ID FA9_HUMAN Reviewed; 461 AA. AC P00740; A8K9N4; F2RM36; Q5FBE1; Q5JYJ8; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 07-JUN-2005, sequence version 2. DT 13-FEB-2019, entry version 250. DE RecName: Full=Coagulation factor IX {ECO:0000303|PubMed:3857619}; DE EC=3.4.21.22 {ECO:0000269|PubMed:12444082, ECO:0000269|PubMed:20121197, ECO:0000269|PubMed:20121198, ECO:0000269|PubMed:2592373}; DE AltName: Full=Christmas factor; DE AltName: Full=Plasma thromboplastin component; DE Short=PTC; DE Contains: DE RecName: Full=Coagulation factor IXa light chain; DE Contains: DE RecName: Full=Coagulation factor IXa heavy chain; DE Flags: Precursor; GN Name=F9; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Liver; RX PubMed=6959130; DOI=10.1073/pnas.79.21.6461; RA Kurachi K., Davie E.W.; RT "Isolation and characterization of a cDNA coding for human factor RT IX."; RL Proc. Natl. Acad. Sci. U.S.A. 79:6461-6464(1982). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Liver; RX PubMed=6687940; DOI=10.1093/nar/11.8.2325; RA Jaye M., de la Salle H., Schamber F., Balland A., Kohli V., RA Findeli A., Tolstoshev P., Lecocq J.-P.; RT "Isolation of a human anti-haemophilic factor IX cDNA clone using a RT unique 52-base synthetic oligonucleotide probe deduced from the amino RT acid sequence of bovine factor IX."; RL Nucleic Acids Res. 11:2325-2335(1983). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-194. RX PubMed=6329734; RA Anson D.S., Choo K.H., Rees D.J.G., Giannelli F., Gould K.G., RA Huddleston J.A., Brownlee G.G.; RT "The gene structure of human anti-haemophilic factor IX."; RL EMBO J. 3:1053-1060(1984). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-194. RX PubMed=2994716; DOI=10.1021/bi00335a049; RA Yoshitake S., Schach B.G., Foster D.C., Davie E.W., Kurachi K.; RT "Nucleotide sequence of the gene for human factor IX (antihemophilic RT factor B)."; RL Biochemistry 24:3736-3750(1985). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ALA-194, SUBCELLULAR RP LOCATION, TISSUE SPECIFICITY, AND PARTIAL PROTEIN SEQUENCE. RX PubMed=3857619; DOI=10.1073/pnas.82.9.2847; RA McGraw R.A., Davis L.M., Noyes C.M., Lundblad R.L., Roberts H.R., RA Graham J.B., Stafford D.W.; RT "Evidence for a prevalent dimorphism in the activation peptide of RT human coagulation factor IX."; RL Proc. Natl. Acad. Sci. U.S.A. 82:2847-2851(1985). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND ALTERNATIVE SPLICING. RC TISSUE=Liver; RA Sata S., Yonemitsu Y., Nakagawa K., Sueishi K.; RT "Alternative splicing variant of Homo sapiens coagulation factor IX RT lacking EGF like domain."; RL Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT PRO-461. RG SeattleSNPs variation discovery resource; RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Liver; RA Nguyen D.T., Nguyen P.V., Nong H.V.; RT "Homo sapiens coagulation factor IX (F9), mRNA."; RL Submitted (MAR-2011) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Liver; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S., RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., RA Williams G., Williams L., Williamson A., Williamson H., Wilming L., RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [13] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 30-84, VARIANT HEMB GLN-43, RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND PROTEOLYTIC RP CLEAVAGE. RX PubMed=8295821; RA de la Salle C., Charmantier J.L., Ravanat C., Ohlmann P., RA Hartmann M.L., Schuhler S., Bischoff R., Ebel C., Roecklin D., RA Balland A.; RT "The Arg-4 mutant factor IX Strasbourg 2 shows a delayed activation by RT factor XIa."; RL Nouv. Rev. Fr. Hematol. 35:473-480(1993). RN [14] RP NUCLEOTIDE SEQUENCE [MRNA] OF 36-326 (ISOFORM 1). RC TISSUE=Liver; RX PubMed=6089357; DOI=10.1007/BF01534851; RA Jagadeeswaran P., Lavelle D.E., Kaul R., Mohandas T., Warren S.T.; RT "Isolation and characterization of human factor IX cDNA: RT identification of Taq I polymorphism and regional assignment."; RL Somat. Cell Mol. Genet. 10:465-473(1984). RN [15] RP PROTEIN SEQUENCE OF 47-461, VARIANT HEMB TRP-226, FUNCTION, CATALYTIC RP ACTIVITY, PROTEOLYTIC CLEAVAGE, SUBCELLULAR LOCATION, SUBUNIT, AND RP TISSUE SPECIFICITY. RX PubMed=2592373; RA Suehiro K., Kawabata S., Miyata T., Takeya H., Takamatsu J., Ogata K., RA Kamiya T., Saito H., Niho Y., Iwanaga S.; RT "Blood clotting factor IX BM Nagoya. Substitution of arginine 180 by RT tryptophan and its activation by alpha-chymotrypsin and rat mast cell RT chymase."; RL J. Biol. Chem. 264:21257-21265(1989). RN [16] RP PROTEIN SEQUENCE OF 47-52, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, RP CHARACTERIZATION OF VARIANTS HEMB GLN-43; LEU-43 AND TRP-43, RP CALCIUM-BINDING, AND PROTEOLYTIC CLEAVAGE. RX PubMed=9169594; DOI=10.1042/bj3230629; RA Wojcik E.G., Van Den Berg M., Poort S.R., Bertina R.M.; RT "Modification of the N-terminus of human factor IX by defective RT propeptide cleavage or acetylation results in a destabilized calcium- RT induced conformation: effects on phospholipid binding and activation RT by factor XIa."; RL Biochem. J. 323:629-636(1997). RN [17] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 290-359. RX PubMed=3340835; DOI=10.1126/science.3340835; RA Stoflet E.S., Koeberl D.D., Sarkar G., Sommer S.S.; RT "Genomic amplification with transcript sequencing."; RL Science 239:491-494(1988). RN [18] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 444-461. RX PubMed=8236150; RA de la Salle C., Charmantier J.L., Baas M.