Affinage

F9

Coagulation factor IX · UniProt P00740

Round 2 corrected
Length
461 aa
Mass
51.8 kDa
Annotated
2026-04-28
130 papers in source corpus 19 papers cited in narrative 17 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Coagulation factor IX (FIX) is a vitamin K-dependent serine protease zymogen that circulates in plasma and, upon proteolytic activation by Factor XIa or the Factor VIIa/tissue factor complex, assembles with Factor VIIIa, Ca²⁺, and phospholipid into the intrinsic tenase (Xase) complex to activate Factor X, thereby propagating the coagulation cascade (PMID:659613, PMID:2248955, PMID:7598447). The mature 416-residue protein undergoes extensive post-translational processing—signal peptide and propeptide cleavage (requiring Arg-4), γ-carboxylation of 12 glutamic acid residues, β-hydroxylation, and glycosylation—and its Ca²⁺-binding EGF-like domain (solved at 1.5 Å) mediates critical protein–protein contacts within the Xase complex (PMID:6959130, PMID:7606779, PMID:3009023). FIX also binds collagen IV in the subendothelial basement membrane, forming a vascular reservoir that modulates plasma recovery and hemostatic efficacy of infused FIX (PMID:30992271). Loss-of-function mutations in the X-linked F9 gene cause hemophilia B through diverse mechanisms including impaired propeptide processing, defective post-translational modification, protein instability, and failure of Xase complex assembly (PMID:2743975, PMID:35269902).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1978 High

    Establishing how Factor IX is converted from a zymogen to an active serine protease answered the fundamental question of FIX's enzymatic mechanism: Factor XIa cleaves two internal peptide bonds to release an activation peptide and generate a disulfide-linked two-chain enzyme whose heavy chain carries the active-site serine and is regulated by antithrombin III.

    Evidence SDS-PAGE, amino acid sequencing, active-site labeling, and antithrombin III inhibition assays with purified human plasma FIX

    PMID:659613

    Open questions at the time
    • Precise cleavage site sequences inferred from protein chemistry, not yet confirmed by cDNA sequencing
    • Structural basis of FXIa recognition of FIX not defined
  2. 1982 High

    Cloning the F9 cDNA and gene resolved the complete primary structure, revealing domain organization (Gla domain with 12 γ-carboxylation sites, EGF-like domains, activation peptide, and catalytic domain with His221/Asp270/Ser366 triad) and establishing F9 as a single X-linked gene spanning ~33.5 kb with 8 exons whose boundaries correspond to functional domains.

    Evidence cDNA cloning from human liver library, complete genomic DNA sequencing, exon-intron mapping, and somatic cell hybrid panel mapping

    PMID:2994716 PMID:6287289 PMID:6320191 PMID:6959130

    Open questions at the time
    • Three-dimensional structure not yet determined
    • Regulatory elements controlling liver-specific expression not characterized
  3. 1986 High

    Identification of the Arg-4→Gln mutation established that propeptide processing is a discrete essential step in FIX maturation, distinct from signal peptide cleavage, and that disruption of this single residue causes hemophilia B by producing an abnormally elongated, non-functional FIX molecule.

    Evidence DNA sequencing of hemophilia B patient, in vitro expression, SDS-PAGE, and N-terminal sequencing of the aberrant protein

    PMID:3009023

    Open questions at the time
    • Whether propeptide retention also impairs γ-carboxylation was not tested
    • Identity of the propeptidase was not established
  4. 1989 High

    Systematic genotype-phenotype correlation across hemophilia B patients revealed that different mutation types produce distinct pathophysiological mechanisms—some abolishing circulating antigen, others selectively destroying function—and identified CpG dinucleotides as mutation hotspots, providing a framework for understanding structure-function relationships across the entire FIX protein.

    Evidence PCR amplification and direct sequencing of F9 genomic DNA from a large cohort of hemophilia B patients

    PMID:2743975

    Open questions at the time
    • Individual variants not reconstituted biochemically
    • Structural basis for each functional defect not defined
  5. 1990 High

    Quantitative kinetic characterization of FIX activation by Factor VIIa/tissue factor demonstrated that FIX is a preferred substrate over Factor X for the extrinsic pathway initiator complex, establishing the dual-pathway activation of FIX and defining the role of tissue factor and phospholipids as cofactors.

