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

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56, 732131411615, 40, 95, 9721, 10535996, 26, 37, 877, 23, 25, 6454, 8910347, 5376, 91, 98, 100592192384914, 75, 96103901810, 12, 19, 43, 6929, 4546, 8010415, 20, 39, 78, 95...829430, 60, 71, 1029481728, 7137, 50, 55, 7794949, 63, 8345, 65, 9636187, 22, 88, 9870244, 80, 835, 51, 67, 68, 72...7457, 103105631cytoplasmthrombin heavy chain CD177 KLKB1(20-390) PROC(212-461) factor VIIIa A3 C1 C2 polypeptide thrombin light chain Ca2+ 8xCbxE-3D-PROC(43-197) activatedkininogen:C1qbinding proteintetramer12xCbxE-3D-F9(47-191) PROCR factor XaSERPINA5KLKB1(20-390) Zn2+8xCbxE-3D-PROC(43-197) GP1BB factor IXaCa2+ prolylcarboxypeptidase dimerKNG1(390-644) Ca2+ C1QBP KLKB1(391-638) KNG1(19-644) PROCR FGA(20-866) GAGfactor XI monomer factor XCa2+ factor V10xCbxE-F7(61-212) 8xCbxE-3D-PROC(43-197) factor XIIa light chain thrombin heavy chain SERPINC1 GP9 Platelet Factor 4SERPINE2:GAGPalmC-F3 factor VIII heavy chain GP5 8xCbxE-3D-PROC(43-197) KNG1(19-380) Ca2+thrombin light chain 11xCbxE-3D-F10(41-179) F2RGP9 antithrombinIII:heparinF13B factor VIIIF5(29-534) factor XIa light chain thrombin light chain factor Xa heavy chain thrombin light chain factor VIIIa B A3acidic polypeptidefactor XI monomer sequestered tissuefactorKNG1(19-644)factor IX activationpeptidefactor Va light chain Ca2+ F5(335-534)thrombin light chain factor VIIIa A2 polypeptide SERPING1 PF4(32-101) SERPINA5:Activatedprotein CGP1BA factor XIII cleavedtetramerF8(356-372)factor VIIIa:factorIXaF13B 10xCbxE-F7(61-466) VWF(764-2813) factor Va heavy chain factor V activationpeptide10xCbxE-F7(61-212) Activated protein Cfactor XIIafactor VIIIa A1 polypeptide Ca2+12xCbxE-3D-F9(47-191) SERPINC1(426-464) activated thrombin(factor IIa)Protein CPRTN3 Ca2+ Extracellularthrombininactivatingcomplexesfactor X heavy chain KNG1(19-644) factor VIIafactor Viprekallikrein:kininogen:C1q binding protein tetramerKNG1(19-644) Fibrinogenfactor VIII:vonWillebrand factormultimerfactor IXa heavy chain PRCP Ca2+ thrombin light chain factor XIIa heavy chain 11xCbxE-3D-F9(47-461)FGA factor XIIICa2+ PRTN3:CD177NH4+factor VIII light chain SERPINC1(33-425) C1QBP KLKB1(391-638) Ca2+ Ca2+ thrombin heavy chain PROCR:Activatedprotein C11xCbxE-3D-F10(41-179) Ca2+KLKB1(391-638) PROCR(18-?) F2R factor XI:GPIb-IX-VcomplexCa2+ factor VIIIa A3 C1 C2 polypeptide factor VIIIa A2 polypeptide FGB(31-44)KLKB1(391-638) SERPING1factor Viintermediate formSERPINA5 factor Xa heavy chain SERPINC1(426-464) thrombin:cleavedantithrombinIII:heparinCa2+ PF4V1(31-104) SERPIND1Ca2+ Ca2+ A2M factor Xa heavy chain TF:F7aFGG factor Va heavy chain factor IXa heavy chain C1q binding proteintetramerCa2+ 10xCbxE-F7(61-212) 8xCbxE-3D-PROC(43-197) TFPI:TF:F7a:factorXaKNG:C1q bindingprotein tetramerF8(582-640)factor VIIa heavy chain SERPING1 Ca2+ Heparin PROC(200-461) thrombin heavy chain factor VIIIaGPIb-IX-V complexfactor XIIa heavy chain PalmC-F3 thrombin light chain BradykininSERPINC1(33-425) factor XIIa:C1InhTFPIKLKB1(20-390) kallikrein:kininogen:C1q binding protein tetramerHeparinPROCR PROC(212-461) Plasma kallikreinfactor XIIIa A chain A2M PROCR:Protein CFGB(31-491) FGB kallikrein:alpha2-macroglobulinthrombin:antithrombin III:heparinactivated thrombin(factor IIa)Ca2+ PROC(212-461) factor X activationpeptideCa2+ PRTN3 von Willibrandfactor multimerFGA thrombin heavy chain fibrin multimerfactor VIII heavy chain factor XIIIa A chain F5(535-737)GP9 PalmC-F3factor XI8xCbxE-3D-PROC(43-197) factor XIII A chainactivation peptideKLKB1(20-638) Va:Xa complex(prothrombinase)factor VIIa heavy chain GP1BB GAG factor XIa heavy chain thrombin light chain Ca2+ FGB Ca2+ FGA(20-35)Ca2+11xCbxE-PROS1 Heparin PROC(200-461) factor VIIIaFGG factor Va light chain factor IXa heavy chain PROCRCa2+ factor Xa heavy chain 8xCbxE-3D-PROC(43-197) thrombin light chain 11xCbxE-3D-F10(41-179) thrombin heavy chain F8(20-355) activatedthrombin:thrombomodulinthrombin heavy chain Ca2+ SERPINC1(33-425) PROC(212-461) fibrin monomerGP1BB FGG A2M tetramerKLKB1(20-390) activated thrombin(factorIIa):SERPIND110xCbxE-F7(61-466)F5(29-334) GP5 10xCbxE-F2(44-622)PROCR:Activatedprotein C:F2Rfactor VIIIa A3 C1 C2 polypeptide C1QBP 12xCbxE-3D-F9(47-191) PalmC-F3 GAG F13BPROC(212-461) factor VIIIa A2 polypeptide factor Va light chain F8(373-581) Inactivated factorVIIITHBDfactor Xa10xCbxE-F2(44-327)PROC(212-461) PROCR(18-?) Activated proteinC:Protein Sthrombin heavy chain SERPINE2:GAG:activated thrombin (factor IIa)8xCbxE-3D-PROC(43-197) factor Va light chain CD177 11xCbxE-3D-F10(41-179) TF:F7SERPINC111xCbxE-3D-F10(41-179) GP1BA PROCR(18-?):PRTN3:CD177factor VIIIa A1 polypeptide factor VIII light chain factor XIIfactor VIIa heavy chain factor XIIa light chain C1QBP factor IXaKLKB1(20-638)PROC(200-211)11xCbxE-PROS1PROCR(18-?)factorXIa:GPIb:GPIX:GPVcomplexkallikrein:C1InhSERPINC1 GP5 Heparin thrombin heavy chain SERPINA5 SERPIND1 Ca2+ VWF(764-2813) thrombin:cleavedantithrombin IIISERPIND1 8xCbxE-3D-PROC(43-197) factor XIII A chain PROCR(18-?):Activated protein CKNG1(19-644)factor VIIIa A1 polypeptide SERPINE2 THBD C1QBP SERPINE2 TFPI factor VIIIa A3 C1 C2 polypeptide fibrin multimer,crosslinkedfactor XIIIaPROC(212-461) factor VaGP1BA SERPINC1(426-464) 13, 1014, 3342, 57, 6213, 42, 6213, 10113, 10110142, 628558, 6610342, 6227, 34, 793, 8542, 57, 624, 3358, 664, 3342, 57, 621127, 34, 791158, 6642, 57, 6233, 10524, 583, 1058124, 58, 663, 8558, 6627, 34, 791132, 6158, 664, 334842, 57, 623, 8558, 664, 3332, 6113, 42, 6242, 57, 6242, 57, 623, 8513, 42, 6258, 661832, 6113, 42, 624832, 614, 3310113, 10113, 42, 6227, 34, 791051842, 624, 3313, 42, 625213, 42, 6242, 57, 628627, 34, 794827, 34, 7910110132, 6113, 42, 624, 3342, 57, 624, 3358, 668113, 42, 62523


