Affinage

TFPI

Tissue factor pathway inhibitor · UniProt P10646

Length
304 aa
Mass
35.0 kDa
Annotated
2026-06-13
100 papers in source corpus 16 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: Affinage preferred

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TFPI is a multivalent Kunitz-type serine protease inhibitor that constitutively downregulates the extrinsic (tissue factor) coagulation pathway (PMID:8473315, PMID:1346095). It achieves this through a two-step, FXa-dependent mechanism in which its second Kunitz domain (KD2) inhibits factor Xa, and formation of the binary FXa-TFPI complex is the rate-limiting step required for subsequent inhibition of TF-FVIIa within a tight quaternary TF-FVIIa-TFPI-FXa complex; KD1 inhibits FVIIa while the KD3-C-terminus region confers cell-surface binding and modulates FVIIa inhibition (PMID:8473315, PMID:23347185, PMID:25163770). Through this same machinery TFPI also inhibits TF:FVIIa-catalyzed activation of factors IX and X, with all three Kunitz domains and the C-terminus required for optimal activity (PMID:25163770). TFPI activity is tuned by multiple cofactors acting on the KD3-C-terminus: protein S forms a plasma complex with full-length TFPI and stimulates FXa inhibition ~10-fold, and negatively charged phospholipids, heparin, and FV further enhance inhibition, while thrombin-activated FVa impairs it (PMID:20002538, PMID:26607136, PMID:23347185). Heparin acts synergistically with TFPI to inhibit TF-induced clotting, and TFPI does not regulate the intrinsic contact pathway (PMID:1346095). Beyond coagulation, TFPI selectively inhibits MASP-2 of the lectin complement pathway via KD2, and its C-terminal region exerts complement-dependent antibacterial activity that is reversible by heparin (PMID:25359215, PMID:19456231). Independently of its protease-inhibitory role, TFPI serves as a host colonic-crypt receptor for hypervirulent clade 2 Clostridioides difficile TcdB variants (TcdB2/TcdB4), binding TcdB through a region homologous to the Frizzled-binding site (PMID:35303428, PMID:36351897).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1992 High

    Establishing that TFPI (LACI) is a synergistic cofactor for heparin specific to the extrinsic pathway defined its position as a dedicated tissue-factor pathway regulator rather than a general anticoagulant.

    Evidence APTT/PT clotting assays with LACI-depleted plasma reconstituted with recombinant LACI and sulfated polysaccharides

    PMID:1346095

    Open questions at the time
    • Did not resolve which domains mediate heparin synergy
    • Mechanism of polysaccharide enhancement not defined at molecular level
  2. 1992 Medium

    Cloning the cDNA across species defined TFPI as a three-tandem-Kunitz-domain protein and mapped broad tissue expression, providing the structural framework for later domain-function studies.

    Evidence Rat liver cDNA cloning, Northern blot, and cross-species sequence alignment

    PMID:1639767

    Open questions at the time
    • Functional roles of individual domains not tested here
    • Two mRNA forms not functionally distinguished
  3. 1993 High

    Assigning KD1 to FVIIa inhibition and KD2 to FXa inhibition on cell surfaces resolved the division of labor between the Kunitz domains and showed KD3/C-terminus governs cell-surface binding rather than catalytic inhibition.

    Evidence In vitro kinetic assays comparing full-length vs. truncated TFPI1-161 on J82 carcinoma cell surfaces

    PMID:8473315

    Open questions at the time
    • Quaternary complex assembly order not directly resolved
    • Physiological cell-surface anchoring partner not identified
  4. 1995 Medium

    Defining the restricted physiologic expression of TFPI to megakaryocytes and microvascular endothelium clarified where the inhibitor is produced and that hepatocytes are not the source.

    Evidence Review synthesizing immunohistochemical and cell-biology localization studies

    PMID:7482419

    Open questions at the time
    • No new primary experiment
    • Quantitative contribution of each source to plasma pool unresolved
  5. 1996 Medium

    Showing that binary FXa-TFPI complex formation is required for TF-FVIIa inhibition and correlates inversely with coagulation markers in vivo extended the two-step mechanism from biochemistry into human plasma physiology.

