Figure 2

A modular architecture is found in all members of the calpain protein family. All the identified human calpain genes (hCAPN) are depicted with selected examples from other species. The presence of domains dI and dII is used to define the family. Domain dIII is defined as the classical calpain C2-like domain; other C2 domains can also be present (see hCAPN5 and 6). Domain dIV is the penta-EF-hand module shared by classical calpains and their small subunit Cpns-1 (where the penta-EF-hand module is known as domain dVI). Domain dV, specific to the small subunit Cpns-1 and without known motifs, is not shown here. The black bars linking modules represent sequences without known motifs and are unique to individual calpains. *The classical calpain hCAPN3 has two insertions, indicated by Δ here. ^†These proteins have lost key catalytic residues and are predicted to lack protease activity. Species: Dm, Drosophila melanogaster; Ce, Caenorhabiditis elegans; En, Emericella (Aspergillus) nidulans; Sc, Saccharomyces cerevisiae; Tt, Tetrahymena thermophila; Tb, Trypanosoma brucei. Domain abbreviations: C2, protein kinase C conserved region 2 (domain involved in calcium-dependent phospholipid binding); IV^dEF, domain dIV with degenerate EF-hand motifs that are unlikely to bind calcium; EF, domain with EF-hand motifs distinct from domain dIV; K_AC, kinetoplastid acylated domain (myristic acid and palmitic acid chains are indicated by zigzag lines); MIT, microtubule interacting and trafficking molecule domain; palB, palB-homologous domain; PKA, protein kinase A regulatory subunit domain; SOL, small optic lobe domain; TMD, transmembrane domain; Zn, zinc finger domain. The functions of some of these protein modules are not yet defined. The domain structures were assembled using SMART [79] and the peptidase database MEROPS [80].