Information on EC 2.7.1.137 - phosphatidylinositol 3-kinase and Organism(s) Homo sapiens and UniProt Accession O00750

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Homo sapiens
UNIPROT: O00750


The taxonomic range for the selected organisms is: Homo sapiens

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.7.1.137
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RECOMMENDED NAME
GeneOntology No.
phosphatidylinositol 3-kinase
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
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Inositol phosphate metabolism
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Metabolic pathways
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SYSTEMATIC NAME
IUBMB Comments
ATP:1-phosphatidyl-1D-myo-inositol 3-phosphotransferase
One mammalian isoform is known.
CAS REGISTRY NUMBER
COMMENTARY hide
115926-52-8
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
additional information
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hyperactivation of the PI3K/AKT/mTOR signaling pathway is common in cancer, and PI3K and mTOR act synergistically in promoting tumor growth, survival, and resistance to chemotherapy
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-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
show the reaction diagram
no activity
-
-
-
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 3,4-bisphosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
show the reaction diagram
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
ATP + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
class I enzyme, preferred substrate of the class III enzyme
-
-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
show the reaction diagram
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 3,4-bisphosphate
show the reaction diagram
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
show the reaction diagram
ATP + phosphatidylinositol-4-phosphate
ADP + phosphatidylinositol-3,4-bisphosphate
show the reaction diagram
additional information
?
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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
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
show the reaction diagram
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
Q8NEB9
hVps34 plays a major role in generating phosphatidylinositol 3-phosphate for internal vesicle formation in multivesicular/late endosomes. The findings also unexpectedly suggest that other wortmannin-sensitive kinases and/or polyphosphoinositide phosphatases may be able to compensate for the loss of hVps34 and maintain phosphatidylinositol 3-phosphate levels required for vesicular trafficking in the early endocytic pathway or the trans-Golgi network
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-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
show the reaction diagram
-
class I enzyme, preferred substrate in vivo, physiologic regulation and mode of action
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-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
show the reaction diagram
ATP + phosphatidylinositol-4-phosphate
ADP + phosphatidylinositol-3,4-bisphosphate
show the reaction diagram
-
synthesis of a second messenger, enzyme is involved in several cellular signaling processes important for cell growth and survival, cell differentiation and motility
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-
?
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Wortmannin
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at nanomolar levels
(1E,4S,4aR,5R,6aS,7S)-5-(acetyloxy)-1-[[[3-(dimethylamino)-propyl](methyl)amino]methylene]-11-hydroxy-4-(methoxymethyl)-4a,6a-dimethyl-2,10-dioxo-1,2,4,4a,5,6,6a,7,8,9,9a,10-dodecahydroindeno[4,5-h]isochromen-7-yl-(1R,2R,4S)-4-[(2R)-2-[(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-1,5,11,28,29-pentaoxo-1,4,5,6,9,10,11,12,13,14,21,22,23,24,25,26,27,28,29,31,32,33,34,34a-tetracosahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriaconti
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-
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(1Z,4S,4aR,6aS,9aR)-1-([[3-(dimethylamino)propyl](methyl)amino]methylidene)-5-ethoxy-7,11-dihydroxy-4-(methoxymethyl)-4a,6a-dimethyl-4a,5,6,6a,7,8,9,9a-octahydroindeno[4,5-h]isochromene-2,10(1H,4H)-dione
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(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-3-[(2R)-1-[(1S,3R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-hexadecahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone
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17-hydroxywortmannin
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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i.e. LY294002
2-morpholin-4-yl-3-phenylchromen-4-one
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weak inhibition, IC50 is above 0.2 mM for the recombinant wild-type enzyme and for the recombinant mutant C838V/I848A
2-morpholin-4-yl-3-propylchromen-4-one
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IC50 is 0.0031 mM for the recombinant wild-type enzyme and 0.068 mM for the recombinant mutant C838V/I848A
3-benzyl-2-morpholin-4-yl-chromen-4-one
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weak inhibition, IC50 is above 0.2 mM for the recombinant wild-type enzyme and for the recombinant mutant C838V/I848A
3-butyl-2-morpholin-4-yl-chromen-4-one