    Evidence Novel sandwich ELISA quantification in 145 healthy adults

    PMID:8982054

    Open questions at the time
    • Correlative/observational design
    • Causal direction not established in vivo
  6. 2009 High

    Identifying protein S as a plasma cofactor that stimulates FXa inhibition ~10-fold defined a constitutively active TFPI/protein S anticoagulant system and explained reduced TFPI in protein S deficiency.

    Evidence Plasma antigen measurements, calibrated thrombography, immunodepletion, and surface plasmon resonance

    PMID:19661488 PMID:20002538

    Open questions at the time
    • Structural basis of protein S-TFPI binding not resolved
    • Relative in vivo weight versus APC pathway not quantified
  7. 2013 High

    Demonstrating direct, TF- and phospholipid-dependent FVIIa inhibition and mapping the KD3-C-terminus contribution refined how TFPI engages the initiating protease complex and quantified protein S enhancement of TF-FVIIa inhibition.

    Evidence Chromogenic FVIIa assays comparing full-length TFPI, TFPI1-150, KD1-KD2, and KD1 constructs

    PMID:23347185

    Open questions at the time
    • Single-lab in vitro reconstitution
    • In vivo relevance of direct FVIIa inhibition vs. FXa-dependent route not weighted
  8. 2014 High

    Establishing binary TFPI:FXa formation as the rate-limiting step for inhibiting TF:FVIIa-catalyzed FIX and FX activation, with all domains required, unified the multi-domain architecture into a single kinetic model.

    Evidence Progress-curve kinetics of FXa/FIXa generation with full-length and truncation constructs

    PMID:25163770

    Open questions at the time
    • Cellular validation of the kinetic model limited
    • Contribution of each cofactor to the rate-limiting step not separated
  9. 2014 High

    Identifying KD2-mediated selective inhibition of MASP-2 revealed a moonlighting role for TFPI as a regulator of the lectin complement pathway, distinct from its coagulation function.

    Evidence Lectin pathway C4-deposition assays and fluid-phase MASP-2 activity with domain-specific antibodies

    PMID:25359215

    Open questions at the time
    • Physiological/in vivo significance of MASP-2 inhibition not established
    • Structural basis of KD2-MASP-2 selectivity unresolved
  10. 2015 High

    Systematic dissection of cofactors (phospholipids, heparin, protein S, FV, FVa) acting through the KD3-C-terminus defined how the TFPI:FXa reaction is environmentally tuned and is antagonized by activated FVa.

    Evidence Progress-curve FXa kinetics with full-length vs. TFPI1-150 across modulator conditions

    PMID:26607136

    Open questions at the time
    • Integration of competing modulators in vivo not modeled
    • Structural mechanism of KD3-C-terminus sensitization unknown
  11. 2009 Medium

    Showing that TFPI C-terminal peptides kill serum-resistant E. coli via the complement pathway, reversibly by heparin, extended TFPI's C-terminus into innate antibacterial defense.

    Evidence Ex vivo blood-culture killing, bacterial surface-binding, and heparin-reversal assays with C-terminal rTFPI fragments

    PMID:19456231

    Open questions at the time
    • In vivo antibacterial relevance not established
    • Molecular target on bacterial surface not identified
  12. 2022 High

    Identifying TFPI as the colonic-crypt host receptor for hypervirulent clade 2 C. difficile TcdB variants, and mapping the binding site, revealed a pathogen-exploited role for TFPI unrelated to protease inhibition.

    Evidence Genome-wide CRISPR screens, cryo-EM of TcdB4-TFPI, mutagenesis defining TFPI vs. Frizzled recognition, and recombinant TFPI epithelial protection assays

