Phosphatase Subfamily PPIP5K

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Phosphatase Classification: Fold HP: Superfamily HP: Family HP, branch 2 (HP2): Subfamily PPIP5K

PPIP5K is a phosphoinositol kinase that also has a pseudophosphatase domain which binds to PtdIns(3,4,5)P3. PPIP5K converts InsP6 and 5-InsP7 to 1-InsP7 and InsP8.


PPIP5K is found in most eukaryotes, but is missing in alveolates. Most vertebrates have at least two copies, while invertebrates usually have one.


PPIP5K has two domains: N-terminal RimK/ATP-grasp kinase domain, and C-terminal HP2 phosphatase domain [1]. The RimK is the active kinase domain [1, 2].

Unlike other HP2 subfamilies which are protein or non-protein phosphatases, the HP2 domain of PPIP5K is not catalytically active. Instead, it binds PtdIns(3,4,5)P3, in part using an inserted partial PH (pleckstrin homology) domain [3]. The HP2 domains of PPIP5Ks are longer than those of other HP2 subfamilies, due to insertions at multiple sites.

Catalytic activity and functions

The phosphatase domains of human PPIP5K1 and PPIP5K2 are catalytically inactive, though they bear the histidine residue at catalytic core (figure 5 in [4]). It is unclear whether PPIP5K are inactive in other genomes.


  1. Fridy PC, Otto JC, Dollins DE, and York JD. Cloning and characterization of two human VIP1-like inositol hexakisphosphate and diphosphoinositol pentakisphosphate kinases. J Biol Chem. 2007 Oct 19;282(42):30754-62. DOI:10.1074/jbc.M704656200 | PubMed ID:17690096 | HubMed [fridy07]
  2. Choi JH, Williams J, Cho J, Falck JR, and Shears SB. Purification, sequencing, and molecular identification of a mammalian PP-InsP5 kinase that is activated when cells are exposed to hyperosmotic stress. J Biol Chem. 2007 Oct 19;282(42):30763-75. DOI:10.1074/jbc.M704655200 | PubMed ID:17702752 | HubMed [choi07]
  3. Gokhale NA, Zaremba A, and Shears SB. Receptor-dependent compartmentalization of PPIP5K1, a kinase with a cryptic polyphosphoinositide binding domain. Biochem J. 2011 Mar 15;434(3):415-26. DOI:10.1042/BJ20101437 | PubMed ID:21222653 | HubMed [gokhale11]
  4. Rigden DJ. The histidine phosphatase superfamily: structure and function. Biochem J. 2008 Jan 15;409(2):333-48. DOI:10.1042/BJ20071097 | PubMed ID:18092946 | HubMed [rigden08]
All Medline abstracts: PubMed | HubMed