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IC50 is 0.025 mM for the recombinant wild-type enzyme and 0.048 mM for the recombinant mutant C838V/I848A
3-ethyl-2-morpholin-4-yl-chromen-4-one
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IC50 is 0.028 mM for the recombinant wild-type enzyme and 0.0044 mM for the recombinant mutant C838V/I848A
3-isopropyl-2-morpholin-4-yl-chromen-4-one
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IC50 is 0.051 mM for the recombinant wild-type enzyme and more than 0.2 mM for the recombinant mutant C838V/I848A
3-methyl-2-morpholin-4-yl-chromen-4-one
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IC50 is 0.033 mM for the recombinant wild-type enzyme and 0.040 mM for the recombinant mutant C838V/I848A
3-Methyladenine
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treatment in full medium for a prolonged period of time leads to marked increases of the autophagic markers in cells. The increase of autophagic markers is the result of enhanced autophagic flux. The autophagy promotion activity is due to its differential temporal effects on class I and class III PI3K enzymes. 3-Methyladenine blocks class I PI3K persistently, whereas its suppressive effect on class III PI3K is transient. Treatment with 3-methyladenine in full medium significantly reduces the level of phosphatidylinositol 3-phosphate, the product of class III PI3K, at early time points, but almost completely blocks the product of phosphatidylinositol 3,4,5-trisphosphate up to 9 h
apocynin
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specific PI3K inhibitor, restores vasorelaxation and hyperpolarization in response to an ATP-sensitive K+ channel opener levcromakalim
Ead125
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GDC-0941
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enzyme PI3K-inhibition via GDC-0941 and PTEN-reconstitution into PTEN-null follicular thyroid carcinomas FTC-133s. GDC-0941 inhibits radiation-induced activation of Ataxia-telangiectasia mutated (ATM), ATM-and Rad3-related (ATR) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Under anoxia, radiation-induced PI3K-related kinase activation is markedly inhibited by GDC-0941. Inhibition of ATM and DNA-protein kinase catalytic subunits is PI3K-dependent
Gö6976
inhibitor directly targets phosphatidylinositol 3-kinase and confers profound inhibition of autophagic flux by inhibiting the formation of autophagosomes. It does not inhibit the cell survival promoting class I phosphoinositide 3-kinase-Akt signaling at the concentrations required for effective autophagy inhibition
IC87114
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KU55933
inhibitor directly targets phosphatidylinositol 3-kinase and confers profound inhibition of autophagic flux by inhibiting the formation of autophagosomes. Inhibits wild-type activity in vitro almost as efficiently as LY294002. It does not inhibit the cell survival promoting class I phosphoinositide 3-kinase-Akt signaling at the concentrations required for effective autophagy inhibition
Ly-294002
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LY292223
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i.e. 2-morpholin-4-yl-chromen-4-one, IC50 is 0.0026 mM for the recombinant wild-type enzyme and 0.025 mM for the recombinant mutant C838V/I848A
LY294002
naloxone
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noggin
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NVP-BEZ235
palmitate
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peptide N24
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a peptide inhibitor derived from p55PIK phosphatidylinositol 3-kinase, N24, regulatory subunit acts as inhibitor in cancer therapy, it blocks cell proliferation and induces cell cycle arrest in all cancer cell lines tested. Modeling of mechanisms of Rb-dependent and Rb-independent cell cycle arrest by N24 peptide, overview
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PWT-458
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i.e. poly(oxy-1,2-ethanediyl)-, R-[2-[[2-[[(1S,6bR,9S,9aS,11R,11bR)-11-(acetyloxy)-1,6,6b,7,8,9,9a,10,11,11b-decahydro-1-(methoxymethyl)-9a,11b-dimethyl-3,6-dioxo-3Hfuro[4,3,2-de]indeno[4,5-h]-2-benzopyran-9-yl]oxy]-2-oxoethyl]thio]ethyl]-omega-methoxy
PX-866
TGFbeta
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significantly inhibits phosphorylation of both p85 and ERK1/2 in vivo. TGFbeta does not activate the ERK pathway but turns off the GM-CSF-induced ERK signal via inhibition of the PI3-kinase-Akt pathway in human leukemia cells, overview
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Tiron
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specific PI3K inhibitor, restores vasorelaxation and hyperpolarization in response to an ATP-sensitive K+ channel opener levcromakalim
Wortmannin
ZSTK474
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a phosphatidylinositol 3-kinase inhibitor, inhibited phosphorylation of Ser65, Thr70 and Thr37/46 in 4E-BP1 by PI3K. Identification of the ZSTK474-sensitive phosphoproteins in A-549 cells, overview
additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
beta-catenin
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tyrosine-phopshorylated
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bone morphogenetic protein-2
