ReviewThrombosis research2014
The mechanism underlying activation of factor IX by factor XIa.
Review in Thrombosis research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed, 53 citations in OpenAlex.
- Structural insights into the exosite-mediated activation of factor IX by factor XIa using cryogenic electron microscopy.Journal of thrombosis and haemostasis : JTH · 2026Article
- Emerging Targets, Novel Directions, and Innovative Approaches in Thrombosis Therapy.Aging and disease · 2025Review
- Multiplex, multimodal mapping of variant effects in secreted proteins.bioRxiv : the preprint server for biology · 2025Article
- Review
- Biology of factor XI.Blood · 2024Review
- The Molecular Basis of FIX Deficiency in Hemophilia B.International journal of molecular sciences · 2022Review
- F9 missense mutations impairing factor IX activation are associated with pleiotropic plasma phenotypes.Journal of thrombosis and haemostasis : JTH · 2022Article
- Lignosulfonic Acid Sodium Is a Noncompetitive Inhibitor of Human Factor XIa.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Studies on fragment-based design of allosteric inhibitors of human factor XIa.Bioorganic & medicinal chemistry · 2020Article
- Model-dependent contributions of FXII and FXI to venous thrombosis in mice.Journal of thrombosis and haemostasis : JTH · 2020Article
- Discovery of Benzyl Tetraphosphonate Derivative as Inhibitor of Human Factor Xia.ChemistryOpen · 2020Article
- Hydrogen-deuterium exchange mass spectrometry highlights conformational changes induced by factor XI activation and binding of factor IX to factor XIa.Journal of thrombosis and haemostasis : JTH · 2019Article
- A non-circulating pool of factor XI associated with glycosaminoglycans in mice.Journal of thrombosis and haemostasis : JTH · 2019Article
- Plasma kallikrein structure reveals apple domain disc rotated conformation compared to factor XI.Journal of thrombosis and haemostasis : JTH · 2019Article
- Genetic analysis of a hemophilia B family with a novel F9 gene mutation: A STROBE-compliant article.Medicine · 2019Observational
- A factor XIa-activatable hirudin-albumin fusion protein reduces thrombosis in mice without promoting blood loss.BMC biotechnology · 2018Article
- Structural Basis for Activity and Specificity of an Anticoagulant Anti-FXIa Monoclonal Antibody and a Reversal Agent.Structure (London, England : 1993) · 2018Article
- Inhibition of Factors XI and XII for Prevention of Thrombosis Induced by Artificial Surfaces.Seminars in thrombosis and hemostasis · 2018Review
- An update on factor XI structure and function.Thrombosis research · 2018Review
- Removal of the C-Terminal Domains of ADAMTS13 by Activated Coagulation Factor XI induces Platelet Adhesion on Endothelial Cells under Flow Conditions.Frontiers in medicine · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Factor XI (fXI) is the zymogen of a plasma protease, factor XIa (fXIa), that contributes to thrombin generation during blood coagulation by proteolytic conversion of factor IX (fIX) to factor IXaβ (fIXaβ). There is considerable interest in fXIa as a therapeutic target because it contributes to thrombosis, while serving a relatively minor role in hemostasis. FXI/XIa has a distinctly different structure than other plasma coagulation proteases. Specifically, the protein lacks a phospholipid-binding Gla-domain, and is a homodimer. Each subunit of a fXIa dimer contains four apple domains (A1 to A4) and one trypsin-like catalytic domain. The A3 domain contains a binding site (exosite) that largely determines affinity and specificity for the substrate fIX. After binding to fXIa, fIX undergoes a single cleavage to form the intermediate fIXα. FIXα then rebinds to the A3 domain to undergo a second cleavage, generating fIXaβ. The catalytic efficiency for the second cleavage is ~7-fold greater than that of the first cleavage, limiting fIXα accumulation. Residues at the N-terminus and C-terminus of the fXIa A3 domain likely form the fIX binding site. The dimeric conformation of fXIa is not required for normal fIX activation in solution. However, monomeric forms of fXI do not reconstitute fXI-deficient mice in arterial thrombosis models, indicating the dimer is required for normal function in vivo. FXI must be a dimer to be activated normal by the protease fXIIa. It is also possible that the dimeric structure is an adaptation that allows fXI/XIa to bind to a surface through one subunit, while binding to its substrate fIX through the other.
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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.