Affinage

CPB2

Carboxypeptidase B2 · UniProt Q96IY4

Length
423 aa
Mass
48.4 kDa
Annotated
2026-04-28
100 papers in source corpus 32 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CPB2 (thrombin-activatable fibrinolysis inhibitor, TAFI) is a hepatically and megakaryocyte-synthesized plasma zymogen that functions as a central regulator linking coagulation, fibrinolysis, and inflammation. The zymogen is cleaved at Arg-92 by the thrombin–thrombomodulin complex—which enhances activation 1250-fold over free thrombin—to generate TAFIa, a carboxypeptidase B-like enzyme that removes C-terminal lysine and arginine residues from partially degraded fibrin (suppressing plasminogen recruitment and fibrinolysis), bradykinin, C3a, C5a, and osteopontin (dampening inflammation) (PMID:7782309, PMID:8663147, PMID:18706698). TAFIa is intrinsically unstable (half-life ~8–15 min at 37 °C depending on the Thr325Ile polymorphism), and crystal structures reveal that this instability is governed by a dynamic 55-residue flap (residues 296–350) that becomes mobile upon activation-peptide release, disrupting the catalytic site and exposing a cryptic thrombin-cleavage site at Arg302 (PMID:18559974, PMID:11684677). TAFIa activity is further tuned by thrombomodulin concentration, the protein C/protein S anticoagulant axis, platelet factor 4, and factor XI–dependent thrombin feedback, establishing TAFI as a dose- and time-sensitive rheostat that balances clot stability against fibrinolytic and inflammatory resolution (PMID:8822928, PMID:11204587, PMID:21041299, PMID:10613658).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1995 High

    Identification of a novel plasma protein that couples thrombin generation to fibrinolytic suppression resolved how coagulation directly attenuates plasminogen activation on fibrin.

    Evidence Purification of a 60-kDa zymogen from human plasma, thrombin cleavage to 35-kDa active form, inhibition of Glu-plasminogen activation on fibrin, reversal by CPB inhibitor GEMSA

    PMID:7782309

    Open questions at the time
    • Physiological activator not yet identified (free thrombin is inefficient)
    • In vivo relevance not established
  2. 1996 High

    Demonstration that the thrombin–thrombomodulin complex is the physiological activator of TAFI (1250-fold enhancement) and that activated protein C exerts its profibrinolytic effect through TAFI-dependent suppression of thrombin generation established the regulatory logic connecting the anticoagulant and fibrinolytic pathways.

    Evidence Kinetic analysis with purified thrombin/TM/TAFI showing kcat increase; TAFI immunodepletion/reconstitution showing APC profibrinolytic effect is entirely TAFI-dependent

    PMID:8663147 PMID:8822928

    Open questions at the time
    • Structural basis of thrombomodulin cofactor effect unknown
    • In vivo activation kinetics not measured
  3. 1998 High

    Characterization of TAFIa's intrinsic thermal instability (~10 min half-life at 37 °C) revealed that the enzyme self-limits its antifibrinolytic effect, making stability rather than concentration the key determinant of activity.

    Evidence Recombinant TAFI expression in BHK cells, fluorescence spectroscopy showing conformational decay, competitive inhibitor stabilization

    PMID:9442053

    Open questions at the time
    • Structural basis of instability unknown
    • Physiological significance of self-inactivation not tested in vivo
  4. 1999 High

    Mapping the activation cleavage site to Arg-92, characterizing the gene structure (11 exons, liver-specific promoter), and showing that factor XI–dependent thrombin feedback (not contact activation) drives TAFI activation during clot formation placed TAFI within the intrinsic coagulation amplification loop.

    Evidence Genomic cloning and reporter assays for promoter; factor XI/XII neutralizing antibodies and factor II-deficient plasma for pathway mapping

    PMID:10350473 PMID:10613658

    Open questions at the time
    • Factor XI dependence measured in plasma system only; in vivo contribution not tested
    • Promoter regulation beyond liver-specific element not characterized
  5. 2001 High

    Discovery that the common Thr325Ile polymorphism nearly doubles TAFIa half-life and increases antifibrinolytic potency by ~60% established a genetic determinant of fibrinolytic capacity, while thrombomodulin concentration and protein S were shown to tune the balance between TAFI and protein C activation.

    Evidence Expression of four TAFI variant combinations in BHK cells with stability/clot lysis assays; TM titration experiments; protein S depletion/reconstitution

    PMID:11204587 PMID:11684677 PMID:11686322

    Open questions at the time
    • Population-level thrombotic risk from Ile325 not definitively established
    • Protein S APC-independent mechanism not fully dissected
  6. 2002 High

    TAFI-knockout mice demonstrated that TAFI is dispensable for normal hemostasis and baseline bradykinin catabolism but is required for thrombin-dependent prolongation of clot lysis, establishing it as a conditional rather than constitutive regulator.

    Evidence Targeted gene disruption in mice; clot lysis, bleeding, arterial/venous thrombosis, and bradykinin writhing tests

    PMID:11781355 PMID:11815293

    Open questions at the time
    • Inflammatory challenge phenotypes not yet tested
    • Compensatory mechanisms not excluded
  7. 2003 High

    Detection of TAFI in human platelets with secretion upon activation and synthesis in megakaryocytes identified a local, non-hepatic source of TAFI that could contribute to thrombus-proximal antifibrinolytic activity.

