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

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The expected taxonomic range for this enzyme is: Bilateria

EC NUMBER
COMMENTARY
2.7.1.154
-
RECOMMENDED NAME
GeneOntology No.
phosphatidylinositol-4-phosphate 3-kinase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phospho-group transfer
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
3-phosphoinositide biosynthesis
-
Inositol phosphate metabolism
-
Metabolic pathways
-
SYSTEMATIC NAME
IUBMB Comments
ATP:1-phosphatidyl-1D-myo-inositol-4-phosphate 3-phosphotransferase
This enzyme also phosphorylates PtdIns to PtdIns3P. Three mammalian isoforms have been found to date.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
C2-domain-containing phosphoinositide 3-kinase
-
-
-
-
C2-PI3K
-
-
-
-
class I phosphoinositide 3-kinase
-
-
class II phosphoinositide 3-kinase
-
-
class II phosphoinositide 3-kinase
O00443
-
class II phosphoinositide 3-kinase C2alpha
-
-
-
-
class II phosphoinositide 3-kinase C2beta
-
-
-
-
class II PI3K
O00443
-
class III phosphoinositide 3-kinase
-
-
class-I PI 3-kinase
O00443
-
class-I PI 3-kinase
Homo sapiens PI3K-C2alpha
O00443
-
-
class-I PI 3-kinase
Q61194
-
class-II PI 3-kinase
O00443
-
class-II PI 3-kinase
Homo sapiens PI3K-C2alpha
O00443
-
-
class-II PI 3-kinase
Q61194
-
HsC3-PI3K
-
-
-
-
kinase (phosphorylating), phosphatidylinositol 4-phosphate 3-
-
-
-
-
p170
-
-
-
-
phosphoinositide 3-kinase
-
-
-
-
phosphoinositide 3-kinase
-
-
phosphoinositide 3-kinase
-
-
phosphoinositide 3-kinase
-
-
phosphoinositide 3-kinase
-
-
phosphoinositide 3-kinase C2 beta
-
-
phosphoinositide 3-kinase C2beta
-
-
-
-
phosphoinositide 3-kinase C2beta
-
-
phosphoinositide 3-kinase C2beta
-
-
phosphoinositide 3-kinase-C2-beta
-
-
-
-
phosphoinositide 3-kinase-C2-gamma
-
-
-
-
PI 3-kinase
-
-
PI 3-kinase C2alpha
-
-
-
-
PI 3-kinase C2beta
-
-
-
-
PI 3-kinase C2gamma
-
-
-
-
PI3K
-
-
PI3K
-
-
PI3K-C2alpha
-
-
-
-
PI3K-C2alpha
O00443
-
PI3K-C2alpha
Homo sapiens PI3K-C2alpha
O00443
-
-
PI3K-C2alpha
Q61194
-
PI3K-C2beta
-
-
-
-
PI3K-C2beta
-
-
PI3K-C2gamma
-
-
-
-
PI3KC2alpha
O00443
-
PI3KC2beta
-
-
PI3KC2beta
O00750
-
PI3KC2gamma
O75747
-
PI3K_C2alpha
-
-
PI3K_C2gamma
-
-
PtdIns-3-kinase C2alpha
-
-
-
-
PtdIns-3-kinase C2beta
-
-
-
-
PtdIns-3-kinase C2gamma
-
-
-
-
type II phosphoinositide 3-kinase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
141176-94-5
-
67053-99-0
cf. EC 2.7.1.137
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
PI3K-C2alpha
-
-
Manually annotated by BRENDA team
Cricetulus griseus PI3K-C2alpha
PI3K-C2alpha
-
-
Manually annotated by BRENDA team
diverse strains
-
-
Manually annotated by BRENDA team
8 isozymes, class IA and class II, e.g. class IA p85/p110alpha or class II PI3K C2beta
-
-
Manually annotated by BRENDA team
class II PI3K, alpha-isoform
SwissProt
Manually annotated by BRENDA team
isozymes of class IA and IB, i.e. p85, and of class II, e.g. isozymes PI3K-C2alpha, PI3K-C2beta, and PI3K-C2gamma
-
-
Manually annotated by BRENDA team
PI3K-C2alpha
SwissProt
Manually annotated by BRENDA team
PI3K-C2alpha; PI3K-C2beta
-
-
Manually annotated by BRENDA team
PI3K-C2beta
SwissProt
Manually annotated by BRENDA team
PI3K-C2beta
-
-
Manually annotated by BRENDA team
PI3K-C2gamma
SwissProt
Manually annotated by BRENDA team
Homo sapiens PI3K-C2alpha
PI3K-C2alpha
-
-
Manually annotated by BRENDA team
Homo sapiens PI3K-C2alpha
PI3K-C2alpha
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
class II isoform PI3K-C2beta; PI3KC2alpha
-
-
Manually annotated by BRENDA team
isozyme PI3K-C2alpha
SwissProt
Manually annotated by BRENDA team
PI3-C2gamma
SwissProt
Manually annotated by BRENDA team
class II enzyme
-
-
Manually annotated by BRENDA team
PI3-C2gamma
SwissProt
Manually annotated by BRENDA team
PI3KC2alpha
-
-
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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
-
preferred substrate of enzyme form PI3K-C2beta
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