-J., Schwartz A., RA Wiesel M.L., Grunebaum L., Cazenave J.-P.; RT "A deletion located in the 3' non translated part of the factor IX RT gene responsible for mild haemophilia B."; RL Thromb. Haemost. 70:370-371(1993). RN [19] RP HYDROXYLATION AT ASP-110. RX PubMed=6688526; DOI=10.1016/0006-291X(83)90961-0; RA McMullen B.A., Fujikawa K., Kisiel W.; RT "The occurrence of beta-hydroxyaspartic acid in the vitamin K- RT dependent blood coagulation zymogens."; RL Biochem. Biophys. Res. Commun. 115:8-14(1983). RN [20] RP PROTEOLYTIC PROCESSING, AND ACTIVE SITE. RX PubMed=659613; DOI=10.1172/JCI109073; RA di Scipio R.G., Kurachi K., Davie E.W.; RT "Activation of human factor IX (Christmas factor)."; RL J. Clin. Invest. 61:1528-1538(1978). RN [21] RP CALCIUM-BINDING, AND DOMAIN. RX PubMed=6425296; RA Morita T., Isaacs B.S., Esmon C.T., Johnson A.E.; RT "Derivatives of blood coagulation factor IX contain a high affinity RT Ca2+-binding site that lacks gamma-carboxyglutamic acid."; RL J. Biol. Chem. 259:5698-5704(1984). RN [22] RP ERRATUM. RA Morita T., Isaacs B.S., Esmon C.T., Johnson A.E.; RL J. Biol. Chem. 260:2583-2583(1985). RN [23] RP GLYCOSYLATION AT SER-99, AND STRUCTURE OF CARBOHYDRATE ON SER-99. RX PubMed=2511201; RA Nishimura H., Kawabata S., Kisiel W., Hase S., Ikenaka T., Takao T., RA Shimonishi Y., Iwanaga S.; RT "Identification of a disaccharide (Xyl-Glc) and a trisaccharide (Xyl2- RT Glc) O-glycosidically linked to a serine residue in the first RT epidermal growth factor-like domain of human factors VII and IX and RT protein Z and bovine protein Z."; RL J. Biol. Chem. 264:20320-20325(1989). RN [24] RP GLYCOSYLATION AT SER-99, AND STRUCTURE OF CARBOHYDRATE ON SER-99. RX PubMed=2129367; RA Iwanaga S., Nishimura H., Kawabata S., Kisiel W., Hase S., Ikenaka T.; RT "A new trisaccharide sugar chain linked to a serine residue in the RT first EGF-like domain of clotting factors VII and IX and protein Z."; RL Adv. Exp. Med. Biol. 281:121-131(1990). RN [25] RP FUNCTION, AND PROTEOLYTIC CLEAVAGE. RX PubMed=1730085; RA Rawala-Sheikh R., Ahmad S.S., Monroe D.M., Roberts H.R., Walsh P.N.; RT "Role of gamma-carboxyglutamic acid residues in the binding of factor RT IXa to platelets and in factor-X activation."; RL Blood 79:398-405(1992). RN [26] RP GLYCOSYLATION AT SER-107, AND STRUCTURE OF CARBOHYDRATE ON SER-107. RX PubMed=1517205; RA Nishimura H., Takao T., Hase S., Shimonishi Y., Iwanaga S.; RT "Human factor IX has a tetrasaccharide O-glycosidically linked to RT serine 61 through the fucose residue."; RL J. Biol. Chem. 267:17520-17525(1992). RN [27] RP GLYCOSYLATION AT THR-205 AND THR-215. RX PubMed=8172892; DOI=10.1021/bi00183a021; RA Agarwala K.L., Kawabata S., Takao T., Murata H., Shimonishi Y., RA Nishimura H., Iwanaga S.; RT "Activation peptide of human factor IX has oligosaccharides O- RT glycosidically linked to threonine residues at 159 and 169."; RL Biochemistry 33:5167-5171(1994). RN [28] RP PHOSPHORYLATION AT SER-114. RA Harris R.J., Papac D.I., Truong L., Smith K.J.; RT "Partial phosphorylation of serine-68 in EGF-1 of human factor IX."; RL (In) Proceedings of XIth international conference on methods in RL protein structure analysis, pp.50-50, Annecy (1996). RN [29] RP SULFATION AT TYR-201, AND PHOSPHORYLATION AT SER-204. RX PubMed=11133752; DOI=10.1182/blood.V97.1.130; RA Arruda V.R., Hagstrom J.N., Deitch J., Heiman-Patterson T., RA Camire R.M., Chu K., Fields P.A., Herzog R.W., Couto L.B., RA Larson P.J., High K.A.; RT "Posttranslational modifications of recombinant myotube-synthesized RT human factor IX."; RL Blood 97:130-138(2001). RN [30] RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF TYR-305; LYS-311; TYR-312 AND RP TYR-391. RX PubMed=12444082; DOI=10.1074/jbc.M210722200; RA Sichler K., Kopetzki E., Huber R., Bode W., Hopfner K.P., RA Brandstetter H.; RT "Physiological fIXa activation involves a cooperative conformational RT rearrangement of the 99-loop."; RL J. Biol. Chem. 278:4121-4126(2003). RN [31] RP GLYCOSYLATION AT SER-99. RX PubMed=21949356; DOI=10.1073/pnas.1109696108; RA Takeuchi H., Fernandez-Valdivia R.C., Caswell D.S., Nita-Lazar A., RA Rana N.A., Garner T.P., Weldeghiorghis T.K., Macnaughtan M.A., RA Jafar-Nejad H., Haltiwanger R.S.; RT "Rumi