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Information on EC 2.7.1.153 - phosphatidylinositol-4,5-bisphosphate 3-kinase and Organism(s) Homo sapiens and UniProt Accession O00329

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EC Tree
IUBMB Comments
This enzyme also catalyses the phosphorylation of PtdIns4P to PtdIns(3,4)P2, and of PtdIns to PtdIns3P. Four mammalian isoforms are known to exist.
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Homo sapiens
UNIPROT: O00329
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
pik3ca, phosphoinositide 3-kinase, pi 3-kinase, pi3-kinase, pi3-k, pi-3k, pik3r1, phosphatidylinositol 3'-kinase, p110alpha, pi 3-k, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
p110delta
catalytic subunit
phosphatidyl-inositol-3-kinase
-
phosphatidylinositol 3'-kinase
-
class I phosphoinositide 3-kinase
class I PI3K
class IA phosphatidylinositol 3-kinase
-
-
class IA phosphatidylinositol-4,5-bisphosphate 3-kinase
-
CXCR2/phosphatidylinositol 3-kinase gamma
-
-
kinase (phosphorylating), phosphatidylinositol 4,5-diphosphate 3-
-
-
-
-
p101-PI3K
-
-
-
-
p110alpha
p110beta
catalytic subunit
p110delta
-
-
-
-
p110gamma/p101
-
-
P120-PI3K
-
-
-
-
phosphatidyl-inositol-3-kinase
-
phosphatidylinositol (4,5)-bisphosphate 3-hydroxykinase
-
-
-
-
phosphatidylinositol 3'-kinase
phosphatidylinositol 3-hydroxyl kinase
-
-
-
-
phosphatidylinositol 3-kinase alpha
-
phosphatidylinositol-4,5-bisphosphate 3-kinase
phosphoinositide 3-kinase
phosphoinositol 3-kinase
-
PI 3-kinase
-
-
PI3-K
-
-
PI3-kinase
-
-
PI3Kalpha
PI3Kbeta
PI3Kgamma
PtdIns(4,5)P2 3-OH kinase
-
-
-
-
PtdIns-3-kinase p101
-
-
-
-
PtdIns-3-kinase p110
-
-
-
-
PtdInsP 3-OH-kinase
-
-
-
-
type I phosphoinositide 3-kinase
-
-
-
-
additional information
-
class I PI3Ks can be further subtyped depending on their associated catalytic subunit into class IA p110alpha, p110beta and p110delta and class IB p110gamma
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho-group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:1-phosphatidyl-1D-myo-inositol-4,5-bisphosphate 3-phosphotransferase
This enzyme also catalyses the phosphorylation of PtdIns4P to PtdIns(3,4)P2, and of PtdIns to PtdIns3P. Four mammalian isoforms are known to exist.
CAS REGISTRY NUMBER
COMMENTARY hide
103843-30-7
-
115926-52-8
cf. EC 2.7.1.137
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 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
show the reaction diagram
ATP + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 4,5-diphosphate
show the reaction diagram
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
show the reaction diagram
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-triphosphate
show the reaction diagram
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
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 + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 4,5-diphosphate
show the reaction diagram
-
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL 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 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
show the reaction diagram
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
show the reaction diagram
-
catalyzed by class I and III, and probably by class II enzymes, overview. PI3K is part of the plasma membrane E-cadherin signaling complex
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-triphosphate
show the reaction diagram
-
catalyzed by class I enzyme, overview. PI3K is part of the plasma membrane E-cadherin signaling complex
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
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
-
catalyzed by class I enzyme, overview. PI3K is part of the plasma membrane E-cadherin signaling complex
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3-phenyl-2-[(S)-1-(9H-purin-6-ylamino)-propyl]-3H-quinazolin-4-one
i.e. CAL-101, highly selective and small molecule inhibitor of isoform PI3Kdelta. Inhibitor blocks constitutive phosphatidylinositol-3-kinase signaling, resulting in decreased phosphorylation of Akt and other downstream effectors, an increase in poly(ADP-ribose) polymerase and caspase cleavage and an induction of apoptosis
IC-87114
p110delta-specific small molecule inhibitor
idelalisib
5-fluoro-3-phenyl-2-[(1S)-1-(9H-purin-6-ylamino)propyl]quinazolin-4(3H)-one, a PI3Kdelta inhibitor used to treat hematological malignancies. The inhibitor idelalisib is selective, noncovalent, reversible, and ATP-competitive. The compound binds reversibly and noncovalently to the p110delta subunit of the kinase, analysis of binding interactions that confer the potency and selectivity of idelalisib, overview. Idelalisib is a propeller-shaped inhibitor
Wortmannin
-
1-[2-methyl-3-(trifluoromethyl)benzyl]-2-methyl-7-(morpholin-4-yl)-6,7-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one
-
1-[2-methyl-3-(trifluoromethyl)benzyl]-7-(morpholin-4-yl)-6,7-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one
-
1-[2-methyl-3-(trifluoromethyl)benzyl]-7-[(2R)-2-methylmorpholin-2-yl]-6,7-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one
-
1-[4-[(4-methylpiperazin-1-yl)carbonyl]phenyl]-3-[4-[4-morpholin-4-yl-7-(2,2,2-trifluoroethyl)-7H-pyrrolo[2,3-d ]pyrimidin-2-yl]phenyl]urea
dual catalytic subunit alpha isoform/mTOR kinase inhibitor, demonstrates inhibition of tumor cell growth in vitro and in vivo and causes suppression of the pathway specific biomarkers in the human MDA-361 cell line
17-hydroxywortmannin
-
-
2-(difluoromethyl)-1-[4,6-di-(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole
lead compound for structure-activity study
2-(methylsulfanyl)-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(morpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
-
2-methyl-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(2methylmorpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
-
2-methyl-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(morpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
-
2-[(6-amino-9H-purin-9-yl)methyl]-5-methyl-3-(2-methylphenyl)-4(3H)-quinazolinone