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activates Akt phopshorylation by PI3K. Cell treatment with BMP-2 exhibits dramatic changes in cell morphology, from a cuboid, epithelial-like shape to a spindle, fibroblastic-like appearance, consistent with epithelial-mesenchymal transition, EMT, overview
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c-Src
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Dlg
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tyrosine-phopshorylated
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insulin-like growth factor-I
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strongly stimulates insulin receptor substrate-1-associated phosphatidylinositol 3-kinase activity about 54fold and total phosphatidylinositol 3-kinase activity abozut 6fold
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monosodium urate
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interaction of monosodium urate crystals with human neutrophils leads to the stimulation of class Ia PI-3Ks by a mechanism that is dependent on the tyrosine kinase Syk. The activation of PI-3Ks by monosodium urate crystals is a critical element regulating phospholipase D activation and degranulation of human neutrophils
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morphine
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morphine treatment enhances the level of phosphorylated, rather than unphosphorylated, PI3K and AKT, which are synchronously recruited to membrane. Levels of PTEN and p53, which are negative regulators of these signal molecules, are reduced, and as a result, the interaction between PTEN and p53 is completely interrupted
oleate
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activates
p38 mitogen-activated protein kinase
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activates PI3K, and proteasome inactivation promotes p38 mitogen-activated protein kinase-dependent phosphatidylinositol 3-kinase activation in retinal piment epithelial cells
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pioglitazone
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a thiazolidinedione, activates PI3K 2-2.5fold at 0.002-0.010 mM, activates adiponectin secretion from adipocytes in vivo
Ron kinase
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Ron plays an essential role in maintaining malignant phenotypes of colon cancer cells through regulating mutant PI3K activity
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Syk
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protein kinase Syk associates with clathrin and mediates phosphatidylinositol 3-kinase activation during human rhinovirus internalization in leukocytes
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additional information
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.011
phosphatidylinositol-4,5-bisphosphate
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preferred free substrate
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.2
2-morpholin-4-yl-3-phenylchromen-4-one
Homo sapiens;
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weak inhibition, IC50 is above 0.2 mM for the recombinant wild-type enzyme and for the recombinant mutant C838V/I848A
0.0031
2-morpholin-4-yl-3-propylchromen-4-one
Homo sapiens;
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IC50 is 0.0031 mM for the recombinant wild-type enzyme and 0.068 mM for the recombinant mutant C838V/I848A
0.2
3-benzyl-2-morpholin-4-yl-chromen-4-one
Homo sapiens;
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weak inhibition, IC50 is above 0.2 mM for the recombinant wild-type enzyme and for the recombinant mutant C838V/I848A
0.025
3-butyl-2-morpholin-4-yl-chromen-4-one
Homo sapiens;
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IC50 is 0.025 mM for the recombinant wild-type enzyme and 0.048 mM for the recombinant mutant C838V/I848A
0.028
3-ethyl-2-morpholin-4-yl-chromen-4-one
Homo sapiens;
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IC50 is 0.028 mM for the recombinant wild-type enzyme and 0.0044 mM for the recombinant mutant C838V/I848A
0.051
3-isopropyl-2-morpholin-4-yl-chromen-4-one
Homo sapiens;
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IC50 is 0.051 mM for the recombinant wild-type enzyme and more than 0.2 mM for the recombinant mutant C838V/I848A
0.033
3-methyl-2-morpholin-4-yl-chromen-4-one
Homo sapiens;
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IC50 is 0.033 mM for the recombinant wild-type enzyme and 0.040 mM for the recombinant mutant C838V/I848A
0.0026
LY292223
Homo sapiens;
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i.e. 2-morpholin-4-yl-chromen-4-one, IC50 is 0.0026 mM for the recombinant wild-type enzyme and 0.025 mM for the recombinant mutant C838V/I848A
0.0011
LY294002
Homo sapiens;
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IC50 is 0.0011 mM for the recombinant wild-type enzyme and for the recombinant mutant C838V/I848A
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0016
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purified recombinant isozyme gamma, at phosphatidylinositol-4,5-bisphosphate surface concentration of 10 mol%
0.0017
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purified recombinant isozyme beta, at phosphatidylinositol-4,5-bisphosphate surface concentration of 7.5 mol%
0.0028
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purified recombinant isozyme delta, at phosphatidylinositol-4,5-bisphosphate surface concentration of 2.5 mol%
0.0086