show the reaction diagram
-
preferred substrate of enzyme form PI3K-C2beta
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
show the reaction diagram
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
show the reaction diagram
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
show the reaction diagram
O00443, O00750, O75747
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol-4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol-4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
show the reaction diagram
O70173
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol-4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
show the reaction diagram
Q7JNX6
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol-4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
show the reaction diagram
-, O00750
at 10% of the activity with phosphatidylinositol, phosphorylation only in presence of Mg2+, not in presence of Ca2+
-
?
ATP + 1-phosphatidyl-1D-myo-inositol-4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
show the reaction diagram
Homo sapiens PI3K-C2alpha
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol-4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-diphosphate
show the reaction diagram
-
strong preference for phosphatidylinositol over 1-phosphatidyl-1D-myo-inositol-4-phosphate
-
-
?
ATP + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-, O00750
-
-
?
ATP + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
O00443, O00750, O75747
-
-
-
?
ATP + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
O70173
-
-
-
?
ATP + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
Q7JNX6
-
-
?
ATP + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
Homo sapiens PI3K-C2alpha
-
-
-
?
ATP + phosphatidylinositol
?
show the reaction diagram
-
strong preference for phosphatidylinositol over 1-phosphatidyl-1D-myo-inositol-4-phosphate
-
-
?
ATP + phosphoinositides
ADP + ?
show the reaction diagram
Q61194
enzyme plays a role in cellular signalling pathways, e.g. the insulin signalling pathways acting via class Ia and PI3K-C2alpha isozymes synthesizing 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate and affecting the glucose metabolism, the enzyme antagonizes with phosphatases both regulating the signalling pathways together, the enzyme is also involved in insulin resistance in peripheral tissues, overview
-
-
?
ATP + phosphoinositides
ADP + ?
show the reaction diagram
O00443
enzyme plays a role in cellular signalling pathways, e.g. the insulin signalling pathways acting via class Ia and PI3K-C2alpha isozymes synthesizing 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate and affecting the glucose metabolism, the enzyme antagonizes with phosphatases both regulating the signalling pathways together, the enzyme is also involved in insulin resistance in peripheral tissues, overview
-
-
?
ATP + phosphoinositides
ADP + ?
show the reaction diagram
Q61194
phosphorylation of the D-3 position on the inositol ring
-
-
?
ATP + phosphoinositides
ADP + ?
show the reaction diagram
O00443
phosphorylation of the D-3 position on the inositol ring
-
-
?
ATP + phosphoinositides
ADP + ?
show the reaction diagram
Homo sapiens PI3K-C2alpha
O00443
enzyme plays a role in cellular signalling pathways, e.g. the insulin signalling pathways acting via class Ia and PI3K-C2alpha isozymes synthesizing 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate and affecting the glucose metabolism, the enzyme antagonizes with phosphatases both regulating the signalling pathways together, the enzyme is also involved in insulin resistance in peripheral tissues, overview, phosphorylation of the D-3 position on the inositol ring
-
-
?
additional information
?
-
O70173
no activity with phosphatidylinositol 4,5-diphosphate
-
-
-
additional information
?
-
Q7JNX6
no activity with phosphatidylinositol 4,5-diphosphate
-
-
-
additional information
?
-
-
TNFalpha and leptin stimulate the alpha-isoform of class II phosphoinositide 3-kinase
-
-
-
additional information
?
