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Information on EC 2.7.1.154 - phosphatidylinositol-4-phosphate 3-kinase and Organism(s) Mus musculus and UniProt Accession O70167
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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.
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Word Map
- 2.7.1.154
- wortmannin
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chemotaxis
- pi3kgamma
- p110alpha
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ptdins3,4,5p3
- pten
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3,4,5-trisphosphate
- p110delta
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pleckstrin
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p110gamma
- ptdins3p
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gpcrs
- rac
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isoform-selective
- pi3-kinase
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pi3k-dependent
- pi3kalpha
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ptdins3,4p2
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p85alpha
- 3-phosphoinositides
- 3,4-bisphosphate
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3-kinase-dependent
- pi3-ks
- pi3kdelta
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kinase-dead
- gbetagamma
- drug development
- diagnostics
The taxonomic range for the selected organisms is: Mus musculus
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
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C2-PI3K
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class II phosphoinositide 3-kinase C2alpha
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class II phosphoinositide 3-kinase C2beta
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class II PI3K
HsC3-PI3K
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kinase (phosphorylating), phosphatidylinositol 4-phosphate 3-
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p170
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phosphoinositide 3-kinase
phosphoinositide 3-kinase C2beta
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phosphoinositide 3-kinase-C2-beta
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phosphoinositide 3-kinase-C2-gamma
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PI 3-kinase C2alpha
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PI 3-kinase C2beta
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PI 3-kinase C2gamma
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PI3K-C2alpha
PI3K-C2beta
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PI3K-C2gamma
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PtdIns-3-kinase C2alpha
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PtdIns-3-kinase C2beta
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PtdIns-3-kinase C2gamma
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type II phosphoinositide 3-kinase
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phosphoinositide 3-kinase
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PI3K-C2alpha
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho-group transfer
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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
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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
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-
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?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
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preferred substrate of enzyme form PI3K-C2beta
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-
?
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
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-
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?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
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?
ATP + phosphoinositides
ADP + ?
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
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?
ATP + phosphoinositides
ADP + ?
phosphorylation of the D-3 position on the inositol ring
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?
additional information
?
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ATP and substrate binding of PI3K isozymes, overview
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additional information
?
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ATP and substrate binding of PI3K isozymes, overview
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additional information
?
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ATP and substrate binding of PI3K isozymes, overview
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additional information
?
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TNFalpha and leptin stimulate the alpha-isoform of class II phosphoinositide 3-kinase
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?
additional information
?
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the enzyme is regulated by intracellular signalling mechanisms
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?
additional information
?
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ATP and substrate binding of PI3K isozymes, overview
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additional information
?
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ATP and substrate binding of PI3K isozymes, overview
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additional information
?
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ATP and substrate binding of PI3K isozymes, overview
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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
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-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
ATP + phosphoinositides
ADP + ?
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
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?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
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?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
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?
additional information
?
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TNFalpha and leptin stimulate the alpha-isoform of class II phosphoinositide 3-kinase
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?
additional information
?