    PMID:35303428 PMID:36351897

    Open questions at the time
    • Physiological consequence of TcdB-TFPI engagement for normal TFPI function unknown
    • Whether toxin binding alters anticoagulant activity untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TFPI's distinct functions — coagulation inhibition, complement/MASP-2 regulation, antibacterial activity, and TcdB receptor role — are coordinated or regulated in a shared tissue context remains unresolved.
  • No structural model integrating multi-functional binding surfaces
  • Tissue-specific regulation of the different roles undefined
  • Causal disease links beyond correlative associations not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0140096 catalytic activity, acting on a protein 3 GO:0001618 virus receptor activity 2 GO:0008289 lipid binding 2
Localization
GO:0005576 extracellular region 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-109582 Hemostasis 4 R-HSA-1643685 Disease 2 R-HSA-168256 Immune System 2
Partners
F10F5F7F9MASP2PROS1TCDB
Complex memberships
FXa-TFPI binary complexTF-FVIIa-TFPI-FXa quaternary complexprotein S-TFPI complex

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 TFPI inhibits factor VIIa-tissue factor complexes on cell surfaces through its first and second Kunitz-type domains (KD1 inhibits FVIIa, KD2 inhibits FXa); the third Kunitz-type domain and C-terminal tail are not essential for inhibition of cell surface FVIIa-tissue factor complexes, but influence cell-surface binding affinity. Factor Xa augments TFPI anticoagulant activity equally for full-length and truncated TFPI (TFPI1-161). In vitro kinetic assay comparing full-length recombinant TFPI vs. truncated TFPI1-161 on human bladder carcinoma J82 cell surfaces; chromogenic substrate assays; displacement studies The Journal of biological chemistry High 8473315
1992 TFPI (as LACI) acts as a cofactor for heparin in inhibiting tissue factor-induced coagulation; TFPI and sulfated polysaccharides act synergistically in plasma to inhibit TF-induced clotting. TFPI does not significantly regulate the intrinsic (contact) pathway of coagulation. APTT and modified prothrombin time clotting assays using LACI-depleted plasma reconstituted with purified recombinant LACI and/or heparin; comparison of various sulfated polysaccharides Blood High 1346095
1995 Under normal physiologic conditions, TFPI expression is restricted to megakaryocytes and endothelium of the microvasculature; it is not synthesized by normal hepatocytes or large vessel endothelium. Under pathologic conditions, adherent monocytes/macrophages express both tissue factor and TFPI. Review synthesizing immunohistochemical and cell biology studies of TFPI expression sites Thrombosis and haemostasis Medium 7482419
1996 Factor Xa-TFPI binary complex formation is required to inhibit factor VIIa-tissue factor; free factor Xa-TFPI (quaternary complex precursor) inversely correlates with factor VIIa and prothrombin fragment 1+2 levels in plasma, consistent with factor Xa-TFPI regulating both factor VIIa-tissue factor and prothrombinase in vivo. ELISA-based quantification of factor VIIa, prothrombin fragment 1+2, TFPI, and factor Xa-TFPI in plasma from 145 healthy adults; novel sandwich ELISA using affinity-purified rabbit anti-human TFPI IgG and chicken anti-human factor Xa-TFPI IgY British journal of haematology Medium 8982054
2009 Protein S acts as a cofactor for full-length TFPI, stimulating inhibition of factor Xa by TFPI approximately 10-fold. Free protein S and full-length TFPI form a complex in plasma, confirmed by protein S immunodepletion experiments and surface plasmon resonance. TFPI levels are reduced in hereditary and acquired protein S deficiency, and concomitant TFPI deficiency substantially contributes to the hypercoagulable state. Plasma TFPI and protein S antigen measurements; calibrated automated thrombography for thrombin generation; protein S immunodepletion; surface plasmon resonance to confirm protein S-TFPI interaction Journal of thrombosis and haemostasis : JTH High 20002538
2009 Protein S stimulates inhibition of factor Xa by full-length TFPI ~10-fold and is required for optimal TFPI anticoagulant activity; the TFPI/protein S system specifically inhibits TF pathway activation at low procoagulant stimuli. Protein S and TFPI constitute a constitutively active anticoagulant system in plasma, distinct from and cooperative with the APC pathway. Review summarizing functional plasma assays, thrombin generation experiments, and biochemical reconstitution studies from the authors' laboratory Arteriosclerosis, thrombosis, and vascular biology High 19661488
2014 TFPI inhibits MASP-2 of the lectin pathway of complement activation via its Kunitz-2 (KD2) domain, without affecting MASP-1, C1s, or C1r. This identifies TFPI as a novel selective inhibitor of MASP-2. Ex vivo lectin pathway activation assay (C4-deposition on mannan-coated plates); fluid-phase MASP-2 chromogenic activity assay; domain-mapping using recombinant TFPI and specific monoclonal antibodies against TFPI domains European journal of immunology High 25359215
