Formation of Fibrin Clot and the Clotting Cascade (Homo sapiens)

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1881, 838880, 84, 8562, 66-682162, 66-6880-82213571, 72, 75, 77797, 8678732, 3469, 7081, 8332, 34212180, 84, 858680-8228, 32, 3321, 2487307, 8689187932, 342136-392727-2928, 32, 338936-3921, 243069, 7027-2939, 42, 49, 508962-65783528, 32, 337840-438621, 241828, 32, 33861821, 242769, 70318927-292139, 42, 49, 503538, 51-5739, 42, 49, 5071-7640-4318878658-6171, 72, 75, 778762-6571, 72, 75, 778977, 868744-4827-2936-398621, 248639, 42, 49, 50312736-3980-827944-4831187871-76891828, 32, 3318867, 8679898681, 837958-6169, 7079267869, 70188980, 84, 858938, 51-5771, 72, 75, 7758-6138, 51-573532, 3439, 42, 49, 5089188971-7671, 72, 75, 7740-4328, 32, 337Activated thrombin factor XIII Alpha2-macroglobulin factor XIa Plasma kallikrein factor XIGPIb-IX-V complex Activated thrombin von Willibrand factor multimer factor Va GPIb-IX-V complex activated thrombin factor Xa GPIb factor VIIIvon Willebrand factor multimer C1q binding protein tetramer factor Va factor VIII GPIb-IX-V complex factor IXa KNGC1q binding protein tetramer cleaved antithrombin III factor XI factor XI GPIb C1q binding protein tetramer factor Xa kallikrein GPIb factor XIII cleaved tetramer KNGC1q binding protein tetramer TFPITFF7afactor Xa cleaved antithrombin III fibrin monomer factor VIIIa antithrombin IIIheparin factor Xa GPIb-IX-V complex activated protein C factor XIIaC1Inh fibrin multimer Fibrinogen factor XIIa prekallikreinkininogenC1q binding protein tetramer TFF7a fibrin monomer kallikreinC1Inh activated thrombin Alpha2-macroglobulin factor IXa factor VIIa TFF7 thrombincleaved antithrombin IIIheparin protein C factor X C1q binding protein tetramer factor VIIa C1q binding protein tetramer kallikreinkininogenC1q binding protein tetramer activated protein C factor VIIa VaXa complex activated kininogen activated thrombinthrombomodulin factor VIIIa Plasma kallikrein activated kininogenC1q binding protein tetramer cytoplasmprolylcarboxypeptidase dimer factor XIIa factor VIIIafactor IXa TFF7a thrombinantithrombin IIIheparin factor XIIIa factor Xa KNGC1q binding protein tetramer C1q binding protein tetramer kallikreinalpha2-macroglobulin activated thrombin factor VIII Plasma kallikrein thrombincleaved antithrombin III factor Vi factor XIaGPIbGPIXGPV complex PalmC-F3 GP5 C1QBP factor VaC1QBP FGBfactor VIII heavy chain factor Xa heavy chain factor VIIa heavy chain factor XIGPIb-IX-V complex8xCbxE-3D-PROCFGAthrombin heavy chain A2M factor VIIIa A3 C1 C2 polypeptide GP9 FGG factor XIIa light chain FGB THBDfactor VIIIa A1 polypeptide factor Va heavy chain Ca2+HeparinCa2+factor VIII light chain thrombin light chain thrombinantithrombin IIIheparinNH4+factor Xa heavy chain factor XI monomer factor XIIa heavy chain Activated thrombin factor VIIa heavy chain KNG1SERPING1 F13BKNG1thrombin light chain KLKB1factor VIIIa A3 C1 C2 polypeptide GP1BA PROCSERPINC1factor IXa heavy chain GP1BA protein C11xCbxE-3D-F10Ca2+ factor VIIIa A2 polypeptide antithrombin IIIheparin10xCbxE-F7FGB 10xCbxE-F7thrombin heavy chain VWFfactor XIIIa A chain SERPING1KLKB1thrombin heavy chain factor XIaGPIbGPIXGPV complexfactor XIIIa A chain PalmC-F3 thrombin light chain factor VIIIathrombincleaved antithrombin IIIheparinCa2+GP1BA von Willibrand factor multimerFGBfactor XIII cleaved tetramerthrombin heavy chain Ca2+ activated protein C11xCbxE-3D-F10PalmC-F3Plasma kallikreinPROC8xCbxE-3D-PROCSERPING1 thrombincleaved antithrombin IIISERPINC1factor Xa heavy chain FGAKNG1GP5 factor X heavy chain C1QBP factor VIIIvon Willebrand factor multimer11xCbxE-PROS1factor XI monomer KLKB1factor XIIa heavy chain factor IXa11xCbxE-3D-F10VWFKLKB1KNG1thrombin heavy chain factor XIII A chain Zn2+TFF7athrombin light chain activated protein CGP9 kallikreinC1Inhfactor XI10xCbxE-F2KNGC1q binding protein tetramerfactor Va light chain C1QBP thrombin light chain Ca2+ KLKB1Ca2+ C1QBP factor XKLKB1factor Va light chain Bradykinin10xCbxE-F7factor Xafactor VIIafactor Xa heavy chain 11xCbxE-3D-F10KLKB1kallikreinkininogenC1q binding protein tetramerfactor VIIIa A2 polypeptide factor XIIa light chain factor XIIIafibrin monomerCa2+ KNG1GP5 PalmC-F3 11xCbxE-3D-F1010xCbxE-F7factor VIIIFGG factor XIIITFF7Ca2+ Ca2+ 12xCbxE-3D-F911xCbxE-3D-F912xCbxE-3D-F9GP1BB GP1BB 10xCbxE-F7factor VIIa heavy chain C1q binding protein tetramerKNG1factor VIIIa B A3 acidic polypeptidefactor XaKLKB1SERPINC1activated kininogenC1q binding protein tetramerFGG factor V activation peptidefactor XIIaC1InhFGA TFPIfactor XIII A chain activation peptideA2M kallikreinalpha2-macroglobulinPROCfactor ViPRCP KLKB1VaXa complex 8xCbxE-3D-PROCfactor IXa heavy chain PROCTFPITFF7afactor XaSERPINC1prolylcarboxypeptidase dimerSERPINC1GP1BB fibrin multimerfactor VIIIa A1 polypeptide factor Va heavy chain factor XIa heavy chain factor XIIaKLKB1F13B Ca2+ Ca2+ 10xCbxE-F2SERPINC1 factor Va light chain activated thrombinthrombomodulinfactor Vfactor XIICa2+ Ca2+ FGA fibrin multimer, crosslinkedfactor VIII light chain THBDCa2+ factor X activation peptidefactor XIa light chain F13B Ca2+Platelet Factor 4GPIb-IX-V complexCa2+ Ca2+ Ca2+ KNG1factor VIII heavy chain FibrinogenAlpha2-macroglobulinfactor IX activation peptideTFPI sequestered tissue factorfactor VIIIafactor IXaprekallikreinkininogenC1q binding protein tetramerSERPINC1 GP9 1, 21, 21, 213-155, 710-12175, 711, 1220195, 61, 23, 4522-248, 965, 63, 41810, 119, 22, 23181713-15253, 471, 285, 610, 1113-15822-2419522, 2313-159, 22, 238, 91722, 231, 210, 1110, 111, 21, 222, 231613-1522, 231, 23, 45, 62183, 4198, 92022-249, 22, 23


Description

The formation of a fibrin clot at the site of an injury to the wall of a normal blood vessel is an essential part of the process to stop blood loss after vascular injury. The reactions that lead to fibrin clot formation are commonly described as a cascade, in which the product of each step is an enzyme or cofactor needed for following reactions to proceed efficiently. The entire clotting cascade can be divided into three portions, the extrinsic pathway, the intrinsic pathway, and the common pathway. The extrinsic pathway begins with the release of tissue factor at the site of vascular injury and leads to the activation of factor X. The intrinsic pathway provides an alternative mechanism for activation of factor X, starting from the activation of factor XII. The common pathway consists of the steps linking the activation of factor X to the formation of a multimeric, cross-linked fibrin clot. Each of these pathways includes not only a cascade of events that generate the catalytic activities needed for clot formation, but also numerous positive and negative regulatory events. <a href=http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=140877>View original pathway at Reactome</a>

