Affinage

F10

Coagulation factor X · UniProt P00742

Round 2 corrected
Length
488 aa
Mass
54.7 kDa
Annotated
2026-04-28
130 papers in source corpus 19 papers cited in narrative 18 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Coagulation Factor X is a vitamin K-dependent serine protease that serves as the convergence point of the extrinsic and intrinsic coagulation pathways and, upon activation to Factor Xa, forms the catalytic subunit of the prothrombinase complex (with Factor Va, phospholipid, and Ca²⁺) to convert prothrombin to thrombin (PMID:3052293, PMID:12524220). Synthesized as a single-chain precursor containing Gla, EGF-like, and serine protease domains, FX undergoes intracellular processing to a disulfide-linked two-chain zymogen; its Gla domain, which carries 11 γ-carboxyglutamic acid residues and a β-hydroxyaspartic acid at position 63, is specifically required for activation by the extrinsic tenase (FVIIa/tissue factor), as demonstrated by the Glu19Ala mutation that selectively impairs this pathway (PMID:6871167, PMID:6587384, PMID:12195695). FXa activity is regulated by TFPI (which first inhibits FXa then uses the FXa–TFPI complex for feedback inhibition of FVIIa/TF), protein S (Kd ~18 nM, direct FXa inhibition independent of activated protein C), protein C inhibitor, and antithrombin (PMID:3422166, PMID:2271516, PMID:8146182, PMID:6323392). Beyond hemostasis, locally expressed FXa in lung tissue signals through PAR1 and integrin αvβ5 to activate TGF-β and drive myofibroblast differentiation in pulmonary fibrosis, and FXa upregulated in lung interstitial macrophages promotes breast cancer metastasis (PMID:19652365, PMID:36976637).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1983 High

    Determination of the complete light-chain amino acid sequence resolved the primary structure of the Gla domain and identified a novel post-translational modification (β-hydroxyaspartic acid at residue 63), establishing the chemical basis for FX's calcium- and membrane-binding properties.

    Evidence Automated Edman degradation with NMR and mass spectrometry confirmation of purified human FX light chain

    PMID:6871167

    Open questions at the time
    • Functional role of β-hydroxyaspartate at position 63 not established
    • Three-dimensional arrangement of Gla residues unknown at this stage
  2. 1984 High

    cDNA sequencing revealed that FX is synthesized as a single-chain precursor processed by cleavage of an internal Arg-Lys-Arg tripeptide into disulfide-linked light and heavy chains, establishing the biosynthetic pathway and confirming homology with other vitamin K-dependent proteases.

    Evidence cDNA library screening with anti-FX antibody and full-length sequencing

    PMID:6587384

    Open questions at the time
    • Intracellular processing site(s) and responsible protease(s) not identified
    • Regulation of FX expression not addressed
  3. 1986 High

    Gene structure analysis showed eight exons with boundaries matching Factor IX and protein C, demonstrating that each exon encodes a discrete functional domain and supporting the model that vitamin K-dependent coagulation factors evolved from a common ancestral gene.

    Evidence Bacteriophage cloning and DNA sequencing of the entire F10 gene with intron/exon mapping

    PMID:3768336

    Open questions at the time
    • Promoter and transcriptional regulation of F10 not characterized
    • No functional correlation between individual exon-encoded domains and activity
  4. 1988 High

    Reconstitution experiments established that FXa is the catalytic subunit of the prothrombinase complex and that TFPI (LACI) inhibits FXa directly, with the resulting FXa–TFPI complex required for feedback inhibition of FVIIa/TF — defining the central regulatory logic of coagulation initiation.

    Evidence In vitro prothrombinase reconstitution with kinetic assays; chromogenic and bioassay inhibition studies with Gla-domain-deleted FXa

    PMID:2271516 PMID:3052293 PMID:3422166

    Open questions at the time
    • Structural basis of FXa–TFPI interaction unknown
    • In vivo stoichiometry and kinetics of quaternary complex not determined
  5. 1993 High

    The first crystal structure of human Factor Xa (des-Gla, 2.2 Å) revealed the catalytic domain fold, inter-domain contacts between EGF2 and the protease domain, a catalytic-domain Ca²⁺ site, and reversed electrostatic polarity at the fibrinogen-recognition-equivalent surface compared to thrombin — explaining FXa's distinct substrate specificity.

    Evidence X-ray crystallography at 2.2 Å resolution

    PMID:8355279

    Open questions at the time
    • Full-length structure including Gla domain not obtained
    • No co-crystal with FVa or prothrombin substrate
  6. 1994 High

    Demonstration that protein S directly binds FXa (Kd ~18 nM) and inhibits its amidolytic and prothrombinase activities independently of activated protein C established a previously unrecognized anticoagulant mechanism operating through direct FXa regulation.

    Evidence Ligand blotting, fluid-phase binding assays, amidolytic and clotting assays with purified protein S and FXa

    PMID:8146182

    Open questions at the time
    • Binding interface on FXa not mapped
    • Physiological relevance relative to APC-dependent pathway not quantified in vivo
  7. 1996 High

    Co-crystal structure of FXa with inhibitor DX-9065a defined the active-site architecture — S1 pocket salt bridge with Asp-189, a unique S4 aryl-binding site lined by carbonyl oxygens, and S2 blockage by Tyr-99 — providing the structural framework that distinguishes FXa from thrombin for selective drug design.