2015 FXa inhibition by full-length TFPI is stimulated by negatively charged phospholipids (~5–6-fold), unfractionated heparin at low concentrations (~8-fold), physiological protein S (~2–3-fold), and FV (~2–3-fold). Thrombin-activated FVa impairs TFPI inhibition of FXa. These modulatory effects require the KD3-C-terminus region of TFPI, as TFPI1-150 is insensitive to these modulators. TFPI potently inhibits FXa-catalyzed prothrombin activation in absence of FVa but not in presence of FVa. Progress curve analysis of FXa inhibition using chromogenic substrate CS11-(65); comparison of full-length TFPI vs. TFPI1-150 constructs; systematic variation of phospholipids, heparin, prothrombin, FV, FVa, protein S Thrombosis and haemostasis High 26607136
2013 TFPI directly inhibits FVIIa in a TF-dependent and phospholipid-dependent manner; the KD3-C-terminus significantly contributes to direct FVIIa inhibition (7–10-fold difference vs. constructs lacking KD3-C-terminus). KD2 also contributes to FVIIa inhibition. In the presence of FXa, a tight quaternary TF-FVIIa-TFPI-FXa complex forms requiring phospholipids and the Gla-domain of FXa but not KD3-C-terminus. Protein S stimulates TF-FVIIa inhibition by full-length TFPI (Ki reduced from 4.6 nM to 0.7 nM). Chromogenic substrate assays for FVIIa activity with relipidated or soluble TF; comparison of full-length TFPI, TFPI1-150, KD1-KD2, and KD1 constructs Journal of thrombosis and haemostasis : JTH High 23347185
2014 Full-length TFPI inhibits TF:FVIIa-catalyzed FIX activation (Ki=16.7 nM) and this is stimulated 16-fold by protein S (Ki=1.0 nM). All three Kunitz domains and the C-terminus are required for optimal inhibition of FIX activation, and single Kunitz domains are poor inhibitors (Ki >800 nM). Preformed FXa:TFPI complexes rapidly and stoichiometrically inhibit FIX and FX activation by TF:FVIIa, establishing binary TFPI:FXa complex formation as the rate-limiting step. Progress curve analysis of FXa and FIXa generation with chromogenic substrates; comparison of full-length TFPI, TFPI1-150, KD1-KD2, and single domain constructs; variation of phospholipid concentration Journal of thrombosis and haemostasis : JTH High 25163770
2022 TFPI serves as a host cell receptor for TcdB from hypervirulent clade 2 Clostridioides difficile (TcdB2 and TcdB4). Cryo-EM structure of full-length TcdB4 with TFPI defined a common receptor-binding region in TcdB that is homologous to the Frizzled (FZD)-binding site in other TcdB variants. TFPI is highly expressed in intestinal glands (colonic crypts), and recombinant TFPI protects colonic epithelium from TcdB2/4. CRISPR/Cas9 genome-wide screen for TcdB4 receptor; cryo-EM structure determination of TcdB4-TFPI complex; recombinant TFPI protection assay of colonic epithelium Cell High 35303428
2022 TFPI is identified as a host receptor for TcdB4 (and TcdB10) from C. difficile. Intragenic micro-recombination events in the TcdB receptor-binding region determine whether TcdB variants bind TFPI or Frizzled proteins. Introduction of B4/B7-haplotype residues into TcdB1 enables dual recognition of TFPI and FZD. TcdB10 recognizes TFPI with species selectivity (chicken > mouse; not human, dog, or cattle). Genome-wide CRISPR-Cas9 screen; sequence analysis of 206 TcdB variants; mutagenesis introducing B4/B7-haplotype residues into TcdB1; cell-based binding and cytotoxicity assays Nature communications High 36351897
1992 Rat TFPI cDNA encodes a 302-amino acid protein with three tandem Kunitz-type inhibitor domains conserved in length across human, rabbit, and rat TFPI. TFPI mRNA is expressed as two forms (4.0 and 1.4 kb) and is abundantly expressed in heart, lung, kidney, and aortic endothelial cells in rats. cDNA cloning from rat liver cDNA library; Northern blot analysis; amino acid sequence alignment and homology analysis Journal of biochemistry Medium 1639767
2009 TFPI C-terminal peptides exhibit complement-dependent antibacterial activity against serum-resistant E. coli; C-terminal rTFPI fragments directly interact with the E. coli bacterial cell surface and kill bacteria through the complement pathway. Both complement-mediated killing and cell-surface binding are reversed by low amounts of heparin. Ex vivo blood culture killing assays with fragmented rTFPI and synthetic C-terminal TFPI peptides; serum complement-dependence assays; cell surface binding assays with reversal by heparin The Journal of infectious diseases Medium 19456231
2012 Protein S acts as a cofactor for full-length TFPI, stimulating FXa inhibition by TFPI. The TFPI/protein S system fails to regulate FXa generation at high TF/FVIIa concentrations but can regain activity in the presence of APC, demonstrating an intertwinement of TFPI- and APC-cofactor activities of protein S. Review summarizing plasma thrombin generation assays, purified component reconstitution experiments, and functional studies from the authors' laboratory Thrombosis research Medium 22425215
2015 TFPI1α (the anticoagulant protein TFPI) plays a role in driving the development of multiple drug resistance (MDR) in cancer but is not required for maintenance of the MDR state. Cancer cell line studies examining TFPI1α expression during doxorubicin resistance development (review with mechanistic discussion of primary experimental work) Cancers Low 26501324

