UniProt functional annotation for P00740



	UniProt functional annotation for P00740

UniProt code: P00740.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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. {ECO:0000269|PubMed:1730085, ECO:0000269|PubMed:19846852, ECO:0000269|PubMed:20121197, ECO:0000269|PubMed:20121198, ECO:0000269|PubMed:2592373, ECO:0000269|PubMed:8295821}.

Catalytic activity: Reaction=Selective cleavage of Arg-|-Ile bond in factor X to form factor Xa.; EC=3.4.21.22; Evidence={ECO:0000269|PubMed:12444082, ECO:0000269|PubMed:20121197, ECO:0000269|PubMed:20121198, ECO:0000269|PubMed:2592373};

Subunit: Heterodimer of a light chain and a heavy chain; disulfide- linked (PubMed:20121198, PubMed:20121197, PubMed:20080729). Interacts with SERPINC1. {ECO:0000269|PubMed:20004170, ECO:0000269|PubMed:20080729, ECO:0000269|PubMed:20121197, ECO:0000269|PubMed:20121198, ECO:0000269|PubMed:2592373}.

Subcellular location: Secreted {ECO:0000269|PubMed:19846852, ECO:0000269|PubMed:2592373, ECO:0000269|PubMed:3857619, ECO:0000269|PubMed:8295821, ECO:0000269|PubMed:9169594}.

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. {ECO:0000269|PubMed:19846852, ECO:0000269|PubMed:2592373, ECO:0000269|PubMed:3857619}.

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). {ECO:0000250|UniProtKB:P00741, ECO:0000269|PubMed:14722079, ECO:0000269|PubMed:1730085, ECO:0000269|PubMed:6425296}.

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). {ECO:0000269|PubMed:1730085, ECO:0000269|PubMed:20004170, ECO:0000269|PubMed:20080729, ECO:0000269|PubMed:2592373, ECO:0000269|PubMed:8295821, ECO:0000269|PubMed:9169594}.

Ptm: The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains. {ECO:0000269|PubMed:6688526}.

Disease: Hemophilia B (HEMB) [MIM:306900]: An X-linked blood coagulation disorder characterized by a permanent tendency to hemorrhage, due to factor IX deficiency. It is phenotypically similar to hemophilia A, but patients present with fewer symptoms. Many patients are asymptomatic until the hemostatic system is stressed by surgery or trauma. {ECO:0000269|PubMed:10094553, ECO:0000269|PubMed:10698280, ECO:0000269|PubMed:11122099, ECO:0000269|PubMed:12588353, ECO:0000269|PubMed:12604421, ECO:0000269|PubMed:1346975, ECO:0000269|PubMed:1615485, ECO:0000269|PubMed:1902289, ECO:0000269|PubMed:1958666, ECO:0000269|PubMed:2162822, ECO:0000269|PubMed:2339358, ECO:0000269|PubMed:2372509, ECO:0000269|PubMed:2472424, ECO:0000269|PubMed:25251685, ECO:0000269|PubMed:25470321, ECO:0000269|PubMed:2592373, ECO:0000269|PubMed:2713493, ECO:0000269|PubMed:2714791, ECO:0000269|PubMed:2738071, ECO:0000269|PubMed:2753873, ECO:0000269|PubMed:2773937, ECO:0000269|PubMed:2775660, ECO:0000269|PubMed:3009023, ECO:0000269|PubMed:3243764, ECO:0000269|PubMed:3401602, ECO:0000269|PubMed:3790720, ECO:0000269|PubMed:6603618, ECO:0000269|PubMed:7981722, ECO:0000269|PubMed:8076946, ECO:0000269|PubMed:8199596, ECO:0000269|PubMed:8257988, ECO:0000269|PubMed:8295821, ECO:0000269|PubMed:8680410, ECO:0000269|PubMed:9169594, ECO:0000269|PubMed:9222764, ECO:0000269|PubMed:9452115, ECO:0000269|PubMed:9590153, ECO:0000269|PubMed:9600455}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Note=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). {ECO:0000269|PubMed:12588353, ECO:0000269|PubMed:2162822, ECO:0000269|PubMed:25251685, ECO:0000269|PubMed:2713493, ECO:0000269|PubMed:2738071, ECO:0000269|PubMed:3009023, ECO:0000269|PubMed:3790720, ECO:0000269|PubMed:6603618, ECO:0000269|PubMed:8076946, ECO:0000269|PubMed:8295821, ECO:0000269|PubMed:9169594, ECO:0000269|PubMed:9600455}.

Disease: Thrombophilia, X-linked, due to factor IX defect (THPH8) [MIM:300807]: A hemostatic disorder characterized by a tendency to thrombosis. {ECO:0000269|PubMed:19846852}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Warfarin sensitivity, X-linked (WARFS) [MIM:301052]: A condition characterized by sensitivity to warfarin, a drugs used as anti-coagulants for the prevention of thromboembolic diseases in subjects with deep vein thrombosis, atrial fibrillation, or mechanical heart valve replacement. Warfarin sensitive individuals develop bleeding complications when they are given warfarin within the therapeutic ranges. {ECO:0000269|PubMed:29450643, ECO:0000269|PubMed:8833911, ECO:0000269|PubMed:9233593}. Note=The disease is caused by variants affecting the gene represented in this entry.

