F10

Summary

Gene Symbol: F10
Description: coagulation factor X
Alias: FXA, coagulation factor X, Stuart-Prower factor, factor Xa, prothrombinase
Species: human

Top Publications

  1. ncbi Prothrombinase complex assembly. Contributions of protein-protein and protein-membrane interactions toward complex formation
    S Krishnaswamy
    Department of Biochemistry, University of Vermont, Burlington 05405
    J Biol Chem 265:3708-18. 1990
  2. pmc Isolation of a protein Z-dependent plasma protease inhibitor
    X Han
    Division of Hematology, Barnes Jewish Hospital at Washington University School of Medicine, 216 South Kingshighway Boulevard, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 95:9250-5. 1998
  3. pmc Structure and dynamics of zymogen human blood coagulation factor X
    Divi Venkateswarlu
    Department of Chemistry, Venable Hall, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Biophys J 82:1190-206. 2002
  4. ncbi Extended interactions with prothrombinase enforce affinity and specificity for its macromolecular substrate
    Steven J Orcutt
    Joseph Stokes Research Institute, Children s Hospital of Philadelphia, and the Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 277:46191-6. 2002
  5. ncbi Identification of a binding site for blood coagulation factor Xa on the heavy chain of factor Va. Amino acid residues 323-331 of factor V represent an interactive site for activated factor X
    Michael Kalafatis
    Department of Chemistry, Cleveland State University, Cleveland, Ohio 44115, USA
    Biochemistry 41:12715-28. 2002
  6. ncbi Binding studies of the enzyme (factor IXa) with the cofactor (factor VIIIa) in the assembly of factor-X activating complex on the activated platelet surface
    S S Ahmad
    The Sol Sherry Thrombosis Research Center and Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA 19140, USA
    J Thromb Haemost 1:2348-55. 2003
  7. ncbi Incorporation of factor Va into prothrombinase is required for coordinated cleavage of prothrombin by factor Xa
    Michael A Bukys
    Department of Chemistry, Cleveland State University, Cleveland, Ohio 44115, USA
    J Biol Chem 280:27393-401. 2005
  8. pmc Ratcheting of the substrate from the zymogen to proteinase conformations directs the sequential cleavage of prothrombin by prothrombinase
    Elsa P Bianchini
    Joseph Stokes Research Institute, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 102:10099-104. 2005
  9. ncbi A control switch for prothrombinase: characterization of a hirudin-like pentapeptide from the COOH terminus of factor Va heavy chain that regulates the rate and pathway for prothrombin activation
    Michael A Bukys
    Department of Chemistry, Cleveland State University, Cleveland, Ohio 44115, USA
    J Biol Chem 281:39194-204. 2006
  10. ncbi Active and exo-site inhibition of human factor Xa: structure of des-Gla factor Xa inhibited by NAP5, a potent nematode anticoagulant protein from Ancylostoma caninum
    Jorge L Rios-Steiner
    Department of Chemistry, Michigan State University, East Lansing, MI 48824 1322, USA
    J Mol Biol 371:774-86. 2007

Research Grants

  1. Steven T Olson; Fiscal Year: 2016
  2. UMESH RAMANLAL DESAI; Fiscal Year: 2016
  3. NOVEL ANTITHROMBOTIC AGENT
    David Wolf; Fiscal Year: 1993
  4. John H Griffin; Fiscal Year: 2014
  5. Structure and Stability Studies of Factor VIII to Overcome the Immune Response
    PAUL CLINTON SPIEGEL; Fiscal Year: 2010
  6. Lipid Regulation of Thrombin Generation
    Barry R Lentz; Fiscal Year: 2012
  7. MOLECULAR BIOLOGY OF HUMAN COAGULATION FACTOR V
    Thomas Ortel; Fiscal Year: 2010
  8. Membrane Receptors Regulating Megakaryocyte Endocytosis of Factor V from Plasma
    BETH BOUCHARD; Fiscal Year: 2012
  9. METAL DEPENDENT COMPLEXES IN BLOOD COAGULATION
    Barbara Furie; Fiscal Year: 2002
  10. MOLECULAR INTERACTIONS OF BLOOD COAGULATION FACTOR XA
    Katherine High; Fiscal Year: 1999

Detail Information

Publications313 found, 100 shown here

  1. ncbi Prothrombinase complex assembly. Contributions of protein-protein and protein-membrane interactions toward complex formation
    S Krishnaswamy
    Department of Biochemistry, University of Vermont, Burlington 05405
    J Biol Chem 265:3708-18. 1990
    Equilibrium binding studies of prothrombinase complex formation were undertaken using phospholipid vesicles composed of phosphatidylcholine and phosphatidylserine (PCPS), factor Va, and factor Xa modified with dansyl ..
  2. pmc Isolation of a protein Z-dependent plasma protease inhibitor
    X Han
    Division of Hematology, Barnes Jewish Hospital at Washington University School of Medicine, 216 South Kingshighway Boulevard, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 95:9250-5. 1998
    ..The procoagulant activity of factor Xa in a one-stage plasma coagulation assay is reduced when factor Xa is first incubated with PZ...
  3. pmc Structure and dynamics of zymogen human blood coagulation factor X
    Divi Venkateswarlu
    Department of Chemistry, Venable Hall, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Biophys J 82:1190-206. 2002
    The solution structure and dynamics of the human coagulation factor X (FX) have been investigated to understand the key structural elements in the zymogenic form that participates in the activation process...
  4. ncbi Extended interactions with prothrombinase enforce affinity and specificity for its macromolecular substrate
    Steven J Orcutt
    Joseph Stokes Research Institute, Children s Hospital of Philadelphia, and the Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 277:46191-6. 2002
    ..of active site docking by unique substrate residues preceding the scissile bond to the function of prothrombinase. Mutagenesis of the authentic P(1)-P(3) sequence in prethrombin 2/fragment 1...
  5. ncbi Identification of a binding site for blood coagulation factor Xa on the heavy chain of factor Va. Amino acid residues 323-331 of factor V represent an interactive site for activated factor X
    Michael Kalafatis
    Department of Chemistry, Cleveland State University, Cleveland, Ohio 44115, USA
    Biochemistry 41:12715-28. 2002
    ..each) spanning amino acid region 307-351 of the heavy chain of factor Va and tested them for inhibition of prothrombinase activity...
  6. ncbi Binding studies of the enzyme (factor IXa) with the cofactor (factor VIIIa) in the assembly of factor-X activating complex on the activated platelet surface
    S S Ahmad
    The Sol Sherry Thrombosis Research Center and Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA 19140, USA
    J Thromb Haemost 1:2348-55. 2003
    ....
  7. ncbi Incorporation of factor Va into prothrombinase is required for coordinated cleavage of prothrombin by factor Xa
    Michael A Bukys
    Department of Chemistry, Cleveland State University, Cleveland, Ohio 44115, USA
    J Biol Chem 280:27393-401. 2005
    ..Kinetic constants for the overall activation of prothrombin by prothrombinase assembled with saturating concentrations of recombinant mutant factor Va were calculated, prothrombin ..
  8. pmc Ratcheting of the substrate from the zymogen to proteinase conformations directs the sequential cleavage of prothrombin by prothrombinase
    Elsa P Bianchini
    Joseph Stokes Research Institute, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 102:10099-104. 2005
    b>Prothrombinase catalyzes thrombin formation by the ordered cleavage of two peptide bonds in prothrombin...
  9. ncbi A control switch for prothrombinase: characterization of a hirudin-like pentapeptide from the COOH terminus of factor Va heavy chain that regulates the rate and pathway for prothrombin activation
    Michael A Bukys
    Department of Chemistry, Cleveland State University, Cleveland, Ohio 44115, USA
    J Biol Chem 281:39194-204. 2006
    ..COOH terminus of the heavy chain of factor Va (Asp-Tyr-Asp-Tyr-Gln, DYDYQ) inhibits prothrombin activation by prothrombinase in a competitive manner with respect to substrate...
  10. ncbi Active and exo-site inhibition of human factor Xa: structure of des-Gla factor Xa inhibited by NAP5, a potent nematode anticoagulant protein from Ancylostoma caninum
    Jorge L Rios-Steiner
    Department of Chemistry, Michigan State University, East Lansing, MI 48824 1322, USA
    J Mol Biol 371:774-86. 2007
    ..One of these nematode anticoagulant proteins, NAP5, inhibits the amidolytic activity of factor Xa (fXa) with K(i)=43 pM, and is the most potent natural fXa inhibitor identified thus far...