functions as both a protein O-glucosyltransferase and a protein RT O-xylosyltransferase."; RL Proc. Natl. Acad. Sci. U.S.A. 108:16600-16605(2011). RN [32] RP GLYCOSYLATION AT THR-85; SER-99; SER-107; THR-205; THR-215 AND RP THR-225, PHOSPHORYLATION AT SER-204 AND THR-205, AND IDENTIFICATION BY RP MASS SPECTROMETRY. RX PubMed=25456591; DOI=10.1016/j.chroma.2014.10.046; RA Huang L.J., Lin J.H., Tsai J.H., Chu Y.Y., Chen Y.W., Chen S.L., RA Chen S.H.; RT "Identification of protein O-glycosylation site and corresponding RT glycans using liquid chromatography-tandem mass spectrometry via RT mapping accurate mass and retention time shift."; RL J. Chromatogr. A 1371:136-145(2014). RN [33] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [34] RP STRUCTURE BY NMR OF 47-93. RX PubMed=7713897; DOI=10.1074/jbc.270.14.7980; RA Freedman S.J., Furie B.C., Furie B., Baleja J.D.; RT "Structure of the metal-free gamma-carboxyglutamic acid-rich membrane RT binding region of factor IX by two-dimensional NMR spectroscopy."; RL J. Biol. Chem. 270:7980-7987(1995). RN [35] RP STRUCTURE BY NMR OF 47-93. RX PubMed=7547952; DOI=10.1021/bi00038a005; RA Freedman S.J., Furie B.C., Furie B., Baleja J.D.; RT "Structure of the calcium ion-bound gamma-carboxyglutamic acid-rich RT domain of factor IX."; RL Biochemistry 34:12126-12137(1995). RN [36] RP STRUCTURE BY NMR OF 47-93. RX PubMed=8663165; DOI=10.1074/jbc.271.27.16227; RA Freedman S.J., Blostein M.D., Baleja J.D., Jacobs M., Furie B.C., RA Furie B.; RT "Identification of the phospholipid binding site in the vitamin K- RT dependent blood coagulation protein factor IX."; RL J. Biol. Chem. 271:16227-16236(1996). RN [37] RP STRUCTURE BY NMR OF 47-93. RX PubMed=9047312; DOI=10.1021/bi962250r; RA Li L., Darden T.A., Freedman S.J., Furie B.C., Furie B., Baleja J.D., RA Smith H., Hiskey R.G., Pedersen L.G.; RT "Refinement of the NMR solution structure of the gamma-carboxyglutamic RT acid domain of coagulation factor IX using molecular dynamics RT simulation with initial Ca2+ positions determined by a genetic RT algorithm."; RL Biochemistry 36:2132-2138(1997). RN [38] RP STRUCTURE BY NMR OF 91-133. RX PubMed=1854745; DOI=10.1021/bi00244a006; RA Huang L.H., Cheng H., Pardi A., Tam J.P., Sweeney W.V.; RT "Sequence-specific 1H NMR assignments, secondary structure, and RT location of the calcium binding site in the first epidermal growth RT factor like domain of blood coagulation factor IX."; RL Biochemistry 30:7402-7409(1991). RN [39] RP STRUCTURE BY NMR OF 92-130, AND DISULFIDE BOND. RX PubMed=1304885; DOI=10.1002/pro.5560010109; RA Baron M., Norman D.G., Harvey T.S., Handford P.A., Mayhew M., RA Tse A.G.D., Brownlee G.G., Campbell I.D.C.; RT "The three-dimensional structure of the first EGF-like module of human RT factor IX: comparison with EGF and TGF-alpha."; RL Protein Sci. 1:81-90(1992). RN [40] RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 92-130 IN COMPLEX WITH RP CALCIUM, AND DISULFIDE BOND. RX PubMed=7606779; DOI=10.1016/0092-8674(95)90059-4; RA Rao Z., Handford P., Mayhew M., Knott V., Brownlee G.G., Stuart D.; RT "The structure of a Ca(2+)-binding epidermal growth factor-like RT domain: its role in protein-protein interactions."; RL Cell 82:131-141(1995). RN [41] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 133-461 IN COMPLEX WITH RP CALCIUM. RX PubMed=10467148; DOI=10.1016/S0969-2126(99)80125-7; RA Hopfner K.-P., Lang A., Karcher A., Sichler K., Kopetzki E., RA Brandstetter H., Huber R., Bode W., Engh R.A.; RT "Coagulation factor IXa: the relaxed conformation of Tyr99 blocks RT substrate binding."; RL Structure 7:989-996(1999). RN [42] RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 47-91 IN COMPLEX WITH RP CALCIUM. RX PubMed=14722079; DOI=10.1074/jbc.M314011200; RA Huang M., Furie B.C., Furie B.; RT "Crystal structure of the calcium-stabilized human factor IX Gla RT domain bound to a conformation-specific anti-factor IX antibody."; RL J. Biol. Chem. 279:14338-14346(2004). RN [43] RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 133-191 AND 227-461 OF RP MUTANTS PHE-305/THR-311/ALA-365/THR-391 IN COMPLEX WITH CALCIUM AND RP SYNTHETIC INHIBITOR, ACTIVE SITE, DISULFIDE BOND, SUBUNIT, AND RP PROTEOLYTIC CLEAVAGE. RX PubMed=20004170; DOI=10.1016/j.str.2009.10.011; RA Zogg T., Brandstetter H.; RT "Structural basis of the cofactor- and substrate-assisted activation RT of human coagulation factor IXa."; RL Structure 17:1669-1678(2009). RN [44] RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 133-461 IN COMPLEX WITH RP CALCIUM, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND DISULFIDE BOND. RX PubMed=20121198; DOI=10.1021/jm901475e; RA Wang S., Beck R., Blench T., Burd A., Buxton S., Malic M., Ayele T., RA Shaikh S., Chahwala S., Chander C., Holland R., Merette S., Zhao L., RA Blackney M., Watts A.; RT "Studies of benzothiophene