The factor VIII protein and its function

• Authors: Anna Mazurkiewicz-Pisarek , Grażyna Płucienniczak , Tomasz Ciach , Andrzej Płucienniczak
• Languages of publication: EN

Abstracts

EN

Factor VIII (FVIII), an essential blood coagulation protein, is a key component of the fluid phase blood coagulation system. Human factor VIII is a single chain of about 300 kDa consisting of domains described as A1-A2-B-A3-C1-C2. The protein undergoes processing prior to secretion into blood resulting in a heavy chain of 200 kDa (A1-A2-B) and a light chain of 80 kDa (A3-C1-C2) linked by metal ions. The role of factor VIII is to increase the catalytic efficiency of factor IXa in the activation of factor X. Variants of these factors lead frequently also to severe bleeding disorders.

Keywords

EN

Factor VIII (FVIII); molecular structure; function; hemophilia A; bleeding disorders

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2016
• Volume: 63
• Issue: 1
• Pages: 11-16

Dates

published

2016

received

2015-05-11

revised

2015-09-22

accepted

2016-01-13

(unknown)

2016-01-28

Contributors

author

Anna Mazurkiewicz-Pisarek

• Institute of Biotechnology and Antibiotics, Bioengineering Department, Warszawa, Poland

author

Grażyna Płucienniczak

• Institute of Biotechnology and Antibiotics, Bioengineering Department, Warszawa, Poland

author

Tomasz Ciach

• Warsaw University of Technology, Faculty of Chemical and Process Engineering, Department of Biotechnology and Bioprocessor Engineering, Warszawa, Poland

author

Andrzej Płucienniczak

• Institute of Biotechnology and Antibiotics, Bioengineering Department, Warszawa, Poland

