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Literature summary for 2.7.1.154 extracted from

  • Falasca, M.; Hamilton, J.R.; Selvadurai, M.; Sundaram, K.; Adamska, A.; Thompson, P.E.
    Class II phosphoinositide 3-kinases as novel drug targets (2017), J. Med. Chem., 60, 47-65 .
    View publication on PubMed
Search for more literature for 2.7.1.154

Activating Compound

Activating Compound Comment Organism Structure
ITSN1 a PI3KC2beta activator Homo sapiens
lysophosphatidic acid activates PI3KC2beta in SKOV3 cells Homo sapiens
lysophosphatidic acid activates PI3KC2beta in SKOV3 cells Mus musculus
additional information PI3KC2alpha can be activated by a range of molecules, including cytokines, chemokines, integrins, as well as insulin and other growth factors Homo sapiens

Application

Application Comment Organism
diagnostics PI3KC2gamma is a potential novel biomarker, whose expression levels may predict CRC recurrence and patient survival Homo sapiens
drug development PI3KC2alpha may be a suitable drug target for the prevention and treatment of thrombosis and cardiovascular disease Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
gene PIK3C2G Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information different types of deficiency of PI3KC2beta are induced in mouse, i.e. global deficiency, and heterozygous kinase-dead inactivating mutation, phenotypes, overview Mus musculus
additional information global deficiency of PI3KC2gamma is induced in mouse, phenotype, overview Mus musculus
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 Mus musculus

Inhibitors

Inhibitors Comment Organism Structure
(2S)-N1-[4-methyl-5-[3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]pyrrolidine-1,2-dicarboxamide
-
 Homo sapiens
(2S)-N1-[4-methyl-5-[3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]pyrrolidine-1,2-dicarboxamide
-
 Mus musculus
(5Z)-5-[[5-(4-fluoro-2-hydroxyphenyl)furan-2-yl]methylidene]-1,3-thiazolidine-2,4-dione
-
 Homo sapiens
(5Z)-5-[[5-(4-fluoro-2-hydroxyphenyl)furan-2-yl]methylidene]-1,3-thiazolidine-2,4-dione
-
 Mus musculus
2-([(1R)-1-[7-methyl-2-(morpholin-4-yl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl]ethyl]amino)benzoic acid
-
 Homo sapiens
2-([(1R)-1-[7-methyl-2-(morpholin-4-yl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl]ethyl]amino)benzoic acid
-
 Mus musculus
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
-
 Homo sapiens
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
-
 Mus musculus
2-methyl-1-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-(morpholin-4-yl)-1H-benzimidazole-4-carboxylic acid
-
 Homo sapiens
2-methyl-1-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-(morpholin-4-yl)-1H-benzimidazole-4-carboxylic acid
-
 Mus musculus
3-amino-N-[3-(3,5-dimethoxyanilino)pyrazin-2-yl]benzene-1-sulfonamide
-
 Homo sapiens
3-amino-N-[3-(3,5-dimethoxyanilino)pyrazin-2-yl]benzene-1-sulfonamide
-
 Mus musculus
3-[4-(morpholin-4-yl)pyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl]phenol
-
 Homo sapiens
3-[4-(morpholin-4-yl)pyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl]phenol
-
 Mus musculus
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
-
 Homo sapiens
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
-
 Mus musculus
5-[2,6-bis(morpholin-4-yl)pyrimidin-4-yl]-4-(trifluoromethyl)pyridin-2-amine
-
 Homo sapiens
5-[2,6-bis(morpholin-4-yl)pyrimidin-4-yl]-4-(trifluoromethyl)pyridin-2-amine
-
 Mus musculus
6-[5-(2,2-dimethylpropane-1-sulfonyl)pyridin-3-yl]-8-fluoro[1,2,4]triazolo[1,5-a]pyridin-2-amine
-
 Homo sapiens
6-[5-(2,2-dimethylpropane-1-sulfonyl)pyridin-3-yl]-8-fluoro[1,2,4]triazolo[1,5-a]pyridin-2-amine
-
 Mus musculus
8-[(1R)-1-(3,5-difluoroanilino)ethyl]-N,N-dimethyl-2-(morpholin-4-yl)-4-oxo-4H-1-benzopyran-6-carboxamide
-
 Homo sapiens
8-[(1R)-1-(3,5-difluoroanilino)ethyl]-N,N-dimethyl-2-(morpholin-4-yl)-4-oxo-4H-1-benzopyran-6-carboxamide
-
 Mus musculus
ceramide selective inhibition of PI3KC2beta Homo sapiens
ceramide selective inhibition of PI3KC2beta Mus musculus
dactolisib
-
 Homo sapiens
dactolisib
-
 Mus musculus
duvelisib
-
 Homo sapiens
duvelisib
-
 Mus musculus
GDC-0941
-
 Homo sapiens
GDC-0941
-
 Mus musculus
LY294002 low inhibition Homo sapiens
LY294002 low inhibition Mus musculus
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; 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, AZD 3147, 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; no or poor inhibition by NVP-BYL719/buparlisib, 5-fluoro-3-phenyl-2-[(1S)-1-[(9H-purin-6-yl)amino]propyl]quinazolin-4(3H)-one, 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, and N-[3-(2-chloro-5-hydroxyanilino)pyrazin-2-yl]benzenesulfonamide Homo sapiens
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; 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; 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 Mus musculus
N-(5-[4-chloro-3-[(2-hydroxyethyl)sulfamoyl]phenyl]-4-methyl-1,3-thiazol-2-yl)acetamide
-
 Homo sapiens
N-(5-[4-chloro-3-[(2-hydroxyethyl)sulfamoyl]phenyl]-4-methyl-1,3-thiazol-2-yl)acetamide
-
 Mus musculus
N-(7,8-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)pyridine-3-carboxamide
-
 Homo sapiens
N-(7,8-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)pyridine-3-carboxamide
-
 Mus musculus
N-[2-[3-[(benzenesulfonyl)amino]phenyl]-4-(morpholin-4-yl)quinazolin-6-yl]acetamide
-
 Homo sapiens
N-[2-[3-[(benzenesulfonyl)amino]phenyl]-4-(morpholin-4-yl)quinazolin-6-yl]acetamide
-
 Mus musculus
N-[3-(2-chloro-5-hydroxyanilino)pyrazin-2-yl]benzenesulfonamide
-
 Homo sapiens
N-[3-(2-chloro-5-hydroxyanilino)pyrazin-2-yl]benzenesulfonamide
-
 Mus musculus
N-[4-(morpholin-4-yl)-2-[3-[(naphthalene-2-sulfonyl)amino]phenyl]quinazolin-6-yl]acetamide
-
 Homo sapiens
N-[4-(morpholin-4-yl)-2-[3-[(naphthalene-2-sulfonyl)amino]phenyl]quinazolin-6-yl]acetamide
-
 Mus musculus
Wortmannin low inhibition Homo sapiens
Wortmannin low inhibition Mus musculus
ZSTK474
-
 Homo sapiens
ZSTK474
-
 Mus musculus
[6-(2-amino-1,3-benzoxazol-5-yl)imidazo[1,2-a]pyridin-3-yl](morpholin-4-yl)methanone
-
 Homo sapiens
[6-(2-amino-1,3-benzoxazol-5-yl)imidazo[1,2-a]pyridin-3-yl](morpholin-4-yl)methanone
-
 Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
plasma membrane
-
 Homo sapiens 5886
-
plasma membrane
-
 Mus musculus 5886
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens
Mg2+ required Mus musculus

