| Primary Identifier | IPR008290 | Type | Family |
| Short Name | PI3K_Vps34 |
| description | Members of this family are Class III phosphatidylinositol 3-kinases (PI3Ks) (catalytic subunits). PI3K is a lipid kinase and a key signalling enzyme involving in cell survival and proliferation, cell motility and adhesion, cytoskeletal rearrangement and vesicle trafficking []. The different PI3K isoforms have cell-specific functions. In yeast, VPS34 is a key enzyme required for cell division, vacuolar protein sorting, and vacuole segregation []. The major components of the yeast VPS intracellular trafficking complex are conserved in humans [].There are three major classes of PI3Ks, I and III (Class I is also subdivided into Ia and Ib), and a more distantly relatedClass IV which contains Ser/Thr kinases. The different classes of PI3K catalyse phosphorylation of the 3'-OH position of phosphatidyl myo-inositol (PtdIns) lipids, generating different 3'-phosphorylated lipid products that act as secondary messengers. The classification of PI3Ks is based upon sequence analysis and domain architecture of the catalytic subunits, but the divisions also reflect the biochemical properties and the differential association with a variety of regulatory adaptor subunits. This division is mirrored not only in their specialised functions but also in the different modes of regulation of the different enzymes in the family []. Furthermore, each of the PI3K classes differ in their preferred lipid substrate. Class III PI3Ks use only phosphatidylinositol as substrate, whereas Class Ia and Ib PI3K activity is focused upon phosphatidylinositol (4,5)-bisphosphate as substrate in vivo []. These substrate-related differences are presumed to result from subtle variations in the structures of the active sites of the different PI3Ks.Class III PI3Ks contain only the core catalytic subunit, which consists of the N-terminal C2 domain, the helical domain and the double-lobed catalytic domain. Class I and II contain an additional Ras-binding domain. The N-terminal C2 domain interacts mainly with the scaffolding helical domain of the enzyme []. The function of the central helical domain is not clear, it has been suggested to be involved in substrate presentation []. The C-terminal catalytic domain is shared by the PI3- and PI4-kinases. This domain is distantly related to the catalytic domain of protein kinases, with a global similarity of the core topological features but significantdifferences in the substrate-binding sites [].For additional information please see []. |
