FUNCTION Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipids, and factor VIIIa.SUBUNIT Heterodimer of a light chain and a heavy chain; disulfide-linked (PubMed:20121198, PubMed:20121197, PubMed:20080729). Interacts with SERPINC1.TISSUE SPECIFICITY Detected in blood plasma (at protein level) (PubMed:3857619, PubMed:8295821, PubMed:2592373, PubMed:9169594, PubMed:19846852). Synthesized primarily in the liver and secreted in plasma.DOMAIN Calcium binds to the gamma-carboxyglutamic acid (Gla) residues in the Gla domain. Calcium can also bind, with stronger affinity, to another site beyond the Gla domain (PubMed:6425296). Under physiological ion concentrations, Ca(2+) is displaced by Mg(2+) from some of the gammaglutamate residues in the N-terminal Gla domain. This leads to a subtle conformation change that may affect the interaction with its binding protein (By similarity).PTM Activated by factor XIa, which excises the activation peptide (PubMed:9169594, PubMed:1730085). The propeptide can also be removed by snake venom protease (PubMed:20004170, PubMed:20080729).PTM The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.DISEASE Mutations in position 43 (Oxford-3, San Dimas) and 46 (Cambridge) prevents cleavage of the propeptide (PubMed:12588353, PubMed:2738071, PubMed:3009023, PubMed:8295821, PubMed:9169594, PubMed:9600455, PubMed:25251685). Mutation in position 93 (Alabama) probably fails to bind to cell membranes (PubMed:3790720). Mutation in position 191 (Chapel-Hill) or in position 226 (Nagoya or Hilo) prevent cleavage of the activation peptide (PubMed:6603618, PubMed:8076946, PubMed:12588353, PubMed:2162822, PubMed:25251685, PubMed:2713493).PHARMACEUTICAL Available under the name BeneFix (Baxter and American Home Products). Used to treat hemophilia B.MISCELLANEOUS In 1952, one of the earliest researchers of the disease, Dr. R.G. Macfarlane used the patient's surname, Christmas, to refer to the disease and also to refer to the clotting factor which he called the 'Christmas Factor' At the time Stephen Christmas was a 5-year-old boy. He died in 1993 at the age of 46 from acquired immunodeficiency syndrome contracted through treatment with blood products.SIMILARITY Belongs to the peptidase S1 family.