Phosphatase Subfamily PPIP5K

Phosphatase Classification: Fold HP: Superfamily HP (histidine phosphatase): Family HP, branch 2: PPIP5K

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

Evolution

PPIP5K is found in most eukaryotes except for some excavate. Most vertebrates have at least two copies, while invertebrates usually have one.

Domain

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

Unlike other members of HP2 family which are protein or non-protein phosphatases, the HP2 domain of PPIP5K is not catalytically active. Instead, this HP2 domain is specialized for binding PtdIns(3,4,5)P3, as a partial PH (pleckstrin homology) consensus sequence is spliced into this HP2 domain [3].

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 conservatively inactive in other genomes.

References

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