Affinage

F11

Coagulation factor XI · UniProt P03951

Round 2 corrected
Length
625 aa
Mass
70.1 kDa
Annotated
2026-04-28
130 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Coagulation factor XI (FXI) is a disulfide-linked homodimeric zymogen of the contact pathway that, upon activation to FXIa, propagates coagulation by cleaving factor IX and thereby sustaining thrombin generation (PMID:19351955, PMID:1652157). Each subunit comprises four N-terminal apple domains arranged as a disk and a C-terminal trypsin-family serine protease domain; FXIIa or thrombin activates FXI by cleaving the Arg369–Ile370 bond, with thrombin feedback activation on negatively charged surfaces and platelet GPIbα representing the physiologically dominant activation route (PMID:3636155, PMID:1652157, PMID:28148841). The thrombin-FXI positive feedback loop sustains thrombin generation specifically when tissue factor pathway inhibitor (TFPI) is active, and FXI disulfide bonds regulated by thioredoxin-1 and protein disulfide isomerase modulate its activation efficiency (PMID:35352494, PMID:22704541). Genetic deficiency of FXI causes a bleeding disorder of variable severity—predominantly due to protein-misfolding mutations—and confers protection against thrombotic events (PMID:2813350, PMID:19652879, PMID:33094904).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1979 High

    Establishing that FXI circulates bound to high-molecular-weight kininogen (HMWK) via the HMWK light chain resolved how FXI localizes to activating surfaces and placed it within the contact system alongside prekallikrein.

    Evidence Quantitative binding and competition assays with purified FXI, prekallikrein, and HMWK

    PMID:291905

    Open questions at the time
    • Exact apple domain responsible for HMWK binding not mapped in this study
    • Physiological surface for contact assembly in vivo not identified
  2. 1986 High

    Determination of the complete primary structure of FXI revealed its unique homodimeric architecture with four apple-domain tandem repeats per subunit and a C-terminal serine protease domain, distinguishing it from other coagulation proteases and establishing its structural framework.

    Evidence cDNA cloning and amino acid sequencing of purified human FXI

    PMID:3636155

    Open questions at the time
    • Three-dimensional structure of apple domains and dimer interface unknown
    • Functional roles of individual apple domains not yet assigned
  3. 1988 High

    Identification of two distinct functional epitopes on the FXI heavy chain—one mediating HMWK binding/surface activation and another mediating FIX activation—demonstrated that the apple domains serve separable roles in cofactor engagement and substrate recognition.

    Evidence Domain-mapping with purified human anti-FXI antibodies (Baltimore, Winston-Salem) using Fab′ inhibition and functional assays

    PMID:2460161

    Open questions at the time
    • Precise apple-domain assignments for each function not resolved
    • Whether additional exosites exist on the heavy chain untested
  4. 1988 High

    Demonstration that protein C inhibitor forms a covalent 1:1 complex with FXIa, enhanced by heparin, established the first physiological serpin-based inhibitory mechanism for FXIa.

    Evidence Kinetic inhibition assays and SDS-PAGE of purified FXIa–PCI complexes

    PMID:2844223

    Open questions at the time
    • Relative in vivo contribution of PCI versus other serpins (e.g., antithrombin, C1-inhibitor) to FXIa regulation unclear
    • Effect of platelet surface on PCI inhibition not tested
  5. 1989 High

    Identification of three founder mutations in Ashkenazi Jewish patients (Type I splice defect, Type II Glu117Stop, Type III Phe283Leu) established the molecular genetic basis of FXI deficiency and linked it to a clinically variable bleeding disorder.

    Evidence PCR-based genotyping and sequencing of patient DNA; genotype–phenotype correlation in a cohort

    PMID:2052060 PMID:2813350

    Open questions at the time
    • Poor genotype–bleeding phenotype correlation left modifiers of clinical severity unresolved
    • Molecular mechanism of Phe283Leu dysfunction (misfolding vs. catalytic defect) not determined
  6. 1991 High

    The discovery that thrombin directly activates FXI—independently of FXIIa—on negatively charged surfaces overturned the view that FXI activation requires the contact pathway and introduced the thrombin-feedback loop as a central amplification mechanism in coagulation.

    Evidence Reconstituted kinetic assays with purified thrombin/FXI; clotting assays in FXII-deficient plasma with dextran sulfate/sulfatide

    PMID:1652157 PMID:2019570

    Open questions at the time
    • The physiological negatively charged surface in vivo was not identified
    • Relative contribution of thrombin-feedback vs. FXIIa-mediated activation in vivo remained unknown
  7. 1991 High

    Complete mapping of all 19 intrachain disulfide bonds per subunit and the single Cys321–Cys321 interchain bond defined the covalent architecture of the FXI homodimer and localized the dimerization linkage to apple domain 4.

    Evidence Peptide fragmentation and amino acid sequencing of purified FXI disulfide-linked fragments

    PMID:1998667

    Open questions at the time
    • Functional consequences of individual disulfide bond reduction not tested
    • Whether disulfide redox status is regulated in vivo was unknown
  8. 1996 High

    Identification of TFPI-2 as a potent Kunitz-type inhibitor of FXIa (Ki 15 nM) expanded the repertoire of endogenous FXIa regulators beyond serpins.

