ArticlePloS one2018
Extended cleavage specificity of human neutrophil cathepsin G: A low activity protease with dual chymase and tryptase-type specificities.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Paneth Cells: Recent Updates on Elucidating Therapeutic Implications in Gastroenterological Disease Management.Current medicinal chemistry · 2025Pooled it
- PhageScout: Protease Cleavage Site Prediction Using an Experimental Substrate Phage Display Motif-Based Approach.International journal of molecular sciences · 2026Article
- Proteolysis activity mapping and substrate discovery platform for identifying tumor-activated biosensors.Nature chemical biology · 2026Article
- Neutrophil cathepsin G potentiates biased signaling through protease-activated receptor 4.Blood advances · 2026Article
- Tandem Duplication of Serpin Genes Yields Functional Variation and Snake Venom Inhibitors.Molecular biology and evolution · 2025Article
- Host Cell Proteases Involved in Human Respiratory Viral Infections and Their Inhibitors: A Review.Viruses · 2024Review
- Peptidomic analysis of endogenous and bacterial protease activity in human plasma and wound fluids.iScience · 2024Article
- Novel and unique rheumatoid factors cross-react with viral epitopes in COVID-19.Journal of autoimmunity · 2024Article
- How Do Microorganisms Influence the Development of Endometriosis? Participation of Genital, Intestinal and Oral Microbiota in Metabolic Regulation and Immunopathogenesis of Endometriosis.International journal of molecular sciences · 2023Review
- Proteolysis of vaginally administered bovine lactoferrin: clearance, inter-subject variability, and implications for clinical dosing.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2023Article
- Single-cell analysis reveals melanocytes may promote inflammation in chronic wounds through cathepsin G.Frontiers in genetics · 2023Article
- Characterization of proteolytic degradation products of vaginally administered bovine lactoferrin.PloS one · 2022Article
- Mast Cells and Basophils in the Defense against Ectoparasites: Efficient Degradation of Parasite Anticoagulants by the Connective Tissue Mast Cell Chymases.International journal of molecular sciences · 2021Article
- The Evolutionary History of theInternational journal of molecular sciences · 2021Review
- Proteolytic Cleavage of Bioactive Peptides and Protease-Activated Receptors in Acute and Post-Colitis.International journal of molecular sciences · 2021Article
- Platelets: "multiple choice" effectors in the immune response and their implication in COVID-19 thromboinflammatory process.International journal of laboratory hematology · 2021Review
- Origin and Expansion of the Serine Protease Repertoire in the Myelomonocyte Lineage.International journal of molecular sciences · 2021Review
- Article
- Hindrance of the Proteolytic Activity of Neutrophil-Derived Serine Proteases by Serine Protease Inhibitors as a Management of Cardiovascular Diseases and Chronic Inflammation.Frontiers in chemistry · 2021Review
- Activity-Based Probes to Utilize the Proteolytic Activity of Cathepsin G in Biological Samples.Frontiers in chemistry · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human neutrophils express at least four active serine proteases, cathepsin G, N-elastase, proteinase 3 and neutrophil serine protease 4 (NSP4). They have all been extensively studied due to their importance in neutrophil biology and immunity. However, their extended cleavage specificities have never been determined in detail. Here we present a detailed cleavage specificity analysis of human cathepsin G (hCG). The specificity was determined by phage display analysis and the importance of individual amino acids in and around the cleavage site was then validated using novel recombinant substrates. To provide a broader context to this serine protease, a comparison was made to the related mast cell protease, human chymase (HC). hCG showed similar characteristics to HC including both the primary and extended specificities. As expected, Phe, Tyr, Trp and Leu were preferred in the P1 position. In addition, both proteases showed a preference for negatively charged amino acids in the P2´ position of substrates and a preference for aliphatic amino acids both upstream and downstream of the cleavage site. However, overall the catalytic activity of hCG was ~10-fold lower than HC. hCG has previously been reported to have a dual specificity consisting of chymase and tryptase-type activities. In our analysis, tryptase activity against substrates with Lys in P1 cleavage position was indeed only 2-fold less efficient as compared to optimal chymase substrates supporting strong dual-type specificity. We hope the information presented here on extended cleavage specificities of hCG and HC will assist in the search for novel in vivo substrates for these proteases as well as aid in the efforts to better understand the role of hCG in immunity and bacterial defence.
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