| Primary Identifier | IPR035020 | Type | Domain |
| Short Name | PI3kinase_P85_cSH2 |
| description | This entry represents the C-terminal SH2 domain (cSH2) found in the PI3K p85 subunit.Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. Class IA PI3Ks are heterodimers of a p110 catalytic (C) subunit and a p85-related regulatory (R) subunit []. p110 is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. p85 is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, a inter SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are two inhibitory interactions between p110alpha and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and 2) p85 iSH2 domain with C2 domain of p110alpha. There are three inhibitory interactions between p110beta and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, 2) p85 iSH2 domain with C2 domain of p110beta, and 3) p85 cSH2 domain with the kinase domain of p110beta []. p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain []. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites [].In mammals, there are multiple class IA PI3K regulatory and catalytic subunits. There are three genes that encode at least five different regulatory subunit proteins (p85alpha, p55alpha, p50alpha, p85beta, and p55gamma) and three genes encoding three catalytic subunits (p110alpha, p110beta, and p110delta) []. |