    Evidence ELISA, Western blot, RT-PCR in megakaryocytic lines DAMI/CHRF, thrombomodulin-dependent activation kinetics

    PMID:12595308

    Open questions at the time
    • Quantitative contribution of platelet vs. plasma TAFI to hemostasis not established
    • Glycosylation differences' functional significance unclear
  8. 2008 High

    Crystal structures of TAFI, TAFI–GEMSA complex, and a hyperstable quadruple mutant revealed that a 55-residue dynamic flap (296–350) is stabilized by the activation peptide in the zymogen; upon activation-peptide release, increased flap mobility disrupts the catalytic site and exposes Arg302 to thrombin cleavage, providing the structural basis for TAFIa's built-in self-inactivation timer.

    Evidence X-ray crystallography of multiple TAFI forms (2.1 Å), mutagenesis cross-validation, thermal stability assays

    PMID:18559974 PMID:18669641

    Open questions at the time
    • No time-resolved structural data capturing intermediate states of flap opening
    • In vivo confirmation of Arg302 cleavage pathway not established
  9. 2008 High

    In vivo evidence that TAFIa inactivates bradykinin, C3a, and C5a by C-terminal arginine removal—using proCPB-deficient mice and a selective thrombin mutant activator—established TAFI as a physiological anti-inflammatory enzyme beyond its antifibrinolytic role.

    Evidence proCPB-knockout mice, E229K thrombin mutant selective for TAFI activation, bradykinin-induced hypotension model, C5a-induced alveolitis model

    PMID:18706698 PMID:19025114

    Open questions at the time
    • Relative quantitative contribution of TAFI vs. other carboxypeptidases (CPN) to anaphylatoxin clearance not resolved
    • Chronic inflammatory disease models limited
  10. 2010 Medium

    Platelet factor 4 was shown to selectively inhibit thrombomodulin-dependent TAFI activation while stimulating protein C activation, revealing an additional layer of substrate-specific modulation of the thrombin–TM complex.

    Evidence In vitro clot lysis, bradykinin conversion assay, NAc-heparin competition binding on TM-expressing cells

    PMID:21041299

    Open questions at the time
    • In vivo relevance of PF4-mediated TAFI inhibition not tested
    • Structural basis of PF4–TM interaction not resolved
    • Single-lab finding
  11. 2013 Medium

    TAFI deficiency promoted liver fibrogenesis and necrosis in injury models, linking TAFI's anti-inflammatory function (anaphylatoxin inactivation) to organ protection beyond the vascular compartment.

    Evidence TAFI-knockout mice in CCl4-induced chronic liver injury and acetaminophen intoxication models with histological and biochemical endpoints

    PMID:23467679

    Open questions at the time
    • Mechanism assumed to be via C3a/C5a inactivation but not directly tested with anaphylatoxin measurements
    • Single-lab study
  12. 2017 High

    Bone marrow transplantation experiments demonstrated that hepatic (not marrow-derived) TAFI is activated locally in pulmonary artery endothelium via thrombin–TM, driving vascular remodeling in chronic thromboembolic pulmonary hypertension.

    Evidence Bone marrow transplantation, TAFIa overexpression in mice, TAFIa inhibitor treatment, hemodynamic measurements in mouse/rat CTEPH models

    PMID:28289017

    Open questions at the time
    • Human CTEPH causation vs. association not established
    • Specific substrate responsible for vascular remodeling not identified
  13. 2020 Medium

    A human pedigree carrying a CPB2 stop-gain variant confirmed that TM-dependent TAFI activation mediates delayed fibrinolysis in vivo, providing natural genetic epistasis evidence in humans.

    Evidence Next-generation sequencing, plasma TAFI levels, clot lysis and thrombin generation assays in family members with high-TM coagulopathy

    PMID:32634856

    Open questions at the time
    • Single pedigree observation
    • Complete TAFI deficiency phenotype in humans not fully characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural dynamics of the flap transition in real time, the quantitative partitioning of TAFI's antifibrinolytic versus anti-inflammatory roles in human disease, and whether pharmacological TAFIa inhibition can safely enhance fibrinolysis without exacerbating inflammation.
  • No time-resolved structural data for the inactivation conformational change
  • No human clinical trial data for selective TAFIa inhibitors
  • Relative contribution of platelet-derived vs. plasma TAFI in vivo not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 5 GO:0140096 catalytic activity, acting on a protein 5
Localization
GO:0005576 extracellular region 4 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-109582 Hemostasis 6 R-HSA-392499 Metabolism of proteins 4 R-HSA-168256 Immune System 2
Partners
F2PF4PLGPROCPROS1THBD

