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
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.
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].
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.
PPM1G is associated with alcohol use disorder [5].
References
- Travis SM and Welsh MJ. PP2C gamma: a human protein phosphatase with a unique acidic domain. FEBS Lett. 1997 Aug 4;412(3):415-9. DOI:10.1016/s0014-5793(97)00837-5 |
- Khoronenkova SV, Dianova II, Ternette N, Kessler BM, Parsons JL, and Dianov GL. ATM-dependent downregulation of USP7/HAUSP by PPM1G activates p53 response to DNA damage. Mol Cell. 2012 Mar 30;45(6):801-13. DOI:10.1016/j.molcel.2012.01.021 |
- Liu J, Stevens PD, Eshleman NE, and Gao T. Protein phosphatase PPM1G regulates protein translation and cell growth by dephosphorylating 4E binding protein 1 (4E-BP1). J Biol Chem. 2013 Aug 9;288(32):23225-33. DOI:10.1074/jbc.M113.492371 |
- Chaudhary N and Maddika S. WWP2-WWP1 ubiquitin ligase complex coordinated by PPM1G maintains the balance between cellular p73 and ΔNp73 levels. Mol Cell Biol. 2014 Oct 1;34(19):3754-64. DOI:10.1128/MCB.00101-14 |
- Ruggeri B, Nymberg C, Vuoksimaa E, Lourdusamy A, Wong CP, Carvalho FM, Jia T, Cattrell A, Macare C, Banaschewski T, Barker GJ, Bokde AL, Bromberg U, Büchel C, Conrod PJ, Fauth-Bühler M, Flor H, Frouin V, Gallinat J, Garavan H, Gowland P, Heinz A, Ittermann B, Martinot JL, Nees F, Pausova Z, Paus T, Rietschel M, Robbins T, Smolka MN, Spanagel R, Bakalkin G, Mill J, Sommer WH, Rose RJ, Yan J, Aliev F, Dick D, Kaprio J, Desrivières S, Schumann G, and IMAGEN Consortium. Association of Protein Phosphatase PPM1G With Alcohol Use Disorder and Brain Activity During Behavioral Control in a Genome-Wide Methylation Analysis. Am J Psychiatry. 2015 Jun;172(6):543-52. DOI:10.1176/appi.ajp.2014.14030382 |
