logo CaMPDB: Calpain for Modulatory Proteolysis Database

Calpain (EC, Clan CA, family C02) is an intracellular Ca2+-dependent cysteine protease, which is ubiquitously distributed, showing limited proteolytic activity at neutral pH. Calpain proteolytically processes, rather than digests, substrates to transform and modulate their structures and activities. Thus, calpain is placed as a representative intracellular “modulator protease” that governs various cellular functions such as signal transductions and cell morphogenesis. Calpain belongs to the papain superfamily, and constitutes one of its three distinct kingdoms, i.e., calpain-, papain-, and bleomycin-hydrolase-sub-superfamilies. Human has 15 genes that encode a calpain-like protease domain, and they generate diverse kinds of calpain homologues with combinations of several functional domains such as Ca2+-binding domain (C2-domain-type and EF-hand-type), Zn-finger domain, etc. Furthermore, calpain homologues are increasingly being found in other organisms including insect, nematode, trypanosome, plant, fungus, yeast, and even some bacteria, thus constituting a superfamily of versatile functions (see Fig. 1). Physiological functions of calpain are so important for the cells that their defects cause variety of deficiencies in many different organisms; muscular dystrophies, diabetes, and tumorigenesis in human, embryonic lethality in mouse, neurogenesis deficiency in fly, incomplete sex determination in nematodeys, defect of aleurone cell development in maize, and alkaline/osmo-shock susceptibility in yeast.


Fig. 1. Schematic structures of calpain superfamily members Calpain homologues have been identified in vertebrates, insects, nematodes, schistosomes, trypanosomes, plants, fungi, yeasts, some bacteria etc. Symbols used are; I: the N-terminal domain with little homology; IIa and IIb: the protease sub-domains containing the active sites Cys, and His, respectively; III: the C2-like Ca2+-binding domain; III’ and III’’: domains moderately and very weakly similar to the domain III, respectively; IV and VI: the 5-EF-hand Ca2+-binding domain; V: Gly-rich hydrophobic domain; NS, IS1, and IS2: p94-specific sequences; T: TRA-3 subfamily-specific C2 domain; MIT: Microtubule-interacting and trafficking domain; Zn: Zn-finger motif containing domain; SOH: SOL subfamily homology domain; DIS: CALPA-specific insertion sequence; TM: transmembrane domain; CSTN: the domain weakly similar to calpastatin.

All sections ≫ open : close

1. History and nomenclature

2. Structure and functions of conventional calpains

3. Calpain superfamily and its members

4. References

A1. Glossary

A2. Crosseye view of m-calpain