-
-
the class II phosphoinositide 3-kinase C2.alpha. is activated by clathrin and regulates clathrin-mediated membrane trafficking
-
-
-
additional information
?
-
-
PI3K-C2alpha and PI3K-C2beta represent two downstream targets of the activated epidermal growth factor
-
-
-
additional information
?
-
Q61194
enzyme regulation, overview
-
-
-
additional information
?
-
O00443
enzyme regulation, overview
-
-
-
additional information
?
-
O00443
isozyme PI3K-C2alpha is a crucial survival factor for the cell
-
-
-
additional information
?
-
-
the enzyme is regulated by intracellular signalling mechanisms
-
-
-
additional information
?
-
-
the isozymes activate different signalling cascades via stem cell factor SCF in overexpressing cancer cell lines, e.g. association with c-Met, IGF-IR, regulation, class II PI3K C2beta blocks both protein kinase and small lung cell carcinoma in reponse to stem cell factor, polypeptide growth factors induce the recruitment of class IA and II isozymes to phosphotyrosine-containing signalling complexes, detailed overview
-
-
-
additional information
?
-
-
the isozymes interact with and effect patterning of receptor signaling pathways, overview
-
-
-
additional information
?
-
O00443, O00750, O75747
PI3KC2alpha functions in vascular smooth muscle contraction, priming of neurosecretory granule exocytosis, insulin signalling and clathrin-mediated membrane trafficking.
-
-
-
additional information
?
-
O00443, O00750, O75747
PI3KC2beta functions in cell migration, and PTK receptor signalling
-
-
-
additional information
?
-
-
PI3KC2beta regulates the migration and survival of human tumor cells by distinct molecular mechanisms. Phosphoinositide 3-kinase C2beta regulates cytoskeletal organization and cell migration via Rac-dependent mechanisms
-
-
-
additional information
?
-
Homo sapiens PI3K-C2alpha
-
PI3K-C2alpha and PI3K-C2beta represent two downstream targets of the activated epidermal growth factor
-
-
-
additional information
?
-
Homo sapiens PI3K-C2alpha
-
the class II phosphoinositide 3-kinase C2.alpha. is activated by clathrin and regulates clathrin-mediated membrane trafficking
-
-
-
additional information
?
-
Homo sapiens PI3K-C2alpha
O00443
enzyme regulation, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
show the reaction diagram
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
show the reaction diagram
-
-
-
-
?
ATP + phosphoinositides
ADP + ?
show the reaction diagram
Q61194
enzyme plays a role in cellular signalling pathways, e.g. the insulin signalling pathways acting via class Ia and PI3K-C2alpha isozymes synthesizing 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate and affecting the glucose metabolism, the enzyme antagonizes with phosphatases both regulating the signalling pathways together, the enzyme is also involved in insulin resistance in peripheral tissues, overview
-
-
?
ATP + phosphoinositides
ADP + ?
show the reaction diagram
Homo sapiens, Homo sapiens PI3K-C2alpha
O00443
enzyme plays a role in cellular signalling pathways, e.g. the insulin signalling pathways acting via class Ia and PI3K-C2alpha isozymes synthesizing 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate and affecting the glucose metabolism, the enzyme antagonizes with phosphatases both regulating the signalling pathways together, the enzyme is also involved in insulin resistance in peripheral tissues, overview
-
-
?
additional information
?
-
-
TNFalpha and leptin stimulate the alpha-isoform of class II phosphoinositide 3-kinase
-
-
-
additional information
?
-
-
the class II phosphoinositide 3-kinase C2.alpha. is activated by clathrin and regulates clathrin-mediated membrane trafficking
-
-
-
additional information
?
-
-
PI3K-C2alpha and PI3K-C2beta represent two downstream targets of the activated epidermal growth factor
-
-
-
additional information
?
-
Q61194
enzyme regulation, overview
-
-
-
additional information
?
-
O00443
enzyme regulation, overview
-
-
-
additional information
?
-
O00443
isozyme PI3K-C2alpha is a crucial survival factor for the cell
-
-
-
additional information
?
-
-
the enzyme is regulated by intracellular signalling mechanisms
-
-
-
additional information
?
-
-
the isozymes activate different signalling cascades via stem cell factor SCF in overexpressing cancer cell lines, e.g. association with c-Met, IGF-IR, regulation, class II PI3K C2beta blocks both protein kinase and small lung cell carcinoma in reponse to stem cell factor, polypeptide growth factors induce the recruitment of class IA and II isozymes to phosphotyrosine-containing signalling complexes, detailed overview
-
-
-
additional information
?