    Evidence In vitro amidolytic inhibition assays and plasma clotting assays with purified TFPI-2

    PMID:8555184

    Open questions at the time
    • In vivo relevance of TFPI-2 inhibition of FXIa not established
    • Whether TFPI-2 encounters FXIa at relevant tissue sites unclear
  9. 2009 High

    Plasma reconstitution experiments with recombinant FXI variants and function-blocking antibodies demonstrated that in FXII-independent coagulation, thrombin activates FXI which then sustains thrombin generation exclusively through FIX activation, placing FXI unambiguously between thrombin feedback and the tenase complex.

    Evidence Thrombin generation assays in FXII-deficient/inhibited plasma; recombinant FXI mutants; anti-FXIa and anti-FXI antibodies

    PMID:19351955

    Open questions at the time
    • Quantitative contribution of this loop in whole blood or under flow conditions not assessed
    • Role of platelet-bound FXI not explored in this system
  10. 2009 Medium

    Structural analysis of >120 missense mutations against the FXI crystal structure revealed that most FXI-deficiency mutations disrupt apple-domain β-sheet folding (CRM− mechanism) rather than active-site catalysis, explaining the predominance of quantitative over qualitative deficiency.

    Evidence Computational structural mapping of mutation database onto FXI dimer crystal structure coordinates

    PMID:19652879

    Open questions at the time
    • Predictions not validated by in vitro expression/folding studies for most variants
    • A minority of mutations lack structural rationalization
  11. 2010 High

    Crystal structures of zymogen FXI and the FXIa catalytic domain revealed the apple-domain disk architecture, localized ligand-binding sites, and explained how the heavy-chain scaffold controls activation and substrate engagement.

    Evidence X-ray crystallography with structure–function analysis

    PMID:20110423

    Open questions at the time
    • Full-length activated FXIa dimer structure not resolved
    • Conformational dynamics during activation not captured by static structures
  12. 2012 High

    Discovery that oxidoreductases TRX-1 and PDI reduce specific FXI disulfide bonds (Cys362–Cys482, Cys118–Cys147), markedly enhancing its activation, introduced redox regulation as a novel layer of FXI control and linked it to thrombotic risk in antiphospholipid syndrome.

    Evidence In vitro reduction and activation kinetics; mass spectrometry identification of reduced bonds; patient plasma ELISA

    PMID:22704541

    Open questions at the time
    • Whether TRX-1/PDI-mediated FXI reduction occurs on platelet surfaces in vivo is unresolved
    • Causal relationship between elevated reduced FXI and thrombosis in APS not established
  13. 2017 High

    Identification of platelet GPIbα as the receptor that facilitates thrombin-dependent FXI activation on platelets in vivo resolved a long-standing question about the physiological surface for thrombin-feedback activation, and ASO-mediated FXI depletion prevented thromboinflammation and hypertension in animal models.

    Evidence Genetic knockouts, anti-GPIbα antibodies, and FXI-targeting ASOs in mouse and rat hypertension models

    PMID:28148841

    Open questions at the time
    • Applicability of GPIbα-dependent mechanism to human platelet FXI activation not directly demonstrated
    • Whether FXI's role in hypertension extends beyond thromboinflammation is unclear
  14. 2020 High

    Genetic FXI deficiency reduced venous thrombus formation in flow-dependent but not stasis models, and FXI and FXII deficiency were non-additive, confirming they function in the same pathway and that FXI is dispensable for thrombus formation under complete stasis.

    Evidence Three distinct venous thrombosis models (stasis, stenosis, electrolytic) in FXI- and FXII-knockout mice

    PMID:33094904

    Open questions at the time
    • Mechanism by which flow selectively engages FXI/FXII pathway not elucidated
    • Extrapolation to human deep vein thrombosis contexts requires clinical validation
  15. 2022 High

    Mathematical modeling and experimental validation demonstrated that thrombin-feedback through FXI contributes to thrombin generation only when TFPI is active, providing a systems-level explanation for why FXI is important for sustained coagulation under physiological regulatory conditions.

    Evidence Extended Hockin-Mann model predictions validated by thrombin generation assays with anti-TFPI antibodies and FXI-depleted plasma

    PMID:35352494

    Open questions at the time
    • Whether additional regulators modulate the FXI–TFPI interplay in vivo is unexplored
    • Model does not incorporate platelet-surface reactions or flow