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the enzyme is regulated by intracellular signalling mechanisms
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?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(5Z)-5-[[5-(4-fluoro-2-hydroxyphenyl)furan-2-yl]methylidene]-1,3-thiazolidine-2,4-dione
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2-amino-N-[(1S)-1-[8-[(1-methyl-1H-pyrazol-4-yl)ethynyl]-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl]ethyl]pyrazolo[1,5-a]pyrimidine-3-carboxamide
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3-amino-N-[3-(3,5-dimethoxyanilino)pyrazin-2-yl]benzene-1-sulfonamide
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5-[2,6-bis(morpholin-4-yl)pyrimidin-4-yl]-4-(trifluoromethyl)pyridin-2-amine
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6-[5-(2,2-dimethylpropane-1-sulfonyl)pyridin-3-yl]-8-fluoro[1,2,4]triazolo[1,5-a]pyridin-2-amine
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(2S)-N1-[4-methyl-5-[3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]pyrrolidine-1,2-dicarboxamide
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2-([(1R)-1-[7-methyl-2-(morpholin-4-yl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl]ethyl]amino)benzoic acid
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2-methyl-1-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-(morpholin-4-yl)-1H-benzimidazole-4-carboxylic acid
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3-amino-N-[3-(3,5-dimethoxyanilino)pyrazin-2-yl]benzene-1-sulfonamide
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3-[4-(morpholin-4-yl)pyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl]phenol
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4-[(3-chloro-4-fluorophenyl)methyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-2H-1,4-benzoxazin-3(4H)-one
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5-[2,6-bis(morpholin-4-yl)pyrimidin-4-yl]-4-(trifluoromethyl)pyridin-2-amine
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8-[(1R)-1-(3,5-difluoroanilino)ethyl]-N,N-dimethyl-2-(morpholin-4-yl)-4-oxo-4H-1-benzopyran-6-carboxamide
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N-(5-[4-chloro-3-[(2-hydroxyethyl)sulfamoyl]phenyl]-4-methyl-1,3-thiazol-2-yl)acetamide
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N-(7,8-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)pyridine-3-carboxamide
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N-[2-[3-[(benzenesulfonyl)amino]phenyl]-4-(morpholin-4-yl)quinazolin-6-yl]acetamide
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N-[3-(2-chloro-5-hydroxyanilino)pyrazin-2-yl]benzenesulfonamide
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N-[4-(morpholin-4-yl)-2-[3-[(naphthalene-2-sulfonyl)amino]phenyl]quinazolin-6-yl]acetamide
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[6-(2-amino-1,3-benzoxazol-5-yl)imidazo[1,2-a]pyridin-3-yl](morpholin-4-yl)methanone
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Wortmannin
class I isozyme inhibitor, isozyme PI3K-C2alpha is resistant to inhibition
additional information
