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Warfarin and the Biochemistry of the Vitamin K Dependent Proteins

  • Chapter
The New Dimensions of Warfarin Prophylaxis

Abstract

The vitamin K-dependent proteins are a diverse group of molecules, all sharing the unique amino acid gamma carboxy glutamic acid (Gla). Gla is produced by the vitamin K-dependent post translational gamma carboxylation of selected glutamic acid residues, a step blocked by warfarin (Fig. 1). Gla-containing proteins have been most thoroughly studied in the blood coagulation system and bone but are found in other tissues such as the kidney. This review will focus on the blood coagulation system but will also touch on other Gla-containing proteins which shed light on common structural and functional features.

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References

  1. Neurath, H., Proteolytic Enzymes, past and present, Federation Proceedings, Vol. 44, No. 14, November 1985 p 2907–2913.

    PubMed  CAS  Google Scholar 

  2. Patthy, L., Evolution of the proteases of blood coauglation and fibrinolysis by assembly from modules. Cell, Vol. 41, pp 657–663 July 1985.

    Article  PubMed  CAS  Google Scholar 

  3. Banyai, L., Varodi, A., Patthy, L. Common evoluntionary origin of the fibrin-binding structures of fibronectin and tissue-type plasminogen activator. FEBS Letter 163 37–41 1983.

    Article  CAS  Google Scholar 

  4. Patthy, L., Trexler, M., Vali, Z., Banyai, L., Varadi, A. Kringles: modules specialized for protein binding. Homology of the gelatin binding region of fibronectin with the kringle structures of proteases. FEBS Letter, 171 131–136 1984.

    Article  CAS  Google Scholar 

  5. Bloom, J.W., Mann, K.G. Metal ion induced conformational transition of prothrombin and prothrombin fragment 1. Biochemistry 1978; 17:4430–4438.

    Article  PubMed  CAS  Google Scholar 

  6. Prendergast, F.G., Mann, K.G. Differentiation of metal ion-induced transitions of prothrombin fragment 1. J. Biol. Chem. 1977, 252:840–850.

    PubMed  CAS  Google Scholar 

  7. Yoshitake, S. Schach, B.G., Foster, D.C., Davie, E.W. Hurachi, K. The complete nucleoside sequence of the gene for human Factor IX. Biochemistry 1985, 24, 3736–3750.

    Article  PubMed  CAS  Google Scholar 

  8. Zonneveld, A.J., Veerman, H., Pannekoek, H. Autonomous functions of structural domains of human tissue-type plasminogen activator. Proc. Nat’l. Acad. Sci. USA. Vol 82 pp 4670–4674 July 1986.

    Article  Google Scholar 

  9. Pan, L.C. Price, P.A. The propeptide of rat bone -carboxyglutamic acid protein shares homology with other vitamin K-dependent protein precursors. Proc. Nat’l. Acad. Sci. USA. Vol. 82 pp 6109–6113 Sept. 1983.

    Article  Google Scholar 

  10. Suttie, J.W., Hoskins, J.A. et al., Vitamin k-dependent carboxylase; a possible role of the “propeptide” as an intracellular recognition site, Proc. Nat’l. Acad. Sci. USA (in press 1986)

    Google Scholar 

  11. Hoskins, J. Norman, D.K., Beckman, R.J., Long, G.L. Cloning and characterization of human liver cDNA encoding a Protein S precursor. Proc. Nat’l. Acad. Sci. USA (in press 1986).

    Google Scholar 

  12. Park, C.H., Tulinsky A., Three dimensional structure of the kringle sequence: structure of prothrombin fragment 1. Biochemistry Vol. 25 No. 14 July 1986 pp 3977–3982.

    Article  PubMed  CAS  Google Scholar 

  13. Bar-Shavit, R., Kahn, A.J., Mann, K.G., Wilner, G.D., Identification of a thrombin sequence with growth factor activity on Macrophages. Proc. Nat’l. Acad. Sci USA, Vol. 83 pp 976–980. February 1986.

    Article  CAS  Google Scholar 

  14. Hojrup, P., Jensen, M.S., Petersen, T.E., Amino acid sequence of bovine protein Z: a vitamin K-dependent serine protease homolog, FEBS Letters, Vol. 184 No. 2, May 1985 pp 333–338.