-
-
the isozymes interact with and effect patterning of receptor signaling pathways, overview
-
-
-
additional information
?
-
O00443, O00750, O75747
PI3KC2alpha functions in vascular smooth muscle contraction, priming of neurosecretory granule exocytosis, insulin signalling and clathrin-mediated membrane trafficking.
-
-
-
additional information
?
-
O00443, O00750, O75747
PI3KC2beta functions in cell migration, and PTK receptor signalling
-
-
-
additional information
?
-
-
PI3KC2beta regulates the migration and survival of human tumor cells by distinct molecular mechanisms. Phosphoinositide 3-kinase C2beta regulates cytoskeletal organization and cell migration via Rac-dependent mechanisms
-
-
-
additional information
?
-
Homo sapiens PI3K-C2alpha
-
PI3K-C2alpha and PI3K-C2beta represent two downstream targets of the activated epidermal growth factor
-
-
-
additional information
?
-
Homo sapiens PI3K-C2alpha
-
the class II phosphoinositide 3-kinase C2.alpha. is activated by clathrin and regulates clathrin-mediated membrane trafficking
-
-
-
additional information
?
-
Homo sapiens PI3K-C2alpha
O00443
enzyme regulation, overview
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-
phosphorylation of phosphatidylinositol but not phosphatidylinositol 4-phosphate in presence of Ca2+
Mg2+
-
phosphorylation of phosphatidylinositol and phosphatidylinositol 4-phosphate in presence of Mg2+
Mg2+
Q7JNX6
the enzyme strictly requires the presence of Mg2+, inactive in presence of Mn2+
Mg2+
O00443
-
Mg2+
Q61194
-
additional information
Q7JNX6
inactive in presence of Mn2+
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
-
i.e. BAPTA-AM, a cell-penetrating Ca2+-chelator
adipokines
O00443
block insulin signalling via PI3K isozymes
-
adipokines
Q61194
block insulin signalling via PI3K isozymes
-
Caffeine
O00443
might inhibit the enzyme
Caffeine
Q61194
might inhibit the enzyme
Calpeptin
-
inhibits proteolytic activation of enzyme form PI3K C2beta in brush border plasma membranes
cytokines
O00443
block insulin signalling via PI3K isozymes
-
cytokines
Q61194
block insulin signalling via PI3K isozymes
-
LY294002
-
IC50: 0.019 mM, maximal inhibition at 1 mM
Naringenin
O00443
might inhibit the enzyme
Naringenin
Q61194
might inhibit the enzyme
Nonidet P-40
O70173
0.5%, almost complete inhibition
Triton X-100
O70173
0.5%, almost complete inhibition
Wortmannin
-
IC50: 1.6 nM
Wortmannin
-
IC50: 420 nM, maximal inhibition at 10 mM
Wortmannin
Q7JNX6
IC50: 11 nM
Wortmannin
-, O70167
-
Wortmannin
O70173
IC50: 12 nM
Wortmannin
O00443
class I isozyme inhibitor, isozyme PI3K-C2alpha is resistant to inhibition
Wortmannin
Q61194
class I isozyme inhibitor, isozyme PI3K-C2alpha is resistant to inhibition
Wortmannin
-
phosphoinositide 3-kinase C2beta
Wortmannin
-
-
Mn2+
O70173
3.5 mM, instead of Mg2+, almost complete inhibition
additional information
-
introduction of phosphatidylserine, produces an 8fold decrease in Vmax for ATP using phosphatidylinositol. Without phosphatidylserine, phosphatidylinositol 4-phosphate produces non-linear enzyme kinetics
-
additional information
O00443
enzyme is regulated by several feedback inhibition possibilities in the insulin signalling pathway, overview
-
additional information
Q61194
enzyme is regulated by several feedback inhibition possibilities in the insulin signalling pathway, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
A23187
-
Ca2+-ionophore, activates enzyme form PI3K-C2beta, mimicks hepatocyte growth factor HGF
growth factors
O00443
addition of serum to growth-factor-deficient medium increases PI3K-C2alpha expression
-
hepatocyte growth factor HGF
-
in renal brush-border and basal lateral plasma membranes, in the latter case mediated by calpain
-
Insulin
-
-
-
Insulin
O00443
-
-
leptin
-
4fold activation of class II isoform PI3K-C2beta by activation of the ERK pathway, no recruitment of tyrosine phosphorylated proteins to the isozyme, blockade of activation by MEK-inhibitor PD98059