    Evidence Steady-state enzyme kinetics with purified recombinant FVIIa under varied cofactor conditions

    PMID:2248955

    Open questions at the time
    • Structural basis for substrate preference not determined
    • Relative contributions of the two activation pathways in vivo not quantified
  6. 1995 High

    The 1.5 Å crystal structure of the Ca²⁺-binding EGF-like domain explained how Ca²⁺ maintains domain conformation and directly mediates protein-protein contacts, while the elucidation of TFPI-mediated shutdown of the extrinsic pathway explained why the intrinsic pathway (and thus FIX) is essential for sustained hemostasis despite extrinsic pathway initiation.

    Evidence X-ray crystallography of recombinant FIX EGF domain; biochemical reconstitution of TFPI inhibition kinetics

    PMID:7598447 PMID:7606779

    Open questions at the time
    • Full-length FIX or FIXa structure not solved
    • Atomic details of FIXa–FVIIIa interface unknown
  7. 2013 Medium

    Analysis of over 1100 unique F9 mutations across >3700 patients established that functional (Type II) mutations predominantly map to regions mediating activation and Xase complex assembly, and that inhibitor development is rare and mutation-specific, providing a comprehensive genotype-phenotype map.

    Evidence Mutation database analysis with homology-based structural modeling of FIXa

    PMID:23617593

    Open questions at the time
    • Structural modeling based on homology rather than experimental FIXa structure
    • No direct functional reconstitution for individual variants in this study
  8. 2019 High

    Discovery that FIX binds collagen IV in the subendothelial basement membrane revealed an extravascular reservoir of FIX that affects pharmacokinetics and therapeutic efficacy—CRM+ hemophilia B patients' dysfunctional FIX competes for binding sites with infused therapeutic FIX, explaining reduced recovery.

    Evidence Mouse hemophilia B models (CRM− and CRM+), saphenous vein bleeding assay, FIX pharmacokinetic analysis

    PMID:30992271

    Open questions at the time
    • Col4 binding site on FIX not mapped
    • Quantitative contribution of the vascular reservoir to normal hemostasis in humans not established
  9. 2022 High

    Three complementary studies expanded understanding of FIX biology: codon optimization of F9 alters cotranslational folding kinetics and MHC class II peptide presentation (affecting immunogenicity despite identical amino acid sequence), comprehensive mutation review catalogued mechanistic classes of hemophilia B, and a CRISPR screen unexpectedly identified FIX as a regulator of CDK4/6-inhibitor-induced cellular senescence.

    Evidence Ribosome profiling and immunopeptidomics of recoded F9 constructs; systematic review of >1000 mutations; genome-wide CRISPR/Cas9 screen with shRNA and recombinant protein validation in MCF7 cells

    PMID:35184131 PMID:35269902 PMID:35413099

    Open questions at the time
    • Mechanism by which FIX protein promotes senescence is unknown
    • Whether codon-usage effects on immunogenicity are clinically significant is untested
    • Whether FIX's senescence role is relevant to hemophilia B pathophysiology is unexplored

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the molecular mechanism by which extracellular/intracellular FIX promotes cellular senescence, the structural basis of the complete FIXa–FVIIIa–phospholipid Xase complex, and the precise mapping of the FIX–collagen IV interaction interface.
  • No full-length FIXa crystal structure or cryo-EM structure of Xase complex available
  • Senescence mechanism entirely undefined at the signaling level
  • FIX–Col4 binding interface not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 3 GO:0016787 hydrolase activity 2
Localization
GO:0005576 extracellular region 3 GO:0031012 extracellular matrix 1
Pathway
R-HSA-109582 Hemostasis 5 R-HSA-1643685 Disease 4
Partners
COL4A1F10F11F7F8SERPINC1
Complex memberships
intrinsic tenase (Xase) complex

