ArticleThe Journal of biological chemistry2005
Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2).
Article in The Journal of biological chemistry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 458 papers, 2 of them syntheses that pooled it.
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Who cites it
458 citing papers in PubMed, 2 syntheses or guidelines pooled it, 706 citations in OpenAlex.
- Genetic Landscape of the ACE2 Coronavirus Receptor.Circulation · 2022Pooled it
- Pooled it
- Naturally occurring ACE2 stalk variants are differentially released from the cell.Scientific reports · 2026Article
- Circulating ACE2 levels and ACE I/D polymorphism in severe aortic stenosis.Scientific reports · 2026Article
- The balance between classical and alternative renin-angiotensin system in ARDS: a narrative review.Journal of intensive care · 2026Review
- Fecal ACE and ACE2 Activities Reflect Intestinal Shedding and Microbiota Modulation of Renin-Angiotensin System.Biology · 2026Article
- Epigenetic and microRNA-mediated regulation of pulmonary fibrosis and immune dysregulation in fatal COVID-19.Molecular medicine (Cambridge, Mass.) · 2026Article
- Naturally occurring ACE2 stalk variants are differentially released from the cell.bioRxiv : the preprint server for biology · 2026Article
- Vascular Immune Crosstalk in COVID-19: RAAS Biomarker Signature Linking Angiotensin II to Respiratory Compromise and Soluble ACE2 to IL-13 and FGF, Revealing Therapeutic Targets.International journal of molecular sciences · 2026Article
- Renin-angiotensin system activation and oxidative stress in hospitalized COVID-19 patients: a single-centre prospective observational study.Intensive care medicine experimental · 2026Article
- The ADAM Family of Proteases: Structure, Substrates, and Roles in Liver Diseases.International journal of molecular sciences · 2026Review
- Leukocytic ADAM10 and ADAM17 modulate disease severity and systemic outcome in bacterial and viral pneumonia.The European respiratory journal · 2026Article
- Microglial activation and RAS signaling: a dual-edged sword in neuroinflammation.American journal of physiology. Regulatory, integrative and comparative physiology · 2026Review
- RAAS antagonists dampen the SARS-CoV-2 infection in ex-vivo cultured human precision-cut lung slices.Respiratory research · 2026Article
- Viral receptors as host-pathogen control nodes linking entry, signalling, and system-level pathogenesis.FEMS microbiology reviews · 2026Review
- Host cell entry receptors as pharmacological targets in respiratory viral infections: from biology to clinical translation.Frontiers in cellular and infection microbiology · 2026Review
- Rosmarinic acid mitigates stress-induced gastric ulcers by targeting the ACE2/GPX4 interaction.Frontiers in pharmacology · 2026Article
- Natural Fatty Acids as Dual ACE2-Inflammatory Modulators: Integrated Computational Framework for Pandemic Preparedness.International journal of molecular sciences · 2025Article
- Targeting ACE2 with a camelid antibody inhibits SARS-CoV-2 binding and has protective effects in vivo.Nature communications · 2025Article
- ACE2: Friend or Foe in Post-COVID-19 Neurodegeneration?International journal of molecular sciences · 2025Review
398 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Angiotensin-converting enzyme-2 (ACE2) is a critical regulator of heart function and a cellular receptor for the causative agent of severe-acute respiratory syndrome (SARS), SARS-CoV (coronavirus). ACE2 is a type I transmembrane protein, with an extracellular N-terminal domain containing the active site and a short intracellular C-terminal tail. A soluble form of ACE2, lacking its cytosolic and transmembrane domains, has been shown to block binding of the SARS-CoV spike protein to its receptor. In this study, we examined the ability of ACE2 to undergo proteolytic shedding and investigated the mechanisms responsible for this shedding event. We demonstrated that ACE2, heterologously expressed in HEK293 cells and endogenously expressed in Huh7 cells, undergoes metalloproteinase-mediated, phorbol ester-inducible ectodomain shedding. By using inhibitors with differing potency toward different members of the ADAM (a disintegrin and metalloproteinase) family of proteases, we identified ADAM17 as a candidate mediator of stimulated ACE2 shedding. Furthermore, ablation of ADAM17 expression using specific small interfering RNA duplexes reduced regulated ACE2 shedding, whereas overexpression of ADAM17 significantly increased shedding. Taken together, these data provided direct evidence for the involvement of ADAM17 in the regulated ectodomain shedding of ACE2. The identification of ADAM17 as the protease responsible for ACE2 shedding may provide new insight into the physiological roles of ACE2.
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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.