    Evidence X-ray crystallography at 3.0 Å with synthetic inhibitor complex

    PMID:8939944

    Open questions at the time
    • No structure with macromolecular inhibitor (TFPI, antithrombin)
    • Dynamics of S4 pocket accommodation of diverse ligands not addressed
  8. 2002 High

    The Glu19Ala Gla-domain mutation demonstrated that a single residue change selectively abolishes extrinsic-pathway activation while leaving intrinsic-pathway activation intact, proving the Gla domain mediates a specific molecular interaction with the FVIIa/TF complex rather than simply anchoring FX to membranes.

    Evidence Recombinant FX mutant expression with activation assays using purified FVIIa/TF, FIXa/FVIIIa, and RVV

    PMID:12195695

    Open questions at the time
    • Exact contact residues between Gla domain and TF/FVIIa not mapped structurally
    • Other Gla-domain residues contributing to extrinsic pathway specificity not systematically tested
  9. 2008 High

    Discovery that the FX Gla domain binds adenovirus serotype 5 hexon (Kd ~229 pM) and that the FX serine protease domain contains a heparin-binding exosite mediating hepatocyte entry revealed an unexpected role for a coagulation factor as a blood-borne bridge enabling viral liver tropism.

    Evidence SPR binding, cryo-EM single-particle reconstruction, hexon-mutant Ad5 with ablated FX binding, in vivo hepatocyte transduction assays

    PMID:18267072 PMID:18391209

    Open questions at the time
    • Cellular receptor on hepatocytes engaged by FX-coated virus not identified
    • Whether other vitamin K-dependent factors can substitute for FX in vivo not tested
  10. 2009 High

    Two key mechanistic advances: (1) mutagenesis of hexon HVR5/HVR7 defined the minimal FX-binding determinants on the adenovirus surface, and (2) locally expressed FXa in fibrotic lung was shown to drive myofibroblast differentiation via PAR1 and integrin αvβ5–mediated TGF-β activation, establishing a non-hemostatic pro-fibrotic signaling axis.

    Evidence Domain swapping/site-directed mutagenesis of Ad5/Ad26 hexon with SPR and in vivo transduction; FXa treatment of primary human lung fibroblasts with PAR1/αvβ5 inhibitors; bleomycin mouse fibrosis model with FXa inhibitor

    PMID:19429866 PMID:19652365

    Open questions at the time
    • Downstream signaling cascade between PAR1/αvβ5 and TGF-β activation not fully delineated
    • Whether FXa's fibrotic role extends beyond the lung not established
    • Hepatocyte receptor for FX-Ad5 complex remains unidentified
  11. 2023 Medium

    Identification of FX upregulation in lung interstitial macrophages after chemotherapy, with FXa promoting breast cancer lung metastasis, extended the non-hemostatic biology of FXa to tumor–immune crosstalk.

    Evidence Transgenic breast cancer model with gemcitabine, flow cytometry, F10 knockdown (siRNA/shRNA), FXa inhibitor, in vivo metastasis quantification

    PMID:36976637

    Open questions at the time
    • Mechanism by which macrophage-derived FXa promotes metastasis (PAR signaling, ECM remodeling, or other) not defined
    • Generalizability beyond breast cancer lung metastasis not tested
    • Single study awaiting independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of FXa interaction with FVa in the assembled prothrombinase complex, the identity of the hepatocyte receptor engaged by FX-coated adenovirus, the full signaling pathway linking macrophage FXa to metastatic niche formation, and whether FXa's non-hemostatic functions (fibrosis, metastasis) share a common PAR-dependent mechanism.
  • No high-resolution structure of full prothrombinase complex
  • Hepatocyte receptor for FX–Ad5 unknown
  • Common vs. distinct signaling of FXa in fibrosis and metastasis not compared

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0008289 lipid binding 3 GO:0016787 hydrolase activity 3
Localization
GO:0005576 extracellular region 4 GO:0005886 plasma membrane 2
Pathway
R-HSA-109582 Hemostasis 6 R-HSA-162582 Signal Transduction 2
Partners
F2F3F5F7PROS1SERPINA5TFPI
Complex memberships
FXa–TFPI–FVIIa/TF quaternary complexProthrombinase complex (FXa/FVa/phospholipid/Ca²⁺)