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 TAFI (CPB2/plasma procarboxypeptidase B) was purified from human plasma as a 60-kDa single-chain protein that, upon cleavage by thrombin, generates a 35-kDa product with carboxypeptidase B-like activity that inhibits fibrinolysis by blocking activation of Glu-plasminogen; the competitive CPB inhibitor GEMSA completely abolishes this antifibrinolytic effect. Purification from plasma, in vitro clot lysis assay, amino-terminal sequence analysis, competitive inhibitor studies The Journal of biological chemistry High 7782309
1996 The thrombin-thrombomodulin complex is the primary physiological activator of TAFI; thrombomodulin increases the catalytic efficiency of TAFI activation 1250-fold (expressed almost exclusively as an increase in kcat), forming a ternary thrombin-thrombomodulin-TAFI complex with kcat = 1.2 s⁻¹ and Km = 1.0 µM for TAFI and Kd = 8.6 nM for thrombomodulin. Kinetic analysis of purified components, thrombomodulin titration, in vitro clot lysis assay The Journal of biological chemistry High 8663147
1996 Activated protein C (APC) exerts its profibrinolytic effect predominantly through TAFI-dependent mechanisms: APC has no profibrinolytic effect in TAFI-immunodepleted plasma, and the effect is fully reconstituted by adding purified TAFI; monoclonal antibody blocking TAFI activation mimics APC's profibrinolytic effect. TAFI immunodepletion, reconstitution with purified TAFI, monoclonal antibody inhibition, turbidity-based clot lysis assay, ELISA (plasma TAFI concentration = 73 nM) Blood High 8822928
1997 TAFIa suppresses fibrinolysis by removing C-terminal lysine residues from partially degraded fibrin, thereby downregulating the cofactor function of fibrin in the fibrinolytic cascade; thrombin generation links coagulation to fibrinolytic suppression through this mechanism. In vitro clot lysis assays with purified components, CPB inhibitor studies Thrombosis and haemostasis High 9198184
1997 Meizothrombin, a thrombin intermediate, can activate TAFI in the presence of thrombomodulin, but is much less potent than thrombin in procoagulant functions, indicating differential substrate specificity in the thrombomodulin-dependent pathway. Recombinant expression of prothrombin mutants, kinetic assays for TAFI activation and protein C activation in presence of thrombomodulin The Journal of biological chemistry Medium 9045633
1998 Recombinant TAFI (rTAFI) expressed in BHK cells has activation kinetics by thrombin/thrombomodulin indistinguishable from plasma TAFI (kcat ~0.55-0.61 s⁻¹, Km ~0.54-0.55 µM); activated TAFIa is intrinsically thermally unstable with a half-life of ~10 min at 37°C, and decay is associated with quenching of intrinsic fluorescence; competitive inhibitors GEMSA and ε-aminocaproic acid stabilize TAFIa. Stable BHK cell expression, purification, kinetics of activation, fluorescence spectroscopy, thermal stability assays, in vitro fibrinolysis assays The Journal of biological chemistry High 9442053
1999 Activation of TAFI by thrombin occurs at Arg-92; the TAFI gene contains 11 exons spanning ~48 kb, shares conserved intron/exon boundaries with pancreatic carboxypeptidase genes, and a ~70 bp liver-specific promoter element was identified by transient transfection reporter assays. Genomic library cloning, exon mapping, transient transfection reporter assays, cDNA sequencing Biochemistry Medium 10350473
2001 Two naturally occurring TAFI variants at position 325 (Thr vs. Ile) differ substantially in TAFIa thermal stability: Ile-325 TAFIa has a half-life of ~15 min vs. ~8 min for Thr-325 at 37°C, conferring ~60% greater antifibrinolytic potency, while the Ala-147/Thr-147 variation has minimal effect on enzymatic properties. Stable BHK cell expression of four variant combinations, purification, thermal stability assays, clot lysis assays, kinetics of activation The Journal of biological chemistry High 11684677
2001 Thrombomodulin concentration determines the balance between fibrinolysis promotion (via protein C activation at high TM) and inhibition (via TAFI activation at low TM); protein C inhibitor (PCI) differentially regulates the thrombin-TM complex to modulate TAFI vs. protein C activation. Plasma-based clot lysis assays with varying thrombomodulin concentrations, TAFI activity measurement, protein C pathway inhibition Thrombosis and haemostasis High 11204587 11686324
2001 Protein S inhibits TAFI activation through two mechanisms: as an APC cofactor reducing maximum TAFIa activity, and independently of APC by inhibiting initial thrombin formation, thereby reducing the rate of TAFI activation. Protein S depletion from plasma, antibody inhibition, measurement of TAFI activation rate and maximum activity Thrombosis and haemostasis Medium 11686322