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full structural basis for FXIa engagement with FIX on physiological membranes, the quantitative balance between FXII-dependent and thrombin-dependent FXI activation in different human vascular beds, and the molecular determinants of the variable bleeding phenotype in FXI-deficient patients.
  • No co-crystal structure of FXIa bound to FIX
  • In vivo quantification of FXII-dependent vs. thrombin-dependent FXI activation in humans lacking
  • Genetic or proteomic modifiers of bleeding severity in FXI deficiency not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 3 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005576 extracellular region 3 GO:0005886 plasma membrane 1
Pathway
R-HSA-109582 Hemostasis 6
Partners
F12F2F9GP1BAKNG1SERPINA5TFPI2
Complex memberships
FXI homodimerFXI–HMWK complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1986 The complete amino acid sequence of human coagulation factor XI was determined from a cDNA library. Each of the two identical polypeptide chains of this disulfide-linked homodimer (607 amino acids) contains four tandem repeats of ~90 amino acids (subsequently named apple domains) in the N-terminal heavy chain and a C-terminal serine protease catalytic domain homologous to trypsin-family proteases. Factor XIIa cleaves the Arg369–Ile370 bond in each chain to generate activated FXIa. FXI shares 58% sequence identity with plasma prekallikrein. cDNA cloning, DNA sequencing, amino acid sequence analysis of purified protein Biochemistry High 3636155
1987 The human F11 gene spans 23 kb and comprises 15 exons and 14 introns. Exons I–II encode the 5′ UTR and signal peptide; exons III–X encode the four apple-domain tandem repeats (each repeat split by one intron at a conserved position); exons XI–XV encode the serine protease catalytic domain. The intron positions in the catalytic domain exons match those in tissue plasminogen activator and urokinase genes. Restriction mapping, Southern blotting, selective DNA sequencing of genomic phage clones Biochemistry High 2827746
1989 The human F11 gene was localized by in situ hybridization to chromosome 4q35 (distal end of the long arm), using a genomic DNA probe containing exons VIII, IX, and X. In situ hybridization with genomic DNA probe Cytogenetics and cell genetics High 2612218
1989 Three point mutations in the F11 gene cause factor XI deficiency in Ashkenazi Jews: a splice-junction mutation disrupting mRNA splicing (Type I), a nonsense mutation Glu117→Stop (Type II), and a missense mutation Phe283→Leu (Type III). Compound heterozygotes for Types II and III were identified, and there was no correlation found between genotype and bleeding tendency in the initial cohort. PCR amplification and restriction-enzyme digestion of patient DNA; direct sequencing Proceedings of the National Academy of Sciences of the United States of America High 2813350
1991 Factor XI is efficiently activated by thrombin (kcat/Km = 1.6 × 10⁵ M⁻¹s⁻¹) independently of factor XII, cleaving the same Arg–Ile bond as FXIIa. Dextran sulfate enhances thrombin-mediated FXI activation ~2000-fold, partly via FXI autoactivation by FXIa. This established a revised coagulation model in which thrombin feedback activates FXI. In vitro kinetic assays with purified proteins; plasma clotting assays with factor XII-deficient plasma Science High 1652157
1991 Human factor XI is activated by thrombin or autoactivation (by FXIa) only in the presence of negatively charged surfaces (dextran sulfate, sulfatide, heparin). The cleavage produces the same 50-kDa heavy chain and 35-kDa light chain as FXIIa-mediated activation, consistent with cleavage at the single Arg–Ile bond. Addition of thrombin plus sulfatide to FXII-deficient plasma shortened clotting time, confirming FXI activation in plasma independent of FXII. In vitro activation assays with purified proteins; SDS-PAGE analysis of cleavage products; plasma clotting time assays with FXII-deficient plasma The Journal of biological chemistry High 2019570
1991 The 19 disulfide bonds in each FXI subunit were mapped by amino acid sequencing of peptide fragments. The four apple domains each contain three internal disulfide bonds. The two identical subunits are covalently linked by a single intermolecular disulfide bond at Cys321 (in apple domain 4). Cys11 (apple domain 1) in each subunit forms an intrachain disulfide bond. Chemical and enzymatic digestion of purified FXI; amino acid sequence analysis of peptide fragments; disulfide bond assignment Biochemistry High 1998667
1979 Factor XI binds directly to high molecular weight kininogen (HMW-kininogen) with an association constant of 4.2 × 10⁸ M⁻¹. Prekallikrein and FXI compete for the same (or overlapping) binding site(s) on HMW-kininogen, and binding is mediated through the isolated light chain of HMW-kininogen. This interaction is essential for HMW-kininogen function as a coagulation cofactor. Binding assays with purified proteins; competition experiments; direct binding to isolated HMW-kininogen light chain Proceedings of the National Academy of Sciences of the United States of America High 291905
1988 Two naturally occurring human antibodies (Baltimore and Winston-Salem) against FXI both bind the heavy chain of FXIa but act on distinct functional domains: the Baltimore antibody (IgG1) blocks FXI binding to HMW-kininogen and thereby inhibits surface-mediated activation by FXIIa, but does not affect FXIa activation of FIX; the Winston-Salem antibody (IgG3) inhibits FXIa-mediated activation of FIX but does not block FXI–HMW-kininogen binding. Both leave the FXIa active site (light chain amidolytic activity) unaffected. Immunoaffinity purification; Fab′ fragment inhibition assays; FIX activation assay; HMW-kininogen binding assay; amidolytic activity assay Blood High 2460161
1988 Protein C inhibitor (PCI) inhibits factor XIa with a second-order rate constant of 0.94 × 10⁴ M⁻¹s⁻¹, which is enhanced ~10-fold by heparin (to 9.1 × 10⁴ M⁻¹s⁻¹). SDS-PAGE demonstrates covalent 1:1 complex formation of FXIa with PCI. The heavy chain of FXIa plays a minor role in the inhibition, as isolated FXIa light chains are inhibited at similar rates. Kinetic inhibition assays with purified proteins; SDS-PAGE and immunoblotting of complexes; isolated light chain experiments Biochemistry High 2844223
1991 Factor XI deficiency in Ashkenazi Jews is caused predominantly by Type II (Glu117Stop) and Type III (Phe283Leu) mutations, each accounting for ~49% and ~47% of alleles, respectively, in 43 probands. Type III homozygotes have residual FXI activity (~9.7% of normal) significantly higher than Type II homozygotes (~1.2%) or Type II/III compound heterozygotes (~3.3%), indicating that the Phe283Leu substitution impairs but does not abolish function. PCR amplification and restriction enzyme digestion of patient DNA; FXI clotting activity assays; clinical correlation The New England journal of medicine High 2052060