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. View original pathway at:Reactome.

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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-F2(44-327)ProteinP00734 (Uniprot-TrEMBL)
10xCbxE-F2(44-622)ProteinP00734 (Uniprot-TrEMBL)
10xCbxE-F7(61-212) ProteinP08709 (Uniprot-TrEMBL)
10xCbxE-F7(61-466) ProteinP08709 (Uniprot-TrEMBL)
10xCbxE-F7(61-466)ProteinP08709 (Uniprot-TrEMBL)
11xCbxE-3D-F10(41-179) ProteinP00742 (Uniprot-TrEMBL)
11xCbxE-3D-F9(47-461)ProteinP00740 (Uniprot-TrEMBL)
11xCbxE-PROS1 ProteinP07225 (Uniprot-TrEMBL)
11xCbxE-PROS1ProteinP07225 (Uniprot-TrEMBL)
12xCbxE-3D-F9(47-191) ProteinP00740 (Uniprot-TrEMBL)
8xCbxE-3D-PROC(43-197) ProteinP04070 (Uniprot-TrEMBL)
A2M ProteinP01023 (Uniprot-TrEMBL)
A2M tetramerComplexR-HSA-158255 (Reactome)
Activated protein C:Protein SComplexR-HSA-5604926 (Reactome)
Activated protein CComplexR-HSA-141050 (Reactome)
BradykininProteinP01042 (Uniprot-TrEMBL)
C1QBP ProteinQ07021 (Uniprot-TrEMBL)
C1q binding protein tetramerComplexR-HSA-158318 (Reactome)
CD177 ProteinQ8N6Q3 (Uniprot-TrEMBL)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
Extracellular