    Article  PubMed  CAS  Google Scholar 

  15. Price, P.A., Williamson, M.K., Primary Structure of Bone Matrix Gla Protein, a new vitamin K-dependent bone protein. J. Biol. Chem., Vol. 260, No. 28, 14971–14975 Sec 5, 1985.

    PubMed  CAS  Google Scholar 

  16. Jesty, J., Spencer, A.K., Nemerson, Y. The mechanism of activation of factor X. Kinetic control of alternative pathways leading to the formation of activated factor X. J. Biol. Chem. 249: 5614–5622, 1974.

    PubMed  CAS  Google Scholar 

  17. Redclifte, R., Nemerson, Y. The activation and control of factor VII by activated factor X and Thrombin. J. Biol. Chem. 250: 388–395, 1975.

    Google Scholar 

  18. Bajaj, S.P., Rapaport, S.I., Brown, S.F., Isolation and characterization of human factor VII. J. Biol.Chem. 256: 283–259 1981.

    Google Scholar 

  19. Hagen, F.S., Gray, C.L. et al, Characterization of a cDNA coding for human factor VII, Proc. Nat’l. Acad. Sci. USA Vol 83, pp 2412–2416, April 1986.

    Article  CAS  Google Scholar 

  20. Fujikawa, K., Davie, E.W. Bovine Factor IX. Methods Enzymol. 45: 74–83, 1974.

    Article  Google Scholar 

  21. Kurachi, K. Davie, E.W. Isolation.and characterization of a cDNA coding for human factor IX, Proc. Nat’l. Acad. Sci. USA Vol 79 pp 6461–6464 Nov. 1982.

    Article  CAS  Google Scholar 

  22. Jesty, J., Silverberg, S.A. Kinetics of the tissue factor dependent activation of coagulation factors IX and X in a bovine plasma system. J. Biol. Chem. 254: 12337–12345, 1979.

    PubMed  CAS  Google Scholar 

  23. Osterud, B., Rapaport, S.I.: Activation of 125-I factor IX and 125I-Factor X: effect of tissue factor and factor VII, factor Xa and thrombin. Scand. J. Haem. 24:213–276 1960.

    Article  Google Scholar 

  24. Titani, K., Fujikawa, A.L., Enfield, D.L., et al, Bovine factor X, (Stuart factor): amino acid sequence of heavy chain. Proc. Nat’l. Acad. Sci. USA 72:3982–3086 1975.

    Google Scholar 

  25. Jackson, CM., Factor X, in CRC Handbook series in clinical laboratory science, Section I: Hematology, edited by Seligson D. Boca Raton, CRC Press pp 101–107 1980.

    Google Scholar 

  26. Mann, K.G., Elion, J., Prothrombin, in CRC Handbook series in Clinical Laboratory Science, Section 1: Hematology, Edited by Seligson, D., Boca Raton, CRC Press 1980 pp. 15–21.

    Google Scholar 

  27. Magnusson, S. Peterson, T.E., Sottrup-Hensen, L. et al, Complete primary structure of prothrombin: Isolation, Structure and reactivity of ten carboxylated glutamic acid residues and regulation of prothrombin activity by thrombin, in Proteases and Biological Control, edited by Reich, E., Ritkin, D.B., Shaw, E. New York, Cold Spring Harbor Laboratories, 1975 pp 123–149.

    Google Scholar 

  28. Beckman, R.J., Schmidt, R.J., Santerre, R.F., Plutzky, J., Crabtree, G., Long, G.L. The structure and evolution of a 461 amino acid human protein C precursor and its messenger RNA, based upon the DNA sequence of cloned human liver DNAs. Nucleic Acids Research Vol. 13 No. 14 1985 pp 5233–5247

    Article  Google Scholar 

  29. Long, G.L., Belagaje, R.M., MacGillivray, R.T. Cloning and sequencing of liver cDNA coding for bovine protein C. Proc. Nat’l. Acad. Sci. USA Vol. 81 pp 5653–5656 September 1984.

    Article  CAS  Google Scholar 

  30. Kisiel, W., Canfield, W.M., Ericsson, L. H. et al. Anticoagulant properties of bovine plasma protein C following activation by thrombin. Biochemistry 16:5824–5881, 1977.