no or poor inhibition by GDC-0941, (2S)-N1-[4-methyl-5-[3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]pyrrolidine-1,2-dicarboxamide, 2-([(1R)-1-[7-methyl-2-(morpholin-4-yl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl]ethyl]amino)benzoic acid, idelalisib, N-(7,8-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)pyridine-3-carboxamide, N-(5-[4-chloro-3-[(2-hydroxyethyl)sulfamoyl]phenyl]-4-methyl-1,3-thiazol-2-yl)acetamide, 4-[(3-chloro-4-fluorophenyl)methyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-2H-1,4-benzoxazin-3(4H)-one, dactolisib, ZSTK474, AZD3147, 5-[4-[(methanesulfonyl)methyl]-6-(morpholin-4-yl)pyrimidin-2-yl]-1H-indole, gedatolisib, 4'-(cyclopropylmethyl)-N2-(pyridin-4-yl)[4,5'-bipyrimidine]-2,2'-diamine, 1-([2-[(2-chloropyridin-4-yl)amino]-4'-(cyclopropylmethyl)[4,5'-bipyrimidin]-2'-yl]amino)-2-methylpropan-2-ol, SAR405, (2S)-2-amino-1-(4-[4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(morpholin-4-yl)-1,3,5-triazin-2-yl]piperazin-1-yl)-3-phenylpropan-1-one, N-[4-(morpholin-4-yl)-2-[3-[(naphthalene-2-sulfonyl)amino]phenyl]quinazolin-6-yl]acetamide, N-[2-[3-[(benzenesulfonyl)amino]phenyl]-4-(morpholin-4-yl)quinazolin-6-yl]acetamide, N-(3-[[3-(2-chloro-5-methoxyanilino)quinoxalin-2-yl]sulfamoyl]phenyl)-2-methylalaninamide, N-[3-(3,5-dimethoxyanilino)quinoxalin-2-yl]-4-fluorobenzene-1-sulfonamide, and N-[3-(2-chloro-5-hydroxyanilino)pyrazin-2-yl]benzenesulfonamide
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additional information
no or poor inhibition by GDC-0941, (2S)-N1-[4-methyl-5-[3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]pyrrolidine-1,2-dicarboxamide, 2-([(1R)-1-[7-methyl-2-(morpholin-4-yl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl]ethyl]amino)benzoic acid, idelalisib, N-(7,8-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)pyridine-3-carboxamide, N-(5-[4-chloro-3-[(2-hydroxyethyl)sulfamoyl]phenyl]-4-methyl-1,3-thiazol-2-yl)acetamide, 4-[(3-chloro-4-fluorophenyl)methyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-2H-1,4-benzoxazin-3(4H)-one, dactolisib, ZSTK474, AZD3147, 5-[4-[(methanesulfonyl)methyl]-6-(morpholin-4-yl)pyrimidin-2-yl]-1H-indole, gedatolisib, 4'-(cyclopropylmethyl)-N2-(pyridin-4-yl)[4,5'-bipyrimidine]-2,2'-diamine, 1-([2-[(2-chloropyridin-4-yl)amino]-4'-(cyclopropylmethyl)[4,5'-bipyrimidin]-2'-yl]amino)-2-methylpropan-2-ol, SAR405, (2S)-2-amino-1-(4-[4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(morpholin-4-yl)-1,3,5-triazin-2-yl]piperazin-1-yl)-3-phenylpropan-1-one, N-[4-(morpholin-4-yl)-2-[3-[(naphthalene-2-sulfonyl)amino]phenyl]quinazolin-6-yl]acetamide, N-[2-[3-[(benzenesulfonyl)amino]phenyl]-4-(morpholin-4-yl)quinazolin-6-yl]acetamide, N-(3-[[3-(2-chloro-5-methoxyanilino)quinoxalin-2-yl]sulfamoyl]phenyl)-2-methylalaninamide, N-[3-(3,5-dimethoxyanilino)quinoxalin-2-yl]-4-fluorobenzene-1-sulfonamide, and N-[3-(2-chloro-5-hydroxyanilino)pyrazin-2-yl]benzenesulfonamide
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additional information
no or poor inhibition by GDC-0941, (2S)-N1-[4-methyl-5-[3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]pyrrolidine-1,2-dicarboxamide, 2-([(1R)-1-[7-methyl-2-(morpholin-4-yl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl]ethyl]amino)benzoic acid, idelalisib, N-(7,8-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)pyridine-3-carboxamide, N-(5-[4-chloro-3-[(2-hydroxyethyl)sulfamoyl]phenyl]-4-methyl-1,3-thiazol-2-yl)acetamide, 4-[(3-chloro-4-fluorophenyl)methyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-2H-1,4-benzoxazin-3(4H)-one, dactolisib, ZSTK474, AZD3147, 