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  1. Kisiel W.; ''Human plasma protein C: isolation, characterization, and mechanism of activation by alpha-thrombin.''; PubMed Europe PMC Scholia
  2. Gailani D, Ho D, Sun MF, Cheng Q, Walsh PN.; ''Model for a factor IX activation complex on blood platelets: dimeric conformation of factor XIa is essential.''; PubMed Europe PMC Scholia
  3. de Maat S, Björkqvist J, Suffritti C, Wiesenekker CP, Nagtegaal W, Koekman A, van Dooremalen S, Pasterkamp G, de Groot PG, Cicardi M, Renné T, Maas C.; ''Plasmin is a natural trigger for bradykinin production in patients with hereditary angioedema with factor XII mutations.''; PubMed Europe PMC Scholia
  4. Mann KG, Butenas S, Brummel K.; ''The dynamics of thrombin formation.''; PubMed Europe PMC Scholia
  5. Hagen FS, Gray CL, O'Hara P, Grant FJ, Saari GC, Woodbury RG, Hart CE, Insley M, Kisiel W, Kurachi K.; ''Characterization of a cDNA coding for human factor VII.''; PubMed Europe PMC Scholia
  6. Kothari H, Pendurthi UR, Rao LV.; ''Analysis of tissue factor expression in various cell model systems: cryptic vs. active.''; PubMed Europe PMC Scholia
  7. Broze GJ.; ''Binding of human factor VII and VIIa to monocytes.''; PubMed Europe PMC Scholia
  8. Pieters J, Lindhout T, Hemker HC.; ''In situ-generated thrombin is the only enzyme that effectively activates factor VIII and factor V in thromboplastin-activated plasma.''; PubMed Europe PMC Scholia
  9. Ni F, Konishi Y, Frazier RB, Scheraga HA, Lord ST.; ''High-resolution NMR studies of fibrinogen-like peptides in solution: interaction of thrombin with residues 1-23 of the A alpha chain of human fibrinogen.''; PubMed Europe PMC Scholia
  10. Wen DZ, Dittman WA, Ye RD, Deaven LL, Majerus PW, Sadler JE.; ''Human thrombomodulin: complete cDNA sequence and chromosome localization of the gene.''; PubMed Europe PMC Scholia
  11. Bock SC, Wion KL, Vehar GA, Lawn RM.; ''Cloning and expression of the cDNA for human antithrombin III.''; PubMed Europe PMC Scholia
  12. Harpel PC, Lewin MF, Kaplan AP.; ''Distribution of plasma kallikrein between C-1 inactivator and alpha 2-macroglobulin in plasma utilizing a new assay for alpha 2-macroglobulin-kallikrein complexes.''; PubMed Europe PMC Scholia
  13. Foster D, Davie EW.; ''Characterization of a cDNA coding for human protein C.''; PubMed Europe PMC Scholia
  14. Yoshitake S, Schach BG, Foster DC, Davie EW, Kurachi K.; ''Nucleotide sequence of the gene for human factor IX (antihemophilic factor B).''; PubMed Europe PMC Scholia
  15. Meier HL, Pierce JV, Colman RW, Kaplan AP.; ''Activation and function of human Hageman factor. The role of high molecular weight kininogen and prekallikrein.''; PubMed Europe PMC Scholia
  16. Roehrig S, Straub A, Pohlmann J, Lampe T, Pernerstorfer J, Schlemmer KH, Reinemer P, Perzborn E.; ''Discovery of the novel antithrombotic agent 5-chloro-N-({(5S)-2-oxo-3- [4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene- 2-carboxamide (BAY 59-7939): an oral, direct factor Xa inhibitor.''; PubMed Europe PMC Scholia
  17. Sottrup-Jensen L, Stepanik TM, Kristensen T, Wierzbicki DM, Jones CM, Lønblad PB, Magnusson S, Petersen TE.; ''Primary structure of human alpha 2-macroglobulin. V. The complete structure.''; PubMed Europe PMC Scholia
  18. Suzuki K, Nishioka J, Kusumoto H, Hashimoto S.; ''Mechanism of inhibition of activated protein C by protein C inhibitor.''; PubMed Europe PMC Scholia
  19. Chiu AT, Mousa SA, Pease LJ, Roscoe WA, Bozarth JM, Reilly TM, Smith RD, Timmermans PB.; ''Inhibition of the thrombin-platelet reactions by DuP 714.''; PubMed Europe PMC Scholia
  20. Lin Y, Harris RB, Yan W, McCrae KR, Zhang H, Colman RW.; ''High molecular weight kininogen peptides inhibit the formation of kallikrein on endothelial cell surfaces and subsequent urokinase-dependent plasmin formation.''; PubMed Europe PMC Scholia
  21. Ruf W, Kalnik MW, Lund-Hansen T, Edgington TS.; ''Characterization of factor VII association with tissue factor in solution. High and low affinity calcium binding sites in factor VII contribute to functionally distinct interactions.''; PubMed Europe PMC Scholia
  22. Orfeo T, Brufatto N, Nesheim ME, Xu H, Butenas S, Mann KG.; ''The factor V activation paradox.''; PubMed Europe PMC Scholia
  23. Chung DW, Fujikawa K, McMullen BA, Davie EW.; ''Human plasma prekallikrein, a zymogen to a serine protease that contains four tandem repeats.''; PubMed Europe PMC Scholia
  24. Foster DC, Sprecher CA, Holly RD, Gambee JE, Walker KM, Kumar AA.; ''Endoproteolytic processing of the dibasic cleavage site in the human protein C precursor in transfected mammalian cells: effects of sequence alterations on efficiency of cleavage.''; PubMed Europe PMC Scholia
  25. Gilbert GE, Arena AA.; ''Activation of the factor VIIIa-factor IXa enzyme complex of blood coagulation by membranes containing phosphatidyl-L-serine.''; PubMed Europe PMC Scholia
  26. Gustafsson D, Antonsson T, Bylund R, Eriksson U, Gyzander E, Nilsson I, Elg M, Mattsson C, Deinum J, Pehrsson S, Karlsson O, Nilsson A, Sörensen H.; ''Effects of melagatran, a new low-molecular-weight thrombin inhibitor, on thrombin and fibrinolytic enzymes.''; PubMed Europe PMC Scholia
  27. Bach R, Gentry R, Nemerson Y.; ''Factor VII binding to tissue factor in reconstituted phospholipid vesicles: induction of cooperativity by phosphatidylserine.''; PubMed Europe PMC Scholia
  28. Rao LV, Pendurthi UR.; ''Regulation of tissue factor coagulant activity on cell surfaces.''; PubMed Europe PMC Scholia
  29. Lottspeich F, Kellermann J, Henschen A, Foertsch B, Müller-Esterl W.; ''The amino acid sequence of the light chain of human high-molecular-mass kininogen.''; PubMed Europe PMC Scholia
  30. Pipe SW, Saenko EL, Eickhorst AN, Kemball-Cook G, Kaufman RJ.; ''Hemophilia A mutations associated with 1-stage/2-stage activity discrepancy disrupt protein-protein interactions within the triplicated A domains of thrombin-activated factor VIIIa.''; PubMed Europe PMC Scholia
  31. Hursting MJ, Alford KL, Becker JC, Brooks RL, Joffrion JL, Knappenberger GD, Kogan PW, Kogan TP, McKinney AA, Schwarz RP.; ''Novastan (brand of argatroban): a small-molecule, direct thrombin inhibitor.''; PubMed Europe PMC Scholia
  32. Saenko EL, Scandella D, Yakhyaev AV, Greco NJ.; ''Activation of factor VIII by thrombin increases its affinity for binding to synthetic phospholipid membranes and activated platelets.''; PubMed Europe PMC Scholia
  33. Ivanov I, Matafonov A, Sun MF, Mohammed BM, Cheng Q, Dickeson SK, Kundu S, Verhamme IM, Gruber A, McCrae K, Gailani D.; ''A mechanism for hereditary angioedema with normal C1 inhibitor: an inhibitory regulatory role for the factor XII heavy chain.''; PubMed Europe PMC Scholia
  34. Kaufman RJ, Pipe SW, Tagliavacca L, Swaroop M, Moussalli M.; ''Biosynthesis, assembly and secretion of coagulation factor VIII.''; PubMed Europe PMC Scholia
  35. Joseph K, Ghebrehiwet B, Peerschke EI, Reid KB, Kaplan AP.; ''Identification of the zinc-dependent endothelial cell binding protein for high molecular weight kininogen and factor XII: identity with the receptor that binds to the globular "heads" of C1q (gC1q-R).''; PubMed Europe PMC Scholia
  36. Pixley RA, Schapira M, Colman RW.; ''The regulation of human factor XIIa by plasma proteinase inhibitors.''; PubMed Europe PMC Scholia
  37. DiScipio RG, Davie EW.; ''Characterization of protein S, a gamma-carboxyglutamic acid containing protein from bovine and human plasma.''; PubMed Europe PMC Scholia
  38. Bouma BN, Griffin JH.; ''Human blood coagulation factor XI. Purification, properties, and mechanism of activation by activated factor XII.''; PubMed Europe PMC Scholia
  39. Esmon CT.; ''The roles of protein C and thrombomodulin in the regulation of blood coagulation.''; PubMed Europe PMC Scholia
  40. Butenas S, Mann KG.; ''Kinetics of human factor VII activation.''; PubMed Europe PMC Scholia
  41. Lawson JH, Mann KG.; ''Cooperative activation of human factor IX by the human extrinsic pathway of blood coagulation.''; PubMed Europe PMC Scholia
  42. Degen SJ, Davie EW.; ''Nucleotide sequence of the gene for human prothrombin.''; PubMed Europe PMC Scholia
  43. Kerbiriou DM, Griffin JH.; ''Human high molecular weight kininogen. Studies of structure-function relationships and of proteolysis of the molecule occurring during contact activation of plasma.''; PubMed Europe PMC Scholia
  44. Ratnoff OD, Pensky J, Ogston D, Naff GB.; ''The inhibition of plasmin, plasma kallikrein, plasma permeability factor, and the C'1r subcomponent of the first component of complement by serum C'1 esterase inhibitor.''; PubMed Europe PMC Scholia
  45. Di Scipio RG, Hermodson MA, Yates SG, Davie EW.; ''A comparison of human prothrombin, factor IX (Christmas factor), factor X (Stuart factor), and protein S.''; PubMed Europe PMC Scholia
  46. Modderman PW, Admiraal LG, Sonnenberg A, von dem Borne AE.; ''Glycoproteins V and Ib-IX form a noncovalent complex in the platelet membrane.''; PubMed Europe PMC Scholia
  47. Baglia FA, Walsh PN.; ''Thrombin-mediated feedback activation of factor XI on the activated platelet surface is preferred over contact activation by factor XIIa or factor XIa.''; PubMed Europe PMC Scholia
  48. Simioni P, Tormene D, Tognin G, Gavasso S, Bulato C, Iacobelli NP, Finn JD, Spiezia L, Radu C, Arruda VR.; ''X-linked thrombophilia with a mutant factor IX (factor IX Padua).''; PubMed Europe PMC Scholia
  49. Mertens K, Cupers R, Van Wijngaarden A, Bertina RM.; ''Binding of human blood-coagulation Factors IXa and X to phospholipid membranes.''; PubMed Europe PMC Scholia
  50. Grover SP, Mackman N.; ''Tissue Factor: An Essential Mediator of Hemostasis and Trigger of Thrombosis.''; PubMed Europe PMC Scholia
  51. Shariat-Madar Z, Mahdi F, Schmaier AH.; ''Identification and characterization of prolylcarboxypeptidase as an endothelial cell prekallikrein activator.''; PubMed Europe PMC Scholia
  52. Oliver JA, Monroe DM, Roberts HR, Hoffman M.; ''Thrombin activates factor XI on activated platelets in the absence of factor XII.''; PubMed Europe PMC Scholia
  53. Mann KG, Kalafatis M.; ''Factor V: a combination of Dr Jekyll and Mr Hyde.''; PubMed Europe PMC Scholia
  54. Mohammed BM, Matafonov A, Ivanov I, Sun MF, Cheng Q, Dickeson SK, Li C, Sun D, Verhamme IM, Emsley J, Gailani D.; ''An update on factor XI structure and function.''; PubMed Europe PMC Scholia
  55. Kurosawa S, Stearns-Kurosawa DJ, Hidari N, Esmon CT.; ''Identification of functional endothelial protein C receptor in human plasma.''; PubMed Europe PMC Scholia
  56. Ichinose A, Hendrickson LE, Fujikawa K, Davie EW.; ''Amino acid sequence of the a subunit of human factor XIII.''; PubMed Europe PMC Scholia
  57. Banner DW, D'Arcy A, Chène C, Winkler FK, Guha A, Konigsberg WH, Nemerson Y, Kirchhofer D.; ''The crystal structure of the complex of blood coagulation factor VIIa with soluble tissue factor.''; PubMed Europe PMC Scholia
  58. Rawala-Sheikh R, Ahmad SS, Ashby B, Walsh PN.; ''Kinetics of coagulation factor X activation by platelet-bound factor IXa.''; PubMed Europe PMC Scholia
  59. Regan LM, Lamphear BJ, Huggins CF, Walker FJ, Fay PJ.; ''Factor IXa protects factor VIIIa from activated protein C. Factor IXa inhibits activated protein C-catalyzed cleavage of factor VIIIa at Arg562.''; PubMed Europe PMC Scholia
  60. Lollar P, Hill-Eubanks DC, Parker CG.; ''Association of the factor VIII light chain with von Willebrand factor.''; PubMed Europe PMC Scholia
  61. McMullen BA, Fujikawa K, Davie EW.; ''Location of the disulfide bonds in human coagulation factor XI: the presence of tandem apple domains.''; PubMed Europe PMC Scholia
  62. Mann KG, Jenny RJ, Krishnaswamy S.; ''Cofactor proteins in the assembly and expression of blood clotting enzyme complexes.''; PubMed Europe PMC Scholia
  63. Ghebrehiwet B, Lim BL, Peerschke EI, Willis AC, Reid KB.; ''Isolation, cDNA cloning, and overexpression of a 33-kD cell surface glycoprotein that binds to the globular "heads" of C1q.''; PubMed Europe PMC Scholia
  64. Eaton D, Rodriguez H, Vehar GA.; ''Proteolytic processing of human factor VIII. Correlation of specific cleavages by thrombin, factor Xa, and activated protein C with activation and inactivation of factor VIII coagulant activity.''; PubMed Europe PMC Scholia
  65. Kaufman RJ, Wasley LC, Dorner AJ.; ''Synthesis, processing, and secretion of recombinant human factor VIII expressed in mammalian cells.''; PubMed Europe PMC Scholia
  66. McMullen BA, Fujikawa K, Kisiel W, Sasagawa T, Howald WN, Kwa EY, Weinstein B.; ''Complete amino acid sequence of the light chain of human blood coagulation factor X: evidence for identification of residue 63 as beta-hydroxyaspartic acid.''; PubMed Europe PMC Scholia
  67. Turner NA, Moake JL.; ''Factor VIII Is Synthesized in Human Endothelial Cells, Packaged in Weibel-Palade Bodies and Secreted Bound to ULVWF Strings.''; PubMed Europe PMC Scholia
  68. Vadivel K, Bajaj SP.; ''Structural biology of factor VIIa/tissue factor initiated coagulation.''; PubMed Europe PMC Scholia
  69. Fujikawa K, McMullen BA.; ''Amino acid sequence of human beta-factor XIIa.''; PubMed Europe PMC Scholia
  70. Zhang P, Huang W, Wang L, Bao L, Jia ZJ, Bauer SM, Goldman EA, Probst GD, Song Y, Su T, Fan J, Wu Y, Li W, Woolfrey J, Sinha U, Wong PW, Edwards ST, Arfsten AE, Clizbe LA, Kanter J, Pandey A, Park G, Hutchaleelaha A, Lambing JL, Hollenbach SJ, Scarborough RM, Zhu BY.; ''Discovery of betrixaban (PRT054021), N-(5-chloropyridin-2-yl)-2-(4-(N,N-dimethylcarbamimidoyl)benzamido)-5-methoxybenzamide, a highly potent, selective, and orally efficacious factor Xa inhibitor.''; PubMed Europe PMC Scholia
  71. Odya CE, Marinkovic DV, Hammon KJ, Stewart TA, Erdös EG.; ''Purification and properties of prolylcarboxypeptidase (angiotensinase C) from human kidney.''; PubMed Europe PMC Scholia
  72. Vehar GA, Keyt B, Eaton D, Rodriguez H, O'Brien DP, Rotblat F, Oppermann H, Keck R, Wood WI, Harkins RN, Tuddenham EG, Lawn RM, Capon DJ.; ''Structure of human factor VIII.''; PubMed Europe PMC Scholia
  73. Wilcox JN, Smith KM, Schwartz SM, Gordon D.; ''Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque.''; PubMed Europe PMC Scholia
  74. Bock SC, Skriver K, Nielsen E, Thøgersen HC, Wiman B, Donaldson VH, Eddy RL, Marrinan J, Radziejewska E, Huber R.; ''Human C1 inhibitor: primary structure, cDNA cloning, and chromosomal localization.''; PubMed Europe PMC Scholia
  75. Walz DA, Hewett-Emmett D, Seegers WH.; ''Amino acid sequence of human prothrombin fragments 1 and 2.''; PubMed Europe PMC Scholia
  76. Geng Y, Verhamme IM, Messer A, Sun MF, Smith SB, Bajaj SP, Gailani D.; ''A sequential mechanism for exosite-mediated factor IX activation by factor XIa.''; PubMed Europe PMC Scholia
  77. Vlot AJ, Koppelman SJ, van den Berg MH, Bouma BN, Sixma JJ.; ''The affinity and stoichiometry of binding of human factor VIII to von Willebrand factor.''; PubMed Europe PMC Scholia
  78. McMullen BA, Fujikawa K.; ''Amino acid sequence of the heavy chain of human alpha-factor XIIa (activated Hageman factor).''; PubMed Europe PMC Scholia
  79. Fay PJ, Haidaris PJ, Smudzin TM.; ''Human factor VIIIa subunit structure. Reconstruction of factor VIIIa from the isolated A1/A3-C1-C2 dimer and A2 subunit.''; PubMed Europe PMC Scholia
  80. Motta G, Rojkjaer R, Hasan AA, Cines DB, Schmaier AH.; ''High molecular weight kininogen regulates prekallikrein assembly and activation on endothelial cells: a novel mechanism for contact activation.''; PubMed Europe PMC Scholia
  81. Hill-Eubanks DC, Parker CG, Lollar P.; ''Differential proteolytic activation of factor VIII-von Willebrand factor complex by thrombin.''; PubMed Europe PMC Scholia
