Procarboxypeptidase U (EC 188.8.131.52) (pro-CpU), also known as plasma procarboxypeptidase B and thrombin-activable fibrinolysis inhibitor, is a human plasma protein that has been implicated in the regulation of fibrinolysis. In this study, we show that pro-CpU serves as a substrate for transglutaminases. Both factor XIIIa and tissue transglutaminase catalyzed the polymerization of pro-CpU and the cross-linking to fibrin as well as the incorporation of 5-dimethylaminonaphthalene-1-sulfonyl cadaverine (dansylcadaverine), [14C]putrescine, and dansyl-PGGQQIV. These findings show that pro-CpU contains both amine acceptor (Gln) and amine donor (Lys) residues. The amine acceptor residues were identified as Gln2, Gln5, and Gln292, suggesting that both the activation peptide and the mature enzyme participate in the cross-linking reaction. These observations imply that transglutaminases may mediate covalent binding of pro-CpU to other proteins and cell surfaces in vivo. In particular, factor XIIIa may cross-link pro-CpU to fibrin during the latter part of the coagulation cascade, thereby helping protect the newly formed fibrin clot from premature plasmin degradation. Moreover, the cross-linking may facilitate the activation of pro-CpU, st...Continue Reading
Sorting-out of acceptor-donor relationships in the transglutaminase-catalyzed cross-linking of crystallins by the enzyme-directed labeling of potential sites
Characterization of the binding of plasminogen to fibrin surfaces: the role of carboxy-terminal lysines
Role of cell-surface lysines in plasminogen binding to cells: identification of alpha-enolase as a candidate plasminogen receptor
High-affinity binding sites for human Glu-plasminogen unveiled by limited plasmic degradation of human fibrin
Interaction of one-chain and two-chain tissue plasminogen activator with intact and plasmin-degraded fibrin
Complementary modes of action of tissue-type plasminogen activator and pro-urokinase by which their synergistic effect on clot lysis may be explained
The molecular form of alpha 2-antiplasmin with affinity for plasminogen is selectively bound to fibrin by factor XIII
Significance of cross-linking of alpha 2-plasmin inhibitor to fibrin in inhibition of fibrinolysis and in hemostasis
Location of the major epsilon-(gamma-glutamyl)lysyl cross-linking site in transglutaminase-modified human plasminogen.
An examination of the inhibitory mechanism of serpins by analysing the interaction of trypsin and chymotrypsin with alpha 2-antiplasmin
Activated human plasma carboxypeptidase B is retained in the blood by binding to alpha2-macroglobulin and pregnancy zone protein.
TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin complex.
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.
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.
Evaluation of a sensitive colorimetric FXIII incorporation assay. Effects of FXIII Val34Leu, plasma fibrinogen concentration and congenital FXIII deficiency
Influence of blood coagulation factor XIII and FXIII Val34Leu on plasma clot formation measured by thrombelastography
Human complement C3 is a substrate for transglutaminases. A functional link between non-protease-based members of the coagulation and complement cascades
Flexibility of the thrombin-activatable fibrinolysis inhibitor pro-domain enables productive binding of protein substrates.
Finding the optimal concentration range for fibrinogen replacement after severe haemodilution: an in vitro model
Hydroxyethyl starch enhances fibrinolysis in human plasma by diminishing alpha2-antiplasmin-plasmin interactions
Evaluating factor XIII specificity for glutamine-containing substrates using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assay
Update on the Serum Biomarkers and Genetic Factors Associated with Safety and Efficacy of rt-PA Treatment in Acute Stroke Patients
Mammalian transglutaminases. Identification of substrates as a key to physiological function and physiopathological relevance
Carboxypeptidase U (TAFIa) activity is induced in vivo in ischemic stroke patients receiving thrombolytic therapy
The intrinsic enzymatic activity of procarboxypeptidase U (TAFI) does not significantly influence the fibrinolytic rate: reply to a rebuttal
Molecular mechanism of the interaction between activated factor XIII and its glutamine donor peptide substrate
Differential clot stabilising effects of rFVIIa and rFXIII-A2 in whole blood from thrombocytopenic patients and healthy volunteers
Plasmin and the thrombin-thrombomodulin complex both contribute to thrombin-activatable fibrinolysis inhibitor activation in whole blood model thrombi
Model thrombi formed under flow reveal the role of factor XIII-mediated cross-linking in resistance to fibrinolysis
Thrombin generation and fibrinolysis in anti-factor IX treated blood and plasma spiked with factor VIII inhibitor bypassing activity or recombinant factor VIIa
The antifibrinolytic function of factor XIII is exclusively expressed through α₂-antiplasmin cross-linking
Genetic and environmental determinants of fibrin structure and function: relevance to clinical disease
Plasma thrombin-activatable fibrinolysis inhibitor antigen concentration and genotype in relation to myocardial infarction in the north and south of Europe
Fibrin clot structure and function: a role in the pathophysiology of arterial and venous thromboembolic diseases
Coagulation factor XIIIa substrates in human plasma: identification and incorporation into the clot.
Factor XIII topology: organization of B subunits and changes with activation studied with single-molecule atomic force microscopy
Factor XIII in plasma, but not in platelets, mediates red blood cell retention in clots and venous thrombus size in mice
The factor XIII-A Val34Leu polymorphism decreases whole blood clot mass at high fibrinogen concentrations
Cross-linking of wild-type and mutant alpha 2-antiplasmins to fibrin by activated factor XIII and by a tissue transglutaminase
Reductions in plasmin inhibitor and fibrinogen predict the improved fibrin clot lysis 6 months after obesity surgery
Role, Laboratory Assessment and Clinical Relevance of Fibrin, Factor XIII and Endogenous Fibrinolysis in Arterial and Venous Thrombosis.
Blood Clotting Disorders
Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.
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