References

• Astermark J, Berntorp E, White GC, Kroner BL (2001) The Malmö International Brother Study (MIBS): further support for genetic predisposition to inhibitor development in haemophilia patients. Haemophilia 7: 267-272.
• Astermark J (2015) FVIII inhibitors: pathogenesis and avoidance. Blood 125: 2045-2051.
• Bagnall RD, Waseem N, Green PM, Giannelli F (2002) Recurrent inversion breaking intron 1 of the factor VIII gen eis a frequent cause of severe heamophilia A. Blood 99: 168-174.
• Bajaj SP, Schmidt AE, Mathur A, Padmanabhan K, Zhong D, Mastri M (2001) Factor IXa:factor VIIIa interaction - helix 330-338 of factor IX interacts with residues 558-565 and spatially adjacent regions of the A2 subunit of factor VIIIa. J Biol Chem 276: 16302-16309.
• Berntorp E (1997) Second generation, B-domain deleted recombinant factor VIII. Thrombosis and Haemostasis 78: 256-260.
• Bhopale GM, Nanda RK (2003) Blood coagulation factor VIII: An overview. J Biosci 28: 783-789.
• Bihoreau N, Paolantonacci P, Bardelle C, Fontaine-Aupart MP, Krishnan S, Yon J, Romet-Lemonne JP (1991) Structural and functional characterization of factor VIII-delta II, a new recombinant factor VIII lacking most of the B-domain. Biochem J 277: 23-31.
• Bolton-Maggs PH, Pasi JK (2003) Haemophilias A and B. Lancet 361: 1801-1809.
• Bray GL, Gomperts ED, Courter S, Gruppo R, Gordon EM (1994) A multicenter study of recombinant factor VIII: safety, efficiency and inhibitor risk in previously untreated patients with haemophilia A. Blood 83: 2428-2435.
• Chen C, Fang XD, Zhu J, Wu XF, Zhang ZC, Gu JX, Wang ZY, Chi CW (1995) The gene expression of coagulation factor VIII in mammalian cell lines. Thromb Res 95: 105-115.
• Eaton DL, Vehar GA (1986) Factor VIII structure and proteolytic processing. Prog Hemost Thromb 8: 47-70.
• Fay PJ, Beattie T, Huggins CF, Regan LM (1994) Factor VIIIa A2 subunit residues 558-565 represent a factor IXa interactive site. J Biol Chem 269: 20522-20527.
• Fay JP (2004) Activation of factor VIII and mechanisms of cofactor action. Blood Reviews 18: 1-15.
• Fussenegger M, Bailey JE, Hauser H, Mueller PP (1999) Genetic optimization of recombinant glycoprotein production by mammalian cells. Trends Biotechnol 17: 35-42.
• Gill JC (1999) The role of genetics in inhibitor formation. Thromb Haemost 82(2): 500-504.
• Gitschier J, Wood WI, Goralka TM, Wion KL, Chen EY, Eaton DH, Vehar GA, Capon DJ, Lawn RM (1984) Characterization of the human factor VIII gene. Nature 312: 326-330.
• Healey JF, Lubin IM, Nakai H, Saenko EL, Hoyer LW, Scandella D (1995) Residues 484-508 contain a major determinant of the inhibitory epitope in the A2 domain of human factor VIII. J Biol Chem 270: 14505-14509.
• Hong F, Leming W, Hongbao W (2007) The protein structure and effect of factor VIII. Thrombosis Res 119: 1-13.
• Kannicht C, Ramstrom M, Kohla G, Tiemeyer M, Casademunt E, Walter O, Sandberg H (2013) Characterisation of the post-translational modifications of a novel, human cell line-derived recombinant human factor VIII. Thromb Res 131: 78-88.
• Kurachi K, Davie EW (1982) Isolation and characterization of a cDNA coding for human factor IX. Proc Natl Acad Sci 79: 6461-6464.
• Laffan M (2015) New products for the treatment of haemophilia. Br J Haematol 172 23-31.
• Lakich D, Kazazian HH Jr, Antonarakis SE, Gitschier J (1993) Inversions disrupting the factor VIII gene are a common cause of severe heamophilia A. Nat Genet 5: 236-241.
• Lapan KA, Fay PJ (1997) Localization of a factor X interactive site in the A1 subunit of factor VIIIa. J Biol Chem 272: 2082-2088.
• Lenting PJ, van de Loo JW, Donath MJ, van Mourik JA, Mertens K (1996) The sequence Glu1811-Lys1818 of human blood coagulation factor VIII comprises a binding site for activated factor VIII comprises a binding site for activated factor IX. J Biol Chem 271: 1935-1940.
• Liu ML, Shen BW, Nakaya S, Pratt KP, Fujikawa K, Davie EW (2000) Hemophilic factor VIII C1- and C2-domain missense mutations and their modeling to the 1.5-angstrom human C2-domain crystal structure. Blood 96: 979-987.
• Lucas KB, Giere LM, DeMarco RA, Shen A, Chisholm V, Crowley CW (1996) High-level production of recombinant proteins in CHO cells using a dicistronic DHFR intron expression vector. Nucleic Acids Res 24: 1774-1779.
• Lusher JM, Arkin S, Abildgaard CF, Schwartz RS (1993) Recombinant factor VIII for the treatment of previously untreated patients with hemophilia A. N Engl J Med 328: 453-459.
• Mannucci PM (2010) The safety and efficacy history of B-domainless factor VIII. Journal Coagulation Disorder, vol 2, issue 2, p 1.