thrombin inactivating

complexes		ComplexR-HSA-5607050 (Reactome)
F13B ProteinP05160 (Uniprot-TrEMBL)
F13BProteinP05160 (Uniprot-TrEMBL)
F2R ProteinP25116 (Uniprot-TrEMBL)
F2RProteinP25116 (Uniprot-TrEMBL)
F5(29-334) ProteinP12259 (Uniprot-TrEMBL)
F5(29-534) ProteinP12259 (Uniprot-TrEMBL)
F5(335-534)ProteinP12259 (Uniprot-TrEMBL)
F5(535-737)ProteinP12259 (Uniprot-TrEMBL)
F8(20-355) ProteinP00451 (Uniprot-TrEMBL)
F8(356-372)ProteinP00451 (Uniprot-TrEMBL)
F8(373-581) ProteinP00451 (Uniprot-TrEMBL)
F8(582-640)ProteinP00451 (Uniprot-TrEMBL)
FGA ProteinP02671 (Uniprot-TrEMBL)
FGA(20-35)ProteinP02671 (Uniprot-TrEMBL)
FGA(20-866) ProteinP02671 (Uniprot-TrEMBL)
FGB ProteinP02675 (Uniprot-TrEMBL)
FGB(31-44)ProteinP02675 (Uniprot-TrEMBL)
FGB(31-491) ProteinP02675 (Uniprot-TrEMBL)
FGG ProteinP02679 (Uniprot-TrEMBL)
FibrinogenComplexR-HSA-114618 (Reactome) Fibrinogen is a hexamer, containing two fibrinogen alpha chains, two fibrinogen beta chains, and two fibrinogen gamma chains, held together by disulfide bonds.
GAG MetaboliteCHEBI:18085 (ChEBI)
GAGMetaboliteCHEBI:18085 (ChEBI)
GP1BA ProteinP07359 (Uniprot-TrEMBL)
GP1BB ProteinP13224 (Uniprot-TrEMBL)
GP5 ProteinP40197 (Uniprot-TrEMBL)
GP9 ProteinP14770 (Uniprot-TrEMBL)
GPIb-IX-V complexComplexR-HSA-114668 (Reactome)
Heparin R-NUL-140798 (Reactome)
HeparinR-NUL-140798 (Reactome)
Inactivated factor VIIIComplexR-HSA-5607059 (Reactome)
KLKB1(20-390) ProteinP03952 (Uniprot-TrEMBL)
KLKB1(20-638) ProteinP03952 (Uniprot-TrEMBL)
KLKB1(20-638)ProteinP03952 (Uniprot-TrEMBL)
KLKB1(391-638) ProteinP03952 (Uniprot-TrEMBL)
KNG1(19-380) ProteinP01042 (Uniprot-TrEMBL)
KNG1(19-644) ProteinP01042 (Uniprot-TrEMBL)
KNG1(19-644)ProteinP01042 (Uniprot-TrEMBL)
KNG1(390-644) ProteinP01042 (Uniprot-TrEMBL)
KNG:C1q binding protein tetramerComplexR-HSA-158172 (Reactome)
NH4+MetaboliteCHEBI:28938 (ChEBI)
PF4(32-101) ProteinP02776 (Uniprot-TrEMBL)
PF4V1(31-104) ProteinP10720 (Uniprot-TrEMBL)
PRCP ProteinP42785 (Uniprot-TrEMBL)
PROC(200-211)ProteinP04070 (Uniprot-TrEMBL)
PROC(200-461) ProteinP04070 (Uniprot-TrEMBL)
PROC(212-461) ProteinP04070 (Uniprot-TrEMBL)
PROCR ProteinQ9UNN8 (Uniprot-TrEMBL)
PROCR(18-?) ProteinQ9UNN8 (Uniprot-TrEMBL)
PROCR(18-?):Activated protein CComplexR-HSA-5610097 (Reactome)
PROCR(18-?):PRTN3:CD177ComplexR-HSA-5610092 (Reactome)
PROCR(18-?)ProteinQ9UNN8 (Uniprot-TrEMBL)
PROCR:Activated protein C:F2RComplexR-HSA-5607093 (Reactome)
PROCR:Activated protein CComplexR-HSA-5603469 (Reactome)
PROCR:Protein CComplexR-HSA-5603321 (Reactome)
PROCRProteinQ9UNN8 (Uniprot-TrEMBL)
PRTN3 ProteinP24158 (Uniprot-TrEMBL)
PRTN3:CD177ComplexR-HSA-5610107 (Reactome)
PalmC-F3 ProteinP13726 (Uniprot-TrEMBL)
PalmC-F3ProteinP13726 (Uniprot-TrEMBL)
Plasma kallikreinComplexR-HSA-158140 (Reactome)
Platelet Factor 4ComplexR-HSA-203105 (Reactome)
Protein CComplexR-HSA-141043 (Reactome)
SERPINA5 ProteinP05154 (Uniprot-TrEMBL)
SERPINA5:Activated protein CComplexR-HSA-5607007 (Reactome)
SERPINA5ProteinP05154 (Uniprot-TrEMBL)
SERPINC1 ProteinP01008 (Uniprot-TrEMBL)
SERPINC1(33-425) ProteinP01008 (Uniprot-TrEMBL)
SERPINC1(426-464) ProteinP01008 (Uniprot-TrEMBL)
SERPINC1ProteinP01008 (Uniprot-TrEMBL)
SERPIND1 ProteinP05546 (Uniprot-TrEMBL)
SERPIND1ProteinP05546 (Uniprot-TrEMBL)
SERPINE2 ProteinP07093 (Uniprot-TrEMBL)
SERPINE2:GAG:activated thrombin (factor IIa)ComplexR-HSA-5607781 (Reactome)
SERPINE2:GAGComplexR-HSA-5607782 (Reactome)
SERPING1 ProteinP05155 (Uniprot-TrEMBL)
SERPING1ProteinP05155 (Uniprot-TrEMBL)
TF:F7ComplexR-HSA-140775 (Reactome)
TF:F7aComplexR-HSA-140734 (Reactome)
TFPI ProteinP10646 (Uniprot-TrEMBL)
TFPI:TF:F7a:factor XaComplexR-HSA-140833 (Reactome)
TFPIProteinP10646 (Uniprot-TrEMBL)
THBD ProteinP07204 (Uniprot-TrEMBL)
THBDProteinP07204 (Uniprot-TrEMBL)
VWF(764-2813) ProteinP04275 (Uniprot-TrEMBL)
Va:Xa complex (prothrombinase)ComplexR-HSA-140662 (Reactome)
Zn2+MetaboliteCHEBI:29105 (ChEBI)
activated

kininogen:C1q binding protein

tetramer		ComplexR-HSA-158257 (Reactome)
activated thrombin:thrombomodulinComplexR-HSA-141038 (Reactome)
activated thrombin

(factor

IIa):SERPIND1		ComplexR-HSA-5578881 (Reactome)
activated thrombin (factor IIa)ComplexR-HSA-140811 (Reactome)
activated thrombin (factor IIa)ComplexR-HSA-156786 (Reactome)
antithrombin III:heparinComplexR-HSA-140799 (Reactome)
factor

XIa:GPIb:GPIX:GPV

complex		ComplexR-HSA-158130 (Reactome)
factor IX activation peptideProteinP00740 (Uniprot-TrEMBL)
factor IXa heavy chain ProteinP00740 (Uniprot-TrEMBL)
factor IXaComplexR-HSA-140896 (Reactome)
factor IXaComplexR-HSA-5633117 (Reactome)
factor V activation peptideProteinP12259 (Uniprot-TrEMBL)
factor VIII heavy chain ProteinP00451 (Uniprot-TrEMBL)
factor VIII light chain ProteinP00451 (Uniprot-TrEMBL)
factor VIII:von