  82. Komiyama Y, Pedersen AH, Kisiel W.; ''Proteolytic activation of human factors IX and X by recombinant human factor VIIa: effects of calcium, phospholipids, and tissue factor.''; PubMed Europe PMC Scholia
  83. Kane WH, Davie EW.; ''Cloning of a cDNA coding for human factor V, a blood coagulation factor homologous to factor VIII and ceruloplasmin.''; PubMed Europe PMC Scholia
  84. Kaufman RJ, Wasley LC, Furie BC, Furie B, Shoemaker CB.; ''Expression, purification, and characterization of recombinant gamma-carboxylated factor IX synthesized in Chinese hamster ovary cells.''; PubMed Europe PMC Scholia
  85. Laudano AP, Doolittle RF.; ''Studies on synthetic peptides that bind to fibrinogen and prevent fibrin polymerization. Structural requirements, number of binding sites, and species differences.''; PubMed Europe PMC Scholia
  86. Ichinose A, McMullen BA, Fujikawa K, Davie EW.; ''Amino acid sequence of the b subunit of human factor XIII, a protein composed of ten repetitive segments.''; PubMed Europe PMC Scholia
  87. Schreiber AD, Kaplan AP, Austen KF.; ''Inhibition by C1INH of Hagemann factor fragment activation of coagulation, fibrinolysis, and kinin generation.''; PubMed Europe PMC Scholia
  88. Celie PH, Van Stempvoort G, Jorieux S, Mazurier C, Van Mourik JA, Mertens K.; ''Substitution of Arg527 and Arg531 in factor VIII associated with mild haemophilia A: characterization in terms of subunit interaction and cofactor function.''; PubMed Europe PMC Scholia
  89. Riewald M, Petrovan RJ, Donner A, Mueller BM, Ruf W.; ''Activation of endothelial cell protease activated receptor 1 by the protein C pathway.''; PubMed Europe PMC Scholia
  90. Bhanwra S, Ahluwalia K.; ''The new factor Xa inhibitor: Apixaban.''; PubMed Europe PMC Scholia
  91. Sorensen AB, Madsen JJ, Frimurer TM, Overgaard MT, Gandhi PS, Persson E, Olsen OH.; ''Allostery in Coagulation Factor VIIa Revealed by Ensemble Refinement of Crystallographic Structures.''; PubMed Europe PMC Scholia
  92. Prandini MH, Reboul A, Colomb MG.; ''Biosynthesis of complement C1 inhibitor by Hep G2 cells. Reactivity of different glycosylated forms of the inhibitor with C1s.''; PubMed Europe PMC Scholia
  93. Leytus SP, Chung DW, Kisiel W, Kurachi K, Davie EW.; ''Characterization of a cDNA coding for human factor X.''; PubMed Europe PMC Scholia
  94. de Maat S, Clark CC, Boertien M, Parr N, Sanrattana W, Hofman ZLM, Maas C.; ''Factor XII truncation accelerates activation in solution.''; PubMed Europe PMC Scholia
  95. Griffin JH, Fernández JA, Gale AJ, Mosnier LO.; ''Activated protein C.''; PubMed Europe PMC Scholia
  96. Gladwell TD.; ''Bivalirudin: a direct thrombin inhibitor.''; PubMed Europe PMC Scholia
  97. McMullen BA, Fujikawa K, Kisiel W.; ''The occurrence of beta-hydroxyaspartic acid in the vitamin K-dependent blood coagulation zymogens.''; PubMed Europe PMC Scholia
  98. Kurachi K, Davie EW.; ''Activation of human factor XI (plasma thromboplastin antecedent) by factor XIIa (activated Hageman factor).''; PubMed Europe PMC Scholia
  99. Naito K, Fujikawa K.; ''Activation of human blood coagulation factor XI independent of factor XII. Factor XI is activated by thrombin and factor XIa in the presence of negatively charged surfaces.''; PubMed Europe PMC Scholia
  100. Minor C, Tellor KB, Armbruster AL.; ''Edoxaban, a Novel Oral Factor Xa Inhibitor.''; PubMed Europe PMC Scholia
  101. Lenting PJ, van Mourik JA, Mertens K.; ''The life cycle of coagulation factor VIII in view of its structure and function.''; PubMed Europe PMC Scholia
  102. Shrimpton CN, Borthakur G, Larrucea S, Cruz MA, Dong JF, López JA.; ''Localization of the adhesion receptor glycoprotein Ib-IX-V complex to lipid rafts is required for platelet adhesion and activation.''; PubMed Europe PMC Scholia
  103. Mushunje A, Zhou A, Carrell RW, Huntington JA.; ''Heparin-induced substrate behavior of antithrombin Cambridge II.''; PubMed Europe PMC Scholia
  104. Graetz TJ, Tellor BR, Smith JR, Avidan MS.; ''Desirudin: a review of the pharmacology and clinical application for the prevention of deep vein thrombosis.''; PubMed Europe PMC Scholia
  105. Stangier J, Rathgen K, Stähle H, Gansser D, Roth W.; ''The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects.''; PubMed Europe PMC Scholia
  106. Hakeos WH, Miao H, Sirachainan N, Kemball-Cook G, Saenko EL, Kaufman RJ, Pipe SW.; ''Hemophilia A mutations within the factor VIII A2-A3 subunit interface destabilize factor VIIIa and cause one-stage/two-stage activity discrepancy.''; PubMed Europe PMC Scholia
  107. Kane WH, Ichinose A, Hagen FS, Davie EW.; ''Cloning of cDNAs coding for the heavy chain region and connecting region of human factor V, a blood coagulation factor with four types of internal repeats.''; PubMed Europe PMC Scholia
  108. Mahdi F, Shariat-Madar Z, Schmaier AH.; ''The relative priority of prekallikrein and factors XI/XIa assembly on cultured endothelial cells.''; PubMed Europe PMC Scholia
  109. Gailani D, Broze GJ.; ''Factor XII-independent activation of factor XI in plasma: effects of sulfatides on tissue factor-induced coagulation.''; PubMed Europe PMC Scholia
  110. Moreira CR, Schmaier AH, Mahdi F, da Motta G, Nader HB, Shariat-Madar Z.; ''Identification of prolylcarboxypeptidase as the cell matrix-associated prekallikrein activator.''; PubMed Europe PMC Scholia
  111. Thim L, Bjoern S, Christensen M, Nicolaisen EM, Lund-Hansen T, Pedersen AH, Hedner U.; ''Amino acid sequence and posttranslational modifications of human factor VIIa from plasma and transfected baby hamster kidney cells.''; PubMed Europe PMC Scholia
  112. Baglia FA, Badellino KO, Li CQ, Lopez JA, Walsh PN.; ''Factor XI binding to the platelet glycoprotein Ib-IX-V complex promotes factor XI activation by thrombin.''; PubMed Europe PMC Scholia
  113. Bondarenko M, Curti C, Montana M, Rathelot P, Vanelle P.; ''Efficacy and toxicity of factor Xa inhibitors.''; PubMed Europe PMC Scholia
  114. Joseph K, Shibayama Y, Ghebrehiwet B, Kaplan AP.; ''Factor XII-dependent contact activation on endothelial cells and binding proteins gC1qR and cytokeratin 1.''; PubMed Europe PMC Scholia
  115. Titani K, Kumar S, Takio K, Ericsson LH, Wade RD, Ashida K, Walsh KA, Chopek MW, Sadler JE, Fujikawa K.; ''Amino acid sequence of human von Willebrand factor.''; PubMed Europe PMC Scholia
  116. Silverberg M, Dunn JT, Garen L, Kaplan AP.; ''Autoactivation of human Hageman factor. Demonstration utilizing a synthetic substrate.''; PubMed Europe PMC Scholia
  117. Li W, Huntington JA.; ''Crystal structures of protease nexin-1 in complex with heparin and thrombin suggest a 2-step recognition mechanism.''; PubMed Europe PMC Scholia
  118. Fay PJ, Smudzin TM.; ''Characterization of the interaction between the A2 subunit and A1/A3-C1-C2 dimer in human factor VIIIa.''; PubMed Europe PMC Scholia
  119. Mahdi F, Madar ZS, Figueroa CD, Schmaier AH.; ''Factor XII interacts with the multiprotein assembly of urokinase plasminogen activator receptor, gC1qR, and cytokeratin 1 on endothelial cell membranes.''; PubMed Europe PMC Scholia
  120. Griffin JH, Cochrane CG.; ''Mechanisms for the involvement of high molecular weight kininogen in surface-dependent reactions of Hageman factor.''; PubMed Europe PMC Scholia
  121. Taylor FB, Peer GT, Lockhart MS, Ferrell G, Esmon CT.; ''Endothelial cell protein C receptor plays an important role in protein C activation in vivo.''; PubMed Europe PMC Scholia
  122. Broze GJ, Girard TJ, Novotny WF.; ''Regulation of coagulation by a multivalent Kunitz-type inhibitor.''; PubMed Europe PMC Scholia
  123. Tan F, Morris PW, Skidgel RA, Erdös EG.; ''Sequencing and cloning of human prolylcarboxypeptidase (angiotensinase C). Similarity to both serine carboxypeptidase and prolylendopeptidase families.''; PubMed Europe PMC Scholia
  124. Davie EW, Fujikawa K, Kisiel W.; ''The coagulation cascade: initiation, maintenance, and regulation.''; PubMed Europe PMC Scholia
  125. Rapaport SI, Rao LV.; ''The tissue factor pathway: how it has become a "prima ballerina".''; PubMed Europe PMC Scholia
  126. Church FC, Noyes CM, Griffith MJ.; ''Inhibition of chymotrypsin by heparin cofactor II.''; PubMed Europe PMC Scholia
  127. Lewis SD, Janus TJ, Lorand L, Shafer JA.; ''Regulation of formation of factor XIIIa by its fibrin substrates.''; PubMed Europe PMC Scholia
  128. Weitz JI, Hudoba M, Massel D, Maraganore J, Hirsh J.; ''Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors.''; PubMed Europe PMC Scholia
  129. Pan S, Iannotti MJ, Sifers RN.; ''Analysis of serpin secretion, misfolding, and surveillance in the endoplasmic reticulum.''; PubMed Europe PMC Scholia
  130. Nemerson Y.; ''Tissue factor and hemostasis.''; PubMed Europe PMC Scholia
  131. Yegneswaran S, Smirnov MD, Safa O, Esmon NL, Esmon CT, Johnson AE.; ''Relocating the active site of activated protein C eliminates the need for its protein S cofactor. A fluorescence resonance energy transfer study.''; PubMed Europe PMC Scholia
  132. Pipe SW, Eickhorst AN, McKinley SH, Saenko EL, Kaufman RJ.; ''Mild hemophilia A caused by increased rate of factor VIII A2 subunit dissociation: evidence for nonproteolytic inactivation of factor VIIIa in vivo.''; PubMed Europe PMC Scholia
  133. Rosing J, Hoekema L, Nicolaes GA, Thomassen MC, Hemker HC, Varadi K, Schwarz HP, Tans G.; ''Effects of protein S and factor Xa on peptide bond cleavages during inactivation of factor Va and factor VaR506Q by activated protein C.''; PubMed Europe PMC Scholia
  134. Di Scipio RG, Hermodson MA, Davie EW.; ''Activation of human factor X (Stuart factor) by a protease from Russell's viper venom.''; PubMed Europe PMC Scholia
  135. Hoeben RC, Fallaux FJ, Cramer SJ, van den Wollenberg DJ, van Ormondt H, Briët E, van der Eb AJ.; ''Expression of the blood-clotting factor-VIII cDNA is repressed by a transcriptional silencer located in its coding region.''; PubMed Europe PMC Scholia
  136. Gilbert GE, Furie BC, Furie B.; ''Binding of human factor VIII to phospholipid vesicles.''; PubMed Europe PMC Scholia
  137. Schmaier AH.; ''The physiologic basis of assembly and activation of the plasma kallikrein/kinin system.''; PubMed Europe PMC Scholia
  138. Kellermann J, Lottspeich F, Henschen A, Müller-Esterl W.; ''Completion of the primary structure of human high-molecular-mass kininogen. The amino acid sequence of the entire heavy chain and evidence for its evolution by gene triplication.''; PubMed Europe PMC Scholia
  139. Wienen W, Stassen JM, Priepke H, Ries UJ, Hauel N.; ''In-vitro profile and ex-vivo anticoagulant activity of the direct thrombin inhibitor dabigatran and its orally active prodrug, dabigatran etexilate.''; PubMed Europe PMC Scholia
  140. Butkowski RJ, Elion J, Downing MR, Mann KG.; ''Primary structure of human prethrombin 2 and alpha-thrombin.''; PubMed Europe PMC Scholia
  141. Shariat-Madar Z, Mahdi F, Schmaier AH.; ''Recombinant prolylcarboxypeptidase activates plasma prekallikrein.''; PubMed Europe PMC Scholia
  142. Greengard JS, Heeb MJ, Ersdal E, Walsh PN, Griffin JH.; ''Binding of coagulation factor XI to washed human platelets.''; PubMed Europe PMC Scholia
  143. Holmer E, Söderberg K, Bergqvist D, Lindahl U.; ''Heparin and its low molecular weight derivatives: anticoagulant and antithrombotic properties.''; PubMed Europe PMC Scholia
  144. Kurosawa S, Esmon CT, Stearns-Kurosawa DJ.; ''The soluble endothelial protein C receptor binds to activated neutrophils: involvement of proteinase-3 and CD11b/CD18.''; PubMed Europe PMC Scholia
  145. Kurachi K, Kurachi S, Furukawa M, Yao SN.; ''Biology of factor IX.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
123618view08:20, 7 August 2022EgonwModified title
114744view16:23, 25 January 2021ReactomeTeamReactome version 75
113188view11:25, 2 November 2020ReactomeTeamReactome version 74
112416view15:35, 9 October 2020ReactomeTeamReactome version 73
101320view11:21, 1 November 2018ReactomeTeamreactome version 66
100857view20:53, 31 October 2018ReactomeTeamreactome version 65
100398view19:27, 31 October 2018ReactomeTeamreactome version 64
99946view16:11, 31 October 2018ReactomeTeamreactome version 63
99502view14:44, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
94025view13:52, 16 August 2017ReactomeTeamreactome version 61
93645view11:29, 9 August 2017ReactomeTeamreactome version 61
87449view13:55, 22 July 2016MkutmonOntology Term : 'coagulation cascade pathway' added !
86761view09:25, 11 July 2016ReactomeTeamreactome version 56
83143view10:09, 18 November 2015ReactomeTeamVersion54
81490view13:01, 21 August 2015ReactomeTeamVersion53
76965view08:24, 17 July 2014ReactomeTeamFixed remaining interactions
76670view12:03, 16 July 2014ReactomeTeamFixed remaining interactions
75999view10:05, 11 June 2014ReactomeTeamRe-fixing comment source
75702view11:04, 10 June 2014ReactomeTeamReactome 48 Update
75538view19:27, 9 June 2014MaintBotchanged description source
75512view12:25, 5 June 2014AnweshaUpdated in Reactome48
75058view13:56, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74702view08:46, 30 April 2014ReactomeTeamReactome46
73650view00:25, 12 February 2014AriuttaRemoved GroupRef="group_comp_1316" because there is no Group with GroupId="group_comp_1316"
73634view20:28, 10 February 2014KhanspersReverted to version '20:24, 8 February 2014' by Khanspers
73633view20:24, 10 February 2014Khanspersremoved cell shape
73632view20:22, 10 February 2014Khanspersremoved all groups to possibly resolve crash
73624view20:24, 8 February 2014MaintBotTrying out new gpml conversion to resolve crash of new pvjs viewer
69011view17:46, 8 July 2013MaintBotUpdated to 2013 gpml schema
42041view21:52, 4 March 2011MaintBotAutomatic update
39844view05:52, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
10xCbxE-F2ProteinP00734 (Uniprot-SwissProt)
10xCbxE-F7ProteinP08709 (Uniprot-SwissProt)
11xCbxE-3D-F10ProteinP00742 (Uniprot-SwissProt)
11xCbxE-3D-F9ProteinP00740 (Uniprot-SwissProt)
11xCbxE-PROS1ProteinP07225 (Uniprot-SwissProt)
12xCbxE-3D-F9ProteinP00740 (Uniprot-SwissProt)
8xCbxE-3D-PROCProteinP04070 (Uniprot-SwissProt)
A2M ProteinP01023 (Uniprot-SwissProt)
Activated thrombin ComplexREACT_3298 (Reactome)
Alpha2-macroglobulinComplexREACT_3449 (Reactome)
BradykininProteinP01042 (Uniprot-SwissProt)
C1QBP ProteinQ07021 (Uniprot-SwissProt)
C1q binding protein tetramerComplexREACT_2937 (Reactome)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
F13B ProteinP05160 (Uniprot-SwissProt)
F13BProteinP05160 (Uniprot-SwissProt)
FGA ProteinP02671 (Uniprot-SwissProt)
FGAProteinP02671 (Uniprot-SwissProt)
FGB ProteinP02675 (Uniprot-SwissProt)
FGBProteinP02675 (Uniprot-SwissProt)
FGG ProteinP02679 (Uniprot-SwissProt)
FibrinogenComplexREACT_4095 (Reactome)
  • Fibrinogen is a hexamer, containing two fibrinogen alpha chains, two fibrinogen beta chains, and two fibrinogen gamma chains, held together by disulfide bonds.
  • Fibrinogen is a hexamer, containing two fibrinogen alpha chains, two fibrinogen beta chains, and two fibrinogen gamma chains, held together by disulfide bonds.
GP1BA ProteinP07359 (Uniprot-SwissProt)
GP1BB ProteinP13224 (Uniprot-SwissProt)
GP5 ProteinP40197 (Uniprot-SwissProt)
GP9 ProteinP14770 (Uniprot-SwissProt)
GPIb-IX-V complexComplexREACT_3007 (Reactome)
HeparinREACT_4737 (Reactome)
KLKB1ProteinP03952 (Uniprot-SwissProt)
KNG C1q binding protein tetramerComplexREACT_4804 (Reactome)
KNG1ProteinP01042 (Uniprot-SwissProt)
NH4+MetaboliteCHEBI:28938 (ChEBI)
PRCP ProteinP42785 (Uniprot-SwissProt)
PROCProteinP04070 (Uniprot-SwissProt)
PalmC-F3 ProteinP13726 (Uniprot-SwissProt)
PalmC-F3ProteinP13726 (Uniprot-SwissProt)
Plasma kallikreinComplexREACT_4124 (Reactome)
Platelet Factor 4REACT_12205 (Reactome)
SERPINC1 ProteinP01008 (Uniprot-SwissProt)
SERPINC1ProteinP01008 (Uniprot-SwissProt)
SERPING1 ProteinP05155 (Uniprot-SwissProt)
SERPING1ProteinP05155 (Uniprot-SwissProt)
TF F7ComplexREACT_4908 (Reactome)
TF F7aComplexREACT_4532 (Reactome)
TFPI