-
TNF-alpha
-
2.8fold activation of class II isoform PI3K-C2beta by activation of the ERK pathway, blockade of activation by MEK-inhibitor PD98059
-
monocyte chemotactic peptide-1
-
agonist-induced activation
-
additional information
-
TNFalpha and leptin stimulate the alpha-isoform of class II phosphoinositide 3-kinase
-
additional information
-
interaction with Grb2 dramatically increases catalytic activity. Proline-rich motifs within the N-terminus of PI3K-C2beta mediate the association of this enzyme with activated EGF receptor and this interaction involves the Grb2 adaptor
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.015
-
ATP
-
pH 7.5, 30C, reaction with phosphatidylinositol, without phosphatidylserine
0.032
-
ATP
-
pH 7.5, 30C, reaction with phosphatidylinositol, in presence of phosphatidylserine
0.054
-
ATP
-
pH 7.5, 30C, reaction with phosphatidylinositol 4-phosphate, without phosphatidylserine
0.12
-
CaATP2-
-
pH 7.4
-
0.12
-
MgATP2-
-
pH 7.4
0.064
-
phosphatidylinositol
-
pH 7.5, 30C, in presence of phosphatidylserine
0.122
-
phosphatidylinositol
-
pH 7.5, 30C, without phosphatidylserine
0.025
-
phosphatidylinositol 4-phosphate
-
pH 7.5, 30C, in presence of phosphatidylserine
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.019
-
LY294002
-
IC50: 0.019 mM, maximal inhibition at 1 mM
1.6e-06
-
Wortmannin
-
IC50: 1.6 nM
1.1e-05
-
Wortmannin
Q7JNX6
IC50: 11 nM
1.2e-05
-
Wortmannin
O70173
IC50: 12 nM
0.00042
-
Wortmannin
-
IC50: 420 nM, maximal inhibition at 10 mM
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
-
-
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
carcinoma-derived cell
Manually annotated by BRENDA team
Homo sapiens PI3K-C2alpha
-
carcinoma-derived cell
-
Manually annotated by BRENDA team
-
moderate expression of PI3K-C2alpha andPI3K-C2beta
Manually annotated by BRENDA team
-
moderate expression of PI3K-C2alpha
Manually annotated by BRENDA team
-
low amount of isozyme PI3K-C2alpha in myoepithelial cells and lactiferous ducts, no isozyme PI3K-C2beta and isozyme p85
Manually annotated by BRENDA team
O00443, O00750, O75747
PI3KC2gamma
Manually annotated by BRENDA team
-
low amount of isozyme p85, isozyme PI3K-C2beta and isozyme PI3K-C2alpha in bronchial epithelium
Manually annotated by BRENDA team
-
isozyme p85, isozyme PI3K-C2beta and isozyme PI3K-C2alpha in colonocytes
Manually annotated by BRENDA team
-
moderate expression of PI3K-C2alpha and PI3K-C2beta
Manually annotated by BRENDA team
-
of Fallopian tube, moderate expression of PI3K-C2alpha and weak expression of PI3K-C2beta
Manually annotated by BRENDA team
-
moderate expression of PI3K-C2alpha and weak expression of PI3K-C2beta
Manually annotated by BRENDA team
-
glomerular, PI3K-C2alpha
Manually annotated by BRENDA team
-
isozyme PI3K-C2alpha, high amount of isozyme p85, and low amount of isozyme PI3K-C2beta
Manually annotated by BRENDA team
-
isozyme PI3K-C2alpha in smooth muscle layer, mononuclear cells, and lining epithelium, isozyme p85 and isozyme PI3K-C2beta in lining epithelium and mononuclear cells
Manually annotated by BRENDA team
-
strong expression of PI3K-C2beta
Manually annotated by BRENDA team
-
high amounts of isozyme p85 and isozyme PI3K-C2beta
Manually annotated by BRENDA team
-
strong expression of PI3K-C2alpha
Manually annotated by BRENDA team
Homo sapiens PI3K-C2alpha
-
-
-
Manually annotated by BRENDA team
-
mRNA is undetectable in kidney
Manually annotated by BRENDA team
-
expression at low level
Manually annotated by BRENDA team
-
isozyme p85 in glomerular macrophages, macula densa, and collecting tubules, high amount of isozyme PI3K-C2alpha in glomerular tuft, low amount of isozyme PI3K-C2beta and isozyme PI3K-C2alpha in proximal, distal, and collecting tubules
Manually annotated by BRENDA team
Homo sapiens PI3K-C2alpha
-
mRNA is undetectable in kidney
