Factor IX (FIX, Christmas Factor) is a vitamin K-dependent glycoprotein produced in the liver. Plasma concentration of FIX is normally around 5 micrograms/milliliters (87 nM) in plasma. The biological importance of FIX is demonstrated in Hemophilia B (Christmas disease), an X-linked congenital bleeding disease resulting from a quantitative (low activity and low antigen) or qualitative (low activity and normal antigen) defect in FIX function. In its zymogen form FIX is a single chain molecule of 55,000 daltons. It contains two EGF-like domains and an amino-terminal domain containing 12 gamma-carboxy-glutamic acid (Gla) residues. These Gla residues allow FIX to bind divalent metal ions and participate in calcium-dependent binding interactions. The activation of FIX occurs by limited proteolysis in the presence of calcium by activated factor XI (FXIa) and/or by a complex of VIIa/tissue factor/phospholipid and activated Factor X between residues Arg¹⁴⁶-Ala¹⁴⁷and between Arg¹⁸⁰-Val¹⁸¹. The terminal activated product in either case is FIXa-beta, a two-chain enzyme consisting of a heavy chain (28,000 daltons), a light chain (18,000 daltons) and an activation peptide product of 11,000 daltons. FIX can also be cleaved into inactive products by thrombin and by elastase. The activity of FIXa-beta in plasma is inhibited by antithrombin and this inhibition is accelerated approximately 1000-fold in the presence of optimal concentrations of heparin.