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1983 The complete amino acid sequence of the light chain of human coagulation Factor X was determined, revealing 139 residues including 11 gamma-carboxyglutamic acid (Gla) residues; residue 63 was identified as L-erythro-beta-hydroxyaspartic acid, a novel post-translational modification not previously described in proteins. Automated Edman degradation of peptides from chemical and enzymatic digests, confirmed by proton NMR and mass spectrometry Biochemistry High 6871167
1984 cDNA sequencing of human Factor X established that it is synthesized as a single-chain polypeptide containing both light and heavy chains connected by an Arg-Lys-Arg tripeptide; the two chains are then generated by cleavage of internal peptide bonds and linked by a disulfide bond in plasma. The heavy chain active site shows high DNA sequence identity with prothrombin and Factor IX. cDNA library screening with anti-Factor X antibody, DNA sequencing of positive clones Proceedings of the National Academy of Sciences of the United States of America High 6587384
1986 The gene organization of human Factor X was characterized, revealing seven introns and eight exons whose boundaries are essentially identical to those in Factor IX and protein C genes, with each exon encoding a discrete structural/functional domain (Gla domain, EGF-like domains, activation peptide, serine protease domain). This organization strongly supports evolution of vitamin K-dependent coagulation factors from a common ancestral gene. Recombinant bacteriophage isolation, DNA sequencing to map intron/exon boundaries Biochemistry High 3768336
1988 Factor Xa functions as a component of the prothrombinase complex, requiring cofactor Factor Va, phospholipid membrane surfaces, and calcium ions to efficiently cleave prothrombin to thrombin. Factor Xa's serine protease activity is the catalytic center of this complex. In vitro reconstitution of prothrombinase complex; kinetic enzyme assays Annual review of biochemistry High 3052293
1988 The lipoprotein-associated coagulation inhibitor (LACI, later named TFPI) directly inhibits Factor Xa at or near its active site, forming a Factor Xa-LACI complex detectable by non-denaturing PAGE. This Xa-LACI complex is required for subsequent feedback inhibition of the Factor VIIa/tissue factor complex, requiring the Gla domain of Xa. Heparin accelerates Xa inhibition ~2.5-fold; phospholipid and Ca2+ slow it ~2.5-fold. Chromogenic substrate assays, bioassays, non-denaturing PAGE, SDS-PAGE complex visualization, use of Gla-domain-lacking BXa(-GD) construct Blood High 3422166
1990 Tissue Factor Pathway Inhibitor (TFPI) regulates coagulation via a two-step mechanism: it first directly inhibits Factor Xa, then in a Factor Xa-dependent manner produces feedback inhibition of the Factor VIIa/tissue factor catalytic complex. This explains why both extrinsic and intrinsic coagulation pathways are clinically required for hemostasis. Kinetic inhibition assays, reconstituted coagulation system Biochemistry High 2271516
1993 The crystal structure of human des(1-45) Factor Xa (lacking the Gla domain) was solved at 2.2 Å resolution, revealing: the catalytic domain fold is similar to alpha-thrombin; the second EGF-like module makes contacts with the catalytic domain; the C-terminal Arg of the A-chain interacts in a substrate-like manner with the S1 specificity pocket of a neighboring molecule; and there is a Ca2+-binding site in the catalytic domain. The structure also showed that the region corresponding to the fibrinogen recognition site of thrombin has reversed electrical polarity in Factor Xa. X-ray crystallography at 2.2 Å resolution, R-value 0.168; automated Edman degradation for fragment identity Journal of molecular biology High 8355279
1994 Protein S directly binds Factor Xa (Kd ~18-19 nM) independent of activated protein C, and directly inhibits Factor Xa amidolytic activity (~50% inhibition at 33 nM protein S). Protein S also inhibits prothrombin conversion by Factor Xa in a phospholipid-independent, Ca2+-stimulated manner. Protein S inhibition of prothrombinase was 2.3-fold more potent in the presence of Factor Va, with ~8 nM protein S causing 50% inhibition. Ligand blotting, immobilized protein binding assays, fluid-phase binding with Kd determination, amidolytic activity assays, one-stage clotting time assay Proceedings of the National Academy of Sciences of the United States of America High 8146182
1984 Protein C inhibitor (from human plasma) inhibits Factor Xa with an inhibition constant (Ki) of 3.1 × 10⁻⁷ M. The inhibitor forms an enzyme-inhibitor complex (apparent Mr ~102,000 non-reduced) with Factor Xa; heparin (5-10 units/ml) accelerates inhibition of activated protein C ~30-fold and also accelerates Factor Xa inhibition. The complex can be dissociated by ammonia or hydroxylamine, releasing active enzyme. Kinetic inhibition assays, SDS-PAGE of enzyme-inhibitor complexes, 125I-labeled inhibitor autoradiography Journal of biochemistry High 6323392
1996 The 3.0 Å crystal structure of human des-Gla Factor Xa in complex with the synthetic inhibitor DX-9065a revealed two principal binding interactions: the naphthamidine group forms a salt bridge with Asp-189 in the S1 pocket, and the pyrrolidine ring binds in a unique aryl-binding site (S4). Unlike thrombin inhibitor complexes, Gly-216 (S3) does not contribute hydrogen bonds. The S2 site is blocked by Tyr-99, distinguishing Factor Xa from thrombin. The S4 site is lined by carbonyl oxygens that accommodate positive charges. X-ray crystallography at 3.0 Å resolution with synthetic inhibitor complex The Journal of biological chemistry High 8939944