1996 TFPI-2/PP5, a Kunitz-type protease inhibitor, potently inhibits FXIa amidolytic activity with a Ki of 15 nM, as well as kallikrein (Ki = 25 nM) and plasmin (Ki = 3 nM). TFPI-2 prolonged coagulation time of plasma initiated by contact activation (which requires FXI), and heparin did not further enhance FXIa inhibition. Inhibition is at the FXIa active site (light chain). In vitro amidolytic inhibition assays with purified proteins; plasma clotting time assays Biochemistry High 8555184
2006 Mutation analysis of 116 UK index cases with FXI deficiency identified 140 causative F11 mutations (57 unique variants including 31 novel), confirming extensive molecular heterogeneity outside the Ashkenazi Jewish population. Common mutations E117X (Type II), F283L (Type III), and C128X account for 39.3% of alleles; whole gene deletions were also identified. Sequencing of F11 gene exons and flanking intronic regions in patient samples Human mutation Medium 16835901
2009 Structural analysis of 120 missense mutations across the F11 gene (70 in apple domains, 47 in serine protease domain) using a consensus apple-domain structure derived from the FXI dimer crystal structure revealed that the majority of FXI deficiency mutations (Type I: CRM-) cause protein misfolding rather than functional active-site defects (Type II: CRM+). The periphery of the apple-domain β-sheet is particularly sensitive to perturbation, and this β-sheet is critical for FXI dimer formation. Residues at the Ap4:Ap4 dimer interface are less directly involved in causing deficiency. Structural modeling using FXI dimer crystal structure; analysis of mutation database (183 mutations); homology modeling Thrombosis and haemostasis Medium 19652879
2009 In plasma systems where FXII is either inhibited or absent, FXI contributes significantly to thrombin generation when coagulation is initiated with low concentrations of tissue factor, FXa, or thrombin. Replacing FXI with a recombinant form that activates FIX poorly, or one that is poorly activated by thrombin, reduced thrombin generation. An antibody blocking FXIa activation of FIX reduced thrombin generation, while an antibody blocking FXI activation by FXIIa did not. This demonstrates a FXII-independent pathway in which thrombin activates FXI, and FXIa sustains thrombin generation via FIX activation. Thrombin generation assays in FXII-deficient or FXII-inhibited plasma; recombinant FXI variants; function-blocking antibodies Blood High 19351955
2010 Crystal structures of zymogen FXI and the FXIa catalytic domain reveal that FXI contains four apple domains forming a disk structure with extensive interface at the base of the catalytic domain. The apple-disk structure controls FXI activation, FXIa interaction with substrate FIX, and FXI binding to platelets. Structural data localize ligand-binding sites and explain how missense mutations impair FXI function. X-ray crystallography of FXI zymogen and FXIa catalytic domain; structure-function analysis Blood High 20110423
2012 FXI contains disulfide bonds (specifically Cys362–Cys482 and Cys118–Cys147) that are reduced to free thiols by oxidoreductases thioredoxin-1 (TRX-1) and protein disulfide isomerase (PDI). TRX-1-treated (reduced) FXI is activated significantly more efficiently by thrombin, FXIIa, or FXIa than non-reduced FXI. Patients with antiphospholipid syndrome (APS) thrombosis have higher plasma levels of reduced FXI than healthy controls. In vitro reduction assays with recombinant TRX-1 and PDI; FXI activation kinetics assays; novel ELISA for reduced FXI in patient plasma; mass spectrometry identification of reduced disulfide bonds Journal of autoimmunity High 22704541
2017 In angiotensin II-induced hypertension in mice, platelet-localized FXI mediates thrombin feedback amplification independently of FXII. The FXI receptor glycoprotein Ibα (GPIbα) on platelets is required for thrombin-dependent FXI feedback activation. Antisense oligonucleotide (ASO) inhibition of FXI synthesis prevented thrombin propagation on platelets, vascular leukocyte infiltration, endothelial dysfunction, and arterial hypertension in mice and rats, and reduced blood pressure in animals with established hypertension. Genetic and pharmacological (ASO) FXI inhibition in mouse/rat models of hypertension; platelet localization studies; GPIbα receptor identification by genetic and antibody experiments Science translational medicine High 28148841
2019 MAA868, a fully human antibody targeting the catalytic domain of FXI/FXIa, binds both the zymogen and activated forms with equal high affinity. Structural studies show MAA868 traps FXI/FXIa in an inactive, zymogen-like conformation, inhibiting the enzyme before it enters the coagulation process. MAA868 showed dose-dependent antithrombotic activity in a murine ferric chloride carotid occlusion model and sustained aPTT prolongation and FXI suppression in cynomolgus monkeys and healthy human subjects. Structural analysis (crystallography/binding studies); in vivo thrombosis model (ferric chloride, mouse); primate pharmacodynamics; phase I human clinical study Blood High 30692123
2020 Using three distinct mouse models of venous thrombosis (IVC stasis, IVC stenosis, and femoral vein electrolytic injury), FXI deficiency reduced thrombus weight and incidence in models with blood flow (stenosis and electrolytic injury) but not in the stasis model. FXI deficiency altered fibrin(ogen) content and neutrophil extracellular trap markers in the stasis model, indicating FXI affects thrombus composition. FXI and FXII deficiency produced equivalent and non-additive effects, consistent with their functioning in the same pathway. Genetic knockout mice (FXI-deficient, FXII-deficient); three in vivo venous thrombosis models; thrombus weight, fibrin, and NETs quantification Journal of thrombosis and haemostasis : JTH High 33094904
2022 Mathematical modeling combined with in vitro thrombin generation assays established that thrombin feedback activation of FXI contributes to thrombin generation propagation, but only when TFPI (tissue factor pathway inhibitor) is active. The extended Hockin-Mann (ext.HM) model predicted that selective elimination of TFPI's inhibitory function abolishes the FXI-positive feedback contribution; this was experimentally validated using anti-TFPI antibodies and FXI-depleted plasma in thrombin generation assays. Systems biology mathematical modeling; in vitro thrombin generation assays; function-blocking antibodies against TFPI; FXI-depleted plasma Journal of thrombosis and haemostasis : JTH High 35352494