TF F7a

factor Xa		ComplexREACT_2685 (Reactome)
TFPI ProteinP10646 (Uniprot-SwissProt)
TFPIProteinP10646 (Uniprot-SwissProt)
THBDProteinP07204 (Uniprot-SwissProt)
VWFProteinP04275 (Uniprot-SwissProt)
Va Xa complex ComplexREACT_5441 (Reactome)
Zn2+MetaboliteCHEBI:29105 (ChEBI)
activated kininogen C1q binding protein tetramerComplexREACT_3121 (Reactome)
activated protein CComplexREACT_2599 (Reactome)
activated protein CComplexREACT_5044 (Reactome)
activated thrombin thrombomodulinComplexREACT_5904 (Reactome)
antithrombin III heparinComplexREACT_2653 (Reactome)
factor IX activation peptideProteinP00740 (Uniprot-SwissProt)
factor IXa heavy chain ProteinP00740 (Uniprot-SwissProt)
factor IXaComplexREACT_3075 (Reactome)
factor V activation peptideProteinP12259 (Uniprot-SwissProt)
factor VIII von Willebrand factor multimerComplexREACT_3248 (Reactome)
factor VIII heavy chain ProteinP00451 (Uniprot-SwissProt)
factor VIII light chain ProteinP00451 (Uniprot-SwissProt)
factor VIIIComplexREACT_4493 (Reactome)
factor VIIIa factor IXaComplexREACT_3217 (Reactome)
factor VIIIa A1 polypeptide ProteinP00451 (Uniprot-SwissProt)
factor VIIIa A2 polypeptide ProteinP00451 (Uniprot-SwissProt)
factor VIIIa A3 C1 C2 polypeptide ProteinP00451 (Uniprot-SwissProt)
factor VIIIa B A3 acidic polypeptideProteinP00451 (Uniprot-SwissProt)
factor VIIIaComplexREACT_4190 (Reactome)
factor VIIa heavy chain ProteinP08709 (Uniprot-SwissProt)
factor VIIaComplexREACT_2419 (Reactome)
factor VProteinP12259 (Uniprot-SwissProt)
factor Va heavy chain ProteinP12259 (Uniprot-SwissProt)
factor Va light chain ProteinP12259 (Uniprot-SwissProt)
factor VaComplexREACT_2497 (Reactome)
factor ViComplexREACT_4020 (Reactome)
factor X activation peptideProteinP00742 (Uniprot-SwissProt)
factor X heavy chain ProteinP00742 (Uniprot-SwissProt)
factor XI GPIb-IX-V complexComplexREACT_5726 (Reactome)
factor XI monomer ProteinP03951 (Uniprot-SwissProt)
factor XIII A chain ProteinP00488 (Uniprot-SwissProt)
factor XIII A chain activation peptideProteinP00488 (Uniprot-SwissProt)
factor XIII cleaved tetramerComplexREACT_2648 (Reactome)
factor XIIIComplexREACT_4285 (Reactome)
factor XIIIa A chain ProteinP00488 (Uniprot-SwissProt)
factor XIIIaComplexREACT_4387 (Reactome)
factor XIIProteinP00748 (Uniprot-SwissProt)
factor XIIa C1InhComplexREACT_2283 (Reactome)
factor XIIa heavy chain ProteinP00748 (Uniprot-SwissProt)
factor XIIa light chain ProteinP00748 (Uniprot-SwissProt)
factor XIIaComplexREACT_4236 (Reactome)
factor XIComplexREACT_4915 (Reactome)
factor XIa

GPIb GPIX

GPV complex		ComplexREACT_4765 (Reactome)
factor XIa heavy chain ProteinP03951 (Uniprot-SwissProt)
factor XIa light chain ProteinP03951 (Uniprot-SwissProt)
factor XComplexREACT_3749 (Reactome)
factor Xa heavy chain ProteinP00742 (Uniprot-SwissProt)
factor XaComplexREACT_3099 (Reactome)
factor XaComplexREACT_5349 (Reactome)
fibrin monomerComplexREACT_5594 (Reactome)
  • Fibrin is a hexamer of two fibrinogen alpha chains, two fibrinogen beta chains, and two fibrinogen gamma chains, held together by disulfide bonds. It is formed in vivo by the thrombin-catalyzed removal of amino terminal fibinopeptides from the A alpha and B beta chains of fibrinogen. This fibrin hexamer ("fibrin monomer") is the subunit that multimerizes to form a fibrin clot ("fibrin multimer").
  • Fibrin is a hexamer of two fibrinogen alpha chains, two fibrinogen beta chains, and two fibrinogen gamma chains, held together by disulfide bonds. It is formed in vivo by the thrombin-catalyzed removal of amino terminal fibinopeptides from the A alpha and B beta chains of fibrinogen. This fibrin hexamer ("fibrin monomer") is the subunit that multimerizes to form a fibrin clot ("fibrin multimer").
fibrin multimer, crosslinkedREACT_2721 (Reactome)
fibrin multimerComplexREACT_4444 (Reactome)
  • The fibrin "monomers" formed by the action of thrombin on fibrinogen associate spontaneously into multimers. This association can follow several distinct pathways and may be able to form several types of higher-order structures. All of these possibilities are represented in Reactome as a fibrin trimer.
  • The fibrin "monomers" formed by the action of thrombin on fibrinogen associate spontaneously into multimers. This association can follow several distinct pathways and may be able to form several types of higher-order structures. All of these possibilities are represented in Reactome as a fibrin trimer.
kallikrein C1InhComplexREACT_5874 (Reactome)
kallikrein alpha2-macroglobulinComplexREACT_4115 (Reactome)
kallikrein

kininogen

C1q binding protein tetramer		ComplexREACT_4714 (Reactome)
prekallikrein

kininogen

C1q binding protein tetramer		ComplexREACT_3461 (Reactome)
prolylcarboxypeptidase dimerComplexREACT_5699 (Reactome)
protein CComplexREACT_4912 (Reactome)
sequestered tissue factorProteinP13726 (Uniprot-SwissProt)
thrombin