5-[4-[(methanesulfonyl)methyl]-6-(morpholin-4-yl)pyrimidin-2-yl]-1H-indole, gedatolisib, 4'-(cyclopropylmethyl)-N2-(pyridin-4-yl)[4,5'-bipyrimidine]-2,2'-diamine, 1-([2-[(2-chloropyridin-4-yl)amino]-4'-(cyclopropylmethyl)[4,5'-bipyrimidin]-2'-yl]amino)-2-methylpropan-2-ol, SAR405, (2S)-2-amino-1-(4-[4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(morpholin-4-yl)-1,3,5-triazin-2-yl]piperazin-1-yl)-3-phenylpropan-1-one, N-[4-(morpholin-4-yl)-2-[3-[(naphthalene-2-sulfonyl)amino]phenyl]quinazolin-6-yl]acetamide, N-[2-[3-[(benzenesulfonyl)amino]phenyl]-4-(morpholin-4-yl)quinazolin-6-yl]acetamide, N-(3-[[3-(2-chloro-5-methoxyanilino)quinoxalin-2-yl]sulfamoyl]phenyl)-2-methylalaninamide, N-[3-(3,5-dimethoxyanilino)quinoxalin-2-yl]-4-fluorobenzene-1-sulfonamide, and N-[3-(2-chloro-5-hydroxyanilino)pyrazin-2-yl]benzenesulfonamide
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additional information
enzyme is regulated by several feedback inhibition possibilities in the insulin signalling pathway, overview
-
additional information
no or poor inhibition by buparlisib, (8S)-2-[(3R)-3-methylmorpholin-4-yl]-9-(3-methyl-2-oxobutyl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one, AZD3147, 5-[4-[(methanesulfonyl)methyl]-6-(morpholin-4-yl)pyrimidin-2-yl]-1H-indole, gedatolisib, 4'-(cyclopropylmethyl)-N2-(pyridin-4-yl)[4,5'-bipyrimidine]-2,2'-diamine, 1-([2-[(2-chloropyridin-4-yl)amino]-4'-(cyclopropylmethyl)[4,5'-bipyrimidin]-2'-yl]amino)-2-methylpropan-2-ol, SAR405, (2S)-2-amino-1-(4-[4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(morpholin-4-yl)-1,3,5-triazin-2-yl]piperazin-1-yl)-3-phenylpropan-1-one, N-(3-[[3-(2-chloro-5-methoxyanilino)quinoxalin-2-yl]sulfamoyl]phenyl)-2-methylalaninamide, and N-[3-(3,5-dimethoxyanilino)quinoxalin-2-yl]-4-fluorobenzene-1-sulfonamide
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additional information
no or poor inhibition by buparlisib, (8S)-2-[(3R)-3-methylmorpholin-4-yl]-9-(3-methyl-2-oxobutyl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one, AZD3147, 5-[4-[(methanesulfonyl)methyl]-6-(morpholin-4-yl)pyrimidin-2-yl]-1H-indole, gedatolisib, 4'-(cyclopropylmethyl)-N2-(pyridin-4-yl)[4,5'-bipyrimidine]-2,2'-diamine, 1-([2-[(2-chloropyridin-4-yl)amino]-4'-(cyclopropylmethyl)[4,5'-bipyrimidin]-2'-yl]amino)-2-methylpropan-2-ol, SAR405, (2S)-2-amino-1-(4-[4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(morpholin-4-yl)-1,3,5-triazin-2-yl]piperazin-1-yl)-3-phenylpropan-1-one, N-(3-[[3-(2-chloro-5-methoxyanilino)quinoxalin-2-yl]sulfamoyl]phenyl)-2-methylalaninamide, and N-[3-(3,5-dimethoxyanilino)quinoxalin-2-yl]-4-fluorobenzene-1-sulfonamide
-
additional information
no or poor inhibition by buparlisib, (8S)-2-[(3R)-3-methylmorpholin-4-yl]-9-(3-methyl-2-oxobutyl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one, AZD3147, 5-[4-[(methanesulfonyl)methyl]-6-(morpholin-4-yl)pyrimidin-2-yl]-1H-indole, gedatolisib, 4'-(cyclopropylmethyl)-N2-(pyridin-4-yl)[4,5'-bipyrimidine]-2,2'-diamine, 1-([2-[(2-chloropyridin-4-yl)amino]-4'-(cyclopropylmethyl)[4,5'-bipyrimidin]-2'-yl]amino)-2-methylpropan-2-ol, SAR405, (2S)-2-amino-1-(4-[4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(morpholin-4-yl)-1,3,5-triazin-2-yl]piperazin-1-yl)-3-phenylpropan-1-one, N-(3-[[3-(2-chloro-5-methoxyanilino)quinoxalin-2-yl]sulfamoyl]phenyl)-2-methylalaninamide, and N-[3-(3,5-dimethoxyanilino)quinoxalin-2-yl]-4-fluorobenzene-1-sulfonamide