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Null mutation of mCOUP-TFI results in defects in morphogenesis of the glossopharyngeal ganglion, axonal projection, and arborization. Genes & development 195 9271116
2008 Requirement for COUP-TFI and II in the temporal specification of neural stem cells in CNS development. Nature neuroscience 189 19160499
2007 COUP-TFI regulates the balance of cortical patterning between frontal/motor and sensory areas. Nature neuroscience 188 17828260
1991 Spontaneous mutation in the Escherichia coli lacI gene. Genetics 187 1660424
2009 Allostery in the LacI/GalR family: variations on a theme. Current opinion in microbiology 133 19269243
2007 COUP-TFI coordinates cortical patterning, neurogenesis, and laminar fate and modulates MAPK/ERK, AKT, and beta-catenin signaling. Cerebral cortex (New York, N.Y. : 1991) 118 18165280
2000 SsrA-mediated tagging and proteolysis of LacI and its role in the regulation of lac operon. The EMBO journal 118 10899129
2016 Epi-Drugs and Epi-miRs: Moving Beyond Current Cancer Therapies. Current cancer drug targets 116 26638884
2000 The aryl hydrocarbon receptor interacts with estrogen receptor alpha and orphan receptors COUP-TFI and ERRalpha1. Archives of biochemistry and biophysics 102 10620335
1995 Sites of tissue factor pathway inhibitor (TFPI) and tissue factor expression under physiologic and pathologic conditions. On behalf of the Subcommittee on Tissue factor Pathway Inhibitor (TFPI) of the Scientific and Standardization Committee of the ISTH. Thrombosis and haemostasis 102 7482419
2000 Differential expression of COUP-TFI, CHL1, and two novel genes in developing neocortex identified by differential display PCR. The Journal of neuroscience : the official journal of the Society for Neuroscience 101 11027229
2020 15-Epi-LXA4 and 17-epi-RvD1 restore TLR9-mediated impaired neutrophil phagocytosis and accelerate resolution of lung inflammation. Proceedings of the National Academy of Sciences of the United States of America 91 32205444
2019 Epigenetic polypharmacology: A new frontier for epi-drug discovery. Medicinal research reviews 88 31218726
1996 Tissue factor pathway inhibitor (TFPI)--an update. Haemostasis 85 8979119
2006 COUP-TFI is required for the formation of commissural projections in the forebrain by regulating axonal growth. Development (Cambridge, England) 81 17021036
2021 Completion of the gut microbial epi-bile acid pathway. Gut microbes 79 33938389
2014 Design and analysis of LacI-repressed promoters and DNA-looping in a cyanobacterium. Journal of biological engineering 71 24467947
1993 Inhibitory properties of full-length and truncated recombinant tissue factor pathway inhibitor (TFPI). Evidence that the third Kunitz-type domain of TFPI is not essential for the inhibition of factor VIIa-tissue factor complexes on cell surfaces. The Journal of biological chemistry 71 8473315
2014 Comparative genomics and evolution of regulons of the LacI-family transcription factors. Frontiers in microbiology 68 24966856
2009 Hereditary and acquired protein S deficiencies are associated with low TFPI levels in plasma. Journal of thrombosis and haemostasis : JTH 66 20002538
2022 TFPI is a colonic crypt receptor for TcdB from hypervirulent clade 2 C. difficile. Cell 61 35303428
2005 Tissue, cell and stage specificity of (epi)mutations in cancers. Nature reviews. Cancer 61 16056260
2019 Primers on nutrigenetics and nutri(epi)genomics: Origins and development of precision nutrition. Biochimie 57 30878492
