Activating Compound | Comment | Organism | Structure |
---|---|---|---|
RAS-GTP | regulatory domain p85 interacts with RAS-GTP. RAS binding is essential for oncogenic transformation by helical domain mutants of p110alpha | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
E542K/E545K | gain-of-function helical domain mutations result in upregulation of enzyme activity, Akt phosphorylation and cell transformation | Homo sapiens |
E545K/H1047R | gain-of-function helical domain mutations result in upregulation of enzyme activity, Akt phosphorylation and cell transformation | Homo sapiens |
H1047R | gain-of-function mutation of subunit p110alpha, the H1047R mutation can substitute for RAS binding, but binding to p85 is essential for H1047R-induced cell transformation | Homo sapiens |
K227E | the mutaion reduces enzyme activity | Homo sapiens |
additional information | helical domain and kinase domain mutations in p110alpha of phosphatidylinositol 3-kinase induce gain of function by different mechanisms, overview. About 30% of prostate, breast, cervix, and endometrium tumors show catalytic subunit p110alpha mutations, the most prominent single amino acid substitutions in the helical or kinase domain result in a gain of enzymatic function, activate AKT signaling, and induce oncogenic transformation, analysis of hot-spot mutations in gene PIK3CA. The gain of function induced by helical domain mutations is independent of binding to p85 but requires interaction with RAS-GTP. In contrast, the kinase domain mutation is active in the absence of RAS-GTP binding but is highly dependent on the interaction with p85. Truncation reduce the activities of all enzymes, truncated wild-type and mutant, overview. Phenotypes, overview | Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
gene PIK3CA encoding for the catalytic subunit p110alpha of PI3K | - |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
breast cancer cell | - |
Homo sapiens | - |
cervical carcinoma cell | - |
Homo sapiens | - |
endometrial cancer cell line | - |
Homo sapiens | - |
prostate cancer cell line | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | regulatory domain p85 interacts with RAS-GTP | Homo sapiens | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
heterodimer | catalytic subunit p110alpha and regulatory subunit p85. p85 binding to p110alpha is required for activity | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
PI3K | - |
Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
metabolism | PI3K is part of the PI3K signaling pathway that is upregulated in cancer | Homo sapiens |