Willebrand factor

multimer		ComplexR-HSA-158363 (Reactome)
factor VIIIComplexR-HSA-158350 (Reactome)
factor VIIIa A1 polypeptide ProteinP00451 (Uniprot-TrEMBL)
factor VIIIa A2 polypeptide ProteinP00451 (Uniprot-TrEMBL)
factor VIIIa A3 C1 C2 polypeptide ProteinP00451 (Uniprot-TrEMBL)
factor VIIIa B A3 acidic polypeptideProteinP00451 (Uniprot-TrEMBL)
factor VIIIa:factor IXaComplexR-HSA-158392 (Reactome)
factor VIIIaComplexR-HSA-158307 (Reactome)
factor VIIIaComplexR-HSA-5633116 (Reactome)
factor VIIa heavy chain ProteinP08709 (Uniprot-TrEMBL)
factor VIIaComplexR-HSA-140751 (Reactome)
factor VProteinP12259 (Uniprot-TrEMBL)
factor Va heavy chain ProteinP12259 (Uniprot-TrEMBL)
factor Va light chain ProteinP12259 (Uniprot-TrEMBL)
factor VaComplexR-HSA-140692 (Reactome)
factor Vi intermediate formComplexR-HSA-141055 (Reactome)
factor ViComplexR-HSA-5605105 (Reactome)
factor X activation peptideProteinP00742 (Uniprot-TrEMBL)
factor X heavy chain ProteinP00742 (Uniprot-TrEMBL)
factor XI monomer ProteinP03951 (Uniprot-TrEMBL)
factor XI:GPIb-IX-V complexComplexR-HSA-158162 (Reactome)
factor XIII A chain activation peptideProteinP00488 (Uniprot-TrEMBL)
factor XIII A chain ProteinP00488 (Uniprot-TrEMBL)
factor XIII cleaved tetramerComplexR-HSA-140789 (Reactome)
factor XIIIComplexR-HSA-140608 (Reactome)
factor XIIIa A chain ProteinP00488 (Uniprot-TrEMBL)
factor XIIIaComplexR-HSA-140849 (Reactome)
factor XIIProteinP00748 (Uniprot-TrEMBL)
factor XIIa heavy chain ProteinP00748 (Uniprot-TrEMBL)
factor XIIa light chain ProteinP00748 (Uniprot-TrEMBL)
factor XIIa:C1InhComplexR-HSA-158141 (Reactome)
factor XIIaComplexR-HSA-158306 (Reactome)
factor XIComplexR-HSA-158234 (Reactome)
factor XIa heavy chain ProteinP03951 (Uniprot-TrEMBL)
factor XIa light chain ProteinP03951 (Uniprot-TrEMBL)
factor XComplexR-HSA-140739 (Reactome)
factor Xa heavy chain ProteinP00742 (Uniprot-TrEMBL)
factor XaComplexR-HSA-140649 (Reactome)
factor XaComplexR-HSA-140689 (Reactome)
fibrin monomerComplexR-HSA-140586 (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 multimer, crosslinkedR-NUL-157771 (Reactome)
fibrin multimerComplexR-HSA-139933 (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.
kallikrein:C1InhComplexR-HSA-158423 (Reactome)
kallikrein:alpha2-macroglobulinComplexR-HSA-158334 (Reactome)
kallikrein:kininogen:C1q binding protein tetramerComplexR-HSA-158197 (Reactome)
prekallikrein:kininogen:C1q binding protein tetramerComplexR-HSA-158404 (Reactome)
prolylcarboxypeptidase dimerComplexR-HSA-158176 (Reactome)
sequestered tissue factorProteinP13726 (Uniprot-TrEMBL)
thrombin heavy chain ProteinP00734 (Uniprot-TrEMBL)
thrombin light chain ProteinP00734 (Uniprot-TrEMBL)
thrombin:antithrombin III:heparinComplexR-HSA-140812 (Reactome)
thrombin:cleaved

antithrombin

III:heparin		ComplexR-HSA-140871 (Reactome)
thrombin:cleaved antithrombin IIIComplexR-HSA-140874 (Reactome)
von Willibrand factor multimerComplexR-HSA-158136 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
10xCbxE-F2(44-327)ArrowR-HSA-140664 (Reactome)
10xCbxE-F2(44-327)ArrowR-HSA-140700 (Reactome)
10xCbxE-F2(44-622)R-HSA-140664 (Reactome)
10xCbxE-F2(44-622)R-HSA-140700 (Reactome)
10xCbxE-F7(61-466)R-HSA-140769 (Reactome)
10xCbxE-F7(61-466)R-HSA-140783 (Reactome)
11xCbxE-3D-F9(47-461)R-HSA-140823 (Reactome)
11xCbxE-3D-F9(47-461)R-HSA-158333 (Reactome)
11xCbxE-PROS1R-HSA-5604929 (Reactome)
A2M tetramerR-HSA-158340 (Reactome)
Activated protein C:Protein SArrowR-HSA-5604929 (Reactome)
Activated protein C:Protein Smim-catalysisR-HSA-141026 (Reactome)
Activated protein C:Protein Smim-catalysisR-HSA-5591040 (Reactome)
Activated protein C:Protein Smim-catalysisR-HSA-5607002 (Reactome)
Activated protein CArrowR-HSA-5603467 (Reactome)
Activated protein CR-HSA-5591086 (Reactome)
Activated protein CR-HSA-5604929 (Reactome)
Activated protein CR-HSA-5606996 (Reactome)
BradykininArrowR-HSA-158311 (Reactome)
C1q binding protein tetramerR-HSA-158354 (Reactome)
Ca2+ArrowR-HSA-158278 (Reactome)
Ca2+ArrowR-HSA-158333 (Reactome)
Ca2+R-HSA-140736 (Reactome)
Ca2+R-HSA-140847 (Reactome)
Ca2+R-HSA-158164 (Reactome)
Extracellular