2002 Amino acids in the P6-P'3 region surrounding the Arg-92 activation cleavage site of TAFI do not determine thrombomodulin dependence of TAFI activation; thrombomodulin's role is to optimally orient thrombin and substrate rather than allosterically alter thrombin active-site specificity. Site-directed mutagenesis of TAFI activation site, expression in mammalian cells, kinetic analysis of activation by thrombin ± thrombomodulin The Journal of biological chemistry Medium 11786552
2002 Crystal structure of human pancreatic procarboxypeptidase B (the structural prototype for plasma TAFI/CPB2) at 1.6 Å resolution reveals a 95-residue pro-segment with globular + alpha-helical topology shielding a preformed active site; the active-site Zn-binding residue has two alternate conformations relevant to substrate binding. X-ray crystallography at 1.6 Å resolution Journal of molecular biology High 12162965
2002 TAFI deficiency in mice (knockout) is compatible with life; TAFI-deficient mice fail to prolong clot lysis time in vitro but show no excess bleeding or altered occlusion times in arterial/venous injury models under normal conditions, and TAFI does not play a major role in bradykinin catabolism under basal conditions. Targeted gene disruption, in vitro clot lysis assay, tail transection bleeding assay, arterial/venous thrombosis models, bradykinin writhing test The Journal of clinical investigation High 11781355 11815293
2003 TAFI is present in human platelets (~50 ng/10⁹ platelets), is secreted upon platelet activation, can be activated by thrombin/thrombomodulin similarly to plasma TAFI, and is synthesized in megakaryocytes (mRNA detected in megakaryocytic cell lines DAMI and CHRF); platelet-TAFI glycosylation differs from plasma TAFI. TAFI ELISA, Western blot, platelet activation assays, RT-PCR in megakaryocytic cell lines, thrombomodulin-dependent activation kinetics Blood High 12595308
2003 Hyperprothrombinemia (prothrombin G20210A mutation) inhibits fibrinolysis through a TAFI-dependent mechanism: increased prothrombin generates more late thrombin, activates more TAFI, and a specific TAFIa inhibitor abolishes the difference in clot lysis time between carriers and non-carriers. TAFIa activity assay during clot lysis, specific TAFIa inhibitor (PTCI), purified prothrombin addition to normal plasma, plasma from G20210A carriers Blood High 14630828
2006 TAFIa zymogen (TAFI itself, before activation) exhibits continuous and stable carboxypeptidase activity against large peptide substrates, suggesting that the zymogen is not completely inactive and may down-regulate fibrinolysis constitutively in vivo. In vitro carboxypeptidase activity assay on purified zymogen with large peptide substrates The Journal of biological chemistry Medium 17138567
2006 Limited mutagenesis of TAFIa can extend its half-life at 37°C from 0.2 h up to 5.5 h; increased stability correlates with thermostability and trypsin resistance; more stable TAFIa mutants more effectively down-regulate fibrinolysis than higher concentrations of less stable wild-type enzyme, demonstrating that TAFIa stability is a greater determinant of antifibrinolytic potency than zymogen concentration. Site-directed mutagenesis, thermal stability assays, trypsin susceptibility, in vitro clot lysis assays The FEBS journal Medium 16441664
2008 Crystal structures of TAFI, a TAFI-GEMSA inhibitor complex, and a quadruple TAFI mutant (70-fold more stable) reveal that TAFIa stability is governed by a dynamic 55-residue flap (residues 296-350) including active-site wall residues; in the zymogen, the activation peptide stabilizes this flap; after activation peptide release, increased flap mobility leads to conformational changes that disrupt the catalytic site and expose a cryptic thrombin-cleavage site at Arg302, establishing a novel auto-regulatory mechanism of enzyme inactivation. X-ray crystallography (TAFI, TAFI-GEMSA, and quadruple mutant), site-directed mutagenesis, thermal stability assays Blood High 18559974
2008 Crystal structure of TAFI at 2.1 Å reveals that the active site is accessible in the zymogen (explaining intrinsic activity), identifies an 'instability region' consistent with mutagenesis data, and identifies sulfate ions bound to this region pointing toward a potential heparin-binding site that could explain how heparin stabilizes TAFIa. X-ray crystallography, site-directed mutagenesis cross-validation The Journal of biological chemistry High 18669641
2008 Activated TAFI (CPB2) inactivates pro-inflammatory mediators bradykinin, C3a, C5a, and thrombin-cleaved osteopontin by removing C-terminal arginines; in vivo, proCPB-deficient mice show enhanced bradykinin-induced hypotension and enhanced C5a-induced pulmonary alveolitis, and a thrombin mutant (E229K) that selectively activates proCPB (not protein C) reverses these inflammatory phenotypes in wild-type but not proCPB-deficient mice. In vitro enzymatic assays, proCPB-deficient mouse models, in vivo infusion of E229K thrombin mutant, C5a-induced alveolitis model, inflammatory arthritis model Molecular immunology High 18706698 19025114