2002 A Glu19Ala mutation in the Gla domain of Factor X causes symptomatic CRMred Factor X deficiency by specifically impairing activation via the Factor VIIa/tissue factor (extrinsic) pathway: complete activation of recombinant 19Ala-FX required 30-fold higher Factor VIIa/TF concentration than wild-type. Activation by Factor IXa/VIIIa or Russell's viper venom (RVV), and thrombin generation activity, were comparable to wild-type, demonstrating the Gla domain mediates specific interaction with the extrinsic pathway. Recombinant protein expression, activation assays with purified Factor VIIa/TF, FIXa/FVIIIa, and RVV; thrombin generation assays; prothrombin time and APTT plasma assays Thrombosis and haemostasis High 12195695
2003 Factor Xa generation through the tissue factor pathway is the central event of hemostasis, with thrombin playing multiple autocatalytic and feedback roles in its own generation and inhibition. Two Factor Xa-generating complexes exist: the extrinsic tenase (Factor VIIa/TF) for initiation, and the intrinsic tenase (Factor IXa/VIIIa) for amplification/propagation; stoichiometric inhibitors (TFPI, antithrombin) and dynamic mechanisms regulate the process. Review integrating in vitro reconstitution and kinetic data from multiple studies Arteriosclerosis, thrombosis, and vascular biology High 12524220
2007 A homozygous nonstop mutation (F10-Augusta) in the Factor X gene — combining an 8-bp insertion in 3'-genomic DNA and a 5-bp deletion in terminal exon 8 — results in complete absence of Factor X protein and severe hemorrhage. The mutant transcript lacks an in-frame stop codon, and its steady-state concentration is markedly lower than wild-type message, implicating the nonstop mRNA decay (NMD) surveillance pathway as the pathogenic mechanism reducing FX expression. Gene sequencing, RT-PCR, 3'-RACE, allele-specific RFLP assay comparing mutant vs. wild-type transcript levels in patient and heterozygous parent RNA Thrombosis and haemostasis High 18064309
2008 Coagulation Factor X (FX) binds to the adenovirus serotype 5 (Ad5) hexon protein — specifically to the hypervariable regions (HVRs) on the hexon surface — via an interaction between the FX Gla domain and hexon. The FX serine protease domain contains a heparin-binding exosite that mediates infection of hepatocytes. Cryo-electron microscopy and single-particle reconstruction localized the FX attachment site to the central depression at the top of the hexon trimer. Hexon-mutated virus with reduced FX binding failed to transduce hepatocytes in vivo. Affinity binding assays (FX binding affinity 229 pM by SPR), cryo-electron microscopy with single-particle image reconstruction, in vivo hepatocyte transduction with hexon-mutated virus Cell High 18267072 18391209
2009 Systematic mutagenesis identified specific amino acids on Ad5 hexon HVR5 and HVR7 critical for FX binding: mutation of 2 amino acids in HVR5 or 4 amino acids in HVR7 (or a single mutation at position 451 in HVR7) was sufficient to ablate FX-mediated liver transduction in vitro and in vivo. FX binding requires the hexon HVR5 and HVR7 regions, as demonstrated by domain swapping with Ad26 (which does not bind FX). Surface plasmon resonance (SPR) binding assays, domain swapping between Ad5 and Ad26, site-directed mutagenesis, in vitro gene delivery, in vivo liver transduction Blood High 19429866
2009 Factor X expression is locally upregulated in fibrotic lung tissue (bronchial and alveolar epithelia) in human idiopathic pulmonary fibrosis and murine bleomycin models. Locally produced FXa drives myofibroblast differentiation in primary human lung fibroblasts via TGF-beta activation mediated through proteinase-activated receptor-1 (PAR1) and integrin αvβ5. Direct FXa inhibition attenuated bleomycin-induced pulmonary fibrosis in mice, establishing a causal mechanistic link. Immunostaining of human biopsy specimens, in vitro myofibroblast differentiation assay with recombinant FXa, PAR1/integrin αvβ5 inhibitor studies, in vivo bleomycin mouse model with FXa inhibitor treatment The Journal of clinical investigation High 19652365
2010 FX-binding ablated Ad5 vectors (with mutations abolishing hexon-FX interaction) show highly reduced liver transduction but preferentially localize to liver and spleen 1 hour post-injection, with spleen transduction (CD11c+, ER-TR7+, MAdCAM-1+ cells in the marginal zone) becoming more efficient at high doses. This demonstrates that FX binding is specifically required for hepatocyte transduction but not for initial hepatic/splenic biodistribution. In vivo biodistribution studies, immunohistochemistry with cell-type markers, transgene co-localization, macrophage depletion experiments Blood High 20610817
2023 Factor X (FX) is upregulated in lung interstitial macrophages following gemcitabine chemotherapy, and activated FX (FXa) contributes to a pro-metastatic host response. Targeting FXa with an FXa inhibitor or F10 gene knockdown reduced chemotherapy-induced pro-metastatic effects, demonstrating that FXa in macrophages promotes breast cancer lung metastasis through interplay between coagulation and inflammation. Transgenic spontaneous breast cancer model, gemcitabine treatment, flow cytometry, CCR2 knockout, F10 gene knockdown with siRNA/shRNA, FXa inhibitor pharmacological treatment, in vivo metastasis quantification JCI insight Medium 36976637

