Journal of Molecular Evolution

, Volume 64, Issue 1, pp 61–70 | Cite as

Evolution of the Metazoan Protein Phosphatase 2C Superfamily

  • Adi Stern
  • Eyal Privman
  • Michal Rasis
  • Sara Lavi
  • Tal Pupko


Members of the protein phosphatase 2C (PP2C) superfamily are Mg2+/Mn2+-dependent serine/threonine phosphatases, which are essential for regulation of cell cycle and stress signaling pathways in cells. In this study, a comprehensive genomic analysis of all available metazoan PP2C sequences was conducted. The phylogeny of PP2C was reconstructed, revealing the existence of 15 vertebrate families which arose following a series of gene duplication events. Relative dating of these duplications showed that they occurred in two active periods: before the divergence of bilaterians and before vertebrate diversification. PP2C families which duplicated during the first period take part in different signaling pathways, whereas PP2C families which diverged in the second period display tissue expression differences yet participate in similar signaling pathways. These differences were found to involve variation of expression in tissues which show higher complexity in vertebrates, such as skeletal muscle and the nervous system. Further analysis was performed with the aim of identifying the functional domains of PP2C. The conservation pattern across the entire PP2C superfamily revealed an extensive domain of more than 50 amino acids which is highly conserved throughout all PP2C members. Several insertion or deletion events were found which may have led to the specialization of each PP2C family.


Protein phosphatase 2C Gene duplication Phylogeny 



We thank Dorothee Huchon for her insightful comments. A.S. is a fellow of the Edmond J. Safra Program in Bioinformatics at Tel Aviv University. S.L was supported by the Linda Tallen and David Paul Kane Educational & Research Foundation. T.P. was supported by ISF Grant 1208/04 and by a grant in Complexity Science from the Yeshaia Horvitz Association.

Supplementary material

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Supplementary material


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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Adi Stern
    • 1
  • Eyal Privman
    • 1
  • Michal Rasis
    • 1
  • Sara Lavi
    • 1
  • Tal Pupko
    • 1
  1. 1.Department of Cell Research and ImmunologyGeorge S. Wise Faculty of Life Sciences, Tel Aviv UniversityTel AvivIsrael

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