2008 Pig thrombomodulin binds human thrombin but is a poor cofactor for activation of human TAFI (and protein C); domain-swapping experiments show that EGF5 of thrombomodulin is the most important determinant of species compatibility for TAFI activation. Cloning of pig TM, domain-swapping, transfection assays measuring TAFI activation efficiency American journal of transplantation Medium 18444940
2008 Streptococcus pyogenes recruits and activates TAFI on its surface; activated TAFI processes bradykinin by C-terminal truncation, converting it from a B2 receptor ligand to a B1 receptor agonist, potentially redirecting inflammation from transient to chronic. Bacterial surface binding assays, TAFI activation assays, bradykinin processing, B1/B2 receptor signaling assays, electron microscopy Journal of innate immunity Medium 20375563
2010 Platelet factor 4 (PF4) inhibits thrombomodulin-dependent activation of TAFI by thrombin while simultaneously stimulating protein C activation, demonstrating that PF4 modulates the substrate specificity of the thrombin-TM complex to selectively suppress TAFIa-mediated antifibrinolytic and anti-inflammatory activities; N-acetylated heparin (NAc-Hep) blocks PF4 binding to TM and reverses this inhibition. In vitro clot lysis assays, bradykinin conversion assay, hemophilia A plasma, TM-expressing cell assays, competition binding experiments The Journal of biological chemistry Medium 21041299
2007 TAFI and pancreatic carboxypeptidase B inhibit in vitro capillary tube formation by human microvascular endothelial cells by removing C-terminal lysine residues from fibrin degradation products and from the cell surface, thereby impairing plasminogen-dependent endothelial cell migration (without affecting proliferation or adhesion). 3D plasma clot matrix tube formation assay, fibrin degradation product measurement, cell migration assay, TAFIa inhibitor (PTCI) Arteriosclerosis, thrombosis, and vascular biology Medium 17673703
2017 Activated TAFI (TAFIa) promotes development of chronic thromboembolic pulmonary hypertension (CTEPH): bone marrow transplantation shows that hepatic TAFI (not marrow-derived) is activated locally in pulmonary artery endothelial cells via thrombin-thrombomodulin; TAFIa increases PA endothelial permeability, smooth muscle cell proliferation, and monocyte/macrophage activation; TAFIa inhibitor reduces pulmonary hypertension in mouse and rat models. Bone marrow transplantation, overexpression of TAFIa in mice, TAFIa inhibitor treatment, immunostaining, clot lysis assays, hemodynamic measurements Circulation research High 28289017
2012 In double TAFI/PAI-1 knockout mice, TAFI deficiency predominantly determines enhanced fibrinolytic capacity as measured by thromboelastometry and fibrin deposition in a thromboembolism model, demonstrating that TAFI is a more critical fibrinolysis regulator than PAI-1 under the conditions tested. TAFI/PAI-1 double-knockout mouse generation, rotational thromboelastometry, thromboembolism model (fibrin deposition in lungs), tail vein bleeding model Journal of thrombosis and haemostasis Medium 23083123
2013 TAFI deficiency promotes liver damage in murine models: TAFI-knockout mice show accelerated fibrogenesis (increased α-SMA, pro-collagen α1), elevated liver enzymes, and increased neutrophil influx in CCl4-induced chronic liver injury, and increased necrosis after acetaminophen intoxication, linking TAFI's anti-inflammatory activity (via anaphylatoxin inactivation) to protection against liver inflammation. TAFI-knockout mice, CCl4-induced chronic liver injury, acetaminophen intoxication model, immunohistochemistry, ALT/AST measurement, hepatic fibrin deposition Thrombosis and haemostasis Medium 23467679
1999 Activation of TAFI during clot formation in plasma is largely factor XI-dependent (reduced ~65% by anti-factor XI antibody), occurs after clot formation via thrombin feedback, and requires conversion of approximately 50% of prothrombin to thrombin for full TAFI activation; the contact system (factor XII) is not required. Factor XI and factor XII neutralizing monoclonal antibodies, factor II-deficient plasma, specific TAFIa activity assay Thrombosis and haemostasis High 10613658
2020 In a pedigree with thrombomodulin-associated coagulopathy carrying a stop-gain variant in CPB2 (encoding TAFI), co-inherited TAFI deficiency partially attenuates the delayed fibrinolysis caused by high thrombomodulin levels without affecting defective thrombin generation, directly confirming that TM-dependent TAFI activation mediates the fibrinolytic delay. Next-generation sequencing, plasma TAFI level measurement, clot lysis assays, thrombin generation assays in human pedigree members Journal of thrombosis and haemostasis Medium 32634856

