ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2022
The collectrin-like part of the SARS-CoV-1 and -2 receptor ACE2 is shed by the metalloproteinases ADAM10 and ADAM17.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Article
- Naturally occurring ACE2 stalk variants are differentially released from the cell.Scientific reports · 2026Article
- Naturally occurring ACE2 stalk variants are differentially released from the cell.bioRxiv : the preprint server for biology · 2026Article
- Leukocytic ADAM10 and ADAM17 modulate disease severity and systemic outcome in bacterial and viral pneumonia.The European respiratory journal · 2026Article
- Optimized ACE2-Fc fusion proteins with picomolar neutralization activity against highly evolved SARS-CoV-2 variants.Protein science : a publication of the Protein Society · 2026Article
- ACE2: Friend or Foe in Post-COVID-19 Neurodegeneration?International journal of molecular sciences · 2025Review
- Risk for COVID-19 Vulnerability in Patients with Inflammatory Bowel Disease: Assessing Alterations in ACE2 and TMPRSS2.Biomedicines · 2025Review
- Increased Cerebrospinal Fluid Angiotensin-Converting Enzyme 2 Fragments as a Read-Out of Brain Infection in Patients With COVID-19 Encephalopathy.The Journal of infectious diseases · 2025Article
- Association of Renin-Angiotensin Pathway Gene Polymorphisms with COVID-19 Susceptibility and Severity in Moroccans: A Case-Control Study.Biochemical genetics · 2025Article
- Angiotensin converting enzyme 2 in patients with sepsis associate with comorbidities but neither with mortality nor with organ failure.Scientific reports · 2025Observational
- Vasoactive Intestinal Peptide (VIP) in COVID-19 Therapy-Shedding of ACE2 and TMPRSS2 via ADAM10.International journal of molecular sciences · 2025Article
- ACE2, From the Kidney to SARS-CoV-2: Donald Seldin Award Lecture 2023.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Potential Effects of Hyperglycemia on SARS-CoV-2 Entry Mechanisms in Pancreatic Beta Cells.Viruses · 2024Review
- Downregulation of the metalloproteinases ADAM10 or ADAM17 promotes osteoclast differentiation.Cell communication and signaling : CCS · 2024Article
- ADAM-17 Activity and Its Relation to ACE2: Implications for Severe COVID-19.International journal of molecular sciences · 2024Article
- Pathological mutations reveal the key role of the cytosolic iRhom2 N-terminus for phosphorylation-independent 14-3-3 interaction and ADAM17 binding, stability, and activity.Cellular and molecular life sciences : CMLS · 2024Article
- A disintegrin and metalloproteinase domain 10 expression inhibition by the small molecules adenosine, cordycepin and N6, N6-dimethyladenosine and immune regulation in malignant cancers.Frontiers in immunology · 2024Article
- Genetic Predisposition to Elevated Levels of Circulating ADAM17 Is Associated with the Risk of Severe COVID-19.International journal of molecular sciences · 2023Article
- A structural model of the iRhom-ADAM17 sheddase complex reveals functional insights into its trafficking and activity.Cellular and molecular life sciences : CMLS · 2023Article
- How the Competition for Cysteine May Promote Infection of SARS-CoV-2 by Triggering Oxidative Stress.Antioxidants (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transmembrane protease angiotensin converting enzyme 2 (ACE2) is a protective regulator within the renin angiotensin system and additionally represents the cellular receptor for SARS-CoV. The release of soluble ACE2 (sACE2) from the cell surface is hence believed to be a crucial part of its (patho)physiological functions, as both, ACE2 protease activity and SARS-CoV binding ability, are transferred from the cell membrane to body fluids. Yet, the molecular sources of sACE2 are still not completely investigated. In this study, we show different sources and prerequisites for the release of sACE2 from the cell membrane. By using inhibitors as well as CRISPR/Cas9-derived cells, we demonstrated that, in addition to the metalloprotease ADAM17, also ADAM10 is an important novel shedding protease of ACE2. Moreover, we observed that ACE2 can also be released in extracellular vesicles. The degree of either ADAM10- or ADAM17-mediated ACE2 shedding is dependent on stimulatory conditions and on the expression level of the pro-inflammatory ADAM17 regulator iRhom2. Finally, by using structural analysis and in vitro verification, we determined for the first time that the susceptibility to ADAM10- and ADAM17-mediated shedding is mediated by the collectrin-like part of ACE2. Overall, our findings give novel insights into sACE2 release by several independent molecular mechanisms.
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