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
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
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2004 The human plasma proteome: a nonredundant list developed by combination of four separate sources. Molecular & cellular proteomics : MCP 658 14718574
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1988 Cofactor proteins in the assembly and expression of blood clotting enzyme complexes. Annual review of biochemistry 534 3052293
2008 Adenovirus serotype 5 hexon mediates liver gene transfer. Cell 526 18267072
1988 The lipoprotein-associated coagulation inhibitor that inhibits the factor VII-tissue factor complex also inhibits factor Xa: insight into its possible mechanism of action. Blood 481 3422166
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2003 The dynamics of thrombin formation. Arteriosclerosis, thrombosis, and vascular biology 387 12524220
1993 Structure of human des(1-45) factor Xa at 2.2 A resolution. Journal of molecular biology 385 8355279
2010 Assessment of laboratory assays to measure rivaroxaban--an oral, direct factor Xa inhibitor. Thrombosis and haemostasis 384 20135059
1990 Regulation of coagulation by a multivalent Kunitz-type inhibitor. Biochemistry 381 2271516
1991 Thymosin beta 4 and Fx, an actin-sequestering peptide, are indistinguishable. The Journal of biological chemistry 308 1999398
2010 Clinical laboratory measurement of direct factor Xa inhibitors: anti-Xa assay is preferable to prothrombin time assay. Thrombosis and haemostasis 302 20978714
2008 Adenovirus serotype 5 hexon is critical for virus infection of hepatocytes in vivo. Proceedings of the National Academy of Sciences of the United States of America 289 18391209
2010 Randomised, parallel-group, multicentre, multinational phase 2 study comparing edoxaban, an oral factor Xa inhibitor, with warfarin for stroke prevention in patients with atrial fibrillation. Thrombosis and haemostasis 284 20694273
1996 X-ray structure of active site-inhibited clotting factor Xa. Implications for drug design and substrate recognition. The Journal of biological chemistry 261 8939944
2009 Increased local expression of coagulation factor X contributes to the fibrotic response in human and murine lung injury. The Journal of clinical investigation 260 19652365
2011 Effects of the oral, direct factor Xa inhibitor rivaroxaban on commonly used coagulation assays. Journal of thrombosis and haemostasis : JTH 247 20946166
1995 Tissue factor pathway inhibitor and the revised theory of coagulation. Annual review of medicine 233 7598447
2006 Influence of coagulation factor, vitamin K epoxide reductase complex subunit 1, and cytochrome P450 2C9 gene polymorphisms on warfarin dose requirements. Clinical pharmacology and therapeutics 219 16580898
1986 Gene for human factor X: a blood coagulation factor whose gene organization is essentially identical with that of factor IX and protein C. Biochemistry 218 3768336
1993 Identification of a region of beta 2-glycoprotein I critical for lipid binding and anti-cardiolipin antibody cofactor activity. Proceedings of the National Academy of Sciences of the United States of America 185 8460120
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
1994 Protein S binds to and inhibits factor Xa. Proceedings of the National Academy of Sciences of the United States of America 160 8146182
2009 Identification of coagulation factor (F)X binding sites on the adenovirus serotype 5 hexon: effect of mutagenesis on FX interactions and gene transfer. Blood 152 19429866
1983 Complete amino acid sequence of the light chain of human blood coagulation factor X: evidence for identification of residue 63 as beta-hydroxyaspartic acid. Biochemistry 151 6871167
1999 Estrogen receptor-alpha detected on the plasma membrane of aldehyde-fixed GH3/B6/F10 rat pituitary tumor cells by enzyme-linked immunocytochemistry. Endocrinology 148 10433242
1984 Characterization of a cDNA coding for human factor X. Proceedings of the National Academy of Sciences of the United States of America 147 6587384
1996 Synthesis of GDP-L-fucose by the human FX protein. The Journal of biological chemistry 146 8910301
1984 Mechanism of inhibition of activated protein C by protein C inhibitor. Journal of biochemistry 145 6323392
2014 A review of exosome separation techniques and characterization of B16-F10 mouse melanoma exosomes with AF4-UV-MALS-DLS-TEM. Analytical and bioanalytical chemistry 135 25084738
2010 Biodistribution and retargeting of FX-binding ablated adenovirus serotype 5 vectors. Blood 94 20610817
2013 Anthocyanin determination in blueberry extracts from various cultivars and their antiproliferative and apoptotic properties in B16-F10 metastatic murine melanoma cells. Phytochemistry 89 23890760
1997 Transforming growth factor-beta1 inhibits basal melanogenesis in B16/F10 mouse melanoma cells by increasing the rate of degradation of tyrosinase and tyrosinase-related protein-1. The Journal of biological chemistry 66 9020101
1999 Tyrosine phosphorylation of A17 during vaccinia virus infection: involvement of the H1 phosphatase and the F10 kinase. Journal of virology 60 10438817
2017 Antiproliferative and proapoptotic activities of anthocyanin and anthocyanidin extracts from blueberry fruits on B16-F10 melanoma cells. Food & nutrition research 58 28680383