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
190000
-
-
 Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate Homo sapiens
-
 ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
-
 ?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate Mus musculus
-
 ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens O00443
-
-
Homo sapiens O00750
-
-
Homo sapiens O75747
-
-
Mus musculus E9QAN8
-
-
Mus musculus O70167
-
-
Mus musculus Q61194
-
-

Source Tissue

Source Tissue Comment Organism Textmining
colon
-
 Homo sapiens
-
epithelium
-
 Homo sapiens
-
esophageal squamous cell carcinoma cell high expression level of PI3KC2beta Homo sapiens
-
additional information PI3KC2alpha is broadly expressed in human cells Homo sapiens
-
neuroblastoma cell
-
 Homo sapiens
-
pancreas
-
 Homo sapiens
-
pancreas low enzyme expression Homo sapiens
-
pancreatic cancer cell
-
 Homo sapiens
-
squamous epithelium
-
 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
 Homo sapiens ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
-
 ?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
 Mus musculus ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
-
 ?
additional information ATP and substrate binding of PI3K isozymes, overview Homo sapiens ?
-
-
additional information ATP and substrate binding of PI3K isozymes, overview Mus musculus ?
-
-

Subunits

Subunits Comment Organism
More class II PI3 kinase architecture, overview Mus musculus
More class II PI3 kinase architecture, overview. PI3KC2alpha has a distinctive N-terminal region containing a clathrin-binding domain, but it lacks proline-rich sequence repeats found in PI3KC2beta Homo sapiens
More class II PI3 kinase architecture, overview. PI3KC2beta lacks a distinctive N-terminal region containing a clathrin-binding domain that is found in PI3KC2alpha Homo sapiens
More class II PI3 kinase architecture, overview. PI3KC2gamma lacks a distinctive N-terminal region containing a clathrin-binding domain that is found in PI3KC2alpha Homo sapiens