-
i.e. IC87114, selectively inhibits isoform p110delta
3-(2-morpholino-6-(2-(pyridin-4-yl)ethylamino)pyrimidin-4-yl)phenol
-
3-(2-morpholino-6-(pyridin-2-ylmethoxy)pyrimidin-4-yl)phenol
-
3-(4-morpholino-6-(pyridin-2-yl)pyrimidin-2-yl)phenol
-
3-Methyladenine
-
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
3-[4-(4-morpholinyl)thieno(3,2-d)pyrimidin-2-yl]-phenol
-
a p110 PI3K isoform selective inhibitor
3-[4-(morpholin-4-yl)pyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl]phenol
among the compounds tested, treatment with 3-[4-(morpholin-4-yl)thieno[3,2-d]pyrimidin-2-yl]phenol or 3-[4-(morpholin-4-yl)pyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl]phenol leads to the most efficient inhibition
3-[4-(morpholin-4-yl)thieno[3,2-d]pyrimidin-2-yl]phenol
among the compounds tested, treatment with 3-[4-(morpholin-4-yl)thieno[3,2-d]pyrimidin-2-yl]phenol or 3-[4-(morpholin-4-yl)pyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl]phenol leads to the most efficient inhibition
4-(2-((6-methoxypyridin-3-yl)amino)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine
not inhibitory to serine/threonine kinase mTOR
4-[2-[(6-methoxypyridin-3-yl)amino]-5-phenylpyridin-3-yl]-6-methyl-1,3,5-triazin-2-amine
not inhibitory to serine/threonine kinase mTOR
4-[4-(morpholin-4-yl)-5a,6-dihydro[1]benzofuro[3,2-d]pyrimidin-2-yl]phenol
4-[5-(3,6-dihydro-2H-pyran-4-yl)-2-[(6-methoxypyridin-3-yl)amino]pyridin-3-yl]-6-methyl-1,3,5-triazin-2-amine
not inhibitory to serine/threonine kinase mTOR
5-[2,2-difluoro-benzo(1,3)-dioxol-5-ylmethylene]-thiazolidine-2,4-dione
-
a p110 PI3K isoform selective inhibitor
6-amino-2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-4-methoxy-1H-benzimidazole
inhibitory against all three class Ia PI 3-kinase enzymes, i.e. p110alpha, p110beta, and p110delta, and also displays significant potency against two mutant forms of the p110alpha isoform, H1047R and E545K. In an in vivo U87MG human glioblastoma tumor xenograftmodel in Rag1-/- mice, and at a dose of 50mg/kg given by intraperitoneal injection it dramatically reduces cancer growth by 81% compared to untreated controls
7-methyl-2-(4-morpholinyl)-9-[1-(phenylamino)ethyl]-4H-pyrido[1,2-a]pyrimidin-4-one
-
i.e. TGX221, selectively inhibits isoform p110beta. Compound decreases secretion of vascular endothelial growth factor and interleukin-6 in nonasthmatic airway smooth muscle cells and lung fibroblasts
Baicalin
-
10 microM, 35.5% inhibition of isoform PI3Kalpha
BYL719
a p110alpha-specific inhibitor, BYL719 fails to display selective growth inhibition in p110alphahigh cells
-
CAL-101
-
a specific inhibitor of the PI3Kdelta isoform
GSK2636771
a p110beta-specific inhibitor
-
HS173
a p110alpha-specific inhibitor
-
IC87114
idelalisib
CAL-101, a p110delta inhibitor
luteolin
-
1 microM, 75.8% inhibition of isoform PI3Kalpha
Ly-294002
-
LY294002
MLN1117
a p110alpha-specific inhibitor
-
myricetin
-
1 microM, almost complete inhibition of isoform PI3Kalpha
N-[(E)-(6-bromoimidazo[1,2-a]pyridin-3-yl)methylidene]-N,2-dimethyl-5-nitrobenzenesulfonohydrazide
-
i.e.PIK75, selectively inhibits isoform p110alpha. In cells stimulated with transforming growth factor-beta and/or 10% fetal bovine serum, compound attenuates transforming growth factor-induced fibronectin deposition in all cell types tested and decreases secretion of vascular endothelial growth factor and interleukin-6 in nonasthmatic airway smooth muscle cells and lung fibroblasts. Compound decreases cell survival in transforming growth factor-stimulated asthmatic, but not nonasthmatic, airway smooth muscle cells
N-[2-(dimethylamino)ethyl]-N-methyl-4-[([4-[4-morpholin-4-yl-7-(2,2,2-trifluoroethyl)-7H-pyrrolo[2,3-d ]pyrimidin-2-yl]phenyl]carbamoyl)amino]benzamide
dual catalytic subunit alpha isoform/mTOR kinase inhibitor, demonstrates inhibition of tumor cell growth in vitro and in vivo and causes suppression of the pathway specific biomarkers in the human MDA-361 cell line. Good in vivo efficacy in the MDA361 human breast tumor xenograft model
PI-103
PI103
-
suppressing phosphatidylinositol 3-kinase activity by inhibitors LY294002 and PI103 selectively reduces both the mRNA and protein levels of peroxisome proliferator-activated receptor gamma coactivator PGC-1beta but not PGC-1alpha. Reducing PGC-1b expression also leads to reduced mRNA expression levels of uncoupling protein 1, 2 and superoxide dismutase 2. Correspondingly, mitochondrial membrane potential and reactive oxygen species levels are increased
PIK-75
PIK75
p110alpha inhibitor PIK75 shows a strong cytotoxicity to all glioblastoma cell lines tested
PX-866
-
irreversible PI3K inhibitor, shows selectivity for the alpha, delta, and gamma class I PI3K isoforms, inhibits the beta isoform at higher concentrations, and shows decreased selectivity for mTor
quercetagetin
-
1 microM, almost complete inhibition of isoform PI3Kalpha
quercetin
-
1 microM, 54.1% inhibition of isoform PI3Kalpha
TGX-221
TGX-221-R
R-enantiomer of inhibitor TGX-221, 100fold more potent as a PI3K-beta inhibitor than the S-enantiomer
WAY-266175
-
-
-
WAY-266176
-
-
Wortmannin
XL147
YM024
a p110alpha-selective PI3K inhibitor
-
ZSTK474
-
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
[(4-[2-[(3-hydroxyphenyl)amino]-1H-benzimidazol-1-yl]-1,3,5-triazin-2-yl)amino]acetonitrile
lead compound for structure-based design of inhibitors, dual inhibitor of phosphatidylinositol 3-kinase and serine/threonine kinase mTOR
[3-[4-morpholin-4-yl-7-(pyrrolidin-1-ylmethyl)-5H-pyrrolo-[3,2-d ]pyrimidin-2-yl]phenyl]methanol
selective for catalytic subunit alpha isoform
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
beta-catenin
-
tyrosine-phopshorylated
-
c-Src
-
-
-
Dlg
-
tyrosine-phopshorylated
-
G-protein alpha, beta and gamma subunit
strong
-
G-protein beta,gamma
in vivo, activation of enzyme by a mechanism assigning specific roles for both enzyme subunits, membrane recruitment via the noncatalytic p101 subunit, and direct stimulation of p110gamma
-
G-protein beta,gamma subunits