thrombin inactivating

complexes		TBarR-HSA-140599 (Reactome)
Extracellular

thrombin inactivating

complexes		TBarR-HSA-140696 (Reactome)
Extracellular

thrombin inactivating

complexes		TBarR-HSA-140840 (Reactome)
Extracellular

thrombin inactivating

complexes		TBarR-HSA-158137 (Reactome)
Extracellular

thrombin inactivating

complexes		TBarR-HSA-158419 (Reactome)
F13BArrowR-HSA-140847 (Reactome)
F2RR-HSA-5607058 (Reactome)
F5(335-534)ArrowR-HSA-5591040 (Reactome)
F5(535-737)ArrowR-HSA-141026 (Reactome)
F8(356-372)ArrowR-HSA-5607002 (Reactome)
F8(582-640)ArrowR-HSA-5607002 (Reactome)
FGA(20-35)ArrowR-HSA-140840 (Reactome)
FGB(31-44)ArrowR-HSA-140840 (Reactome)
FibrinogenR-HSA-140840 (Reactome)
GAGArrowR-HSA-5578883 (Reactome)
GAGArrowR-HSA-5591086 (Reactome)
GPIb-IX-V complexR-HSA-158145 (Reactome)
HeparinArrowR-HSA-140872 (Reactome)
HeparinR-HSA-140806 (Reactome)
Inactivated factor VIIIArrowR-HSA-5607002 (Reactome)
KLKB1(20-638)R-HSA-158218 (Reactome)
KNG1(19-644)ArrowR-HSA-158313 (Reactome)
KNG1(19-644)R-HSA-158354 (Reactome)
KNG:C1q binding protein tetramerArrowR-HSA-158354 (Reactome)
KNG:C1q binding protein tetramerR-HSA-158218 (Reactome)
NH4+ArrowR-HSA-140851 (Reactome)
PROC(200-211)ArrowR-HSA-141040 (Reactome)
PROCR(18-?):Activated protein CArrowR-HSA-5606996 (Reactome)
PROCR(18-?):Activated protein CTBarR-HSA-5591052 (Reactome)
PROCR(18-?):PRTN3:CD177ArrowR-HSA-5607004 (Reactome)
PROCR(18-?)R-HSA-5606996 (Reactome)
PROCR(18-?)R-HSA-5607004 (Reactome)
PROCR:Activated protein C:F2RArrowR-HSA-5607058 (Reactome)
PROCR:Activated protein CArrowR-HSA-141040 (Reactome)
PROCR:Activated protein CR-HSA-5603467 (Reactome)
PROCR:Activated protein CR-HSA-5607058 (Reactome)
PROCR:Protein CArrowR-HSA-5591052 (Reactome)
PROCR:Protein CR-HSA-141040 (Reactome)
PROCRArrowR-HSA-5603467 (Reactome)
PROCRR-HSA-5591052 (Reactome)
PRTN3:CD177R-HSA-5607004 (Reactome)
PalmC-F3ArrowR-HSA-140761 (Reactome)
PalmC-F3R-HSA-140748 (Reactome)
PalmC-F3R-HSA-140783 (Reactome)
Plasma kallikreinArrowR-HSA-158311 (Reactome)
Plasma kallikreinR-HSA-158340 (Reactome)
Plasma kallikreinR-HSA-158399 (Reactome)
Platelet Factor 4ArrowR-HSA-141040 (Reactome)
Protein CR-HSA-5591052 (Reactome)
R-HSA-140599 (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.
R-HSA-140664 (Reactome) The membrane-bound Va:Xa (prothrombinase) complex rapidly activates large amounts of thrombin.
R-HSA-140686 (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.
R-HSA-140696 (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.
R-HSA-140700 (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.
R-HSA-140736 (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.)
R-HSA-140748 (Reactome) Tissue factor exposed at the endothelial cell surface forms a complex with F7a (activated factor VII) from the plasma
R-HSA-140761 (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.
R-HSA-140769 (Reactome) Factor Xa catalyzes the activation of factor VII from plasma.
R-HSA-140777 (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.)
R-HSA-140783 (Reactome) Tissue factor exposed at the endothelial cell surface forms a complex with factor VII from plasma.
R-HSA-140791 (Reactome) Activated thrombin binds to the antithrombin III:heparin complex on the cell surface.
R-HSA-140806 (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.
R-HSA-140823 (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.)
R-HSA-140825 (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.
R-HSA-140840 (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).
R-HSA-140842 (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.
R-HSA-140847 (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).
R-HSA-140851 (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.
R-HSA-140870 (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.
R-HSA-140872 (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.
R-HSA-141026 (Reactome) Activated protein C cleaves peptide bonds in activated factor V (factor Va), converting it to an inactive form (factor Vi). APC proteolysis involves cleavage of the factor Va heavy chain at Arg-334 (306 if signal peptide is not included) and Arg-534 (506 with no signal peptide) (Nicolaes et al. 1985). Most factor Va molecules are initially cleaved at Arg-534, yielding a partially active intermediate, followed by complete inactivation through cleavage at Arg-334 (Kalafatis et al. 1994). Factor Xa inhibits Arg-534 cleavage but this effect is mitigated by Protein S (Norstrom et al. 2006). A mutation of the APC cleavage sites in Fv at Arg-534Gln a.k.a. FVLeiden is the most common identifiable hereditary risk factor for venous thrombosis among Caucasians (Camire 2011).
R-HSA-141040 (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.
R-HSA-141046 (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.
R-HSA-158118 (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.

R-HSA-158137 (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)
R-HSA-158145 (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).
R-HSA-158164 (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.)
R-HSA-158218 (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).
R-HSA-158251 (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).
R-HSA-158278 (Reactome) Factors VIIIa and IXa associate on cell surfaces 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).
R-HSA-158300 (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).
R-HSA-158311 (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.
R-HSA-158313 (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).
R-HSA-158333 (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.)
R-HSA-158340 (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).
R-HSA-158354 (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.
R-HSA-158357 (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).
R-HSA-158399 (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).
R-HSA-158419 (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).
R-HSA-5578883 (Reactome) SERPIND1 (Heparin cofactor 2) is a serine endopeptidase inhibitor (SERPIN) that acts as a pseudosubstrate for activated thrombin, forming a stable complex which has the effect of inactivating thrombin protease activity (Church et al. 1985), although with slower kinetics than SERPINC1 (antithrombin-III). The presence of the glycosaminoglycans heparin or dermatan sulphate increases thrombin inactivation 1000-fold (Van Deerlin & Tollefsen 199) by facilitating the interaction between the active site of thrombin and the reactive site of SERPIND1. Thrombin specificity is conferred by a 90-residue N-terminal extension that contains two acidic motifs containing sulphated Tyr residues, resembling the C-terminus of hirudin (Tollefsen et al. 1997). SERPIND1 also inhibits chymotrypsin and neutrophil cathepsin G, but in a glycosaminoglycan independent manner (Church et al. 1985). In contrast to SERPINC1 deficiency, SERPIND1 deficiency is not associated with venous thrombosis (Corral et al. 2004).
R-HSA-5591040 (Reactome) Protein C is best known for its anticoagulant activity, the proteolytic inactivation of FVa and FVIIIa on negatively charged phospholipid membranes. This is enhanced by cofactors protein S and FV (Rosing et al. 1995, Norstrom et al. 2006). Inactivation of FVa involves APC-mediated cleavages at Arg306 and Arg506. The rapid cleavage at Arg506 is kinetically favored over cleavage at Arg306, but results only in partial inactivation of FVa, whereas the slower cleavage at Arg306 results in a complete loss of FVa function (Kalafatis et al. 1994, Nicolaes et al. 1995). Protein S accelerates factor Va inactivation by selectively promoting the slow cleavage at Arg306 (Rosing et al. 1995). A mutation of the APC cleavage sites in FV Arg506Gln a.k.a. FVLeiden is the most common identifiable hereditary risk factor for venous thrombosis among Caucasians (Camire 2011). APC also has a role in the inactivation of FVIIIa (Regan et al. 1994). Similar to FVa inactivation, FVIIIa is cleaved by APC at Arg336 in the A1 subunit and at Arg562 in the A2 subunit, with either resulting in a complete loss of cofactor activity (O'Brien et al. 2000, Manithody et al. 2003). Both protein S and FV but not FVa enhance inactivation of FVIIIa by APC (O'Brien et al. 2000,57). By acting on FVa and FVIIIa Protein C down-regulates both primary and secondary thrombin formation, delaying clot formation and diminishing activation of TAFI, enhanced susceptibility of the clot to fibrinolysis, respectively. The latter effects of APC on secondary thrombin formation is sometimes referred to as APC’s profibrinolytic effect (Bajzar et al. 1996).
R-HSA-5591052 (Reactome) Physiological activation of protein C on the endothelial cell surface requires the binding of protein C to the endothelial protein C receptor PROCR (EPCR) as well as binding of thrombin to thrombomodulin (TM) (Stavenuiter et al. 2013). PROCR binding to protein C (Fukudome & Esmon 1994) augments by at least 5-fold the effect of thrombin-thrombomodulin on the rate of protein C activation (Stearns-Kurosawa et al. 1996, Taylor et al. 2001).
R-HSA-5591086 (Reactome) SERPINA5, also called Plasma serine protease inhibitor or Protein C inhibitor, inactivates serine proteases by binding irreversibly to their serine activation site. It is involved in the regulation of intravascular and extravascular proteolytic activities, promoting coagulation by inhibiting the anticoagulant complex Activated protein C (APC), but also acts as an anticoagulant factor by inhibiting blood coagulation factors such as prothrombin, factor XI, factor Xa, plasma kallikrein and fibrinolytic enzymes such as tissue- and urinary-type plasminogen activators. Its inhibitory activity is greatly enhanced in the presence of glycosaminoglycans (GAGs), heparin, thrombomodulin and phospholipids vesicles (Suzuki et al. 1985).