2023 Endometriosis: Update of Pathophysiology, (Epi) Genetic and Environmental Involvement. Biomedicines 56 36979957
2011 COUP-TFI promotes radial migration and proper morphology of callosal projection neurons by repressing Rnd2 expression. Development (Cambridge, England) 56 21965613
2009 Regulation of TFPI function by protein S. Journal of thrombosis and haemostasis : JTH 55 19630792
1992 Lipoprotein-associated coagulation inhibitor (LACI) is a cofactor for heparin: synergistic anticoagulant action between LACI and sulfated polysaccharides. Blood 55 1346095
2004 The nuclear orphan receptor COUP-TFI is important for differentiation of oligodendrocytes. Developmental biology 54 14738874
1998 Correlates of antithrombin, protein C, protein S, and TFPI in a healthy elderly cohort. Thrombosis and haemostasis 53 9684799
2018 The pleiotropic transcriptional regulator COUP-TFI plays multiple roles in neural development and disease. Brain research 49 29709504
2018 Anti-tissue factor pathway inhibitor (TFPI) therapy: a novel approach to the treatment of haemophilia. International journal of hematology 49 30302740
2009 Protein S as cofactor for TFPI. Arteriosclerosis, thrombosis, and vascular biology 49 19661488
2008 Genetics, epigenetics and pharmaco-(epi)genomics in angiogenesis. Journal of cellular and molecular medicine 47 19210754
2009 EGCG inhibits growth and induces apoptosis in renal cell carcinoma through TFPI-2 overexpression. Oncology reports 46 19212621
2013 Pericardioscopy and epi- and pericardial biopsy - a new window to the heart improving etiological diagnoses and permitting targeted intrapericardial therapy. Heart failure reviews 44 23479317
2018 Inhibition of Tissue Factor Pathway Inhibitor (TFPI) as a Treatment for Haemophilia: Rationale with Focus on Concizumab. Drugs 43 29845491
2010 Atorvastatin or transgenic expression of TFPI inhibits coagulation initiated by anti-nonGal IgG binding to porcine aortic endothelial cells. Journal of thrombosis and haemostasis : JTH 43 20553382
2010 TFPI-2 is a putative tumor suppressor gene frequently inactivated by promoter hypermethylation in nasopharyngeal carcinoma. BMC cancer 43 21062455
2009 Expression of tissue factor pathway inhibitor (TFPI) in human breast and colon cancer tissue. Thrombosis and haemostasis 42 20062932
2012 Methylation of TFPI-2 is an early event of esophageal carcinogenesis. Epigenomics 41 22449186
2006 COUP-TFI controls Notch regulation of hair cell and support cell differentiation. Development (Cambridge, England) 41 16914494
2002 Formation of an hER alpha-COUP-TFI complex enhances hER alpha AF-1 through Ser118 phosphorylation by MAPK. The EMBO journal 38 12093745
2003 Repression of the luteinizing hormone receptor gene promoter by cross talk among EAR3/COUP-TFI, Sp1/Sp3, and TFIIB. Molecular and cellular biology 37 12972613
2022 Epi-immunotherapy for cancers: rationales of epi-drugs in combination with immunotherapy and advances in clinical trials. Cancer communications (London, England) 36 35642676
2019 The evolving (epi)genetic landscape of pancreatic neuroendocrine tumours. Endocrine-related cancer 36 31252410
2010 Genome-wide analysis of binding sites and direct target genes of the orphan nuclear receptor NR2F1/COUP-TFI. PloS one 36 20111703
2018 Epigenetics and Epi-miRNAs: Potential markers/therapeutics in leukemia. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 35 30170355
2021 Applications and potentials of nanopore sequencing in the (epi)genome and (epi)transcriptome era. Innovation (Cambridge (Mass.)) 34 34901902