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1978 Human Factor IX (FIX) is a single-chain plasma glycoprotein that is activated to a serine protease (Factor IXaβ) by Factor XIa through cleavage of two internal peptide bonds (Arg145-Ala146 and Arg180-Val181), releasing an activation peptide and generating a two-chain enzyme (light chain + heavy chain held by disulfide bond). The heavy chain contains the active-site serine. Factor IXaβ is inhibited by antithrombin III via tight binding to the heavy chain. Protein biochemistry: SDS-PAGE, amino acid sequencing, active-site labeling, antithrombin III inhibition assay The Journal of clinical investigation High 659613
1982 Human Factor IX cDNA encodes a 416-amino acid mature protein with a 46-amino acid leader sequence. The protein contains 12 N-terminal glutamic acid residues (substrate for gamma-carboxylation), an activation peptide (35 aa), a light chain (145 aa), and a heavy chain (236 aa) with catalytic triad His221, Asp270, Ser366 homologous to chymotrypsin His57, Asp102, Ser195. Two N-linked glycosylation sites are in the activation peptide. cDNA cloning and sequencing of human liver library; translation product analysis Proceedings of the National Academy of Sciences of the United States of America High 6959130
1982 The F9 gene encoding human coagulation Factor IX was molecularly cloned from a human genomic library using bovine factor IX cDNA as probe, establishing it as a single large gene (≥20 kb) on the X chromosome. Molecular cloning, Southern blotting, hybridization with heterologous cDNA probe Nature High 6287289
1984 The F9 gene spans approximately 33.5 kb on the X chromosome (Xq26-q27) and contains 8 exons and 7 introns; exons correspond roughly to functional protein domains (prepro leader, Gla domain, EGF-like domains, activation peptide, catalytic domain split across two exons). The gene was mapped to the Xq26-q27 region, and a TaqI restriction fragment length polymorphism was identified for carrier/prenatal diagnosis. Complete genomic DNA sequencing (~38 kb), exon-intron mapping, human-mouse somatic cell hybrid panel mapping, RFLP analysis Biochemistry / Proceedings of the National Academy of Sciences High 2994716 6320191 6329734
1986 A point mutation changing Arg-4 to Gln in the propeptide region of Factor IX causes hemophilia B by blocking proteolytic removal of the propeptide during post-translational maturation; signal peptidase cleaves between positions -18 and -19, but further processing to mature FIX requires the Arg at -4. The result is a stable longer protein with 18 extra N-terminal propeptide residues still attached. DNA sequencing of hemophilia B patient, in vitro expression, protein analysis by SDS-PAGE and N-terminal sequencing Cell High 3009023
1989 Molecular pathology of hemophilia B established by direct sequencing of amplified genomic DNA from patients: substitutions of Cys336 or Asn120 cause loss of circulating FIX antigen; deletion of Arg37 causes gross reduction of circulating protein and loss of activity; substitutions of Arg-4, Arg333, Asp64, and Pro55 cause loss of function without marked protein reduction; frameshift/nonsense mutations are associated with inhibitor (antibody) development; CpG dinucleotides show enhanced mutation rates accounting for ~25% of all point mutations. PCR amplification and direct sequencing of F9 genomic DNA from hemophilia B patients The EMBO journal High 2743975
1990 Recombinant Factor VIIa activates both Factor IX and Factor X in the presence of calcium, phospholipids, and tissue factor. Under all cofactor conditions, the kcat/Km ratio for FIX activation by FVIIa was considerably greater than for FX activation, suggesting FIX is a preferred substrate. Tissue factor markedly increases both Vmax and kcat/Km for FIX activation. Steady-state enzyme kinetics with purified recombinant FVIIa and chromogenic substrates/clotting assays; varied calcium and phospholipid concentrations Biochemistry High 2248955
1995 The crystal structure of the Ca2+-binding EGF-like domain of human Factor IX was solved at 1.5 Å resolution in complex with Ca2+. Ca2+ adopts a pentagonal bipyramidal coordination with six ligands from one polypeptide and the seventh from a neighboring EGF domain. Ca2+ maintains the conformation of the N-terminal region of the domain and directly mediates protein-protein contacts, providing a structural basis for EGF-domain interactions in FIX and related proteins. X-ray crystallography at 1.5 Å resolution of recombinant Factor IX EGF-like domain Cell High 7606779
1995 Tissue factor pathway inhibitor (TFPI) directly inhibits activated Factor X and, in a FXa-dependent manner, produces feedback inhibition of the FVIIa/tissue factor complex, thereby limiting the extrinsic pathway initiation of coagulation and explaining the clinical requirement for the intrinsic pathway (including FIX) for sustained hemostasis. Biochemical reconstitution assays with purified proteins; kinetic inhibition studies Annual review of medicine High 7598447