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. {ECO:0000255|PROSITE- ProRule:PRU00274}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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. {ECO:0000269\|PubMed:1730085, ECO:0000269\|PubMed:19846852, ECO:0000269\|PubMed:20121197, ECO:0000269\|PubMed:20121198, ECO:0000269\|PubMed:2592373, ECO:0000269\|PubMed:8295821}.


Catalytic activity:		Reaction=Selective cleavage of Arg-\|-Ile bond in factor X to form factor Xa.; EC=3.4.21.22; Evidence={ECO:0000269\|PubMed:12444082, ECO:0000269\|PubMed:20121197, ECO:0000269\|PubMed:20121198, ECO:0000269\|PubMed:2592373};
Subunit:		Heterodimer of a light chain and a heavy chain; disulfide- linked (PubMed:20121198, PubMed:20121197, PubMed:20080729). Interacts with SERPINC1. {ECO:0000269\|PubMed:20004170, ECO:0000269\|PubMed:20080729, ECO:0000269\|PubMed:20121197, ECO:0000269\|PubMed:20121198, ECO:0000269\|PubMed:2592373}.
Subcellular location:		Secreted {ECO:0000269\|PubMed:19846852, ECO:0000269\|PubMed:2592373, ECO:0000269\|PubMed:3857619, ECO:0000269\|PubMed:8295821, ECO:0000269\|PubMed:9169594}.
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. {ECO:0000269\|PubMed:19846852, ECO:0000269\|PubMed:2592373, ECO:0000269\|PubMed:3857619}.
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). {ECO:0000250\|UniProtKB:P00741, ECO:0000269\|PubMed:14722079, ECO:0000269\|PubMed:1730085, ECO:0000269\|PubMed:6425296}.
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). {ECO:0000269\|PubMed:1730085, ECO:0000269\|PubMed:20004170, ECO:0000269\|PubMed:20080729, ECO:0000269\|PubMed:2592373, ECO:0000269\|PubMed:8295821, ECO:0000269\|PubMed:9169594}.
Ptm:		The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains. {ECO:0000269\|PubMed:6688526}.
Disease:		Hemophilia B (HEMB) [MIM:306900]: An X-linked blood coagulation disorder characterized by a permanent tendency to hemorrhage, due to factor IX deficiency. It is phenotypically similar to hemophilia A, but patients present with fewer symptoms. Many patients are asymptomatic until the hemostatic system is stressed by surgery or trauma. {ECO:0000269\|PubMed:10094553, ECO:0000269\|PubMed:10698280, ECO:0000269\|PubMed:11122099, ECO:0000269\|PubMed:12588353, ECO:0000269\|PubMed:12604421, ECO:0000269\|PubMed:1346975, ECO:0000269\|PubMed:1615485, ECO:0000269\|PubMed:1902289, ECO:0000269\|PubMed:1958666, ECO:0000269\|PubMed:2162822, ECO:0000269\|PubMed:2339358, ECO:0000269\|PubMed:2372509, ECO:0000269\|PubMed:2472424, ECO:0000269\|PubMed:25251685, ECO:0000269\|PubMed:25470321, ECO:0000269\|PubMed:2592373, ECO:0000269\|PubMed:2713493, ECO:0000269\|PubMed:2714791, ECO:0000269\|PubMed:2738071, ECO:0000269\|PubMed:2753873, ECO:0000269\|PubMed:2773937, ECO:0000269\|PubMed:2775660, ECO:0000269\|PubMed:3009023, ECO:0000269\|PubMed:3243764, ECO:0000269\|PubMed:3401602, ECO:0000269\|PubMed:3790720, ECO:0000269\|PubMed:6603618, ECO:0000269\|PubMed:7981722, ECO:0000269\|PubMed:8076946, ECO:0000269\|PubMed:8199596, ECO:0000269\|PubMed:8257988, ECO:0000269\|PubMed:8295821, ECO:0000269\|PubMed:8680410, ECO:0000269\|PubMed:9169594, ECO:0000269\|PubMed:9222764, ECO:0000269\|PubMed:9452115, ECO:0000269\|PubMed:9590153, ECO:0000269\|PubMed:9600455}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Note=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). {ECO:0000269\|PubMed:12588353, ECO:0000269\|PubMed:2162822, ECO:0000269\|PubMed:25251685, ECO:0000269\|PubMed:2713493, ECO:0000269\|PubMed:2738071, ECO:0000269\|PubMed:3009023, ECO:0000269\|PubMed:3790720, ECO:0000269\|PubMed:6603618, ECO:0000269\|PubMed:8076946, ECO:0000269\|PubMed:8295821, ECO:0000269\|PubMed:9169594, ECO:0000269\|PubMed:9600455}.
Disease:		Thrombophilia, X-linked, due to factor IX defect (THPH8) [MIM:300807]: A hemostatic disorder characterized by a tendency to thrombosis. {ECO:0000269\|PubMed:19846852}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Warfarin sensitivity, X-linked (WARFS) [MIM:301052]: A condition characterized by sensitivity to warfarin, a drugs used as anti-coagulants for the prevention of thromboembolic diseases in subjects with deep vein thrombosis, atrial fibrillation, or mechanical heart valve replacement. Warfarin sensitive individuals develop bleeding complications when they are given warfarin within the therapeutic ranges. {ECO:0000269\|PubMed:29450643, ECO:0000269\|PubMed:8833911, ECO:0000269\|PubMed:9233593}. Note=The disease is caused by variants affecting the gene represented in this entry.
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. {ECO:0000255\|PROSITE- ProRule:PRU00274}.