Any feedback?
Information on EC 2.7.1.154 - phosphatidylinositol-4-phosphate 3-kinase and Organism(s) Rattus norvegicus and UniProt Accession O70173
for references in articles please use BRENDA:EC2.7.1.154Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
2.7.1.154 phosphatidylinositol-4-phosphate 3-kinaseIUBMB Comments
This enzyme also phosphorylates PtdIns to PtdIns3P. Three mammalian isoforms have been found to date.
Specify your search results
Word Map
- 2.7.1.154
- wortmannin
-
chemotaxis
- pi3kgamma
- p110alpha
-
ptdins3,4,5p3
- pten
-
3,4,5-trisphosphate
- p110delta
-
pleckstrin
-
p110gamma
- ptdins3p
-
gpcrs
- rac
-
isoform-selective
- pi3-kinase
-
pi3k-dependent
- pi3kalpha
-
ptdins3,4p2
-
p85alpha
- 3-phosphoinositides
- 3,4-bisphosphate
-
3-kinase-dependent
- pi3-ks
- pi3kdelta
-
kinase-dead
- gbetagamma
- drug development
- diagnostics
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
phosphoinositide 3-kinases, pi3k-c2alpha, pi3k-c2beta, class ii pi3k, pik3c2g, class ii phosphoinositide 3-kinase, pi3kc2beta, pi3kc2a, pi3kc2b, phosphatidylinositol-4-phosphate 3-kinase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
C2-domain-containing phosphoinositide 3-kinase
-
-
-
-
C2-PI3K
-
-
-
-
class II phosphoinositide 3-kinase C2alpha
-
-
-
-
class II phosphoinositide 3-kinase C2beta
-
-
-
-
HsC3-PI3K
-
-
-
-
kinase (phosphorylating), phosphatidylinositol 4-phosphate 3-
-
-
-
-
p170
-
-
-
-
phosphoinositide 3-kinase
phosphoinositide 3-kinase C2beta
phosphoinositide 3-kinase-C2-beta
-
-
-
-
phosphoinositide 3-kinase-C2-gamma
-
-
-
-
PI 3-kinase C2alpha
-
-
-
-
PI 3-kinase C2beta
-
-
-
-
PI 3-kinase C2gamma
-
-
-
-
PI3K-C2alpha
PI3K-C2beta
PI3K-C2gamma
-
-
-
-
PtdIns-3-kinase C2alpha
-
-
-
-
PtdIns-3-kinase C2beta
-
-
-
-
PtdIns-3-kinase C2gamma
-
-
-
-
type II phosphoinositide 3-kinase
-
-
-
-
phosphoinositide 3-kinase
-
-
-
-
phosphoinositide 3-kinase C2beta
-
-
-
-
PI3K-C2alpha
-
-
-
-
PI3K-C2beta
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho-group transfer
-
-
-
-
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.
CAS REGISTRY NUMBER
COMMENTARY
141176-94-5
-
67053-99-0
cf. EC 2.7.1.137
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + 1-phosphatidyl-1D-myo-inositol-4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
-
-
?
ATP + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
-
preferred substrate of enzyme form PI3K-C2beta
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
ATP + 1-phosphatidyl-1D-myo-inositol-4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-diphosphate
-
strong preference for phosphatidylinositol over 1-phosphatidyl-1D-myo-inositol-4-phosphate
-
-
?
ATP + phosphatidylinositol
?
-
strong preference for phosphatidylinositol over 1-phosphatidyl-1D-myo-inositol-4-phosphate
-
-
?
additional information
?