2005 Self-complementary AAV (scAAV) vectors with a liver-specific mini-hFIX expression cassette achieve 20-fold higher FIX expression in mice compared to single-stranded AAV vectors, correcting the bleeding phenotype in FIX knock-out mice at only 1×10^10 particles (producing supraphysiologic FIX levels) and achieving therapeutic FIX levels (3–30% normal) in nonhuman primates at lower doses. In vivo gene delivery in FIX-KO mice and nonhuman primates; molecular analysis of vector genome forms; FIX clotting activity assays Blood High 16322469
2008 The silent mutation G17736A/Val107Val in the F9 gene causes mild hemophilia B (FIX activity 15–20 U/dL) in five Swedish families, without exon skipping or intron retention detectable by RT-PCR. The probable mechanism involves subtle effects on splicing enhancer sites or altered codon usage reducing translation rate and thereby affecting FIX protein folding in vivo. RT-PCR and cDNA sequencing of patient lymphocyte mRNA; mutation scanning; FIX activity and antigen measurement Haemophilia Medium 18459950
2013 Analysis of 1113 unique F9 mutations in 3721 hemophilia B patients revealed that mutations occur in 336/461 (73%) FIX residues. Type II (qualitative, predominantly functional) mutations account for 64% of mild-severity cases with known protein phenotypes, and structural modeling indicates these predominantly disrupt regions involved in functional interactions (activation, Xase complex formation). Inhibitor development is rare (1.6%) and associated with 25 specific mutations. Mutation database analysis combined with homology modeling of FIXa structure based on closely related crystal structures Journal of thrombosis and haemostasis Medium 23617593
2014 Fusion of FIX to the Fc fragment of IgG (rFIXFc) prolongs FIX half-life 3–4 fold in Phase I/IIa studies by exploiting physiological binding of the Fc domain to the neonatal Fc receptor (FcRn), demonstrating that the FcRn recycling pathway can extend FIX circulatory half-life without altering FIX functional activity. Recombinant protein engineering; pharmacokinetic studies in preclinical models and Phase I/IIa/III clinical trials Drug design, development and therapy High 24729686
2019 Factor IX binds to collagen IV (Col4) in the subendothelial basement membrane, creating a vascular cache of FIX (estimated ~405 nM available Col4 binding capacity) that reduces plasma recovery of infused FIX and contributes to hemostasis. In CRM+ hemophilia B mice expressing dysfunctional FIXR333Q, endogenous dysfunctional FIX competes with infused therapeutic FIX for Col4 binding sites, impairing prophylactic hemostatic therapy. Mouse hemophilia B models (CRM- and CRM+), saphenous vein bleeding assay, pharmacokinetic analysis of FIX plasma recovery, comparison of FIXWT, FIXFC (Alprolix), and FIXAlb (Idelvion) Blood High 30992271
2022 FIX deficiency in hemophilia B results from diverse mechanisms depending on mutation type: deletions/insertions/indels in exons cause frameshift or inframe mutations; intronic mutations cause aberrant splicing; F9 promoter point mutations cause hemophilia B Leyden (developmentally regulated loss of expression); nonsense mutations produce truncated non-functional FIX; missense mutations impair translation, protein folding, stability, post-translational modifications (including gamma-carboxylation, beta-hydroxylation, glycosylation, phosphorylation), FIX activation to FIXa, or formation of the functional Xase complex. Systematic review of >1000 F9 mutations correlated with structural/functional data from published biochemical studies International journal of molecular sciences High 35269902
2022 Codon optimization (recoding) of F9 alters cotranslational folding kinetics as revealed by ribosome profiling showing differences in local translation kinetics. Recoded FIX variants show altered protein conformations and suboptimal post-translational modifications due to overexpression. Furthermore, MHC class II-associated peptide proteomics revealed distinct presentation of FIX-derived peptides from recoded versus wild-type F9, indicating that synonymous codon substitutions can alter FIX immunogenicity despite identical amino acid sequence. Ribosome profiling, protein conformation analysis, MHC-associated peptide proteomics, post-translational modification analysis of multiple recoded F9 constructs Blood advances High 35413099
2022 A genome-wide CRISPR/Cas9 screen identified F9 (coagulation Factor IX) as a regulator of cellular senescence. Downregulation of F9 using sgRNA or shRNA prevents cell cycle arrest and the senescent-like phenotype induced by CDK4/6 inhibitor (Palbociclib) in MCF7 breast cancer cells. Conversely, treatment with recombinant FIX protein is sufficient to induce cell cycle arrest and senescence-like state in MCF7 cells. Endogenous F9 is upregulated in primary human cells undergoing senescence. Genome-wide CRISPR/Cas9 loss-of-function screen; shRNA knockdown; recombinant FIX protein treatment; cell cycle analysis; validation in T47D cells and with Abemaciclib; panel of 22 cancer cell lines Cell death & disease Medium 35184131

