Phosphatase Subfamily PPM1G

Phosphatase Classification: Fold PPM (PP2C): Superfamily PPM (PP2C): Family PPM (PP2C): Subfamily PPM1G

Evolution

PPM1G emerged in holozoa, usually single copy per genome. Human has a single PPM1G (PP2CG/PP2Cγ/FIN13).

Domain

PPM1G has a single structural domain, the phosphatase domain of PPM fold. Unlike any other known phosphatase, PPM1G has a highly acidic domain: 75% of the 54 residues are glutamate or aspartate [1].

Functions

Like known PPM (PP2Cs), recombinant PPM1G requires Mg2+ or Mn2+ for activity [1]. Human PPM1G has the substrates below:

• Deubiquitylation enzyme USP7/HAUSP. PPM1G dephosphorylates USP7S which leads to USP7S downregulation, followed by Mdm2 downregulation and accumulation of p53 [2].

• 4E binding protein 1 (4E-BP1). PPM1G regulates protein translation and cell growth by dephosphorylating 4E binding protein 1 (4E-BP1), which binds to translation initiation factor 4E and inhibits cap-dependent translation in a phosphorylation-dependent manner [3].

Northern blot analysis shows that human PPM1G is widely expressed, and is most abundant in testis, skeletal muscle, and heart [1]. RNA-seq data from GTEx also shows its broad expression in different tissues and particularly abundant in testis.

PPM1G may have other functions and/or be involved in other processes. PPM1G inactivates monomeric the E3 ligase WWP2 and promotes the assembly of two E3 ligases WWP2-WWP1 heterodimeric complex [4]. It is unclear whether PPM1G dephosphorylates WWP1 or WWP2.

Besides, PPM1G is associated with alcohol use disorder [5].

References

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