-
Manually annotated by BRENDA team
-
strong expression of PI3K-C2alpha and moderate expression of PI3K-C2beta
Manually annotated by BRENDA team
-, O70167
exclusively expressed in liver
Manually annotated by BRENDA team
O70173
PI3K-IIgamma mRNA expression is confined to the liver throughout the development with much higher expression in adult liver than in fetal liver. Expression increases during liver regeneration after partial hepatectomy. PI3K-gamma may function mainly in highly differentiated hepatic cells
Manually annotated by BRENDA team
-
isozyme PI3K-C2alpha in bile ducts, no isozyme PI3K-C2beta and isozyme p85
Manually annotated by BRENDA team
-
in the nuclear matrix harvested 20 h after partial hepatectomy, an increase in immunoprecipitable PI3K-C2beta activity is observed
Manually annotated by BRENDA team
O00443, O00750, O75747
PI3KC2gamma
Manually annotated by BRENDA team
-
isozyme p85, isozyme PI3K-C2beta and isozyme PI3K-C2alpha in alveolar macrophages
Manually annotated by BRENDA team
-
weak expression of PI3K-C2alpha and PI3K-C2beta in germinal centre mononuclear cells, moderate expression of PI3K-C2alpha and PI3K-C2beta in tissue macrophages, strong expression of PI3K-C2alpha in polymorphonuclear leucocytes, weak expression of PI3K-C2alpha and moderate expression of PI3K-C2beta in medulla mononuclear cells, no expression in lymphoid follicles
Manually annotated by BRENDA team
-
isozyme p85 in medulla, germinal centre mononuclear cells, low amount in polymorphnuclear leucocytes, and high amount in tissue macrophages, isozyme PI3K-C2alpha and isozyme PI3K-C2beta in medulla, tissue macrophages, and germinal centre mononuclear cells, high amount of isozyme PI3K-C2alpha in polymorphnuclear leucocytes
Manually annotated by BRENDA team
-
cell culture; cell culture, cell line J774.2
Manually annotated by BRENDA team
-
dermal, moderate expression of PI3K-C2alpha and PI3K-C2beta; glomerular, moderate expression of PI3K-C2beta; PI3K-C2alpha and PI3K-C2beta
Manually annotated by BRENDA team
-
isozyme PI3K-C2beta
Manually annotated by BRENDA team
-
moderate expression of PI3K-C2alpha and strong expression of PI3K-C2beta
Manually annotated by BRENDA team
-
moderate expression of PI3K-C2alpha
Manually annotated by BRENDA team
-
non-myelinated, moderate expression of PI3K-C2beta
Manually annotated by BRENDA team
-
isozyme p85, low amount of isozyme PI3K-C2beta and isozyme PI3K-C2alpha in follicular cells
Manually annotated by BRENDA team
Homo sapiens PI3K-C2alpha
-
-
-
Manually annotated by BRENDA team
-
moderate expression of PI3K-C2alpha and PI3K-C2beta
Manually annotated by BRENDA team
-
high amount of isozyme p85 in acini, isozyme PI3K-C2alpha in acini and ducts, no isozyme PI3K-C2beta
Manually annotated by BRENDA team
-
moderate expression of PI3K-C2alpha and PI3K-C2beta
Manually annotated by BRENDA team
-
expression at low level
Manually annotated by BRENDA team
-
highest expression in thymus and placenta
Manually annotated by BRENDA team
Homo sapiens PI3K-C2alpha
-
-
-
Manually annotated by BRENDA team
-
fibromuscular stroma, moderate expression of PI3K-C2alpha
Manually annotated by BRENDA team
O00443, O00750, O75747
PI3KC2gamma
Manually annotated by BRENDA team
-
isozyme PI3K-C2alpha inbasal epithelium and fibromuscular stroma, no isozyme PI3K-C2beta and isozyme p85
Manually annotated by BRENDA team
-
expression at low level
Manually annotated by BRENDA team
-
isozyme p85 in Langerhans cells, dermal macrophages, and in low amounts in sebaceous glands, hair follicles, and sweat gland, isozyme PI3K-C2beta and isozyme PI3K-C2alpha in dermal macrophages, low amount of isozyme PI3K-C2alpha in sweat gland
Manually annotated by BRENDA team
-
different cell lines overexpress different isozymes, e.g. cell lines H-69, HC-33, H-510, H-1045, and H-209
Manually annotated by BRENDA team
-
moderate expression of PI3K-C2alpha and weak expression of PI3K-C2beta