antithrombin III

heparin		ComplexREACT_2423 (Reactome)
thrombin

cleaved antithrombin III

heparin		ComplexREACT_2621 (Reactome)
thrombin cleaved antithrombin IIIComplexREACT_4175 (Reactome)
thrombin heavy chain ProteinP00734 (Uniprot-SwissProt)
thrombin light chain ProteinP00734 (Uniprot-SwissProt)
von Willibrand factor multimerComplexREACT_5706 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
10xCbxE-F2ArrowREACT_1097 (Reactome)
  • Membrane-bound factor Xa catalyzes the activation of small amounts of thrombin. The amino terminal portion of prothrombin is released as an activation peptide, which can be cleaved further by activated thrombin. Neither the full-length activation peptide nor its cleavage products have known functions.
  • Membrane-bound factor Xa catalyzes the activation of small amounts of thrombin. The amino terminal portion of prothrombin is released as an activation peptide, which can be cleaved further by activated thrombin. Neither the full-length activation peptide nor its cleavage products have known functions.
10xCbxE-F2ArrowREACT_1446 (Reactome)
  • The membrane-bound Va:Xa (prothrombinase) complex rapidly activates large amounts of thrombin.
  • The membrane-bound Va:Xa (prothrombinase) complex rapidly activates large amounts of thrombin.
10xCbxE-F2REACT_1097 (Reactome)
  • Membrane-bound factor Xa catalyzes the activation of small amounts of thrombin. The amino terminal portion of prothrombin is released as an activation peptide, which can be cleaved further by activated thrombin. Neither the full-length activation peptide nor its cleavage products have known functions.
  • Membrane-bound factor Xa catalyzes the activation of small amounts of thrombin. The amino terminal portion of prothrombin is released as an activation peptide, which can be cleaved further by activated thrombin. Neither the full-length activation peptide nor its cleavage products have known functions.
10xCbxE-F2REACT_1446 (Reactome)
  • The membrane-bound Va:Xa (prothrombinase) complex rapidly activates large amounts of thrombin.
  • The membrane-bound Va:Xa (prothrombinase) complex rapidly activates large amounts of thrombin.
10xCbxE-F7REACT_1669 (Reactome)
  • Tissue factor exposed at the endothelial cell surface forms a complex with factor VII from plasma.
  • Tissue factor exposed at the endothelial cell surface forms a complex with factor VII from plasma.
10xCbxE-F7factor VIIaArrowREACT_9 (Reactome)
  • Factor Xa catalyzes the activation of factor VII from plasma.
  • Factor Xa catalyzes the activation of factor VII from plasma.
11xCbxE-3D-F9REACT_158 (Reactome)
  • Factor VIIa, bound to tissue factor at the endothelial cell surface, catalyzes the formation of activated factor IX with high efficiency. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.)
  • Factor VIIa, bound to tissue factor at the endothelial cell surface, catalyzes the formation of activated factor IX with high efficiency. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.)
11xCbxE-3D-F9REACT_2073 (Reactome)
  • Factor XIa, bound to platelet glycoprotein (GP) Ib:IX:V on the platelet cell surface, catalyzes the formation of activated factor IX with high efficiency in a reaction that requires Ca++. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.)
  • Factor XIa, bound to platelet glycoprotein (GP) Ib:IX:V on the platelet cell surface, catalyzes the formation of activated factor IX with high efficiency in a reaction that requires Ca++. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.)
11xCbxE-PROS1ArrowREACT_1071 (Reactome)
  • Activated protein C cleaves peptide bonds in activated factor V (factor Va), converting it to an inactive form (factor Vi). The exact site(s) of cleavage are unknown. Protein S, on the endothelial cell surface, positively regulates this reaction. Although the mechanism of this regulation is unclear, the regulation is physiologically important, as people with reduced amounts of protein S, like people with reduced amounts of protein C, are susceptible to thromboembolism.
  • Activated protein C cleaves peptide bonds in activated factor V (factor Va), converting it to an inactive form (factor Vi). The exact site(s) of cleavage are unknown. Protein S, on the endothelial cell surface, positively regulates this reaction. Although the mechanism of this regulation is unclear, the regulation is physiologically important, as people with reduced amounts of protein S, like people with reduced amounts of protein C, are susceptible to thromboembolism.
Activated thrombin ArrowREACT_1097 (Reactome)
  • Membrane-bound factor Xa catalyzes the activation of small amounts of thrombin. The amino terminal portion of prothrombin is released as an activation peptide, which can be cleaved further by activated thrombin. Neither the full-length activation peptide nor its cleavage products have known functions.
  • Membrane-bound factor Xa catalyzes the activation of small amounts of thrombin. The amino terminal portion of prothrombin is released as an activation peptide, which can be cleaved further by activated thrombin. Neither the full-length activation peptide nor its cleavage products have known functions.
Activated thrombin ArrowREACT_1446 (Reactome)
  • The membrane-bound Va:Xa (prothrombinase) complex rapidly activates large amounts of thrombin.
  • The membrane-bound Va:Xa (prothrombinase) complex rapidly activates large amounts of thrombin.
Activated thrombin REACT_1822 (Reactome)
  • Activated thrombin binds to the antithrombin III:heparin complex on the cell surface.
  • Activated thrombin binds to the antithrombin III:heparin complex on the cell surface.
Activated thrombin REACT_1834 (Reactome)
  • Activated thrombin (factor IIa) binds to thrombomodulin at the external face of the plasma membrane, forming a thrombin:thrombomodulin complex. In this complexed form, the activity of thrombin towards protein C is greatly increased, and as thrombomodulin is particularly abundant on the surfaces of endothelial cells, this association plays a major role in restricting clot formation.
  • Activated thrombin (factor IIa) binds to thrombomodulin at the external face of the plasma membrane, forming a thrombin:thrombomodulin complex. In this complexed form, the activity of thrombin towards protein C is greatly increased, and as thrombomodulin is particularly abundant on the surfaces of endothelial cells, this association plays a major role in restricting clot formation.
Activated thrombin mim-catalysisREACT_1536 (Reactome)
  • Activated thrombin cleaves the A chains of factor XIII tetramers in a reaction stimulated by the presence of fibrin multimers. The amino terminal portions of the A chains are released as activation peptides, which have no known function. The resulting factor XIII tetramer remains catalytically inactive.
  • Activated thrombin cleaves the A chains of factor XIII tetramers in a reaction stimulated by the presence of fibrin multimers. The amino terminal portions of the A chains are released as activation peptides, which have no known function. The resulting factor XIII tetramer remains catalytically inactive.
Activated thrombin mim-catalysisREACT_1581 (Reactome)
  • Factor XI, bound to the cell surface, is converted to activated factor XI (factor XIa). In the body, this reaction occurs on the surfaces of activated platelets (Baglia et al. 2002). Small quantities of factor XI can be activated in a reaction catalyzed by factor XIIa, to initiate formation of a fibrin clot. However, the efficient activation of larger quantities of factor XI, needed to propagate the blood clotting process, appears to be mediated by thrombin (Baglia and Walsh 2000; Gailani and Broze 1993; Naito and Fujikawa 1991; Oliver et al. 1999; Monroe et al. 2002).
  • Factor XI, bound to the cell surface, is converted to activated factor XI (factor XIa). In the body, this reaction occurs on the surfaces of activated platelets (Baglia et al. 2002). Small quantities of factor XI can be activated in a reaction catalyzed by factor XIIa, to initiate formation of a fibrin clot. However, the efficient activation of larger quantities of factor XI, needed to propagate the blood clotting process, appears to be mediated by thrombin (Baglia and Walsh 2000; Gailani and Broze 1993; Naito and Fujikawa 1991; Oliver et al. 1999; Monroe et al. 2002).
Activated thrombin mim-catalysisREACT_214 (Reactome)
  • The alpha and beta chains of fibrinogen hexamer are cleaved by thrombin to generate fibrin monomer. The amino terminal regions of the cleaved alpha and beta chains are released (fibrinopeptides A and B respectively).
  • The alpha and beta chains of fibrinogen hexamer are cleaved by thrombin to generate fibrin monomer. The amino terminal regions of the cleaved alpha and beta chains are released (fibrinopeptides A and B respectively).
Activated thrombin mim-catalysisREACT_217 (Reactome)
  • Factor VIII complexed to von Willibrand factor in the blood is cleaved into several smaller polypeptides that remain associated. The acidic polypeptide on the aminoterminal side of the A3 domain of the light chain is released, however, and as this polypeptide mediates the association of factor VIII with von Willibrand factor, the activated factor VIII is released. While several proteases are capable of catalyzing these cleavages in vitro, only thrombin is active on factor VIII:von Willibrand factor complexes under physiological conditions (Eaton et al. 1986; Hill-Eubanks et al. 1989; Lollar et al. 1988; Pieters et al. 1989)
  • Factor VIII complexed to von Willibrand factor in the blood is cleaved into several smaller polypeptides that remain associated. The acidic polypeptide on the aminoterminal side of the A3 domain of the light chain is released, however, and as this polypeptide mediates the association of factor VIII with von Willibrand factor, the activated factor VIII is released. While several proteases are capable of catalyzing these cleavages in vitro, only thrombin is active on factor VIII:von Willibrand factor complexes under physiological conditions (Eaton et al. 1986; Hill-Eubanks et al. 1989; Lollar et al. 1988; Pieters et al. 1989)
Activated thrombin mim-catalysisREACT_708 (Reactome)
  • Activated thrombin (factor IIa) catalyzes the conversion of factor V to factor Va (activated factor V). The activation peptide released in this reaction has no known function.
  • Activated thrombin (factor IIa) catalyzes the conversion of factor V to factor Va (activated factor V). The activation peptide released in this reaction has no known function.
Alpha2-macroglobulinREACT_25 (Reactome)
  • Activated kallikrein binds to alpha2-macroglobulin (Sottrup-Jensen et al. 1984), forming a stable and enzymatically inactive complex. Under normal conditions in vivo, this reaction appears to be responsible for the inactivation of about 1/6 of activated kallikrein (with C1Inh responsible for the inactivation of about 5/6) (Harpel et al. 1985).
  • Activated kallikrein binds to alpha2-macroglobulin (Sottrup-Jensen et al. 1984), forming a stable and enzymatically inactive complex. Under normal conditions in vivo, this reaction appears to be responsible for the inactivation of about 1/6 of activated kallikrein (with C1Inh responsible for the inactivation of about 5/6) (Harpel et al. 1985).
BradykininArrowREACT_2004 (Reactome)
  • The cleavage of kininogen (HK, high molecular weight kininogen) yields activated kininogen and the vasoactive peptide bradykinin (Kerbirou and Griffin 1979; Lottspeich et al. 1985; Kellerman et al. 1986). In vivo, this reaction is catalyzed by activated kallikrein, takes places within the kallikrein:kininogen:C1q binding protein tetramer complex on the endothelial cell surface, and results in the release of kallikrein and bradykinin (Motta et al. 1998). The hormonal functions of bradykinin will be annotated in a future version of Reactome.
  • The cleavage of kininogen (HK, high molecular weight kininogen) yields activated kininogen and the vasoactive peptide bradykinin (Kerbirou and Griffin 1979; Lottspeich et al. 1985; Kellerman et al. 1986). In vivo, this reaction is catalyzed by activated kallikrein, takes places within the kallikrein:kininogen:C1q binding protein tetramer complex on the endothelial cell surface, and results in the release of kallikrein and bradykinin (Motta et al. 1998). The hormonal functions of bradykinin will be annotated in a future version of Reactome.
C1q binding protein tetramerREACT_2239 (Reactome)
  • Kininogen (high molecular weight kininogen; HK) associates with C1q binding protein on the cell surface in a reaction dependent on Zn++ (Joseph et al. 1996). In the body, the Zn++ needed to drive this reaction may be provided locally by Zn++ release from activated platelets (Mahdi et al. 2002). The C1q binding protein is inferred to form tetramers based on the properties of purified recombinant protein in vitro (Ghebrehiwet et al. 1994); the stoichiometry of the cell surface complex has not been determined directly.
  • Kininogen (high molecular weight kininogen; HK) associates with C1q binding protein on the cell surface in a reaction dependent on Zn++ (Joseph et al. 1996). In the body, the Zn++ needed to drive this reaction may be provided locally by Zn++ release from activated platelets (Mahdi et al. 2002). The C1q binding protein is inferred to form tetramers based on the properties of purified recombinant protein in vitro (Ghebrehiwet et al. 1994); the stoichiometry of the cell surface complex has not been determined directly.
Ca2+ArrowREACT_112 (Reactome)
  • The activated forms of factors VIII and IX associate on a cell surface to form a complex that very efficiently catalyzes the activation of factor X, the so-called "intrinsic tenase complex". In vitro, negatively charged phospholipids can provide an appropriate surface. In the body, the surface is provided by the plasma membranes of activated platelets (Gilbert and Arena 1996).
  • The activated forms of factors VIII and IX associate on a cell surface to form a complex that very efficiently catalyzes the activation of factor X, the so-called "intrinsic tenase complex". In vitro, negatively charged phospholipids can provide an appropriate surface. In the body, the surface is provided by the plasma membranes of activated platelets (Gilbert and Arena 1996).
Ca2+ArrowREACT_2073 (Reactome)
  • Factor XIa, bound to platelet glycoprotein (GP) Ib:IX:V on the platelet cell surface, catalyzes the formation of activated factor IX with high efficiency in a reaction that requires Ca++. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.)
  • Factor XIa, bound to platelet glycoprotein (GP) Ib:IX:V on the platelet cell surface, catalyzes the formation of activated factor IX with high efficiency in a reaction that requires Ca++. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.)
Ca2+REACT_1314 (Reactome)
  • Once the A chains of the Factor XIII tetramer have been cleaved by thrombin, the complex dissociates and the resulting A chain dimer binds Ca++ (one per peptide monomer) to form activated factor XIII (factor XIIIa).
  • Once the A chains of the Factor XIII tetramer have been cleaved by thrombin, the complex dissociates and the resulting A chain dimer binds Ca++ (one per peptide monomer) to form activated factor XIII (factor XIIIa).
Ca2+REACT_1668 (Reactome)
  • Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
  • Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
Ca2+REACT_245 (Reactome)
  • Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
  • Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
F13BArrowREACT_1314 (Reactome)
  • Once the A chains of the Factor XIII tetramer have been cleaved by thrombin, the complex dissociates and the resulting A chain dimer binds Ca++ (one per peptide monomer) to form activated factor XIII (factor XIIIa).
  • Once the A chains of the Factor XIII tetramer have been cleaved by thrombin, the complex dissociates and the resulting A chain dimer binds Ca++ (one per peptide monomer) to form activated factor XIII (factor XIIIa).
FGAArrowREACT_214 (Reactome)
  • The alpha and beta chains of fibrinogen hexamer are cleaved by thrombin to generate fibrin monomer. The amino terminal regions of the cleaved alpha and beta chains are released (fibrinopeptides A and B respectively).
  • The alpha and beta chains of fibrinogen hexamer are cleaved by thrombin to generate fibrin monomer. The amino terminal regions of the cleaved alpha and beta chains are released (fibrinopeptides A and B respectively).
FGBArrowREACT_214 (Reactome)
  • The alpha and beta chains of fibrinogen hexamer are cleaved by thrombin to generate fibrin monomer. The amino terminal regions of the cleaved alpha and beta chains are released (fibrinopeptides A and B respectively).
  • The alpha and beta chains of fibrinogen hexamer are cleaved by thrombin to generate fibrin monomer. The amino terminal regions of the cleaved alpha and beta chains are released (fibrinopeptides A and B respectively).
FibrinogenREACT_214 (Reactome)
  • The alpha and beta chains of fibrinogen hexamer are cleaved by thrombin to generate fibrin monomer. The amino terminal regions of the cleaved alpha and beta chains are released (fibrinopeptides A and B respectively).
  • The alpha and beta chains of fibrinogen hexamer are cleaved by thrombin to generate fibrin monomer. The amino terminal regions of the cleaved alpha and beta chains are released (fibrinopeptides A and B respectively).
GPIb-IX-V complexREACT_177 (Reactome)
  • Plasma factor XI binds to the platelet glycoprotein Ib:IX:V complex (Baglia et al. 2002; Greengard et al. 1986). In the body, this reaction occurs specifically on the surfaces of activated platelets, but not on endothelial cells (Baird and Walsh 2002). The stoichiometry of the platelet glycoprotein Ib:IX:V complex has not been established directly, but is inferred from the relative abundances of its components in platelet membranes (Modderman et al. 1992; Shrimpton et al. 2002).
  • Plasma factor XI binds to the platelet glycoprotein Ib:IX:V complex (Baglia et al. 2002; Greengard et al. 1986). In the body, this reaction occurs specifically on the surfaces of activated platelets, but not on endothelial cells (Baird and Walsh 2002). The stoichiometry of the platelet glycoprotein Ib:IX:V complex has not been established directly, but is inferred from the relative abundances of its components in platelet membranes (Modderman et al. 1992; Shrimpton et al. 2002).
HeparinArrowREACT_1283 (Reactome)
  • The same conformational change that traps thrombin in its complex with cleaved antithrombin III also decreases the affinity of the latter for heparin, and the complex of cleaved antithrombin III and thrombin dissociates from the cell-bound heparin molecule.
  • The same conformational change that traps thrombin in its complex with cleaved antithrombin III also decreases the affinity of the latter for heparin, and the complex of cleaved antithrombin III and thrombin dissociates from the cell-bound heparin molecule.
HeparinREACT_102 (Reactome)
  • Antithrombin III binds to membrane-associated heparin, e.g., on the surface of a normal endothelial cell. This binding event increases the affinity of antithrombin III for thrombin approximately 1000-fold.
  • Antithrombin III binds to membrane-associated heparin, e.g., on the surface of a normal endothelial cell. This binding event increases the affinity of antithrombin III for thrombin approximately 1000-fold.
KLKB1REACT_1335 (Reactome)
  • Prekallikrein (PK) associates specifically with kininogen (HK) on cell surfaces. In vivo, this reaction may occur primarily on the surfaces of endothelial cells in response to platelet activation (Lin et al. 1997; Motta et al. 1998; Mahdi et al. 2003).
  • Prekallikrein (PK) associates specifically with kininogen (HK) on cell surfaces. In vivo, this reaction may occur primarily on the surfaces of endothelial cells in response to platelet activation (Lin et al. 1997; Motta et al. 1998; Mahdi et al. 2003).
KNG C1q binding protein tetramerArrowREACT_2239 (Reactome)
  • Kininogen (high molecular weight kininogen; HK) associates with C1q binding protein on the cell surface in a reaction dependent on Zn++ (Joseph et al. 1996). In the body, the Zn++ needed to drive this reaction may be provided locally by Zn++ release from activated platelets (Mahdi et al. 2002). The C1q binding protein is inferred to form tetramers based on the properties of purified recombinant protein in vitro (Ghebrehiwet et al. 1994); the stoichiometry of the cell surface complex has not been determined directly.
  • Kininogen (high molecular weight kininogen; HK) associates with C1q binding protein on the cell surface in a reaction dependent on Zn++ (Joseph et al. 1996). In the body, the Zn++ needed to drive this reaction may be provided locally by Zn++ release from activated platelets (Mahdi et al. 2002). The C1q binding protein is inferred to form tetramers based on the properties of purified recombinant protein in vitro (Ghebrehiwet et al. 1994); the stoichiometry of the cell surface complex has not been determined directly.
KNG C1q binding protein tetramerREACT_1335 (Reactome)
  • Prekallikrein (PK) associates specifically with kininogen (HK) on cell surfaces. In vivo, this reaction may occur primarily on the surfaces of endothelial cells in response to platelet activation (Lin et al. 1997; Motta et al. 1998; Mahdi et al. 2003).
  • Prekallikrein (PK) associates specifically with kininogen (HK) on cell surfaces. In vivo, this reaction may occur primarily on the surfaces of endothelial cells in response to platelet activation (Lin et al. 1997; Motta et al. 1998; Mahdi et al. 2003).
KNG1ArrowREACT_1455 (Reactome)
  • Cleavage of a single peptide bond converts factor XII to activated factor XII (factor XIIa) (Fujikawa and McMullen 1983; McMullen and Fujikawa 1985). Identification of the catalytic activity or activities responsible for this cleavage has not been straightforward. Studies in vitro have demonstrated the autoactivation of factor XII as well as activation by kallikrein. Both reactions require the presence of negatively charged surfaces and are accelerated in the presence of kininogen (high molecular weight kininogen, HK) (Griffin and Cochrane 1976; Meier et al. 1977; Silverberg et al. 1980). Recent work suggests that factor XII activation in vivo may occur primarily on endothelial cell surfaces and that, as in vitro, association with kininogen may accelerate the reaction (Mahdi et al. 2002; Schmaier 2004), although alternative pathways and alternative mechanisms for associating factor XII with the cell surface have not been excluded (Joseph et al. 2001).
  • Cleavage of a single peptide bond converts factor XII to activated factor XII (factor XIIa) (Fujikawa and McMullen 1983; McMullen and Fujikawa 1985). Identification of the catalytic activity or activities responsible for this cleavage has not been straightforward. Studies in vitro have demonstrated the autoactivation of factor XII as well as activation by kallikrein. Both reactions require the presence of negatively charged surfaces and are accelerated in the presence of kininogen (high molecular weight kininogen, HK) (Griffin and Cochrane 1976; Meier et al. 1977; Silverberg et al. 1980). Recent work suggests that factor XII activation in vivo may occur primarily on endothelial cell surfaces and that, as in vitro, association with kininogen may accelerate the reaction (Mahdi et al. 2002; Schmaier 2004), although alternative pathways and alternative mechanisms for associating factor XII with the cell surface have not been excluded (Joseph et al. 2001).
KNG1REACT_2239 (Reactome)
  • Kininogen (high molecular weight kininogen; HK) associates with C1q binding protein on the cell surface in a reaction dependent on Zn++ (Joseph et al. 1996). In the body, the Zn++ needed to drive this reaction may be provided locally by Zn++ release from activated platelets (Mahdi et al. 2002). The C1q binding protein is inferred to form tetramers based on the properties of purified recombinant protein in vitro (Ghebrehiwet et al. 1994); the stoichiometry of the cell surface complex has not been determined directly.
  • Kininogen (high molecular weight kininogen; HK) associates with C1q binding protein on the cell surface in a reaction dependent on Zn++ (Joseph et al. 1996). In the body, the Zn++ needed to drive this reaction may be provided locally by Zn++ release from activated platelets (Mahdi et al. 2002). The C1q binding protein is inferred to form tetramers based on the properties of purified recombinant protein in vitro (Ghebrehiwet et al. 1994); the stoichiometry of the cell surface complex has not been determined directly.
NH4+ArrowREACT_1852 (Reactome)
  • Fibrin multimers are stabilized by the formation of multiple covalent crosslinks between the side chains of specific lysine and glutamine residues in fibrinogen alpha and gamma chains, catalyzed by factor XIIIa.
  • Fibrin multimers are stabilized by the formation of multiple covalent crosslinks between the side chains of specific lysine and glutamine residues in fibrinogen alpha and gamma chains, catalyzed by factor XIIIa.
PROCArrowREACT_374 (Reactome)
  • Thrombin complexed with thrombomodulin at the endothelial cell surface cleaves the heavy chain of protein C, generating activated protein C and an activation peptide. The activation peptide has no known function.
  • Thrombin complexed with thrombomodulin at the endothelial cell surface cleaves the heavy chain of protein C, generating activated protein C and an activation peptide. The activation peptide has no known function.
PalmC-F3REACT_137 (Reactome)
  • Tissue factor exposed at the endothelial cell surface forms a complex with F7a (activated factor VII) from the plasma
  • Tissue factor exposed at the endothelial cell surface forms a complex with F7a (activated factor VII) from the plasma
PalmC-F3REACT_1669 (Reactome)
  • Tissue factor exposed at the endothelial cell surface forms a complex with factor VII from plasma.
  • Tissue factor exposed at the endothelial cell surface forms a complex with factor VII from plasma.
Plasma kallikreinArrowREACT_2004 (Reactome)
  • The cleavage of kininogen (HK, high molecular weight kininogen) yields activated kininogen and the vasoactive peptide bradykinin (Kerbirou and Griffin 1979; Lottspeich et al. 1985; Kellerman et al. 1986). In vivo, this reaction is catalyzed by activated kallikrein, takes places within the kallikrein:kininogen:C1q binding protein tetramer complex on the endothelial cell surface, and results in the release of kallikrein and bradykinin (Motta et al. 1998). The hormonal functions of bradykinin will be annotated in a future version of Reactome.
  • The cleavage of kininogen (HK, high molecular weight kininogen) yields activated kininogen and the vasoactive peptide bradykinin (Kerbirou and Griffin 1979; Lottspeich et al. 1985; Kellerman et al. 1986). In vivo, this reaction is catalyzed by activated kallikrein, takes places within the kallikrein:kininogen:C1q binding protein tetramer complex on the endothelial cell surface, and results in the release of kallikrein and bradykinin (Motta et al. 1998). The hormonal functions of bradykinin will be annotated in a future version of Reactome.
Plasma kallikreinREACT_1486 (Reactome)
  • Activated kallikrein binds to C1Inh (plasma protease C1 inhibitor) (Bock et al. 1986), forming a stable and enzymatically inactive complex. This reaction appears to be the major means by which kallikrein is inactivated (kallikrein can also be inactivated by binding to alpha2-macroglobulin) (Harpel et al. 1985; Ratnoff et al. 1969).
  • Activated kallikrein binds to C1Inh (plasma protease C1 inhibitor) (Bock et al. 1986), forming a stable and enzymatically inactive complex. This reaction appears to be the major means by which kallikrein is inactivated (kallikrein can also be inactivated by binding to alpha2-macroglobulin) (Harpel et al. 1985; Ratnoff et al. 1969).
Plasma kallikreinREACT_25 (Reactome)
  • Activated kallikrein binds to alpha2-macroglobulin (Sottrup-Jensen et al. 1984), forming a stable and enzymatically inactive complex. Under normal conditions in vivo, this reaction appears to be responsible for the inactivation of about 1/6 of activated kallikrein (with C1Inh responsible for the inactivation of about 5/6) (Harpel et al. 1985).
  • Activated kallikrein binds to alpha2-macroglobulin (Sottrup-Jensen et al. 1984), forming a stable and enzymatically inactive complex. Under normal conditions in vivo, this reaction appears to be responsible for the inactivation of about 1/6 of activated kallikrein (with C1Inh responsible for the inactivation of about 5/6) (Harpel et al. 1985).
Platelet Factor 4ArrowREACT_374 (Reactome)
  • Thrombin complexed with thrombomodulin at the endothelial cell surface cleaves the heavy chain of protein C, generating activated protein C and an activation peptide. The activation peptide has no known function.
  • Thrombin complexed with thrombomodulin at the endothelial cell surface cleaves the heavy chain of protein C, generating activated protein C and an activation peptide. The activation peptide has no known function.
REACT_1314 (Reactome)
  • Once the A chains of the Factor XIII tetramer have been cleaved by thrombin, the complex dissociates and the resulting A chain dimer binds Ca++ (one per peptide monomer) to form activated factor XIII (factor XIIIa).
  • Once the A chains of the Factor XIII tetramer have been cleaved by thrombin, the complex dissociates and the resulting A chain dimer binds Ca++ (one per peptide monomer) to form activated factor XIII (factor XIIIa).
REACT_1668 (Reactome)
  • Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
  • Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
REACT_245 (Reactome)
  • Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
  • Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
SERPINC1REACT_102 (Reactome)
  • Antithrombin III binds to membrane-associated heparin, e.g., on the surface of a normal endothelial cell. This binding event increases the affinity of antithrombin III for thrombin approximately 1000-fold.
  • Antithrombin III binds to membrane-associated heparin, e.g., on the surface of a normal endothelial cell. This binding event increases the affinity of antithrombin III for thrombin approximately 1000-fold.
SERPING1REACT_1486 (Reactome)
  • Activated kallikrein binds to C1Inh (plasma protease C1 inhibitor) (Bock et al. 1986), forming a stable and enzymatically inactive complex. This reaction appears to be the major means by which kallikrein is inactivated (kallikrein can also be inactivated by binding to alpha2-macroglobulin) (Harpel et al. 1985; Ratnoff et al. 1969).
  • Activated kallikrein binds to C1Inh (plasma protease C1 inhibitor) (Bock et al. 1986), forming a stable and enzymatically inactive complex. This reaction appears to be the major means by which kallikrein is inactivated (kallikrein can also be inactivated by binding to alpha2-macroglobulin) (Harpel et al. 1985; Ratnoff et al. 1969).
SERPING1REACT_825 (Reactome)
  • Activated factor XII (factor XIIa) binds to C1Inh (C1 inhibitor - Bock et al. 1986) to form a stable, inactive complex (Schneider et al. 1973). While several protease inhibitors can form stable complexes with XIIa in vitro, only C1Inh does so to a significant extent under normal conditions in vivo (Pixley et al. 1985).
  • Activated factor XII (factor XIIa) binds to C1Inh (C1 inhibitor - Bock et al. 1986) to form a stable, inactive complex (Schneider et al. 1973). While several protease inhibitors can form stable complexes with XIIa in vitro, only C1Inh does so to a significant extent under normal conditions in vivo (Pixley et al. 1985).
TF F7ArrowREACT_1669 (Reactome)
  • Tissue factor exposed at the endothelial cell surface forms a complex with factor VII from plasma.
  • Tissue factor exposed at the endothelial cell surface forms a complex with factor VII from plasma.
TF F7aArrowREACT_137 (Reactome)
  • Tissue factor exposed at the endothelial cell surface forms a complex with F7a (activated factor VII) from the plasma
  • Tissue factor exposed at the endothelial cell surface forms a complex with F7a (activated factor VII) from the plasma
TF F7aREACT_654 (Reactome)
  • TFPI binds to the factor VIIa:TF complex and to factor Xa at the endothelial surface, forming a stable heterotetrameric complex in which factor VIIa is catalytically inactive.
  • TFPI binds to the factor VIIa:TF complex and to factor Xa at the endothelial surface, forming a stable heterotetrameric complex in which factor VIIa is catalytically inactive.
TF F7amim-catalysisREACT_158 (Reactome)
  • Factor VIIa, bound to tissue factor at the endothelial cell surface, catalyzes the formation of activated factor IX with high efficiency. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.)
  • Factor VIIa, bound to tissue factor at the endothelial cell surface, catalyzes the formation of activated factor IX with high efficiency. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.)
TF F7amim-catalysisREACT_245 (Reactome)
  • Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
  • Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
TF F7mim-catalysisREACT_493 (Reactome)
  • Factor VII, bound to tissue factor at the endothelial cell surface, catalyzes the activation of factor X from plasma with moderate efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
  • Factor VII, bound to tissue factor at the endothelial cell surface, catalyzes the activation of factor X from plasma with moderate efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
TFPI

