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Human Factor IX (Christmas factor) is a single-chain plasma glycoprotein (mol wt 57,000) that participates in the middle phase of the intrinsic pathway of blood coagulation. It is present in plasma as a zymogen and is converted to a serine protease, Factor IXabeta, by Factor XIa (activated plasma thromboplastin antecedent) in the presence of calcium ions. In the activation reaction, two internal peptide bonds are hydrolyzed in Factor IX. These cleavages occur at a specific arginyl-alanine peptide bond and a specific arginyl-valine peptide bond. This results in the release of an activation peptide (mol wt approximately equal to 11,000) from the internal region of the precursor molecule and the generation of Factor IXabeta (mol wt approximately equal to 46,000). Factor IXabeta is composed of a light chain (mol wt approximately equal to 18,000) and a heavy chain (mol wt approximately equal to 28,000), and these chains are held together by a disulfide bond(s). The light chain originates from the amino terminal portion of the precursor molecule and has an amino terminal sequence of Tyr-Asn-Ser-Gly-Lys. The heavy chain originates from the carboxyl terminal region of the precursor molecule and contains an amino terminal sequence of Val-Val-Gly-Gly-Glu. The heavy chain of Factor IXabeta also contains the active site sequence of Phe-Cys-Ala-Gly-Phe-His-Glu-Gly-Arg-Asp-Ser-Cys-Gln-Gly-Asp-SER-Gly-Gly-Pro. The active site serine residue is shown in capital letters. Factor IX is also converted to Factor IXaalpha by a protease from Russell's viper venom. This activation reaction, however, occurs in a single step and involves only the cleavage of the internal arginyl-valine peptide bond. Human Factor IXabeta was inhibited by human antithrombin III by the formation of a one-to-one complex of enzyme and inhibitor. In this reaction, the inhibitor was tightly bound to the heavy chain of the enzyme. These data indicate that the mechanism of activation of human Factor IX and its inhibition by antithrombin III is essentially identical to that previously shown for bovine Factor IX.


R G Di Scipio, K Kurachi, E W Davie


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Citations to this article in year 2011 (6)

Title and authors Publication Year
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CS Craik, MJ Page, EL Madison
Biochemical Journal 2011
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M Popović, K Smiljanić, B Dobutović, T Syrovets, T Simmet, ER Isenović
Molecular and Cellular Biochemistry 2011
Protein molecular function influences mutation rates in human genetic diseases with allelic heterogeneity
S Chavali, A Mahajan, S Ghosh, B Mondal, D Bharadwaj
Biochemical and Biophysical Research Communications 2011
Stable and high-level production of recombinant Factor IX in human hepatic cell line
AC Fernandes, A Fontes, N Gonsales, K Swiech, V Picanco-Castro, S Faca, D Covas
Biotechnology and Applied Biochemistry 2011
The Role of Factor XIa (FXIa) Catalytic Domain Exosite Residues in Substrate Catalysis and Inhibition by the Kunitz Protease Inhibitor Domain of Protease Nexin 2*
YC Su, TN Miller, D Navaneetham, RT Schoonmaker, D Sinha, PN Walsh
The Journal of biological chemistry 2011
Productive recognition of factor IX by factor XIa exosites requires disulfide linkage between heavy and light chains of factor XIa
MM Marcinkiewicz, D Sinha, PN Walsh
The Journal of biological chemistry 2011