template as potent factor IXa (FIXa) RT inhibitors in thrombosis."; RL J. Med. Chem. 53:1465-1472(2010). RN [45] RP X-RAY CRYSTALLOGRAPHY (2.62 ANGSTROMS) OF 133-188 AND 227-461 IN RP COMPLEX WITH CALCIUM, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND RP DISULFIDE BOND. RX PubMed=20121197; DOI=10.1021/jm901476x; RA Wang S., Beck R., Burd A., Blench T., Marlin F., Ayele T., Buxton S., RA Dagostin C., Malic M., Joshi R., Barry J., Sajad M., Cheung C., RA Shaikh S., Chahwala S., Chander C., Baumgartner C., Holthoff H.P., RA Murray E., Blackney M., Giddings A.; RT "Structure based drug design: development of potent and selective RT factor IXa (FIXa) inhibitors."; RL J. Med. Chem. 53:1473-1482(2010). RN [46] RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 131-188 AND 227-461 IN RP COMPLEX WITH SERPINC1 AND CALCIUM, DISULFIDE BOND, PROTEOLYTIC RP CLEAVAGE, AND SUBUNIT. RX PubMed=20080729; DOI=10.1073/pnas.0910144107; RA Johnson D.J., Langdown J., Huntington J.A.; RT "Molecular basis of factor IXa recognition by heparin-activated RT antithrombin revealed by a 1.7-A structure of the ternary complex."; RL Proc. Natl. Acad. Sci. U.S.A. 107:645-650(2010). RN [47] RP MOLECULAR PATHOLOGY OF HEMB B. RX PubMed=2743975; RA Green P.M., Bentley D.R., Mibashan R.S., Nilsson I.M., Giannelli F.; RT "Molecular pathology of haemophilia B."; RL EMBO J. 8:1067-1072(1989). RN [48] RP REVIEW ON HEMB VARIANTS. RX PubMed=1634040; RA Sommer S.S.; RT "Assessing the underlying pattern of human germline mutations: lessons RT from the factor IX gene."; RL FASEB J. 6:2767-2774(1992). RN [49] RP REVIEW ON HEMB VARIANTS. RX PubMed=8392713; DOI=10.1093/nar/21.13.3075; RA Giannelli F., Green P.M., High K.A., Sommer S., Poon M.-C., Ludwig M., RA Schwaab R., Reitsma P.H., Goossens M., Yoshioka A., Brownlee G.G.; RT "Haemophilia B: database of point mutations and short additions and RT deletions -- fourth edition, 1993."; RL Nucleic Acids Res. 21:3075-3087(1993). RN [50] RP VARIANT HEMB HIS-191. RX PubMed=6603618; DOI=10.1073/pnas.80.14.4200; RA Noyes C.M., Griffith M.J., Roberts H.R., Lundblad R.L.; RT "Identification of the molecular defect in factor IX Chapel Hill: RT substitution of histidine for arginine at position 145."; RL Proc. Natl. Acad. Sci. U.S.A. 80:4200-4202(1983). RN [51] RP VARIANT HEMB GLN-43, AND CHARACTERIZATION OF VARIANT HEMB GLN-43. RX PubMed=3009023; DOI=10.1016/0092-8674(86)90319-3; RA Bentley A.K., Rees D.J., Rizza C., Brownlee G.G.; RT "Defective propeptide processing of blood clotting factor IX caused by RT mutation of arginine to glutamine at position -4."; RL Cell 45:343-348(1986). RN [52] RP VARIANT HEMB GLY-93. RX PubMed=3790720; RA Davis L.M., McGraw R.A., Ware J.L., Roberts H.R., Stafford D.W.; RT "Factor IXAlabama: a point mutation in a clotting protein results in RT hemophilia B."; RL Blood 69:140-143(1987). RN [53] RP VARIANT HEMB THR-443. RX PubMed=3401602; RA Ware J., Davis L., Frazier D., Bajaj S.P., Stafford D.W.; RT "Genetic defect responsible for the dysfunctional protein: factor IX RT (Long Beach)."; RL Blood 72:820-822(1988). RN [54] RP VARIANT HEMB VAL-436. RX PubMed=3243764; RA Sugimoto M., Miyata T., Kawabata S., Yoshioka A., Fukui H., RA Takahashi H., Iwanaga S.; RT "Blood clotting factor IX Niigata: substitution of alanine-390 by RT valine in the catalytic domain."; RL J. Biochem. 104:878-880(1988). RN [55] RP VARIANT HEMB GLN-226. RX PubMed=2713493; RA Monroe D.M., McCord D.M., Huang M.N., High K.A., Lundblad R.L., RA Kasper C.K., Roberts H.R.; RT "Functional consequences of an arginine180 to glutamine mutation in RT factor IX Hilo."; RL Blood 73:1540-1544(1989). RN [56] RP VARIANT HEMB ARG-442. RX PubMed=2714791; DOI=10.1016/0888-7543(89)90330-3; RA Attree O., Vidaud D., Vidaud M., Amselem S., Lavergne J.-M., RA Goossens M.; RT "Mutations in the catalytic domain of human coagulation factor IX: RT rapid characterization by direct genomic sequencing of DNA fragments RT displaying an altered melting behavior."; RL Genomics 4:266-272(1989). RN [57] RP VARIANTS HEMB GLN-75; ASP-79; TRP-268; THR-279; SER-306; MET-342; RP ARG-357 AND ARG-453, AND VARIANT PHE-7. RX PubMed=2773937; RA Koeberl D.D., Bottema C.D., Buerstedde J.-M., Sommer S.S.; RT "Functionally important regions of the factor IX gene have a low rate RT of polymorphism and a high rate of mutation in the dinucleotide CpG."; RL Am. J. Hum. Genet. 45:448-457(1989). RN [58] RP VARIANT HEMB CYS-191. RX PubMed=2775660; DOI=10.1111/j.1365-2141.1989.tb04323.x; RA Liddell M.B., Peake I.R., Taylor S.A., Lillicrap D.P., Giddings J.C., RA Bloom A.L.; RT "Factor IX Cardiff: a variant factor IX protein that shows abnormal RT activation is caused by an arginine to cysteine substitution at RT position 145."; RL Br. J. Haematol. 