significant stimulation of enzyme beta and gamma isoforms in the presence as well as in the absence of non-catalytic subunits such as p85alpha or p101, stimulation of autophosphorylation of the catalytic subunit of enzyme
-
monocyte chemotactic peptide-1
-
i.e. MCP-1, stimulation can be inhibited by pertussis toxin, but not by wortmannin
-
Pasteurella multocida toxin
-
mediated by G protein betagamma-subunits and G protein alpha-subunit, EC 3.6.5.1
-
Ras
-
active RAs activates class 1 enzymes
-
RAS-GTP
-
regulatory domain p85 interacts with RAS-GTP. RAS binding is essential for oncogenic transformation by helical domain mutants of p110alpha
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0000025 - 0.00082
3-phenyl-2-[(S)-1-(9H-purin-6-ylamino)-propyl]-3H-quinazolin-4-one
0.000001
1-[2-methyl-3-(trifluoromethyl)benzyl]-2-methyl-7-(morpholin-4-yl)-6,7-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.000003
1-[2-methyl-3-(trifluoromethyl)benzyl]-7-(morpholin-4-yl)-6,7-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.000001
1-[2-methyl-3-(trifluoromethyl)benzyl]-7-[(2R)-2-methylmorpholin-2-yl]-6,7-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.0000024
1-[4-[(4-methylpiperazin-1-yl)carbonyl]phenyl]-3-[4-[4-morpholin-4-yl-7-(2,2,2-trifluoroethyl)-7H-pyrrolo[2,3-d ]pyrimidin-2-yl]phenyl]urea
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.0000004 - 0.0013
2-(methylsulfanyl)-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(morpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
0.0000003 - 0.00032
2-methyl-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(2methylmorpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
0.0000006 - 0.00079
2-methyl-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(morpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
0.00014 - 0.0016
3-(2-morpholino-6-(2-(pyridin-4-yl)ethylamino)pyrimidin-4-yl)phenol
0.00011 - 0.00073
3-(2-morpholino-6-(pyridin-2-ylmethoxy)pyrimidin-4-yl)phenol
0.000044 - 0.0001
3-(4-morpholino-6-(pyridin-2-yl)pyrimidin-2-yl)phenol
0.00058
3-[4-(4-morpholinyl)thieno(3,2-d)pyrimidin-2-yl]-phenol
Homo sapiens
-
versus p110alpha PI3K
0.000002 - 0.000009
4-(2-((6-methoxypyridin-3-yl)amino)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine
0.000001 - 0.000007
4-[2-[(6-methoxypyridin-3-yl)amino]-5-phenylpyridin-3-yl]-6-methyl-1,3,5-triazin-2-amine
0.000002 - 0.000005
4-[5-(3,6-dihydro-2H-pyran-4-yl)-2-[(6-methoxypyridin-3-yl)amino]pyridin-3-yl]-6-methyl-1,3,5-triazin-2-amine
0.00025
5-[2,2-difluoro-benzo(1,3)-dioxol-5-ylmethylene]-thiazolidine-2,4-dione
Homo sapiens
-
about, versus p110gamma PI3K
0.00000022 - 0.0000014
6-amino-2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-4-methoxy-1H-benzimidazole
0.008
LY294002
Homo sapiens
-
inhibition of bacterial entry into macrophages
0.0000009
N-[2-(dimethylamino)ethyl]-N-methyl-4-[([4-[4-morpholin-4-yl-7-(2,2,2-trifluoroethyl)-7H-pyrrolo[2,3-d ]pyrimidin-2-yl]phenyl]carbamoyl)amino]benzamide
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.00004
TGX-221
Homo sapiens
-
about, versus p110beta PI3K
0.000006
TGX-221-R
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.0000025
Wortmannin
Homo sapiens
-
inhibition of bacterial entry into macrophages
0.000052 - 0.00035
[(4-[2-[(3-hydroxyphenyl)amino]-1H-benzimidazol-1-yl]-1,3,5-triazin-2-yl)amino]acetonitrile
0.000021
[3-[4-morpholin-4-yl-7-(pyrrolidin-1-ylmethyl)-5H-pyrrolo-[3,2-d ]pyrimidin-2-yl]phenyl]methanol
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
additional information
additional information
Homo sapiens
-
IC50 value of inhibitor 4-[4-(morpholin-4-yl)-5a,6-dihydro[1]benzofuro[3,2-d]pyrimidin-2-yl]phenol is 2 nmol/l against recombinant isoform p110alpha, 3 nmol/l against recombinant isoform p110beta, 3 nmol/l against recombinant isoform p110delta, 15 nmol/l against recombinant isoform p110agamma
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
assay at
7
-
assay at
7.5
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
assay at
22
-
assay at room temperature
30
assay at
37
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
high expression
Manually annotated by BRENDA team
high expression
Manually annotated by BRENDA team
-
an airway epithelial cell line
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
recombinant isoforms PI3Kalpha, beta, delta and gamma
Manually annotated by BRENDA team
renal proximal tubule epithelial cell
Manually annotated by BRENDA team
primary human acute myeloid leukemia (AML) cells
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
68% of clinical cases and the MCL cell lines harbor a gain of PIK3 catalytic subunit alpha gene copy number. In addition, cases with increased PIK3CA gene copy number have elevated PIK3CA mRNA levels
Manually annotated by BRENDA team
-
PI3Kdelta isoform is most prominently expressed in myeloid cells
Manually annotated by BRENDA team
-
osteoclasts express multiple regulatory subunits of class IA PI3-K, although the expression of the full-length form of p85alpha is most abundant
Manually annotated by BRENDA team
-
an epithelial ovarian cancer cell line SKOV3 with constitutively active PI3K
Manually annotated by BRENDA team
-
all cell lines express the catalytic subunit isoforms p110alpha, p110beta, p110gamma, and p110delta
Manually annotated by BRENDA team
-
monocytic cell line
Manually annotated by BRENDA team
-
PI3Kgamma, small amounts
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
evolution
malfunction
metabolism
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
PK3CD_HUMAN
1044
0
119479
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
110000
119471
x * 119471, p110delta subunit, can bind the p85 adaptor subunit, calculation from nucleotide sequence
119505
x * 119505, calculated, x * 110000, SDS-PAGE
110000
120000
x * 120000, calculated, x * 110000, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
heterodimer
1 * 110000, subunit p110, + 1 * 85000, subunit p85, class IA PI3K isoforms are heterodimers consisting of a catalytic subunit (p110delta) and a smaller regulatory subunit (p85)
?