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1999 Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nature genetics 1381 10391209
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
1991 Factor XI activation in a revised model of blood coagulation. Science (New York, N.Y.) 656 1652157
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2005 Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. Journal of proteome research 350 16335952
2000 Activation of hepatocyte growth factor and urokinase/plasminogen activator by matriptase, an epithelial membrane serine protease. The Journal of biological chemistry 347 10962009
1991 Activation of human blood coagulation factor XI independent of factor XII. Factor XI is activated by thrombin and factor XIa in the presence of negatively charged surfaces. The Journal of biological chemistry 328 2019570
1991 Factor XI deficiency in Ashkenazi Jews in Israel. The New England journal of medicine 313 2052060
2008 Reduced incidence of ischemic stroke in patients with severe factor XI deficiency. Blood 265 18268095
1986 Amino acid sequence of human factor XI, a blood coagulation factor with four tandem repeats that are highly homologous with plasma prekallikrein. Biochemistry 243 3636155
1989 Neural cell recognition molecule F11: homology with fibronectin type III and immunoglobulin type C domains. Neuron 217 2627374
2010 Patients with severe factor XI deficiency have a reduced incidence of deep-vein thrombosis. Thrombosis and haemostasis 211 21057700
2010 Genome-wide association of lipid-lowering response to statins in combined study populations. PloS one 190 20339536
2010 Structure and function of factor XI. Blood 183 20110423
1993 The axonal recognition molecule F11 is a multifunctional protein: specific domains mediate interactions with Ng-CAM and restrictin. Neuron 179 7682821
1992 Neuronal cell adhesion molecule contactin/F11 binds to tenascin via its immunoglobulin-like domains. The Journal of cell biology 168 1382076
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
1991 Transfected F3/F11 neuronal cell surface protein mediates intercellular adhesion and promotes neurite outgrowth. Neuron 161 2015094
2007 Association of genetic variations with nonfatal venous thrombosis in postmenopausal women. JAMA 152 17284699
1996 Inhibitory properties of a novel human Kunitz-type protease inhibitor homologous to tissue factor pathway inhibitor. Biochemistry 142 8555184
1987 Organization of the gene for human factor XI. Biochemistry 138 2827746
1988 Inactivation of human plasma kallikrein and factor XIa by protein C inhibitor. Biochemistry 137 2844223
1991 Location of the disulfide bonds in human coagulation factor XI: the presence of tandem apple domains. Biochemistry 135 1998667
2013 Congenital factor XI deficiency: an update. Seminars in thrombosis and hemostasis 129 23929304
2011 Genetics of venous thrombosis: insights from a new genome wide association study. PloS one 128 21980494
2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine. Journal of proteomics 126 23376485
1993 Direct coupling of opioid receptors to both stimulatory and inhibitory guanine nucleotide-binding proteins in F-11 neuroblastoma-sensory neuron hybrid cells. Proceedings of the National Academy of Sciences of the United States of America 124 8385355
2009 Factor XI contributes to thrombin generation in the absence of factor XII. Blood 120 19351955
2009 Coagulation factors IX through XIII and the risk of future venous thrombosis: the Longitudinal Investigation of Thromboembolism Etiology. Blood 116 19617576
1979 Studies of binding of prekallikrein and Factor XI to high molecular weight kininogen and its light chain. Proceedings of the National Academy of Sciences of the United States of America 116 291905
1987 Neurochemical characteristics of a novel dorsal root ganglion X neuroblastoma hybrid cell line, F-11. Journal of neurochemistry 114 2435852
1993 Induction of axonal growth by heterophilic interactions between the cell surface recognition proteins F11 and Nr-CAM/Bravo. Neuron 113 8274278
2014 Pseudoginsenoside-F11 (PF11) exerts anti-neuroinflammatory effects on LPS-activated microglial cells by inhibiting TLR4-mediated TAK1/IKK/NF-κB, MAPKs and Akt signaling pathways. Neuropharmacology 111 24467851
1992 F3/F11 cell surface molecule expression in the developing mouse cerebellum is polarized at synaptic sites and within granule cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 111 1729438
1989 Factor XI (plasma thromboplastin antecedent) deficiency in Ashkenazi Jews is a bleeding disorder that can result from three types of point mutations. Proceedings of the National Academy of Sciences of the United States of America 110 2813350
2019 MAA868, a novel FXI antibody with a unique binding mode, shows durable effects on markers of anticoagulation in humans. Blood 98 30692123
2001 Distinct subpopulations of sensory afferents require F11 or axonin-1 for growth to their target layers within the spinal cord of the chick. Neuron 93 11430805