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Purification and characterization of TAFI, a thrombin-activable fibrinolysis inhibitor. The Journal of biological chemistry 584 7782309
1996 TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin complex. The Journal of biological chemistry 537 8663147
1996 The profibrinolytic effect of activated protein C in clots formed from plasma is TAFI-dependent. Blood 259 8822928
1997 Thrombin, thrombomodulin and TAFI in the molecular link between coagulation and fibrinolysis. Thrombosis and haemostasis 221 9198184
1998 Plasma TAFI levels influence the clot lysis time in healthy individuals in the presence of an intact intrinsic pathway of coagulation. Thrombosis and haemostasis 196 9843179
2021 Pollen PCP-B peptides unlock a stigma peptide-receptor kinase gating mechanism for pollination. Science (New York, N.Y.) 168 33833120
1998 Plasma and recombinant thrombin-activable fibrinolysis inhibitor (TAFI) and activated TAFI compared with respect to glycosylation, thrombin/thrombomodulin-dependent activation, thermal stability, and enzymatic properties. The Journal of biological chemistry 156 9442053
2001 Two naturally occurring variants of TAFI (Thr-325 and Ile-325) differ substantially with respect to thermal stability and antifibrinolytic activity of the enzyme. The Journal of biological chemistry 150 11684677
2001 Identification of polymorphisms in the promoter and the 3' region of the TAFI gene: evidence that plasma TAFI antigen levels are strongly genetically controlled. Blood 124 11264171
2006 Salmonella enterica serovar Typhimurium requires the Lpf, Pef, and Tafi fimbriae for biofilm formation on HEp-2 tissue culture cells and chicken intestinal epithelium. Infection and immunity 121 16714543
2002 Thrombin-activatable fibrinolysis inhibitor (TAFI) deficiency is compatible with murine life. The Journal of clinical investigation 120 11781355
2003 Prevalence of cpb2, encoding beta2 toxin, in Clostridium perfringens field isolates: correlation of genotype with phenotype. Veterinary microbiology 117 12781480
2001 Thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B, procarboxypeptidase R, procarboxypeptidase U). Thrombosis research 112 11297751
2001 Regulation of fibrinolysis in plasma by TAFI and protein C is dependent on the concentration of thrombomodulin. Thrombosis and haemostasis 109 11204587
2001 The defective down regulation of fibrinolysis in haemophilia A can be restored by increasing the TAFI plasma concentration. Thrombosis and haemostasis 104 11686321
2008 Pig thrombomodulin binds human thrombin but is a poor cofactor for activation of human protein C and TAFI. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 103 18444940
2001 Identification of polymorphisms in the 5'-untranslated region of the TAFI gene: relationship with plasma TAFI levels and risk of venous thrombosis. Haematologica 97 11410415
2003 Identification of thrombin activatable fibrinolysis inhibitor (TAFI) in human platelets. Blood 95 12595308
1996 NAP-I is a functional homologue of TAF-I that is required for replication and transcription of the adenovirus genome in a chromatin-like structure. Genes to cells : devoted to molecular & cellular mechanisms 94 9077453
2002 Multiple interactions between RNA polymerase I, TIF-IA and TAF(I) subunits regulate preinitiation complex assembly at the ribosomal gene promoter. EMBO reports 81 12393749
1999 Recruitment of TATA-binding protein-TAFI complex SL1 to the human ribosomal DNA promoter is mediated by the carboxy-terminal activation domain of upstream binding factor (UBF) and is regulated by UBF phosphorylation. Molecular and cellular biology 79 10082553
2016 PCP-B class pollen coat proteins are key regulators of the hydration checkpoint in Arabidopsis thaliana pollen-stigma interactions. The New phytologist 75 27596924
1999 Characterization of the gene encoding human TAFI (thrombin-activable fibrinolysis inhibitor; plasma procarboxypeptidase B). Biochemistry 74 10350473
2006 Curiouser and curiouser: recent advances in measurement of thrombin-activatable fibrinolysis inhibitor (TAFI) and in understanding its molecular genetics, gene regulation, and biological roles. Clinical biochemistry 73 17331488
2005 Atypical cpb2 genes, encoding beta2-toxin in Clostridium perfringens isolates of nonporcine origin. Infection and immunity 68 15618211
2003 The Leishmania mexicana cysteine protease, CPB2.8, induces potent Th2 responses. Journal of immunology (Baltimore, Md. : 1950) 66 12574338
2003 Hyperprothrombinemia associated with prothrombin G20210A mutation inhibits plasma fibrinolysis through a TAFI-mediated mechanism. Blood 64 14630828
2008 Crystal structures of TAFI elucidate the inactivation mechanism of activated TAFI: a novel mechanism for enzyme autoregulation. Blood 63 18559974
2008 The occurrence of cpb2-toxigenic Clostridium perfringens and the possible role of the beta2-toxin in enteric disease of domestic animals, wild animals and humans. Veterinary journal (London, England : 1997) 59 19101180
2003 Association between TAFI antigen and Ala147Thr polymorphism of the TAFI gene and the angina pectoris incidence. The PRIME Study (Prospective Epidemiological Study of MI). Thrombosis and haemostasis 59 12624641
2007 Thrombin activatable fibrinolysis inhibitor activation peptide shows association with all major subtypes of ischemic stroke and with TAFI gene variation. Arteriosclerosis, thrombosis, and vascular biology 58 17272741
2019 Heterogeneous CPU+GPU-Enabled Simulations for DFTB Molecular Dynamics of Large Chemical and Biological Systems. Journal of chemical theory and computation 54 30916958
2004 Assessment of thrombin-activatable fibrinolysis inhibitor (TAFI) plasma levels in inflammatory bowel diseases. The American journal of gastroenterology 53 15447757
2002 Human procarboxypeptidase B: three-dimensional structure and implications for thrombin-activatable fibrinolysis inhibitor (TAFI). Journal of molecular biology 52 12162965
