InterPro domain: IPR002420

Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that phosphorylate 4,5-bisphonate (PI(4,5) P2 or PIP2) at the 3-position of the inositol ring, and thus generate phosphatidylinositol 3,4,5-trisphosphate (PIP3), which, in turns, initiates a vast array of signaling events. PI3Ks can be grouped intothree classes based on their domain organisation. Class I PI3Ks are heterodimers consisting of a p110 catalytic subunit and a regulatory subunit of either the p85 type (associated with the class IA p110 isoforms p110alpha, p110beta or p110delta) or the p101 type (associated with the class IB p110isoform p110gamma). Common to all catalytic subunits are an N-terminal adaptor-binding domain (ABD) that binds to p85, a Ras- binding domain (RBD), a putative membrane-binding domain (C2), a helical domain of unknown function, and a kinase catalytic domain. Class II PI3Ks lack the ABD domain and are distinguished by a carboxy terminal C2 domain. Class III enzymes lack the ABD and RBD domains [ 1 , 2 , 3 , 4 ].

The PI3K-type C2 domain is an eight-stranded antiparallel beta-sandwich consisting of two four-stranded beta-sheets [ 5 , 5 , 5 , 5 ].

1. Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit. Science 317, 239-42
2. The structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations. Science 318, 1744-8
3. The p110 delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors. Nat. Chem. Biol. 6, 117-24
4. Structural insights into phosphoinositide 3-kinase catalysis and signalling. Nature 402, 313-20