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
2005 The DNA sequence of the human X chromosome. Nature 816 15772651
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
1985 Nucleotide sequence of the gene for human factor IX (antihemophilic factor B). Biochemistry 657 2994716
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1982 Isolation and characterization of a cDNA coding for human factor IX. Proceedings of the National Academy of Sciences of the United States of America 409 6959130
2003 The dynamics of thrombin formation. Arteriosclerosis, thrombosis, and vascular biology 387 12524220
1984 The gene structure of human anti-haemophilic factor IX. The EMBO journal 361 6329734
2005 Self-complementary adeno-associated virus vectors containing a novel liver-specific human factor IX expression cassette enable highly efficient transduction of murine and nonhuman primate liver. Blood 356 16322469
1998 The life cycle of coagulation factor VIII in view of its structure and function. Blood 333 9834200
2010 DNA resection in eukaryotes: deciding how to fix the break. Nature structural & molecular biology 317 20051983
1995 The structure of a Ca(2+)-binding epidermal growth factor-like domain: its role in protein-protein interactions. Cell 312 7606779
2006 Association of warfarin dose with genes involved in its action and metabolism. Human genetics 299 17048007
1988 Genomic amplification with transcript sequencing. Science (New York, N.Y.) 282 3340835
1982 Molecular cloning of the gene for human anti-haemophilic factor IX. Nature 264 6287289
1978 Activation of human factor IX (Christmas factor). The Journal of clinical investigation 248 659613
1995 Tissue factor pathway inhibitor and the revised theory of coagulation. Annual review of medicine 233 7598447
1975 Basic mechanisms in blood coagulation. Annual review of biochemistry 216 237463
1989 Molecular pathology of haemophilia B. The EMBO journal 206 2743975
2014 Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver. BMC cancer 203 25037231
2009 Deep-sea archaea fix and share nitrogen in methane-consuming microbial consortia. Science (New York, N.Y.) 201 19833965
1986 Defective propeptide processing of blood clotting factor IX caused by mutation of arginine to glutamine at position -4. Cell 183 3009023
2005 Chromatin in need of a fix: phosphorylation of H2AX connects chromatin to DNA repair. Molecular cell 178 15949437
1990 Proteolytic activation of human factors IX and X by recombinant human factor VIIa: effects of calcium, phospholipids, and tissue factor. Biochemistry 176 2248955
1984 Regional localization on the human X chromosome and polymorphism of the coagulation factor IX gene (hemophilia B locus). Proceedings of the National Academy of Sciences of the United States of America 174 6320191
1981 Mutation near the polyoma DNA replication origin permits productive infection of F9 embryonal carcinoma cells. Cell 170 6261957
1989 Expression of REX-1, a gene containing zinc finger motifs, is rapidly reduced by retinoic acid in F9 teratocarcinoma cells. Molecular and cellular biology 169 2511439
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
1983 Isolation of a human anti-haemophilic factor IX cDNA clone using a unique 52-base synthetic oligonucleotide probe deduced from the amino acid sequence of bovine factor IX. Nucleic acids research 155 6687940
2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. Proteomics 138 23533145
2013 An interactive mutation database for human coagulation factor IX provides novel insights into the phenotypes and genetics of hemophilia B. Journal of thrombosis and haemostasis : JTH 134 23617593
2011 F8 and F9 mutations in US haemophilia patients: correlation with history of inhibitor and race/ethnicity. Haemophilia : the official journal of the World Federation of Hemophilia 110 22103590
1999 Retinoid receptor-dependent and -independent effects of N-(4-hydroxyphenyl)retinamide in F9 embryonal carcinoma cells. Cancer research 107 9892176
1980 Growth and differentiation of embryonal carcinoma cell line F9 in defined media. Proceedings of the National Academy of Sciences of the United States of America 107 6244561