• McMullen BA, Fujikawa K, Davie EW, Hedner U, Ezban M (1995) Locations of disulfide bonds and free cysteines in the heavy and light chains of recombinant human factor VIII (anti-hemophilic factor). Protein Sci 4: 740-746.
• Mikaelsson M, Oswaldsson U, Jankowski MA (2001) Measurement of factor VIII activity of B-domain deleted recombinant factor VIII. Seminars in Hematology 38: 13-23.
• Myles T, Yun TH, Leung LL (2002) Structural requirements for the activation of human factor VIII by thrombin. Blood 100: 2820.
• Ngo JC, Huang M, Roth DA, Furie BC, Furie B (2008) Crystal structure of human factor VIII: implications for the formation of the factor IXa-factor VIIIa complex. Structure 16: 597-606.
• Nogami K, Zhou Q, Myles T, Leung LL, Wakabayashi H, Fay PJ (2005) Exosite-interactive regions in the A1 and A2 domains of factor VIII facilitate thrombin-catalyzed cleavage of heavy chain. J Biol Chem 280: 18476-18487.
• O'Brien LM, Mastri M, Fay PJ (2000) Regulation of factor VIIIa by human activated protein C and protein S: inactivation of cofactor in the intrinsic factor Xase. Blood 95: 1714-1720.
• O'Brien LM, Medved LV, Fay PJ (1995) Localization of factor IXa and factor interactive sites. J Biol Chem 270: 27087-27092.
• Pittman DD, Alderman E, Tomkinson KN, Wang JH, Giles AR, Kaufman RJ (1993) Biochemical, immunological, and in vivo functional characterization of B-domain deleted factor VIII. Blood 81: 2925-2935.
• Plug I, Mauser-Bunschoten EP, Brocker-Vriends AH, van Amstel HK, van der Bom JG, van Diemen-Homan JE, Willemse J, Rosendaal FR (2006) Bleeding in carriers of hemophilia. Blood 108: 52-56.
• Pratt KP, Shen BW, Takeshima K, Davie EW, Fujikawa K, Stoddard BL (1999) Structure of the C2 domain of human factor VIII at 1.5 A resolution. Nature 402: 439-442.
• Rossiter JP, Young N, Kimberland ML (1994) Factor VIII gene inversions causing severe heamophilia A originate almost exclusivelly in male germ cells. Hum Mol Genet 3: 135-139.
• Saenko EL, Ananyeva NM, Shima M, Hauser CA, Pipe SW (2003) The future of recombinant coagulation factor. J Thromb Haemost 1: 922-930.
• Sandberg H, Almstedt A, Brandt J, Gray E, Holmquist L, Oswaldsson U, Sebring S, Mikaelsson M (2001) Structural and functional characteristics of the B-domain-deleted recombinant factor VIII protein, r-VIII SQ. Thromb Haemost 85: 93-100.
• Sandberg H, Kannicht C, Stenlund P, Dadaian M, Oswaldsson U, Cordula C., Walter O (2012) Functional characteristics of the novel, human-derived recombinant FVIII protein product, human-cl rhFVIII. Thromb Res 130: 808-817.
• Tagliavacca L, Moon N, Dunham WR, Kaufman RJ (1997) Identification and functional requirement of Cu(I) and its ligands within coagulation factor VIII. J Biol Chem 272: 27428-27434.
• Thompson AR (2003) Structure and function of the factor VIII gene and protein. Seminars in Thrombosis and Hemostasis 29: 11-21.
• Toole JJ, Knopf JL, Wozney JM, Sultzman LA, Buecker JL, Pittman DD, Kauffman RJ, Brown E, Shoemaker C, Orr EC, et al. (1984) Molecular cloning of a cDNA encoding human antiheamophilic factor. Nature 312: 342-347.
• Toole JT, Pittman DB, Orr EC, Murtha P, Wasley LC, Kaufman RJ (1986) A large region (approximately equal to 95 kDa) of human factor VIII is dispensable for in vitro procoagulant activity. Proc Natl Acad Sci 83: 5939-5942.
• 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 (1984) Structure of human factor VIII. Nature 312: 337-342.
• Waaler BA (1957) Simultaneous contribution to the formation of thrombin by the intrinsic and extrinsic blood clotting systems. Scand J Clin Lab Invest 9: 322-330.
• Windyga J (2004) Recombinant coagulation factorts. Acta Haematologica Polonica 35: 1-10.
• Windyga J, Chojnowski K, Klukowska A, Łętowska M, Mital A, Podolak-Dawidziak M, Zdziarska J, Zawilska K (2008) Treatment procedures in heamophilias A and B. Acta Haematol Pol 39: 537-564 (in Polish).
• Windyga J, Łopaciuk S, Stefańska E (2004) Hemophilia and other inherited blood coagulation disorders in Poland. Pol Arch Med Wewn 112: 1197-1202 (in Polish).
• Windyga J (2003) Diagnostyka laboratoryjna zaburzeń hemostazy. Laboratory diagnostics of hemostasis disorders. Manual for medical studies. PZWL 192-225 (in Polish).
• Zollner S, Raquet E, Claar P, Muller-Cohrs J, Metzner HJ, Weimer T, Pragst I, Dickneite G, Schulte S (2014) Non-clinical pharmacokinetics and pharmacodynamics of rVIII-SingleChain, a novel recombinant single-chain factor VIII. Thromb Res 134: 125-131.

Identifiers

DOI

10.18388/abp.2015_1056