ArticleThe Journal of biological chemistry2020
Intracellular autoactivation of TMPRSS11A, an airway epithelial transmembrane serine protease.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Polymorphism of tmprss2 (rs12329760) but not ace2 (rs4240157), tmprss11a (rs353163) and cd147 (rs8259) is associated with the severity of COVID-19 in the Ukrainian population.Acta bio-medica : Atenei Parmensis · 2023Pooled it
- TMPRSS11E-mediated TFR1 cleavage influences IFN-γR2 internalization and the macrophage innate response.Communications biology · 2025Article
- The impact of TMPRSS11A rs353163 and rs977728 polymorphisms on COVID-19 severity: genotypic and clinical associations.Molecular biology reports · 2025Article
- Cellular heterogeneity and patterning strategies as revealed by upper respiratory epithelium single cell atlas.iScience · 2025Article
- Structural basis of TMPRSS11D specificity and autocleavage activation.Nature communications · 2025Article
- Epithelial and immune transcriptomic characteristics and possible regulatory mechanisms in asthma exacerbation: insights from integrated studies.Frontiers in immunology · 2025Article
- Type II Transmembrane Serine Proteases as Modulators in Adipose Tissue Phenotype and Function.Biomedicines · 2023Review
- Identification and differential usage of a host metalloproteinase entry pathway by SARS-CoV-2 Delta and Omicron.iScience · 2022Article
- Evolutionary history of type II transmembrane serine proteases involved in viral priming.Human genetics · 2022Article
- TMPRSS13 zymogen activation, surface localization, and shedding is regulated by proteolytic cleavage within the non-catalytic stem region.Biological chemistry · 2022Article
- Structure and activity of human TMPRSS2 protease implicated in SARS-CoV-2 activation.Nature chemical biology · 2022Article
- Article
- Mechanism of N-0385 blocking SARS-CoV-2 to treat COVID-19 based on molecular docking and molecular dynamics.Frontiers in microbiology · 2022Article
- Neurotropism of SARS-CoV-2 and neurological diseases of the central nervous system in COVID-19 patients.Experimental brain research · 2022Review
- SARS-CoV-2-host proteome interactions for antiviral drug discovery.Molecular systems biology · 2021Article
- Priming of SARS-CoV-2 S protein by several membrane-bound serine proteinases could explain enhanced viral infectivity and systemic COVID-19 infection.The Journal of biological chemistryReview
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type II transmembrane serine proteases (TTSPs) are a group of enzymes participating in diverse biological processes. Some members of the TTSP family are implicated in viral infection. TMPRSS11A is a TTSP expressed on the surface of airway epithelial cells, which has been shown to cleave and activate spike proteins of the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome coronaviruses (CoVs). In this study, we examined the mechanism underlying the activation cleavage of TMPRSS11A that converts the one-chain zymogen to a two-chain enzyme. By expression in human embryonic kidney 293, esophageal EC9706, and lung epithelial A549 and 16HBE cells, Western blotting, and site-directed mutagenesis, we found that the activation cleavage of human TMPRSS11A was mediated by autocatalysis. Moreover, we found that TMPRSS11A activation cleavage occurred before the protein reached the cell surface, as indicated by studies with trypsin digestion to remove cell surface proteins, treatment with cell organelle-disturbing agents to block intracellular protein trafficking, and analysis of a soluble form of TMPRSS11A without the transmembrane domain. We also showed that TMPRSS11A was able to cleave the SARS-CoV-2 spike protein. These results reveal an intracellular autocleavage mechanism in TMPRSS11A zymogen activation, which differs from the extracellular zymogen activation reported in other TTSPs. These findings provide new insights into the diverse mechanisms in regulating TTSP activation.
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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.