1983 Synthesis of laminin and entactin by F9 cells induced with retinoic acid and dibutyryl cyclic AMP. The Journal of biological chemistry 104 6305950
1986 Sequential expression of murine homeo box genes during F9 EC cell differentiation. The EMBO journal 99 2877873
2017 The utility of MASS-FIX to detect and monitor monoclonal proteins in the clinic. American journal of hematology 97 28439985
1990 Retinoic acid, dibutyryl-cAMP, and differentiation affect the expression of retinoic acid receptors in F9 cells. Proceedings of the National Academy of Sciences of the United States of America 94 2162058
1992 Transcriptional regulation of the c-jun gene by retinoic acid and E1A during differentiation of F9 cells. The EMBO journal 84 1310930
1990 Elevation of AP1 activity during F9 cell differentiation is due to increased c-jun transcription. The New biologist 79 1963081
2016 Are Regulatory T Cells Defective in Type 1 Diabetes and Can We Fix Them? Journal of immunology (Baltimore, Md. : 1950) 75 27815439
2007 The role of F9 fimbriae of uropathogenic Escherichia coli in biofilm formation. Microbiology (Reading, England) 73 17600076
2001 F9 embryocarcinoma cells: a cell autonomous model to study the functional selectivity of RARs and RXRs in retinoid signaling. Histology and histopathology 72 11510982
1989 Retinoic acid receptor expression vector inhibits differentiation of F9 embryonal carcinoma cells. Genes & development 72 2558044
2011 Dissecting the retinoid-induced differentiation of F9 embryonal stem cells by integrative genomics. Molecular systems biology 70 21988834
2006 Cloning, expression, and characterization of fimbrial operon F9 from enterohemorrhagic Escherichia coli O157:H7. Infection and immunity 68 16552054
1984 Selection and characterization of F9 teratocarcinoma stem cell mutants with altered responses to retinoic acid. The Journal of biological chemistry 67 6325455
2007 Retinoic acid receptor isotype specificity in F9 teratocarcinoma stem cells results from the differential recruitment of coregulators to retinoic response elements. The Journal of biological chemistry 65 17875646
1992 Thrombomodulin gene regulation by cAMP and retinoic acid in F9 embryonal carcinoma cells. Proceedings of the National Academy of Sciences of the United States of America 58 1312715
1991 The F9-EC cell line as a model for the analysis of differentiation. The International journal of developmental biology 58 1666294
1993 Expression of chicken vinculin complements the adhesion-defective phenotype of a mutant mouse F9 embryonal carcinoma cell. The Journal of cell biology 51 8491782
2003 Identification and characterization of retinoic acid receptor beta2 target genes in F9 teratocarcinoma cells. Molecular cancer research : MCR 50 12805409
2003 Teratogenic phthalate esters and metabolites activate the nuclear receptors PPARs and induce differentiation of F9 cells. Toxicology and applied pharmacology 48 12668118
1989 Induction of in vitro differentiation of mouse embryonal carcinoma (F9) and erythroleukemia (MEL) cells by herbimycin A, an inhibitor of protein phosphorylation. The Journal of cell biology 47 2745553
2019 Fix Your Membrane Receptor Imaging: Actin Cytoskeleton and CD4 Membrane Organization Disruption by Chemical Fixation. Frontiers in immunology 44 31024536
1985 Expression of c-fos in parietal endoderm, amnion and differentiating F9 teratocarcinoma cells. Differentiation; research in biological diversity 44 2419195
2014 Big spleens and hypersplenism: fix it or forget it? Liver international : official journal of the International Association for the Study of the Liver 42 25312770
1988 Expression of c-fos antisense RNA inhibits the differentiation of F9 cells to parietal endoderm. Developmental biology 42 2457527
2007 Wnt6 induces the specification and epithelialization of F9 embryonal carcinoma cells to primitive endoderm. Cellular signalling 41 18160257
2014 F9 fimbriae of uropathogenic Escherichia coli are expressed at low temperature and recognise Galβ1-3GlcNAc-containing glycans. PloS one 39 24671091