x * 120000, calculated, x * 110000, SDS-PAGE
dimer
heterodimer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
stimulation of autophosphorylation of catalytic sunbunit by G-protein beta,gamma subunits
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified enzyme mutant, mixing of 25 nl 11 mg/ml protein with 0.9 mM inhibitor delalisib in 20 mM Tris, pH 7.2, 50 mM (NH4)2SO4, 1% v/v ethylene glycol, 1% w/v betaine, 300 mM CHAPS, and 5 mM TCEP, with 25 nl of reservoir solution containing 25% w/v PEG 3350, 0.1 M Bis-Tris, pH 6.5, microseeding in 480 nl of 2.5% w/v n-dodecyl-beta-D-maltoside, 300 nl of 20 mM ligand, and 0.12 ml of 12 mg/ml DELTAABD-p110delta in storage buffer 20 mM Tris, pH 7.2, 50 mM (NH4)2SO4, 1% v/v ethylene glycol, 1% w/v betaine, 300 nM CHAPS, and 5mM TCEP, X-ray diffraction structure determination and analysis at 2.4-2.5 A resolution
cocrystal strucutre of inhibitor 4-(2-((6-methoxypyridin-3-yl)amino)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine bound to catalytic subunit gamma isoform. Compound binds with two hydrogen bonds from the aminotriazine ring to the hinge, with the triazine methyl substituent oriented toward the Tyr867 side chain, and with the 4-methoxypyridine substituent projected into the affinity pocket. The methoxypyridine nitrogen atom makes a hydrogen bond to an ordered water molecule sitting between Tyr867 and Asp841, and the piperazine sulfonamide extended into the ribose pocket
docking of inhibitor TGX-221-R into a homology model of the PI3K-beta enzyme. The morpholine-oxygen accepts an H-bond from the hinge region Val854 while the pyrido-pyrimidinone template core interacts in the central pocket lined by Met926 and Ile residues 803, 851 and 936 from the N and C-terminal of the kinase domain
structure activity relationship study of inhibitor 2-(difluoromethyl)-1-[4,6-di-(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole, i.e. ZSTK474, with catalytic subunit gamma isoform, PDB entry 2CHX
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A1066V
-
a common naturally occuring mutation involved in cancer development
D1017H
-
a common naturally occuring somatic mutation involved in cancer development
D915A
complete loss of enzymic activity
D933A/F934A
complete loss of enzymic activity
E542K
-
a common naturally occuring mutation in the helical domain, the mutation is involved in cancer development, the mutant requires RAS binding but bot p85 binding
E542K/E545K
E545K
E545K/H1047R
-
gain-of-function helical domain mutations result in upregulation of enzyme activity, Akt phosphorylation and cell transformation
E970A
90% of wild-type activity
H1047R
K227E
-
the mutaion reduces enzyme activity
K802R
mutation in subunit p110alpha, inactive mutant
M1043I
-
a common naturally occuring somatic mutation involved in cancer development
M326I
-
a common naturally occuring polymorphism of the regulatory subunit p85alpha in women involved in the polycystic ovary syndrome, PCOS, genotyping in polycystic ovary syndrome patients from Korean female population
N345K
P124L
-
a common naturally occuring somatic mutation involved in cancer development. P124L lies in a region of four helices in the protein between the adapter-binding and RAS-binding domains
P124T
-
a naturally occuring missense mutation in codon 124 from a colorectal cancer cell
Q643R
-
a common naturally occuring somatic mutation involved in cancer development
R274A
-
the GTPase-activating protein activity toward Rab5 and Rab4 of PI3K p85alpha subunit is abolished in the mutant. Expression of p85alpha-R274A results in increased platelet-derived growth factor receptor, PDGFR, activation and downstream signaling, via Akt and MAPK pathways, and in decreased PDGFR degradation. Disrupted RabGAP function of the p85 subunit of phosphatidylinositol 3-kinase results in cell transformation, co-expression of a dominant negative Rab5-S34N mutant attenuates these transformed properties
R38C/R88C
the mutation significantly change the distance distribution for helical domain residues K379, I381 and K382
R922A
80% of wild-type activity
additional information
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant N-terminally His6-tagged p110 and nontagged p85 subunits from Spodoptera frugiperda Sf21 cells by nickel affinity chromatography
recombinant His6-tagged wild-type full-length PI3Kgamma isozyme from Spodoptera frugiperda Sf9 cells by nickel affinity chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
coexpression of N-terminally His6-tagged p110 and nontagged p85 subunits in Spodoptera frugiperda Sf21 cells via baculovirus transfection method, recombinant expression of DELTAABC mutant p110delta with the iSH2 domain of p85alpha
expression in Saccharomyces cerevisiae
expression of HA-tagged p85alpha in NIH 3T3 cells in a mouse cell model
-
expression of P110delta in Sf9 insect cells
-
expression of p85 constructus from a retroviral vector
-
functional recombinant expression of wild-type and K802R mutant enzymes in Saccharomyces cerevisiae, the transcriptional profile of PI3K-expressing cells is consistent with sustained CWI activation, Pkc1 localizes to endosomes in PI3K-expressing cells, PI3K expression relocates Pkc1 to endosomal compartments. PI3K effects in yeast signaling and trafficking are reversible by a competitive inhibitor in a dose-dependent manner
gene PIK3CA, encodes the catalytic subunit of PI3K, and resides in chromosomal area 3q26
-
overexpression of the dominant negative PI3K mutant in J774A.1 cells
-
PI 3-kinase genotyping
-
quantitative RT-PCR enzyme expression analysis
-
recombinant coexpression of N-terminally His-tagged full-length wild-type and mutant class 1a isoform catalytic subunits with the p85 regulatory subunit, impacct of the His-tag on the catalytic activity, overview
recombinant coexpression of N-terminally His-tagged full-length wild-type and mutant class 1b isoform catalytic subunits with the p85alpha regulatory subunit, impact of the His-tag on the catalytic activity, overview
recombinant expression of His6-tagged wild-type full-length PI3Kgamma isozyme in Spodoptera frugiperda Sf9 cells using the baculovirus transfection method
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
gain of copy number of PIK3CA gene by gene amplification in mantle cell lymphoma is one mechanism of oncogenic activation of PI3K. Expression of PIK3CA in mantle cell lymphoma correlates with gene copy numbers determined by real-time PCR, overview
-
upregulation of class I PI3K isozymes in cancer cells
-
virulent Legionella pneumophila infection induces PI3K in human macrophages, while PI3K and protein kinase B, PKB/Akt, activities are lower in macrophages infected with an avirulent bacterial strain
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
low-cost bioassay that readily measures phosphatidylinositol 3-kinase inhibition. The in vivo assay is based on the fact that the overproduction of phosphatidylinositol 3-kinase is toxic in yeast, and uses the ability of commercial phosphatidylinositol 3-kinase inhibitors to rescue cell growth. The use of 0.003% sodium dodecyl sulfate and the elimination of the Snq2 detoxification pump, optimize the bioassay by enhancing its sensitivity. From 9600 extracts tested, 0.6% lead to a recovery of yeast growth reproducibly, selectively, and in a dose-dependent manner
medicine
pharmacology
-
the PI3Kgamma signaling pathway may represent a suitable target for the development of therapeutic strategies for human diseases characterized by vascular leakage
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Vanhaesebroeck, B.; Leevers, S.J.; Ahmadi, K.; Timms, J.; Katso, R.; Driscoll, P.C.; Woscholski, R.; Parker, P.J.; Waterfield, M.D.