SERPINA5 inhibits activated protein C In the blood plasma and inhibits thromibin as part of the thrombin:thrombomodulin complex (Rezaie et al. 1995). On the other hand, PCI can also inhibit coagulation factors (Radtke et al. 2007). The SERPINA5:APC complex is a marker of thrombotic events (Kolbel et al. 2006), which suggests that despite low circulating SERPINA5 concentrations and rates of APC inhibition, its predominant role is procoagulatory (Li & Huntington 2008). This is due to the enhancing effect of GAGs, which line the vascular endothelium. Both SERPINA5 and APC bind to GAGs. The presence of heparin in vitro accelerates the maximal rate of inhibition by over 2000-fold (when accounting for dissociation constants) (Yang et al. 2002).
R-HSA-5602080 (Reactome) SERPINE2 (Protease nexin-1, PN1) is a specific and extremely efficient inhibitor of thrombin. Unlike other thrombin inhibitors belonging to the serpin family, SERPINE2 does not circulate in the blood (Bouton et al. 2012). Rather, it is bound to glycosaminoglycans on the surface of cell types including macrophages, smooth muscle cells and platelets, where it inhibits the signaling functions of thrombin. SERPINE2 sets the threshold for thrombin-induced platelet activation (Gronke et al. 1987, Boulaftali et al. 2010) and has been implicated in atherosclerosis (Bouton et al. 2012). Recent studies have demonstrated an important antithrombotic effect of platelet SERPINE2 in vitro and in vivo (Boulaftali et al. 2010).
R-HSA-5603467 (Reactome) Activated protein C (APC) can either dissociate from PROCR to exert its anticoagulant activity, or remain bound to PROCR where it influences multiple direct cellular activities. Dissociation of APC from PROCR allows APC to associate with other cell membrane surface molecules, various microparticles, or lipoproteins (e.g., high-density lipoprotein). As an anticoagulant, APC cleaves the activated cofactors Va (fVa) and VIIIa (fVIIIa), yielding inactivated cofactors, fVi and fVIIIi. This proteolytic inactivation is enhanced by protein cofactors (e.g., protein S, factor V) and lipids cofactors (e.g., phosphatidylserine, cardiolipin, glucosylceramide, or HDL).
R-HSA-5604929 (Reactome) Activated protein C binds to Protein S on appropriate cell surfaces where it inactivates factors Va and VIIIa.
Protein S is best known as a cofactor for the Activated protein C (APC)-catalyzed inactivation of factor Va (Walker 1980). Protein S must be membrane-bound to display this cofactor activity (Hackeng et al. 1993). Protein S binding brings the active site of APC closer to the phospholipid cell surface (Yegneswaran et al. 1999).

APC proteolysis involves cleavage of the factor Va heavy chain at Arg-306 and Arg-506 (Nicolaes et al. 1985). Most factor Va molecules are initially cleaved at Arg506, yielding a partially active intermediate, followed by complete inactivation through cleavage at Arg306 (Kalafatis et al. 1994). Protein S stimulates the cleavage at Arg306 ~20-fold (Rosing et al. 1995) and also counteracts the protective effect of factor Xa on Arg506 cleavage (Norstrom et al. 2006).

Protein S also enhances the APC-mediated inactivation of factor VIIIa (van de Poel et al. 2001). Protein S and factor V act as synergistic cofactors in the APC-mediated inactivation of factor VIIIa (Shen & Dahlback 1994, Somajo et al. 2014).
R-HSA-5606996 (Reactome) A soluble form of PROCR (sEPCR) fully retains the ability to bind Protein C and Activated protein C (Kurosawa et al. 1997). This form increases up to 5-fold in patients with sepsis or systemic lupus erythematosus (Kurosawa et al. 1998), either from vascular injury or through a regulated proteolytic release of soluble receptor (Gu et al. 2000). sEPCR inhibits protein C activation over large vessel endothelium in culture, reflecting competition between the soluble and cell surface forms of PROCR (Liaw et al. 2000).
R-HSA-5607002 (Reactome) Activated Protein C (APC) is best known for its anticoagulant activity, the proteolytic inactivation of FVa and FVIIIa on negatively charged phospholipid membranes. This is enhanced by cofactors protein S and factor V (Rosing et al. 1995, Norstrom et al. 2006).

APC inactivates FVIIIa (Regan et al. 1994) with a mechanism similar to its inactivation of FVa. FVIIIa is cleaved by APC at Arg355 (336 if numbering excludes signal peptide) in the A1 subunit and at Arg581 (562 if numbering excludes signal peptide) in the A2 subunit (O'Brien et al. 2000, Manithody et al. 2003). The Arg355 cleavage is 6-fold faster than the Arg581 cleavage but does not fully inactivate factor VIIIa if dissociation of the A2 subunit is blocked (Gale et al. 2008). Protein S and Factor V (but not FVa) enhance the inactivation of FVIIIa by APC (O'Brien et al. 2000). Protein S and factor V both enhance cleavage at both sites, more so at Arg581 (Gale et al. 2008).

The A2 subunit of FVIIIa spontaneously dissociates, inactivating FVIIIa with a half-life of about 2 min (Fay et al. 1991).