TF F7a

factor Xa		ArrowREACT_654 (Reactome)
  • TFPI binds to the factor VIIa:TF complex and to factor Xa at the endothelial surface, forming a stable heterotetrameric complex in which factor VIIa is catalytically inactive.
  • TFPI binds to the factor VIIa:TF complex and to factor Xa at the endothelial surface, forming a stable heterotetrameric complex in which factor VIIa is catalytically inactive.
TFPIREACT_654 (Reactome)
  • TFPI binds to the factor VIIa:TF complex and to factor Xa at the endothelial surface, forming a stable heterotetrameric complex in which factor VIIa is catalytically inactive.
  • TFPI binds to the factor VIIa:TF complex and to factor Xa at the endothelial surface, forming a stable heterotetrameric complex in which factor VIIa is catalytically inactive.
THBDREACT_1834 (Reactome)
  • Activated thrombin (factor IIa) binds to thrombomodulin at the external face of the plasma membrane, forming a thrombin:thrombomodulin complex. In this complexed form, the activity of thrombin towards protein C is greatly increased, and as thrombomodulin is particularly abundant on the surfaces of endothelial cells, this association plays a major role in restricting clot formation.
  • Activated thrombin (factor IIa) binds to thrombomodulin at the external face of the plasma membrane, forming a thrombin:thrombomodulin complex. In this complexed form, the activity of thrombin towards protein C is greatly increased, and as thrombomodulin is particularly abundant on the surfaces of endothelial cells, this association plays a major role in restricting clot formation.
Va Xa complex ArrowREACT_675 (Reactome)
  • Factors Va and Xa associate on a membrane surface to form a complex in which the activity of factor Xa on prothrombin is greatly increased (Mann et al. 1988). The presence of negatively charged phospholipid in the membrane greatly facilitates this process, a feature that may contribute to its localization, as such phospholipids are normally on the cytosolic face of the plasma membrane (Devaux 1992), but could be exposed to the extracellular space following platelet activation or mechanical injury to endothelial cells.
  • Factors Va and Xa associate on a membrane surface to form a complex in which the activity of factor Xa on prothrombin is greatly increased (Mann et al. 1988). The presence of negatively charged phospholipid in the membrane greatly facilitates this process, a feature that may contribute to its localization, as such phospholipids are normally on the cytosolic face of the plasma membrane (Devaux 1992), but could be exposed to the extracellular space following platelet activation or mechanical injury to endothelial cells.
Va Xa complex mim-catalysisREACT_1446 (Reactome)
  • The membrane-bound Va:Xa (prothrombinase) complex rapidly activates large amounts of thrombin.
  • The membrane-bound Va:Xa (prothrombinase) complex rapidly activates large amounts of thrombin.
Zn2+ArrowREACT_2239 (Reactome)
  • Kininogen (high molecular weight kininogen; HK) associates with C1q binding protein on the cell surface in a reaction dependent on Zn++ (Joseph et al. 1996). In the body, the Zn++ needed to drive this reaction may be provided locally by Zn++ release from activated platelets (Mahdi et al. 2002). The C1q binding protein is inferred to form tetramers based on the properties of purified recombinant protein in vitro (Ghebrehiwet et al. 1994); the stoichiometry of the cell surface complex has not been determined directly.
  • Kininogen (high molecular weight kininogen; HK) associates with C1q binding protein on the cell surface in a reaction dependent on Zn++ (Joseph et al. 1996). In the body, the Zn++ needed to drive this reaction may be provided locally by Zn++ release from activated platelets (Mahdi et al. 2002). The C1q binding protein is inferred to form tetramers based on the properties of purified recombinant protein in vitro (Ghebrehiwet et al. 1994); the stoichiometry of the cell surface complex has not been determined directly.
activated kininogen C1q binding protein tetramerArrowREACT_2004 (Reactome)
  • The cleavage of kininogen (HK, high molecular weight kininogen) yields activated kininogen and the vasoactive peptide bradykinin (Kerbirou and Griffin 1979; Lottspeich et al. 1985; Kellerman et al. 1986). In vivo, this reaction is catalyzed by activated kallikrein, takes places within the kallikrein:kininogen:C1q binding protein tetramer complex on the endothelial cell surface, and results in the release of kallikrein and bradykinin (Motta et al. 1998). The hormonal functions of bradykinin will be annotated in a future version of Reactome.
  • The cleavage of kininogen (HK, high molecular weight kininogen) yields activated kininogen and the vasoactive peptide bradykinin (Kerbirou and Griffin 1979; Lottspeich et al. 1985; Kellerman et al. 1986). In vivo, this reaction is catalyzed by activated kallikrein, takes places within the kallikrein:kininogen:C1q binding protein tetramer complex on the endothelial cell surface, and results in the release of kallikrein and bradykinin (Motta et al. 1998). The hormonal functions of bradykinin will be annotated in a future version of Reactome.
activated protein CArrowREACT_374 (Reactome)
  • Thrombin complexed with thrombomodulin at the endothelial cell surface cleaves the heavy chain of protein C, generating activated protein C and an activation peptide. The activation peptide has no known function.
  • Thrombin complexed with thrombomodulin at the endothelial cell surface cleaves the heavy chain of protein C, generating activated protein C and an activation peptide. The activation peptide has no known function.
activated protein Cmim-catalysisREACT_1071 (Reactome)
  • Activated protein C cleaves peptide bonds in activated factor V (factor Va), converting it to an inactive form (factor Vi). The exact site(s) of cleavage are unknown. Protein S, on the endothelial cell surface, positively regulates this reaction. Although the mechanism of this regulation is unclear, the regulation is physiologically important, as people with reduced amounts of protein S, like people with reduced amounts of protein C, are susceptible to thromboembolism.
  • Activated protein C cleaves peptide bonds in activated factor V (factor Va), converting it to an inactive form (factor Vi). The exact site(s) of cleavage are unknown. Protein S, on the endothelial cell surface, positively regulates this reaction. Although the mechanism of this regulation is unclear, the regulation is physiologically important, as people with reduced amounts of protein S, like people with reduced amounts of protein C, are susceptible to thromboembolism.
activated thrombin thrombomodulinArrowREACT_1834 (Reactome)
  • Activated thrombin (factor IIa) binds to thrombomodulin at the external face of the plasma membrane, forming a thrombin:thrombomodulin complex. In this complexed form, the activity of thrombin towards protein C is greatly increased, and as thrombomodulin is particularly abundant on the surfaces of endothelial cells, this association plays a major role in restricting clot formation.
  • Activated thrombin (factor IIa) binds to thrombomodulin at the external face of the plasma membrane, forming a thrombin:thrombomodulin complex. In this complexed form, the activity of thrombin towards protein C is greatly increased, and as thrombomodulin is particularly abundant on the surfaces of endothelial cells, this association plays a major role in restricting clot formation.
activated thrombin thrombomodulinmim-catalysisREACT_374 (Reactome)
  • Thrombin complexed with thrombomodulin at the endothelial cell surface cleaves the heavy chain of protein C, generating activated protein C and an activation peptide. The activation peptide has no known function.
  • Thrombin complexed with thrombomodulin at the endothelial cell surface cleaves the heavy chain of protein C, generating activated protein C and an activation peptide. The activation peptide has no known function.
antithrombin III heparinArrowREACT_102 (Reactome)
  • Antithrombin III binds to membrane-associated heparin, e.g., on the surface of a normal endothelial cell. This binding event increases the affinity of antithrombin III for thrombin approximately 1000-fold.
  • Antithrombin III binds to membrane-associated heparin, e.g., on the surface of a normal endothelial cell. This binding event increases the affinity of antithrombin III for thrombin approximately 1000-fold.
antithrombin III heparinREACT_1822 (Reactome)
  • Activated thrombin binds to the antithrombin III:heparin complex on the cell surface.
  • Activated thrombin binds to the antithrombin III:heparin complex on the cell surface.
factor IX activation peptideArrowREACT_158 (Reactome)
  • Factor VIIa, bound to tissue factor at the endothelial cell surface, catalyzes the formation of activated factor IX with high efficiency. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.)
  • Factor VIIa, bound to tissue factor at the endothelial cell surface, catalyzes the formation of activated factor IX with high efficiency. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.)
factor IX activation peptideArrowREACT_2073 (Reactome)
  • Factor XIa, bound to platelet glycoprotein (GP) Ib:IX:V on the platelet cell surface, catalyzes the formation of activated factor IX with high efficiency in a reaction that requires Ca++. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.)
  • Factor XIa, bound to platelet glycoprotein (GP) Ib:IX:V on the platelet cell surface, catalyzes the formation of activated factor IX with high efficiency in a reaction that requires Ca++. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.)
factor IXaArrowREACT_158 (Reactome)
  • Factor VIIa, bound to tissue factor at the endothelial cell surface, catalyzes the formation of activated factor IX with high efficiency. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.)
  • Factor VIIa, bound to tissue factor at the endothelial cell surface, catalyzes the formation of activated factor IX with high efficiency. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.)
factor IXaArrowREACT_2073 (Reactome)
  • Factor XIa, bound to platelet glycoprotein (GP) Ib:IX:V on the platelet cell surface, catalyzes the formation of activated factor IX with high efficiency in a reaction that requires Ca++. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.)
  • Factor XIa, bound to platelet glycoprotein (GP) Ib:IX:V on the platelet cell surface, catalyzes the formation of activated factor IX with high efficiency in a reaction that requires Ca++. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.)
factor IXaREACT_112 (Reactome)
  • The activated forms of factors VIII and IX associate on a cell surface to form a complex that very efficiently catalyzes the activation of factor X, the so-called "intrinsic tenase complex". In vitro, negatively charged phospholipids can provide an appropriate surface. In the body, the surface is provided by the plasma membranes of activated platelets (Gilbert and Arena 1996).
  • The activated forms of factors VIII and IX associate on a cell surface to form a complex that very efficiently catalyzes the activation of factor X, the so-called "intrinsic tenase complex". In vitro, negatively charged phospholipids can provide an appropriate surface. In the body, the surface is provided by the plasma membranes of activated platelets (Gilbert and Arena 1996).
factor V activation peptideArrowREACT_708 (Reactome)
  • Activated thrombin (factor IIa) catalyzes the conversion of factor V to factor Va (activated factor V). The activation peptide released in this reaction has no known function.
  • Activated thrombin (factor IIa) catalyzes the conversion of factor V to factor Va (activated factor V). The activation peptide released in this reaction has no known function.
factor VIII von Willebrand factor multimerArrowREACT_531 (Reactome)
  • Factor VIII binds to von Willebrand factor to form a complex. This complex stabilizes factor VIII, which otherwise has a very short half-life in the blood.

    Factor VIII (Vehar et al. 1984) is a heterodimer containing a heavy and a light polypeptide chain, generated by the proteolytic cleavage of a single large precursor polypeptide. Several forms of the heavy chain are found in vivo, all functionally the same but differing in the amount of the B domain removed by proteolysis. The single form annotated here is the shortest one (Eaton et al. 1986; Hill-Eubanks et al. 1989).

    In vitro, von Willebrand factor (Titani et al. 1986) can form complexes with factor VIII with a 1:1 stoichiometry. The complexes that form in vivo, however, involve large multimers of von Willebrand factor and varied, but always low, proportions of factor VIII (Vlot et al. 1995). A stoichiometry of one molecule of factor VIII associated with 50 of von Willebrand factor is typical in vivo, and is used here to annotate the factor VIII:von Willebrand factor complex.

  • Factor VIII binds to von Willebrand factor to form a complex. This complex stabilizes factor VIII, which otherwise has a very short half-life in the blood.

    Factor VIII (Vehar et al. 1984) is a heterodimer containing a heavy and a light polypeptide chain, generated by the proteolytic cleavage of a single large precursor polypeptide. Several forms of the heavy chain are found in vivo, all functionally the same but differing in the amount of the B domain removed by proteolysis. The single form annotated here is the shortest one (Eaton et al. 1986; Hill-Eubanks et al. 1989).

    In vitro, von Willebrand factor (Titani et al. 1986) can form complexes with factor VIII with a 1:1 stoichiometry. The complexes that form in vivo, however, involve large multimers of von Willebrand factor and varied, but always low, proportions of factor VIII (Vlot et al. 1995). A stoichiometry of one molecule of factor VIII associated with 50 of von Willebrand factor is typical in vivo, and is used here to annotate the factor VIII:von Willebrand factor complex.

factor VIII von Willebrand factor multimerREACT_217 (Reactome)
  • Factor VIII complexed to von Willibrand factor in the blood is cleaved into several smaller polypeptides that remain associated. The acidic polypeptide on the aminoterminal side of the A3 domain of the light chain is released, however, and as this polypeptide mediates the association of factor VIII with von Willibrand factor, the activated factor VIII is released. While several proteases are capable of catalyzing these cleavages in vitro, only thrombin is active on factor VIII:von Willibrand factor complexes under physiological conditions (Eaton et al. 1986; Hill-Eubanks et al. 1989; Lollar et al. 1988; Pieters et al. 1989)
  • Factor VIII complexed to von Willibrand factor in the blood is cleaved into several smaller polypeptides that remain associated. The acidic polypeptide on the aminoterminal side of the A3 domain of the light chain is released, however, and as this polypeptide mediates the association of factor VIII with von Willibrand factor, the activated factor VIII is released. While several proteases are capable of catalyzing these cleavages in vitro, only thrombin is active on factor VIII:von Willibrand factor complexes under physiological conditions (Eaton et al. 1986; Hill-Eubanks et al. 1989; Lollar et al. 1988; Pieters et al. 1989)
factor VIIIREACT_531 (Reactome)
  • Factor VIII binds to von Willebrand factor to form a complex. This complex stabilizes factor VIII, which otherwise has a very short half-life in the blood.

    Factor VIII (Vehar et al. 1984) is a heterodimer containing a heavy and a light polypeptide chain, generated by the proteolytic cleavage of a single large precursor polypeptide. Several forms of the heavy chain are found in vivo, all functionally the same but differing in the amount of the B domain removed by proteolysis. The single form annotated here is the shortest one (Eaton et al. 1986; Hill-Eubanks et al. 1989).

    In vitro, von Willebrand factor (Titani et al. 1986) can form complexes with factor VIII with a 1:1 stoichiometry. The complexes that form in vivo, however, involve large multimers of von Willebrand factor and varied, but always low, proportions of factor VIII (Vlot et al. 1995). A stoichiometry of one molecule of factor VIII associated with 50 of von Willebrand factor is typical in vivo, and is used here to annotate the factor VIII:von Willebrand factor complex.

  • Factor VIII binds to von Willebrand factor to form a complex. This complex stabilizes factor VIII, which otherwise has a very short half-life in the blood.

    Factor VIII (Vehar et al. 1984) is a heterodimer containing a heavy and a light polypeptide chain, generated by the proteolytic cleavage of a single large precursor polypeptide. Several forms of the heavy chain are found in vivo, all functionally the same but differing in the amount of the B domain removed by proteolysis. The single form annotated here is the shortest one (Eaton et al. 1986; Hill-Eubanks et al. 1989).

    In vitro, von Willebrand factor (Titani et al. 1986) can form complexes with factor VIII with a 1:1 stoichiometry. The complexes that form in vivo, however, involve large multimers of von Willebrand factor and varied, but always low, proportions of factor VIII (Vlot et al. 1995). A stoichiometry of one molecule of factor VIII associated with 50 of von Willebrand factor is typical in vivo, and is used here to annotate the factor VIII:von Willebrand factor complex.

factor VIIIa factor IXaArrowREACT_112 (Reactome)
  • The activated forms of factors VIII and IX associate on a cell surface to form a complex that very efficiently catalyzes the activation of factor X, the so-called "intrinsic tenase complex". In vitro, negatively charged phospholipids can provide an appropriate surface. In the body, the surface is provided by the plasma membranes of activated platelets (Gilbert and Arena 1996).
  • The activated forms of factors VIII and IX associate on a cell surface to form a complex that very efficiently catalyzes the activation of factor X, the so-called "intrinsic tenase complex". In vitro, negatively charged phospholipids can provide an appropriate surface. In the body, the surface is provided by the plasma membranes of activated platelets (Gilbert and Arena 1996).
factor VIIIa factor IXamim-catalysisREACT_1668 (Reactome)
  • Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
  • Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
factor VIIIa B A3 acidic polypeptideArrowREACT_217 (Reactome)
  • Factor VIII complexed to von Willibrand factor in the blood is cleaved into several smaller polypeptides that remain associated. The acidic polypeptide on the aminoterminal side of the A3 domain of the light chain is released, however, and as this polypeptide mediates the association of factor VIII with von Willibrand factor, the activated factor VIII is released. While several proteases are capable of catalyzing these cleavages in vitro, only thrombin is active on factor VIII:von Willibrand factor complexes under physiological conditions (Eaton et al. 1986; Hill-Eubanks et al. 1989; Lollar et al. 1988; Pieters et al. 1989)
  • Factor VIII complexed to von Willibrand factor in the blood is cleaved into several smaller polypeptides that remain associated. The acidic polypeptide on the aminoterminal side of the A3 domain of the light chain is released, however, and as this polypeptide mediates the association of factor VIII with von Willibrand factor, the activated factor VIII is released. While several proteases are capable of catalyzing these cleavages in vitro, only thrombin is active on factor VIII:von Willibrand factor complexes under physiological conditions (Eaton et al. 1986; Hill-Eubanks et al. 1989; Lollar et al. 1988; Pieters et al. 1989)
factor VIIIaArrowREACT_217 (Reactome)
  • Factor VIII complexed to von Willibrand factor in the blood is cleaved into several smaller polypeptides that remain associated. The acidic polypeptide on the aminoterminal side of the A3 domain of the light chain is released, however, and as this polypeptide mediates the association of factor VIII with von Willibrand factor, the activated factor VIII is released. While several proteases are capable of catalyzing these cleavages in vitro, only thrombin is active on factor VIII:von Willibrand factor complexes under physiological conditions (Eaton et al. 1986; Hill-Eubanks et al. 1989; Lollar et al. 1988; Pieters et al. 1989)
  • Factor VIII complexed to von Willibrand factor in the blood is cleaved into several smaller polypeptides that remain associated. The acidic polypeptide on the aminoterminal side of the A3 domain of the light chain is released, however, and as this polypeptide mediates the association of factor VIII with von Willibrand factor, the activated factor VIII is released. While several proteases are capable of catalyzing these cleavages in vitro, only thrombin is active on factor VIII:von Willibrand factor complexes under physiological conditions (Eaton et al. 1986; Hill-Eubanks et al. 1989; Lollar et al. 1988; Pieters et al. 1989)
factor VIIIaREACT_112 (Reactome)
  • The activated forms of factors VIII and IX associate on a cell surface to form a complex that very efficiently catalyzes the activation of factor X, the so-called "intrinsic tenase complex". In vitro, negatively charged phospholipids can provide an appropriate surface. In the body, the surface is provided by the plasma membranes of activated platelets (Gilbert and Arena 1996).
  • The activated forms of factors VIII and IX associate on a cell surface to form a complex that very efficiently catalyzes the activation of factor X, the so-called "intrinsic tenase complex". In vitro, negatively charged phospholipids can provide an appropriate surface. In the body, the surface is provided by the plasma membranes of activated platelets (Gilbert and Arena 1996).
factor VIIaREACT_137 (Reactome)
  • Tissue factor exposed at the endothelial cell surface forms a complex with F7a (activated factor VII) from the plasma
  • Tissue factor exposed at the endothelial cell surface forms a complex with F7a (activated factor VII) from the plasma
factor VREACT_708 (Reactome)
  • Activated thrombin (factor IIa) catalyzes the conversion of factor V to factor Va (activated factor V). The activation peptide released in this reaction has no known function.
  • Activated thrombin (factor IIa) catalyzes the conversion of factor V to factor Va (activated factor V). The activation peptide released in this reaction has no known function.
factor VaArrowREACT_708 (Reactome)
  • Activated thrombin (factor IIa) catalyzes the conversion of factor V to factor Va (activated factor V). The activation peptide released in this reaction has no known function.
  • Activated thrombin (factor IIa) catalyzes the conversion of factor V to factor Va (activated factor V). The activation peptide released in this reaction has no known function.
factor VaREACT_675 (Reactome)
  • Factors Va and Xa associate on a membrane surface to form a complex in which the activity of factor Xa on prothrombin is greatly increased (Mann et al. 1988). The presence of negatively charged phospholipid in the membrane greatly facilitates this process, a feature that may contribute to its localization, as such phospholipids are normally on the cytosolic face of the plasma membrane (Devaux 1992), but could be exposed to the extracellular space following platelet activation or mechanical injury to endothelial cells.
  • Factors Va and Xa associate on a membrane surface to form a complex in which the activity of factor Xa on prothrombin is greatly increased (Mann et al. 1988). The presence of negatively charged phospholipid in the membrane greatly facilitates this process, a feature that may contribute to its localization, as such phospholipids are normally on the cytosolic face of the plasma membrane (Devaux 1992), but could be exposed to the extracellular space following platelet activation or mechanical injury to endothelial cells.
factor Vafactor ViArrowREACT_1071 (Reactome)
  • Activated protein C cleaves peptide bonds in activated factor V (factor Va), converting it to an inactive form (factor Vi). The exact site(s) of cleavage are unknown. Protein S, on the endothelial cell surface, positively regulates this reaction. Although the mechanism of this regulation is unclear, the regulation is physiologically important, as people with reduced amounts of protein S, like people with reduced amounts of protein C, are susceptible to thromboembolism.
  • Activated protein C cleaves peptide bonds in activated factor V (factor Va), converting it to an inactive form (factor Vi). The exact site(s) of cleavage are unknown. Protein S, on the endothelial cell surface, positively regulates this reaction. Although the mechanism of this regulation is unclear, the regulation is physiologically important, as people with reduced amounts of protein S, like people with reduced amounts of protein C, are susceptible to thromboembolism.
factor X activation peptideArrowREACT_1668 (Reactome)
  • Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
  • Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
factor X activation peptideArrowREACT_245 (Reactome)
  • Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
  • Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
factor X activation peptideArrowREACT_493 (Reactome)
  • Factor VII, bound to tissue factor at the endothelial cell surface, catalyzes the activation of factor X from plasma with moderate efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
  • Factor VII, bound to tissue factor at the endothelial cell surface, catalyzes the activation of factor X from plasma with moderate efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
factor XI GPIb-IX-V complexArrowREACT_177 (Reactome)
  • Plasma factor XI binds to the platelet glycoprotein Ib:IX:V complex (Baglia et al. 2002; Greengard et al. 1986). In the body, this reaction occurs specifically on the surfaces of activated platelets, but not on endothelial cells (Baird and Walsh 2002). The stoichiometry of the platelet glycoprotein Ib:IX:V complex has not been established directly, but is inferred from the relative abundances of its components in platelet membranes (Modderman et al. 1992; Shrimpton et al. 2002).
  • Plasma factor XI binds to the platelet glycoprotein Ib:IX:V complex (Baglia et al. 2002; Greengard et al. 1986). In the body, this reaction occurs specifically on the surfaces of activated platelets, but not on endothelial cells (Baird and Walsh 2002). The stoichiometry of the platelet glycoprotein Ib:IX:V complex has not been established directly, but is inferred from the relative abundances of its components in platelet membranes (Modderman et al. 1992; Shrimpton et al. 2002).
factor XI GPIb-IX-V complexfactor XIa

