Phosphatase Subfamily PPM1A

Phosphatase Classification: Fold PPM (PP2C): Superfamily PPM (PP2C): Family PPM (PP2C): Subfamily PPM1A

Evolution

The PPM1A subfamily is found across holozoan.

PPM1N probably emerged in placentals and lost by independent evolutionary events in different lineages, as implied by internal orthology database and BLAST NR database. For BLAST, human PPM1N was defined as the hits that have a better (lower) E-values than human PPM1A and PPM1B.

Functions

Human PPM1B

PPM1B is expressed in a broad types of tissues, most abundantly in skeletal muscle (see RNA-seq data from GTEx). It dephosphorylates Ser-172 of kinase TBK1 and negatively regulates antiviral response [1].

PKA phosphorylates PPM1B at Ser-195 [2]. The Ser-195 and PKA regulation on its phosphorylation state is a signature of PPM1A subfamily, because 1) all PPM1A members have serine at the position, 2) PPMs of other subfamilies only have serine, occasionally.

Human PPM1N

PPM1N's function is unknown. It is generally expressed at low level across tissues except spleen (see RNA-seq data from GTEx).

Fruit fly alph (alphabet): negatively regulates RAS/MAPK and SAPK

Alphabet, the PPM1A in fruit fly, negatively regulates RAS/MAPK signaling in Drosophila [3] and stress-activated protein kinase (SAPK) [4]. However, its substrates in these signaling pathways are unclear.

References

1. Zhao Y, Liang L, Fan Y, Sun S, An L, Shi Z, Cheng J, Jia W, Sun W, Mori-Akiyama Y, Zhang H, Fu S, and Yang J. PPM1B negatively regulates antiviral response via dephosphorylating TBK1. Cell Signal. 2012 Nov;24(11):2197-204. DOI:10.1016/j.cellsig.2012.06.017 |
2. Choi HK, Park SY, Oh HJ, Han EJ, Lee YH, Lee J, Jun WJ, Choi KC, and Yoon HG. PKA negatively regulates PP2Cβ to activate NF-κB-mediated inflammatory signaling. Biochem Biophys Res Commun. 2013 Jul 5;436(3):473-7. DOI:10.1016/j.bbrc.2013.05.129 |
3. Baril C and Therrien M. Alphabet, a Ser/Thr phosphatase of the protein phosphatase 2C family, negatively regulates RAS/MAPK signaling in Drosophila. Dev Biol. 2006 Jun 1;294(1):232-45. DOI:10.1016/j.ydbio.2006.02.046 |
3. Baril C, Sahmi M, Ashton-Beaucage D, Stronach B, and Therrien M. The PP2C Alphabet is a negative regulator of stress-activated protein kinase signaling in Drosophila. Genetics. 2009 Feb;181(2):567-79. DOI:10.1534/genetics.108.096461 |