Pathways & interactions
Phosphatidylinositol 3-/4-kinase, catalytic domain (IPR000403)
Short name: PI3/4_kinase_cat_dom
Overlapping homologous superfamilies
- Phosphatidylinositol 3-/4-kinase, catalytic domain (IPR000403)
- DNA-dependent protein kinase catalytic subunit, catalytic domain (IPR037706)
- PI3K-C2-alpha, catalytic domain (IPR037705)
- PI3K-C2-gamma, catalytic domain (IPR037707)
- PI3Kalpha, catalytic domain (IPR037704)
- PI3Kbeta, catalytic domain (IPR037702)
- PI3Kdelta, catalytic domain (IPR037703)
- SMG1, PIKK catalytic domain (IPR039414)
Phosphatidylinositol 3-kinase (PI3-kinase) (EC:188.8.131.52) [PMID: 1322797] is an enzyme that 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) (EC:184.108.40.206) [PMID: 8194527] is an enzyme that 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 [PMID: 12456783].
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 of protein kinases [PMID: 8387896, PMID: 12151228]. The catalytic domain of PI3K has the typical bilobal structure that is seen in other ATP-dependent kinases, 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 provides a 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 the phosphates 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.
This domain is also found in a number of pseudokinases, where a lack of typical motifs at the calatytic site suggest a lack of kinase activity.