ArticleBlood advances2020
The evolution of factor XI and the kallikrein-kinin system.
Article in Blood advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- Prekallikrein: the catalytic crossroads of inflammation and thrombosis.Current opinion in hematology · 2026Review
- Evolutionary conservation and divergence of phagocytic and coagulation programs across bilaterian circulating immune cells.Molecular biology and evolution · 2026Article
- Mechanism(s) of factor XI inhibition in clinical practice.Blood advances · 2026Article
- Crystal structure of coagulation factor XII N-terminal domains 1-5.Acta crystallographica. Section D, Structural biology · 2025Article
- High-throughput amino acid-level characterization of the interactions of plasminogen activator inhibitor-1 with variably divergent proteases.Protein science : a publication of the Protein Society · 2025Article
- Green biosynthetic silver nanoparticles fromMaterials today. Bio · 2025Article
- Keratin 1 modulates intestinal barrier and immune responseWorld journal of gastroenterology · 2025Article
- Factor XII Structure-Function Relationships.Seminars in thrombosis and hemostasis · 2024Review
- Plasma kallikrein supports FXII-independent thrombin generation in mouse whole blood.Blood advances · 2024Article
- Pharmacologic targeting of coagulation factors XII and XI by monoclonal antibodies reduces thrombosis in nitinol stents under flow.Journal of thrombosis and haemostasis : JTH · 2024Article
- Review
- Biochemical Approach to Poly(Lactide)-Copper Composite-Impact on Blood Coagulation Processes.Materials (Basel, Switzerland) · 2024Article
- High molecular weight kininogen interactions with the homologs prekallikrein and factor XI: importance to surface-induced coagulation.Journal of thrombosis and haemostasis : JTH · 2024Article
- Discovery of Teleost Plasma Kallikrein/Coagulation Factor XI-Like Gene from Channel Catfish (Ictalurus punctatus) and the Evidence that the Protein Encoded by it Acts as a Lectin.Journal of molecular evolution · 2023Article
- A site on factor XII required for productive interactions with polyphosphate.Journal of thrombosis and haemostasis : JTH · 2023Article
- Titanium is a potent inducer of contact activation: implications for intravascular devices.Journal of thrombosis and haemostasis : JTH · 2023Article
- Human plasma kallikrein: roles in coagulation, fibrinolysis, inflammation pathways, and beyond.Frontiers in physiology · 2023Review
- Domain Evolution of Vertebrate Blood Coagulation Cascade Proteins.Journal of molecular evolution · 2022Article
- Comparative sequence analysis of vitamin K-dependent coagulation factors.Journal of thrombosis and haemostasis : JTH · 2022Article
- Nanobodies against factor XI apple 3 domain inhibit binding of factor IX and reveal a novel binding site for high molecular weight kininogen.Journal of thrombosis and haemostasis : JTH · 2022Article
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Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
Abstract
Factor XI (FXI) is the zymogen of a plasma protease (FXIa) that contributes to hemostasis by activating factor IX (FIX). In the original cascade model of coagulation, FXI is converted to FXIa by factor XIIa (FXIIa), a component, along with prekallikrein and high-molecular-weight kininogen (HK), of the plasma kallikrein-kinin system (KKS). More recent coagulation models emphasize thrombin as a FXI activator, bypassing the need for FXIIa and the KKS. We took an evolutionary approach to better understand the relationship of FXI to the KKS and thrombin generation. BLAST searches were conducted for FXI, FXII, prekallikrein, and HK using genomes for multiple vertebrate species. The analysis shows the KKS appeared in lobe-finned fish, the ancestors of all land vertebrates. FXI arose later from a duplication of the prekallikrein gene early in mammalian evolution. Features of FXI that facilitate efficient FIX activation are present in all living mammals, including primitive egg-laying monotremes, and may represent enhancement of FIX-activating activity inherent in prekallikrein. FXI activation by thrombin is a more recent acquisition, appearing in placental mammals. These findings suggest FXI activation by FXIIa may be more important to hemostasis in primitive mammals than in placental mammals. FXI activation by thrombin places FXI partially under control of the vitamin K-dependent coagulation mechanism, reducing the importance of the KKS in blood coagulation. This would explain why humans with FXI deficiency have a bleeding abnormality, whereas those lacking components of the KKS do not.
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