-
no activity with phosphatidylinositol 4,5-diphosphate
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
-
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
-
i.e. BAPTA-AM, a cell-penetrating Ca2+-chelator
calpeptin
-
inhibits proteolytic activation of enzyme form PI3K C2beta in brush border plasma membranes
Isoflurane
ISO, inhibits KCl-stimulated PI3K-C2alpha membrane translocation
LY294002
a PI3K inhibitor, inhibits KCl-elicited rapid and sustained contraction of rat aortic smooth muscle
sevoflurane
SEVO, inhibits KCl-stimulated PI3K-C2alpha membrane translocation
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
A23187
-
Ca2+-ionophore, activates enzyme form PI3K-C2beta, mimicks hepatocyte growth factor HGF
hepatocyte growth factor HGF
-
in renal brush-border and basal lateral plasma membranes, in the latter case mediated by calpain
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00042
Wortmannin
Rattus norvegicus
-
isozyme PI3K-C2alpha, pH and temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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
-
in the nuclear matrix harvested 20 h after partial hepatectomy, an increase in immunoprecipitable PI3K-C2beta activity is observed
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
renal brush-border and basal lateral, enzyme form phosphoinositide 3-kinase C2beta occurs only in renal brush-border plasma membrane
-
existence of PI3K-C2alpha and 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate on CD63-positive large vesicles in FceRI-stimulated RBL-2H3 cells
additional information
membrane translocation of PI3K-C2alpha in response to KCl
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
-
involvement of PI3K-C2alpha in the antigen-induced degranulation pathway
physiological function
malfunction
-
PI3K-C2alpha knockdown decreases the FceRI-triggered release of a lysosomal enzyme, namely beta-hexosaminidase, protein levels of PI3K-C2beta are not significantly affected by the shRNAs. siRNA against PI3K-C2beta impairs the FceRI-induced increase in intracellular Ca2+ and degranulation. Release of NPY-mRFP, a reporter of the regulated exocytosis of mast cells is increased by PI3K-C2alpha overexpression and is impaired in the PI3K-C2alpha-deficient cells
malfunction
effects of LY294002, sevoflurane (SEVO) and isoflurane (ISO) on KCl-elicited PI3KC2alpha mediated vasoconstriction in rat aortic smooth muscle, overview. PI3K inhibitor LY294002 inhibits PI3K-C2alpha membrane translocation in response to KCl. SEVO and ISO inhibit KCl-stimulated MLC phosphorylation, PI3K-C2alpha and Rock-II, but not PI3K p85, membrane translocation in a concentration-dependent manner in rat aorta
physiological function
-
PI3K-C2beta regulates the FceRI-stimulated activation of the KCa3.1 channel and the FceRI-induced Ca2+ influx and degranulation in BMMCs. PI3K-C2alpha regulates the FceRI-triggered degranulation by a mechanism different from that induced by PI3K-C2beta. PI3KC2alpha and PI3K-C2beta share different roles in the FceRI-regulated degranulation pathway
physiological function
class II phosphoinositide 3-kinase alpha-isoform (PI3K-C2alpha) is involved in regulating KCl-induced vascular smooth muscle contraction. PI3K-C2alpha mediates part of sevoflurane (SEVO)- and isoflurane (ISO)-mediated vasodilation in rat aorta
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). P3C2G_RAT
1505
0
170975
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
-
activation of enzyme form PI3K C2beta occurs probably via proteolysis in the brush broder plasma membrane
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
partially by subcellular fractionation of renal cortex, plasma membrane preparation
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
real-time PCR analysis of PI3K-C2alpha and PI3K-C2beta in cells transfected with the control or shRNA expression vector NPY-mRFP and EGFP-PI3K-C2alpha are transfected into RBL-2H3 cells
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ono, F.; Nakagawa, T.; Saito, S.; Owada, Y.; Sakagami, H.; Goto, K.; Suzuki, M.; Matsuno, S.; Kondo, H.
A novel class II phosphoinositide 3-kinase predominantly expressed in the liver and its enhanced expression during liver regeneration
J. Biol. Chem.
273
7731-7736
1998
Rattus norvegicus (O70173)
Prior, I.A.; Clague, M.J.
Localization of a class II phosphatidylinositol 3-kinase, PI3KC2a, to clathrin-coated vesicles
Mol. Cell. Biol.
1
162-166
1999
Rattus norvegicus
Domin, J.; Gaidarov, I.; Smith, M.E.K.; Keen, J.H.; Waterfield, M.D.
The class II phosphoinositide 3-kinase PI3K-C2alpha is concentrated in the trans-Golgi network and present in clathrin-coated vesicles
J. Biol. Chem.
275
11943-11950
2000
Cricetulus griseus, Cricetulus griseus PI3K-C2alpha, Homo sapiens, Homo sapiens PI3K-C2alpha, Rattus norvegicus
Crljen, V.; Volinia, S.; Banfic, H.
Hepatocyte growth factor activates phosphoinositide 3-kinase C2beta in renal brush-border plasma membranes
Biochem. J.
365
791-799
2002
Rattus norvegicus
Sindic, A.; Crljen, V.; Matkovic, K.; Lukinovic-Skudar, V.; Visnjic, D.; Banfic, H.
Activation of phosphoinositide 3-kinase C2 beta in the nuclear matrix during compensatory liver growth
Adv. Enzyme Regul.
46
280-287
2006
Rattus norvegicus
Falasca, M.; Maffucci, T.
Role of class II phosphoinositide 3-kinase in cell signalling
Biochem. Soc. Trans.
35
211-214
2007
Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus
Nigorikawa, K.; Hazeki, K.; Guo, Y.; Hazeki, O.
Involvement of class II phosphoinositide 3-kinase ?-isoform in antigen-induced degranulation in RBL-2H3 cells.
PLoS ONE
9
e111698
2014
Rattus norvegicus
EXTERNAL LINKS (specific for EC-Number 2.7.1.154)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