GPIb GPIX

GPV complex		ArrowREACT_1581 (Reactome)
  • Factor XI, bound to the cell surface, is converted to activated factor XI (factor XIa). In the body, this reaction occurs on the surfaces of activated platelets (Baglia et al. 2002). Small quantities of factor XI can be activated in a reaction catalyzed by factor XIIa, to initiate formation of a fibrin clot. However, the efficient activation of larger quantities of factor XI, needed to propagate the blood clotting process, appears to be mediated by thrombin (Baglia and Walsh 2000; Gailani and Broze 1993; Naito and Fujikawa 1991; Oliver et al. 1999; Monroe et al. 2002).
  • Factor XI, bound to the cell surface, is converted to activated factor XI (factor XIa). In the body, this reaction occurs on the surfaces of activated platelets (Baglia et al. 2002). Small quantities of factor XI can be activated in a reaction catalyzed by factor XIIa, to initiate formation of a fibrin clot. However, the efficient activation of larger quantities of factor XI, needed to propagate the blood clotting process, appears to be mediated by thrombin (Baglia and Walsh 2000; Gailani and Broze 1993; Naito and Fujikawa 1991; Oliver et al. 1999; Monroe et al. 2002).
factor XI GPIb-IX-V complexfactor XIa

GPIb GPIX

GPV complex		ArrowREACT_905 (Reactome)
  • Factor XI, bound to the cell surface, is converted to activated factor XI (factor XIa). Chemically, this reaction involves the cleavage of a single peptide bond in each subunit of the factor XI homodimer; intra- and inter-chain disulfide bonds hold the resulting four polypeptides together (Bouma and Griffin 1977; Kurachi and Davie 1977; McMullen et al. 1991). In the body, this reaction occurs on the surfaces of activated platelets (Greengard et al. 1986; Baglia et al. 2002; Baird and Walsh 2002); when this reaction occurs as a step in the intrinsic ("contact") pathway of blood coagulation, it is catalyzed by activated factor XIIa (Kurachi and Davie 1977, Baglia and Walsh 2000) which in turn is generated through the interactions of factor XII, kallikrein, and kininogen on endothelial cell surfaces (Schmaier 2004).
  • Factor XI, bound to the cell surface, is converted to activated factor XI (factor XIa). Chemically, this reaction involves the cleavage of a single peptide bond in each subunit of the factor XI homodimer; intra- and inter-chain disulfide bonds hold the resulting four polypeptides together (Bouma and Griffin 1977; Kurachi and Davie 1977; McMullen et al. 1991). In the body, this reaction occurs on the surfaces of activated platelets (Greengard et al. 1986; Baglia et al. 2002; Baird and Walsh 2002); when this reaction occurs as a step in the intrinsic ("contact") pathway of blood coagulation, it is catalyzed by activated factor XIIa (Kurachi and Davie 1977, Baglia and Walsh 2000) which in turn is generated through the interactions of factor XII, kallikrein, and kininogen on endothelial cell surfaces (Schmaier 2004).
factor XIII A chain activation peptideArrowREACT_1536 (Reactome)
  • Activated thrombin cleaves the A chains of factor XIII tetramers in a reaction stimulated by the presence of fibrin multimers. The amino terminal portions of the A chains are released as activation peptides, which have no known function. The resulting factor XIII tetramer remains catalytically inactive.
  • Activated thrombin cleaves the A chains of factor XIII tetramers in a reaction stimulated by the presence of fibrin multimers. The amino terminal portions of the A chains are released as activation peptides, which have no known function. The resulting factor XIII tetramer remains catalytically inactive.
factor XIII cleaved tetramerArrowREACT_1536 (Reactome)
  • Activated thrombin cleaves the A chains of factor XIII tetramers in a reaction stimulated by the presence of fibrin multimers. The amino terminal portions of the A chains are released as activation peptides, which have no known function. The resulting factor XIII tetramer remains catalytically inactive.
  • Activated thrombin cleaves the A chains of factor XIII tetramers in a reaction stimulated by the presence of fibrin multimers. The amino terminal portions of the A chains are released as activation peptides, which have no known function. The resulting factor XIII tetramer remains catalytically inactive.
factor XIII cleaved tetramerREACT_1314 (Reactome)
  • Once the A chains of the Factor XIII tetramer have been cleaved by thrombin, the complex dissociates and the resulting A chain dimer binds Ca++ (one per peptide monomer) to form activated factor XIII (factor XIIIa).
  • Once the A chains of the Factor XIII tetramer have been cleaved by thrombin, the complex dissociates and the resulting A chain dimer binds Ca++ (one per peptide monomer) to form activated factor XIII (factor XIIIa).
factor XIIIREACT_1536 (Reactome)
  • Activated thrombin cleaves the A chains of factor XIII tetramers in a reaction stimulated by the presence of fibrin multimers. The amino terminal portions of the A chains are released as activation peptides, which have no known function. The resulting factor XIII tetramer remains catalytically inactive.
  • Activated thrombin cleaves the A chains of factor XIII tetramers in a reaction stimulated by the presence of fibrin multimers. The amino terminal portions of the A chains are released as activation peptides, which have no known function. The resulting factor XIII tetramer remains catalytically inactive.
factor XIIIaArrowREACT_1314 (Reactome)
  • Once the A chains of the Factor XIII tetramer have been cleaved by thrombin, the complex dissociates and the resulting A chain dimer binds Ca++ (one per peptide monomer) to form activated factor XIII (factor XIIIa).
  • Once the A chains of the Factor XIII tetramer have been cleaved by thrombin, the complex dissociates and the resulting A chain dimer binds Ca++ (one per peptide monomer) to form activated factor XIII (factor XIIIa).
factor XIIIamim-catalysisREACT_1852 (Reactome)
  • Fibrin multimers are stabilized by the formation of multiple covalent crosslinks between the side chains of specific lysine and glutamine residues in fibrinogen alpha and gamma chains, catalyzed by factor XIIIa.
  • Fibrin multimers are stabilized by the formation of multiple covalent crosslinks between the side chains of specific lysine and glutamine residues in fibrinogen alpha and gamma chains, catalyzed by factor XIIIa.
factor XIIa C1InhArrowREACT_825 (Reactome)
  • Activated factor XII (factor XIIa) binds to C1Inh (C1 inhibitor - Bock et al. 1986) to form a stable, inactive complex (Schneider et al. 1973). While several protease inhibitors can form stable complexes with XIIa in vitro, only C1Inh does so to a significant extent under normal conditions in vivo (Pixley et al. 1985).
  • Activated factor XII (factor XIIa) binds to C1Inh (C1 inhibitor - Bock et al. 1986) to form a stable, inactive complex (Schneider et al. 1973). While several protease inhibitors can form stable complexes with XIIa in vitro, only C1Inh does so to a significant extent under normal conditions in vivo (Pixley et al. 1985).
factor XIIaREACT_825 (Reactome)
  • Activated factor XII (factor XIIa) binds to C1Inh (C1 inhibitor - Bock et al. 1986) to form a stable, inactive complex (Schneider et al. 1973). While several protease inhibitors can form stable complexes with XIIa in vitro, only C1Inh does so to a significant extent under normal conditions in vivo (Pixley et al. 1985).
  • Activated factor XII (factor XIIa) binds to C1Inh (C1 inhibitor - Bock et al. 1986) to form a stable, inactive complex (Schneider et al. 1973). While several protease inhibitors can form stable complexes with XIIa in vitro, only C1Inh does so to a significant extent under normal conditions in vivo (Pixley et al. 1985).
factor XIIamim-catalysisREACT_905 (Reactome)
  • Factor XI, bound to the cell surface, is converted to activated factor XI (factor XIa). Chemically, this reaction involves the cleavage of a single peptide bond in each subunit of the factor XI homodimer; intra- and inter-chain disulfide bonds hold the resulting four polypeptides together (Bouma and Griffin 1977; Kurachi and Davie 1977; McMullen et al. 1991). In the body, this reaction occurs on the surfaces of activated platelets (Greengard et al. 1986; Baglia et al. 2002; Baird and Walsh 2002); when this reaction occurs as a step in the intrinsic ("contact") pathway of blood coagulation, it is catalyzed by activated factor XIIa (Kurachi and Davie 1977, Baglia and Walsh 2000) which in turn is generated through the interactions of factor XII, kallikrein, and kininogen on endothelial cell surfaces (Schmaier 2004).
  • Factor XI, bound to the cell surface, is converted to activated factor XI (factor XIa). Chemically, this reaction involves the cleavage of a single peptide bond in each subunit of the factor XI homodimer; intra- and inter-chain disulfide bonds hold the resulting four polypeptides together (Bouma and Griffin 1977; Kurachi and Davie 1977; McMullen et al. 1991). In the body, this reaction occurs on the surfaces of activated platelets (Greengard et al. 1986; Baglia et al. 2002; Baird and Walsh 2002); when this reaction occurs as a step in the intrinsic ("contact") pathway of blood coagulation, it is catalyzed by activated factor XIIa (Kurachi and Davie 1977, Baglia and Walsh 2000) which in turn is generated through the interactions of factor XII, kallikrein, and kininogen on endothelial cell surfaces (Schmaier 2004).
factor XIIfactor XIIaArrowREACT_1455 (Reactome)
  • Cleavage of a single peptide bond converts factor XII to activated factor XII (factor XIIa) (Fujikawa and McMullen 1983; McMullen and Fujikawa 1985). Identification of the catalytic activity or activities responsible for this cleavage has not been straightforward. Studies in vitro have demonstrated the autoactivation of factor XII as well as activation by kallikrein. Both reactions require the presence of negatively charged surfaces and are accelerated in the presence of kininogen (high molecular weight kininogen, HK) (Griffin and Cochrane 1976; Meier et al. 1977; Silverberg et al. 1980). Recent work suggests that factor XII activation in vivo may occur primarily on endothelial cell surfaces and that, as in vitro, association with kininogen may accelerate the reaction (Mahdi et al. 2002; Schmaier 2004), although alternative pathways and alternative mechanisms for associating factor XII with the cell surface have not been excluded (Joseph et al. 2001).
  • Cleavage of a single peptide bond converts factor XII to activated factor XII (factor XIIa) (Fujikawa and McMullen 1983; McMullen and Fujikawa 1985). Identification of the catalytic activity or activities responsible for this cleavage has not been straightforward. Studies in vitro have demonstrated the autoactivation of factor XII as well as activation by kallikrein. Both reactions require the presence of negatively charged surfaces and are accelerated in the presence of kininogen (high molecular weight kininogen, HK) (Griffin and Cochrane 1976; Meier et al. 1977; Silverberg et al. 1980). Recent work suggests that factor XII activation in vivo may occur primarily on endothelial cell surfaces and that, as in vitro, association with kininogen may accelerate the reaction (Mahdi et al. 2002; Schmaier 2004), although alternative pathways and alternative mechanisms for associating factor XII with the cell surface have not been excluded (Joseph et al. 2001).
factor XIREACT_177 (Reactome)
  • Plasma factor XI binds to the platelet glycoprotein Ib:IX:V complex (Baglia et al. 2002; Greengard et al. 1986). In the body, this reaction occurs specifically on the surfaces of activated platelets, but not on endothelial cells (Baird and Walsh 2002). The stoichiometry of the platelet glycoprotein Ib:IX:V complex has not been established directly, but is inferred from the relative abundances of its components in platelet membranes (Modderman et al. 1992; Shrimpton et al. 2002).
  • Plasma factor XI binds to the platelet glycoprotein Ib:IX:V complex (Baglia et al. 2002; Greengard et al. 1986). In the body, this reaction occurs specifically on the surfaces of activated platelets, but not on endothelial cells (Baird and Walsh 2002). The stoichiometry of the platelet glycoprotein Ib:IX:V complex has not been established directly, but is inferred from the relative abundances of its components in platelet membranes (Modderman et al. 1992; Shrimpton et al. 2002).
factor XIa

GPIb GPIX

GPV complex		mim-catalysisREACT_2073 (Reactome)
  • Factor XIa, bound to platelet glycoprotein (GP) Ib:IX:V on the platelet cell surface, catalyzes the formation of activated factor IX with high efficiency in a reaction that requires Ca++. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.)
  • Factor XIa, bound to platelet glycoprotein (GP) Ib:IX:V on the platelet cell surface, catalyzes the formation of activated factor IX with high efficiency in a reaction that requires Ca++. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.)
factor XREACT_1668 (Reactome)
  • Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
  • Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
factor XREACT_245 (Reactome)
  • Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
  • Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
factor XREACT_493 (Reactome)
  • Factor VII, bound to tissue factor at the endothelial cell surface, catalyzes the activation of factor X from plasma with moderate efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
  • Factor VII, bound to tissue factor at the endothelial cell surface, catalyzes the activation of factor X from plasma with moderate efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
factor XaArrowREACT_1668 (Reactome)
  • Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
  • Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
factor XaArrowREACT_245 (Reactome)
  • Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
  • Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
factor XaArrowREACT_493 (Reactome)
  • Factor VII, bound to tissue factor at the endothelial cell surface, catalyzes the activation of factor X from plasma with moderate efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
  • Factor VII, bound to tissue factor at the endothelial cell surface, catalyzes the activation of factor X from plasma with moderate efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.)
factor XaREACT_654 (Reactome)
  • TFPI binds to the factor VIIa:TF complex and to factor Xa at the endothelial surface, forming a stable heterotetrameric complex in which factor VIIa is catalytically inactive.
  • TFPI binds to the factor VIIa:TF complex and to factor Xa at the endothelial surface, forming a stable heterotetrameric complex in which factor VIIa is catalytically inactive.
factor XaREACT_675 (Reactome)
  • Factors Va and Xa associate on a membrane surface to form a complex in which the activity of factor Xa on prothrombin is greatly increased (Mann et al. 1988). The presence of negatively charged phospholipid in the membrane greatly facilitates this process, a feature that may contribute to its localization, as such phospholipids are normally on the cytosolic face of the plasma membrane (Devaux 1992), but could be exposed to the extracellular space following platelet activation or mechanical injury to endothelial cells.
  • Factors Va and Xa associate on a membrane surface to form a complex in which the activity of factor Xa on prothrombin is greatly increased (Mann et al. 1988). The presence of negatively charged phospholipid in the membrane greatly facilitates this process, a feature that may contribute to its localization, as such phospholipids are normally on the cytosolic face of the plasma membrane (Devaux 1992), but could be exposed to the extracellular space following platelet activation or mechanical injury to endothelial cells.
factor Xamim-catalysisREACT_1097 (Reactome)
  • Membrane-bound factor Xa catalyzes the activation of small amounts of thrombin. The amino terminal portion of prothrombin is released as an activation peptide, which can be cleaved further by activated thrombin. Neither the full-length activation peptide nor its cleavage products have known functions.
  • Membrane-bound factor Xa catalyzes the activation of small amounts of thrombin. The amino terminal portion of prothrombin is released as an activation peptide, which can be cleaved further by activated thrombin. Neither the full-length activation peptide nor its cleavage products have known functions.
factor Xamim-catalysisREACT_9 (Reactome)
  • Factor Xa catalyzes the activation of factor VII from plasma.
  • Factor Xa catalyzes the activation of factor VII from plasma.
fibrin monomerArrowREACT_214 (Reactome)
  • The alpha and beta chains of fibrinogen hexamer are cleaved by thrombin to generate fibrin monomer. The amino terminal regions of the cleaved alpha and beta chains are released (fibrinopeptides A and B respectively).
  • The alpha and beta chains of fibrinogen hexamer are cleaved by thrombin to generate fibrin monomer. The amino terminal regions of the cleaved alpha and beta chains are released (fibrinopeptides A and B respectively).
fibrin monomerfibrin multimerArrowREACT_1329 (Reactome)
  • Fibrin monomers rapidly and spontaneously associate into large multimers, binding to one another via sites created by fibrinopeptide release (Laudano and Doolittelle 1980). The process of multimerization, and the range of multimer structures that can form in vivo and in vitro, have been studied in detail (Doolittle 1984). Here, multimer size has arbitrarily been set to three fibrin monomers.
  • Fibrin monomers rapidly and spontaneously associate into large multimers, binding to one another via sites created by fibrinopeptide release (Laudano and Doolittelle 1980). The process of multimerization, and the range of multimer structures that can form in vivo and in vitro, have been studied in detail (Doolittle 1984). Here, multimer size has arbitrarily been set to three fibrin monomers.
fibrin multimer, crosslinkedArrowREACT_1852 (Reactome)
  • Fibrin multimers are stabilized by the formation of multiple covalent crosslinks between the side chains of specific lysine and glutamine residues in fibrinogen alpha and gamma chains, catalyzed by factor XIIIa.
  • Fibrin multimers are stabilized by the formation of multiple covalent crosslinks between the side chains of specific lysine and glutamine residues in fibrinogen alpha and gamma chains, catalyzed by factor XIIIa.
fibrin multimerArrowREACT_1536 (Reactome)
  • Activated thrombin cleaves the A chains of factor XIII tetramers in a reaction stimulated by the presence of fibrin multimers. The amino terminal portions of the A chains are released as activation peptides, which have no known function. The resulting factor XIII tetramer remains catalytically inactive.
  • Activated thrombin cleaves the A chains of factor XIII tetramers in a reaction stimulated by the presence of fibrin multimers. The amino terminal portions of the A chains are released as activation peptides, which have no known function. The resulting factor XIII tetramer remains catalytically inactive.
fibrin multimerREACT_1852 (Reactome)
  • Fibrin multimers are stabilized by the formation of multiple covalent crosslinks between the side chains of specific lysine and glutamine residues in fibrinogen alpha and gamma chains, catalyzed by factor XIIIa.
  • Fibrin multimers are stabilized by the formation of multiple covalent crosslinks between the side chains of specific lysine and glutamine residues in fibrinogen alpha and gamma chains, catalyzed by factor XIIIa.
kallikrein C1InhArrowREACT_1486 (Reactome)
  • Activated kallikrein binds to C1Inh (plasma protease C1 inhibitor) (Bock et al. 1986), forming a stable and enzymatically inactive complex. This reaction appears to be the major means by which kallikrein is inactivated (kallikrein can also be inactivated by binding to alpha2-macroglobulin) (Harpel et al. 1985; Ratnoff et al. 1969).
  • Activated kallikrein binds to C1Inh (plasma protease C1 inhibitor) (Bock et al. 1986), forming a stable and enzymatically inactive complex. This reaction appears to be the major means by which kallikrein is inactivated (kallikrein can also be inactivated by binding to alpha2-macroglobulin) (Harpel et al. 1985; Ratnoff et al. 1969).
kallikrein alpha2-macroglobulinArrowREACT_25 (Reactome)
  • Activated kallikrein binds to alpha2-macroglobulin (Sottrup-Jensen et al. 1984), forming a stable and enzymatically inactive complex. Under normal conditions in vivo, this reaction appears to be responsible for the inactivation of about 1/6 of activated kallikrein (with C1Inh responsible for the inactivation of about 5/6) (Harpel et al. 1985).
  • Activated kallikrein binds to alpha2-macroglobulin (Sottrup-Jensen et al. 1984), forming a stable and enzymatically inactive complex. Under normal conditions in vivo, this reaction appears to be responsible for the inactivation of about 1/6 of activated kallikrein (with C1Inh responsible for the inactivation of about 5/6) (Harpel et al. 1985).
kallikrein