Synthesis and function of 3-phosphorylated inositol lipids
Annu. Rev. Biochem.
70
535-602
2001
Caenorhabditis elegans, Dictyostelium discoideum, Drosophila melanogaster, Homo sapiens, Mammalia
Manually annotated by BRENDA team
Metzner, B.; Heger, M.; Hofmann, C.; Czech, W.; Norgauer, J.
Evidence for the involvement of phosphatidylinositol 4,5-bisphosphate 3-kinase in CD18-mediated adhesion of human neutrophils to fibrinogen
Biochem. Biophys. Res. Commun.
232
719-723
1997
Homo sapiens
Manually annotated by BRENDA team
Vanhaesebroeck, B.; Welham, M.J.; Kotani, K.; Stein, R.; Warne, P.H.; Zvelebil, M.J.; Higashi, K.; Volinia, S.; Downward, J.; Waterfield, M.D.
P110delta, a novel phosphoinositide 3-kinase in leukocytes
Proc. Natl. Acad. Sci. USA
94
4330-4335
1997
Homo sapiens (O00329)
Manually annotated by BRENDA team
Chantry, D.; Vojtek, A.; Kashishian, A.; Holtzman, D.A.; Wood, C.; Gray, P.W.; Cooper, J.A.; Hoekstra, M.F.
p110delta, a novel phosphatidylinositol 3-kinase catalytic subunit that associates with p85 and is expressed predominantly in leukocytes
J. Biol. Chem.
272
19236-19241
1997
Homo sapiens (O00329), Homo sapiens
Manually annotated by BRENDA team
Stoyanov, B.; Volinia, S.; Hanck, T.; Rubio, I.; Loubtchenkov, M.; Malek, D.; Stoyanova, S.; Vanhaesebroeck, B.; Dhand, R.; et al.
Cloning and characterization of a G protein-activated human phosphoinositide-3 kinase
Science
269
690-693
1995
Homo sapiens (P48736)
Manually annotated by BRENDA team
Stirdivant, S.M.; Ahern, J.; Conroy, R.R.; Barnett, S.F.; Ledder, L.M.; Oliff, A.; Heimbrook, D.C.
Cloning and mutagenesis of the p110 alpha subunit of human phosphoinositide 3'-hydroxykinase
Bioorg. Med. Chem.
5
65-74
1997
Homo sapiens (P42336)
Manually annotated by BRENDA team
Turner, S.J.; Domin, J.; Waterfield, M.D.; Ward, S.G.; Westwick, J.
The CC chemokine monocyte chemotactic peptide-1 activates both the class I p85/p110 phosphatidylinositol 3-kinase and the class II PI3K-C2alpha
J. Biol. Chem.
273
25987-25995
1998
Homo sapiens
Manually annotated by BRENDA team
Jackson, S.P.; Schoenwaelder, S.M.; Matzaris, M.; Brown, S.; Mitchell, C.A.
Phosphatidylinositol 3,4,5-trisphosphate is a substrate for the 75 kDa inositol polyphosphate 5-phosphatase and a novel 5-phosphatase which forms a complex with the p85/p110 form of phosphoinositide 3-kinase
EMBO J.
14
4490-4500
1995
Homo sapiens
Manually annotated by BRENDA team
Kurosu, H.; Katada, T.
Association of phosphatidylinositol 3-kinase composed of p110beta-catalytic and p85-regulatory subunits with the small GTPase Rab5
J. Biochem.
130
73-78
2001
Homo sapiens
Manually annotated by BRENDA team
Maier, U.; Babich, A.; Nurnberg, B.
Roles of non-catalytic subunits in Gbg-induced activation of class I phosphoinositide 3-kinase isoforms b and g
J. Biol. Chem.
274
29311-29317
1999
Homo sapiens (P48736)
Manually annotated by BRENDA team
Brock, C.; Schaefer, M.; Reusch, H.P.; Czupalla, C.; Michalke, M.; Spicher, K.; Schultz, G.; Nurnberg, B.
Roles of Gbg in membrane recruitment and activation of p110gamma/p101 phosphoinositide 3-kinase gamma
J. Cell Biol.
160
89-99
2003
Homo sapiens (P48736)
Manually annotated by BRENDA team
Hu, P.; Mondino, A.; Skolnik, E.Y.; Schlessinger, J.
Cloning of a novel, ubiquitously expressed human phosphatidylinositol 3-kinase and identification of its binding site on p85
Mol. Cell. Biol.
13
7677-7688
1993
Homo sapiens (P42338), Homo sapiens
Manually annotated by BRENDA team
Raynaud, F.I.; Eccles, S.; Clarke, P.A.; Hayes, A.; Nutley, B.; Alix, S.; Henley, A.; Di-Stefano, F.; Ahmad, Z.; Guillard, S.; Bjerke, L.M.; Kelland, L.; Valenti, M.; Patterson, L.; Gowan, S.; de Haven Brandon, A.; Hayakawa, M.; Kaizawa, H.; Koizumi, T.; Ohishi, T.; Patel, S.; Saghir, N.; Parker, P.; Waterfield, M.; Workman, P.