    Article  PubMed  CAS  Google Scholar 

  31. Vehar, G.A., Davie, E.W., Preparation and Properties of bovine factor VIII (anti-hemophitic factor) Biochemistry 19: 401–410 1980.

    Article  PubMed  CAS  Google Scholar 

  32. Di Scipio, R.G., Davie, E.W. A characterization of protein S, acarboxyglutamic acid containing protein from bovine and human plasma. Biochemistry 18: 899–904 1979.

    Article  Google Scholar 

  33. Suzuki, K. Nishioka, J. Matsuda, M. Murayama, H. Hashimoto S, Protein S is essential for the activated protein C-catalyzed inactivation of platelet associated Va J. Biochem. 96, 455–460 1984

    PubMed  CAS  Google Scholar 

  34. Walker, F. Regulation of activated protein C by protein S. J. Biol. Chem. 256: No. 21 pp 11128–11131 1986.

    Google Scholar 

  35. Suzuki, K., Nishioka, J. Hushimoto, S., Regulation of activated protein C by thrombin modified protein S. J. Biochem. 94 699–705 1983

    PubMed  CAS  Google Scholar 

  36. Dahlback, B. Inhibition of Protein C cofactor function of human and bovine protein S by C4b-binding protein. J. Biol.Chem. 261: 26 pp 12022–12027.

    Google Scholar 

  37. Walker, F. Identification of a new protein involved in the regulation of the anticoagulant activity of activated Protein C. J. Bio. Chem. 261 No. 23: pp 10941–10944.

    Google Scholar 

  38. Seegers, W.H., Ghosh, A. Way V-Y. Function of previously unrecognized plasma protein M in thrombin generation. In Vitamin K metabolism and vitamin K-dependent proteins. Edited by Suttie, J.W., Baltimore, Universityy Press, 1980 pp 96–101.

    Google Scholar 

  39. Katzmann, J.A., Nesheim, M. Hibbard, L.S. eta al. Isolation of functional human coagulation factor V using a hybridoma antibody. Proc. Nat’l. Acad. Sc. USA 78: 162–166, 1981.

    Article  CAS  Google Scholar 

  40. Nesheim, M., Mann, K.G. Thrombin catalyzed activation of single chain bovine factor V. J. Biol. Chem. 254: 1226–1234, 1979.

    Google Scholar 

  41. Hibbard, L.S., Mann, K.G. The calcium binding properties of bovine factor V. J. Biol. Chem. 255: 638–645, 1980.

    PubMed  CAS  Google Scholar 

  42. Hoyer, L.W., Trabold, N.C. The effect of thrombin on human factor VIII J. Lab. Clin. Med. 8–97: 50–64 1981.

    Google Scholar 

  43. Rotblat, F. Obrien, D.P., Middleton, S.M. Purification and characterization of human factor VIII C Thrombin, Haemost. 50:108 (abstract 19) 1983.

    Google Scholar 

  44. Fass, D.N., Knutson, G.J., Katzmann, J.A. Monoclonal antibodies to porcine factor VIII coagulant and their use in isolation of active coagulant protein. Blood 59, 594–600 1982.

    PubMed  CAS  Google Scholar 

  45. Fulcher, C.A., Roberts, J.R., Zimmerman, T.S. Thrombin proteolysis of purified factor VIII procoagulant protein: Correlation of activation with generation of a specific polypeptide. Blood 61: 807–811 1983.

    PubMed  CAS  Google Scholar 

  46. Bach, R., Nemerson, Y., Konigsberg, W. Purification and characterization of bovine tissue factor. J. Biol. Chem. 256: 8324–8331, 1981.

    PubMed  CAS  Google Scholar 

  47. Esmon, N.L., Owen, W.R., Esmon, C.T. Isplation of a membrane-bound cofactor for thrombin-catalyzed activation of protein C. J. Biol. Chem. 257:859–864, 1982.

    PubMed  CAS  Google Scholar 

  48. Davie, E.W., Ratnoff, O.D. Waterfall sequence for intrinsic blood clotting Science 145: 1310 1965.

    Google Scholar 

  49. Macfarlane, R.B. An enzyme cascade in the blood clotting mechanism, and its function as a biochemical multiplier. Nature 202, 498 1964.