-
additional information
no or poor inhibition by buparlisib, idelalisib, 3-[4-(morpholin-4-yl)pyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl]phenol, (8S)-2-[(3R)-3-methylmorpholin-4-yl]-9-(3-methyl-2-oxobutyl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one, AZD3147, 5-[4-[(methanesulfonyl)methyl]-6-(morpholin-4-yl)pyrimidin-2-yl]-1H-indole, gedatolisib, 4'-(cyclopropylmethyl)-N2-(pyridin-4-yl)[4,5'-bipyrimidine]-2,2'-diamine, 1-([2-[(2-chloropyridin-4-yl)amino]-4'-(cyclopropylmethyl)[4,5'-bipyrimidin]-2'-yl]amino)-2-methylpropan-2-ol, SAR405, (2S)-2-amino-1-(4-[4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(morpholin-4-yl)-1,3,5-triazin-2-yl]piperazin-1-yl)-3-phenylpropan-1-one, N-[4-(morpholin-4-yl)-2-[3-[(naphthalene-2-sulfonyl)amino]phenyl]quinazolin-6-yl]acetamide, N-[2-[3-[(benzenesulfonyl)amino]phenyl]-4-(morpholin-4-yl)quinazolin-6-yl]acetamide, N-(3-[[3-(2-chloro-5-methoxyanilino)quinoxalin-2-yl]sulfamoyl]phenyl)-2-methylalaninamide, N-[3-(3,5-dimethoxyanilino)quinoxalin-2-yl]-4-fluorobenzene-1-sulfonamide, 3-amino-N-[3-(3,5-dimethoxyanilino)pyrazin-2-yl]benzene-1-sulfonamide, N-[3-(2-chloro-5-hydroxyanilino)pyrazin-2-yl]benzenesulfonamide
-
additional information
no or poor inhibition by buparlisib, idelalisib, 3-[4-(morpholin-4-yl)pyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl]phenol, (8S)-2-[(3R)-3-methylmorpholin-4-yl]-9-(3-methyl-2-oxobutyl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one, AZD3147, 5-[4-[(methanesulfonyl)methyl]-6-(morpholin-4-yl)pyrimidin-2-yl]-1H-indole, gedatolisib, 4'-(cyclopropylmethyl)-N2-(pyridin-4-yl)[4,5'-bipyrimidine]-2,2'-diamine, 1-([2-[(2-chloropyridin-4-yl)amino]-4'-(cyclopropylmethyl)[4,5'-bipyrimidin]-2'-yl]amino)-2-methylpropan-2-ol, SAR405, (2S)-2-amino-1-(4-[4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(morpholin-4-yl)-1,3,5-triazin-2-yl]piperazin-1-yl)-3-phenylpropan-1-one, N-[4-(morpholin-4-yl)-2-[3-[(naphthalene-2-sulfonyl)amino]phenyl]quinazolin-6-yl]acetamide, N-[2-[3-[(benzenesulfonyl)amino]phenyl]-4-(morpholin-4-yl)quinazolin-6-yl]acetamide, N-(3-[[3-(2-chloro-5-methoxyanilino)quinoxalin-2-yl]sulfamoyl]phenyl)-2-methylalaninamide, N-[3-(3,5-dimethoxyanilino)quinoxalin-2-yl]-4-fluorobenzene-1-sulfonamide, 3-amino-N-[3-(3,5-dimethoxyanilino)pyrazin-2-yl]benzene-1-sulfonamide, N-[3-(2-chloro-5-hydroxyanilino)pyrazin-2-yl]benzenesulfonamide
-
additional information
no or poor inhibition by buparlisib, idelalisib, 3-[4-(morpholin-4-yl)pyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl]phenol, (8S)-2-[(3R)-3-methylmorpholin-4-yl]-9-(3-methyl-2-oxobutyl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one, AZD3147, 5-[4-[(methanesulfonyl)methyl]-6-(morpholin-4-yl)pyrimidin-2-yl]-1H-indole, gedatolisib, 4'-(cyclopropylmethyl)-N2-(pyridin-4-yl)[4,5'-bipyrimidine]-2,2'-diamine, 1-([2-[(2-chloropyridin-4-yl)amino]-4'-(cyclopropylmethyl)[4,5'-bipyrimidin]-2'-yl]amino)-2-methylpropan-2-ol, SAR405, (2S)-2-amino-1-(4-[4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(morpholin-4-yl)-1,3,5-triazin-2-yl]piperazin-1-yl)-3-phenylpropan-1-one, N-[4-(morpholin-4-yl)-2-[3-[(naphthalene-2-sulfonyl)amino]phenyl]quinazolin-6-yl]acetamide, N-[2-[3-[(benzenesulfonyl)amino]phenyl]-4-(morpholin-4-yl)quinazolin-6-yl]acetamide, N-(3-[[3-(2-chloro-5-methoxyanilino)quinoxalin-2-yl]sulfamoyl]phenyl)-2-methylalaninamide, N-[3-(3,5-dimethoxyanilino)quinoxalin-2-yl]-4-fluorobenzene-1-sulfonamide, 3-amino-N-[3-(3,5-dimethoxyanilino)pyrazin-2-yl]benzene-1-sulfonamide, N-[3-(2-chloro-5-hydroxyanilino)pyrazin-2-yl]benzenesulfonamide
