| Type: | Family | Name: | Protein-tyrosine phosphatase, non-receptor type-6, -11 |
| Description: | 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; ) 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 [, ]. The PTP superfamily can be divided into four subfamilies []:(1) pTyr-specific phosphatases(2) dual specificity phosphatases (dTyr and dSer/dThr)(3) Cdc25 phosphatases (dTyr and/or dThr)(4) LMW (low molecular weight) phosphatasesBased on their cellular localisation, PTPases are also classified as:Receptor-like, which are transmembrane receptors that contain PTPase domains []Non-receptor (intracellular) PTPases []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 []. Functional diversity between PTPases is endowed by regulatory domains and subunits. This entry represents non-receptor PTPase types 6 and 11, also known as SHP-1 and SHP-2 respectively. SHP-1 is expressed predominantly in haematopoietic and epithelial cells, playing an important role in haematopoiesis and functioning as a terminator of signalling transduction, predominantly by dephosphorylation of appropriate substrate proteins []. SHP-2 is expressed in most cell types and is involved in signal transduction stimulated by epidermal growth factor, platelet-derived growth factor, and insulin, acting as a positive regulator of cell proliferation []. The structure of human SHP-2 () shows that its catalytic activity is regulated by its two SH2 domains []. In the absence of protein, the N-terminal SH2 domain binds the phosphatase domain, inhibiting its activity, while the binding of a tyrosine-phosphorylated substrate to this domain causes a conformational change which activates the enzyme. The C-terminal SH2 domain does not play a direct role in activation, but contributes to substrate specificity and binding energy. | Short Name: | Tyr_Pase_non-rcpt_typ-6/11 |