72:556-560(1989). RN [59] RP VARIANT HEMB PHE-228. RX PubMed=2753873; RA Sakai T., Yoshioka A., Yamamoto K., Niinomi K., Fujimura Y., Fukui H., RA Miyata T., Iwanaga S.; RT "Blood clotting factor IX Kashihara: amino acid substitution of RT valine-182 by phenylalanine."; RL J. Biochem. 105:756-759(1989). RN [60] RP VARIANT HEMB GLN-43. RX PubMed=2738071; RA Ware J., Diuguid D.L., Liebman H.A., Rabiet M.J., Kasper C.K., RA Furie B.C., Furie B., Stafford D.W.; RT "Factor IX San Dimas. Substitution of glutamine for Arg-4 in the RT propeptide leads to incomplete gamma-carboxylation and altered RT phospholipid binding properties."; RL J. Biol. Chem. 264:11401-11406(1989). RN [61] RP VARIANTS HEMB LYS-73; SER-106 AND GLN-294. RX PubMed=2472424; DOI=10.1172/JCI114130; RA Chen S.H., Thompson A.R., Zhang M., Scott C.R.; RT "Three point mutations in the factor IX genes of five hemophilia B RT patients. Identification strategy using localization by altered RT epitopes in their hemophilic proteins."; RL J. Clin. Invest. 84:113-118(1989). RN [62] RP VARIANT HEMB VAL-73. RX PubMed=2339358; RA Wang N.S., Zhang M., Thompson A.R., Chen S.H.; RT "Factor IX Chongqing: a new mutation in the calcium-binding domain of RT factor IX resulting in severe hemophilia B."; RL Thromb. Haemost. 63:24-26(1990). RN [63] RP VARIANT HEMB LEU-228. RX PubMed=2372509; DOI=10.1111/j.1365-2141.1990.tb02652.x; RA Taylor S.A., Liddell M.B., Peake I.R., Bloom A.L., Lillicrap D.P.; RT "A mutation adjacent to the beta cleavage site of factor IX (valine RT 182 to leucine) results in mild haemophilia Bm."; RL Br. J. Haematol. 75:217-221(1990). RN [64] RP VARIANTS HEMB GLN-226; TRP-226; PHE-227 AND THR-414. RX PubMed=2162822; RA Bertina R.M., van der Linden I.K., Mannucci P.M., Reinalda-Poot H.H., RA Cupers R., Poort S.R., Reitsma P.H.; RT "Mutations in hemophilia Bm occur at the Arg180-Val activation site or RT in the catalytic domain of factor IX."; RL J. Biol. Chem. 265:10876-10883(1990). RN [65] RP VARIANT HEMB GLU-357. RX PubMed=1958666; DOI=10.1021/bi00111a014; RA Miyata T., Sakai T., Sugimoto M., Naka H., Yamamoto K., Yoshioka A., RA Fukui H., Mitsui K., Kamiya K., Umeyama H., Iwanaga S.; RT "Factor IX Amagasaki: a new mutation in the catalytic domain resulting RT in the loss of both coagulant and esterase activities."; RL Biochemistry 30:11286-11291(1991). RN [66] RP VARIANT HEMB THR-443. RX PubMed=1902289; DOI=10.1093/nar/19.5.1165; RA Sarkar G., Cassady J.D., Pyeritz R.E., Gilchrist G.S., Sommer S.S.; RT "Isoleucine-397 is changed to threonine in two females with hemophilia RT B."; RL Nucleic Acids Res. 19:1165-1165(1991). RN [67] RP VARIANTS HEMB VAL-291; GLN-294; HIS-410; GLY-411 AND ILE-411. RX PubMed=1346975; RA Ludwig M., Sabharwal A.K., Brackmann H.H., Olek K., Smith K.J., RA Birktoft J.J., Bajaj S.P.; RT "Hemophilia B caused by five different nondeletion mutations in the RT protease domain of factor IX."; RL Blood 79:1225-1232(1992). RN [68] RP VARIANT HEMB SER-252. RX PubMed=1615485; RA Taylor S.A., Duffin J., Cameron C., Teitel J., Garvey B., RA Lillicrap D.P.; RT "Characterization of the original Christmas disease mutation (cysteine RT 206-->serine): from clinical recognition to molecular pathogenesis."; RL Thromb. Haemost. 67:63-65(1992). RN [69] RP VARIANTS HEMB ARG-253; GLN-294; GLN-379; PRO-426 AND ILE-TYR-THR-445 RP INS. RX PubMed=8257988; DOI=10.1002/humu.1380020506; RA David D., Rosa H.A.V., Pemberton S., Diniz M.J., Campos M., RA Lavinha J.; RT "Single-strand conformation polymorphism (SSCP) analysis of the RT molecular pathology of hemophilia B."; RL Hum. Mutat. 2:355-361(1993). RN [70] RP VARIANTS HEMB HIS-191; GLY-226; THR-279; GLN-379; GLU-419 AND GLN-449. RX PubMed=8076946; DOI=10.1007/BF00208285; RA Aguilar-Martinez P., Romey M.-C., Schved J.-F., Gris J.-C., RA Demaille J., Claustres M.; RT "Factor IX gene mutations causing haemophilia B: comparison of SSC RT screening versus systematic DNA sequencing and diagnostic RT applications."; RL Hum. Genet. 94:287-290(1994). RN [71] RP VARIANT HEMB GLU-419. RX PubMed=8199596; DOI=10.1002/humu.1380030211; RA Aguilar-Martinez P., Romey M.-C., Gris J.-C., Schved J.-F., RA Demaille J., Claustres M.; RT "A novel mutation (Val-373 to Glu) in the catalytic domain of factor RT IX, resulting in moderately/severe hemophilia B in a southern French RT patient."; RL Hum. Mutat. 3:156-158(1994). RN [72] RP VARIANTS HEMB GLN-294 AND ARG-413. RX PubMed=7981722; DOI=10.1002/humu.1380040214; RA Caglayan S.H., Vielhaber E., Guersel T., Aktuglu G., Sommer S.S.; RT "Identification of mutations in four hemophilia B patients of Turkish RT origin, including a novel deletion of base 6411."; RL Hum. Mutat. 4:163-165(1994). RN [73] RP VARIANTS HEMB. RX PubMed=8680410; DOI=10.1002/humu.1380060410; RA Wulff K., Schroeder W., Wehnert M., Herrmann F.H.; RT "Twenty-five novel mutations of the factor IX gene in haemophilia B."; RL Hum. Mutat. 