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Welcome to Phosphatase Wiki, a resource for phosphatases and phosphatase signaling focused on genomics and evolution. This is a pilot project for sharing and publication of discoveries that do not fit into traditional publications or haven't yet been polished for publication. This also includes supporting data and results for our 2017 Science Signaling paper on the genomics and evolution of phosphatases [1]. Initial content is mostly from the Manning lab at Salk (moved to Genentech in 2012), but we welcome anyone who would like to contribute. Like other wikis, just go to the login page to request an account.

Protein Phosphatase Classification and Evolution

This is the heart of this wiki - a set of articles on individual families, subfamilies and folds of phosphatases, with a focus on genomics, evolution, and biological functions shared across organisms.

Classification chart

In contrast with kinases, there are multiple folds of protein phosphatases, which means protein phosphatases have multiple independent evolutionary origins, while most kinases have a single origin. We classified protein phosphatases into a hierarchy scheme of four levels: fold, superfamily, family and subfamily.


Some phosphatases are catalytically inactive, due to alterations in the active site, but are conserved and frequently function in signaling pathways.

Protein phosphatase evolution

Each of the protein phosphatase fold are able to be found in early eukaryotes, so are most of the protein phosphatase families. The subfamilies have a dynamic evolutionary pattern. Some subfamilies have been lost multiple times through independent evolutionary events. While many subfamilies expanded in gene number in vertebrates, some subfamily has a single member in almost all the sequenced eukaryotic genomes. Protein phosphatase also underwent gains and losses of accessory domain.

Human protein phosphatase pseudogenes

There are about 80 pseudogenes which originated from the protein-coding genes that encode protein phosphatases in human. They are functional at least in some cases. For instance, PTENP1 is a processed pseudogene of PTEN and regulates PTEN by both sense and antisense RNAs.

Additional Topics

Phosphatase Glossary

Technical Notes



  1. Chen MJ, Dixon JE, and Manning G. Genomics and evolution of protein phosphatases. Sci Signal. 2017 Apr 11;10(474). DOI:10.1126/scisignal.aag1796 | PubMed ID:28400531 | HubMed [Chen]