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
-
additional information
-
TNFalpha and leptin stimulate the alpha-isoform of class II phosphoinositide 3-kinase
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
isozyme PI3KC2alpha is widely expressed in mammalian cells
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
global deficiency of PI3KC2gamma causes a phenotype of hyperlipidemia, adiposity, and insulin resistance
malfunction
physiological function
malfunction
agonist-induced 3-phosphorylated phosphoinositide production and cellular activation are normal in PI3KC2alpha-deficient platelets. PI3KC2alpha deficiency exacerbates bleeding and impairs thrombosis. Phenotype of Pik3c2alpha-/- mice. PI3KC2alpha deficiency alters platelet and megakaryocyte internal membrane structures, overview. PI3KC2alpha deficiency causes unstable platelet thrombi and enhances shear-dependent platelet adhesion
malfunction
different deficiency types of PI3KC2alpha can cause different phenotypes, including stunted growth, decreased survival, renal abnormalities, embryonic lethality, decreased retinal angiogenesis, impaired revascularization following ischemic injury, and impaired platelet function during thrombosis. Mouse models of PI3KC2alpha deficiency. While homozygosity for kinase-dead PI3KC2alpha is embryonic lethal, heterozygous PI3KC2alpha KI mice are viable and fertile, with no significant histopathological findings. Male heterozygous mice show early onset leptin resistance, with a defect in leptin signaling in the hypothalamus, correlating with a mild, age-dependent obesity, insulin resistance, and glucose intolerance
malfunction
heterozygous kinase-dead inactivating mutation of PI3KC2gamma causes a phenotype of decreased circulating insulin levels, increased glucose tolerance, and protection against steatosis. Inhibition of PI3KC2beta significantly reduced ovarian cancer metastasis in mice
physiological function
PI3KC2alpha is important for mouse platelet function in vivo and plays an important role in regulating endothelial cell barrier function and vasculogenesis. Role for PI3KC2alpha in regulating the internal membrane reserve structure of megakaryocytes (demarcation membrane system) and platelets (open canalicular system) that results in dysregulated platelet adhesion under haemodynamic shear stress. Important role for PI3KC2alpha in regulating shear-dependent platelet adhesion via regulation of membrane structure, rather than acute signalling
physiological function
importance of PI3KC2beta in ovarian cancer cell migration
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_MOUSE
1506
0
171580
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
110000
x * 110000, catalytic subunit, + x * 85000, catalytically inactive adaptor subunit
85000
x * 110000, catalytic subunit, + x * 85000, catalytically inactive adaptor subunit
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
?
