ArticlePloS one2012
The extended cleavage specificity of human thrombin.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed, 126 citations in OpenAlex.
- Reactive Oxygen Species-Induced Modifications of Fibrin Clots as a Link Between Immune Responses and Atherothrombosis in Systemic Lupus Erythematosus.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Plasma ECRG4 as a novel diagnostic marker for Alzheimer's disease associated with oligodendrocyte dysfunction.American journal of translational research · 2026Article
- The Influence of PAR 1 and Endothelin 1 on the Course of Specific Kidney Diseases.Journal of clinical medicine · 2025Article
- Catalytic Site Inhibitors of Group 1 Allergens Prevent Toll-like Receptor (TLR)4- and TLR1/2-Dependent Innate Responses in Keratinocytes and Airway Epithelial Cells Exposed to House Dust Mite Allergenic Extract.ACS pharmacology & translational science · 2025Article
- Structural determinants of protease-activated receptor 1 cleavage by activated protein C.Journal of thrombosis and haemostasis : JTH · 2025Article
- Serine proteases and protease-activated receptors signaling in the kidney.American journal of physiology. Cell physiology · 2025Review
- Thrombin cleaves membrane-bound endoglin potentially contributing to the heterogeneity of circulating endoglin in preeclampsia.Communications biology · 2025Article
- In vivo thrombin activity in the diatom Phaeodactylum tricornutum: biotechnological insights.Applied microbiology and biotechnology · 2024Article
- Oxidative stress-induced fibrinogen modifications in liver transplant recipients: unraveling a novel potential mechanism for cardiovascular risk.Research and practice in thrombosis and haemostasis · 2024Article
- Host Cell Proteases Involved in Human Respiratory Viral Infections and Their Inhibitors: A Review.Viruses · 2024Review
- Advanced nanomedicines and immunotherapeutics to treat respiratory diseases especially COVID-19 induced thrombosis.World journal of clinical cases · 2024Review
- Revealing the extracellular function of HMGB1 N-terminal region acetylation assisted by a protein semi-synthesis approach.Chemical science · 2023Article
- Chemical Tools to Image the Activity of PAR-Cleaving Proteases.ACS bio & med chem Au · 2023Review
- Thrombin cleavage of the hepatitis E virus polyprotein at multiple conserved locations is required for genome replication.PLoS pathogens · 2023Article
- Current Status of Oligonucleotide-Based Protein Degraders.Pharmaceutics · 2023Review
- Highly Efficient Cardiac Differentiation and Maintenance by Thrombin-Coagulated Fibrin Hydrogels Enriched with Decellularized Porcine Heart Extracellular Matrix.International journal of molecular sciences · 2023Article
- ZNF185 prevents stress fiber formation through the inhibition of RhoA in endothelial cells.Communications biology · 2023Article
- Extended cleavage specificities of human granzymes A and K, two closely related enzymes with conserved but still poorly defined functions in T and NK cell-mediated immunity.Frontiers in immunology · 2023Article
- Human plasma kallikrein: roles in coagulation, fibrinolysis, inflammation pathways, and beyond.Frontiers in physiology · 2023Review
- Comparative sequence analysis of vitamin K-dependent coagulation factors.Journal of thrombosis and haemostasis : JTH · 2022Article
2 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
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thrombin is one of the most extensively studied of all proteases. Its central role in the coagulation cascade as well as several other areas has been thoroughly documented. Despite this, its consensus cleavage site has never been determined in detail. Here we have determined its extended substrate recognition profile using phage-display technology. The consensus recognition sequence was identified as, P2-Pro, P1-Arg, P1'-Ser/Ala/Gly/Thr, P2'-not acidic and P3'-Arg. Our analysis also identifies an important role for a P3'-arginine in thrombin substrates lacking a P2-proline. In order to study kinetics of this cooperative or additive effect we developed a system for insertion of various pre-selected cleavable sequences in a linker region between two thioredoxin molecules. Using this system we show that mutations of P2-Pro and P3'-Arg lead to an approximate 20-fold and 14-fold reduction, respectively in the rate of cleavage. Mutating both Pro and Arg results in a drop in cleavage of 200-400 times, which highlights the importance of these two positions for maximal substrate cleavage. Interestingly, no natural substrates display the obtained consensus sequence but represent sequences that show only 1-30% of the optimal cleavage rate for thrombin. This clearly indicates that maximal cleavage, excluding the help of exosite interactions, is not always desired, which may instead cause problems with dysregulated coagulation. It is likely exosite cooperativity has a central role in determining the specificity and rate of cleavage of many of these in vivo substrates. Major effects on cleavage efficiency were also observed for residues as far away as 4 amino acids from the cleavage site. Insertion of an aspartic acid in position P4 resulted in a drop in cleavage by a factor of almost 20 times.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.