Synonyms

Synonyms Comment Organism
class II phosphoinositide 3-kinase
-
 Homo sapiens
class II phosphoinositide 3-kinase
-
 Mus musculus
class II PI3K
-
 Homo sapiens
class II PI3K
-
 Mus musculus
PI3KC2alpha
-
 Mus musculus
PI3KC2alpha
-
 Homo sapiens
PI3KC2beta
-
 Homo sapiens
PI3KC2beta
-
 Mus musculus
PI3KC2gamma
-
 Mus musculus
PI3KC2gamma
-
 Homo sapiens
PIK3C2G
-
 Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Homo sapiens
ATP
-
 Mus musculus

Expression

Organism Comment Expression
Homo sapiens PI3KC2alpha mRNA is downregulated in islets from type 2 diabetic patients compared to nondiabetic individuals down

General Information

General Information Comment Organism
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 Mus musculus
malfunction downregulation of PI3KC2beta results the inhibition of early stage neuroblastoma formation. Serum-dependent lamellipodia formation has been significantly reduced in cells lacking PI3KC2beta. Selective inhibition of PI3KC2beta with ceramide has been shown to diminish PI3KC2beta-dependent lamellipodia formation, reducing ovarian cancer cell mobility. Blocking of PI3KC2? pathway results in the impairment of SKOV3 cell migration. Depletion of PI3KC2beta can increase resistance of cells to chemotherapeutics Homo sapiens
malfunction global deficiency of PI3KC2gamma causes a phenotype of hyperlipidemia, adiposity, and insulin resistance Mus musculus
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 Mus musculus
malfunction PI3KC2alpha mRNA is downregulated in islets from type 2 diabetic patients compared to nondiabetic individuals. PI3KC2alpha plays a sex-dependent role in the modulation of hypothalamic leptin action and systemic glucose homeostasis Homo sapiens
additional information PI3KC2beta catalytic site structure, overview Homo sapiens
physiological function importance of PI3KC2beta in ovarian cancer cell migration Mus musculus
physiological function PI3KC2alpha has a role in glucose transport and secretion. Possible role of PI3KC2alpha in carcinogenesis, possible involvement of PI3KC2alpha in breast cancer development, and potential involvement of PI3KC2alpha in tumor angiogenesis favoring lung cancer and melanoma. Role for PI3KC2alpha in platelet function. PI3KC2alpha regulates a basal pool of PtdIns3P in platelets that may lead to impaired regulation of the platelet's cytoskeletal-membrane system Homo sapiens
physiological function PI3KC2beta plays an essential role in neuroblastoma development by mediating functions of ITSN1 and by stabilizing metylocytomatosis viral oncogene (MYCN), an oncogene found in 20% of neuroblastoma cases and a marker for poor prognosis. Correlation between PI3KC2beta expression levels and esophageal squamous-cell carcinoma (ESCC) metastasis. PI3KC2beta is involved in the regulation of cell invasion in PCa cells, partly by activation of MEK/ERK pathways and partly by regulation of cell migration through regulation of Slug protein. This protein is essential for epithelial-mesenchymal transition (EMT), a process which enables cells to gain migratory and invasive properties. PI3KC2beta has no influence on PCa cell proliferation. But it plays crucial roles in cell motility, migration, and invasion. PI3KC2beta is involved in the regulation of cell migration and invasion in different cancers. Implication of PI3KC2beta in metastasis has been demonstrated in breast, prostate, and ovarian cancers. The enzyme has a key role in lamellipodia formation in ovarian cancer SKOV3 cells, allowing for the increase in cell motility. A specific role for this enzyme in ovarian cancer cell motility and, as a consequence, in cancer metastasis. Importance of PI3KC2beta in ovarian cancer cell migration. Overexpression of PI3KC2beta has been also found to enhance migration of A-431 epidermoid carcinoma cells, HeLa and ovarian cancer cells, whereas overexpression of the negative PI3KC2beta is able to reduce this process. Possible mechanism of contribution of PI3KC2beta in cancer cell migration and metastasis included PIK3C2B is regulated by miR-515-5p, which plays a role in the control of cancer cell migration and metastasis. Overexpression of miR-515-5p downregulates PIK3C2B, among others, binding directly to its 3'-UTR region Homo sapiens
physiological function PIK3C2G, the gene encoding PI3KC2gamma, acts mainly as a tumor suppressor gene. Low PI3KC2gamma expression influences colorectal cancer (CRC) development, with low copy number of PIK3C2G associated with a 2.5fold increase in the risk of death Homo sapiens