Protein tyrosine phosphatases

The kinases have been implicated in controlling the amplitude of a signalling response, whereas phosphatases are thought to have an important role in controlling the rate and duration of the response [1, 2].

The classical PTPs. The classical protein tyrosine phosphatases (PTPs) can be categorized as receptor-like (R) or non-transmembrane (NT) proteins. However, this is not an absolute distinction. For example, use of alternative promoters (as in the case of PTPRE) or alternative splicing (as in the case of GLEPP1 (PTPRO)) leads to the production of transmembrane and cytoplasmic forms of some PTPs from a single gene. In the PTPR7 subgroup, receptor-like and nontransmembrane variants of PCPTP1 (PTPRR) and STEP (PTPN5) have been described; however, as no receptor-like isoforms of HePTP (PTPN7) have been identified, this is included with the non-transmembrane enzymes. For those receptor-like PTPs (RPTP) with two intracellular PTP domains, the membrane-proximal D1 domain is catalytically active. In receptor subtype R4, PTPalpha is unique among the RPTPs in that the membrane-distal D2 domain also displays a low residual activity. For the remaining RPTPs, including PTPepsilon, which is the other enzyme in receptor subtype R4, the D2 domain maintains a PTP fold but lacks activity and can be classified as a pseudophosphatase domain. In each case, the PTPs have been designated by a name that is commonly used in the literature. Where this differs from the gene symbol, the latter is included in parentheses for clarification. In each case, the various subdivisions are based upon sequence similarity [3].



PTPs's competitive and allosteric inhibitors


PTPs's open and closed catalytic domain structure


UniProt and GeneCards links to all human Protein Tyrosine Phosphatases


D1 domain sequence alignment