Pharmacologic characterization of a potent inhibitor of class I phosphatidylinositide 3-kinases
Cancer Res.
67
5840-5850
2007
Homo sapiens
Manually annotated by BRENDA team
Park, S.; Chapuis, N.; Bardet, V.; Tamburini, J.; Gallay, N.; Willems, L.; Knight, Z.A.; Shokat, K.M.; Azar, N.; Viguie, F.; Ifrah, N.; Dreyfus, F.; Mayeux, P.; Lacombe, C.; Bouscary, D.
PI-103, a dual inhibitor of class IA phosphatidylinositide 3-kinase and mTOR, has antileukemic activity in AML
Leukemia
22
1698-1706
2008
Homo sapiens
Manually annotated by BRENDA team
Preuss, I.; Kurig, B.; Nuernberg, B.; Orth, J.H.; Aktories, K.
Pasteurella multocida toxin activates Gbetagamma dimers of heterotrimeric G proteins
Cell. Signal.
21
551-558
2009
Homo sapiens
Manually annotated by BRENDA team
Knowles, M.A.; Platt, F.M.; Ross, R.L.; Hurst, C.D.
Phosphatidylinositol 3-kinase (PI3K) pathway activation in bladder cancer
Cancer Metastasis Rev.
28
305-316
2009
Homo sapiens
Manually annotated by BRENDA team
Renner, O.; Blanco-Aparicio, C.; Grassow, M.; Canamero, M.; Leal, J.F.; Carnero, A.
Activation of phosphatidylinositol 3-kinase by membrane localization of p110alpha predisposes mammary glands to neoplastic transformation
Cancer Res.
68
9643-9653
2008
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Chiarini, F.; Fala, F.; Tazzari, P.L.; Ricci, F.; Astolfi, A.; Pession, A.; Pagliaro, P.; McCubrey, J.A.; Martelli, A.M.
Dual inhibition of class IA phosphatidylinositol 3-kinase and mammalian target of rapamycin as a new therapeutic option for T-cell acute lymphoblastic leukemia
Cancer Res.
69
3520-3528
2009
Homo sapiens
Manually annotated by BRENDA team
Psyrri, A.; Papageorgiou, S.; Liakata, E.; Scorilas, A.; Rontogianni, D.; Kontos, C.K.; Argyriou, P.; Pectasides, D.; Harhalakis, N.; Pappa, V.; Kolialexi, A.; Economopoulou, C.; Kontsioti, F.; Maratou, E.; Dimitriadis, G.; Economopoulou, P.; Economopoulos, T.
Phosphatidylinositol 3-kinase catalytic subunit alpha gene amplification contributes to the pathogenesis of mantle cell lymphoma
Clin. Cancer Res.
15
5724-5732
2009
Homo sapiens
Manually annotated by BRENDA team
Rivard, N.
Phosphatidylinositol 3-kinase: a key regulator in adherens junction formation and function
Front. Biosci.
14
510-522
2009
Canis lupus familiaris, Homo sapiens
Manually annotated by BRENDA team
Kim, J.J.; Choi, Y.M.; Hong, M.A.; Hwang, S.S.; Yoon, S.H.; Chae, S.J.; Jee, B.C.; Ku, S.Y.; Kim, J.G.; Moon, S.Y.
Phosphatidylinositol 3-kinase p85alpha regulatory subunit gene Met326Ile polymorphism in women with polycystic ovary syndrome
Hum. Reprod.
24
1184-1190
2009
Homo sapiens
Manually annotated by BRENDA team
Chamberlain, M.D.; Chan, T.; Oberg, J.C.; Hawrysh, A.D.; James, K.M.; Saxena, A.; Xiang, J.; Anderson, D.H.
Disrupted RabGAP function of the p85 subunit of phosphatidylinositol 3-kinase results in cell transformation
J. Biol. Chem.
283
15861-15868
2008
Homo sapiens
Manually annotated by BRENDA team
Cammer, M.; Gevrey, J.C.; Lorenz, M.; Dovas, A.; Condeelis, J.; Cox, D.
The mechanism of CSF-1-induced Wiskott-Aldrich syndrome protein activation in vivo: a role for phosphatidylinositol 3-kinase and Cdc42
J. Biol. Chem.
284
23302-23311
2009
Homo sapiens
Manually annotated by BRENDA team
Desai, L.P.; White, S.R.; Waters, C.M.
Cyclic mechanical stretch decreases cell migration by inhibiting phosphatidylinositol 3-kinase (PI3-kinase) and focal adhesion kinase (FAK) mediated c-Jun N-terminal kinase-1 (JNK1) activation
J. Biol. Chem.
285
4511-4519
2009
Homo sapiens
Manually annotated by BRENDA team
Ihle, N.T.; Powis, G.
Take your PIK: phosphatidylinositol 3-kinase inhibitors race through the clinic and toward cancer therapy
Mol. Cancer Ther.
8
1-9
2009
Homo sapiens
Manually annotated by BRENDA team
Munugalavadla, V.; Vemula, S.; Sims, E.C.; Krishnan, S.; Chen, S.; Yan, J.; Li, H.; Niziolek, P.J.; Takemoto, C.; Robling, A.G.; Yang, F.C.; Kapur, R.
The p85alpha subunit of class IA phosphatidylinositol 3-kinase regulates the expression of multiple genes involved in osteoclast maturation and migration
Mol. Cell. Biol.
28
7182-7198
2008
Homo sapiens
Manually annotated by BRENDA team
Gavard, J.; Hou, X.; Qu, Y.; Masedunskas, A.; Martin, D.; Weigert, R.; Li, X.; Gutkind, J.S.
A role for a CXCR2/phosphatidylinositol 3-kinase gamma signaling axis in acute and chronic vascular permeability
Mol. Cell. Biol.
29
2469-2480
2009
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Zhang, X.; Deng, H.X.; Zhao, X.; Su, D.; Chen, X.C.; Chen, L.J.; Wei, Y.Q.; Zhong, Q.; Li, Z.Y.; He, X.; Yi, T.
RNA interference-mediated silencing of the phosphatidylinositol 3-kinase catalytic subunit attenuates growth of human ovarian cancer cells in vitroand in vivo
Oncology
77
22-32
2009
Homo sapiens
Manually annotated by BRENDA team
Tachado, S.D.; Samrakandi, M.M.; Cirillo, J.D.
