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. 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.
- Phosphatases and diseases
- Phosphatases as drug and/or inhibitor targets
- Miscellaneous biological and clinic significance of phosphorylation
- (De)phosphorylation on unusual amino acids: unusual evidence for phosphorylation on histidine, aspartate, cysteine, lysine, and arginine.
- Regulatory subunits: some phosphatases, particularly PPPs, consist of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits.
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.
Catalytically inactive phosphatases (pseudophosphatases)
Protein phosphatases have various functions. Some protein phosphatases lack catalytically activity, but them play critical roles in various cellular 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.
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.