  11. pmc Adenovirus serotype 5 hexon is critical for virus infection of hepatocytes in vivo
    O Kalyuzhniy
    Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195 7720, USA
    Proc Natl Acad Sci U S A 105:5483-8. 2008
    ..Here, we report that the major Ad5 capsid protein, hexon, binds human coagulation factor X (FX) with an affinity of 229 pM...
  12. pmc Fate of membrane-bound reactants and products during the activation of human prothrombin by prothrombinase
    Parvathi Kamath
    Joseph Stokes Research Institute, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 283:30164-73. 2008
    ..mediated by its N-terminal fragment 1 (F1) domain, plays an essential role in its proteolytic activation by prothrombinase. Thrombin is produced in two cleavage reactions...
  13. pmc Identification of coagulation factor (F)X binding sites on the adenovirus serotype 5 hexon: effect of mutagenesis on FX interactions and gene transfer
    Raul Alba
    British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, G12 8TA, UK
    Blood 114:965-71. 2009
    Recent studies have demonstrated the importance of coagulation factor X (FX) in adenovirus (Ad) serotype 5-mediated liver transduction in vivo. FX binds to the adenovirus hexon hypervariable regions (HVRs)...
  14. pmc Increased local expression of coagulation factor X contributes to the fibrotic response in human and murine lung injury
    Chris J Scotton
    Centre for Respiratory Research, University College London, London, United Kingdom
    J Clin Invest 119:2550-63. 2009
    ..Here we report that expression of coagulation factor X (FX) is locally increased in human and murine fibrotic lung tissue, with marked immunostaining associated ..
  15. pmc Regulated cleavage of prothrombin by prothrombinase: repositioning a cleavage site reveals the unique kinetic behavior of the action of prothrombinase on its compound substrate
    Harlan N Bradford
    Joseph Stokes Research Institute, Children s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 285:328-38. 2010
    b>Prothrombinase converts prothrombin to thrombin via cleavage at Arg(320) followed by cleavage at Arg(271)...
  16. doi Assessment of laboratory assays to measure rivaroxaban--an oral, direct factor Xa inhibitor
    Meyer Michel Samama
    Hotel Dieu University Hospital, Paris, France 2Biomnis Laboratory, Ivry sur Seine, France
    Thromb Haemost 103:815-25. 2010
    ..Standard methods for HepTest and two-step prothrombinase-induced clotting time (PiCT) resulted in a paradoxical response, with low concentrations of rivaroxaban ..
  17. pmc Requirements for receptor engagement during infection by adenovirus complexed with blood coagulation factor X
    Angela C Bradshaw
    Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
    PLoS Pathog 6:e1001142. 2010
    Human adenoviruses from multiple species bind to coagulation factor X (FX), yet the importance of this interaction in adenovirus dissemination is unknown...
  18. doi Clinical laboratory measurement of direct factor Xa inhibitors: anti-Xa assay is preferable to prothrombin time assay
    Yu Chen Barrett
    Bristol Myers Squibb, Princeton, New Jersey, USA
    Thromb Haemost 104:1263-71. 2010
    Apixaban and other factor Xa (FXa) inhibitors are in late-stage clinical development for prevention and treatment of thromboembolic diseases...
  19. doi Co-localization of Protein Z, Protein Z-Dependent protease inhibitor and coagulation factor X in human colon cancer tissue: implications for coagulation regulation on tumor cells
    Ewa Sierko
    Department of Oncology, Medical University, Bialystok, Poland
    Thromb Res 129:e112-8. 2012
    ..The Protein Z (PZ)/protein Z-dependent protease inhibitor (ZPI) complex directly inhibits factor Xa proteolytic activity...
  20. ncbi Identification of distinct sequences in human blood coagulation factor Xa and prothrombin essential for substrate and cofactor recognition in the prothrombinase complex
    Subramanian Yegneswaran
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 278:33312-8. 2003
    To identify amino acid sequences in factor Xa (fXa) and prothrombin (fII) that may be involved in prothrombinase complex (fXa.factor Va.fII...
  21. ncbi The critical role of the 185-189-loop in the factor Xa interaction with Na+ and factor Va in the prothrombinase complex
    Alireza R Rezaie
    Edward A Doisy Department of Biochemistry and Molecular Biology, St Louis University School of Medicine, St Louis, Missouri 63104, USA
    J Biol Chem 279:48262-9. 2004
    ..Both prothrombinase and direct binding studies indicated that K186A also has an approximately 6-fold impaired affinity for factor ..
  22. ncbi Intermolecular interactions and characterization of the novel factor Xa exosite involved in macromolecular recognition and inhibition: crystal structure of human Gla-domainless factor Xa complexed with the anticoagulant protein NAPc2 from the hematophagou
    M T Murakami
    Department of Physics, IBILCE UNESP, Sao Jose do Rio Preto, SP 15054 000, Brazil
    J Mol Biol 366:602-10. 2007
    ..blood coagulation pathway by a two step mechanism, initially interacting with the hitherto uncharacterized factor Xa exosite involved in macromolecular recognition and subsequently inhibiting factor VIIa (K(i)=8...
  23. doi Adenovirus serotype 5 hexon mediates liver gene transfer
    Simon N Waddington
    Department of Haematology, Haemophilia Centre and Haemostasis Unit, Royal Free and University College Medical School, London NW3 2PF, UK
    Cell 132:397-409. 2008
    ..Liver infection by the FX-Ad5 complex is mediated through a heparin-binding exosite in the FX serine protease domain. This study reveals an unanticipated function for hexon in mediating liver gene transfer in vivo...
  24. ncbi The factor V activation paradox
    Thomas Orfeo
    Department of Biochemistry, University of Vermont, 89 Beaumont Avenue, Burlington, VT 05405 0068, USA
    J Biol Chem 279:19580-91. 2004
    The prothrombinase complex consists of the protease factor Xa, Ca2+, and factor Va assembled on an anionic membrane...
  25. ncbi The use of low-molecular-weight heparins in cardiovascular disease
    R Verhaeghe
    Centre for Molecular and Vascular Biology, University of Leuven, Belgium
    Acta Cardiol 53:15-21. 1998
    ..Fragments above 5,000 D which contain the pentasaccharide maintain their property to inhibit Factor Xa but with increasing chain length, they become stronger inhibitors of thrombin...
  26. ncbi Efficacy of a synthetic pentasaccharide, a pure factor Xa inhibitor, as an antithrombotic agent--a pilot study in the setting of coronary angioplasty
    A Vuillemenot
    , , France
    Thromb Haemost 81:214-20. 1999
    ..Thus we conclude that the anti-thrombotic activity of pentasaccharide, as shown in this pilot trial in the setting of coronary angioplasty, deserves further investigation...
  27. ncbi [Therapeutic indications of low molecular weight heparins]
    M M Samama
    , , Paris
    Arch Mal Coeur Vaiss 84:1733-43. 1991
    ..The specific biological and pharmacokinetic properties of LMWH with greater inhibition of factor Xa than of thrombin activity, less interaction with platelets, better bioavailability and a longer half life of ..
  28. ncbi Novel inhibitors of factor X for use in cardiovascular diseases
    F A Spencer
    Cardiovascular Thrombosis Research Center, UMass Memorial Medical Center, 55 Lake Avenue North, Worcester, MA 01655, USA
    Curr Cardiol Rep 2:395-404. 2000
    ..Regardless, investigators have become increasingly interested in factor Xa as a potential target for antithrombotic therapy...
  29. ncbi Biochemical and pharmacological properties of SANORG 32701. Comparison with the "synthetic pentasaccharide' (SR 90107/ORG 31540) and standard heparin
    J M Herbert
    Haemobiology Research Department, Sanofi Recherche, Toulouse, France
    Circ Res 79:590-600. 1996
    ..7 +/- 0.7 nmol/L) and is a potent catalyst of its inhibitory effect with regard to factor Xa (1100 +/- 31 versus 850 +/- 27 anti-Xa U/mg for SR 90107)...
  30. ncbi Biochemical and pharmacological properties of SANORG 34006, a potent and long-acting synthetic pentasaccharide
    J M Herbert
    Haemobiology Research Department, Sanofi Recherche, Toulouse, France; and NV Organon, Oss, The Netherlands
    Blood 91:4197-205. 1998
    ..4 +/- 0.3 v 48 +/- 11 nmol/L), and it is a potent and selective catalyst of the inhibitory effect of AT on factor Xa (1,240 +/- 15 anti-factor Xa U/mg v 850 +/- 27 anti-factor Xa U/mg for SR 90107/ORG 31540)...
