Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.22.54 (calpain 3)
 430 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our previous studies have demonstrated that, in addition to the conventional mu- and m-calpains ubiquitously expressed in tissues, a muscle-specific calpain comprising a novel member of the large subunit family (p94 or nCL-1, which stands for novel Calpain Large subunit) exists in muscle cells. To clarify the physiological function of nCL-1, we screened cDNA libraries of various rat tissues for other tissue-specific calpains and, as a result, discovered a novel member of the calpain large subunit family. RNA blot analysis showed that the mRNA is expressed predominantly in the stomach. Isolated cDNA clones could be structurally divided into two groups, whose 5'-halves of about 1.1 kilobase pairs were identical, but whose 3'-halves bore no similarity at all. This suggests generation by an alternative splicing mechanism, which was proved by genomic DNA cloning. Open reading frames were found encoding 703 and 381 amino acid residues with calculated molecular masses of 79,554 and 42,591 for nCL-2 and -2', respectively. The deduced amino acid sequence of nCL-2 is very similar to those of other calpain large subunits and can be aligned without significant insertions or deletions, suggesting that nCL-2 should possess cysteine protease activity and calcium binding ability. nCL-2' is identical to the N-terminal half of nCL-2 and, thus, contains only the cysteine protease domain but not the calcium binding domain. Possible roles of the calpain family are discussed based on these findings.
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PMID:A novel tissue-specific calpain species expressed predominantly in the stomach comprises two alternative splicing products with and without Ca(2+)-binding domain. 769 35

The recent discovery of several new calpain species other than the two species thus far studied reveals that calpain, especially the calpain large subunit, constitutes a family comprising at least six members that can be classified into ubiquitous (mu, m- and mu/m-types) and tissue-specific (p94 or nCL-1 specific for skeletal muscle, and nCL-2 and -2' specific for stomach) calpains. The newly identified tissue-specific calpains have various characteristics distinct from conventional calpains in structure, manner of expression, and enzyme activity. Unique features of tissue specific calpains are discussed together with the evolutionary view of the calpain large subunit.
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PMID:New era of calpain research. Discovery of tissue-specific calpains. 816 8

Calpains are calcium-dependent intracellular nonlysosomal proteases that are believed to participate in signal transduction. In vertebrates, five different calpains have so far been identified, of which three, mu-, m-, and mu/m-calpain, are ubiquitously expressed while the other two, nCL-1 (p94) and nCL-2, exhibit a restricted tissue distribution. We have identified two new vertebrate calpain genes, Capn5 and Capn6. The human and mouse amino acid sequences of these new calpains are the most divergent of the vertebrate calpains identified. They possess most of the residues conserved in calpain family members but the C-terminal region lacks any homology to the calmodulin-like domain of other vertebrate calpains. They both exhibit significant homology over the entire coding region to the protein encoded by the gene tra-3, involved in nematode sex determination, and Capn5 may represent its vertebrate orthologue. The predicted Capn6 protein lacks critical active site residues and may not be proteolytically active. Both genes are differentially expressed in human tissues with highest RNA levels for Capn5 occurring in the testis, liver, trachea, colon, and kidney, while Capn6 is highly expressed only in the placenta sample of the 50 tissues examined. Phylogenetic analysis suggests that the vertebrate calpains arose through a series of gene duplication events that began before the initial divergence of the vertebrate and invertebrate lineages. The discovery of these two new calpains highlights a hitherto unknown complexity of the calpain family with subclasses perhaps possessing different modes of regulation.
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PMID:A new subfamily of vertebrate calpains lacking a calmodulin-like domain: implications for calpain regulation and evolution. 933 74

The proteins nCL-2 and nCL-2' are members of the Ca2+-dependent cysteine protease (calpain) superfamily, with stomach-specific expression. Like other typical calpains, nCL-2 has three distinct domains, a protease, a C2-like, and a 5EF-hand Ca2+-binding domain, as well as the N-terminal propeptide region. On the other hand, nCL-2' lacks the C2-like and 5EF-hand domains but is otherwise identical to nCL-2, except for the three C-terminal residues. To examine the stomach-specific and presumed alternative expression mechanisms of nCL-2 and nCL-2', we have cloned and characterized the mouse gene for nCL-2 and nCL-2'. The mouse nCL-2 gene contains at least 23 exons, spanning more than 50 kb, and possesses an exon specific for nCL-2' in the middle. Therefore, nCL-2 and nCL-2' are generated by alternative splicing of the same gene, Capn8. Capn8 shows the highly conserved gene organization of the other typical calpain large subunit genes, CAPN1, CAPN2, CAPN3, CAPN9, CAPN11, and Capn12, except for the unique exon between exon 9 and exon 10 of Capn8, which encodes the 3' half of the nCL-2' transcript. No such exon in the corresponding regions was found in CAPN1, CAPN2, CAPN3, CAPN9, or CAPN11. Gene and cDNA structures of a presumed human orthologue of mouse nCL-2, CAPN8, were determined, revealing that it overlaps human CAPN2, the gene for the m-calpain large subunit, in head-to-head orientation at 1q32-41. These features of Capn8 and CAPN8 illustrate a process of calpain gene evolution, i.e., the protease, C2-like, and 5EF-hand domains presumably functioned as independent genes, and the calpain superfamily has evolved by ordered fusions of these ancestral gene units, with subsequent amplifications.
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PMID:Both the conserved and the unique gene structure of stomach-specific calpains reveal processes of calpain gene evolution. 1152 6