2006 Embryonic stem cell-derived dendritic cells expressing glypican-3, a recently identified oncofetal antigen, induce protective immunity against highly metastatic mouse melanoma, B16-F10. Cancer research 58 16489048
2002 Pax3 down-regulation and shut-off of melanogenesis in melanoma B16/F10.9 by interleukin-6 receptor signaling. The Journal of biological chemistry 58 11830592
2010 Antitumor properties of aloe-emodin and induction of transglutaminase 2 activity in B16-F10 melanoma cells. Life sciences 57 20624404
2008 Alkylphenol xenoestrogens with varying carbon chain lengths differentially and potently activate signaling and functional responses in GH3/B6/F10 somatomammotropes. Environmental health perspectives 57 19479013
2017 An Alkynyl-Fucose Halts Hepatoma Cell Migration and Invasion by Inhibiting GDP-Fucose-Synthesizing Enzyme FX, TSTA3. Cell chemical biology 56 29033318
2013 Stress hormones promote growth of B16-F10 melanoma metastases: an interleukin 6- and glutathione-dependent mechanism. Journal of translational medicine 54 23517603
2022 A randomized, controlled trial of ZYN002 cannabidiol transdermal gel in children and adolescents with fragile X syndrome (CONNECT-FX). Journal of neurodevelopmental disorders 50 36434514
2004 Tumor-microenvironment interactions: the fucose-generating FX enzyme controls adhesive properties of colorectal cancer cells. Cancer research 49 15374970
2002 Growth inhibition of established B16-F10 lung metastases by sequential aerosol delivery of p53 gene and 9-nitrocamptothecin. Gene therapy 44 11938455
2016 Cytosolic DNA Sensor Upregulation Accompanies DNA Electrotransfer in B16.F10 Melanoma Cells. Molecular therapy. Nucleic acids 43 27271988
2019 Potential Properties of Lactobacillus plantarum F-10 as a Bio-control Strategy for Wound Infections. Probiotics and antimicrobial proteins 42 30523603
2016 FX knockout CHO hosts can express desired ratios of fucosylated or afucosylated antibodies with high titers and comparable product quality. Biotechnology and bioengineering 42 27666939
2009 In vitro and in vivo evaluation of mutagenicity of fucoxanthin (FX) and its metabolite fucoxanthinol (FXOH). The Journal of toxicological sciences 40 19952505
2014 Hinokitiol, a tropolone derivative, inhibits mouse melanoma (B16-F10) cell migration and in vivo tumor formation. European journal of pharmacology 39 25449038
2006 Identification of FX in the heliobacterial reaction center as a [4Fe-4S] cluster with an S = 3/2 ground spin state. Biochemistry 39 16716087
2014 Increased coagulation activity and genetic polymorphisms in the F5, F10 and EPCR genes are associated with breast cancer: a case-control study. BMC cancer 37 25407022
2014 Antitumor effect of iRGD-modified liposomes containing conjugated linoleic acid-paclitaxel (CLA-PTX) on B16-F10 melanoma. International journal of nanomedicine 36 25028548
2003 Overexpression of a set of genes, including WISP-1, common to pulmonary metastases of both mouse D122 Lewis lung carcinoma and B16-F10.9 melanoma cell lines. British journal of cancer 35 12865923
2018 Thymoquinone Induces Apoptosis in B16-F10 Melanoma Cell Through Inhibition of p-STAT3 and Inhibits Tumor Growth in a Murine Intracerebral Melanoma Model. World neurosurgery 34 29510292
2016 Review of the Mechanism of Action for Supartz FX in Knee Osteoarthritis. Cartilage 33 29219021
2014 Growth and metastasis of B16-F10 melanoma cells is not critically dependent on host CD73 expression in mice. BMC cancer 33 25465225
2004 Evidence for an essential catalytic role of the F10 protein kinase in vaccinia virus morphogenesis. Journal of virology 33 14671107
1996 Decreased expression of a single tropomyosin isoform, TM5/TM30nm, results in reduction in motility of highly metastatic B16-F10 mouse melanoma cells. Biochemical and biophysical research communications 33 8753779
2019 Single injection of IL-12 coacervate as an effective therapy against B16-F10 melanoma in mice. Journal of controlled release : official journal of the Controlled Release Society 32 31866503
2017 Commentary on: "Comprehensive transcriptional analysis of early-stage urothelial carcinoma." Hedegaard J, Lamy P, Nordentoft I, Algaba F, Høyer S, Ulhøi BP, Vang S, Reinert T, Hermann GG, Mogensen K, Thomsen MB, Nielsen MM, Marquez M, Segersten U, Aine M, Höglund M, Birkenkamp-Demtröder K, Fristrup N, Borre M, Hartmann A, Stöhr R, Wach S, Keck B, Seitz AK, Nawroth R, Maurer T, Tulic C, Simic T, Junker K, Horstmann M, Harving N, Petersen AC, Calle ML, Steyerberg EW, Beukers W, van Kessel KE, Jensen JB, Pedersen JS, Malmström PU, Malats N, Real FX, Zwarthoff EC, Ørntoft TF, Dyrskjøt L. Cancer Cell. 2016 Jul 11;30(1):27-42. Urologic oncology 32 28789929
2014 A lectin from Bothrops leucurus snake venom raises cytosolic calcium levels and promotes B16-F10 melanoma necrotic cell death via mitochondrial permeability transition. Toxicon : official journal of the International Society on Toxinology 32 24593964
2021 Gene electrotransfer of IL-2 and IL-12 plasmids effectively eradicated murine B16.F10 melanoma. Bioelectrochemistry (Amsterdam, Netherlands) 31 34139572
