Phosphatase Subfamily PGP

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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.

Yeast has a single member PHO13, which has phosphatase activity on the serines of proteins histone II-A and casein [8].

References

  1. Jang YM, Kim DW, Kang TC, Won MH, Baek NI, Moon BJ, Choi SY, and Kwon OS. Human pyridoxal phosphatase. Molecular cloning, functional expression, and tissue distribution. J Biol Chem. 2003 Dec 12;278(50):50040-6. DOI:10.1074/jbc.M309619200 | PubMed ID:14522954 | HubMed [Jang03]
  2. Gao G and Fonda ML. Identification of an essential cysteine residue in pyridoxal phosphatase from human erythrocytes. J Biol Chem. 1994 Mar 18;269(11):8234-9. PubMed ID:8132548 | HubMed [Gao94]
  3. Kim DW, Eum WS, Choi HS, Kim SY, An JJ, Lee SH, Sohn EJ, Hwang SI, Kwon OS, Kang TC, Won MH, Cho SW, Lee KS, Park J, and Choi SY. Human brain pyridoxal-5'-phosphate phosphatase: production and characterization of monoclonal antibodies. J Biochem Mol Biol. 2005 Nov 30;38(6):703-8. DOI:10.5483/bmbrep.2005.38.6.703 | PubMed ID:16336786 | HubMed [Kim05]
  4. Gohla A, Birkenfeld J, and Bokoch GM. Chronophin, a novel HAD-type serine protein phosphatase, regulates cofilin-dependent actin dynamics. Nat Cell Biol. 2005 Jan;7(1):21-9. DOI:10.1038/ncb1201 | PubMed ID:15580268 | HubMed [Gohla05]
  5. Huang TY, Minamide LS, Bamburg JR, and Bokoch GM. Chronophin mediates an ATP-sensing mechanism for cofilin dephosphorylation and neuronal cofilin-actin rod formation. Dev Cell. 2008 Nov;15(5):691-703. DOI:10.1016/j.devcel.2008.09.017 | PubMed ID:19000834 | HubMed [Huang08]
  6. Kestler C, Knobloch G, Tessmer I, Jeanclos E, Schindelin H, and Gohla A. Chronophin dimerization is required for proper positioning of its substrate specificity loop. J Biol Chem. 2014 Jan 31;289(5):3094-103. DOI:10.1074/jbc.M113.536482 | PubMed ID:24338687 | HubMed [Kestler14]
  7. Seifried A, Knobloch G, Duraphe PS, Segerer G, Manhard J, Schindelin H, Schultz J, and Gohla A. Evolutionary and structural analyses of mammalian haloacid dehalogenase-type phosphatases AUM and chronophin provide insight into the basis of their different substrate specificities. J Biol Chem. 2014 Feb 7;289(6):3416-31. DOI:10.1074/jbc.M113.503359 | PubMed ID:24338473 | HubMed [Seifried14]
  8. Tuleva B, Vasileva-Tonkova E, and Galabova D. A specific alkaline phosphatase from Saccharomyces cerevisiae with protein phosphatase activity. FEMS Microbiol Lett. 1998 Apr 1;161(1):139-44. DOI:10.1111/j.1574-6968.1998.tb12940.x | PubMed ID:9561742 | HubMed [Tuleva98]
All Medline abstracts: PubMed | HubMed