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Conventional calpains

Calpains are found in a variety of living organisms with divergent domain structures. Among them, the most studied calpain molecules are mammalian μ-calpain and m-calpain, which we suggest calling CAPN1/S1 and CAPN2/S1, respectively. These are considered the “conventional calpains”. To avoid confusion, this web site uses the format “proposed name[previous name]”.

Conventional calpains are heterodimers consisting of a larger catalytic subunit (CAPN1[μCL] and CAPN2[mCL] for μ-calpain and m-calpain, respectively) and a common smaller regulatory subunit (CAPNS1[30K]).

The catalytic subunits contain four functional region/domains, and the regulatory subunits contain two domains. Ohno et al (Ohno et al., 1984) first described the domain structure of chicken CAPN11[μ/mCL] from the primary structure. Hosfield et al (Hosfield et al., 1999) and Strobl et al (Strobl et al., 2000) solved the 3D structure of CAPN2/S1[m-calpain], and defined the domains from the 3D structural viewpoint. Historically, the domains have been given several names that are not necessarily consistent. We propose that the domain boundaries be mainly defined according to their 3D structure and evolutionary conservation (Drs. Robert L. Campbell and Peter L. Davies, personal communication), and that the old domain names I, II, III, etc. be replaced by acronyms representing each domain's function and/or structure (see Fig. 1).

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Fig. 1 Domain structure and nomenclature of conventional calpains.

The historically defined domains were not necessarily consistent. We propose that the domains be defined and named as indicated (bottom of figure). The domain boundaries are mainly defined according to their 3D structure and evolutionary conservation (see text). In the proposed format, the domain names I, II, III, etc. are replaced with acronyms representing the function and/or structure of each domain.

CBSW domain was formerly called "C2-like (C2L)" domain. Its 3D structure, however, is not topologically identical (or even similar) to that of the C2 domain, although their overall characteristics composed of eight anti-parallel β-strands look similar. Therefore, it was proposed to rename C2L to CBSW at 2013 FASEB calpain meeting, and was approved by a majority of the participants.

Abbreviations used for domain names:
CysPc: calpain-like cysteine protease sequence motif defined in the conserved domain database at the National Center for Biotechnology Information (cd00044), which is composed of two protease core domains 1 and 2 (PC1 and PC2)
PC1: protease core domain 1
PC2: protease core domain 2
CBSW: calpain-type beta-sandwich domain (formerly called "C2-domain-like (C2L)" domain)
PEF(L): penta-EF-hand domain in the catalytic large subunit
PEF(S): penta-EF-hand domain in the regulatory small subunit
GR: glycine-rich hydrophobic domain

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