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]. It is not known whether paladin acts as a protein or non-protein phosphatases. Most Paladins have two active domains, as seen by retention of the Cx5R catalytic motif, but some have a single inactive domain, and rarely, both domains are inactive.

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 shown to inhibit of insulin signaling by decreasing phosphorylation of Akt, both by knockdown and overexpression, though it was not determined if paladin is an Akt phosphatase [5]. In a related patent filing it was claimed that mutation of the catalytic cysteine in the first domain abolished this activity, but mutation of the second domain did not, and that paladin physically associates with the insulin receptor. Similar over- and under-expression showed a role in neural crest cell formation and migration in chicken [6] and mutation of the two Cx5R cysteines did not affect this function. Paladin's physiological substrate(s) is unclear. Bacterial cysteine phytases dephosphorylate myo-inositol 1,2,3,4,5,6-hexakisphosphate, but not pTyr [1].

References

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