home *** CD-ROM | disk | FTP | other *** search
- ******************************************************
- * Tyrosine specific protein phosphatases active site *
- ******************************************************
-
- Tyrosine specific protein phosphatases (EC 3.1.3.48) (PTPase) [1 to 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:
-
- Soluble PTPases.
-
- - PTPN3 (H1) and PTPN4 (MEG), enzymes that contain an N-terminal band 4.1-
- like domain (see the relevant section) and could act at junctions between
- the membrane and cytoskeleton.
- - PTPN6 (PTP-1C or HCP or SHP) and PTPN11, enzymes which contain two copies
- of the SH2 domain at its N-terminal extremity. The Drosophila protein
- corkscrew (gene csw) also belongs to this subgroup.
- - PTPN7 (CL100 or 3CH134), which could play an important regulatory role in
- the cellular response to adverse environmental challenges, including
- oxidants and hyperthermia.
- - PTPN1 (PTP-1B).
- - PTPN2 (T-cell PTPase; TC-PTP).
- - PTPN5 (STEP).
- - PTP-G1.
- - Nuclear PAC-1.
-
- - Yeast CDC14 which may be involved in chromosome segregation.
- - Yeast PTP1.
- - Yeast PTP2 which may be involved in the ubiquitin-mediated protein
- degradation pathway.
- - Yeast YVH1.
- - Fission yeast pyp1 and pyp2 which play a role in inhibiting the onset of
- mitosis.
- - Fission yeast pyp3 which contributes to the dephosphorylation of cdc2.
- - Yersinia virulence plasmid PTPAses (gene yopH).
- - Vaccinia virus H1 PTPase.
- - Autographa californica nuclear polyhedrosis virus 19 Kd PTPase.
-
- Receptor 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 0 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.
-
- -Consensus pattern: [LIVM]-H-C-x(2)-G-x(3)-[STC]-[STAG]-x-[LIVMFY]
- [C is the active site residue]
- -Sequences known to belong to this class detected by the pattern: ALL, except
- for rat PTPN5 and yeast YVH1.
- -Other sequence(s) detected in SWISS-PROT: a putative helicase from potato
- virus M, a hypothetical 12 Kd protein from the avirulence AVRSB1 region of
- Xanthomonas campestris.
-
- -Note: the M-phase inducer phosphatases (cdc25-type phosphatase) are tyrosine-
- protein phosphatases which, while structurally related to other PTPases, are
- divergent enough to justify a separate entry.
-
- -Last update: June 1994 / Pattern and text revised.
-
- [ 1] Fischer E.H., Charbonneau H., Tonks N.K.
- Science 253:401-406(1991).
- [ 2] Charbonneau H., Tonks N.K.
- Annu. Rev. Cell Biol. 8:463-493(1992).
- [ 3] Trowbridge I.S.
- J. Biol. Chem. 266:23517-23520(1991).
- [ 4] Tonks N.K., Charbonneau H.
- Trends Biochem. Sci. 14:497-500(1989).
- [ 5] Hunter T.
- Cell 58:1013-1016(1989).
-