  31. ncbi Aromatic amidines: inhibitory effect on purified plasma serine proteinases, blood coagulation and platelet aggregation
    R Ferroni
    Dipartimento di Scienze Farmaceutiche, , Italy
    Farmaco Sci 43:5-13. 1988
    ..derivatives (with Cl, Br or I) on (i) the catalytic properties of purified plasma serine proteinases (notably, factor Xa, factor VIIa, thrombin and plasmin), (ii) blood coagulation, and (iii) platelet aggregation was investigated in ..
  32. ncbi Control of the cultivation process of antithrombin III and its characterization by capillary electrophoresis
    O W Reif
    , Hannover, Germany
    J Chromatogr A 680:383-94. 1994
    ..by baby hamster kidney cells of recombinant antithrombin III (r-AT III), the main inhibitor of thrombin, factor Xa and other proteases of the clotting cascade, was monitored by capillary isotachophoresis using mixtures of ..
  33. ncbi [Anti-Xa molecules]
    B Boneu
    , , Toulouse
    Arch Mal Coeur Vaiss 89:1491-4. 1996
    b>Factor Xa plays a central role in the mechanisms of thrombin generation...
  34. ncbi The effect of the synthetic pentasaccharide SR 90107/ORG 31540 on thrombin generation ex vivo is uniquely due to ATIII-mediated neutralization of factor Xa
    J C Lormeau
    Sanofi Recherche, Haemobiology Research Department, Toulouse, France
    Thromb Haemost 74:1474-7. 1995
    ..SP impaired TG in plasma for up to 18 h after injection, and the time-courses of TG and factor Xa inhibitions were similar...
  35. ncbi Synthetic pentasaccharides do not cause platelet activation by antiheparin-platelet factor 4 antibodies
    S Ahmad
    Cardiovascular Institute, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois, USA
    Clin Appl Thromb Hemost 5:259-66. 1999
    A synthetic selective inhibitor of factor Xa, the pentasaccharide SR90107A/Org31540 is in clinical development for the prophylaxis of postsurgical deep vein thrombosis...
  36. ncbi A method for determining the in vivo topology of yeast polytopic membrane proteins demonstrates that Gap1p fully integrates into the membrane independently of Shr3p
    C F Gilstring
    Ludwig Institute for Cancer Research, Box 240, S 171 77 Stockholm, Sweden
    J Biol Chem 275:31488-95. 2000
    ..right-side-out microsomes from sec12-1 strains expressing six different Gap1p constructs containing functional factor Xa protease cleavage sites...
  37. ncbi The antithrombotic efficacy of the GP IIb/IIIa antagonist SR121787 is potentiated by antithrombin-dependent factor Xa inhibition without an increase in the bleeding risk in the rabbit
    A Bernat
    Haemobiology Research Department, Sanofi Recherche, Toulouse, France
    J Cardiovasc Pharmacol 33:573-9. 1999
    ..of the novel glycoprotein (GP) IIb/IIIa antagonist SR121787 in combination with the indirect inhibitor of factor Xa, SR90107/ORG31540...
  38. ncbi Antithrombotic effects of synthetic pentasaccharide with high affinity for plasma antithrombin III in non-human primates
    Y Cadroy
    , , Toulouse, France
    Thromb Haemost 70:631-5. 1993
    ..comprising the minimal heparin structure capable of binding with antithrombin III (ATIII) and exhibiting anti-factor Xa (anti-fXa) activity in plasma without producing detectable antithrombin activity, has been evaluated for its ..
  39. ncbi Pharmacokinetic study of three synthetic AT-binding pentasaccharides in various animal species-extrapolation to humans
    J P Herault
    Haemobiology Research Department, Sanofi Recherche, Toulouse, France
    Blood Coagul Fibrinolysis 8:161-7. 1997
    ..SR 90107A/Org 31540 (SP) representing the minimal AT-binding sequence of heparin is a catalyst of factor Xa inhibition...
  40. ncbi Antagonism of SR 90107A/Org 31540-induced bleeding by protamine sulfate in rats and mice
    A Bernat
    Sanofi Recherche, Toulouse, France
    Thromb Haemost 76:715-9. 1996
    The neutralization by protamine sulfate of bleeding enhancement induced by the potent anti-factor Xa pentasaccharide SR 90107A/Org 31540 and by heparin has been studied in rats and mice...
  41. ncbi Antifactor Xa activity and antithrombotic activity in rats of structural analogues of the minimum antithrombin III binding sequence: discovery of compounds with a longer duration of action than of the natural pentasaccharide
    D G Meuleman
    Scientific Development Group, Organon International B.V, Oss, The Netherlands
    Semin Thromb Hemost 17:112-7. 1991
    ..All these structural analogues elicit a higher specific anti-Factor Xa activity than the natural pentasaccharide (700 anti-Factor Xa U/kg)...
  42. ncbi Determination of the anti-factor Xa activity of the synthetic pentasaccharide SR 90107A/ORG 31540 and of two structural analogues
    J C Lormeau
    Sanofi Recherche, Toulouse, France
    Thromb Res 85:67-75. 1997
    The anti-factor Xa activity of the synthetic pentasaccharide SR 90107A/ORG 31540 was assayed by a chromogenic method at pH 8.4 and pH 7...
  43. ncbi [Prevalence and description of cardiac involvements in primary antiphospholipid syndrome]
    G Derumeaux
    Service de cardiologie,
    Arch Mal Coeur Vaiss 85:1811-8. 1992
    ..Twelve patients had high anticardiolipin antibody levels (> or = 15 U GPL) and 12 had a raised anti-prothrombinase antibody title...
  44. pmc Binding sites for blood coagulation factor Xa and protein S involving residues 493-506 in factor Va
    M J Heeb
    Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037, USA
    Protein Sci 5:1883-9. 1996
    ..comprising FVa heavy chain residues 481-525 were tested for their ability to inhibit prothrombin activation by prothrombinase complexes [Factor Xa (FXa):FVa:phospholipids:Ca2+]...
  45. ncbi Coagulation factor V: a plethora of anticoagulant molecules
    Michael Kalafatis
    Department of Chemistry, Cleveland State University, Cleveland, OH 44114, USA
    Curr Opin Hematol 12:141-8. 2005
    Thrombin is necessary for survival and is produced after activation of prothrombin by prothrombinase at the site of a vascular injury...
  46. ncbi Contribution of the prothrombin fragment 2 domain to the function of factor Va in the prothrombinase complex
    S Krishnaswamy
    Department of Medicine, Emory University, Atlanta, Georgia 30322, USA
    Biochemistry 36:3319-30. 1997
    The prothrombinase complex assembles through reversible interactions between factor Xa, factor Va and acidic phospholipid-containing membranes in the presence of calcium ions...
  47. ncbi Structure-function relationships and mechanism of anticoagulant phospholipase A2 enzymes from snake venoms
    R Manjunatha Kini
    Protein Science Laboratory, Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore
    Toxicon 45:1147-61. 2005
    ..The strongly anticoagulant CM-IV inhibits both the extrinsic tenase and prothrombinase complexes, whereas the weakly anticoagulant PLA(2) enzymes (CM-I and CM-II) inhibit only the extrinsic tenase ..
  48. pmc Contribution of amino acid region 659-663 of Factor Va heavy chain to the activity of factor Xa within prothrombinase
    JAMILA HIRBAWI
    Department of Chemistry, Cleveland State University, Cleveland, Ohio 44115, USA
    Biochemistry 49:8520-34. 2010
    Factor Va, the cofactor of prothrombinase, is composed of heavy and light chains associated noncovalently in the presence of divalent metal ions...
  49. ncbi Population pharmacokinetics and pharmacodynamics of rivaroxaban--an oral, direct factor Xa inhibitor--in patients undergoing major orthopaedic surgery
    Wolfgang Mueck
    Clinical Pharmacology, Bayer HealthCare AG, Aprather Weg 18a, Wuppertal, Germany
    Clin Pharmacokinet 47:203-16. 2008
    ..Rivaroxaban is an oral direct Factor Xa (FXa) inhibitor in clinical development for the prevention and treatment of thromboembolic disorders...
  50. ncbi Amino acids Glu323, Tyr324, Glu330, and Val331 of factor Va heavy chain are essential for expression of cofactor activity
    Lisam S Singh
    Department of Chemistry, Cleveland State University, Cleveland, Ohio 44115, USA
    J Biol Chem 278:28335-45. 2003
    ..peptides (5 amino acids each) spanning the amino acid region 323-331 and tested them for their effect on prothrombinase complex assembly and function...
