Phosphatase Subfamily PGP

Phosphatase Classification: Fold HAD: Superfamily HAD: Family NagD: Subfamily PGP

PGP is ubiquitous in eukaryotes. The two members in human have distinct functions: PDXP (aka chronophin) dephosphorylates protein cofilin on serine residue, as well as pyridoxal 5'-phosphate; PGP is a putative tyrosine-specific protein phosphatase. PDXP is mainly expressed in brain; PGP is widely expressed in different tissues.

Evolution

The PGP subfamily is extremely conserved in eukaryotes, rarely absent from eukaryotic genomes. Human has two members of this subfamily: PGP and PDXP. Specific PGP and PDXP orthologs are found in all vertebrates and likely originate in the vertebrate whole genome duplication.

Domain

The PGP subfamily has a single domain: HAD domain.

Function

PDXP (Chronophin) is abundantly expressed in brain [1] (see also GTEx RNA-seq data). PDXP has two distinct substrates.

• Pyridoxal 5'-phosphate. PDXP was first identified as pyridoxal phosphatase, which catalyzes the dephosphorylation of pyridoxal 5'-phosphate (PLP) and pyridoxine 5'-phosphate. PLP is the active form of vitamin B6 that acts as a coenzyme in maintaining biochemical homeostasis [1, 2, 3].

• Protein cofilin. PDXP dephosphorylates cofilin at serine, therefore regulating assembly and disassembly of actin filaments [4, 5, 6]. It is worthy pointing out that another phosphatse subfamily, slingshot, also dephosphorylates cofilin.

In contrast with PDXP, PGP (AUM) is widely expressed in different tissues (see also GTEx RNA-seq data). PGP is a putative tyrosine-specific phosphatase [7], but its physiological substrate needs to be found.

References

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