PI3K-C2α has a clathrin-binding domain (CBD) containing the clathrin box motif consensus sequence, whereas the N-terminal proline-rich region of PI3K-C2β directly binds to the SH3 domain of intersectin-1 (ITSN) via its ITSN-binding domain. PI3K-C2α also present a PX-domain that is responsible to the binding of PI(4,5)P2 in plasma membranes. C2, protein kinase C conserved region 2 (C2 domain), Catalytic, catalytic domain; CBD, clathrin-binding domain; Helical, helical domain; P, proline-rich region; PX, phox homology (PX domain). Ras, Ras-binding domain.