  51. ncbi Proexosite-1 on prothrombin is a factor Va-dependent recognition site for the prothrombinase complex
    Lin Chen
    Edward A Doisy Department of Biochemistry and Molecular Biology, St Louis University School of Medicine, St Louis, Missouri 63104, USA
    J Biol Chem 278:27564-9. 2003
    ..has been studied extensively, their role in the specificity of prothrombin recognition by factor Xa in the prothrombinase complex (factor Xa, factor Va, phosphatidylcholine/phosphatidylserine vesicles, and Ca2+) has not been ..
  52. ncbi Structural basis for inhibition promiscuity of dual specific thrombin and factor Xa blood coagulation inhibitors
    H Nar
    Department of Medicinal Chemistry, Boehringer Ingelheim Pharma KG, 88397 Biberach an der Riss, Germany
    Structure 9:29-37. 2001
    ..pharmaceutical research is the development of selective inhibitors of the blood coagulation enzymes thrombin or factor Xa to be used as orally bioavailable anticoagulant drugs in thromboembolic disorders and in the prevention of ..
  53. ncbi Probing the molecular basis of factor Xa specificity by mutagenesis of the serpin, antithrombin
    A R Rezaie
    Edward A Doisy Department of Biochemistry and Molecular Biology, St Louis University School of Medicine, 1402 South Grand Boulevard, St Louis, MO 63104, USA
    Biochim Biophys Acta 1528:167-76. 2001
    The molecular basis of the substrate and inhibitor specificity of factor Xa, the serine proteinase of the prothrombinase complex, was investigated by constructing two mutants of human antithrombin (HAT) in which the reactive site loop of ..
  54. ncbi Prothrombinase assembly and S1 site occupation restore the catalytic activity of FXa impaired by mutation at the sodium-binding site
    Rodney M Camire
    Joseph Stokes, Jr Research Institute, Division of Hematology, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 277:37863-70. 2002
    ..the allosteric relationship between the Na(+) site and other structural determinants in factor Xa and prothrombinase was investigated...
  55. pmc An anticoagulant RNA aptamer that inhibits proteinase-cofactor interactions within prothrombinase
    Sai K Buddai
    Joseph Stokes Research Institute, Children s Hospital of Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 285:5212-23. 2010
    The interaction of factor Xa with factor Va on membranes to form prothrombinase profoundly increases the rate of the proteolytic conversion of prothrombin to thrombin...
  56. ncbi Proteolysis of factor V by cathepsin G and elastase indicates that cleavage at Arg1545 optimizes cofactor function by facilitating factor Xa binding
    R M Camire
    Department of Biochemistry, University of Vermont, College of Medicine, Burlington, Vermont 05405, USA
    Biochemistry 37:11896-906. 1998
    ..functional activity of each cofactor species was assessed either by clotting assay or by employing a purified prothrombinase assay using saturating amounts of factor Xa...
  57. ncbi Design and quantitative structure-activity relationship of 3-amidinobenzyl-1H-indole-2-carboxamides as potent, nonchiral, and selective inhibitors of blood coagulation factor Xa
    Hans Matter
    Aventis Pharma Deutschland GmbH, DI and A, Molecular Modeling, Building G 878, D 65926 Frankfurt am Main, Germany
    J Med Chem 45:2749-69. 2002
    ..nonchiral 3-amidinobenzyl-1H-indole-2-carboxamides and analogues as inhibitors of the blood coagulation enzyme factor Xa (fXa) were designed, synthesized, and investigated by X-ray structure analysis and 3D quantitative structure-..
  58. ncbi The tissue factor region that interacts with factor Xa in the activation of factor VII
    D Kirchhofer
    Department of Cardiovascular Research, Genentech Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Biochemistry 40:675-82. 2001
    ..the conversion of factor VII to factor VIIa which, in vitro, is efficiently catalyzed by low concentrations of factor Xa. To identify the tissue factor region that interacts with the activator factor Xa during this process, we ..
  59. ncbi Role of zymogen and activated factor X as scaffolds for the inhibition of the blood coagulation factor VIIa-tissue factor complex by recombinant nematode anticoagulant protein c2
    P W Bergum
    Corvas International, Inc, San Diego, California 92121, USA
    J Biol Chem 276:10063-71. 2001
    Recombinant nematode anticoagulant protein c2 (rNAPc2) is a potent, factor Xa (fXa)-dependent small protein inhibitor of factor VIIa-tissue factor (fVIIa...
  60. ncbi Razaxaban, a direct factor Xa inhibitor, in combination with aspirin and/or clopidogrel improves low-dose antithrombotic activity without enhancing bleeding liability in rabbits
    Pancras C Wong
    Department of Thrombosis Research, Bristol Myers Squibb Company, 311 Pennington Rocky Hill Road, Pennington, NJ 08534, USA
    J Thromb Thrombolysis 24:43-51. 2007
    ..evaluated the antithrombotic and bleeding profiles of dual and triple therapy with razaxaban, a direct factor Xa inhibitor, plus aspirin and/or clopidogrel in rabbit models of electrolytic injury-induced carotid artery ..
  61. pmc Ixolaris binding to factor X reveals a precursor state of factor Xa heparin-binding exosite
    Robson Q Monteiro
    Instituto de Bioquimica Medica, Centro de Ciencias de Saude, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
    Protein Sci 17:146-53. 2008
    ..In contrast to human TFPI, Ixolaris specifically binds to factor Xa (FXa) heparin-binding exosite (HBE). In addition, Ixolaris interacts with zymogen FX...
  62. ncbi Coagulation factor Xa synergistically interacts with serotonin in inducing vascular smooth muscle cell proliferation
    Rajbabu Pakala
    Division of Cardiology, Department of Internal Medicine, University of Texas Health Science Center Medical School, Houston, TX 77030, USA
    Cardiovasc Radiat Med 4:69-76. 2003
    ..of coagulation cascade results in conversion of inactive zymogens such as factor X to its active form (factor Xa)...
  63. ncbi Use of a fixed activated partial thromboplastin time ratio to establish a therapeutic range for unfractionated heparin
    S M Bates
    Department of Medicine, McMaster University, Hamilton, Ontario, Canada
    Arch Intern Med 161:385-91. 2001
    ..We sought to identify an aPTT ratio that corresponds to therapeutic anti--factor Xa heparin levels for combinations of several reagents and coagulometers that are commonly used.
  64. ncbi Roles of coagulation pathway and factor Xa in rat mesangioproliferative glomerulonephritis
    Keiko Nomura
    Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
    Lab Invest 87:150-60. 2007
    Tissue factor initiates the extrinsic coagulation pathway by activating coagulation factor X to factor Xa, and factor V is a cofactor for the prothrombin activation by factor Xa...
  65. doi Interlaboratory agreement in the monitoring of unfractionated heparin using the anti-factor Xa-correlated activated partial thromboplastin time
    A Cuker
    Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    J Thromb Haemost 7:80-6. 2009
    ..APTT) be defined in each laboratory through correlation with a direct measure of heparin activity such as the factor Xa inhibition assay...
  66. ncbi Basic residues of human group IIA phospholipase A2 are important for binding to factor Xa and prothrombinase inhibition comparison with other mammalian secreted phospholipases A2
    C M Mounier
    Unite des Venins, Institut Pasteur, Paris, France
    Eur J Biochem 267:4960-9. 2000
    Human secreted group IIA phospholipase A2 (hGIIA) was reported to inhibit prothrombinase activity because of binding to factor Xa...
  67. ncbi Pharmacological characterization of a novel factor Xa inhibitor, FXV673
    V Chu
    Aventis Pharmaceuticals, Mail Stop EM A1B, Route 202 and 206, P O Box 6800, Bridgewater, NJ 08807, USA
    Thromb Res 103:309-24. 2001
    ..92 (rabbit), and 1.69 (rat). A coupled-enzyme assay was performed to measure thrombin activity following prothrombinase conversion of prothrombin to thrombin. FXV673 showed IC(50)s of 1.38 and 2...
  68. doi RANKL induces components of the extrinsic coagulation pathway in osteoclasts
    Erik Karlström
    Karolinska Institutet, Department of Laboratory Medicine, Division of Pathology, SE 141 86 Stockholm, Sweden
    Biochem Biophys Res Commun 394:593-9. 2010
    Prothrombin is converted to thrombin by factor Xa in the cell-associated prothrombinase complex. Prothrombin is present in calcified bone matrix and thrombin exerts effects on osteoblasts as well as on bone resorption by osteoclasts...