2017 Gradient COUP-TFI Expression Is Required for Functional Organization of the Hippocampal Septo-Temporal Longitudinal Axis. Cerebral cortex (New York, N.Y. : 1991) 34 26813976
2015 Role of exosite binding modulators in the inhibition of Fxa by TFPI. Thrombosis and haemostasis 34 26607136
1998 The lacI gene as a target for mutation in transgenic rodents and Escherichia coli. Genetics 34 9560364
2014 TFPI inhibits lectin pathway of complement activation by direct interaction with MASP-2. European journal of immunology 33 25359215
2011 Knockdown of TFPI-2 promotes migration and invasion of glioma cells. Neuroscience letters 33 21530612
1992 cDNA cloning and expression of rat tissue factor pathway inhibitor (TFPI). Journal of biochemistry 33 1639767
2022 Epi-Drugs in Heart Failure. Frontiers in cardiovascular medicine 32 35911511
2016 Targeting TFPI for hemophilia treatment. Thrombosis research 32 27207418
2014 COUP-TFI modifies CXCL12 and CXCR4 expression by activating EGF signaling and stimulates breast cancer cell migration. BMC cancer 32 24906407
2011 Tissue factor/TFPI and blood cells. Thrombosis research 32 22197177
2007 COUP-TFI modulates estrogen signaling and influences proliferation, survival and migration of breast cancer cells. Breast cancer research and treatment 30 17674191
2015 Development, Maintenance, and Reversal of Multiple Drug Resistance: At the Crossroads of TFPI1, ABC Transporters, and HIF1. Cancers 29 26501324
2013 COUP-TFI controls activity-dependent tyrosine hydroxylase expression in adult dopaminergic olfactory bulb interneurons. Development (Cambridge, England) 28 24227652
2003 Transcriptional silencing of the TFPI-2 gene by promoter hypermethylation in choriocarcinoma cells. Biological chemistry 28 12956419
2008 Blood coagulation and fibrinolysis in patients with acromegaly: increased plasminogen activator inhibitor-1 (PAI-1), decreased tissue factor pathway inhibitor (TFPI), and an inverse correlation between growth hormone and TFPI. Endocrine 27 19016004
2001 EAR2 and EAR3/COUP-TFI regulate transcription of the rat LH receptor. Molecular endocrinology (Baltimore, Md.) 27 11682620
2021 Concizumab: a novel anti-TFPI therapeutic for hemophilia. Blood advances 26 33570646
2015 RNA (Epi)genetics in cardiovascular diseases. Journal of molecular and cellular cardiology 26 26205296
2014 Inhibition of tissue factor:factor VIIa-catalyzed factor IX and factor X activation by TFPI and TFPI constructs. Journal of thrombosis and haemostasis : JTH 26 25163770
2001 COUP-TFI and COUP-TFII regulate expression of the NHE through a nuclear hormone responsive element with enhancer activity. European journal of biochemistry 26 11168401
2020 Remodeling the epigenome and (epi)cytoskeleton: a new paradigm for co-regulation by methylation. The Journal of experimental biology 25 32620673
2015 Transcription factors COUP-TFI and COUP-TFII are required for the production of granule cells in the mouse olfactory bulb. Development (Cambridge, England) 24 25922524
2015 Epi-fingerprinting and epi-interventions for improved crop production and food quality. Frontiers in plant science 24 26097484
2007 Deoxyribonucleic acid methyl transferases 3a and 3b associate with the nuclear orphan receptor COUP-TFI during gene activation. Molecular endocrinology (Baltimore, Md.) 24 17579209
1996 Probable regulation of factor VIIa-tissue factor and prothrombinase by factor Xa-TFPI and TFPI in vivo. British journal of haematology 24 8982054
2022 Identification of TFPI as a receptor reveals recombination-driven receptor switching in Clostridioides difficile toxin B variants. Nature communications 23 36351897
