Inositol-1,4,5-Trisphosphate-3-Kinase A (ITPKA)

Regulates inositol phosphate metabolism by phosphorylation of second messenger inositol 1,4,5-trisphosphate to Ins(1,3,4,5)P4. The activity of the inositol 1,4,5-trisphosphate 3-kinase is responsible for regulating the levels of a large number of inositol polyphosphates that are important in cellular signaling.

The N-terminal and C-terminal lobes bind ATP and resemble other protein and lipid kinases. In the apo form, the N-terminal helix of the N-terminal lobe occupies much of the volume of the positively charged ATP binding pocket. The alpha-only subdomain binds all of the phosphates of Ins(1,4,5)P3 in a positively charged pocket, explaining the enzyme's substrate specificity and its inability to phosphorylate PtdIns(4,5)P2 due to stearic hindrance.