  69. doi Effects of fondaparinux and a direct factor Xa inhibitor TAK-442 on platelet-associated prothrombinase in the balloon-injured artery of rats
    Noriko Konishi
    Pharmacology Research Laboratories, Takeda Pharmaceutical Company Ltd, Osaka, Japan
    J Cardiovasc Pharmacol 57:201-6. 2011
    Endothelial damage triggers platelet adhesion and platelet-associated prothrombinase formation at the point of injury, resulting in the progression of thrombus formation...
  70. pmc Effector protease receptor 1 mediates the mitogenic activity of factor Xa for vascular smooth muscle cells in vitro and in vivo
    J Herbert
    Haemobiology Research Department, Sanofi Recherche, 31036 Toulouse, France
    J Clin Invest 101:993-1000. 1998
    The binding of 125I-factor Xa to human aortic smooth muscle cell (SMC) monolayers was studied. At 4 degreesC, 125I-factor Xa bound to a single class of binding sites with a dissociation constant value of 3.6+/-0...
  71. ncbi Potent arterial antithrombotic effect of direct factor-Xa inhibition with ZK-807834 administered to coronary artery disease patients
    M Urooj Zafar
    Zena and Michael A Wiener, Cardiovascular Institute, New York, NY 10029, USA
    Thromb Haemost 97:487-92. 2007
    ..Plasma levels of ZK-807834 show a strong linear correlation with PT ratio. This direct factor-Xa inhibitor may reduce the need for additional potent glycoprotein IIbIIIa inhibition...
  72. ncbi Characterization of the protein Z-dependent protease inhibitor
    X Han
    Division of Hematology, Barnes Jewish Hospital at Washington University Medical Center, St Louis, MO 63110, USA
    Blood 96:3049-55. 2000
    ..Thus, the major effect of PZ and ZPI is to dampen the coagulation response prior to the formation of the prothrombinase complex. Besides factor Xa, ZPI also inhibits factor XIa in the absence of PZ, phospholipids, and Ca(++)...
  73. doi Clinical pharmacology of direct and indirect factor Xa inhibitors
    Hans Juergen Rupprecht
    GPR Klinikum Ruesselsheim, Ruesselsheim, Germany
    Drugs 70:2153-70. 2010
    ..Direct inhibitors may bind free FXa and, in contrast to indirect inhibitors, FXa within the prothrombinase complex or within clots as well...
  74. ncbi Ecotin is a potent anticoagulant and reversible tight-binding inhibitor of factor Xa
    J L Seymour
    Department of Protein Engineering, Genentech, Inc, South San Francisco, California 94080
    Biochemistry 33:3949-58. 1994
    ..has been characterized as an extremely potent anticoagulant and reversible tight-binding inhibitor of human factor Xa (FXa). The ecotin gene was cloned by PCR, highly expressed in E. coli, and purified from the E. coli periplasm...
  75. ncbi Macrophage migration inhibitory factor is induced by thrombin and factor Xa in endothelial cells
    Tadamichi Shimizu
    Departments of Dermatology and Molecular Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo 060 8638, Japan
    J Biol Chem 279:13729-37. 2004
    ..Thrombin, factor Xa (FXa), and trypsin induced MIF expression in human dermal microvascular endothelial cells and human umbilical ..
  76. ncbi Identification of basic residues in the heparin-binding exosite of factor Xa critical for heparin and factor Va binding
    A R Rezaie
    Edward A Doisy Department of Biochemistry, St Louis University School of Medicine, St Louis, Missouri 63104, USA
    J Biol Chem 275:3320-7. 2000
    ..Interestingly, further study suggested that certain basic residues of this site, particularly Arg(165) and Lys(169), play key roles in factor Va and/or prothrombin recognition by FXa in prothrombinase.
  77. ncbi Defining the factor Xa-binding site on factor Va by site-directed glycosylation
    Marten Steen
    Department of Clinical Chemistry, Division of Laboratory Medicine, Lund University, The Wallenberg Laboratory, Malmo General Hospital, Malmo SE 205 02, Sweden
    J Biol Chem 277:50022-9. 2002
    ..This indicates that the enzyme:cofactor assembly of the prothrombinase and the tenase complexes are homologous and provide a useful platform for further investigation of specific ..
  78. ncbi Factor Va-factor Xa interactions: molecular sites involved in enzyme:cofactor assembly
    M Steen
    Department of Laboratory Medicine, Division of Clinical Chemistry, Lund University, The Wallenberg Laboratory, University Hospital, Malmo, Sweden
    Scand J Clin Lab Invest Suppl 237:5-11. 2002
    The generation of thrombin by the prothrombinase complex is a key event in coagulation...
  79. pmc Zymogen-like factor Xa variants restore thrombin generation and effectively bypass the intrinsic pathway in vitro
    Matthew W Bunce
    Department of Pediatrics, Division of Hematology, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Blood 117:290-8. 2011
    ..Notably, assembly of FXa(I16L) and FXa(V17A) on activated platelets with factor Va to form prothrombinase completely restores biologic activity...
  80. ncbi Human protein S cleavage and inactivation by coagulation factor Xa
    G L Long
    Department of Biochemistry, University of Vermont College of Medicine, Burlington, Vermont 05405 0068, USA
    J Biol Chem 273:11521-6. 1998
    Human factor Xa specifically cleaves the anticoagulant protein S within the thrombin-sensitive domain...
  81. ncbi Effects of activation peptide bond cleavage and fragment 2 interactions on the pathway of exosite I expression during activation of human prethrombin 1 to thrombin
    Patricia J Anderson
    Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Biol Chem 278:44482-8. 2003
    Activation of prothrombin (Pro) by factor Xa to form thrombin occurs by proteolysis of Arg271-Thr272 and Arg320-Ile321, resulting in expression of regulatory exosites I and II...
  82. ncbi In vitro and in vivo antithrombotic activity of PD-198961, a novel synthetic factor Xa inhibitor
    Liguo Chi
    Cardiovascular Pharmacology, Pfizer Global R and D, Ann Arbor Laboratories, Ann Arbor, Michigan 48105, USA
    J Cardiovasc Pharmacol 44:493-500. 2004
    ..is a novel, synthetic factor Xa inhibitor with a Ki of 2.7 nM against human factor Xa...
  83. doi Comparative effects of atrial polypeptide and neurohormone C on the interaction of factor Xa with antithrombin III
    Martin H Coggin
    Department of Biological Sciences, Bowling Green State University, Bowling Green, OH 43403, USA
    Blood Coagul Fibrinolysis 19:645-51. 2008
    The effects of atrial polypeptide and neurohormone C upon the interaction of human factor Xa (FXa) and human antithrombin III (ATIII) were followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis...
  84. ncbi Characterization of purified recombinant Bet v 1 with authentic N-terminus, cloned in fusion with maltose-binding protein
    M D Spangfort
    Research Department, ALK ABELLO Group, Hørsholm, Denmark
    Protein Expr Purif 8:365-73. 1996
    ..White Birch) has been cloned and expressed in Escherichia coli as a fusion with maltose-binding protein and a Factor Xa proteolytic cleavage site...
  85. ncbi Pharmacodynamic activity and antithrombotic efficacy of RPR120844, a novel inhibitor of coagulation factor Xa
    R J Leadley
    Cardiovascular Drug Discovery, Rhône Poulenc Rorer International, Collegeville, Pennsylvania 19426, USA
    J Cardiovasc Pharmacol 34:791-9. 1999
    ..the pharmacodynamic profile and antithrombotic efficacy of RPR120844, a competitive inhibitor of coagulation factor Xa, with a K(i) of 7 nM against human factor Xa...
  86. ncbi Nonpeptide factor Xa inhibitors: DPC423, a highly potent and orally bioavailable pyrazole antithrombotic agent
    Pancras C Wong
    Cardiovascular Biology, Bristol Myers Squibb Company, Experimental Station, Wilmington, DE 19880 0400, USA
    Cardiovasc Drug Rev 20:137-52. 2002
    ..is a synthetic, orally bioavailable, competitive, and selective inhibitor of human coagulation factor Xa (K(i) [nM]: factor Xa, 0...
  87. ncbi Enoxaparin, a low molecular weight heparin, inhibits platelet-dependent prothrombinase assembly and activity by factor-Xa neutralization
    F A Spencer
    Cardiovascular Thrombosis Research Center, Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, MA 01685, USA
    J Thromb Thrombolysis 9:223-8. 2000
    ..tissue-factor and its activation of factor X, which in the presence of factor Va, calcium, and phospholipid (prothrombinase complex) effectively converts prothrombin to thrombin...