2013 (Epi)genetics of pregnancy-associated diseases. Frontiers in genetics 23 24058367
2012 TFPI-dependent activities of protein S. Thrombosis research 23 22425215
1998 COUP-TFI expression in human adrenocortical adenomas: possible role in steroidogenesis. The Journal of clinical endocrinology and metabolism 23 9851803
1998 Mutation studies in lacI transgenic mice after exposure to radiation or cyclophosphamide. Mutagenesis 23 9862192
2017 COUP-TFI mitotically regulates production and migration of dentate granule cells and modulates hippocampal Cxcr4 expression. Development (Cambridge, England) 22 28506990
2006 Protein and mRNA expression of tissue factor pathway inhibitor-1 (TFPI-1) in breast, pancreatic and colorectal cancer cells. Molecular biology reports 22 17180732
2014 Multiple LacI-mediated loops revealed by Bayesian statistics and tethered particle motion. Nucleic acids research 21 25120267
2013 Direct inhibition of factor VIIa by TFPI and TFPI constructs. Journal of thrombosis and haemostasis : JTH 21 23347185
2012 Hemostatic properties of a TFPI antibody. Thrombosis research 21 22405586
2005 Dynamic expression of COUP-TFI and COUP-TFII during development and functional maturation of the mouse inner ear. Gene expression patterns : GEP 21 15907456
1996 Cloning of the cDNA encoding mouse PP5/TFPI-2 and mapping of the gene to chromosome 6. DNA and cell biology 21 8945635
2001 Ion concentration and temperature dependence of DNA binding: comparison of PurR and LacI repressor proteins. Biochemistry 20 11434780
2021 Diffusion-Weighted MRI to Assess Sacroiliitis: Improved Image Quality and Diagnostic Performance of Readout-Segmented Echo-Planar Imaging (EPI) Over Conventional Single-Shot EPI. AJR. American journal of roentgenology 19 32903053
2016 TFPI-2 expression is decreased in bladder cancer and is related to apoptosis. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 19 28039717
1993 Large-scale mutational analysis of EMS-induced mutation in the lacI gene of Escherichia coli. Mutation research 19 7686256
2007 Integration host factor alters LacI-induced DNA looping. Biophysical chemistry 18 17543441
2022 Epi-miRNAs: Modern mediators of methylation status in human cancers. Wiley interdisciplinary reviews. RNA 17 35580998
2019 Enhancement of LacI binding in vivo. Nucleic acids research 17 31396617
2015 Adding 'epi-' to behaviour genetics: implications for animal domestication. The Journal of experimental biology 17 25568449
2015 Flexibility and Disorder in Gene Regulation: LacI/GalR and Hox Proteins. The Journal of biological chemistry 17 26342073
2009 Fragmented tissue factor pathway inhibitor (TFPI) and TFPI C-terminal peptides eliminate serum-resistant Escherichia coli from blood cultures. The Journal of infectious diseases 17 19456231
2006 LacO-LacI interaction in affinity adsorption of plasmid DNA. Biotechnology and bioengineering 17 16646090
2000 Future possibilities in the regulation of the extrinsic pathway: rFVIIa and TFPI. Annals of medicine 17 11209985
1994 Use of transgenic mouse lacI/Z mutation assays in genetic toxicology. Mutagenesis 17 7934956
2024 OptoLacI: optogenetically engineered lactose operon repressor LacI responsive to light instead of IPTG. Nucleic acids research 16 38860425
2022 TFPI and FXIII negatively and S100A8/A9 and Cystatin C positively correlate with D-dimer in COVID-19. Experimental biology and medicine (Maywood, N.J.) 16 35723053

Missed literature

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