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Information on EC 3.1.3.78 - phosphatidylinositol-4,5-bisphosphate 4-phosphatase and Organism(s) Homo sapiens
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3.1.3.78 phosphatidylinositol-4,5-bisphosphate 4-phosphataseIUBMB Comments
Two pathways exist in mammalian cells to degrade 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate [PtdIns(4,5)P2] . One is catalysed by this enzyme and the other by EC 3.1.3.36, phosphoinositide 5-phosphatase, where the product is PtdIns4P. The enzyme from human is specific for PtdIns(4,5)P2 as substrate, as it cannot use PtdIns(3,4,5)P3, PtdIns(3,4)P2, PtdIns(3,5)P2, PtdIns5P, PtdIns4P or PtdIns3P . In humans, the enzyme is localized to late endosomal/lysosomal membranes . It can control nuclear levels of PtdIns5P and thereby control p53-dependent apoptosis .
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The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Synonyms
type i 4-phosphatase, type i phosphatidylinositol-4,5-bisphosphate 4-phosphatase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
PtdIns-4,5-P2 4-phosphatase type I
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-
-
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PtdIns-4,5-P2 4-phosphatase type II
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-
-
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PATHWAY SOURCE
PATHWAYS
-
-, -
SYSTEMATIC NAME
IUBMB Comments
1-phosphatidyl-1D-myo-inositol-4,5-bisphosphate 4-phosphohydrolase
Two pathways exist in mammalian cells to degrade 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate [PtdIns(4,5)P2] [2]. One is catalysed by this enzyme and the other by EC 3.1.3.36, phosphoinositide 5-phosphatase, where the product is PtdIns4P. The enzyme from human is specific for PtdIns(4,5)P2 as substrate, as it cannot use PtdIns(3,4,5)P3, PtdIns(3,4)P2, PtdIns(3,5)P2, PtdIns5P, PtdIns4P or PtdIns3P [2]. In humans, the enzyme is localized to late endosomal/lysosomal membranes [2]. It can control nuclear levels of PtdIns5P and thereby control p53-dependent apoptosis [3].
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-4,5-bisphosphate + H2O
phosphatidylinositol-5-phosphate + phosphate
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-
-
-
?
phosphatidylinositol-4,5-bisphosphate + H2O
phosphatidylinositol-5-phosphate + phosphate
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-
-
?
additional information
?
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the enzyme affects epithelial growth factor receptor EGFR degradation upon epithelial growth factor EGF stimulation via phosphatidylinositol-5-phosphate, overview
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-
?
additional information
?
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the enzyme affects epithelial growth factor receptor EGFR degradation upon epithelial growth factor EGF stimulation via phosphatidylinositol-5-phosphate, overview
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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
phosphatidylinositol-4,5-bisphosphate + H2O
phosphatidylinositol-5-phosphate + phosphate
-
-
-
?
additional information
?
-
the enzyme affects epithelial growth factor receptor EGFR degradation upon epithelial growth factor EGF stimulation via phosphatidylinositol-5-phosphate, overview
-
-
?
additional information
?
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the enzyme affects epithelial growth factor receptor EGFR degradation upon epithelial growth factor EGF stimulation via phosphatidylinositol-5-phosphate, overview
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
RNAi
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siRNA of type I 4-phosphatase reduces type I 4-phosphatase levels, which is followed by a dramatic decrease in p53 levels in response to the genotoxic agent etoposide. siRNA of type II 4-phosphatase does not reduce p53 expression
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
etoposide
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significantly increases type I 4-phosphatase in the nuclear fraction, in both the endogenous and overexpression system
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
additional information
isozyme II is ubiquitously expressed, comparison of expression patterns of isozymes I and II, overview
additional information
isozyme II is ubiquitously expressed, comparison of expression patterns of isozymes I and II, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
when HeLa cells are treated with etoposide or doxorubicin, type I 4-phosphatase translocates to the nucleus and nuclear levels of phosphatidylinositol 5-phosphate increase
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
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PtdIns(4,5)P2 4-phosphatase expression induces Src kinase and Akt, but not ERK activation and enhances interleukin II promoter activity in T-cells. Expression of a PtdIns5P interacting domain, PH-Dok-5, blocks IpgD-induced T-cell activation and selective signaling molecules downstream of TCR triggering, evaluation, overview
additional information
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phosphatidylinositol 5-phosphate may play a sensor function in setting the threshold of T-cell activation and contributing to maintain T-cell homeostasis
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). PP4P1_HUMAN
277
2
29470
Swiss-Prot
other Location (Reliability: 1)
PP4P2_HUMAN
257
2
28081
Swiss-Prot
other Location (Reliability: 2)
G3V5T5_HUMAN
43
0
4726
TrEMBL
other Location (Reliability: 2)
E5RFT4_HUMAN
250
2
27327
TrEMBL
other Location (Reliability: 1)
E5RIY0_HUMAN
166
0
17746
TrEMBL
other Location (Reliability: 2)
H0YJ90_HUMAN
112
2
12583
TrEMBL
other Location (Reliability: 3)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
expression of isozyme I siRNA in HeLa cells does not affect phosphatidylinositol-4,5-bisphosphate levels or EGFR degradation
additional information
expression of isozyme I siRNA in HeLa cells does not affect phosphatidylinositol-4,5-bisphosphate levels or EGFR degradation
additional information
expression of isozyme II siRNA in HeLa cells does not affect phosphatidylinositol-4,5-bisphosphate levels or EGFR degradation
additional information
expression of isozyme II siRNA in HeLa cells does not affect phosphatidylinositol-4,5-bisphosphate levels or EGFR degradation
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
FLAG-tagged isozyme I from Sf9 insect cells by anti-FLAG immunoaffinity chromatography
FLAG-tagged isozyme II from Sf9 insect cells by anti-FLAG immunoaffinity chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
stably transfected HEK-293 TRex cells in a tetracycline-inducible vector expressing type I and II 4-phosphatase
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type I isozyme, DNA and amino acid sequence determination and analysis, transient transfection of functional enzyme to HeLa and COS-7 cells leading to increased EGFR degradation via increased phosphatidylinositol-5-phosphate content, functional overexpression of FLAG-tagged enzyme in Spodoptera frugiperda Sf9 cells using the baculovirus infection system, stable inducible expression of labeled isozyme I in HEK293 cells
type II isozyme, DNA and amino acid sequence determination and analysis, transient transfection of functional enzyme to HeLa and COS-7 cells leading to increased EGFR degradation via increased phosphatidylinositol-5-phosphate content, functional overexpression of FLAG-tagged enzyme in Spodoptera frugiperda Sf9 cells using the baculovirus infection system
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
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type I 4-phosphatase regulates nuclear phosphatidylinositol 5-phosphate levels, which in turn mediate p53-dependent apoptosis through interaction with inhibitor of growth protein-2 in response to genotoxic stress
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ungewickell, A.; Hugge, C.; Kisseleva, M.; Chang, S.C.; Zou, J.; Feng, Y.; Galyov, E.E.; Wilson, M.; Majerus, P.W.
The identification and characterization of two phosphatidylinositol-4,5-bisphosphate 4-phosphatases
Proc. Natl. Acad. Sci. USA
102
18854-18859
2005
Homo sapiens (Q86T03), Homo sapiens (Q8N4L2)
Zou, J.; Marjanovic, J.; Kisseleva, M.V.; Wilson, M.; Majerus, P.W.
Type I phosphatidylinositol-4,5-bisphosphate 4-phosphatase regulates stress-induced apoptosis
Proc. Natl. Acad. Sci. USA
104
16834-16839
2007
Homo sapiens
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