1999 Transcriptional regulation of the Bmp2 gene. Retinoic acid induction in F9 embryonal carcinoma cells and Saccharomyces cerevisiae. The Journal of biological chemistry 39 9880512
2004 Using DSP, a reversible cross-linker, to fix tissue sections for immunostaining, microdissection and expression profiling. Nucleic acids research 38 15604454
2013 Can we fix it? Evaluating the potential of placental stem cells for the treatment of pregnancy disorders. Placenta 37 24406265
2006 The phosphoinositide 3-kinase/Akt pathway is essential for the retinoic acid-induced differentiation of F9 cells. Oncogene 35 16288212
1983 Molecular characterization of Tn5-induced symbiotic (Fix-) mutants of Rhizobium meliloti. Journal of bacteriology 35 6196347
2022 The Molecular Basis of FIX Deficiency in Hemophilia B. International journal of molecular sciences 34 35269902
2020 How to fix DNA-protein crosslinks. DNA repair 34 32683310
1999 alpha-catenin-deficient F9 cells differentiate into signet ring cells. The American journal of pathology 34 10329584
2018 Muscle Cells Fix Breaches by Orchestrating a Membrane Repair Ballet. Journal of neuromuscular diseases 32 29480214
2013 The tight-junction protein claudin-6 induces epithelial differentiation from mouse F9 and embryonic stem cells. PloS one 29 24116027
1990 Adenovirus 12S E1A gene represses differentiation of F9 teratocarcinoma cells. Proceedings of the National Academy of Sciences of the United States of America 29 1702220
1985 Induction of F9 embryonal carcinoma cell differentiation by inhibition of polyamine synthesis. European journal of cell biology 29 3930245
2018 Vitamin K-Dependent Coagulation Factors That May be Responsible for Both Bleeding and Thrombosis (FII, FVII, and FIX). Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 28 30428703
1999 The coactivators p300 and CBP have different functions during the differentiation of F9 cells. Journal of molecular medicine (Berlin, Germany) 28 10475063
1992 Expression of SPARC is correlated with altered morphologies in transfected F9 embryonal carcinoma cells. Experimental cell research 28 1310471
2020 How Long Does It Take to Fix a Favorable Mutation, and Why Should We Care? The American naturalist 27 32364783
2019 CRISPR to fix bad blood: a new tool in basic and clinical hematology. Haematologica 26 30923099
1995 Regulation of DNA methyltransferase during differentiation of F9 mouse embryonal carcinoma cells. Journal of cellular physiology 25 7593206
1992 Expression of a 91-kilodalton PEA3-binding protein is down-regulated during differentiation of F9 embryonal carcinoma cells. Molecular and cellular biology 25 1569949
2016 Streptomyces thermoautotrophicus does not fix nitrogen. Scientific reports 24 26833023
2008 Why does the mutation G17736A/Val107Val (silent) in the F9 gene cause mild haemophilia B in five Swedish families? Haemophilia : the official journal of the World Federation of Hemophilia 24 18459950
1992 Localization of endoderm-specific mRNAs in differentiating F9 embryoid bodies. Mechanisms of development 24 1376612
2022 Genome wide CRISPR/Cas9 screen identifies the coagulation factor IX (F9) as a regulator of senescence. Cell death & disease 23 35184131
2014 Fc-fusion technology and recombinant FVIII and FIX in the management of the hemophilias. Drug design, development and therapy 23 24729686
1988 Differential regulation of N-myc and c-myc expression in F9 teratocarcinoma cells. Oncogene research 23 3060804
1987 Expression of the murine apolipoprotein E gene is coupled to the differentiated state of F9 embryonal carcinoma cells. Proceedings of the National Academy of Sciences of the United States of America 23 3468509
2023 Do chromosome rearrangements fix by genetic drift or natural selection? Insights from Brenthis butterflies. Molecular ecology 22 37807966
1990 Differentiation of F9 cells is independent of c-myc expression. Oncogene 22 1695728
1990 Differential expression of fetomodulin and tissue plasminogen activator to characterize parietal endoderm differentiation of F9 embryonal carcinoma cells. Developmental biology 22 1698671