6:346-348(1995). RN [74] RP VARIANT WARFARIN SENSITIVITY THR-37. RX PubMed=8833911; DOI=10.1172/JCI118956; RA Chu K., Wu S.M., Stanley T., Stafford D.W., High K.A.; RT "A mutation in the propeptide of factor IX leads to warfarin RT sensitivity by a novel mechanism."; RL J. Clin. Invest. 98:1619-1625(1996). RN [75] RP VARIANTS HEMB LYS-113; MET-342; ARG-413 AND VAL-424. RX PubMed=9222764; RX DOI=10.1002/(SICI)1098-1004(1997)10:1<76::AID-HUMU11>3.3.CO;2-0; RA Caglayan S.H., Goekmen Y., Aktuglu G., Guergey A., Sommer S.S.; RT "Mutations associated with hemophilia B in Turkish patients."; RL Hum. Mutat. 10:76-79(1997). RN [76] RP VARIANT HEMB PRO-397. RX PubMed=9590153; RX DOI=10.1002/(SICI)1096-8652(199805)58:1<72::AID-AJH13>3.0.CO;2-7; RA Chan V., Chan V.W.Y., Yip B., Chim C.S., Chan T.K.; RT "Hemophilia B in a female carrier due to skewed inactivation of the RT normal X-chromosome."; RL Am. J. Hematol. 58:72-76(1998). RN [77] RP VARIANTS HEMB ARG-119 AND THR-454. RX PubMed=9452115; RA David D., Moreira I., Morais S., de Deus G.; RT "Five novel factor IX mutations in unrelated hemophilia B patients."; RL Hum. Mutat. Suppl. 1:S301-S303(1998). RN [78] RP VARIANTS HEMB GLN-43; TRP-43; THR-46; SER-106; CYS-115; PHE-155; RP GLN-379; GLU-387; VAL-432 AND CYS-450. RX PubMed=9600455; RX DOI=10.1002/(SICI)1098-1004(1998)11:5<372::AID-HUMU4>3.0.CO;2-M; RA Heit J.A., Thorland E.C., Ketterling R.P., Lind T.J., Daniels T.M., RA Zapata R.E., Ordonez S.M., Kasper C.K., Sommer S.S.; RT "Germline mutations in Peruvian patients with hemophilia B: pattern of RT mutation in Amerindians is similar to the putative endogenous germline RT pattern."; RL Hum. Mutat. 11:372-376(1998). RN [79] RP VARIANTS HEMB. RX PubMed=10698280; RA Wulff K., Bykowska K., Lopaciuk S., Herrmann F.H.; RT "Molecular analysis of hemophilia B in Poland: 12 novel mutations of RT the factor IX gene."; RL Acta Biochim. Pol. 46:721-726(1999). RN [80] RP VARIANTS HEMB. RX PubMed=10094553; RX DOI=10.1002/(SICI)1098-1004(1999)13:2<160::AID-HUMU9>3.0.CO;2-C; RA Montejo J.M., Magallon M., Tizzano E., Solera J.; RT "Identification of twenty-one new mutations in the factor IX gene by RT SSCP analysis."; RL Hum. Mutat. 13:160-165(1999). RN [81] RP VARIANT ALA-194. RX PubMed=10391209; DOI=10.1038/10290; RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RT "Characterization of single-nucleotide polymorphisms in coding regions RT of human genes."; RL Nat. Genet. 22:231-238(1999). RN [82] RP ERRATUM. RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RL Nat. Genet. 23:373-373(1999). RN [83] RP VARIANTS HEMB CYS-169 AND THR-333. RX PubMed=11122099; DOI=10.1046/j.1365-2141.2000.02389.x; RA Vidal F., Farssac E., Altisent C., Puig L., Gallardo D.; RT "Factor IX gene sequencing by a simple and sensitive 15-hour procedure RT for haemophilia B diagnosis: identification of two novel mutations."; RL Br. J. Haematol. 111:549-551(2000). RN [84] RP VARIANTS HEMB TYR-28; LEU-43; GLN-43; SER-52; ASP-106; LYS-124; RP TYR-134; GLN-226; GLY-226; TRP-226; LYS-241; TYR-252; GLN-294; RP PHE-316; ARG-318; GLY-379; ILE-383; PHE-383; ILE-395; PHE-396; ARG-407 RP AND GLU-412. RX PubMed=12588353; DOI=10.1046/j.1365-2141.2003.04141.x; RA Onay U.V., Kavakli K., Kilinc Y., Gurgey A., Aktuglu G., Kemahli S., RA Ozbek U., Caglayan S.H.; RT "Molecular pathology of haemophilia B in Turkish patients: RT identification of a large deletion and 33 independent point RT mutations."; RL Br. J. Haematol. 120:656-659(2003). RN [85] RP VARIANTS HEMB TRP-43; ARG-84; ARG-125; VAL-125; PHE-170; ARG-302; RP MET-342; LEU-344; LEU-395; THR-414; TYR-435; GLU-442 AND TRP-449. RX PubMed=12604421; RA Espinos C., Casana P., Haya S., Cid A.R., Aznar J.A.; RT "Molecular analyses in hemophilia B families: identification of six RT new mutations in the factor IX gene."; RL Haematologica 88:235-236(2003). RN [86] RP VARIANT THPH8 LEU-384, CHARACTERIZATION OF VARIANT THPH8 LEU-384, RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=19846852; DOI=10.1056/NEJMoa0904377; RA Simioni P., Tormene D., Tognin G., Gavasso S., Bulato C., RA Iacobelli N.P., Finn J.D., Spiezia L., Radu C., Arruda V.R.; RT "X-linked thrombophilia with a mutant factor IX (factor IX Padua)."; RL N. Engl. J. Med. 361:1671-1675(2009). RN [87] RP VARIANTS HEMB ALA-194 AND HIS-241. RX PubMed=25470321; DOI=10.1111/hae.12553; RA Saini S., Hamasaki-Katagiri N., Pandey G.S., Yanover C., Guelcher C., RA Simhadri V.L., Dandekar S., Guerrera M.F., Kimchi-Sarfaty C., RA Sauna Z.E.; RT "Genetic determinants of immunogenicity to factor IX during the RT treatment of haemophilia B."; RL Haemophilia 21:210-218(2015). RN [88] RP VARIANTS HEMB SER-20; TYR-28; SER-46; ASP-54; GLU-58; ARG-84; HIS-138; RP GLN-226; ILE-284 DEL; MET-296; LYS-328; TYR-328; THR-414 AND RP TYR-THR-LYS-VAL-447 INS, AND CHARACTERIZATION OF VARIANTS HEMB SER-20; RP TYR-28; SER-46; ASP-54; GLU-58; ARG-84; HIS-138; GLN-226; ILE-284 DEL; RP MET-296; LYS-328; TYR-328; THR-414 AND TYR-THR-LYS-VAL-447 INS. RX PubMed=25251685; DOI=10.1111/hae.12534; RA Guo Z.P., Yang L.H., Qin X.Y., Liu X.E., Chen J.F., Zhang Y.F.; RT "Comprehensive analysis of phenotypes and genetics in 21 Chinese RT families with haemophilia B: characterization of five novel RT mutations."; RL Haemophilia 20:859-865(2014). CC -!