Information on EC 2.7.1.153 - phosphatidylinositol-4,5-bisphosphate 3-kinase and Organism(s) Mus musculus and UniProt Accession P42337

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Mus musculus
UNIPROT: P42337


The taxonomic range for the selected organisms is: Mus musculus

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.7.1.153
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RECOMMENDED NAME
GeneOntology No.
phosphatidylinositol-4,5-bisphosphate 3-kinase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho-group transfer
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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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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
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115926-52-8
cf. EC 2.7.1.137
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
class Ia phosphatidylinositol 3-kinase isoform p110alpha is crucial for receptor tyrosine kinases signaling, thus affecting proliferation, migration, and survival of smooth muscle cells, Receptor tyrosine kinases–induced phosphatidylinositol 3'-kinase signaling via the p110alpha isoform plays a central role for vascular remodeling
malfunction
metabolism
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Rac1 regulates peptidoglycan-induced nuclear factor-kappaB activation and cyclooxygenase-2 expression in RAW 264.7 macrophages by activating the phosphatidylinositol 3-kinase/Akt pathway
physiological function
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 + 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
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phosphatidylinositol-3,4,5-triphosphate is a major product of active PI3K, and recruits Akt/PKB to the plasma membrane and the phosphorylation of Akt occurs
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?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
show the reaction diagram
ATP + Akt
ADP + Akt phosphate
show the reaction diagram
ATP + p70S6K
ADP + p70S6K phosphate
show the reaction diagram
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-
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
show the reaction diagram
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-
-
-
?
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 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
show the reaction diagram
O35904, P42337
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-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-triphosphate
show the reaction diagram
-
-
phosphatidylinositol-3,4,5-triphosphate is a major product of active PI3K, and recruits Akt/PKB to the plasma membrane and the phosphorylation of Akt occurs
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
show the reaction diagram
ATP + Akt
ADP + Akt phosphate
show the reaction diagram
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-
-
-
?
ATP + p70S6K
ADP + p70S6K phosphate
show the reaction diagram
-
-
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
show the reaction diagram
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-
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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
Mg2+
required
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
PIK-75
p110alpha-specific small molecule inhibitor
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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i.e. LY294002, treatment prevents interleukin-13-induced hyper-responsiveness
2-(6-aminopurin-9-ylmethyl)-5-methyl-3-O-tolyl-3H-quinazolin-4-one
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i.e.IC87114, selective for isoform p110delta. Treatment prevents interleukin-13-induced hyper-responsiveness
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
AS604850
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PI3Kgamma inhibitor 2
AS605240
LY294002
PIK-75
p110alpha-specific small molecule inhibitor
PX-866
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a PI3K inhibitor, inhibits also the oncogenic K-ras-induced bronchioalveolar stem cell accumulation and tumor growth in vivo
quercetin
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from red wine extract, quercetin and red wine polyphenol extract inhibit the phosphorylation of Akt in vivo and show inhibitory effects on TNF-alpha-induced upregulation of MMP-9 and on the migratory phenotype of JB6 P+ mouse epidermal, mediated by suppression of the phosphorylation of Akt and the transactivation of activator protein-1 and nuclear factor-kappaB. Red wine extract and quercetin suppress TNF-alpha-induced PI3K activity by binding specifically to PI3K
Wortmannin
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
influenza A virus NS1 protein
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influenza A virus infection activates the PI3K/Akt pathway by binding influenza A virus NS1 protein to Val573 of the inter-SH2 domain of the p85beta, but not the p85alpha, regulatory subunit of PI3K. NS1-p85-p110 forms a complex in the cells. The interaction is mediated by the interaction interface between the NS1 SH3 binding motif 1, amino acids 164-167, p85beta Val573, and amino acids 137-142 of NS1, molecular modeling and mechanism, overview. Mutant virus PR8-NS1-141/142 is not able to activate Akt phosphorylation
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interleukin-13
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treatment of tracheal tissue is associated with an early activation of phosphoinositide 3-kinase
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platelet-derived growth factor
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stimulates synthesis of 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
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thyroid receptor
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i.e. PV, nongenomic activation of phosphatidylinositol 3-kinase signaling by thyroid hormone receptors, overview. PI3Kactivation through thyroid recptor via protein–protein interaction, i.e. binding to regulatory subunit p85alpha. The thyroid receptorbeta mutant physically interacts with the regulatory p85alpha subunit of PI3K to activate the downstream AKT-mammalian target of rapamycin and p70S6K and PI3K-integrin-linked kinase-matrix metalloproteinase-2 signaling pathways. PI3K activation results in increased cell proliferation, motility, migration, and metastasis. Nuclear receptor corepressor, NCoR, is a regulator of thyroid receptor-activated PI3K signaling
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TNF-alpha
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activates PI3K
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additional information
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
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assay at
7.6
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assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20
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assay at
30
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assay at
37
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assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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the cells are located at the terminal bronchi, and have the capacity to selfrenew and undergo multi-linage differentiation
Manually annotated by BRENDA team
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PI3Kgamma
Manually annotated by BRENDA team
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PI3Kgamma, small amounts
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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p110delta is highly expressed. p110delta as an important signaling component for efficient axonal elongation in the developing and regenerating nervous system
Manually annotated by BRENDA team
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tracheal smooth muscle
Manually annotated by BRENDA team
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PI3Kgamma, small amounts
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
UNIPROT
ORGANISM
P42337
Mus musculus;
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SUBUNITS
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 (p110alpha) and a smaller regulatory subunit (p85)
heterodimer
additional information
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant tagged proteins by the specific affinity chromatographies
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in HEK-293T cell
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expression of His-, FLAG-, or GSt-tagged p85beta in HEK-293T or A-549 cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
upregulation of class I PI3K isozymes in cancer cells
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
M582V
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site-directed mutagenesis, the full-length p85alpha isoform inter-SH2 domain mutation enables the mutant PI3K to bind influenza A virus NS1 protein leading to activation of the mutant PI3K enzyme activity, molecular modeling, overview
V573M
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site-directed mutagenesis, the p85beta isoform inter-SH2 domain mutation abrogates mutant PI3K binding to influenza A virus NS1 protein, molecular modeling, overview
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine