Coagulation factor IXa

1CFH, 1CFI, 1EDM, 1IXA, 1MGX, 1NL0, 1RFN, 2WPH, 2WPI, 2WPJ, 2WPK, 2WPL, 2WPM, 3KCG, 3LC3, 3LC5, 4YZU, 4Z0K, 4ZAE, 4WM0, 4WMA, 4WMI, 4WMK, 4WN2, 4WNH, 5EGM, 5JBC, 5JB9, 5JBB, 5JB8, 5JBA215814071ENSG00000101981ENSMUSG00000031138P00740P16294NM_000133NM_001313913NM_007979NM_001305797NP_000124NP_001300842NP_001292726NP_032005Factor IX (or Christmas factor) (EC 3.4.21.22) is one of the serine proteases of the coagulation system; it belongs to peptidase family S1. Deficiency of this protein causes haemophilia B. It was discovered in 1952 after a young boy named Stephen Christmas was found to be lacking this exact factor, leading to haemophilia.1cfh: STRUCTURE OF THE METAL-FREE GAMMA-CARBOXYGLUTAMIC ACID-RICH MEMBRANE BINDING REGION OF FACTOR IX BY TWO-DIMENSIONAL NMR SPECTROSCOPY1cfi: NMR STRUCTURE OF CALCIUM ION-BOUND GAMMA-CARBOXY-GLUTAMIC ACID-RICH DOMAIN OF FACTOR IX1edm: EPIDERMAL GROWTH FACTOR-LIKE DOMAIN FROM HUMAN FACTOR IX1ixa: THE THREE-DIMENSIONAL STRUCTURE OF THE FIRST EGF-LIKE MODULE OF HUMAN FACTOR IX: COMPARISON WITH EGF AND TGF-A1j34: Crystal Structure of Mg(II)-and Ca(II)-bound Gla Domain of Factor IX Complexed with Binding Protein1j35: Crystal Structure of Ca(II)-bound Gla Domain of Factor IX Complexed with Binding Protein1mgx: COAGULATION FACTOR, MG(II), NMR, 7 STRUCTURES (BACKBONE ATOMS ONLY)1nl0: Crystal structure of human factor IX Gla domain in complex of an inhibitory antibody, 10C121rfn: HUMAN COAGULATION FACTOR IXA IN COMPLEX WITH P-AMINO BENZAMIDINE Factor IX (or Christmas factor) (EC 3.4.21.22) is one of the serine proteases of the coagulation system; it belongs to peptidase family S1. Deficiency of this protein causes haemophilia B. It was discovered in 1952 after a young boy named Stephen Christmas was found to be lacking this exact factor, leading to haemophilia. Factor IX complex is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system. Factor IX is produced as a zymogen, an inactive precursor. It is processed to remove the signal peptide, glycosylated and then cleaved by factor XIa (of the contact pathway) or factor VIIa (of the tissue factor pathway) to produce a two-chain form where the chains are linked by a disulfide bridge. When activated into factor IXa, in the presence of Ca2+, membrane phospholipids, and a Factor VIII cofactor, it hydrolyses one arginine-isoleucine bond in factor X to form factor Xa. Factor IX is inhibited by antithrombin. Factor IX expression increases with age in humans and mice. In mouse models mutations within the promoter region of factor IX have an age-dependent phenotype. Factors VII, IX, and X all play key roles in blood coagulation and also share a common domain architecture. The factor IX protein is composed of four protein domains: the Gla domain, two tandem copies of the EGF domain and a C-terminal trypsin-like peptidase domain which carries out the catalytic cleavage. The N-terminal EGF domain has been shown to at least in part be responsible for binding tissue factor. Wilkinson et al. conclude that residues 88 to 109 of the second EGF domain mediate binding to platelets and assembly of the factor X activating complex. The structures of all four domains have been solved. A structure of the two EGF domains and the trypsin-like domain was determined for the pig protein. The structure of the Gla domain, which is responsible for Ca(II)-dependent phospholipid binding, was also determined by NMR. Several structures of 'super active' mutants have been solved, which reveal the nature of factor IX activation by other proteins in the clotting cascade.