x * 110000, catalytic subunit, + x * 85000, catalytically inactive adaptor subunit
additional information
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
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
global deficiency of PI3KC2gamma is induced in mouse, phenotype, overview
additional information
global deficiency of PI3KC2gamma is induced in mouse, phenotype, overview
additional information
global deficiency of PI3KC2gamma is induced in mouse, phenotype, overview
additional information
disruption of gene Pik3c2alpha. Insertion of a gene trap vector encoding a splice acceptor beta-galactosidase (trap) and a polyA stop site into the Pik3c2alpha locus occur either between exons 19 and 20 (Pik3c2alphagt1) or exons 23 and 24 (Pik3c2alphagt2), and is predicted to yield a truncated fusion protein of the first 837 or 1029 amino acids of PI3KC2alpha-linked to beta-galactosidase, respectively. shRNA expression using the cytomegalovirus (CMV) promoter
additional information
different types of deficiency of PI3KC2beta are induced in mouse, i.e. global deficiency, and heterozygous kinase-dead inactivating mutation, phenotypes, overview
additional information
different types of deficiency of PI3KC2beta are induced in mouse, i.e. global deficiency, and heterozygous kinase-dead inactivating mutation, phenotypes, overview
additional information
different types of deficiency of PI3KC2beta are induced in mouse, i.e. global deficiency, and heterozygous kinase-dead inactivating mutation, phenotypes, overview
additional information
several types of deficiency of PI3KC2alpha are induced in mouse, i.e. hypomorph (global but variable), global deficiency, endothelial-cell-specific deficiency, induced endothelial-cell-specific deficiency, induced global deficiency, heterozygous kinase-dead inactivating mutation, phenotypes, overview
additional information
several types of deficiency of PI3KC2alpha are induced in mouse, i.e. hypomorph (global but variable), global deficiency, endothelial-cell-specific deficiency, induced endothelial-cell-specific deficiency, induced global deficiency, heterozygous kinase-dead inactivating mutation, phenotypes, overview
additional information
several types of deficiency of PI3KC2alpha are induced in mouse, i.e. hypomorph (global but variable), global deficiency, endothelial-cell-specific deficiency, induced endothelial-cell-specific deficiency, induced global deficiency, heterozygous kinase-dead inactivating mutation, phenotypes, overview
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cloned into the baculovirus expression vector pAcG3x and expressed in Sf9 cells
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Molz, L.; Chen, Y.W.; Hirano, M.; Williams, L.T.
CpK is a novel class of Drosophila PtdIns 3-kinase containing a C2 domain
J. Biol. Chem.
271
13892-13899
1996
Drosophila melanogaster (Q7JNX6), Mus musculus (Q61194)
Virbasius, J.V.; Guilherme, A.; Czech, M.P.
Mouse p170 is a novel phosphatidylinositol 3-kinase containing a C2 domain
J. Biol. Chem.
271
13304-13307
1996
Homo sapiens, Homo sapiens PI3K-C2alpha, Mus musculus
Misawa, H.; Ohtsubo, M.; Copeland, N.G.; Gilbert, D.J.; Jenkins, N.A.; Yoshimura, A.
Cloning and characterization of a novel class II phosphoinositide 3-kinase containing C2 domain
Biochem. Biophys. Res. Commun.
244
531-539
1998
Mus musculus (O70167), Mus musculus
Ktori, C.; Shepherd, P.R.; O'Rourke, L.
TNF-alpha and leptin activate the alpha-isoform of class II phosphoinositide 3-kinase
Biochem. Biophys. Res. Commun.
306
139-143
2003
Mus musculus
Shepherd, P.R.
Mechanisms regulating phosphoinositide 3-kinase signalling in insulin-sensitive tissues
Acta Physiol. Scand.
183
3-12
2005
Homo sapiens (O00443), Mus musculus (Q61194), Homo sapiens PI3K-C2alpha (O00443)
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
Mountford, J.K.; Petitjean, C.; Putra, H.W.; McCafferty, J.A.; Setiabakti, N.M.; Lee, H.; T?nnesen, L.L.; McFadyen, J.D.; Schoenwaelder, S.M.; Eckly, A.; Gachet, C.; Ellis, S.; Voss, A.K.; Dickins, R.A.; Hamilton, J.R.; Jackson, S.P.
The class II PI 3-kinase, PI3KC2alpha, links platelet internal membrane structure to shear-dependent adhesive function
Nat. Commun.
6
6535
2015
Mus musculus (Q61194)
Falasca, M.; Hamilton, J.R.; Selvadurai, M.; Sundaram, K.; Adamska, A.; Thompson, P.E.
Class II phosphoinositide 3-kinases as novel drug targets
J. Med. Chem.
60
47-65
2017
Mus musculus (E9QAN8), Mus musculus (O70167), Mus musculus (Q61194), Homo sapiens (O00443), Homo sapiens (O00750), Homo sapiens (O75747)
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