Family I29
Summary for family I29
| Name | Inhibitor family I29 (CTLA family) |
|---|
| Family type peptidase | I29.002 - cytotoxic T-lymphocyte antigen-2 alpha (Mus musculus), MEROPS Accession MER0018379 (inhibitor unit: 28-137) |
| Content of family | Inhibitor family I29 contains inhibitors of cysteine peptidases from family C1. |
| History |
Identifier created: MEROPS 6.1 (10 January 2003)
Cytotoxic T-lymphocyte antigens CTLA-2 alpha and beta were first discovered by Denizot et al., 1989, when the sequence relationship to the propeptides of some members of peptidase family C1 was also noted. CTLA-2 beta was shown to be an effective inhibitor of cathepsin L (C01.032) by Delaria et al., 1994. The related BCPI inhibitor (I29.002) from Bombyx mori has also been characterized (Kurata et al., 2001). |
| Peptidases inhibited | Peptidases inhibited are in family C1 (Guay et al., 2000). Where a propeptide and peptidase are released from the precursor, specific inhibition of the peptidase by the propeptide has been shown, for example a Fasciola hepatica cysteine endopeptidase (Roche et al., 1999), cathepsins K (C01.036), L and S (C01.034; Guay et al., 2000). |
| Mechanism of inhibition | CTLA-2 alpha and beta are assumed to inhibit by the same mechanism as the cathepsin L propeptide, namely by binding in the active site in the reverse orientation to that of a substrate. |
| Molecular structure | The tertiary structure of procathepsin L was determined by Coulombe et al., 1996. The N-terminal portion of the propeptide forms a globular domain with three helices and a small hydrophobic core, whereas the C-terminal portion has an extended structure and occupies the binding cleft but in the opposite direction to that of a substrate. The propeptide domain is not classified in the SCOP or CATH databases. The sequence of the cathepsin B propeptides is only very distantly related to that of cathepsin L. Most members of family I29 have only one inhibitor unit, but salarin (I29.006) has four (Rawlings et al., 2004). |
| Clan | JF |
| Biological functions | CTLA-2 beta is expressed in the uterus during early pregnancy and has probably a role in embryo implantation by inhibiting the cathepsin L that is expressed in giant trophoblast cells (Cheon et al., 2003).
The propeptide of papain-like cysteine peptidases is essential not only for preventing unwanted proteolysis before the enzyme reaches its targeted location, but also acts as a chaperone, required for correct folding and targeting of the peptidase. The hydrophobic core has been shown by mutation studies to be essential for the correct processing and targeting of cathepsin S (Wiederanders, 2000). |
| Statistics for family I29 | Sequences: | 6754 |
| Identifiers: | 13 |
| Identifiers with PDB entries: | 3 |
| Downloadable files |
Sequence library (FastA format) |
| Sequence alignment (FastA format) |
| Phylogenetic tree (Newick format) |
