PROSITE documentation PDOC50203Cysteine proteinase, calpain-type, catalytic domain profile
Calpains are a family of cytosolic cysteine proteinases (see <PDOC00126>). Members of the calpain family are believed to function in various biological processes, including integrin-mediated cell migration, cytoskeletal remodeling, cell differentiation and apoptosis [1,2].
The calpain family includes numerous members from C. elegans to mammals and with homologs in yeast and bacteria. The best characterized members are the m- and mu-calpains, both proteins are heterodimer composed of a large catalytic subunit and a small regulatory subunit. The large subunit comprises four domains (dI-dIV) while the small subunit has two domains (dV-dVI). Domain dI is a short region cleaved by autolysis, dII is the catalytic core, dIII is a C2-like domain, dIV consists of five calcium binding EF-hand motifs [2].
The crystal structure of calpain has been solved (see <PDB:1DF0>) [3,4]. The catalytic region consists of two distinct structural domains (dIIa and dIIb). dIIa contains a central helix flanked on three faces by a cluster of α-helices and is entirely unrelated to the corresponding domain in the typical thiol proteinases. The fold of dIIb is similar to the corresponding domain in other cysteine proteinases and contains two three-stranded anti-parallel β-sheets. The catalytic triad residues (C,H,N) are located in dIIa and dIIb. The activation of the domain is dependent on the binding of two calcium atoms in two non EF-hand calcium binding sites located in the catalytic core, one close to the Cys active site in dIIa and one at the end of dIIb. Calcium-binding induced conformational changes in the catalytic domain which align the active site [4,5].
The profile we developed covers the whole catalytic domain.
Last update:August 2003 / First entry.
Note:These proteins belong to family C2 in the classification of peptidases [6,E1].
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Glading A. Lauffenburger D.A. Wells A. |
| Title | Cutting to the chase: calpain proteases in cell motility. | |
| Source | Trends Cell Biol. 12:46-54(2002). | |
| PubMed ID | 11854009 |
| 2 | Authors | Perrin B.J. Huttenlocher A. |
| Title | Calpain. | |
| Source | Int. J. Biochem. Cell Biol. 34:722-725(2002). | |
| PubMed ID | 11950589 |
| 3 | Authors | Hosfield C.M. Elce J.S. Davies P.L. Jia Z. |
| Title | Crystal structure of calpain reveals the structural basis for Ca(2+)-dependent protease activity and a novel mode of enzyme activation. | |
| Source | EMBO J. 18:6880-6889(1999). | |
| PubMed ID | 10601010 | |
| DOI | 10.1093/emboj/18.24.6880 |
| 4 | Authors | Moldoveanu T. Hosfield C.M. Lim D. Elce J.S. Jia Z. Davies P.L. |
| Title | A Ca(2+) switch aligns the active site of calpain. | |
| Source | Cell 108:649-660(2002). | |
| PubMed ID | 11893336 |
| 5 | Authors | Khorchid A. Ikura M. |
| Title | How calpain is activated by calcium. | |
| Source | Nat. Struct. Biol. 9:239-241(2002). | |
| PubMed ID | 11914728 | |
| DOI | 10.1038/nsb0402-239 |
| 6 | Authors | Rawlings N.D. Barrett A.J. |
| Title | Families of cysteine peptidases. | |
| Source | Methods Enzymol. 244:461-486(1994). | |
| PubMed ID | 7845226 |
| E1 | Title | https://www.uniprot.org/docs/peptidas |
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