|PROSITE documentation PDOC00323|
Tyrosine specific protein phosphatases (EC 188.8.131.52) (PTPase) [1,2,3,4,5] are enzymes that catalyze the removal of a phosphate group attached to a tyrosine residue. These enzymes are very important in the control of cell growth, proliferation, differentiation and transformation. Multiple forms of PTPase have been characterized and can be classified into two categories: soluble PTPases and transmembrane receptor proteins that contain PTPase domain(s). The currently known PTPases are listed below:
Dual specificity PTPases.
Structurally, all known receptor PTPases, are made up of a variable length extracellular domain, followed by a transmembrane region and a C-terminal catalytic cytoplasmic domain. Some of the receptor PTPases contain fibronectin type III (FN-III) repeats, immunoglobulin-like domains, MAM domains or carbonic anhydrase-like domains in their extracellular region. The cytoplasmic region generally contains two copies of the PTPAse domain. The first seems to have enzymatic activity, while the second is inactive but seems to affect substrate specificity of the first. In these domains, the catalytic cysteine is generally conserved but some other, presumably important, residues are not.
In the following table, the domain structure of known receptor PTPases is shown:
Extracellular Intracellular ------------------- ------------- Ig FN-3 CAH MAM PTPase Leukocyte common antigen (LCA) (CD45) 0 2 0 0 2 Leukocyte antigen related (LAR) 3 8 0 0 2 Drosophila DLAR 3 9 0 0 2 Drosophila DPTP 2 2 0 0 2 PTP-alpha (LRP) 0 0 0 0 2 PTP-beta 0 16 0 0 1 PTP-gamma 0 1 1 0 2 PTP-delta 0 >7 0 0 2 PTP-epsilon 0 0 0 0 2 PTP-kappa 1 4 0 1 2 PTP-mu 1 4 0 1 2 PTP-zeta 0 1 1 0 2
PTPase domains consist of about 300 amino acids. There are two conserved cysteines, the second one has been shown to be absolutely required for activity. Furthermore, a number of conserved residues in its immediate vicinity have also been shown to be important.
We derived a signature pattern for PTPase domains centered on the active site cysteine.
There are three profiles for PTPases, the first one spans a short region that is common to both dual-specificity protein phosphatases and PTPases. The second and third ones cover the whole domain and are respectively specific for Ser/Thr and Tyr protein phosphatases and Tyr protein phosphatases.Note:
The M-phase inducer phosphatases (cdc25-type phosphatase) are tyrosine- protein phosphatases that are not structurally related to the above PTPases.Last update:
August 2007 / Pattern revised.
PROSITE methods (with tools and information) covered by this documentation:
|1||Authors||Fischer E.H., Charbonneau H., Tonks N.K.|
|Title||Protein tyrosine phosphatases: a diverse family of intracellular and transmembrane enzymes.|
|2||Authors||Charbonneau H., Tonks N.K.|
|Title||1002 protein phosphatases?|
|Source||Annu. Rev. Cell Biol. 8:463-493(1992).|
|Title||CD45. A prototype for transmembrane protein tyrosine phosphatases.|
|Source||J. Biol. Chem. 266:23517-23520(1991).|
|4||Authors||Tonks N.K., Charbonneau H.|
|Title||Protein tyrosine dephosphorylation and signal transduction.|
|Source||Trends Biochem. Sci. 14:497-500(1989).|
|Title||Protein-tyrosine phosphatases: the other side of the coin.|