2019 Comprehensive Evaluation of Compendial USP<71>, BacT/Alert Dual-T, and Bactec FX for Detection of Product Sterility Testing Contaminants. Journal of clinical microbiology 31 30541938
2018 Hydroalcoholic extract of Spartium junceum L. flowers inhibits growth and melanogenesis in B16-F10 cells by inducing senescence. Phytomedicine : international journal of phytotherapy and phytopharmacology 31 30097108
2014 Wogonin suppresses melanoma cell B16-F10 invasion and migration by inhibiting Ras-medicated pathways. PloS one 31 25203554
2018 Melanogenesis Inhibitors from the Rhizoma of Ligusticum Sinense in B16-F10 Melanoma Cells In Vitro and Zebrafish In Vivo. International journal of molecular sciences 29 30545008
1995 Evidence for a mixed-ligand [4Fe-4S] cluster in the C14D mutant of PsaC. Altered reduction potentials and EPR spectral properties of the FA and FB clusters on rebinding to the P700-FX core. Biochemistry 29 7794897
2012 Linking αMSH with PPARγ in B16-F10 melanoma. Pigment cell & melanoma research 28 22863076
1999 Cytostatic activity of coumarin metabolites and derivatives in the B16-F10 murine melanoma cell line. Melanoma research 28 10465579
2015 Ilexgenin A induces B16-F10 melanoma cell G1/S arrest in vitro and reduces tumor growth in vivo. International immunopharmacology 27 25596038
2006 ESR signal of the iron-sulfur center F(X) and its function in the homodimeric reaction center of Heliobacterium modesticaldum. Biochemistry 27 16700542
1997 Unmasking by soluble IL-6 receptor of IL-6 effect on metastatic melanoma: growth inhibition and differentiation of B16-F10.9 tumor cells. Oncogene 27 9247310
2009 Proliferative and anti-proliferative effects of dietary levels of phytoestrogens in rat pituitary GH3/B6/F10 cells - the involvement of rapidly activated kinases and caspases. BMC cancer 26 19765307
2013 Modulation of membrane phospholipids, the cytosolic calcium influx and cell proliferation following treatment of B16-F10 cells with recombinant phospholipase-D from Loxosceles intermedia (brown spider) venom. Toxicon : official journal of the International Society on Toxinology 25 23462381
2010 Anthraquinones danthron and quinizarin exert antiproliferative and antimetastatic activity on murine B16-F10 melanoma cells. Anticancer research 25 20332452
1985 Inhibition of recombinant interferon-gamma-induced Ia antigen expression by shed B16 F10 melanoma cell membrane vesicles. Journal of immunology (Baltimore, Md. : 1950) 25 3917273
2014 Metastatic potential of B16-F10 melanoma cells is enhanced by extracellular S100A4 derived from RAW264.7 macrophages. Biochemical and biophysical research communications 24 24613382
2014 Inhibition of cell proliferation, migration and invasion of B16-F10 melanoma cells by α-mangostin. Biochemical and biophysical research communications 24 25019992
2002 Reduced activation of the Gla19Ala FX variant via the extrinsic coagulation pathway results in symptomatic CRMred FX deficiency. Thrombosis and haemostasis 23 12195695
2020 Anti-Melanogenic Effect of Ethanolic Extract of Sorghum bicolor on IBMX-Induced Melanogenesis in B16/F10 Melanoma Cells. Nutrients 22 32245029
2018 Improved potency of F10 relative to 5-fluorouracil in colorectal cancer cells with p53 mutations. Cancer drug resistance (Alhambra, Calif.) 22 30613833
2007 Contributions of the protein environment to the midpoint potentials of the A1 phylloquinones and the Fx iron-sulfur cluster in photosystem I. Biochemistry 22 17725326
2004 Modifications in the head group and in the spacer of cholesterol-based cationic lipids promote transfection in melanoma B16-F10 cells and tumours. Journal of drug targeting 22 15203909
2017 Peroxisome proliferator-activated receptor α (PPARα) contributes to control of melanogenesis in B16 F10 melanoma cells. Archives of dermatological research 20 28084540
2016 Melanogenesis inhibits respiration in B16-F10 melanoma cells whereas enhances mitochondrial cell content. Experimental cell research 20 27864061
2016 Innate immunity based cancer immunotherapy: B16-F10 murine melanoma model. BMC cancer 20 27927165
2008 Unifying principles in homodimeric type I photosynthetic reaction centers: properties of PscB and the FA, FB and FX iron-sulfur clusters in green sulfur bacteria. Biochimica et biophysica acta 20 18835244
1993 Prominent expression of the actin-sequestering peptide Fx gene in the hippocampal region of rat brain. Neuroscience letters 20 8515877
1988 IFN-treatment of B16-F1 versus B16-F10: relative impact on non-adaptive and T-cell-mediated immune defense in metastatic spread. Clinical & experimental metastasis 19 3132343
2018 Ginkgo biloba Exocarp Extract Inhibits the Metastasis of B16-F10 Melanoma Involving PI3K/Akt/NF-κB/MMP-9 Signaling Pathway. Evidence-based complementary and alternative medicine : eCAM 18 30046339
2016 Phenylethanoid Glycosides from Cistanche tubulosa Inhibits the Growth of B16-F10 Cells both in Vitro and in Vivo by Induction of Apoptosis via Mitochondria-dependent Pathway. Journal of Cancer 18 27698928
2014 Thymineless death in F10-treated AML cells occurs via lipid raft depletion and Fas/FasL co-localization in the plasma membrane with activation of the extrinsic apoptotic pathway. Leukemia research 18 25510486