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purified recombinant isozyme alpha, at phosphatidylinositol-4,5-bisphosphate surface concentration of 10 mol%
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
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assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
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assay at room temperature
37
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assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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U937 monocyte
Manually annotated by BRENDA team
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U937 monocyte
Manually annotated by BRENDA team
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colorectal tumors exhibit enhanced PI 3-kinase activity compared with normal colonic mucosa
Manually annotated by BRENDA team
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colorectal tumors exhibit enhanced PI 3-kinase activity compared with normal colonic mucosa
Manually annotated by BRENDA team
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umbilical vein endothelial cells
Manually annotated by BRENDA team
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primary tumor cell line
Manually annotated by BRENDA team
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nodal metastasis cell line
Manually annotated by BRENDA team
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primary glioblastoma
Manually annotated by BRENDA team
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HCT-116 cells are heterozygous for gain of function mutant PIK3CA H1047R
Manually annotated by BRENDA team
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a promyelocytic leukemia cell line, expression of different PI3K isoforms during granulocyte differentiation of NB4 cells induced by all-trans-retinoic acid, 9-cis-retinoic acid or retinoic acid receptor agonists, overview
Manually annotated by BRENDA team
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KF, KFTx, SHIN-3, KOC-2S, and SK-OV-3. Simultaneous inhibition of the mitogen-activated protein kinase kinase and phosphatidylinositol 3-kinase pathways enhances sensitivity to paclitaxel in ovarian carcinoma
Manually annotated by BRENDA team
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a cell line overexpressing the HER2/c-erb-2 gene product
Manually annotated by BRENDA team
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insulin-stimulated insulin receptor substrate-2-associated phosphatidylinositol 3-kinase activity is enhanced in human skeletal muscle after exercise
Manually annotated by BRENDA team
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anaplastic and follicular thyroid carcinoma
Manually annotated by BRENDA team
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ATCC CRTL-1486
Manually annotated by BRENDA team
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glioblastoma cell
Manually annotated by BRENDA team
additional information
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isozymes Ia alpha and Ia beta are widely expressed in tissues
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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in quiescent cells, PI3-kinase is distributed through the cytoplasm, although a portion is present in the nucleus, following stimulation with IL-1, PI3-kinase is redistributed, increasing in the nuclear compartment. PI3-kinase translocation to the nucleus upon IL-1R activation is an early event in IL-1 signaling mechanism, and may be involved in transcriptional activation
Manually annotated by BRENDA team
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cytosol is partly associated with the cytoskeletal filaments
Manually annotated by BRENDA team
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
110000
128900
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1 * 128900, catalytic subunit, recombinant isozyme alpha, + 1 * 83400, regulatory subunit, recombinant isozyme alpha, mass spectrometry, 1 * 110000, catalytic subunit, + 1 * 85000, regulatory subunit, recombinant isozymes alpha-delta, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
heterodimer
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystal structure of PI3K SH3 domain at 2.0 A resolution
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in complex with inhibitor E5E2, hanging drop vapour diffusion method, 100 mM Tris pH 7.2, 200 mM ammonium sulfate, 21% PEG 4000
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purified detagged recombinant PI3K SH3 domain, residues 1-83, crystallized in presence of peptide ligands PD1R or PD1, the crystals do not contain the PD1 ligand, instead, the ligand binding site is partially occupied by residues Arg18 and Trp55 from the symmetry-related PI3K SH3 molecule. Sitting drop vapor diffusion method by mixing of 0.001 ml of protein-peptide mixture and 0.001 ml of reservoir solution containing for PD1R crystals 100 mM CAPS buffer, pH 10.5, 2 M ammonium sulfate and 0.2 M lithium sulfate or for PD1 crystals 100 mM Na-citrate buffer, pH 5.5, 0.5 M ammonium sulfate and 1 M lithium sulfate, 17°C, several weeks, X-ray diffraction structure determination and analysis at 1.7 A resolution
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant GST-tagged PI3K SH3 domain from Escherichia coli strain BL21 by glutathione affinity chromatography, followed by removal of the tag and gel filtration
