ArticleBlood advances2022
Model for surface-dependent factor XII activation: the roles of factor XII heavy chain domains.
Article in Blood advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Prekallikrein: the catalytic crossroads of inflammation and thrombosis.Current opinion in hematology · 2026Review
- Potential Role of Contact Pathway Factors in Catheter-Related Thrombosis: Emerging Evidence and Therapeutic Strategies.Biomolecules · 2026Review
- Bacterial factors required for biofilm formation inFrontiers in cellular and infection microbiology · 2026Article
- The immunomodulatory potential of bradykinin signaling in autoimmune conditions.Frontiers in immunology · 2026Review
- Crystal structure of coagulation factor XII N-terminal domains 1-5.Acta crystallographica. Section D, Structural biology · 2025Article
- A brief comparison of human factor XII-AlaResearch and practice in thrombosis and haemostasis · 2025Article
- Coagulation Factor XII Is an Antibacterial Protein That Acts Against Bacterial Infection via Its Heavy Chain.International journal of molecular sciences · 2025Article
- Article
- Advancements in research on the thrombo-inflammation mechanisms mediated by factor XII in ischemic stroke.Journal of thrombosis and thrombolysis · 2025Review
- ECMO-induced coagulopathy: strategic initiatives for research and clinical practice (a workshop report of the NHLBI).Blood vessels, thrombosis & hemostasis · 2025Review
- A model of zymogen factor XII: insights into protease activation.Blood advances · 2025Article
- Antithrombotic coating with sheltered positive charges prevents contact activation by controlling factor XII-biointerface binding.Nature materials · 2025Article
- Antifouling Zwitterionic Polymer Coatings for Blood-Bearing Medical Devices.Langmuir : the ACS journal of surfaces and colloids · 2025Review
- The physicochemical properties of lipopolysaccharide chemotypes regulate activation of the contact pathway of blood coagulation.The Journal of biological chemistry · 2025Article
- Factor XII Structure-Function Relationships.Seminars in thrombosis and hemostasis · 2024Review
- Targeting the Contact Pathway of Coagulation for the Prevention and Management of Medical Device-Associated Thrombosis.Seminars in thrombosis and hemostasis · 2024Review
- Factor XII signaling via uPAR-integrin β1 axis promotes tubular senescence in diabetic kidney disease.Nature communications · 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
- A site on factor XII required for productive interactions with polyphosphate.Journal of thrombosis and haemostasis : JTH · 2023Article
- Editorial: Kinin 2022 Meeting, Annecy, France.Journal of clinical medicine · 2023Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Factor XII (FXII) is the zymogen of a plasma protease (FXIIa) that contributes to bradykinin generation by converting prekallikrein to the protease plasma kallikrein (PKa). FXII conversion to FXIIa by autocatalysis or PKa-mediated cleavage is enhanced when the protein binds to negatively charged surfaces such as polymeric orthophosphate. FXII is composed of noncatalytic (heavy chain) and catalytic (light chain) regions. The heavy chain promotes FXII surface-binding and surface-dependent activation but restricts activation when FXII is not surface bound. From the N terminus, the heavy chain contains fibronectin type 2 (FN2), epidermal growth factor-1 (EGF1), fibronectin type 1 (FN1), EGF2, and kringle (KNG) domains and a proline-rich region. It shares this organization with its homolog, pro-hepatocyte growth factor activator (Pro-HGFA). To study the importance of heavy chain domains in FXII function, we prepared FXII with replacements of each domain with corresponding Pro-HGFA domains and tested them in activation and activity assays. EGF1 is required for surface-dependent FXII autoactivation and surface-dependent prekallikrein activation by FXIIa. KNG and FN2 are important for limiting FXII activation in the absence of a surface by a process that may require interactions between a lysine/arginine binding site on KNG and basic residues elsewhere on FXII. This interaction is disrupted by the lysine analog ε-aminocaproic acid. A model is proposed in which an ε-aminocaproic acid-sensitive interaction between the KNG and FN2 domains maintains FXII in a conformation that restricts activation. Upon binding to a surface through EGF1, the KNG/FN2-dependent mechanism is inactivated, exposing the FXII activation cleavage site.
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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.