  88. ncbi Calcium enhances heparin catalysis of the antithrombin-factor Xa reaction by promoting the assembly of an intermediate heparin-antithrombin-factor Xa bridging complex. Demonstration by rapid kinetics studies
    A R Rezaie
    Edward A Doisy Department of Biochemistry and Molecular Biology, St Louis University School of Medicine, St Louis, Missouri 63104, USA
    Biochemistry 39:12083-90. 2000
    Heparin catalyzes the inhibition of factor Xa by antithrombin mainly through an allosteric activation of the serpin inhibitor, but an alternative heparin bridging mechanism has been suggested to enhance the catalysis in the presence of ..
  89. ncbi [Determination of factor Xa inhibition doses of low-molecular heparin, nadroparin and reviparin in urological patients]
    Svetlana Pavlovic
    Klinicki centar Nic, Klinika za urologiju, 18 000 Nis, Srbija
    Vojnosanit Pregl 64:538-42. 2007
    The inhibition of factor Xa (FX) by the use of low-molecular heparin (LMH) is important clinical procedure in patients with moderate and high risk for the development of venous thromboembolism (VTE) and pulmonary embolism (PE)...
  90. ncbi The effect of leukocyte elastase on tissue factor pathway inhibitor
    D A Higuchi
    Department of Medicine, Jewish Hospital, Washington University Medical Center, St Louis, MO 63110
    Blood 79:1712-9. 1992
    Tissue factor pathway inhibitor (TFPI) is a multivalent Kunitz-type inhibitor that directly inhibits factor Xa and, in a factor Xa-dependent fashion, also inhibits the factor VIIa/tissue factor (TF) catalytic complex...
  91. ncbi Identification of a factor Xa-interactive site within residues 337-372 of the factor VIII heavy chain
    Keiji Nogami
    Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    J Biol Chem 279:15763-71. 2004
    ..demonstrated that the residues 337-372, comprising the acidic C-terminal region in A1 subunit, interact with factor Xa during the proteolytic inactivation of factor VIIIa (Nogami, K., Wakabayashi, H., and Fay, P. J. (2003) J. Biol...
  92. doi Anti-factor Xa plasma levels in pregnant women receiving low molecular weight heparin thromboprophylaxis
    Nathan S Fox
    Maternal Fetal Medicine Associates, PLLC, 70 East 90th Street, New York, NY 10128, USA
    Obstet Gynecol 112:884-9. 2008
    To report the incidence of prophylactic, subprophylactic, and supraprophylactic anti-factor Xa activity in pregnant patients receiving low molecular weight heparin for venous thromboembolism prophylaxis, and to evaluate whether maternal ..
  93. ncbi Factor Xa stimulates fibroblast procollagen production, proliferation, and calcium signaling via PAR1 activation
    Olivier P Blanc-Brude
    Royal Free and University College London Medical School, Centre for Cardiopulmonary Biochemistry and Respiratory Medicine, 5 University Street, London WC1E 6JJ, UK
    Exp Cell Res 304:16-27. 2005
    ..During hemostasis, the coagulation cascade proteinase factor X is converted into factor Xa. We have previously shown that factor Xa upregulates fibroblast proliferation via production of autocrine PDGF...
  94. doi Prognostic values of the factor Xa-activated clotting time and endogenous thrombin potential in patients suspected of having disseminated intravascular coagulation
    Ji Weon Seo
    Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea
    Thromb Res 123:565-72. 2009
    ..The factor Xa-activated clotting time (XACT) represents plasma levels of procoagulant phospholipids...
  95. ncbi Immunotoxicity of polyunsaturated fatty acids in serum-free medium
    B U Tezabwala
    Center for Human Nutrition, University of Texas Southwestern Medical Center at Dallas 75235, USA
    Immunopharmacol Immunotoxicol 17:365-83. 1995
    ..Similar effects were observed with cultured B16 F10 murine melanoma cells...
  96. ncbi Augmentation of murine natural killer cell activity by swainsonine, a new antimetastatic immunomodulator
    M J Humphries
    Department of Oncology, Howard University Cancer Center, Washington, DC 20060
    Cancer Res 48:1410-5. 1988
    Swainsonine, an indolizidine alkaloid, has been found to inhibit the experimental metastasis of B16-F10 melanoma cells when administered systemically to syngeneic C57BL/6 mice...
  97. ncbi Structure of human des(1-45) factor Xa at 2.2 A resolution
    K Padmanabhan
    Department of Chemistry, Michigan State University, East Lansing 48824 1322
    J Mol Biol 232:947-66. 1993
    The structure of a large molecular fragment of factor Xa that lacks only a Gla (gamma-carboxyglutamic acid) domain (N-terminal 45 residues) has been solved by X-ray crystallography and refined at 2...
  98. ncbi A pharmacokinetic study of dalteparin (Fragmin) during late pregnancy
    M Blomback
    Department of Laboratory Medicine Coagulation Research, Karolinska Institute Karolinska Hospital, Stockholm, Sweden
    Blood Coagul Fibrinolysis 9:343-50. 1998
    ..Fifteen women injected themselves subcutaneously with 5000 IU and two with 2500 IU dalteparin once daily. An anti-FXa activity of 0.20-0.40 IU/ml 3 h after injection was obtained...
  99. ncbi Boophilus microplus anticoagulant protein: an antithrombin inhibitor isolated from the cattle tick saliva
    F Horn
    Centro de Biotecnologia, Departamento de Biofisica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brasil
    Arch Biochem Biophys 384:68-73. 2000
    ..It also inhibited thrombin, but not fXa, amidolytic activity...
  100. ncbi Platelet factor V New York: a defect in factor V distinct from that in factor V Quebec resulting in impaired prothrombinase generation
    H J Weiss
    Department of Medicine, St Luke s Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, New York, USA
    Am J Hematol 66:130-9. 2001
    ..were performed on a patient with a longstanding bleeding disorder whose major defects were impaired platelet prothrombinase activity in the absence of added factor Va, and a platelet factor V value that was either decreased or at the ..
  101. ncbi Four hydrophobic amino acids of the factor VIII C2 domain are constituents of both the membrane-binding and von Willebrand factor-binding motifs
    Gary E Gilbert
    Veterans Affairs Boston Healthcare System, Brigham and Women s Hospital, and Harvard Medical School, West Roxbury, Massachusetts 02132, USA
    J Biol Chem 277:6374-81. 2002
    ..In a phospholipid-limiting factor Xa activation assay, these mutants had a 65, 85, and 96% reduction in specific activity...

Research Grants67

  1. Steven T Olson; Fiscal Year: 2016
    ..by heparin in showing that activation is mediated principally by the relief of repulsive interactions with factor Xa and factor IXa and secondarily by the relief of structural constraints of the reactive site that promote ..
  2. UMESH RAMANLAL DESAI; Fiscal Year: 2016
    ..3) Mechanistically, the new molecules inhibit thrombin, factor Xa and factor XIa with IC50 values in the range of 10-240 nM...
  3. NOVEL ANTITHROMBOTIC AGENT
    David Wolf; Fiscal Year: 1993
    ..Thrombin is a potent thrombogenic agonist and is derived from prothrombin by the catalytic activity of the prothrombinase complex...
  4. John H Griffin; Fiscal Year: 2014
    ..Based on Surface Plasmon Resonance (SPR) binding studies and on prothrombinase assays, we hypothesize that the anticoagulant soluble lipids bind and directly inhibit factor Xa...
  5. Structure and Stability Studies of Factor VIII to Overcome the Immune Response
    PAUL CLINTON SPIEGEL; Fiscal Year: 2010
    ..response result in antibodies that block the activation of factor VIII by the serine proteases, thrombin or factor Xa. These "non-classical" antibodies possess a high level of pathogenicity and display positive cooperativity with "..
  6. Lipid Regulation of Thrombin Generation
    Barry R Lentz; Fiscal Year: 2012
    ..molecule of blood coagulation, is produced by prothrombin (II) proteolysis by a platelet-membrane-bound enzyme (factor Xa) and its associated cofactor (factor Va). The membrane accelerates II activation by 105-fold...
  7. MOLECULAR BIOLOGY OF HUMAN COAGULATION FACTOR V
    Thomas Ortel; Fiscal Year: 2010
    Thrombin generated by the prothrombinase complex contributes significantly to the pathogenesis of common clinical disorders such as myocardial infarction, deep vein thrombosis, pulmonary embolism, and stroke...
