InterPro domain: IPR043001

This superfamily represents the N-terminal lobe found in inositol-pentakisphosphate 2-kinases (also known as inositol 1,3,4,5,6-pentakisphosphate 2-kinase, Ins(1,3,4,5,6)P5 2-kinase, InsP5 2-kinase, and IP5 2-K). This enzyme phosphorylates Ins(1,3,4,5,6)P5 to form Ins(1,2,3,4,5,6)P6 (also known as InsP6 or phytate). InsP6 is involved in many processes such as mRNA export, nonhomologous end-joining, endocytosis and ion channel regulation [ 1 , 2 ].

The IP5 2-K fold consists of two lobes connected by a hinge, referred to as N-terminal lobe and C-terminal lobe. The N-terminal lobe has an alpha/beta fold, the core of this lobe being formed by an antiparallel and twisted main beta-sheet comprised of five beta-strands. The C-terminal lobe is almost twice the size of the N-terminal lobe and also has an alpha/beta fold. The beta-strands form an antiparallel twisted beta-sheet. The alpha-helices in this lobe are distributed in three noncontinuous regions that emerge from the beta-sheet and comprise almost half of the protein, they are involved in the inositide binding (CIP-lobe) [ 3 ].

1. Biochemical and functional characterization of inositol 1,3,4,5, 6-pentakisphosphate 2-kinases. J. Biol. Chem. 275, 36575-83
2. Inositol 1,3,4,5,6-pentakisphosphate 2-kinase is a distant IPK member with a singular inositide binding site for axial 2-OH recognition. Proc. Natl. Acad. Sci. U.S.A. 107, 9608-13