1996 A HERG-like K+ channel in rat F-11 DRG cell line: pharmacological identification and biophysical characterization. The Journal of physiology 93 8910192
1998 Dissection of complex molecular interactions of neurofascin with axonin-1, F11, and tenascin-R, which promote attachment and neurite formation of tectal cells. The Journal of cell biology 92 9722619
2017 Platelet-localized FXI promotes a vascular coagulation-inflammatory circuit in arterial hypertension. Science translational medicine 90 28148841
2000 Cloning of the human platelet F11 receptor: a cell adhesion molecule member of the immunoglobulin superfamily involved in platelet aggregation. Blood 88 10753840
2000 Suppression of ganglioside GD3 expression in a rat F-11 tumor cell line reduces tumor growth, angiogenesis, and vascular endothelial growth factor production. Cancer research 84 11118051
2002 F11-receptor (F11R/JAM) mediates platelet adhesion to endothelial cells: role in inflammatory thrombosis. Thrombosis and haemostasis 82 12428104
1996 Neurofascin induces neurites by heterophilic interactions with axonal NrCAM while NrCAM requires F11 on the axonal surface to extend neurites. The Journal of cell biology 82 8922386
2006 Inhibition of spontaneous breast cancer metastasis by anti-Thomsen-Friedenreich antigen monoclonal antibody JAA-F11. Neoplasia (New York, N.Y.) 81 17132226
1995 Mechanisms of platelet activation by a stimulatory antibody: cross-linking of a novel platelet receptor for monoclonal antibody F11 with the Fc gamma RII receptor. The Biochemical journal 81 7646439
1992 Integrins on rat osteoclasts: characterization of two monoclonal antibodies (F4 and F11) to rat beta 3. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 80 1585837
1989 Factor XI gene (F11) is located on the distal end of the long arm of human chromosome 4. Cytogenetics and cell genetics 76 2612218
1987 Modulation of bradykinin-induced inositol trisphosphate release in a novel neuroblastoma x dorsal root ganglion sensory neuron cell line (F-11). Journal of neurochemistry 73 3494104
1995 The glypiated neuronal cell adhesion molecule contactin/F11 complexes with src-family protein tyrosine kinase Fyn. Molecular and cellular neurosciences 70 7496631
2013 Anti-amnesic effect of pseudoginsenoside-F11 in two mouse models of Alzheimer's disease. Pharmacology, biochemistry, and behavior 69 23541491
2018 Biodegradation of Diclofenac by the bacterial strain Labrys portucalensis F11. Ecotoxicology and environmental safety 65 29407776
1993 The hypertensive Y chromosome elevates blood pressure in F11 normotensive rats. Hypertension (Dallas, Tex. : 1979) 59 8505094
1995 Characterization of functional domains of the tenascin-R (restrictin) polypeptide: cell attachment site, binding with F11, and enhancement of F11-mediated neurite outgrowth by tenascin-R. The Journal of cell biology 57 7615642
2009 F11-mediated inhibition of RhoA signalling enhances the spread of vaccinia virus in vitro and in vivo in an intranasal mouse model of infection. PloS one 52 20041165
2007 Association of plasma levels of F11 receptor/junctional adhesion molecule-A (F11R/JAM-A) with human atherosclerosis. Journal of the American College of Cardiology 51 17964041
2007 The F11 receptor (F11R/JAM-A) in atherothrombosis: overexpression of F11R in atherosclerotic plaques. Thrombosis and haemostasis 47 17264957
2021 The F11 Receptor (F11R)/Junctional Adhesion Molecule-A (JAM-A) (F11R/JAM-A) in cancer progression. Molecular and cellular biochemistry 46 34533648
2014 Application of a subtractive genomics approach for in silico identification and characterization of novel drug targets in Mycobacterium tuberculosis F11. Interdisciplinary sciences, computational life sciences 45 24464704
2012 Factor XI is a substrate for oxidoreductases: enhanced activation of reduced FXI and its role in antiphospholipid syndrome thrombosis. Journal of autoimmunity 45 22704541
2005 The neuronal growth and regeneration associated Cntn1 (F3/F11/Contactin) gene is duplicated in fish: expression during development and retinal axon regeneration. Molecular and cellular neurosciences 45 15691716
1993 Identification of F11 fimbriae on chicken Escherichia coli strains. Infection and immunity 45 8094382
1992 F11 neuroblastoma x DRG neuron hybrid cells express inhibitory mu- and delta-opioid receptors which increase voltage-dependent K+ currents upon activation. Brain research 45 1330216
2013 Vaccinia virus F11 promotes viral spread by acting as a PDZ-containing scaffolding protein to bind myosin-9A and inhibit RhoA signaling. Cell host & microbe 44 23870313
2002 Two regions of the human platelet F11-receptor (F11R) are critical for platelet aggregation, potentiation and adhesion. Thrombosis and haemostasis 43 12008956
2000 Reduced cell migration, tumor growth and experimental metastasis of rat F-11 cells whose expression of GD3-synthase is suppressed. International journal of cancer 42 10962439
