| Type: | Conserved_site | Name: | Phosphatidylinositol 3/4-kinase, conserved site |
| Description: | Phosphatidylinositol 3-kinase (PI3-kinase) () [] is an enzymethat phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol ring. The three products of PI3-kinase - PI-3-P,PI-3,4-P(2) and PI-3,4,5-P(3) function as secondary messengers in cell signalling. Phosphatidylinositol 4-kinase (PI4-kinase) () [] is an enzymethat acts on phosphatidylinositol (PI) in the first committed step in the production of the secondary messenger inositol-1'4'5'-trisphosphate. This domain is also present in a wide range of protein kinases, involved in diverse cellular functions, such as control of cell growth, regulation of cell cycle progression, a DNA damage checkpoint, recombination, and maintenance of telomere length. Despite significant homology to lipid kinases, no lipid kinase activity has been demonstrated for any of the PIK-related kinases [].The PI3- and PI4-kinases share a well conserved domain at their C-terminal section; this domain seems to be distantly related to the catalytic domain ofprotein kinases [, ]. The catalytic domain of PI3K has the typical bilobal structure that is seen in other ATP-dependentkinases, with a small N-terminal lobe and a large C-terminal lobe. The core of this domain is the most conserved region of the PI3Ks. The ATP cofactor binds in the crevice formed by the N-and C-terminal lobes, a loop between two strands providesa hydrophobic pocket for binding of the adenine moiety, and a lysine residue interacts with the alpha-phosphate. In contrast to protein kinases, the PI3K loop which interacts with thephosphates of the ATP and is known as the glycine-rich or P-loop, contains no glycine residues. Instead, contact with the ATP -phosphate is maintained through the side chain of a conserved serine residue. | Short Name: | PI3/4_kinase_CS |