2022 Bone marrow mesenchymal stromal cells for diabetes therapy: touch, fuse, and fix? Stem cell research & therapy 21 35883121
2021 Lin_F9: A Linear Empirical Scoring Function for Protein-Ligand Docking. Journal of chemical information and modeling 21 34469692
2015 The role of Arabidopsis glutathione transferase F9 gene under oxidative stress in seedlings. Acta biologica Hungarica 21 26616373
2009 Induction of immune tolerance to FIX following muscular AAV gene transfer is AAV-dose/FIX-level dependent. Molecular therapy : the journal of the American Society of Gene Therapy 21 19240690
2005 Apical membrane and junctional complex formation during simple epithelial cell differentiation of F9 cells. Genes to cells : devoted to molecular & cellular mechanisms 21 16236135
2019 Dysfunctional endogenous FIX impairs prophylaxis in a mouse hemophilia B model. Blood 20 30992271
2012 Spectrum of F9 mutations in Chinese haemophilia B patients: identification of 20 novel mutations. Pathology 20 22544209
2010 DNA-functionalised blend micelles: mix and fix polymeric hybrid nanostructures. Chemical communications (Cambridge, England) 20 20523952
2003 [The chromosome number and gonadal structure of F9-F11 allotetraploid crucian-carp]. Yi chuan xue bao = Acta genetica Sinica 20 12924154
2022 Rnf and Fix Have Specific Roles during Aerobic Nitrogen Fixation in Azotobacter vinelandii. Applied and environmental microbiology 19 36000884
1989 Exogenous c-myc gene overexpression interferes with early events in F9 cell differentiation. Oncogene research 19 2671866
2020 Pseudomonas orientalis F9 Pyoverdine, Safracin, and Phenazine Mutants Remain Effective Antagonists against Erwinia amylovora in Apple Flowers. Applied and environmental microbiology 18 32033956
2018 Paired CRISPR/Cas9 Nickases Mediate Efficient Site-Specific Integration of F9 into rDNA Locus of Mouse ESCs. International journal of molecular sciences 18 30301136
2006 Migration of F9 parietal endoderm cells is regulated by the ERK pathway. Journal of cellular biochemistry 18 16329137
2003 Hepatic regeneration: If it ain't broke, don't fix it. Canadian journal of gastroenterology = Journal canadien de gastroenterologie 17 12915914
1993 Specific uptake of retinol-binding protein by variant F9 cell lines. The Journal of biological chemistry 17 8360175
1989 Plasminogen activator expression in F9 teratocarcinoma embryoid bodies and their endoderm derivatives. Development (Cambridge, England) 17 2516796
2016 Correlation between FIX genotype and pharmacokinetics of Nonacog alpha according to a multicentre Italian study. Haemophilia : the official journal of the World Federation of Hemophilia 16 26988465
2014 Characterisation of large F9 deletions in seven unrelated patients with severe haemophilia B. Thrombosis and haemostasis 15 24816826
2006 Roles of the Nanog protein in murine F9 embryonal carcinoma cells and their endoderm-differentiated counterparts. Cell research 15 16773043
2006 Galpha13 activation rescues moesin-depletion induced apoptosis in F9 teratocarcinoma cells. Experimental cell research 15 16860319
2022 To Fix or Not to Fix: Maintenance of Chromosome Ends Versus Repair of DNA Double-Strand Breaks. Cells 14 36291091
2014 Oral gene therapy for hemophilia B using chitosan-formulated FIX mutants. Journal of thrombosis and haemostasis : JTH 14 24679056
2006 Differential activity of the FGF-4 enhancer in F9 and P19 embryonal carcinoma cells. Journal of cellular physiology 14 16523502
1990 Altered uvomorulin expression in a noncompacting mutant cell line of F9 embryonal carcinoma cells. Developmental biology 14 2180751
1987 Reversible interconversion between primitive endoderm- and parietal endoderm-like F9 cells demonstrated by mRNAs expression. Journal of biochemistry 14 2822687
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2019 CX-F9, a novel RSK2 inhibitor, suppresses cutaneous melanoma cells proliferation and metastasis through regulating autophagy. Biochemical pharmacology 11 31207212
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