Non-opsonic phagocytosis of Legionella pneumophila by macrophages is mediated by phosphatidylinositol 3-kinase
PLoS ONE
3
e3324
2008
Homo sapiens
Manually annotated by BRENDA team
Zhao, L.; Vogt, P.K.
Helical domain and kinase domain mutations in p110alpha of phosphatidylinositol 3-kinase induce gain of function by different mechanisms
Proc. Natl. Acad. Sci. USA
105
2652-2657
2008
Homo sapiens
Manually annotated by BRENDA team
Akashi, T.; Yamori, T.
Proteomic analysis of phosphoproteins sensitive to a phosphatidylinositol 3-kinase inhibitor, ZSTK474, by using SELDI-TOF MS
Proteome Sci.
7
14
2009
Homo sapiens
Manually annotated by BRENDA team
Marwick, J.A.; Chung, K.F.; Adcock, I.M.
Phosphatidylinositol 3-kinase isoforms as targets in respiratory disease
Ther. Adv. Respir. Dis.
2009
1-16
2010
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Lin, H.; Erhard, K.; Hardwicke, M.A.; Luengo, J.I.; Mack, J.F.; McSurdy-Freed, J.; Plant, R.; Raha, K.; Rominger, C.M.; Sanchez, R.M.; Schaber, M.D.; Schulz, M.J.; Spengler, M.D.; Tedesco, R.; Xie, R.; Zeng, J.J.; Rivero, R.A.
Synthesis and structure-activity relationships of imidazo[1,2-a]pyrimidin-5(1H)-ones as a novel series of beta isoform selective phosphatidylinositol 3-kinase inhibitors
Bioorg. Med. Chem. Lett.
22
2230-2234
2012
Homo sapiens (P42338)
Manually annotated by BRENDA team
Sanchez, R.M.; Erhard, K.; Hardwicke, M.A.; Lin, H.; McSurdy-Freed, J.; Plant, R.; Raha, K.; Rominger, C.M.; Schaber, M.D.; Spengler, M.D.; Moore, M.L.; Yu, H.; Luengo, J.I.; Tedesco, R.; Rivero, R.A.
Synthesis and structure-activity relationships of 1,2,4-triazolo[1,5-a]pyrimidin-7(3H)-ones as novel series of potent beta isoform selective phosphatidylinositol 3-kinase inhibitors
Bioorg. Med. Chem. Lett.
22
3198-3202
2012
Homo sapiens (P42338)
Manually annotated by BRENDA team
Large, J.M.; Torr, J.E.; Raynaud, F.I.; Clarke, P.A.; Hayes, A.; Stefano, F.d.; Urban, F.; Shuttleworth, S.J.; Saghir, N.; Sheldrake, P.; Workman, P.; McDonald, E.
Preparation and evaluation of trisubstituted pyrimidines as phosphatidylinositol 3-kinase inhibitors. 3-Hydroxyphenol analogues and bioisosteric replacements
Bioorg. Med. Chem.
19
836-851
2011
Homo sapiens (P42336)
Manually annotated by BRENDA team
Lannutti, B.J.; Meadows, S.A.; Herman, S.E.; Kashishian, A.; Steiner, B.; Johnson, A.J.; Byrd, J.C.; Tyner, J.W.; Loriaux, M.M.; Deininger, M.; Druker, B.J.; Puri, K.D.; Ulrich, R.G.; Giese, N.A.
CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability
Blood
117
591-594
2011
Homo sapiens (O00329)
Manually annotated by BRENDA team
Gao, M.; Wang, J.; Wang, W.; Liu, J.; Wong, C.W.
Phosphatidylinositol 3-kinase affects mitochondrial function in part through inducing peroxisome proliferator-activated receptor gamma coactivator-1beta expression
Br. J. Pharmacol.
162
1000-1008
2011
Homo sapiens
Manually annotated by BRENDA team
Wu, Y.; Tan, H.; Shui, G.; Bauvy, C.; Huang, Q.; Wenk, M.; Ong, C.; Codogno, P.; Shen, H.
Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase
J. Biol. Chem.
285
10850-10861
2010
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Runyan, C.E.; Liu, Z.; Schnaper, H.W.
Phosphatidylinositol 3-kinase and Rab5 GTPase inversely regulate the Smad anchor for receptor activation (SARA) protein independently of transforming growth factor-beta1
J. Biol. Chem.
287
35815-35824
2012
Homo sapiens (P27986)
Manually annotated by BRENDA team
Fernandez-Acero, T.; Rodriguez-Escudero, I.; Vicente, F.; Monteiro, M.C.; Tormo, J.R.; Cantizani, J.; Molina, M.; Cid, V.J.
A yeast-based in vivo bioassay to screen for class I phosphatidylinositol 3-kinase specific inhibitors
J. Biomol. Screen.
17
1018-1029
2012
Homo sapiens (P42336)
Manually annotated by BRENDA team
Arancibia, S.; Benitez, D.; Nunez, L.; Jewell, C.; Langjahr, P.; Candia, E.; Zapata-Torres, G.; Cidlowski, J.; Gonzalez, M.; Hermoso, M.
Phosphatidylinositol 3-kinase interacts with the glucocorticoid receptor upon TLR2 activation
J. Cell. Mol. Med.
15
339-349
2011
Homo sapiens
Manually annotated by BRENDA team
Chen, Z.; Venkatesan, A.M.; Dehnhardt, C.M.; Ayral-Kaloustian, S.; Brooijmans, N.; Mallon, R.; Feldberg, L.; Hollander, I.; Lucas, J.; Yu, K.; Kong, F.; Mansour, T.S.
Synthesis and SAR of novel 4-morpholinopyrrolopyrimidine derivatives as potent phosphatidylinositol 3-kinase inhibitors
J. Med. Chem.
53
3169-3182
2010
Homo sapiens (P42336), Homo sapiens
Manually annotated by BRENDA team
Rewcastle, G.W.; Gamage, S.A.; Flanagan, J.U.; Frederick, R.; Denny, W.A.; Baguley, B.C.; Kestell, P.; Singh, R.; Kendall, J.D.; Marshall, E.S.; Lill, C.L.; Lee, W.J.; Kolekar, S.; Buchanan, C.M.; Jamieson, S.M.; Shepherd, P.R.
