ArticleMolecules and cells2011
The murine goblet cell protein mCLCA3 is a zinc-dependent metalloprotease with autoproteolytic activity.
Article in Molecules and cells, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- Effect of Shin'iseihaito (Xinyiqingfeitang) on MUC5AC expression in cultured pulmonary epithelial cells and the role of its component gypsum.Journal of natural medicines · 2026Article
- Zinc Deficiency and the Severity of Pneumonia in Vietnamese Children: A Hospital-Based Study.Cureus · 2024Article
- Article
- Intestinal mucus components and secretion mechanisms: what we do and do not know.Experimental & molecular medicine · 2023Review
- Article
- Ion Channels in Lung Cancer.Reviews of physiology, biochemistry and pharmacology · 2021Review
- Calcium-activated chloride channel regulator 1 (CLCA1) forms non-covalent oligomers in colonic mucus and has mucin 2-processing properties.The Journal of biological chemistry · 2019Article
- Calcium-activated chloride channel regulator 1 (CLCA1): More than a regulator of chloride transport and mucus production.The World Allergy Organization journal · 2019Article
- Calcium-activated Chloride Channel Regulator 1 (CLCA1) Controls Mucus Expansion in Colon by Proteolytic Activity.EBioMedicine · 2018Article
- Soluble mucus component CLCA1 modulates expression of leukotactic cytokines and BPIFA1 in murine alveolar macrophages but not in bone marrow-derived macrophages.Histochemistry and cell biology · 2018Article
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- Murine CLCA5 is uniquely expressed in distinct niches of airway epithelial cells.Histochemistry and cell biology · 2015Article
- Novel Roles for Chloride Channels, Exchangers, and Regulators in Chronic Inflammatory Airway Diseases.Mediators of inflammation · 2015Review
- Article
- Naturally Occurring Deletion Mutants of the Pig-Specific, Intestinal Crypt Epithelial Cell Protein CLCA4b without Apparent Phenotype.PloS one · 2015Article
- Studies of mucus in mouse stomach, small intestine, and colon. II. Gastrointestinal mucus proteome reveals Muc2 and Muc5ac accompanied by a set of core proteins.American journal of physiology. Gastrointestinal and liver physiology · 2013Article
- CLCAs - a family of metalloproteases of intriguing phylogenetic distribution and with cases of substituted catalytic sites.PloS one · 2013Article
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- Self-cleavage of human CLCA1 protein by a novel internal metalloprotease domain controls calcium-activated chloride channel activation.The Journal of biological chemistry · 2012Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several members of the CLCA family of proteins, originally named chloride channels, calcium-activated, have been shown to modulate chloride conductance in various cell types via an unknown mechanism. Moreover, the human (h) hCLCA1 is thought to modulate the severity of disease in asthma and cystic fibrosis (CF) patients. All CLCA proteins are post-translationally cleaved into two subunits, and recently, a conserved HEXXH zinc-binding amino acid motif has been identified, suggesting a role for CLCA proteins as metalloproteases. Here, we have characterized the cleavage and autoproteolytic activity of the murine model protein mCLCA3, which represents the murine orthologue of human hCLCA1. Using crude membrane fractions from transfected HEK293 cells, we demonstrate that mCLCA3 cleavage is zinc-dependent and exclusively inhibited by cation-chelating metalloprotease inhibitors. Cellular transport and secretion were not affected in response to a cleavage defect that was introduced by the insertion of an E157Q mutation within the HEXXH motif of mCLCA3. Interspecies conservation of these key results was further confirmed with the porcine (p) orthologue of hCLCA1 and mCLCA3, pCLCA1. Importantly, the mCLCA3E157Q mutant was cleaved after co-transfection with the wild-type mCLCA3 in HEK293 cells, suggesting that an intermolecular autoproteolytic event takes place. Edman degradation and MALDI-TOF-MS of the protein fragments identified a single cleavage site in mCLCA3 between amino acids 695 and 696. The data strongly suggest that secreted CLCA proteins have zinc-dependent autoproteolytic activity and that they may cleave additional proteins.
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