Pathways & interactions
Protein-tyrosine phosphatase, KIM-containing (IPR008356)
Short name: Tyr_Pase_KIM-con
Overlapping homologous superfamilies
- Protein-tyrosine phosphatase-like (IPR029021)
- Protein-tyrosine phosphatase, KIM-containing (IPR008356)
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; EC:126.96.36.199) 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 [PMID: 9818190, PMID: 14625689]. The PTP superfamily can be divided into four subfamilies [PMID: 12678841]:
- (1) pTyr-specific phosphatases
- (2) dual specificity phosphatases (dTyr and dSer/dThr)
- (3) Cdc25 phosphatases (dTyr and/or dThr)
- (4) LMW (low molecular weight) phosphatases
Based on their cellular localisation, PTPases are also classified as:
- Receptor-like, which are transmembrane receptors that contain PTPase domains [PMID: 16672235]
- Non-receptor (intracellular) PTPases [PMID: 8948575]
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 [PMID: 9646865]. Functional diversity between PTPases is endowed by regulatory domains and subunits.
The structures of receptor PTPases comprise a variable length extracellular domain, followed by a TM region and a cytoplasmic C-terminal catalytic domain. The extracellular regions of some receptor PTPases house fibronectin type III repeats, immunoglobulin-like domains, MAM domains or carbonic anhydrase-like domains. The cytoplasmic region generally contains 2 copies of the PTPase domain: the first of these is enzymatically active; the second is inactive, but appears to affect substrate specificity in the first. PTPase domains contain ~300 residues, including 2 conserved cysteines, the second of which is required for activity. Other conserved residues in its immediate vicinity are also catalytically important [PMID: 9857190].
This entry represents protein-tyrosine phosphatases that contain a Kinase Interaction Motif (KIM), including receptor PTPases and non-receptor (types 2 and 7) PTPases. Enzymes PTP-STEP, PTP-SL and LC-PTP each contain a KIM in the N-terminal portion of the molecule. The KIM sequence mediates interaction with MAP kinases, predominantly ERK1 and ERK2. It has been experimentally shown that over-expression of PTP-SL down-regulates the activation of ERK2 and its nuclear translocation [PMID: 9857190].