2003 Herpes simplex virus type 1 tegument protein VP22 interacts with TAF-I proteins and inhibits nucleosome assembly but not regulation of histone acetylation by INHAT. The Journal of general virology 51 12917472
2008 Regulation of tissue inflammation by thrombin-activatable carboxypeptidase B (or TAFI). Molecular immunology 50 18706698
2006 The effect of genetic variants in the thrombin activatable fibrinolysis inhibitor (TAFI) gene on TAFI-antigen levels, clot lysis time and the risk of venous thrombosis. British journal of haematology 48 16803573
2013 CUDASW++ 3.0: accelerating Smith-Waterman protein database search by coupling CPU and GPU SIMD instructions. BMC bioinformatics 47 23557111
2005 TAFI gene haplotypes, TAFI plasma levels and future risk of coronary heart disease: the PRIME Study. Journal of thrombosis and haemostasis : JTH 47 15978108
1997 Functional characterization of recombinant human meizothrombin and Meizothrombin(desF1). Thrombomodulin-dependent activation of protein C and thrombin-activatable fibrinolysis inhibitor (TAFI), platelet aggregation, antithrombin-III inhibition. The Journal of biological chemistry 44 9045633
2017 Activated TAFI Promotes the Development of Chronic Thromboembolic Pulmonary Hypertension: A Possible Novel Therapeutic Target. Circulation research 43 28289017
2003 Functional interaction of the DNA-binding transcription factor Sp1 through its DNA-binding domain with the histone chaperone TAF-I. The Journal of biological chemistry 43 12759364
2003 Weak and non-independent association between plasma TAFI antigen levels and the insulin resistance syndrome. Journal of thrombosis and haemostasis : JTH 42 12871417
2005 Antibiotic-induced expression of a cryptic cpb2 gene in equine beta2-toxigenic Clostridium perfringens. Molecular microbiology 41 16135225
1999 Factor XI dependent and independent activation of thrombin activatable fibrinolysis inhibitor (TAFI) in plasma associated with clot formation. Thrombosis and haemostasis 41 10613658
2012 The epidemiology of Clostridium perfringens type A on Ontario swine farms, with special reference to cpb2-positive isolates. BMC veterinary research 38 22947389
2003 Association between thrombin-activatable fibrinolysis inhibitor (TAFI) and clinical outcome in patients with unstable angina pectoris. Thrombosis and haemostasis 38 12876631
2006 Limited mutagenesis increases the stability of human carboxypeptidase U (TAFIa) and demonstrates the importance of CPU stability over proCPU concentration in down-regulating fibrinolysis. The FEBS journal 36 16441664
2005 Quantification of thrombin activatable fibrinolysis inhibitor (TAFI) gene polymorphism effects on plasma levels of TAFI measured with assays insensitive to isoform-dependent artefact. Thrombosis and haemostasis 36 16113828
2005 Development of ELISAs measuring the extent of TAFI activation. Arteriosclerosis, thrombosis, and vascular biology 36 16339503
2002 Enhancement of endogenous plasminogen activator-induced thrombolysis by argatroban and APC and its control by TAFI, measured in an arterial thrombolysis model in vivo using rat mesenteric arterioles. Thrombosis and haemostasis 36 11848438
2010 Thrombin-activatable fibrinolysis inhibitor (TAFI) deficient mice are susceptible to intracerebral thrombosis and ischemic stroke. PloS one 35 20657835
2018 Trajectory-based training enables protein simulations with accurate folding and Boltzmann ensembles in cpu-hours. PLoS computational biology 33 30589834
2006 Elevated thrombin activatable fibrinolysis inhibitor (TAFI) antigen levels in overt and subclinical hypothyroid patients were reduced by levothyroxine replacement. Endocrine journal 33 17090955
2014 Silencing of IFN-stimulated gene transcription is regulated by histone H1 and its chaperone TAF-I. Nucleic acids research 32 24878923
2006 Thrombin-activable fibrinolysis inhibitor (TAFI) zymogen is an active carboxypeptidase. The Journal of biological chemistry 32 17138567
2001 Combined segregation-linkage analysis of plasma thrombin activatable fibrinolysis inhibitor (TAFI) antigen levels with TAFI gene polymorphisms. Human genetics 32 11511925
2008 The crystal structure of thrombin-activable fibrinolysis inhibitor (TAFI) provides the structural basis for its intrinsic activity and the short half-life of TAFIa. The Journal of biological chemistry 31 18669641
2004 A functional single nucleotide polymorphism in the thrombin-activatable fibrinolysis inhibitor (TAFI) gene associates with outcome of meningococcal disease. Journal of thrombosis and haemostasis : JTH 31 14717966
2008 Regulation of tissue inflammation by thrombin-activatable carboxypeptidase B (or TAFI). Advances in experimental medicine and biology 30 19025114
2002 Evidence for natural horizontal transfer of the pcpB gene in the evolution of polychlorophenol-degrading sphingomonads. Applied and environmental microbiology 30 12200305
2005 CPU 86017, p-chlorobenzyltetrahydroberberine chloride, attenuates monocrotaline-induced pulmonary hypertension by suppressing endothelin pathway. Acta pharmacologica Sinica 29 16225752
2005 Pharmacological efficacy of CPU 86017 on hypoxic pulmonary hypertension in rats: mediated by direct inhibition of calcium channels and antioxidant action, but indirect effects on the ET-1 pathway. Journal of cardiovascular pharmacology 29 16306794
2001 Protein C inhibitor regulates the thrombin-thrombomodulin complex in the up- and down regulation of TAFI activation. Thrombosis and haemostasis 29 11686324
2006 The recent evolution of pentachlorophenol (PCP)-4-monooxygenase (PcpB) and associated pathways for bacterial degradation of PCP. Biodegradation 28 17123025
2004 New insights into factors affecting clot stability: A role for thrombin activatable fibrinolysis inhibitor (TAFI; plasma procarboxypeptidase B, plasma procarboxypeptidase U, procarboxypeptidase R). Seminars in hematology 28 14872415
2008 Activation of TAFI on the surface of Streptococcus pyogenes evokes inflammatory reactions by modulating the kallikrein/kinin system. Journal of innate immunity 27 20375563