    Article  PubMed  CAS  Google Scholar 

  50. Mann, K.G. Membrane bound enzyme complexes in blood coagulation in Progress in Hemostasis and Thrombosis éd. Spaet, T., vol. 7 p 1–24, 1984.

    CAS  Google Scholar 

  51. Rao, M.V., Rapaport, S.I., Bajaj, P.S. Activation of human factor VII in the initiation of tissue factor dependent coagulation. Blood 1986, 68 No. 3, pp 685–691.

    PubMed  CAS  Google Scholar 

  52. Nesheim, M., Taswell, J.B., Mann, K.G. The contribution of bovine Factor V and Factor Va to the activity of prothrombinase. J. Biol. Chem. 254:10952, 1979.

    PubMed  CAS  Google Scholar 

  53. Miletich, J.P., Jackson, C.M., Majerus, P.W. Interaction of coagulation factor Xa with platelets. Proc. Nat’l. Acad. Sci. USA 74: 4033, 1983.

    Article  Google Scholar 

  54. Mann, K.G., Downing, M.R., Thrombin generation. In: Lundblad R.L., Fenton, J.W., Mann, K.G. (eds) Chemistry and Biology of Thrombin, Ann Arbor, Michigan, Ann Arbor Press, 1977, pp 11–22.

    Google Scholar 

  55. Esmon, C.T., Owen, W.G.: Identification of an endothelial cell cofactor for thrombin catalyzed activation of Protein C Proc. Nat’l Acad. Sci. USA 78:2249 1981.

    Article  CAS  Google Scholar 

  56. Nesheim, M.E. Taswell, J.B., Mann, K.G. The contribution of bovine factor V and factor Va to the activity of prothrombinase J.Biol. Chem 254: 10952–10962, 1979.

    PubMed  CAS  Google Scholar 

  57. Tracy, P.B., Nesheim, M.E., Mann, K.G. Coordinate binding of factor Va and factor Xa to the unstimulated platelet. J. Biol. Chem. 256: 743–751, 1981.

    PubMed  CAS  Google Scholar 

  58. Nesheim, M.E., Kettner, C. Shaw, E. et al Cofactor dependence of factor Xa incorporation into the prothrombinase complex. J. Biol. Chem. 256: 6537–6540 1981.

    PubMed  CAS  Google Scholar 

  59. Nesheim, M.E., Eid, S., Mann, K.G. Assembly of the prothrombinase complex in the absence of prothrombin. J. Biol. Chem. 256, 9874 1981.

    PubMed  CAS  Google Scholar 

  60. Rosing, J., Tan, G. Grovers-Riemslag, J.W.P., Zwaal, R.F.A., Hemker, H.C. The role of phospholipids and factor Va in the prothrombinase complex. J. Biol. Chem. 255:274, 1980.

    PubMed  CAS  Google Scholar 

  61. va Rijn, J.L. M.C., Grovers-Riemslag, J.W.P., Zwaal, R.F.A. Kinetic studies of prothrombin activation: effect of factor Va and phospholipids on the formation of the enzyme substrate complex. Biochemistry 23: 4557, 1984.

    Article  PubMed  Google Scholar 

  62. Lim, T.K., Bloomfield, V.A., Nelsestuen, G.L. Structure of the prothrombin and blood clotting factor X-membrane complexes. Biochemistry 16: 4177, 1977.

    Article  PubMed  CAS  Google Scholar 

  63. Mann, K.G., Odegaard, B.H., Krishnaswamy, S., Tracy, P.B., Nesheim, M. Expression of blood clotting enzymes on natural and synthetic membranes in Proceedings of UCLA Symposium on Proteases and Biological Control 1986, J. Cellular Biochemistry (1986 in press).

    Google Scholar 

  64. Mann, K.G., Nesheim, M.E., Tracy, P.B.: The molecular weight of undegraded plasma Factor V. Biochemistry 20:28–33, 1981.