kininogen

C1q binding protein tetramer		REACT_2004 (Reactome)
  • The cleavage of kininogen (HK, high molecular weight kininogen) yields activated kininogen and the vasoactive peptide bradykinin (Kerbirou and Griffin 1979; Lottspeich et al. 1985; Kellerman et al. 1986). In vivo, this reaction is catalyzed by activated kallikrein, takes places within the kallikrein:kininogen:C1q binding protein tetramer complex on the endothelial cell surface, and results in the release of kallikrein and bradykinin (Motta et al. 1998). The hormonal functions of bradykinin will be annotated in a future version of Reactome.
  • The cleavage of kininogen (HK, high molecular weight kininogen) yields activated kininogen and the vasoactive peptide bradykinin (Kerbirou and Griffin 1979; Lottspeich et al. 1985; Kellerman et al. 1986). In vivo, this reaction is catalyzed by activated kallikrein, takes places within the kallikrein:kininogen:C1q binding protein tetramer complex on the endothelial cell surface, and results in the release of kallikrein and bradykinin (Motta et al. 1998). The hormonal functions of bradykinin will be annotated in a future version of Reactome.
kallikrein

kininogen

C1q binding protein tetramer		mim-catalysisREACT_1455 (Reactome)
  • Cleavage of a single peptide bond converts factor XII to activated factor XII (factor XIIa) (Fujikawa and McMullen 1983; McMullen and Fujikawa 1985). Identification of the catalytic activity or activities responsible for this cleavage has not been straightforward. Studies in vitro have demonstrated the autoactivation of factor XII as well as activation by kallikrein. Both reactions require the presence of negatively charged surfaces and are accelerated in the presence of kininogen (high molecular weight kininogen, HK) (Griffin and Cochrane 1976; Meier et al. 1977; Silverberg et al. 1980). Recent work suggests that factor XII activation in vivo may occur primarily on endothelial cell surfaces and that, as in vitro, association with kininogen may accelerate the reaction (Mahdi et al. 2002; Schmaier 2004), although alternative pathways and alternative mechanisms for associating factor XII with the cell surface have not been excluded (Joseph et al. 2001).
  • Cleavage of a single peptide bond converts factor XII to activated factor XII (factor XIIa) (Fujikawa and McMullen 1983; McMullen and Fujikawa 1985). Identification of the catalytic activity or activities responsible for this cleavage has not been straightforward. Studies in vitro have demonstrated the autoactivation of factor XII as well as activation by kallikrein. Both reactions require the presence of negatively charged surfaces and are accelerated in the presence of kininogen (high molecular weight kininogen, HK) (Griffin and Cochrane 1976; Meier et al. 1977; Silverberg et al. 1980). Recent work suggests that factor XII activation in vivo may occur primarily on endothelial cell surfaces and that, as in vitro, association with kininogen may accelerate the reaction (Mahdi et al. 2002; Schmaier 2004), although alternative pathways and alternative mechanisms for associating factor XII with the cell surface have not been excluded (Joseph et al. 2001).
kallikrein

kininogen

C1q binding protein tetramer		mim-catalysisREACT_2004 (Reactome)
  • The cleavage of kininogen (HK, high molecular weight kininogen) yields activated kininogen and the vasoactive peptide bradykinin (Kerbirou and Griffin 1979; Lottspeich et al. 1985; Kellerman et al. 1986). In vivo, this reaction is catalyzed by activated kallikrein, takes places within the kallikrein:kininogen:C1q binding protein tetramer complex on the endothelial cell surface, and results in the release of kallikrein and bradykinin (Motta et al. 1998). The hormonal functions of bradykinin will be annotated in a future version of Reactome.
  • The cleavage of kininogen (HK, high molecular weight kininogen) yields activated kininogen and the vasoactive peptide bradykinin (Kerbirou and Griffin 1979; Lottspeich et al. 1985; Kellerman et al. 1986). In vivo, this reaction is catalyzed by activated kallikrein, takes places within the kallikrein:kininogen:C1q binding protein tetramer complex on the endothelial cell surface, and results in the release of kallikrein and bradykinin (Motta et al. 1998). The hormonal functions of bradykinin will be annotated in a future version of Reactome.
prekallikrein

kininogen

C1q binding protein tetramer		ArrowREACT_1335 (Reactome)
  • Prekallikrein (PK) associates specifically with kininogen (HK) on cell surfaces. In vivo, this reaction may occur primarily on the surfaces of endothelial cells in response to platelet activation (Lin et al. 1997; Motta et al. 1998; Mahdi et al. 2003).
  • Prekallikrein (PK) associates specifically with kininogen (HK) on cell surfaces. In vivo, this reaction may occur primarily on the surfaces of endothelial cells in response to platelet activation (Lin et al. 1997; Motta et al. 1998; Mahdi et al. 2003).
prekallikrein

kininogen

C1q binding protein tetramer		kallikrein

kininogen

C1q binding protein tetramer		ArrowREACT_6 (Reactome)
  • Prekallikrein in a complex with kininogen and C1q binding protein on the plasma membrane is cleaved to generate active kallikrein, which remains bound to the complex. In the body, this reaction appears to occur on the surfaces of endothelial cells and may require the presence of activated platelets. Recent work indicates that the protease that cleaves prekallikrein under these conditions is prolylcarboxypeptidase. Although this enzyme was originally isolated from lysosomes (Odya et al. 1978; Tan et al. 1993), it is associated with plasma membranes of cultured human endothelial cells in vitro (Moreira et al. 2002; Shariat-Madar et al. 2002), and the purified recombinant enzyme efficiently cleaves prekallikrein (Shariat-Madar et al. 2004). In contrast factor XII, despite its activity on prekallikrein in vitro, appears not to be responsible for prekallikrein activation on the cell surface (Rojkjaer et al. 1998).
  • Prekallikrein in a complex with kininogen and C1q binding protein on the plasma membrane is cleaved to generate active kallikrein, which remains bound to the complex. In the body, this reaction appears to occur on the surfaces of endothelial cells and may require the presence of activated platelets. Recent work indicates that the protease that cleaves prekallikrein under these conditions is prolylcarboxypeptidase. Although this enzyme was originally isolated from lysosomes (Odya et al. 1978; Tan et al. 1993), it is associated with plasma membranes of cultured human endothelial cells in vitro (Moreira et al. 2002; Shariat-Madar et al. 2002), and the purified recombinant enzyme efficiently cleaves prekallikrein (Shariat-Madar et al. 2004). In contrast factor XII, despite its activity on prekallikrein in vitro, appears not to be responsible for prekallikrein activation on the cell surface (Rojkjaer et al. 1998).
prolylcarboxypeptidase dimermim-catalysisREACT_6 (Reactome)
  • Prekallikrein in a complex with kininogen and C1q binding protein on the plasma membrane is cleaved to generate active kallikrein, which remains bound to the complex. In the body, this reaction appears to occur on the surfaces of endothelial cells and may require the presence of activated platelets. Recent work indicates that the protease that cleaves prekallikrein under these conditions is prolylcarboxypeptidase. Although this enzyme was originally isolated from lysosomes (Odya et al. 1978; Tan et al. 1993), it is associated with plasma membranes of cultured human endothelial cells in vitro (Moreira et al. 2002; Shariat-Madar et al. 2002), and the purified recombinant enzyme efficiently cleaves prekallikrein (Shariat-Madar et al. 2004). In contrast factor XII, despite its activity on prekallikrein in vitro, appears not to be responsible for prekallikrein activation on the cell surface (Rojkjaer et al. 1998).
  • Prekallikrein in a complex with kininogen and C1q binding protein on the plasma membrane is cleaved to generate active kallikrein, which remains bound to the complex. In the body, this reaction appears to occur on the surfaces of endothelial cells and may require the presence of activated platelets. Recent work indicates that the protease that cleaves prekallikrein under these conditions is prolylcarboxypeptidase. Although this enzyme was originally isolated from lysosomes (Odya et al. 1978; Tan et al. 1993), it is associated with plasma membranes of cultured human endothelial cells in vitro (Moreira et al. 2002; Shariat-Madar et al. 2002), and the purified recombinant enzyme efficiently cleaves prekallikrein (Shariat-Madar et al. 2004). In contrast factor XII, despite its activity on prekallikrein in vitro, appears not to be responsible for prekallikrein activation on the cell surface (Rojkjaer et al. 1998).
protein CREACT_374 (Reactome)
  • Thrombin complexed with thrombomodulin at the endothelial cell surface cleaves the heavy chain of protein C, generating activated protein C and an activation peptide. The activation peptide has no known function.
  • Thrombin complexed with thrombomodulin at the endothelial cell surface cleaves the heavy chain of protein C, generating activated protein C and an activation peptide. The activation peptide has no known function.
sequestered tissue factorPalmC-F3ArrowREACT_1596 (Reactome)
  • Tissue factor sequestered in the wall of a blood vessel is exposed to circulating blood when the endothelial lining of the vessel is injured.
  • Tissue factor sequestered in the wall of a blood vessel is exposed to circulating blood when the endothelial lining of the vessel is injured.
thrombin

antithrombin III

heparin		ArrowREACT_1822 (Reactome)
  • Activated thrombin binds to the antithrombin III:heparin complex on the cell surface.
  • Activated thrombin binds to the antithrombin III:heparin complex on the cell surface.
thrombin

antithrombin III

heparin		mim-catalysisREACT_1500 (Reactome)
  • Antithrombin III in the complex is cleaved by thrombin, thereupon undergoing a conformational change that stabilizes the thrombin:antithrombin III complex, trapping and inactivating the thrombin moiety.
  • Antithrombin III in the complex is cleaved by thrombin, thereupon undergoing a conformational change that stabilizes the thrombin:antithrombin III complex, trapping and inactivating the thrombin moiety.
thrombin

antithrombin III

heparin		thrombin

cleaved antithrombin III

heparin		ArrowREACT_1500 (Reactome)
  • Antithrombin III in the complex is cleaved by thrombin, thereupon undergoing a conformational change that stabilizes the thrombin:antithrombin III complex, trapping and inactivating the thrombin moiety.
  • Antithrombin III in the complex is cleaved by thrombin, thereupon undergoing a conformational change that stabilizes the thrombin:antithrombin III complex, trapping and inactivating the thrombin moiety.
thrombin

cleaved antithrombin III

heparin		REACT_1283 (Reactome)
  • The same conformational change that traps thrombin in its complex with cleaved antithrombin III also decreases the affinity of the latter for heparin, and the complex of cleaved antithrombin III and thrombin dissociates from the cell-bound heparin molecule.
  • The same conformational change that traps thrombin in its complex with cleaved antithrombin III also decreases the affinity of the latter for heparin, and the complex of cleaved antithrombin III and thrombin dissociates from the cell-bound heparin molecule.
thrombin cleaved antithrombin IIIArrowREACT_1283 (Reactome)
  • The same conformational change that traps thrombin in its complex with cleaved antithrombin III also decreases the affinity of the latter for heparin, and the complex of cleaved antithrombin III and thrombin dissociates from the cell-bound heparin molecule.
  • The same conformational change that traps thrombin in its complex with cleaved antithrombin III also decreases the affinity of the latter for heparin, and the complex of cleaved antithrombin III and thrombin dissociates from the cell-bound heparin molecule.
von Willibrand factor multimerArrowREACT_217 (Reactome)
  • Factor VIII complexed to von Willibrand factor in the blood is cleaved into several smaller polypeptides that remain associated. The acidic polypeptide on the aminoterminal side of the A3 domain of the light chain is released, however, and as this polypeptide mediates the association of factor VIII with von Willibrand factor, the activated factor VIII is released. While several proteases are capable of catalyzing these cleavages in vitro, only thrombin is active on factor VIII:von Willibrand factor complexes under physiological conditions (Eaton et al. 1986; Hill-Eubanks et al. 1989; Lollar et al. 1988; Pieters et al. 1989)
  • Factor VIII complexed to von Willibrand factor in the blood is cleaved into several smaller polypeptides that remain associated. The acidic polypeptide on the aminoterminal side of the A3 domain of the light chain is released, however, and as this polypeptide mediates the association of factor VIII with von Willibrand factor, the activated factor VIII is released. While several proteases are capable of catalyzing these cleavages in vitro, only thrombin is active on factor VIII:von Willibrand factor complexes under physiological conditions (Eaton et al. 1986; Hill-Eubanks et al. 1989; Lollar et al. 1988; Pieters et al. 1989)
von Willibrand factor multimerREACT_531 (Reactome)
  • Factor VIII binds to von Willebrand factor to form a complex. This complex stabilizes factor VIII, which otherwise has a very short half-life in the blood.

    Factor VIII (Vehar et al. 1984) is a heterodimer containing a heavy and a light polypeptide chain, generated by the proteolytic cleavage of a single large precursor polypeptide. Several forms of the heavy chain are found in vivo, all functionally the same but differing in the amount of the B domain removed by proteolysis. The single form annotated here is the shortest one (Eaton et al. 1986; Hill-Eubanks et al. 1989).

    In vitro, von Willebrand factor (Titani et al. 1986) can form complexes with factor VIII with a 1:1 stoichiometry. The complexes that form in vivo, however, involve large multimers of von Willebrand factor and varied, but always low, proportions of factor VIII (Vlot et al. 1995). A stoichiometry of one molecule of factor VIII associated with 50 of von Willebrand factor is typical in vivo, and is used here to annotate the factor VIII:von Willebrand factor complex.

  • Factor VIII binds to von Willebrand factor to form a complex. This complex stabilizes factor VIII, which otherwise has a very short half-life in the blood.

    Factor VIII (Vehar et al. 1984) is a heterodimer containing a heavy and a light polypeptide chain, generated by the proteolytic cleavage of a single large precursor polypeptide. Several forms of the heavy chain are found in vivo, all functionally the same but differing in the amount of the B domain removed by proteolysis. The single form annotated here is the shortest one (Eaton et al. 1986; Hill-Eubanks et al. 1989).

    In vitro, von Willebrand factor (Titani et al. 1986) can form complexes with factor VIII with a 1:1 stoichiometry. The complexes that form in vivo, however, involve large multimers of von Willebrand factor and varied, but always low, proportions of factor VIII (Vlot et al. 1995). A stoichiometry of one molecule of factor VIII associated with 50 of von Willebrand factor is typical in vivo, and is used here to annotate the factor VIII:von Willebrand factor complex.

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