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recombinant His-tagged class Ia isozymes and recombinant His-tagged p85 and p110 subunits from insect cells by nickel affinity chromatography to homogeneity
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
C2 domain-containing phosphoinositide 3-kinase, HsC2-PI3K
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class II phosphoinositide 3-kinase with a C2 domain, cloned from a U937 monocyte cDNA library, expression in mammalian and insect cells
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class Ia isozymes, DNA sequence determination and analysis, expression of His-tagged isozymes or P85 and p110 subunits alone in Spodoptera frugiperda Sf9 insect cells utilizing the baculovirus infection system
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class II phosphoinositide 3-kinase, PI 3-kinase C2b, with a C2 domain is cloned from a U937 monocyte cDNA library and expressed in mammalian and insect cells
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cloning of a human phosphoinositide 3-kinase with a C2 domain that displays reduced sensitivity to the inhibitor wortmannin
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construction of a tetracycline-inducible expression system by introducing a regulatory plasmid, which constitutively expresses tetracycline-sensitive transactivator, and a response plasmid, containing a tetracycline response element in form of a heptameric repeat of the tetR binding site, under control of a minimal CMV promotor, into Jurkat cells, individual and coexpression of the Myc-tagged enzyme subunits in the Jurkat cell system, determination of expression levels, overview
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expressed in Escherichia coli
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expression of GST-tagged PI3K SH3 domain in Escherichia coli strain Bl21
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expression of the catalytic subunit p110alpha of the wild-type and mutant enzymes in COS-1 cells
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expression of the wild-type p110 alpha protein in CHO cells
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gene PIK3R2
genotyping
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phosphoinositide-3 kinase isotype, p110 gamma
PIK3C2G is mapped to chromosome 12
stable expression of GFP-tagged Atg14 in NIH3T3 cells, transient co-expression of N-terminally Myc-, HA-, or FLAG-tagged Atg14, Beclin 1, and UVRAG in HEK-293T cells
transient co-expression of N-terminally Myc-, HA-, or FLAG-tagged Beclin 1 in HEK-293T cells
transient co-expression of N-terminally Myc-, HA-, or FLAG-tagged UVRAG in HEK-293T cells
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C838C/I848A
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site-directed mutagenesis, 10% activity compared to the wild-type enzyme
C838I/I848A
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site-directed mutagenesis, below 10% activity compared to the wild-type enzyme
C838L/I848A
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site-directed mutagenesis, highly reduced activity, 0.1% compared to the wild-type enzyme
D743N
kinase-dead catalytic loop mutant
E545K
-
a dominant activating mutation of the catalytic subunit PIK3CA that is prevalent in breast cancer and confers resistance to lapatinib, lapatinib effectively inhibits the transactivation of EGFR and HER2 by IGF-I signaling
G373R
naturally occuring mutation in gene PIK3R2 involved in bilateral perisylvian polymicrogyria
H1047R
I848A
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site-directed mutagenesis, mutation of a catalytic subunit p110 residue, highly reduced activity, 1% compared to the wild-type enzyme
I848G
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site-directed mutagenesis, mutation of a catalytic subunit p110 residue, highly reduced activity, 0.1% compared to the wild-type enzyme
K376E
naturally occuring mutation in gene PIK3R2 involved in bilateral perisylvian polymicrogyria
L750M
mutation in the ATP-binding pocket. Mutant is less sensitive to inhibition by KU55933 than wild-type, mutant is similarly sensitive to inhibition by LY294002 as wild-type
Y836A
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site-directed mutagenesis, completely inactive p110alpha mutant
Y836D
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site-directed mutagenesis, completely inactive p110alpha mutant
Y836G
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site-directed mutagenesis, completely inactive p110alpha mutant
Y836H
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site-directed mutagenesis, completely inactive p110alpha mutant
Y836L
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site-directed mutagenesis, completely inactive p110alpha mutant
Y836M
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site-directed mutagenesis, completely inactive p110alpha mutant
Y836T
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site-directed mutagenesis, completely inactive p110alpha mutant
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
medicine
pharmacology
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development of specific isozyme inhibitors may offer therapeutic benefit in a broad range of clinical settings related to cancer, inflammatory and immunological diseases