Information on EC 2.7.1.137 - phosphatidylinositol 3-kinase and Organism(s) Mus musculus and UniProt Accession P42337

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UNIPROT: P42337
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The taxonomic range for the selected organisms is: Mus musculus

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.7.1.137
-
RECOMMENDED NAME
GeneOntology No.
phosphatidylinositol 3-kinase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
3-phosphoinositide biosynthesis
-
-
Inositol phosphate metabolism
-
-
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
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
?
ATP + 1,2-dibutanoylphosphatidylinositol 4,5-diphosphate
ADP + 1,2-dibutanoylphosphatidylinositol 3,4,5-trisphosphate
show the reaction diagram
-
-
-
-
?
ATP + 1,2-dioctanoylphosphatidylinositol 4,5-diphosphate
ADP + 1,2-dioctanoylphosphatidylinositol 3,4,5-trisphosphate
show the reaction diagram
-
-
-
-
?
ATP + 1-O-octadecyl-2-O-methyl-rac-3-glycerophospho-myo-inositol
ADP + ?
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-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
?
-
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 + 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
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(+/-)-2-[hydroxy[tetrahydro-2-(octadecyloxy)methylfuran-2-yl]methoxyl]phosphinyloxy-N,N,N-trimethylethaniminium hydroxide
-
-
(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]oxazacyclohentriacontin
-
-
-
(1E,4S,4aR,5R,6aS,7S,9aR)-1-({[3-(dimethylamino)propyl](methyl)amino}methylidene)-7,11-dihydroxy-4-(methoxymethyl)-4a,6a,9a-trimethyl-2,10-dioxo-1,2,4,4a,5,6,6a,7,8,9,9a,10-dodecahydroindeno[4,5-h]isochromen-5-yl acetate
-
-
(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-3-{(2R)-1-[(1S,3R)-3-hydroxycyclohexyl]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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-
1-O-octadecyl-2-O-methyl-rac-3-glycerophospho-myo-inositol
-
-
1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine
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noncompetitive with ATP
17-hydroxywortmannin
-
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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i.e. LY294002
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
EDTA
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hexadexylphosphocholine
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-
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LY294002
PI3Kalpha inhibitor IV
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-
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PI3Kbeta inhibitor VI
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i.e. TGX-221
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PI3Kgamma inhibitor
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-
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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
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i.e. acetic acid 4-diallylaminomethylene-6-hydroxy-1-alpha-methoxymethyl-10beta,13beta-dimethyl-3,7,17-trioxo-1,3,4,7,10,11beta,12,13,14alpha,15,16,17-dodecahydro-2-oxacyclopenta[a]phenanthren-11-yl ester
staurosporine
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Wortmannin
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
activated PDGFRbeta
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PI3K binding to the cytoplasmic domain of activated PDGFRbeta receptors requires phosphorylation at residues 739 and 750 and this interaction in turn activates the kinase
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G-protein betagamma subunits
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betagamma subunits of heterotrimeric G-protein
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low density lipoprotein receptor-related protein 1
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LRP1, positively regulates PI3K activation. LRP1-deficient smooth muscle cells show disorganized actin in the form of membrane ruffling and enhanced cell migration, and show abnormal activation of TGFbeta signaling
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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
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.05
1,2-dioctanoylphosphatidylinositol 4,5-diphosphate
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pH 7.4, recombinant enzyme
0.035
ATP
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pH 7.4, recombinant enzyme
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0056
LY294002
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pH 7.4, recombinant enzyme
0.0038
staurosporine
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pH 7.4, recombinant enzyme
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000012
Wortmannin
Mus musculus;
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specific irreversible inhibition, binds covalently to the active site, mixed type inhibition, IC50 is 12 nM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
assay method development and optimization, phosphoinositide quantification via labeled and/or tagged ligands binding to the pleckstrin homology PH domain of the recombinant enzyme in competition with phosphoinositides, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
-
assay at
7.5
-
kinase assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
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kinase assay at
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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microglial cell
Manually annotated by BRENDA team
the regulatory subunit p87PIKAP and the catalytic subunit p101 are both expressed
Manually annotated by BRENDA team
isoform P110d
Manually annotated by BRENDA team
-
,sympathetic superior cervical ganglia and sensory trigeminal ganglia. In cultured sympathetic superior cervical ganglia and dorsal root ganglia neurons, p110a, b, and g immunoreactivity is in the sympathetic superior cervical ganglia and DRG growth cones, and predominantly in puncta throughout the growth cone varicosity
Manually annotated by BRENDA team
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IL-3-dependent FDCP-1/Mac-1 murine hemopoietic progenitors
Manually annotated by BRENDA team
-
a primary cell type in the liver responsible for excess collagen deposition during fibrosis
Manually annotated by BRENDA team
a N-terminal truncated form is found in lung
Manually annotated by BRENDA team
the regulatory subunit p87PIKAP and the catalytic subunit p101 are both expressed
Manually annotated by BRENDA team
-
primary
Manually annotated by BRENDA team
-
insulinoma cell
Manually annotated by BRENDA team
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of obese diabetic mouse
Manually annotated by BRENDA team
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isozyme phosphatidylinositol 3-kinase gamma
Manually annotated by BRENDA team
the regulatory subunit p87PIKAP and the catalytic subunit p101 are both expressed
Manually annotated by BRENDA team
-
the phosphatidylinositol 3-kinase-mediated production of interferon-beta is critical for the lipopolysaccharide inhibition of osteoclastogenesis
Manually annotated by BRENDA team
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T cell line CTLL-2
Manually annotated by BRENDA team
additional information
-
the phosphatidylinositol 3-kinase, PI3K, family is a family of conserved lipid and protein kinases that are ubiquitously expressed in many cells, including the heart
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
p110a is localized predominantly at the plasma membrane, while p110b and g is localized in the perinuclear region of the cells
-
Manually annotated by BRENDA team
colocalization with synaptic marker, synaptophysin at day 21 in vitro
Manually annotated by BRENDA team
additional information
-
actin filaments facilitate the insulin-mediated association of the p85-p110 PI 3-kinase with glucose-transporter-containing compartments
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
85000
1 * 85000 + 1 * 110000; 85000 Da subunit, previously thought to have only a linking role in localizing the p110 catalytic subunit, is an important component of the catalytic complex
110000
1 * 85000 + 1 * 110000
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
1 * 85000 + 1 * 110000
additional information
85000 Da subunit, previously thought to have only a linking role in localizing the p110 catalytic subunit, is an important component of the catalytic complex
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
vapor diffusion hanging drop method. Crystal structure of the C2 domain
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant GRP1 domain, comprising residues 263-380, from Escherichia coli by glutathione affinity chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloning, structural organization, and chromosomal localization of the mouse PI3-kinase p110a gene
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expression of the GRP1 domain, comprising residues 263-380, in Escherichia coli
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expression of wild-type and mutant HA-tagged PI3K isozyme gamma and of subunit p110 in COS-7 cells, stimulation of the protein kinases Erk, JNK, and PKB
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PI 3-kinase p170
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PI3K-C2 gamma gene locus is mapped to the distal region of mouse chromosome 6 in a region of homology with human chromosome 12p
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
-
reduction of PI3K/PKCdelta activity represents a therapeutic target to downregulate adhesion molecule L1, CHL1, expression and thus benefit axonal regeneration after spinal cord injury
medicine
-
preclinical evidence for the in vivo efficacy for the phosphatidylinositol 3-kinase inhibitor LY294002 in the treatment of follicular thyroid cancer