Information on EC 2.7.1.154 - phosphatidylinositol-4-phosphate 3-kinase

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The expected taxonomic range for this enzyme is: Bilateria

EC NUMBER
COMMENTARY hide
2.7.1.154
-
RECOMMENDED NAME
GeneOntology No.
phosphatidylinositol-4-phosphate 3-kinase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
show the reaction diagram
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-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho-group transfer
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-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
3-phosphoinositide biosynthesis
-
-
Inositol phosphate metabolism
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Metabolic pathways
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SYSTEMATIC NAME
IUBMB Comments
ATP:1-phosphatidyl-1D-myo-inositol-4-phosphate 3-phosphotransferase
This enzyme also phosphorylates PtdIns to PtdIns3P. Three mammalian isoforms have been found to date.
CAS REGISTRY NUMBER
COMMENTARY hide
141176-94-5
-
67053-99-0
cf. EC 2.7.1.137
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
PI3K-C2alpha
-
-
Manually annotated by BRENDA team
Cricetulus griseus PI3K-C2alpha
PI3K-C2alpha
-
-
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
show the reaction diagram
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
show the reaction diagram
ATP + 1-phosphatidyl-1D-myo-inositol-4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
show the reaction diagram
ATP + 1-phosphatidyl-1D-myo-inositol-4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-diphosphate
show the reaction diagram
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strong preference for phosphatidylinositol over 1-phosphatidyl-1D-myo-inositol-4-phosphate
-
-
?
ATP + phosphatidylinositol
?
show the reaction diagram
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strong preference for phosphatidylinositol over 1-phosphatidyl-1D-myo-inositol-4-phosphate
-
-
?
ATP + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
ATP + phosphoinositides
ADP + ?
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
show the reaction diagram
ATP + phosphoinositides
ADP + ?
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
inactive in presence of Mn2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
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i.e. BAPTA-AM, a cell-penetrating Ca2+-chelator
adipokines
Caffeine
Calpeptin
-
inhibits proteolytic activation of enzyme form PI3K C2beta in brush border plasma membranes
cytokines
LY294002
Mn2+
3.5 mM, instead of Mg2+, almost complete inhibition
naringenin
Nonidet P-40
0.5%, almost complete inhibition
Triton X-100
0.5%, almost complete inhibition
Wortmannin
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
A23187
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Ca2+-ionophore, activates enzyme form PI3K-C2beta, mimicks hepatocyte growth factor HGF
growth factors
addition of serum to growth-factor-deficient medium increases PI3K-C2alpha expression
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hepatocyte growth factor HGF
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in renal brush-border and basal lateral plasma membranes, in the latter case mediated by calpain
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Insulin
leptin
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4fold activation of class II isoform PI3K-C2beta by activation of the ERK pathway, no recruitment of tyrosine phosphorylated proteins to the isozyme, blockade of activation by MEK-inhibitor PD98059
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monocyte chemotactic peptide-1
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agonist-induced activation
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TNF-alpha
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2.8fold activation of class II isoform PI3K-C2beta by activation of the ERK pathway, blockade of activation by MEK-inhibitor PD98059
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additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.015 - 0.054
ATP
0.12
CaATP2-
0.064 - 0.122
phosphatidylinositol
0.025
phosphatidylinositol 4-phosphate
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pH 7.5, 30C, in presence of phosphatidylserine
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.019
LY294002
Homo sapiens
-
IC50: 0.019 mM, maximal inhibition at 1 mM
0.0000016 - 0.00042
Wortmannin
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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adipocyte
Manually annotated by BRENDA team
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moderate expression of PI3K-C2alpha andPI3K-C2beta
Manually annotated by BRENDA team
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moderate expression of PI3K-C2alpha
Manually annotated by BRENDA team
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low amount of isozyme p85, isozyme PI3K-C2beta and isozyme PI3K-C2alpha in bronchial epithelium
Manually annotated by BRENDA team
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isozyme p85, isozyme PI3K-C2beta and isozyme PI3K-C2alpha in colonocytes
Manually annotated by BRENDA team
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moderate expression of PI3K-C2alpha and PI3K-C2beta
Manually annotated by BRENDA team
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of Fallopian tube, moderate expression of PI3K-C2alpha and weak expression of PI3K-C2beta
Manually annotated by BRENDA team
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PI3K-C2alpha
Manually annotated by BRENDA team
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moderate expression of PI3K-C2alpha and weak expression of PI3K-C2beta
Manually annotated by BRENDA team
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isozyme PI3K-C2alpha, high amount of isozyme p85, and low amount of isozyme PI3K-C2beta
Manually annotated by BRENDA team
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isozyme PI3K-C2alpha in smooth muscle layer, mononuclear cells, and lining epithelium, isozyme p85 and isozyme PI3K-C2beta in lining epithelium and mononuclear cells
Manually annotated by BRENDA team
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strong expression of PI3K-C2alpha
Manually annotated by BRENDA team
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; macrophage
Manually annotated by BRENDA team
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strong expression of PI3K-C2alpha and moderate expression of PI3K-C2beta
Manually annotated by BRENDA team
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isozyme p85, isozyme PI3K-C2beta and isozyme PI3K-C2alpha in alveolar macrophages
Manually annotated by BRENDA team
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moderate expression of PI3K-C2alpha
Manually annotated by BRENDA team
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non-myelinated, moderate expression of PI3K-C2beta
Manually annotated by BRENDA team
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moderate expression of PI3K-C2alpha and PI3K-C2beta
Manually annotated by BRENDA team
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expression at low level
Manually annotated by BRENDA team
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isozyme PI3K-C2alpha inbasal epithelium and fibromuscular stroma, no isozyme PI3K-C2beta and isozyme p85
Manually annotated by BRENDA team
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expression at low level
Manually annotated by BRENDA team
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isozyme p85 in Langerhans cells, dermal macrophages, and in low amounts in sebaceous glands, hair follicles, and sweat gland, isozyme PI3K-C2beta and isozyme PI3K-C2alpha in dermal macrophages, low amount of isozyme PI3K-C2alpha in sweat gland
Manually annotated by BRENDA team
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different cell lines overexpress different isozymes, e.g. cell lines H-69, HC-33, H-510, H-1045, and H-209
Manually annotated by BRENDA team
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strong expression of PI3K-C2beta
Manually annotated by BRENDA team
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isozyme PI3K-C2beta and isozyme PI3K-C2alpha, and high amount of isozyme p85 in peptic cells
Manually annotated by BRENDA team
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isozyme PI3K-C2alpha in cervical smooth muscle, no isozyme PI3K-C2beta and isozyme p85
Manually annotated by BRENDA team
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isozyme p85 in proliferative endometrium and in low amounts in secretory endometrium, isozyme PI3K-C2alpha in myometrium, no isozyme PI3K-C2beta
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
predominantly localised to intracellular membranes; predominantly localised to intracellular membranes; predominantly localised to intracellular membranes
Manually annotated by BRENDA team
additional information
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the recombinant enzyme is localized mainly in the low density microsomal fraction, with a small amount being present in the plasma membrane and the cytosolic fraction
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Manually annotated by BRENDA team
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
proteolytic modification
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activation of enzyme form PI3K C2beta occurs probably via proteolysis in the brush broder plasma membrane
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
partially by subcellular fractionation of renal cortex, plasma membrane preparation
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloned into the baculovirus expression vector pAcG3x and expressed in Sf9 cells
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expression in COS-7 cells
expression in COS-7 cells. Specific activity of the enzyme purified from Drosophila lysate is significantly higher than that of Cpk derived from exogenous expression in COS-7 cells
expression of class I isozyme Dp110 enhances organ size by increasing the size of cells without perturbing patterning, ectopic expression of wild-type and catalytically inactive mutant of class II isozyme PI3K_68D in different patterns during Drosophila melanogaster disk development, phenotype analysis of adult cuticle
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expression of class IA and class II isozymes in HEK293 cells alter the regulation of protein kinases in response to growth factors as part of signalling cascades, overview
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Glu-tagged PI 3-kinase C2beta protein is expressed in both HEK293 cells and Sf9 cells
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suppression of expression of recombinant alpha-isoform of class II PI3K and endogenous enzyme in transfected CHO-R1 cells by expression of antisense constructs or DNA fragmentation leads to apoptotic cells death, overview
the region of human PI3K-C2alpha cDNA corresponding to residues 2-144 is cloned into the SmaI-ECoRI sites of pGEX-2T, the fusion protein is expressed in Escherichia coli BL21, transfection to COS cells
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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the catalytically inactive mutant of class II isozyme PI3K_68D can bind the Drk adaptor protein in vitro