By acting on FVa and FVIIIa Protein C down-regulates both primary and secondary thrombin formation, delaying clot formation and diminishing activation of TAFI, enhanced susceptibility of the clot to fibrinolysis, respectively. The latter effects of APC on secondary thrombin formation is sometimes referred to as APC’s profibrinolytic effect (Bajzar et al. 1996).
R-HSA-5607004 (Reactome) Soluble PROCR binds to activated neutrophils via PRTN3, also cknown as myeloblastin and (Leukocyte) proteinase-3 (Kurosawa et al. 2000). PRTN3 is the most abundant serine protease in neutrophils (Campbell et al. 2000). After neutrophil activation, PRTN3 is secreted from azurophil granules, rebinding to the neutrophil surface through an association with CD177 (NB1) a 60-kDa glycosyl-phosphatidylinositol (GPI)-linked cell surface glycoprotein, which is expressed on a subpopulation of neutrophils in 97% of healthy individuals (Knuckleburg et al. 2012). PRTN3 is partially protected from inactivation when associated with CD177 (Campbell et al. 2000) which may increase its efficacy. CD177 is a heterophilic binding partner for endothelial cell platelet-endothelial cell adhesion molecule (PECAM)-1, which is expressed at endothelial cell junctions where transmigration occurs (Sun et al. 2000) suggesting that CD177 directs at least a subpopulation of PRTN3 molecules to these areas to aid neutrophil diapedesis, perhaps through PRTN3 degradation of cell junction proteins or the extracellular matrix.
R-HSA-5607023 (Reactome) Membrane-bound thrombin-activated factor VIII (fVIIIa) functions as a cofactor for factor IXa in the factor Xase complex. Factors VIIIa and IXa associate with anionic phospholipid surfaces with high affinity (Respective Kd values ?1 nM and ~15nM, Gilbert et al. 1990, Mertens & Bertina 1984, Greengard et al. 1986). Studies using physiologic surfaces provide evidence for coordinated binding interactions of the enzyme, cofactor and substrate to discrete surface structures. For example, the presence of both (active site-modified) factor IXa and factor X increased both the number and the affinity of binding sites on activated platelets for factor VIIIa (Ahmad et al. 2000). However classical receptors for the constituents of factor Xase have not been identified (Fay 2004).
R-HSA-5607043 (Reactome) Cleavage of factor VIII light chain promotes a change in the conformation of the C2 domain that facilitates dissociation from VWF and enhances the affinity of factor VIIIa for anionic phospholipid surfaces (Saenko et al. 1998).

Membrane-bound thrombin-activated factor VIII (fVIIIa) functions as a cofactor for factor IXa in the factor Xase complex. Factors VIIIa and IXa associate with anionic phospholipid surfaces with high affinity (Respective Kd values ?1 nM and ~15nM, Gilbert et al. 1990, Mertens & Bertina 1984, Greengard et al. 1986). Studies using physiologic surfaces provide evidence for coordinated binding interactions of the enzyme, cofactor and substrate to discrete surface structures. For example, the presence of both (active site-modified) factor IXa and factor X increased both the number and the affinity of binding sites on activated platelets for factor VIIIa (Ahmad et al. 2000). However classical receptors for the constituents of factor Xase have not been identified (Fay 2004).


R-HSA-5607058 (Reactome) F2R (PAR1) mediates multiple cytoprotective effects of Activated proein C (APC) (Riewald et al. 2002, Griffin et al. 2007). In most, but not all, reported studies of APC’s beneficial effects on endothelial cells, the cellular receptors EPCR and F2R are required. These cytoprotective effects include anti-apoptotic activities, anti-inflammatory activities, protection of endothelial barrier functions, and favorable alteration of gene expression profiles. This paradigm in which EPCR-bound APC activates F2R to initiate signaling is consistent with many in vitro and in vivo data. Localization of APC signaling to caveolin-1-rich microdomains (caveolae) may help differentiate mechanisms for cytoprotective APC signaling versus proinflammatory thrombin signaling. Additional mechanisms for APC effects on cells may involve other receptors. These effects include APC anti-inflammatory effects on leukocytes or cytoprotective effects on dendritic cells and neurons. Other receptors may include F2RL2 (PAR3), various integrins e.g., Mac-1 (CD11b/CD18), Beta-1 integrins, Beta-3 integrins, S1P1, or the apolipoprotein E receptor 2 (LRP8) (Mosnier et al. 2007).
SERPINA5:Activated protein CArrowR-HSA-5591086 (Reactome)
SERPINA5R-HSA-5591086 (Reactome)
SERPINC1R-HSA-140806 (Reactome)
SERPIND1R-HSA-5578883 (Reactome)
SERPINE2:GAG:activated thrombin (factor IIa)ArrowR-HSA-5602080 (Reactome)
SERPINE2:GAGR-HSA-5602080 (Reactome)
SERPING1R-HSA-158357 (Reactome)
SERPING1R-HSA-158399 (Reactome)
TBarR-HSA-140599 (Reactome)
TBarR-HSA-140696 (Reactome)
TBarR-HSA-158137 (Reactome)
TBarR-HSA-158419 (Reactome)
TF:F7ArrowR-HSA-140783 (Reactome)
TF:F7aArrowR-HSA-140748 (Reactome)
TF:F7aR-HSA-140825 (Reactome)
TF:F7amim-catalysisR-HSA-140736 (Reactome)
TF:F7amim-catalysisR-HSA-140823 (Reactome)
TF:F7mim-catalysisR-HSA-140777 (Reactome)
TFPI:TF:F7a:factor XaArrowR-HSA-140825 (Reactome)
TFPIR-HSA-140825 (Reactome)
THBDR-HSA-141046 (Reactome)
Va:Xa complex (prothrombinase)ArrowR-HSA-140686 (Reactome)
Va:Xa complex (prothrombinase)mim-catalysisR-HSA-140664 (Reactome)
Zn2+ArrowR-HSA-158354 (Reactome)
activated

kininogen:C1q binding protein

tetramer		ArrowR-HSA-158311 (Reactome)
activated thrombin:thrombomodulinArrowR-HSA-141046 (Reactome)
activated thrombin:thrombomodulinmim-catalysisR-HSA-141040 (Reactome)
activated thrombin

(factor

IIa):SERPIND1		ArrowR-HSA-5578883 (Reactome)
activated thrombin (factor IIa)ArrowR-HSA-140664 (Reactome)
activated thrombin (factor IIa)ArrowR-HSA-140700 (Reactome)
activated thrombin (factor IIa)R-HSA-140791 (Reactome)
activated thrombin (factor IIa)R-HSA-141046 (Reactome)
activated thrombin (factor IIa)R-HSA-5578883 (Reactome)
activated thrombin (factor IIa)R-HSA-5602080 (Reactome)
activated thrombin (factor IIa)mim-catalysisR-HSA-140599 (Reactome)
activated thrombin (factor IIa)mim-catalysisR-HSA-140696 (Reactome)
activated thrombin (factor IIa)mim-catalysisR-HSA-140840 (Reactome)
activated thrombin (factor IIa)mim-catalysisR-HSA-158137 (Reactome)
activated thrombin (factor IIa)mim-catalysisR-HSA-158419 (Reactome)
antithrombin III:heparinArrowR-HSA-140806 (Reactome)
antithrombin III:heparinR-HSA-140791 (Reactome)
factor