2006 Spectrum of factor XI (F11) mutations in the UK population--116 index cases and 140 mutations. Human mutation 41 16835901
2001 The 1.55 A resolution structure of Nicotiana alata S(F11)-RNase associated with gametophytic self-incompatibility. Journal of molecular biology 41 11724536
2018 Pseudoginsenoside-F11 alleviates cognitive deficits and Alzheimer's disease-type pathologies in SAMP8 mice. Pharmacological research 40 30394318
2004 Signaling pathways of the F11 receptor (F11R; a.k.a. JAM-1, JAM-A) in human platelets: F11R dimerization, phosphorylation and complex formation with the integrin GPIIIa. Journal of receptor and signal transduction research 39 15344881
1989 Neural cell recognition molecule F11: membrane interaction by covalently attached phosphatidylinositol. Biochemical and biophysical research communications 37 2735929
2006 Degradation of fluorobenzene by Rhizobiales strain F11 via ortho cleavage of 4-fluorocatechol and catechol. Applied and environmental microbiology 36 16980423
1997 Evidence for nicotinic receptors potentially modulating nociceptive transmission at the level of the primary sensory neuron: studies with F11 cells. Journal of neurochemistry 36 9282914
2021 PK/PD modeling of FXI antisense oligonucleotides to bridge the dose-FXI activity relation from healthy volunteers to end-stage renal disease patients. CPT: pharmacometrics & systems pharmacology 35 34085768
2005 The temperature-sensitive ion channel TRPV2 is endogenously expressed and functional in the primary sensory cell line F-11. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 35 15665528
2019 Pseudoginsenoside-F11 Protects against Transient Cerebral Ischemia Injury in Rats Involving Repressing Calcium Overload. Neuroscience 34 31129202
2018 Pseudoginsenoside-F11 attenuates cognitive impairment by ameliorating oxidative stress and neuroinflammation in d‑galactose-treated mice. International immunopharmacology 34 30537634
2011 Characterization of a dipartite iron uptake system from uropathogenic Escherichia coli strain F11. The Journal of biological chemistry 34 21596746
2009 Structural analysis of eight novel and 112 previously reported missense mutations in the interactive FXI mutation database reveals new insight on FXI deficiency. Thrombosis and haemostasis 34 19652879
2005 Genomic structure, organization and promoter analysis of the human F11R/F11 receptor/junctional adhesion molecule-1/JAM-A. Gene 34 16337094
1993 mu and delta opioid agonists at low concentrations decrease voltage-dependent K+ currents in F11 neuroblastoma x DRG neuron hybrid cells via cholera toxin-sensitive receptors. Brain research 34 8386968
2019 Long non-coding RNA F11-AS1 inhibits HBV-related hepatocellular carcinoma progression by regulating NR1I3 via binding to microRNA-211-5p. Journal of cellular and molecular medicine 32 31880390
2013 Neuroprotective effect of pseudoginsenoside-f11 on a rat model of Parkinson's disease induced by 6-hydroxydopamine. Evidence-based complementary and alternative medicine : eCAM 32 24386001
1999 Functional interactions of the immunoglobulin superfamily member F11 are differentially regulated by the extracellular matrix proteins tenascin-R and tenascin-C. The Journal of biological chemistry 32 10446214
1985 Monoclonal antibodies that recognize the P fimbriae F71, F72, F9, and F11 from uropathogenic Escherichia coli. Infection and immunity 32 2415458
1975 Endo-arabinanase from Bacillus subtilis F-11. Biochimica et biophysica acta 32 1096
2020 The bioremediation potentials and mercury(II)-resistant mechanisms of a novel fungus Penicillium spp. DC-F11 isolated from contaminated soil. Journal of hazardous materials 31 32361297
1994 Tenascin-contactin/F11 interactions: a clue for a developmental role? Perspectives on developmental neurobiology 31 7530143
2022 Association of FXI activity with thrombo-inflammation, extracellular matrix, lipid metabolism and apoptosis in venous thrombosis. Scientific reports 30 35697739
2015 Pseudoginsenoside-F11 inhibits methamphetamine-induced behaviors by regulating dopaminergic and GABAergic neurons in the nucleus accumbens. Psychopharmacology 30 26621348
2012 Nanotopography induced contact guidance of the F11 cell line during neuronal differentiation: a neuronal model cell line for tissue scaffold development. Nanotechnology 30 22710035
2003 Dual expression of mouse and rat VRL-1 in the dorsal root ganglion derived cell line F-11 and biochemical analysis of VRL-1 after heterologous expression. European journal of biochemistry 30 14622291
2013 Pseudoginsenoside F11, a Novel Partial PPAR γ Agonist, Promotes Adiponectin Oligomerization and Secretion in 3T3-L1 Adipocytes. PPAR research 28 24454336
2001 Overexpression of BETA2/NeuroD induces neurite outgrowth in F11 neuroblastoma cells. Journal of neurochemistry 28 11279266
