The significance of the 1-kinase/1-phosphatase activities of the PPIP5K family

Adv Biol Regul. 2017 Jan;63:98-106. doi: 10.1016/j.jbior.2016.10.003. Epub 2016 Oct 17.


The inositol pyrophosphates (diphosphoinositol polyphosphates), which include 1-InsP7, 5-InsP7, and InsP8, are highly 'energetic' signaling molecules that play important roles in many cellular processes, particularly with regards to phosphate and bioenergetic homeostasis. Two classes of kinases synthesize the PP-InsPs: IP6Ks and PPIP5Ks. The significance of the IP6Ks - and their 5-InsP7 product - has been widely reported. However, relatively little is known about the biological significance of the PPIP5Ks. The purpose of this review is to provide an update on developments in our understanding of key features of the PPIP5Ks, which we believe strengthens the hypothesis that their catalytic activities serve important cellular functions. Central to this discussion is the recent discovery that the PPIP5K is a rare example of a single protein that catalyzes a kinase/phosphatase futile cycle.

Publication types

  • Review

MeSH terms

  • Acid Anhydride Hydrolases / genetics
  • Acid Anhydride Hydrolases / metabolism*
  • Amino Acid Motifs
  • Energy Metabolism / genetics
  • Gene Expression Regulation
  • Humans
  • Inositol Phosphates / metabolism*
  • Phosphotransferases (Phosphate Group Acceptor) / chemistry
  • Phosphotransferases (Phosphate Group Acceptor) / genetics
  • Phosphotransferases (Phosphate Group Acceptor) / metabolism*
  • Phytic Acid / metabolism*
  • Protein Domains
  • Signal Transduction


  • Inositol Phosphates
  • inositol heptakisphosphate
  • Phytic Acid
  • Phosphotransferases (Phosphate Group Acceptor)
  • PPIP5K1 protein, human
  • Acid Anhydride Hydrolases
  • diphosphoinositol polyphosphate phosphohydrolase