2012 Synthetic phosphoethanolamine a precursor of membrane phospholipids reduce tumor growth in mice bearing melanoma B16-F10 and in vitro induce apoptosis and arrest in G2/M phase. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 18 22902646
2007 Congenital FX deficiency combined with other clotting defects or with other abnormalities: a critical evaluation of the literature. Haemophilia : the official journal of the World Federation of Hemophilia 18 18081833
2006 Novel role of IL-6/SIL-6R signaling in the expression of inducible nitric oxide synthase (iNOS) in murine B16, metastatic melanoma clone F10.9, cells. Free radical biology & medicine 18 17189827
2018 Combined SEP and anti-PD-L1 antibody produces a synergistic antitumor effect in B16-F10 melanoma-bearing mice. Scientific reports 17 29317734
2012 Acute and long-term effects of hyperthermia in B16-F10 melanoma cells. PloS one 17 22532856
2008 Paullinia cupana Mart var. sorbilis, guaraná, reduces cell proliferation and increases apoptosis of B16/F10 melanoma lung metastases in mice. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 17 18392453
2023 Targeting the monocarboxylate transporter MCT2 and lactate dehydrogenase A LDHA in cancer cells with FX-11 and AR-C155858 inhibitors. European review for medical and pharmacological sciences 16 37522672
2014 Cytotoxicity of lipophilic statins depends on their combined actions on HIF-1α expression and redox status in B16.F10 melanoma cells. Anti-cancer drugs 16 24441744
2007 A nonstop mutation in the factor (F)X gene of a severely haemorrhagic patient with complete absence of coagulation FX. Thrombosis and haemostasis 16 18064309
2023 Inhibition of cancer-type amino acid transporter LAT1 suppresses B16-F10 melanoma metastasis in mouse models. Scientific reports 15 37626086
2021 0D/2D heteronanostructure-integrated bimetallic CoCu-ZIF nanosheets and MXene-derived carbon dots for impedimetric cytosensing of melanoma B16-F10 cells. Mikrochimica acta 15 33547501
2019 Thymoquinone Enhances the Effect of Gamma Knife in B16-F10 Melanoma Through Inhibition of Phosphorylated STAT3. World neurosurgery 15 31054338
2016 DTDP-rhamnosyl transferase RfbF, is a newfound receptor-related regulatory protein for phage phiYe-F10 specific for Yersinia enterocolitica serotype O:3. Scientific reports 15 26965493
2013 FX cloning: a versatile high-throughput cloning system for characterization of enzyme variants. Methods in molecular biology (Clifton, N.J.) 15 23423894
2015 Anti-melanogenesis and antigenotoxic activities of eriodictyol in murine melanoma (B16-F10) and primary human keratinocyte cells. Life sciences 14 26141996
2015 Antineoplastic effects of Rhodiola crenulata treatment on B16-F10 melanoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 14 26159852
2013 Inhibition of metastatic potential of B16-F10 melanoma cell line in vivo and in vitro by biflorin. Life sciences 14 23743169
2022 Combination Therapy of Curcumin and Disulfiram Synergistically Inhibits the Growth of B16-F10 Melanoma Cells by Inducing Oxidative Stress. Biomolecules 13 36358950
2019 Evaluation of [11C]KB631 as a PET tracer for in vivo visualisation of HDAC6 in B16.F10 melanoma. Nuclear medicine and biology 13 31421440
2019 Phellinus gilvus‑derived protocatechualdehyde induces G0/G1 phase arrest and apoptosis in murine B16‑F10 cells. Molecular medicine reports 13 31894337
2017 Cytotoxicity of the coagulant Moringa oleifera lectin (cMoL) to B16-F10 melanoma cells. Toxicology in vitro : an international journal published in association with BIBRA 13 28645635
2006 GM-CSF-surface-modified B16.F10 melanoma cell vaccine. Vaccine 13 16713660
2001 The FX enzyme is a functional component of lymphocyte activation. Cellular immunology 13 11831876
2023 Reactive myelopoiesis and FX-expressing macrophages triggered by chemotherapy promote cancer lung metastasis. JCI insight 12 36976637
2020 FMR1 mRNA from full mutation alleles is associated with ABC-CFX scores in males with fragile X syndrome. Scientific reports 12 32678152
2019 Uncovering the anti-proliferation mechanism and bioactive compounds in red kidney bean coat against B16-F10 melanoma cells by metabolomics and network pharmacology analysis. Food & function 12 30698192
2018 Upregulation of DNA Sensors in B16.F10 Melanoma Spheroid Cells After Electrotransfer of pDNA. Technology in cancer research & treatment 12 29879868
2018 Cycloartane triterpenoid (23R, 24E)-23-acetoxymangiferonic acid inhibited proliferation and migration in B16-F10 melanoma via MITF downregulation caused by inhibition of both β-catenin and c-Raf-MEK1-ERK signaling axis. Journal of natural medicines 12 30084054
2009 Regression of established subcutaneous B16-F10 murine melanoma tumors after gef gene therapy associated with the mitochondrial apoptotic pathway. Experimental dermatology 12 19645856
2008 Role of transglutaminase 2 in quercetin-induced differentiation of B16-F10 murine melanoma cells. Amino acids 12 18688565
2020 Himachalol induces apoptosis in B16-F10 murine melanoma cells and protects against skin carcinogenesis. Journal of ethnopharmacology 11 31918014
2018 BNIP3 modulates the interface between B16-F10 melanoma cells and immune cells. Oncotarget 11 29707136
2014 F10 Inhibits Growth of PC3 Xenografts and Enhances the Effects of Radiation Therapy. Journal of clinical oncology and research 11 26020060