Manually annotated by BRENDA team
-
isozyme PI3K-C2alpha, high amount of isozyme p85, and low amount of isozyme PI3K-C2beta in enterocytes, isozyme p85 in Paneth cells
Manually annotated by BRENDA team
-
bronchial and cervical, moderate expression of PI3K-C2alpha
Manually annotated by BRENDA team
-
isozyme PI3K-C2alpha
Manually annotated by BRENDA team
-
strong expression of PI3K-C2beta
Manually annotated by BRENDA team
-
strong expression of PI3K-C2alpha in red pulp splenic sinusoids, weak expression of PI3K-C2alpha and moderate expression of PI3K-C2beta in red pulp mononuclear cells, no expression in white pulp
Manually annotated by BRENDA team
-
isozyme p85, isozyme PI3K-C2beta and isozyme PI3K-C2alpha in red pulp
Manually annotated by BRENDA team
-
isozyme PI3K-C2beta and isozyme PI3K-C2alpha, and high amount of isozyme p85 in peptic cells
Manually annotated by BRENDA team
-
high content of isozyme p85 and isozyme PI3K-C2beta in spermatogenic cells, high content of isozyme PI3K-C2alpha in Leydig cells, isozyme p85 and PI3K-C2beta in Leydig cells
Manually annotated by BRENDA team
Homo sapiens PI3K-C2alpha
-
-
-
Manually annotated by BRENDA team
Homo sapiens PI3K-C2alpha
-
monocyte
-
Manually annotated by BRENDA team
-
highest expression in thymus and placenta
Manually annotated by BRENDA team
O00443, O00750, O75747
high activity of PI3KC2beta
Manually annotated by BRENDA team
Homo sapiens PI3K-C2alpha
-
monocyte
-
Manually annotated by BRENDA team
-
moderate expression of PI3K-C2alpha and weak expression of PI3K-C2beta
Manually annotated by BRENDA team
-
isozyme PI3K-C2alpha in muscularis and transitional epithelium, isozyme p85 and isozyme PI3K-C2beta in transitional epithelium
Manually annotated by BRENDA team
-
isozyme PI3K-C2alpha in cervical smooth muscle, no isozyme PI3K-C2beta and isozyme p85
Manually annotated by BRENDA team
-
isozyme p85 in proliferative endometrium and in low amounts in secretory endometrium, isozyme PI3K-C2alpha in myometrium, no isozyme PI3K-C2beta
Manually annotated by BRENDA team
additional information
-
immunohistological analysis, no expression of isozymes in endocrine pancreas, thyroid, or parathyroid, topographical expression of class IA and class II isozymes in normal human tissues is consistent with a role in differentiation
Manually annotated by BRENDA team
additional information
-
isozyme expression pattern and phenotype, Drk adaptor protein might be involved in localization of the isozymes, overview
Manually annotated by BRENDA team
additional information
O00443, O00750, O75747
widely expressed, but not ubiquitous
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
colocalization of the enzyme with plasma membrane-coated pits in COS-cells
Manually annotated by BRENDA team
-
constitutively associated with phospholipid membranes
Manually annotated by BRENDA team
-
renal brush-border and basal lateral, enzyme form phosphoinositide 3-kinase C2beta occurs only in renal brush-border plasma membrane
Manually annotated by BRENDA team
Cricetulus griseus PI3K-C2alpha
-
constitutively associated with phospholipid membranes
-
Manually annotated by BRENDA team
Homo sapiens PI3K-C2alpha
-
colocalization of the enzyme with plasma membrane-coated pits in COS-cells; constitutively associated with phospholipid membranes
-
Manually annotated by BRENDA team
O00443, O00750, O75747
predominantly localised to intracellular membranes; predominantly localised to intracellular membranes; predominantly localised to intracellular membranes
Manually annotated by BRENDA team
additional information
-
the recombinant enzyme is localized mainly in the low density microsomal fraction, with a small amount being present in the plasma membrane and the cytosolic fraction
-
Manually annotated by BRENDA team
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 182000, calculation from nucleotide sequence
?
