Nature 312, 337 - 342 (22 November 1984); doi:10.1038/312337a0

Structure of human factor VIII

Gordon A. Vehar^*, Bruce Keyt^*, Dan Eaton^*, Henry Rodriguez^*, Donogh P. O'Brien^†, Frances Rotblat^†, Herman Oppermann^‡, Rodney Keck^*, William I. Wood^‡, Richard N. Harkins^*, Edward G. D. Tuddenham^†, Richard M. Lawn^‡ & Daniel J. Capon^‡

^*Department of Protein Biochemistry and ^‡Department of Molecular Biology, Genentech, Inc., 460 Point San Bruno Boulevard, South San Francisco, California 94080, USA
^†Haemophilia Centre, Academic Department of Haematology, Royal Free Hospital School of Medicine, London WC1N 1BP, UK

The deduced amino acid sequence of human factor VIII, obtained from the DNA sequence, predicts a mature polypeptide of 2,332 amino acids containing a triplicated domain structure. The polypeptide has 35% sequence homology with the copper-binding plasma protein, ceruloplasmin. Determination of the thrombin cleavage sites in plasma-derived factor VIII polypeptides allows prediction of the domains involved in the associated activation and inactivation of the protein.

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