Figure 3: Factor 8 and factor 9 genes and proteins: Factor 8 gene is 186 kilobases (kb) in length and encodes a messenger RNA of ~9kb. The newly synthesised factor VIII protein molecule is composed of a pre-sequence of 19 amino acids and a mature peptide of 2332 amino acids. The mature multi-domain factor VIII protein contains triplicated A domains, duplicated C domains and a single B domain. The arginine residues, which are the sites for proteolytic activation, are R372, R740, R1689. Activated factor VIII is a heterotrimer in which the dimeric N-terminal heavy chain is held together with the monomeric C-terminal light chain by a metal ion bridge (Ca2+). Factor 9 is 1/6th the size of factor 8 gene, ~ 34 kb and encoding a transcript of ~1.4 kb. The mature factor IX protein consists of a pre- and pro-sequence and a mature peptide of 415 amino acids (total length, 461 amino acids). Activated factor IX has an N-terminal light chain and a C-terminal heavy chain held together by a disulphide bridge between cysteine resides 132 and 279. GLA, “Gla” domain, in which 12 glutamic acid residues undergo post-translational gamma-carboxylation by a vitamin K dependent carboxylase; EGF, epidermal growth factor-like domain; activation peptide released after proteolytic activation at arginine 145 and arginine 180; catalytic, the serine protease domain responsible for cleavage of factor X to Xa.