1995 Chronic opioid treatment of neuroblastoma x dorsal root ganglion neuron hybrid F11 cells results in elevated GM1 ganglioside and cyclic adenosine monophosphate levels and onset of naloxone-evoked decreases in membrane K+ currents. Journal of neuroscience research 28 8568936
1988 Bradykinin induces the bi-phasic production of lysophosphatidyl inositol and diacylglycerol in a dorsal root ganglion X neurotumor hybrid cell line, F-11. Biochemical and biophysical research communications 28 3259133
2019 Functional inhibition of F11 receptor (F11R/junctional adhesion molecule-A/JAM-A) activity by a F11R-derived peptide in breast cancer and its microenvironment. Breast cancer research and treatment 27 31650345
2013 Computational screening of the human TF-glycome provides a structural definition for the specificity of anti-tumor antibody JAA-F11. PloS one 27 23365681
2020 Model-dependent contributions of FXII and FXI to venous thrombosis in mice. Journal of thrombosis and haemostasis : JTH 26 33094904
2019 Carbamazepine is degraded by the bacterial strain Labrys portucalensis F11. The Science of the total environment 26 31301512
2019 Pseudoginsenoside-F11 Accelerates Microglial Phagocytosis of Myelin Debris and Attenuates Cerebral Ischemic Injury Through Complement Receptor 3. Neuroscience 26 31790669
2014 The pseudoginsenoside F11 ameliorates cisplatin-induced nephrotoxicity without compromising its anti-tumor activity in vivo. Scientific reports 26 24832194
2009 Elevated plasma level of soluble F11 receptor/junctional adhesion molecule-A (F11R/JAM-A) in hypertension. American journal of hypertension 26 19214165
1995 Contactin/F11 and tenascin-C co-expression in the chick retina correlates with formation of the synaptic plexiform layers. Current eye research 26 8549157
2014 Preclinical studies with JAA-F11 anti-Thomsen-Friedenreich monoclonal antibody for human breast cancer. Future oncology (London, England) 25 24559446
2007 LMO4 mRNA stability is regulated by extracellular ATP in F11 cells. Biochemical and biophysical research communications 25 17418808
1992 Differential responses of Ca-activated K channels to bradykinin in sensory neurons and F-11 cells. The American journal of physiology 24 1539633
2021 Pseudoginsenoside F11 ameliorates the dysfunction of the autophagy-lysosomal pathway by activating calcineurin-mediated TFEB nuclear translocation in neuron during permanent cerebral ischemia. Experimental neurology 23 33422553
2020 Pseudoginsenoside-F11 attenuates cognitive dysfunction and tau phosphorylation in sporadic Alzheimer's disease rat model. Acta pharmacologica Sinica 23 33277592
1993 A volume-sensitive Cl- conductance in a mouse neuroblastoma x rat dorsal root ganglion cell line (F11). Brain research 23 8394184
1986 Functional relationship among the gene clusters encoding F7(1), F7(2), F9, and F11 fimbriae of human uropathogenic Escherichia coli. Journal of bacteriology 23 2873130
2019 Pseudoginsenoside-F11 Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Suppressing Neutrophil Infiltration and Accelerating Neutrophil Clearance. Inflammation 22 31332661
2018 Pseudoginsenoside-F11 alleviates oligomeric β-amyloid-induced endosome-lysosome defects in microglia. Traffic (Copenhagen, Denmark) 22 30375163
2017 High incidence of FXI deficiency in a Spanish town caused by 11 different mutations and the first duplication of F11: Results from the Yecla study. Haemophilia : the official journal of the World Federation of Hemophilia 22 28960694
2016 The anti-HER3 (ErbB3) therapeutic antibody 9F7-F11 induces HER3 ubiquitination and degradation in tumors through JNK1/2- dependent ITCH/AIP4 activation. Oncotarget 22 27203743
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2022 Revised model of the tissue factor pathway of thrombin generation: Role of the feedback activation of FXI. Journal of thrombosis and haemostasis : JTH 21 35352494
2014 Therapeutic application of CCK2R-targeting PP-F11: influence of particle range, activity and peptide amount. EJNMMI research 21 26116111
2012 Two new compounds from marine-derived fungus Penicillium sp. F11. Journal of Asian natural products research 21 22248032
2012 Modulation of the myxoma virus plaque phenotype by vaccinia virus protein F11. Journal of virology 21 22514354
1992 Solubility and posttranslational regulation of GP130/F11--a neuronal GPI-linked cell adhesion molecule enriched in the neuronal membrane skeleton. European journal of cell biology 21 1386308
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2000 Platelet agonist F11 receptor is a member of the immunoglobulin superfamily and identical with junctional adhesion molecule (JAM): regulation of expression in human endothelial cells and macrophages. IUBMB life 20 11087121
2019 Pseudoginsenoside-F11 improves long-term neurological function and promotes neurogenesis after transient cerebral ischemia in mice. Neurochemistry international 19 31756514
1997 The neural cell recognition molecule F11 is expressed on Müller cells and Schwann cells in vitro. Journal fur Hirnforschung 19 9059919