- FUNCTION: Factor IX is a vitamin K-dependent plasma protein that CC participates in the intrinsic pathway of blood coagulation by CC converting factor X to its active form in the presence of Ca(2+) CC ions, phospholipids, and factor VIIIa. CC {ECO:0000269|PubMed:1730085, ECO:0000269|PubMed:19846852, CC ECO:0000269|PubMed:20121197, ECO:0000269|PubMed:20121198, CC ECO:0000269|PubMed:2592373, ECO:0000269|PubMed:8295821}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Selective cleavage of Arg-|-Ile bond in factor X to form CC factor Xa.; EC=3.4.21.22; Evidence={ECO:0000269|PubMed:12444082, CC ECO:0000269|PubMed:20121197, ECO:0000269|PubMed:20121198, CC ECO:0000269|PubMed:2592373}; CC -!- SUBUNIT: Heterodimer of a light chain and a heavy chain; CC disulfide-linked (PubMed:20121198, PubMed:20121197, CC PubMed:20080729). Interacts with SERPINC1. CC {ECO:0000269|PubMed:20004170, ECO:0000269|PubMed:20080729, CC ECO:0000269|PubMed:20121197, ECO:0000269|PubMed:20121198, CC ECO:0000269|PubMed:2592373}. CC -!- INTERACTION: CC P00451:F8; NbExp=2; IntAct=EBI-9640450, EBI-11621603; CC Q3U4G3:Xxylt1 (xeno); NbExp=3; IntAct=EBI-9640450, EBI-16178491; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:19846852, CC ECO:0000269|PubMed:2592373, ECO:0000269|PubMed:3857619, CC ECO:0000269|PubMed:8295821, ECO:0000269|PubMed:9169594}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P00740-1; Sequence=Displayed; CC Name=2; CC IsoId=P00740-2; Sequence=VSP_047689; CC -!- TISSUE SPECIFICITY: Detected in blood plasma (at protein level) CC (PubMed:3857619, PubMed:8295821, PubMed:2592373, PubMed:9169594, CC PubMed:19846852). Synthesized primarily in the liver and secreted CC in plasma. {ECO:0000269|PubMed:19846852, CC ECO:0000269|PubMed:2592373, ECO:0000269|PubMed:3857619}. CC -!- DOMAIN: Calcium binds to the gamma-carboxyglutamic acid (Gla) CC residues in the Gla domain. Calcium can also bind, with stronger CC affinity, to another site beyond the Gla domain (PubMed:6425296). CC Under physiological ion concentrations, Ca(2+) is displaced by CC Mg(2+) from some of the gammaglutamate residues in the N-terminal CC Gla domain. This leads to a subtle conformation change that may CC affect the interaction with its binding protein (By similarity). CC {ECO:0000250|UniProtKB:P00741, ECO:0000269|PubMed:14722079, CC ECO:0000269|PubMed:1730085, ECO:0000269|PubMed:6425296}. CC -!- PTM: Activated by factor XIa, which excises the activation peptide CC (PubMed:9169594, PubMed:1730085). The propeptide can also be CC removed by snake venom protease (PubMed:20004170, CC PubMed:20080729). {ECO:0000269|PubMed:1730085, CC ECO:0000269|PubMed:20004170, ECO:0000269|PubMed:20080729, CC ECO:0000269|PubMed:2592373, ECO:0000269|PubMed:8295821, CC ECO:0000269|PubMed:9169594}. CC -!- PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of CC aspartate and asparagine is (R) stereospecific within EGF domains. CC {ECO:0000269|PubMed:6688526}. CC -!- PTM: Predominantly O-glucosylated at Ser-99 by POGLUT1 in vitro. CC Xylosylation at this site is minor. CC -!- DISEASE: Hemophilia B (HEMB) [MIM:306900]: An X-linked blood CC coagulation disorder characterized by a permanent tendency to CC hemorrhage, due to factor IX deficiency. It is phenotypically CC similar to hemophilia A, but patients present with fewer symptoms. CC Many patients are asymptomatic until the hemostatic system is CC stressed by surgery or trauma. {ECO:0000269|PubMed:10094553, CC ECO:0000269|PubMed:10698280, ECO:0000269|PubMed:11122099, CC ECO:0000269|PubMed:12588353, ECO:0000269|PubMed:12604421, CC ECO:0000269|PubMed:1346975, ECO:0000269|PubMed:1615485, CC ECO:0000269|PubMed:1902289, ECO:0000269|PubMed:1958666, CC ECO:0000269|PubMed:2162822, ECO:0000269|PubMed:2339358, CC ECO:0000269|PubMed:2372509, ECO:0000269|PubMed:2472424, CC ECO:0000269|PubMed:25251685, ECO:0000269|PubMed:25470321, CC ECO:0000269|PubMed:2592373, ECO:0000269|PubMed:2713493, CC ECO:0000269|PubMed:2714791, ECO:0000269|PubMed:2738071, CC ECO:0000269|PubMed:2753873, ECO:0000269|PubMed:2773937, CC ECO:0000269|PubMed:2775660, ECO:0000269|PubMed:3009023, CC ECO:0000269|PubMed:3243764, ECO:0000269|PubMed:3401602, CC ECO:0000269|PubMed:3790720, ECO:0000269|PubMed:6603618, CC ECO:0000269|PubMed:7981722, ECO:0000269|PubMed:8076946, CC ECO:0000269|PubMed:8199596, ECO:0000269|PubMed:8257988, CC ECO:0000269|PubMed:8295821, ECO:0000269|PubMed:8680410, CC ECO:0000269|PubMed:9169594, ECO:0000269|PubMed:9222764, CC ECO:0000269|PubMed:9452115, ECO:0000269|PubMed:9590153, CC