    Article  PubMed  CAS  Google Scholar 

  65. Mosesson, M.W., Nesheim M.E., Di Orio, J., Hainfield J.F., Wall, J.S., Mann, K.G: Studies on the structure of bovine Factor V by scanning transmission electron microscopy.(STEM) Blood 65: 1158, 1985.

    Google Scholar 

  66. Lampe, P.D., Pusey, M.I., Wei, G.J., Nelsestuen, G.L. Electron microscopy and hydrodynamic properties of blood clotting factor V and activation fragments of factor V with phospholipid vesicles. J. Biol. Chem. 259: 9959, 1984.

    PubMed  CAS  Google Scholar 

  67. Bajaj, S.P., Butkowski, R.J., Mann, K.G.: Prothrombin fragments. Ca2+ binding and activation kinetics. J. Biol. Chem. 250:2150–2156, 1975.

    PubMed  CAS  Google Scholar 

  68. Esmon, C.T., Jackson, C.M.: The conversion of prothrombin to thrombin: IV the function of the fragment 2 region during activation in the presence of factor V. J. Biol. Chem. 249: 7791 1974.

    PubMed  CAS  Google Scholar 

  69. Nesheim, M.E., Canfield, W.M., Kisiel, W.M. et al. Studies of the capacity of factor Xa to protect factor Va from inactivation by activated protein C. J. Biol. Chem. 247: 1443, 1982.

    Google Scholar 

  70. Miletich, J.P., Kane, W.H., Hofmann, S.L. et al. Deficiency of factor Xa-factor Va binding sites on the platelets of a patient with a bleeding disorder. Blood 54: 1015 1979.

    PubMed  CAS  Google Scholar 

  71. Malhotra, O.P. Dicoumarol-induced prothrombins. Ann.N.Y. Acad. Sci. 1981; 370: 426–437.

    Article  PubMed  CAS  Google Scholar 

  72. Malhotra, O.P. Partially carboxylated prothrombins I Comparison of activation properties and purification of 1 and 0 carboxyglutamyl variants. Biochem. Biophys. Acta. 1982: 702, 178–184.

    Article  CAS  Google Scholar 

  73. Malhotra, O.P. Partially carboxylated prothrombins II. Effect of gamma carboxyglutamyl residues on the properties of prothrombin fragment 1. Biochem. Biophys. Acta. 1982, 702:185–192.

    Article  CAS  Google Scholar 

  74. Friedman, P.A. Rosenberg, R.D., Hanschka, P.V., Fitz-James, A., A spectrum of partially carboxylated prothrombins in the plasma of coumarin treated patients. Biochem. Biophys Acta. 1977, 494, 271–276.

    Article  PubMed  CAS  Google Scholar 

  75. Malhotra, O.P., Nesheim, M.E., Mann, K.G. The kinetics of activation of normal and carboxyglutamic acid deficient prothrombins. J. Biol. Chem. 260:279–287, 1985.

    PubMed  CAS  Google Scholar 

  76. Bovill, E., Malhotra, O.P., Nesheim, M.E., Mann, K.G. Future Directions in Monitoring Oral Anticoagulant Therapy. In: Advances in Coagulation Testing (Triplett, D. ed.) pp. 79–89, College of American Pathologist Press, Skokie, IL (in press 1986).

    Google Scholar 

  77. Tuhy, P., Bloom, J., Mann, K.G. Decarboxylation of bovine prothrombin fragment 1 and prothrombin. Biochemistry 1979; 18, 5842–5848.

    Article  PubMed  CAS  Google Scholar 

  78. Borowsi, M. Furie, B.C., Furie, B. Distribution of carboxyglutamic acid residues in partially carboxylated human prothrombins, J. Biol. Chem., Vol. 261 No. 4 Feb 5 pp 1624–1628.

    Google Scholar 

  79. Sugo, T. Ulla, P., Stenflo, J. Protein C. in Bovine Plasma after Warfarin Treatment Journal of Biol. Chem. Vol. 260 No. 19 September 5 pp 20453–10457.

    Google Scholar 

  80. Mann, K.G.: Prothrombin. In: Methods in Enzymology, Proteolytic Enzymes, Part B, (Lorand, L. ed.) p. 123, Academic Pres, New York, 1976.

