ArticleThe international journal of biochemistry & cell biology2009
The ion channel activity of the SARS-coronavirus 3a protein is linked to its pro-apoptotic function.
Article in The international journal of biochemistry & cell biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed.
- Comparative Genomics of Viral Genomes and Identification of Three Novel Viroporin-Like Superfamilies.Microbial physiology · 2026Article
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- Subcellular localization of SARS-CoV-2 E and 3a proteins along the secretory pathway.Journal of molecular histology · 2025Article
- SARS-CoV-2-ORF-3a Mediates Apoptosis Through Mitochondrial Dysfunction Modulated by the KInternational journal of molecular sciences · 2025Article
- SARS-CoV-2 ORF3a accessory protein is a water-permeable channel that induces lysosome swelling.Communications biology · 2025Article
- Acute COVID-19 and LongCOVID syndrome - molecular implications for therapeutic strategies - review.Frontiers in immunology · 2025Review
- SARS-CoV-2 ORF 3a-mediated currents are inhibited by antiarrhythmic drugs.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2024Article
- Article
- The SARS coronavirus accessory protein ORF3a rescues potassium conductance in yeast.microPublication biology · 2024Article
- SARS-CoV-2-ORF3a variant Q57H reduces its pro-apoptotic activity in host cells.F1000Research · 2024Article
- Article
- Targeting Viral ORF3a Protein: A New Approach to Mitigate COVID-19 Induced Immune Cell Apoptosis and Associated Respiratory Complications.Advanced pharmaceutical bulletin · 2023Review
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- Article
- Coronavirus accessory protein ORF3 biology and its contribution to viral behavior and pathogenesis.iScience · 2023Review
- Channel activity of SARS-CoV-2 viroporin ORF3a inhibited by adamantanes and phenolic plant metabolites.Scientific reports · 2023Article
- The SARS-CoV-2 accessory protein Orf3a is not an ion channel, but does interact with trafficking proteins.eLife · 2023Article
- Contribution to pathogenesis of accessory proteins of deadly human coronaviruses.Frontiers in cellular and infection microbiology · 2023Review
- Unique mutations in SARS-CoV-2 Omicron subvariants' non-spike proteins: Potential impacts on viral pathogenesis and host immune evasion.Microbial pathogenesis · 2022Review
- Cell deaths: Involvement in the pathogenesis and intervention therapy of COVID-19.Signal transduction and targeted therapy · 2022Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The severe acute respiratory syndrome-coronavirus (SARS-CoV) caused an outbreak of atypical pneumonia in 2003. The SARS-CoV viral genome encodes several proteins which have no homology to proteins in any other coronaviruses, and a number of these proteins have been implicated in viral cytopathies. One such protein is 3a, which is also known as X1, ORF3 and U274. 3a expression is detected in both SARS-CoV infected cultured cells and patients. Among the different functions identified, 3a is a capable of inducing apoptosis. We previously showed that caspase pathways are involved in 3a-induced apoptosis. In this study, we attempted to find out protein domains on 3a that are essential for its pro-apoptotic function. Protein sequence analysis reveals that 3a possesses three major protein signatures, the cysteine-rich, Yxx phi and diacidic domains. We showed that 3a proteins carrying respective mutations in these protein domains exhibit reduced pro-apoptotic activities, indicating the importance of these domains on 3a's pro-apoptotic function. It was previously reported that 3a possesses potassium ion channel activity. We further demonstrated that the blockade of 3a's potassium channel activity abolished caspase-dependent apoptosis. This report provides the first evidence that ion channel activity of 3a is required for its pro-apoptotic function. As ion channel activity has been reported to regulate apoptosis in different pathologic conditions, finding ways to modulate the ion channel activity may offer a new direction toward the inhibition of apoptosis triggered by SARS-CoV.
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