XIa:GPIb:GPIX:GPV

complex		ArrowR-HSA-158300 (Reactome)
factor

XIa:GPIb:GPIX:GPV

complex		ArrowR-HSA-158419 (Reactome)
factor

XIa:GPIb:GPIX:GPV

complex		mim-catalysisR-HSA-158333 (Reactome)
factor IX activation peptideArrowR-HSA-140823 (Reactome)
factor IX activation peptideArrowR-HSA-158333 (Reactome)
factor IXaArrowR-HSA-140823 (Reactome)
factor IXaArrowR-HSA-158333 (Reactome)
factor IXaArrowR-HSA-5607023 (Reactome)
factor IXaR-HSA-158278 (Reactome)
factor IXaR-HSA-5607023 (Reactome)
factor V activation peptideArrowR-HSA-140696 (Reactome)
factor VArrowR-HSA-5607002 (Reactome)
factor VIII:von

Willebrand factor

multimer		ArrowR-HSA-158118 (Reactome)
factor VIII:von

Willebrand factor

multimer		R-HSA-158137 (Reactome)
factor VIIIR-HSA-158118 (Reactome)
factor VIIIa B A3 acidic polypeptideArrowR-HSA-158137 (Reactome)
factor VIIIa:factor IXaArrowR-HSA-158278 (Reactome)
factor VIIIa:factor IXamim-catalysisR-HSA-158164 (Reactome)
factor VIIIaArrowR-HSA-158137 (Reactome)
factor VIIIaArrowR-HSA-5607043 (Reactome)
factor VIIIaR-HSA-158278 (Reactome)
factor VIIIaR-HSA-5607002 (Reactome)
factor VIIIaR-HSA-5607043 (Reactome)
factor VIIaArrowR-HSA-140769 (Reactome)
factor VIIaR-HSA-140748 (Reactome)
factor VR-HSA-140696 (Reactome)
factor VaArrowR-HSA-140696 (Reactome)
factor VaR-HSA-140686 (Reactome)
factor VaR-HSA-141026 (Reactome)
factor Vi intermediate formArrowR-HSA-141026 (Reactome)
factor Vi intermediate formR-HSA-5591040 (Reactome)
factor ViArrowR-HSA-5591040 (Reactome)
factor X activation peptideArrowR-HSA-140736 (Reactome)
factor X activation peptideArrowR-HSA-140777 (Reactome)
factor X activation peptideArrowR-HSA-158164 (Reactome)
factor XI:GPIb-IX-V complexArrowR-HSA-158145 (Reactome)
factor XI:GPIb-IX-V complexR-HSA-158300 (Reactome)
factor XI:GPIb-IX-V complexR-HSA-158419 (Reactome)
factor XIII A chain activation peptideArrowR-HSA-140599 (Reactome)
factor XIII cleaved tetramerArrowR-HSA-140599 (Reactome)
factor XIII cleaved tetramerR-HSA-140847 (Reactome)
factor XIIIR-HSA-140599 (Reactome)
factor XIIIaArrowR-HSA-140847 (Reactome)
factor XIIIamim-catalysisR-HSA-140851 (Reactome)
factor XIIR-HSA-158313 (Reactome)
factor XIIa:C1InhArrowR-HSA-158357 (Reactome)
factor XIIaArrowR-HSA-158313 (Reactome)
factor XIIaR-HSA-158357 (Reactome)
factor XIIamim-catalysisR-HSA-158300 (Reactome)
factor XIR-HSA-158145 (Reactome)
factor XR-HSA-140736 (Reactome)
factor XR-HSA-140777 (Reactome)
factor XR-HSA-158164 (Reactome)
factor XaArrowR-HSA-140736 (Reactome)
factor XaArrowR-HSA-140777 (Reactome)
factor XaArrowR-HSA-158164 (Reactome)
factor XaR-HSA-140686 (Reactome)
factor XaR-HSA-140825 (Reactome)
factor Xamim-catalysisR-HSA-140700 (Reactome)
factor Xamim-catalysisR-HSA-140769 (Reactome)
fibrin monomerArrowR-HSA-140840 (Reactome)
fibrin monomerR-HSA-140842 (Reactome)
fibrin multimer, crosslinkedArrowR-HSA-140851 (Reactome)
fibrin multimerArrowR-HSA-140599 (Reactome)
fibrin multimerArrowR-HSA-140842 (Reactome)
fibrin multimerR-HSA-140851 (Reactome)
kallikrein:C1InhArrowR-HSA-158399 (Reactome)
kallikrein:alpha2-macroglobulinArrowR-HSA-158340 (Reactome)
kallikrein:kininogen:C1q binding protein tetramerArrowR-HSA-158251 (Reactome)
kallikrein:kininogen:C1q binding protein tetramerR-HSA-158311 (Reactome)
kallikrein:kininogen:C1q binding protein tetramermim-catalysisR-HSA-158311 (Reactome)
kallikrein:kininogen:C1q binding protein tetramermim-catalysisR-HSA-158313 (Reactome)
prekallikrein:kininogen:C1q binding protein tetramerArrowR-HSA-158218 (Reactome)
prekallikrein:kininogen:C1q binding protein tetramerR-HSA-158251 (Reactome)
prolylcarboxypeptidase dimermim-catalysisR-HSA-158251 (Reactome)
sequestered tissue factorR-HSA-140761 (Reactome)
thrombin:antithrombin III:heparinArrowR-HSA-140791 (Reactome)
thrombin:antithrombin III:heparinR-HSA-140870 (Reactome)
thrombin:antithrombin III:heparinmim-catalysisR-HSA-140870 (Reactome)
thrombin:cleaved

antithrombin

III:heparin		ArrowR-HSA-140870 (Reactome)
thrombin:cleaved

antithrombin

III:heparin		R-HSA-140872 (Reactome)
thrombin:cleaved antithrombin IIIArrowR-HSA-140872 (Reactome)
von Willibrand factor multimerArrowR-HSA-158137 (Reactome)
von Willibrand factor multimerR-HSA-158118 (Reactome)
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