-
x * 190000, calculation from nucleotide sequence
?
-
x * 170000, calculation from nucleotide sequence
?
O70173
x * 170972, calculation from nucleotide sequence
?
O00443
x * 110000, catalytic subunit, + x * 85000, catalytically inactive adaptor subunit
?
Q61194
x * 110000, catalytic subunit, + x * 85000, catalytically inactive adaptor subunit
?
-
x * 180000, enzyme form PI3K C2beta, SDS-PAGE
?
Homo sapiens PI3K-C2alpha
-
; x * 110000, catalytic subunit, + x * 85000, catalytically inactive adaptor subunit; x * 190000, calculation from nucleotide sequence
-
additional information
O00443
domain structure of the adaptor subunit containing a SH3 domain and 2 SH2 domains, three different isozymes of the catalytically subunits P110alpha, P110beta, and P110gamma determine the 3 isozymes alpha, beta, gamma of the enzyme, all P110 subunits can interact with the p85 adaptor subunit
additional information
Q61194
domain structure of the adaptor subunit containing a SH3 domain and 2 SH2 domains, three different isozymes of the catalytically subunits P110alpha, P110beta, and P110gamma determine the 3 isozymes alpha, beta, gamma of the enzyme, all P110 subunits can interact with the p85 adaptor subunit
additional information
-
class II PI3K enzymes are distinguished from other PI3K isoenzymes by the presence of two tandem domains at their C-termini, the first one is termed a Phox homology domain, which is revealed as a novel phosphoinositide-binding domain, whereas the second is the C2 domain, which is a phospholipid-binding domain that can confer Ca2+ sensitivity
additional information
Homo sapiens PI3K-C2alpha
-
domain structure of the adaptor subunit containing a SH3 domain and 2 SH2 domains, three different isozymes of the catalytically subunits P110alpha, P110beta, and P110gamma determine the 3 isozymes alpha, beta, gamma of the enzyme, all P110 subunits can interact with the p85 adaptor subunit
-
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phosphoprotein
O00443
the phosphorylated enzyme is inactive
phosphoprotein
-
the enzyme is regulated by phosphorylation, involving different kinases and polypeptide growth factors, overview
phosphoprotein
Homo sapiens PI3K-C2alpha
-
the phosphorylated enzyme is inactive
-
phosphoprotein
Q61194
the phosphorylated enzyme is inactive
proteolytic modification
-
activation of enzyme form PI3K C2beta occurs probably via proteolysis in the brush broder plasma membrane
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
partially by subcellular fractionation of renal cortex, plasma membrane preparation
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in COS-7 cells. Specific activity of the enzyme purified from Drosophila lysate is significantly higher than that of Cpk derived from exogenous expression in COS-7 cells
Q7JNX6
expression of class I isozyme Dp110 enhances organ size by increasing the size of cells without perturbing patterning, ectopic expression of wild-type and catalytically inactive mutant of class II isozyme PI3K_68D in different patterns during Drosophila melanogaster disk development, phenotype analysis of adult cuticle
-
expression of class IA and class II isozymes in HEK293 cells alter the regulation of protein kinases in response to growth factors as part of signalling cascades, overview
-
Glu-tagged PI 3-kinase C2beta protein is expressed in both HEK293 cells and Sf9 cells
-
suppression of expression of recombinant alpha-isoform of class II PI3K and endogenous enzyme in transfected CHO-R1 cells by expression of antisense constructs or DNA fragmentation leads to apoptotic cells death, overview
O00443
the region of human PI3K-C2alpha cDNA corresponding to residues 2-144 is cloned into the SmaI-ECoRI sites of pGEX-2T, the fusion protein is expressed in Escherichia coli BL21, transfection to COS cells
-
-
-, O70167
cloned into the baculovirus expression vector pAcG3x and expressed in Sf9 cells
-
expression in COS-7 cells
Q61194
expression in COS-7 cells
O70173
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
the catalytically inactive mutant of class II isozyme PI3K_68D can bind the Drk adaptor protein in vitro