<p>Protein tyrosine (pTyr) phosphorylation is a common post-translational modification which can create novel recognition motifs for protein interactions and cellular localisation, affect protein stability, and regulate enzyme activity. Consequently, maintaining an appropriate level of protein tyrosine phosphorylation is essential for many cellular functions. Tyrosine-specific protein phosphatases (PTPase; <db_xref db="EC" dbkey="3.1.3.48"/>) catalyse the removal of a phosphate group attached to a tyrosine residue, using a cysteinyl-phosphate enzyme intermediate. These enzymes are key regulatory components in signal transduction pathways (such as the MAP kinase pathway) and cell cycle control, and are important in the control of cell growth, proliferation, differentiation and transformation [<cite idref="PUB00035793"/>, <cite idref="PUB00035794"/>]. The PTP superfamily can be divided into four subfamilies [<cite idref="PUB00035795"/>]:</p><p> <ul><li>(1) pTyr-specific phosphatases</li><li>(2) dual specificity phosphatases (dTyr and dSer/dThr)</li><li>(3) Cdc25 phosphatases (dTyr and/or dThr)</li><li>(4) LMW (low molecular weight) phosphatases</li></ul> </p><p>Based on their cellular localisation, PTPases are also classified as:</p><p> <ul><li>Receptor-like, which are transmembrane receptors that contain PTPase domains [<cite idref="PUB00035796"/>]</li><li>Non-receptor (intracellular) PTPases [<cite idref="PUB00035797"/>]</li></ul> </p><p>All PTPases carry the highly conserved active site motif C(X)5R (PTP signature motif), employ a common catalytic mechanism, and share a similar core structure made of a central parallel beta-sheet with flanking alpha-helices containing a beta-loop-alpha-loop that encompasses the PTP signature motif [<cite idref="PUB00035798"/>]. Functional diversity between PTPases is endowed by regulatory domains and subunits. </p><p>This entry repesents several receptor and non-receptor protein-tyrosine phosphatases.</p><p>Structurally, all known receptor PTPases, are made up of a variable lengthextracellular domain, followed by a transmembrane region and a C-terminalcatalytic cytoplasmic domain. Some of the receptor PTPases contain fibronectintype III (FN-III) repeats, immunoglobulin-like domains, MAM domains orcarbonic anhydrase-like domains in their extracellular region. The cytoplasmicregion generally contains two copies of the PTPase domain. The first seems tohave enzymatic activity, while the second is inactive. The inactive domains of tandem phosphatases can be divided into two classes. Those which bind phosphorylated tyrosine residues may recruit multi-phosphorylated substrates for the adjacent active domains and are more conserved, while the other class have accumulated several variable amino acid substitutions and have a complete loss of tyrosine binding capability. The second class shows a release of evolutionary constraint for the sites around the catalytic centre, which emphasises a difference in function from the first group. There is a region of higher conservation common to both classes, suggesting a new regulatory centre [<cite idref="PUB00014502"/>]. 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.</p> Protein-tyrosine phosphatase, receptor/non-receptor type