Inositol-pentakisphosphate 2-kinase (IPPK)

Inositol-pentakisphosphate 2-kinase (IPPK) is an enzyme of the inositol kinase family responsible for catalyzing the phosphorylation of inositol 1,3,4,5,6-pentakisphosphate (InsP5) to produce inositol hexakisphosphate (InsP6 or phytic acid), using ATP as a phosphate donor[1][2][3]. IPPK is highly specific for transferring a phosphate to the axial 2-OH position of the myo-inositol ring—a unique feature among inositol kinases[2]. The enzyme and its product, InsP6, are essential for multiple cellular processes, including mRNA export, chromatin remodeling, DNA repair, embryonic development, apoptosis, and act as cofactors for other enzymatic activities[1][2]. Disruption or genetic knockout of IPPK is embryonically lethal in mice, indicating a non-redundant and essential function[1][2]. Human and mammalian orthologues have unique protein structural features, including distinct zinc-binding sites and basic protein surface patches that may mediate interactions with other proteins or nucleic acids[1]. While no clinically approved drugs directly targeting IPPK exist, its central role in inositol phosphate metabolism makes it a point of interest for the development of inhibitors to probe cellular function and possibly for cancer research, as InsP6 analogs have shown antitumor effects, likely through pathway modulation (e.g., PI3K/Akt inhibition)[2].

Other names

Inositol-pentakisphosphate 2-kinaseIPPKC9orf12InsP5 2-kinaseINSP5K2FLJ13163IP5KIPK1IPK1 homologInositol-1,3,4,5,6-pentakisphosphate 2-kinaseIns(1,3,4,5,6)P5 2-kinasebA476B13.1inositol-pentakisphosphate 2-kinaseinositol 1,3,4,5,6-pentakisphosphate 2-kinaseins(1,3,4,5,6)P5 2-kinaseinsP5 2-kinase

For hypothetical/experimental inhibitors: competitive inhibition of catalytic kinase activity; blockage of ATP or substrate binding, inhibition of phosphate transfer to substrate