Synthesis and biological evaluation of novel analogues of the pan class I phosphatidylinositol 3-kinase (PI3K) inhibitor 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474)
J. Med. Chem.
54
7105-7126
2011
Homo sapiens (P48736), Homo sapiens
Manually annotated by BRENDA team
Smith, A.L.; DAngelo, N.D.; Bo, Y.Y.; Booker, S.K.; Cee, V.J.; Herberich, B.; Hong, F.T.; Jackson, C.L.; Lanman, B.A.; Liu, L.; Nishimura, N.; Pettus, L.H.; Reed, A.B.; Tadesse, S. et al.
Structure-based design of a novel series of potent, selective inhibitors of the class I phosphatidylinositol 3-kinases
J. Med. Chem.
55
5188-5219
2012
Homo sapiens (P42336), Homo sapiens (P48736)
Manually annotated by BRENDA team
Moir, L.M.; Trian, T.; Ge, Q.; Shepherd, P.R.; Burgess, J.K.; Oliver, B.G.; Black, J.L.
Phosphatidylinositol 3-kinase isoform-specific effects in airway mesenchymal cell function
J. Pharmacol. Exp. Ther.
337
557-566
2011
Homo sapiens
Manually annotated by BRENDA team
Kong, D.; Zhang, Y.; Yamori, T.; Duan, H.; Jin, M.
Inhibitory activity of flavonoids against class I phosphatidylinositol 3-kinase isoforms
Molecules
16
5159-5167
2011
Homo sapiens
Manually annotated by BRENDA team
Vantler, M.; Jesus, J.; Leppaenen, O.; Scherner, M.; Berghausen, E.M.; Mustafov, L.; Chen, X.; Kramer, T.; Zierden, M.; Gerhardt, M.; Ten Freyhaus, H.; Blaschke, F.; Sterner-Kock, A.; Baldus, S.; Zhao, J.J.; Rosenkranz, S.
Class IA phosphatidylinositol 3-kinase isoform p110alpha mediates vascular remodeling
Arterioscler. Thromb. Vasc. Biol.
35
1434-1444
2015
Rattus norvegicus, Rattus norvegicus (A0A0G2K344), Rattus norvegicus (Q9Z1L0), Homo sapiens (O00329), Homo sapiens (P42336), Homo sapiens (P42338), Homo sapiens, Mus musculus (O35904), Mus musculus (P42337), Mus musculus
Manually annotated by BRENDA team
Dickson, J.; Lee, W.; Shepherd, P.; Buchanan, C.
Enzyme activity effects of N-terminal His-tag attached to catalytic sub-unit of phosphoinositide-3-kinase
Biosci. Rep.
33
857-863
2013
Homo sapiens (P27986 AND P42336), Homo sapiens (P42338 AND O00329)
-
Manually annotated by BRENDA team
Fernandez-Acero, T.; Rodriguez-Escudero, I.; Molina, M.; Cid, V.J.
The yeast cell wall integrity pathway signals from recycling endosomes upon elimination of phosphatidylinositol (4,5)-bisphosphate by mammalian phosphatidylinositol 3-kinase
Cell. Signal.
27
2272-2284
2015
Homo sapiens (P42336 AND P27986)
Manually annotated by BRENDA team
Watson, L.J.; Alexander, K.M.; Mohan, M.L.; Bowman, A.L.; Mangmool, S.; Xiao, K.; Naga Prasad, S.V.; Rockman, H.A.
Phosphorylation of Src by phosphoinositide 3-kinase regulates beta-adrenergic receptor-mediated EGFR transactivation
Cell. Signal.
28
1580-1592
2016
Homo sapiens (P48736)
Manually annotated by BRENDA team
Echeverria, I.; Liu, Y.; Gabelli, S.; Amzel, L.
Oncogenic mutations weaken the interactions that stabilize the p110?-p85? heterodimer in phosphatidylinositol 3-kinase ?.
FEBS J.
282
3528-3542
2015
Homo sapiens (P42336)
Manually annotated by BRENDA team
Thapa, N.; Choi, S.; Tan, X.; Wise, T.; Anderson, R.A.
Phosphatidylinositol phosphate 5-kinase Igamma and phosphoinositide 3-kinase/Akt signaling couple to promote oncogenic growth
J. Biol. Chem.
290
18843-18854
2015
Homo sapiens (P42336), Homo sapiens (P42338)
Manually annotated by BRENDA team
Somoza, J.R.; Koditek, D.; Villasenor, A.G.; Novikov, N.; Wong, M.H.; Liclican, A.; Xing, W.; Lagpacan, L.; Wang, R.; Schultz, B.E.; Papalia, G.A.; Samuel, D.; Lad, L.; McGrath, M.E.
Structural, biochemical, and biophysical characterization of idelalisib binding to phosphoinositide 3-kinase delta
J. Biol. Chem.
290
8439-8446
2015
Homo sapiens (O00329), Homo sapiens
Manually annotated by BRENDA team
Thomas, D.; Powell, J.A.; Green, B.D.; Barry, E.F.; Ma, Y.; Woodcock, J.; Fitter, S.; Zannettino, A.C.; Pitson, S.M.; Hughes, T.P.; Lopez, A.F.; Shepherd, P.R.; Wei, A.H.; Ekert, P.G.; Guthridge, M.A.
Protein kinase activity of phosphoinositide 3-kinase regulates cytokine-dependent cell survival
PLoS Biol.
11
e1001515
2013
Homo sapiens (P42336), Homo sapiens
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
Pridham, K.J.; Varghese, R.T.; Sheng, Z.
The role of class IA phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunits in glioblastoma
Front. Oncol.
7
312
2017
Homo sapiens (P42336 AND P42338 AND P48736 AND O00329)
Manually annotated by BRENDA team
Bhattacharya, S.; McElhanon, K.E.; Gushchina, L.V.; Weisleder, N.
Role of phosphatidylinositol-4,5-bisphosphate 3-kinase signaling in vesicular trafficking
Life Sci.
167
39-45
2016
Homo sapiens (P42336 AND P42338 AND P48736 AND O00329)
Manually annotated by BRENDA team
Denorme, P.; Morren, M.A.; Hollants, S.; Spaepen, M.; Suaer, K.; Zutterman, N.; Labarque, V.; Legius, E.; Brems, H.
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-related overgrowth spectrum A brief report
Pediatr. Dermatol.
35
e186-e188
2018
Homo sapiens (P42336)
Manually annotated by BRENDA team