2010 Platelet factor 4 inhibits thrombomodulin-dependent activation of thrombin-activatable fibrinolysis inhibitor (TAFI) by thrombin. The Journal of biological chemistry 26 21041299
2007 Genetic variation in thrombin-activatable fibrinolysis inhibitor (TAFI) is associated with the risk of splanchnic vein thrombosis. Thrombosis and haemostasis 26 17264944
2005 Regulated expression of the beta2-toxin gene (cpb2) in Clostridium perfringens type a isolates from horses with gastrointestinal diseases. Journal of clinical microbiology 26 16081942
2009 Tissue factor-expressing monocytes inhibit fibrinolysis through a TAFI-mediated mechanism, and make clots resistant to heparins. Haematologica 25 19377079
2008 Absolute risk of venous and arterial thromboembolism in thrombophilic families is not increased by high thrombin-activatable fibrinolysis inhibitor (TAFI) levels. Thrombosis and haemostasis 25 18612536
2001 The role of protein S in the activation of thrombin activatable fibrinolysis inhibitor (TAFI) and regulation of fibrinolysis. Thrombosis and haemostasis 25 11686322
2001 Association of a single nucleotide polymorphism in CPB2 encoding the thrombin-activable fibrinolysis inhibitor (TAF1) with blood pressure. Clinical genetics 24 11903334
2012 The hyperfibrinolytic state of mice with combined thrombin-activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor-1 gene deficiency is critically dependent on TAFI deficiency. Journal of thrombosis and haemostasis : JTH 23 23083123
2004 Thrombin activatable fibrinolysis inhibitor (TAFI) and markers of endothelial cell injury in dialyzed patients with diabetic nephropathy. Thrombosis and haemostasis 23 14983223
2002 Amino acid residues in the P6-P'3 region of thrombin-activable fibrinolysis inhibitor (TAFI) do not determine the thrombomodulin dependence of TAFI activation. The Journal of biological chemistry 23 11786552
2021 Carboxypeptidase U (CPU, TAFIa, CPB2) in Thromboembolic Disease: What Do We Know Three Decades after Its Discovery? International journal of molecular sciences 22 33477318
2020 A new pedigree with thrombomodulin-associated coagulopathy in which delayed fibrinolysis is partially attenuated by co-inherited TAFI deficiency. Journal of thrombosis and haemostasis : JTH 22 32634856
2011 The relationship among TAFI, t-PA, PAI-1 and F1 + 2 in type 2 diabetic patients with normoalbuminuria and microalbuminuria. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 22 21519232
2018 Fabrication of omega-shaped microwell arrays for a spheroid culture platform using pins of a commercial CPU to minimize cell loss and crosstalk. Biofabrication 21 30074487
2002 Thrombin-activatable fibrinolysis inhibitor (TAFI) deficient mice. Frontiers in bioscience : a journal and virtual library 20 11815293
2022 Lactobacillus salivarius CPU-01 Ameliorates Temozolomide-Induced Intestinal Mucositis by Modulating Gut Microbiota, Maintaining Intestinal Barrier, and Blocking Pro-inflammatory Cytokines. Probiotics and antimicrobial proteins 19 35639268
2017 Alternative SET/TAFI Promoters Regulate Embryonic Stem Cell Differentiation. Stem cell reports 19 28966118
2012 Thrombin-activatable fibrinolysis inhibitor (TAFI) is enhanced in major trauma patients without infectious complications. Immunobiology 19 22749979
2007 TAFI and pancreatic carboxypeptidase B modulate in vitro capillary tube formation by human microvascular endothelial cells. Arteriosclerosis, thrombosis, and vascular biology 19 17673703
2006 Characterization of rat thrombin-activatable fibrinolysis inhibitor (TAFI)--a comparative study assessing the biological equivalence of rat, murine and human TAFI. Journal of thrombosis and haemostasis : JTH 19 17002650
2001 Thrombin activable fibrinolysis inhibitor (TAFI): molecular genetics of an emerging potential risk factor for thrombotic disorders. Current drug targets. Cardiovascular & haematological disorders 19 12769657
1999 Identification of a site critical for kinase regulation on the central processing unit (CPU) helix of the aspartate receptor. Biochemistry 19 9890914
2013 TAFI deficiency promotes liver damage in murine models of liver failure through defective down-regulation of hepatic inflammation. Thrombosis and haemostasis 17 23467679
2014 Beta2 toxin is not involved in in vitro cell cytotoxicity caused by human and porcine cpb2-harbouring Clostridium perfringens. Veterinary microbiology 16 24768003
2004 TAFI polymorphisms at amino acids 147 and 325 are not risk factors for cerebral infarction. British journal of haematology 16 15521922
2020 A case of thrombomodulin mutation causing defective thrombin binding with absence of protein C and TAFI activation. Blood advances 15 32556284
2017 Procarboxypeptidase U (proCPU, TAFI, proCPB2) in cerebrospinal fluid during ischemic stroke is associated with stroke progression, outcome and blood-brain barrier dysfunction. Journal of thrombosis and haemostasis : JTH 15 29194929
2015 Plasma levels of carboxypeptidase U (CPU, CPB2 or TAFIa) are elevated in patients with acute myocardial infarction. Journal of thrombosis and haemostasis : JTH 15 26340515
2009 Procarboxypeptidase U (TAFI) contributes to the risk of thrombosis in patients with hereditary thrombophilia. Thrombosis research 15 19195685
2023 Characterization of Cetobacterium somerae CPU-CS01 isolated from the intestine of healthy crucian carp (Carassius auratus) as potential probiotics against Aeromonas hydrophila infection. Microbial pathogenesis 14 37169311
2017 Thrombin activatable fibrinolysis inhibitor (TAFI) - A possible link between coagulation and complement activation in the antiphospholipid syndrome (APS). Thrombosis research 14 28669410
2015 Lack of TAFI increases brain damage and microparticle generation after thrombolytic therapy in ischemic stroke. Thrombosis research 14 26118976
2013 Multi-core CPU or GPU-accelerated Multiscale Modeling for Biomolecular Complexes. Molecular based mathematical biology 14 24352481