It has been found that PtdIns is only phosphorylated on three (3,4,5) of its five hydroxyl groups, possibly because D-2 and D-6 hydroxyl groups cannot be phosphorylated because of steric hindrance.
[2] PIPKs are today divided into three groups, type I, II and III that share significant sequence homology but differ in the substrate specificities, subcellular localisations and functions.
Type II PIPKs phosphorylate PtdIns5P at the D-4 site and are called PtdIns5P 4-kinases.
The substrate specificity of type I and II depends on the so-called activation loop.
The activation loop is a segment of 22 to 27 amino acid residues, located close to the C-terminal end of the catalytic domain in all PIPKs.