Domain

PI3K p85 subunit, inter-SH2 domain (IPR032498)

Short name: PI3K_P85_iSH2

Domain relationships

None.

Description

This domain is found between the two SH2 domains in phosphatidylinositol 3-kinase regulatory subunit P85 (PI3K p85 subunit).

Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and 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 [PMID: 21362552].

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 [PMID: 19915146]. 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 [PMID: 19926274].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
Pfam