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 .
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.
August 2003 / First entry.
These proteins belong to family C2 in the classification of peptidases
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