Phosphatase Subamily Paladin

Phosphatase Classification: Fold CC1: Superfamily CC1: Family Paladin: Subfamily Paladin

Evolution

Paladins are found in vertebrates and early metazoa such as sponge, trichoplax and nematostella but absent from arthropoda and nematoda. Paladins are also found in most plants and a small number of fungi (see internal database gOrtholog).

Domain

Paladins have two CC1 phosphatase domains similar to each other in sequence. They are similar to bacterial cysteine phytases whose crystal structures have a CC1 fold (so called "PTP-like") [1, 2, 3, 4]. Similar to protein phosphatases of CC1 fold such as PTPs and DSPs, these phytases are cysteine-based and have CX₅R motif. Both of phosphatase domains of paladin contain CX₅R motif. Based upon our current understanding of CC1 fold phosphatases, we predict paladin to be catalytically active.

Notes:

• The cysteine phytases is a class of phytases. The phytases remove phosphate from myo-inositol 1,2,3,4,5,6-hexakisphosphate. They have four distinct folds, including purple acid phosphatase in human.
• The homology between paladin and cysteine phytases were detected by HHpred and BLASTing against PDB database. The top hits of HHpred are cysteine phytases with identity around 20% followed by DSPs with slightly higher identity but lower coverage.

Function

Paladin has been very little studied. Human Paladin (PALD, PALD1) was found as an inhibitor of insulin signaling by knockdown and overexpression. Similar over and under-expression showed a role in neural crest cell formation and migration in chicken [5] and mutation of the two Cx5R cysteines did not affect this function.

Paladin's physiological substrate(s) is unclear. But, the bacterial cysteine phytases dephosphorylate myo-inositol 1,2,3,4,5,6-hexakisphosphate, but not pTyr [1].

References

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