ArticleThe Journal of biological chemistry2012
Self-cleavage of human CLCA1 protein by a novel internal metalloprotease domain controls calcium-activated chloride channel activation.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
52 citing papers in PubMed, 76 citations in OpenAlex.
- Integrated molecular mechanisms of salinity response in Apostichopus japonicus: focus on miRNA-driven core pathways and target gene regulation.Marine biotechnology (New York, N.Y.) · 2026Review
- Identification of rectal mucosa-secreted proteins by enzyme-linked immunosorbent assay for the investigation of sexual assault cases with anal penetration.International journal of legal medicine · 2026Article
- Function and Regulation of the Calcium-Activated Chloride Channel Anoctamin 1 (TMEM16A).Handbook of experimental pharmacology · 2024Article
- Structure and Function of Calcium-Activated Chloride Channels and Phospholipid Scramblases in the TMEM16 Family.Handbook of experimental pharmacology · 2024Review
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- AlphaFold predicts novel human proteins with knots.Protein science : a publication of the Protein Society · 2023Article
- Hormonal regulation of non-cystic fibrosis transmembrane conductance regulator ion channels in the endocervix.F&S science · 2023Article
- Intestinal mucus components and secretion mechanisms: what we do and do not know.Experimental & molecular medicine · 2023Review
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- A unique self-truncation of bacterial GH5 endoglucanases leads to enhanced activity and thermostability.BMC biology · 2022Article
- Polymodal Control of TMEM16x Channels and Scramblases.International journal of molecular sciences · 2022Review
- Circulating Tumor Cells: Does Ion Transport Contribute to Intravascular Survival, Adhesion, Extravasation, and Metastatic Organotropism?Reviews of physiology, biochemistry and pharmacology · 2022Review
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- ADAM17 Mediates Proteolytic Maturation of Voltage-Gated Calcium Channel Auxiliary αFunction (Oxford, England) · 2022Article
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- Article
- Molecular mechanisms of activation and regulation of ANO1-Encoded CaChannels (Austin, Tex.) · 2021Review
- Chloride channel accessory 1 integrates chloride channel activity and mTORC1 in aging-related kidney injury.Aging cell · 2021Article
- The calcium-activated chloride channel-associated protein rCLCA2 is expressed throughout rat epidermis, facilitates apoptosis and is downmodulated by UVB.Histochemistry and cell biology · 2021Article
- Urinary bladder smooth muscle ion channels: expression, function, and regulation in health and disease.American journal of physiology. Renal physiology · 2020Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
The chloride channel calcium-activated (CLCA) family are secreted proteins that regulate both chloride transport and mucin expression, thus controlling the production of mucus in respiratory and other systems. Accordingly, human CLCA1 is a critical mediator of hypersecretory lung diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis, that manifest mucus obstruction. Despite relevance to homeostasis and disease, the mechanism of CLCA1 function remains largely undefined. We address this void by showing that CLCA proteins contain a consensus proteolytic cleavage site recognized by a novel zincin metalloprotease domain located within the N terminus of CLCA itself. CLCA1 mutations that inhibit self-cleavage prevent activation of calcium-activated chloride channel (CaCC)-mediated chloride transport. CaCC activation requires cleavage to unmask the N-terminal fragment of CLCA1, which can independently gate CaCCs. Gating of CaCCs mediated by CLCA1 does not appear to involve proteolytic cleavage of the channel because a mutant N-terminal fragment deficient in proteolytic activity is able to induce currents comparable with that of the native fragment. These data provide both a mechanistic basis for CLCA1 self-cleavage and a novel mechanism for regulation of chloride channel activity specific to the mucosal interface.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.