    Chapter  Google Scholar 

  81. Jackson, C.M., Esmon, C.T., Owen, W.G. The activation of bovine prothrombin, in Reich, E., Rutkin, D.B., Shaw, E.(ed.): Proteases and Biological Control, Cold Spring Harbor 1975, p 95.

    Google Scholar 

  82. Hibbard, L.S., Nesheim, M.E., Mann, K.G.: Progressive development of a thrombin inhibitor binding site. Biochemistry 21: 2285–2292, 1982.

    Article  PubMed  CAS  Google Scholar 

  83. Nesheim, M.E., Mann, K.G., The kinetics and cofactor dependence of two cleavages involved in prothrombin activation. J. Biol. Chem. 258: 5386–5391, 1983.

    PubMed  CAS  Google Scholar 

  84. Krishnaswamy, S., Mann, K.G., Nesheim, M.E., The prothrombinase-catalyzed activation of prothrombin proceeds through the intermediate meizothrombin in an ordered, sequential reaction. J.Biol. Chem. 261: No. 19, pp 8977–8984 1986.

    PubMed  CAS  Google Scholar 

  85. Malhotra, O.P., Nesheim, M.E., Mann, K.G. The kinetics of activation of normal and GLA-deficient prothrombins. J. Biol. Chem. 260:279–287, 1985.

    PubMed  CAS  Google Scholar 

  86. Kazmier, F.J., Spittell, J.A., Thompson, J.J., Owen, C.A., Effect of oral anticoagulantson factors VII, IX, X and II. Arch. Int. Med. 1965 115, pp 667–673.

    Article  CAS  Google Scholar 

  87. O’Reilly, R.A., Aggeler, P.M., Studies on Courmarin Anticoagulant drugs. Initiation of warfarin therapy without a loading dose. Circulation 1968; 38, 169–177.

    Article  PubMed  Google Scholar 

  88. Taberner, D.A., Thompson, J.M., Poller, L., Comparison of prothrombin complex concentrate and vitamin K in oral anticoagulant reversal. Br. Med. J. 1976, 2, 83–85.

    Article  PubMed  CAS  Google Scholar 

  89. Mann, K., Katzmann, J.A., Foster, W.B., Fass, D.N., Monoclonal Antibodies and Coagulation in Handbook of Monoclonal Antibodies ed. Ferrone, S. and Dierich, M., Noyes, Inc., 1985 Chap. 11 pp 166–194.

    Google Scholar 

  90. Lewis, R.M., Furie, B.C., Furie, B. Conformation-specific monoclonal antibodies directed against the calcium-stabilized structure of human prothrombin. Biochemistry 1983, 22, pp. 948–954.

    Article  PubMed  CAS  Google Scholar 

  91. Blanchard, R.A., Furie, B.C., Kruger, S.F. Waneck, G., Jorgensen, M.J., Furie, G. Immunoassays of human prothrombin species which correlated iron functional coagulation activities. J. Lab. Clin. Med. 1983, 101, 24.

    Google Scholar 

  92. Laurell, M., Ikeda, K., Lindgren, S., Stenflo, J. Characterization of monoclonal antibodies against human protein C specific for the calcium ion. FEBS Letters Vol. 191 No. 1 0ct5ober 1985 pp 75–81.

    Article  PubMed  CAS  Google Scholar 

  93. Wakabayashi, K., Sakata, Y., Aoki, N., Conformation specific monoclonal antibodies to the calcium induced structure of protein C. J. Biol. chem. 261:24 pp 11097–11105 1986.

    PubMed  CAS  Google Scholar 

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  1. Departments of Biochemistry and Pathology, University of Vermont, Given Building, Burlington, Vt., 05405, USA

    Edwin G. Bovill & Kenneth G. Mann

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  1. New York University School of Medicine, New York, New York, USA

    Stanford Wessler

  2. Cornell University Medical College, New York, New York, USA

    Carl G. Becker

  3. Mt. Sinai School of Medicine of the City University of New York, New York, New York, USA

    Yale Nemerson

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Bovill, E.G., Mann, K.G. (1987). Warfarin and the Biochemistry of the Vitamin K Dependent Proteins. In: Wessler, S., Becker, C.G., Nemerson, Y. (eds) The New Dimensions of Warfarin Prophylaxis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-5985-3_3

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