  8. Membrane Receptors Regulating Megakaryocyte Endocytosis of Factor V from Plasma
    BETH BOUCHARD; Fiscal Year: 2012
    Platelet- and plasma-derived factor Va serve an essential role in thrombin generation catalyzed by the prothrombinase complex, a 1:1, Ca2+-dependent complex of the cofactor factor Va and the serine protease factor Xa bound to activated ..
  9. METAL DEPENDENT COMPLEXES IN BLOOD COAGULATION
    Barbara Furie; Fiscal Year: 2002
    ..Elucidating the determinants of prothrombinase complex assembly may provide insights into methods of regulating complex formation in pathologic states such ..
  10. MOLECULAR INTERACTIONS OF BLOOD COAGULATION FACTOR XA
    Katherine High; Fiscal Year: 1999
    Blood coagulation Factor X occupies a central role in the clotting cascade. It can be activated by either Factor VIIa-tissue factor (extrinsic tenase) or by Factor IXa-VIIIa-phospholipid (intrinsic tenase)...
  11. The Prothrombinase Complex: A Model of an Enzyme-Cofactor Complex
    MARIA CRISTINA BRAVO; Fiscal Year: 2010
    ..The prothrombinase complex, formed between a noncovalent association between the enzyme factor Xa and cofactor Va, serves as the ..
  12. TIMOTHY OLEARY; Fiscal Year: 2015
    ..Heparin bound to AT inhibits the coagulation cascade enzymes factor Xa and factor IIa (thrombin)...
  13. LAURENT OLIVIER MOSNIER; Fiscal Year: 2016
    ..g. thrombin and factor Xa) on cells and initiated novel perspectives on the intricate complex networks of receptor-mediated cross talk in ..
  14. FUNCTION AND DYSFUNCTION IN HUMAN ANTITHROMBINS
    PETER GETTINS; Fiscal Year: 2007
    ..Antithrombin is the principal[unreadable] inhibitor of the blood coagulation proteinases factor Xa and thrombin[unreadable] and is regulated by heparin...
  15. Structure and Function of the Factor VIII - von Willebrand Factor Complex
    JOHN S LOLLAR; Fiscal Year: 2010
    ..the identification of a novel class of C2 domain Abs that inhibit the activation of fVIII by either thrombin or factor Xa. These Abs make a dominant contribution to the inhibitory immune response to fVIII in hemophilia A mice and in ..
  16. Studies on Na+ binding to thrombin
    Enrico Di Cera; Fiscal Year: 2010
    ..griseus and tissue-type plasminogen activator, to introduce Na+ activation as found in human thrombin and factor Xa, and molecular mimicry of Na+ activation as found in murine thrombin...
  17. TORRY ALLE TUCKER; Fiscal Year: 2016
    ..Our preliminary data support the concept that procoagulants induce MT. The role of factor Xa and thrombin in MT is now unknown and will be elucidated in this project. Dr...
  18. BLOOD COAGULATION HOMESTASIS: REGULATION OF TFPI
    Alan Schwartz; Fiscal Year: 2003
    ..which produces feedback inhibition of the factor VIIa/tissue factor complex and directly binds and inhibits factor Xa. TFPI is rapidly cleared in vivo via the endocytosis receptor, LRP (low density lipoprotein receptor-related ..
  19. Thrombin Formation Inhibitors
    James Phillips; Fiscal Year: 2004
    ..Generation of DVT is strongly correlated with the function of factor V, a protein cofactor for prothrombinase. Prothrombinase is the enzymatic complex responsible for thrombin generation...
  20. Novel Self-Limiting Prothrombinase Inhibitors
    MICHAEL N BLACKBURN; Fiscal Year: 2012
    ..Our molecular target is the prothrombinase complex...
  21. DEFINITION OF FUNCTIONAL SITES ON COAGULATION FACTOR X
    WILLIAM CHURCH; Fiscal Year: 1993
    ..Activated Factor X in turn forms a supramolecular complex, termed prothrombinase, consisting of an enzyme (Factor X alpha), a protein cofactor (Factor V alpha), calcium ion, and a ..
  22. MEMBRANE BIOPHYSICS AND CONTROL OF THROMBIN GENERATION
    BARRY LENTZ; Fiscal Year: 1999
    ..that PS exposure is critical in regulating prothrombin activation because it apparently serves to assemble the prothrombinase, activate factor Xa, place the appropriate peptide bond of prothrombin near the factor Xa active site, and ..
  23. PROTHROMBIN ACTIVATION ON BLOOD MONONUCLEAR CELLS
    PAULA TRACY; Fiscal Year: 1990
    ..is generated at the monocyte/macrophage surface through the assembly of the multicomponent coagulation enzyme prothrombinase, which consists of a membrane-bound, Ca++-dependent complex of factor Va and factor Xa...
  24. Processed Defining Megakaryocyte Endocytosis of Factor V
    PAULA TRACY; Fiscal Year: 2005
    Platelet- and plasma-derived factor Va serve an essential role in thrombin generation catalyzed by Prothrombinase, which consists of 1:1, stoichiometric, calcium-dependent complex of the cofactor factor Va and the serine protease factor ..
  25. PROTHROMBINASE COMPLEX--STOPPED-FLOW KINETICS
    Sriram Krishnaswamy; Fiscal Year: 1991
    b>Prothrombinase is the coagulation complex composed of the serine protease factor Xa, the protein cofactor factor Va, phospholipid or cellular surface and calcium ions...
  26. NOVEL ANTITHROMBOTIC AGENT
    David Wolf; Fiscal Year: 1990
    ..Thrombin is generated from the zymogen prothrombin by the prothrombinase complex which consists of factor Xa (a serine protease), factor Va (a co-factor) and Ca2+ assembled on a ..
  27. George J Broze; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): Tissue factor pathway inhibitor (TFPI) produces factor Xa (FXa)-dependent feedback inhibition of factor VIIa/tissue factor (FVIIa/TF)-induced coagulation. In humans, TFPI is expressed as two isoforms...
  28. PROTEIN Z DEPENDENT PROTEINASE INHIBITOR
    George J Broze; Fiscal Year: 2011
    Protein Z (PZ) is a vitamin K-dependent plasma protein that serves as a cofactor for the inhibition of factor Xa by PZ-dependent Protease Inhibitor (ZPI)...
  29. INTERACTION OF PLATELETS WITH COAGULATION FACTORS IX & X
    Peter Walsh; Fiscal Year: 1992
    Platelets possess specific, high-affinity, saturable receptors for factor XI, factor XIa, factor Xa, thrombin, high molecular weight kininogen, and factor Va and promote the proteolytic activation of factor XII, factor XI, factor X, and ..
  30. MOLECULAR INTERACTIONS OF BLOOD COAGULATION FACTOR X
    RICHARD PAINTER; Fiscal Year: 1991
    ..Once activated, factor Xa (enzyme) associates with factor Va (cofactor) in another membrane surface complex responsible for the activation ..
  31. RAFAL L PAWLINSKI; Fiscal Year: 2016
    ..In a complementary proof-of-concept clinical trial with the newly available factor Xa (FXa) inhibitor rivaroxaban, we will determine whether the effect of FXa inhibition extends beyond simple ..
  32. The Molecular Pathogenesis of Hookworm Anemia
    Michael Cappello; Fiscal Year: 2005
    ..ceylanicum RNA, and the recombinant protein inhibits the activity of coagulation factor Xa by a novel mechanism...
  33. The Molecular Pathogenesis of Hookworm Anemia
    Michael Cappello; Fiscal Year: 2001
    ..ceylanicum RNA, and the recombinant protein inhibits the activity of coagulation factor Xa by a potentially novel mechanism...
  34. FACTOR VA INTERACTIONS REGULATING PROTHROMBIN ACTIVATION
    Paul Bock; Fiscal Year: 1991
    ..The interdependent interactions among factor Xa (enzyme), prothrombin (substrate), factor Va (cofactor) and the surfaces of blood platelets are required to ..
  35. Molecular Recognition in Factor VIIa Induced Coagulation
    S Bajaj; Fiscal Year: 2005
    ..Tissue factor pathway inhibitor (TFPI) contains two functional Kunitz domains (K1 and K2) and it first inhibits factor Xa via its K2 domain...
  36. Antithrombin targeting to HSPG & heparin coated surfaces
    Susan Bock; Fiscal Year: 2006
    Activation of thrombin and factor Xa (fXa) occurs on vascular and biomaterial surfaces and initiates coagulation, platelet, signaling and cell proliferation reactions, which may then promote pathological thrombosis, occlusion and ..
