EPW0)
brenda
Chen, H.; Luo, Q.; Li, H.
MicroRNA-590-3p promotes cell proliferation and invasion by targeting inositol polyphosphate 4-phosphatase type II in human prostate cancer cells
Tumour Biol.
39
FEHLT
2017
Homo sapiens (O15327), Homo sapiens
brenda
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