  37. Structure/Function Study of the Anticoagulant Protein S
    Alan Rigby; Fiscal Year: 2005
    ..The APC-independent activity of protein S has been ascribed to its ability to inhibit the "prothrombinase" and "tenase" procoagulant complexes...
  38. Gary E Gilbert; Fiscal Year: 2015
    ..Our preliminary data demonstrates that stressed or stimulated endothelial cells support assembly of the prothrombinase complex in focal areas on the cell while maintaining anticoagulant proteins on other parts of the cell...
  39. Chemistry and Biology of Coagulation
    Sriram Krishnaswamy; Fiscal Year: 2013
    ..Project 1 (Krishnaswamy) uses the prothrombinase complex as a paradigm to investigate the role of extended macromolecular interactions between the protein ..
  40. Enrico Di Cera; Fiscal Year: 2015
    ..mutant that auto-activates to thrombin without the need for the snake venom ecarin or the physiological prothrombinase complex...
  41. Alireza R Rezaie; Fiscal Year: 2015
    ..serpin which, unlike AT, exhibits a narrower protease specificity, thus capable of inhibiting only factors Xa (fXa) and XIa (fXIa)...
  42. FACTOR VA INTERACTIONS REGULATING PROTHROMBIN ACTIVATION
    Paul E Bock; Fiscal Year: 2010
    ..is postulated to control one or both steps in substrate recognition through interactions with factor Va in the prothrombinase complex...
  43. SUSAN ANTONE MARONEY; Fiscal Year: 2014
    ..physiological inhibitor of tissue factor, the initiator of clotting after a blood vessel has been damaged, and FXa, a major component of the clotting system that produces a large amount of thrombin resulting in clot formation...
  44. ANTIBODIES WITH PROTHROMBINASE ACTIVITY IN LUPUS
    Perumal Thiagarajan; Fiscal Year: 2003
    ..e. the catalytic cleavage of prothrombin. This proposal is based on the hypothesis that prothrombinase autoantibodies promote thrombus formation by generating thrombin-like activities from prothrombin, like factor ..
  45. Structural Mechanisms for the Inhibition of Thrombosis
    JAMES HUNTINGTON; Fiscal Year: 2009
    ..of the blood coagulation cascade: 1) prevention of thrombin formation through inhibition of upstream coagulation factor Xa;2) direct inhibition of thrombin by serpins antithrombin (AT) and heparin cofactor II (HCII);and, 3) attenuation ..
  46. SUBSTRATE RECOGNITION IN BLOOD COAGULATION
    Sriram Krishnaswamy; Fiscal Year: 2003
    ..Evidence suggests that prothrombin activation by the prothrombinase complex, results from interactions at an extended macromolecular recognition site (Exosites) on the enzyme ..
  47. Designing Mechanism-based Anticoagulants
    Umesh Desai; Fiscal Year: 2006
    ..Heparin anticoagulation therapy is primarily based on the ability to accelerate the inhibition of factor Xa and thrombin by antithrombin, a plasma serine proteinase inhibitor...
  48. MARIO CESAR RICO; Fiscal Year: 2014
    ..TSP1 promotes the assembly of the prothrombinase complex on cell surfaces with subsequent generation of serine proteases...
  49. Structure, Function &Genetics of Coagulation Factors
    Darrel W Stafford; Fiscal Year: 2013
    ..to extend known structural data: to construct solvent-equilibrated models that bear on the action of prothrombinase, and to study the regulation of tissue factor, encrypted and unencrypted, bound and unbound to FVIIa...
  50. Factor Va regulation of prothrombinase activity
    JAMILA HIRBAWI; Fiscal Year: 2010
    ..amino acid residue(s) of factor V that interact with the blood coagulation factor prothrombin (flla), during prothrombinase complex assembly and function...
  51. CONTROL OF BLOOD ACTIVATION DURING OPEN HEART SURGERY
    L Edmunds; Fiscal Year: 2002
    ..This project focuses on suppressing formation of the prothrombinase complex, complement activation and activation of neutrophils, monocytes and platelets...
  52. STRUCTURES OF COAGULATION COFACTORS
    STEPHEN EVERSE; Fiscal Year: 2003
    ..and activity modulators in assembling their respective serine protease partners into the enzymatic complexes (prothrombinase and intrinsic tenase, respectively) without which thrombin generation is negligible...
  53. FACTOR V GENE DEFECTS IN THROMBOPHILIA
    WILLIAM KANE; Fiscal Year: 2001
    Defects in regulation of the prothrombinase complex play a central role in the pathogenesis of thrombosis...
  54. The Role of Membranes in Thrombus Formation In Viva
    Barbara Furie; Fiscal Year: 2005
    ..is important for the assembly of the coagulation enzyme complexes tenase, the activator of factor X and prothrombinase, the activator of prothrombin on the membrane surface...
  55. Roles for coagulation in immunity
    STEPHEN SMILEY; Fiscal Year: 2005
    DESCRIPTION (provided by investigator): Prothrombinase (PTase) activity generates thrombin, a serine protease that cleaves fibrinogen, prompting the deposition of polymerized fibrin...
  56. Serpin Modulation of Inflammatory Vasculitis; Potential for Immunomodulatory Ther
    ALEXANDRA ROSE LUCAS; Fiscal Year: 2010
    ..dissolving thrombolytic (uPA, tPA for Serp-1 and NSP;plasmin for Serp-1 ) and clot forming thrombotic pathways (fXa for Serp-1)...
  57. Richard G Vile; Fiscal Year: 2014
    ..c. tumors, LN and lung metastases arising from spontaneous metastasis from a primary B16.F10-ova tumor...
  58. Stimulation of broadly neutralizing antibodies against influenza in a pig model
    RADHEY SHYAM KAUSHIK; Fiscal Year: 2011
    ..Perhaps the most significant progress is the discovery of CR6261, F10, and 12D1 antibodies apparently targeting viral fusion machinery largely constituted by HA2, rather than the ..
  59. Genetic control over the gut microbiome composition
    Daniel Pomp; Fiscal Year: 2010
    ..Gut microbiome QTL identified in this cohort will then be fine-mapped using an F10 intercross population from the same origin...
  60. Shiladitya Sengupta; Fiscal Year: 2014
    ..a luciferase-expressing RAS-activated ovarian mouse transgenic cancer model, a 4T1 breast cancer model and a B16/F10 melanoma syngeneic model with activated MAPK signaling, which will be used in this study. Aim 3...
  61. Therapeutic Potential of IL-15 Plasmid Delivery to Tumors Using Electroporation
    Richard Heller; Fiscal Year: 2013
    ..The study will be designed to accomplish the following specific aims: i. to evaluate B16.F10 melanoma growth or regression in response to electrically mediated IL-15 plasmid delivery. ii...
  62. New Fluorescent Caspase Detection Probes to Label Apoptotic Tumor Cells In Vivo
    Brian Lee; Fiscal Year: 2009
    ..Specific Aim IV. Detection of apoptotic tumor cells in mice bearing the B16-F10 melanoma and treated with B16a cell vaccine, and Specific Aim V...
  63. Genetic Environmental Relationship Between Bone Obesity and Leptin in Mice
    James M Cheverud; Fiscal Year: 2010
    ..Trait Loci, QTLs) affecting bone and its relationship to obesity in the Rl strains, F2 intercross, and an F10 Advanced Intercross (Al) line population...
  64. RAS and injury: ACE and resistance to cancer and viral infection
    Kenneth E Bernstein; Fiscal Year: 2010
    ..Challenge of ACE 10/10 mice with the aggressive mouse melanoma cell line B16-F10 showed that these mice are remarkably resistance to tumor growth...
  65. Artificial Immune Moduating (AIM??)Platform for the Treatment of Cancer
    Jonathan P Schneck; Fiscal Year: 2013
    ..In Specific Aim #3, in vivo efficacy studies will be conducted using the murine B16 F10 melanoma model...
  66. "Mixtures of Xenoestrogens Alter Estradiol-induced Non-Genomic Signaling"
    René Viñas; Fiscal Year: 2013
    ..regulation of signaling via membrane estrogen receptor (mER) subtypes in a pituitary cell line (GH3/B6/F10)...
  67. Wolfram Ruf; Fiscal Year: 2016
    ..by activating cancer cell-expressed protease receptors and delineates the respective contributions of FVIIa and FXa to cancer cell PAR2 activation...