ECO:0000269|PubMed:9600455}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Note=Mutations in position 43 (Oxford-3, San Dimas) and CC 46 (Cambridge) prevents cleavage of the propeptide CC (PubMed:12588353, PubMed:2738071, PubMed:3009023, PubMed:8295821, CC PubMed:9169594, PubMed:9600455, PubMed:25251685). Mutation in CC position 93 (Alabama) probably fails to bind to cell membranes CC (PubMed:3790720). Mutation in position 191 (Chapel-Hill) or in CC position 226 (Nagoya or Hilo) prevent cleavage of the activation CC peptide (PubMed:6603618, PubMed:8076946, PubMed:12588353, CC PubMed:2162822, PubMed:25251685, PubMed:2713493). CC {ECO:0000269|PubMed:12588353, ECO:0000269|PubMed:2162822, CC ECO:0000269|PubMed:25251685, ECO:0000269|PubMed:2713493, CC ECO:0000269|PubMed:2738071, ECO:0000269|PubMed:3009023, CC ECO:0000269|PubMed:3790720, ECO:0000269|PubMed:6603618, CC ECO:0000269|PubMed:8076946, ECO:0000269|PubMed:8295821, CC ECO:0000269|PubMed:9169594, ECO:0000269|PubMed:9600455}. CC -!- DISEASE: Thrombophilia, X-linked, due to factor IX defect (THPH8) CC [MIM:300807]: A hemostatic disorder characterized by a tendency to CC thrombosis. {ECO:0000269|PubMed:19846852}. Note=The disease is CC caused by mutations affecting the gene represented in this entry. CC -!- PHARMACEUTICAL: Available under the name BeneFix (Baxter and CC American Home Products). Used to treat hemophilia B. CC -!- MISCELLANEOUS: In 1952, one of the earliest researchers of the CC disease, Dr. R.G. Macfarlane used the patient's surname, CC Christmas, to refer to the disease and also to refer to the CC clotting factor which he called the 'Christmas Factor' At the time CC Stephen Christmas was a 5-year-old boy. He died in 1993 at the age CC of 46 from acquired immunodeficiency syndrome contracted through CC treatment with blood products. CC -!- SIMILARITY: Belongs to the peptidase S1 family. CC {ECO:0000255|PROSITE-ProRule:PRU00274}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Factor IX entry; CC URL="https://en.wikipedia.org/wiki/Factor_IX"; CC -!- WEB RESOURCE: Name=Factor IX Mutation Database; CC URL="http://www.factorix.org/"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/f9/"; CC -!- WEB RESOURCE: Name=BeneFix; Note=Clinical information on BeneFix; CC URL="https://www.pfizer.com/products/product-detail/benefix"; CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The Christmas Factor CC - Issue 41 of December 2003; CC URL="https://web.expasy.org/spotlight/back_issues/041"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; J00136; AAA98726.1; -; mRNA. DR EMBL; J00137; AAA52763.1; -; mRNA. DR EMBL; K02053; AAA56822.1; -; Genomic_DNA. DR EMBL; K02048; AAA56822.1; JOINED; Genomic_DNA. DR EMBL; K02049; AAA56822.1; JOINED; Genomic_DNA. DR EMBL; K02051; AAA56822.1; JOINED; Genomic_DNA. DR EMBL; K02052; AAA56822.1; JOINED; Genomic_DNA. DR EMBL; K02402; AAB59620.1; -; Genomic_DNA. DR EMBL; M11309; AAA52023.1; -; mRNA. DR EMBL; AL033403; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AB186358; BAD89383.1; -; mRNA. DR EMBL; AF536327; AAM96188.1; -; Genomic_DNA. DR EMBL; FR846239; CCA61111.1; -; mRNA. DR EMBL; AK292749; BAF85438.1; -; mRNA. DR EMBL; CH471150; EAW88433.1; -; Genomic_DNA. DR EMBL; BC109214; AAI09215.1; -; mRNA. DR EMBL; BC109215; AAI09216.1; -; mRNA. DR EMBL; S68634; AAB29758.1; -; Genomic_DNA. DR EMBL; M35672; AAA51981.1; -; mRNA. DR EMBL; M19063; AAA52456.1; -; Genomic_DNA. DR EMBL; S66752; AAB28588.1; -; Genomic_DNA. DR CCDS; CCDS14666.1; -. [P00740-1] DR CCDS; CCDS83495.1; -. [P00740-2] DR PIR; A00922; KFHU. DR RefSeq; NP_000124.1; NM_000133.3. [P00740-1] DR RefSeq; NP_001300842.1; NM_001313913.1. [P00740-2] DR UniGene; Hs.522798; -. DR PDB; 1CFH; NMR; -; A=47-93. DR PDB; 1CFI; NMR; -; A=47-93. DR PDB; 1EDM; X-ray; 1.50 A; B/C=92-130. DR PDB; 1IXA; NMR; -; A=92-130. DR PDB; 1MGX; NMR; -; A=47-93. DR PDB; 1NL0; X-ray; 2.20 A; G=47-91. DR PDB; 1RFN; X-ray; 2.80 A; A=227-461, B=133-188. DR PDB; 2WPH; X-ray; 1.50 A; E=133-191, S=227-461. DR PDB; 2WPI; X-ray; 1.99 A; E=133-191, S=227-461. DR PDB; 2WPJ; X-ray; 1.60 A; E=133-191, S=227-461. DR PDB; 2WPK; X-ray; 2.21 A; E=133-191, S=227-461. DR PDB; 2WPL; X-ray; 1.82 A; E=133-191, S=227-461. DR PDB; 2WPM; X-ray; 2.00 A; E=133-191, S=227-461. DR PDB; 3KCG; X-ray; 1.70 A; H=227-461, L=131-188. DR PDB; 3LC3; X-ray; 1.90 A; A/C=227-461, B/D=133-188. DR PDB; 3LC5; X-ray; 2.62 A; A=227-461, B=133-188. DR PDB; 4WM0; X-ray; 2.37 A; D=92-130. DR PDB; 4WMA; X-ray; 1.62 A; D=92-130. DR PDB; 4WMB; X-ray; 2.05 A; D=92-130. DR PDB; 4WMI; X-ray; 1.87 A; D=92-130. DR PDB; 4WMK; X-ray; 2.08 A; D=92-130. DR PDB; 4WN2; X-ray; 1.95 A; D=92-130. DR PDB; 4WNH; X-ray; 1.95 A; D=92-130. DR PDB; 4YZU; X-ray; 1.41 A; A=227-461, B=131-191. DR PDB; 4Z0K; X-ray; 1.41 A; A=227-461, B=131-191. DR PDB; 4ZAE; X-ray; 1.86 A; A=227-461, B=131-191. DR PDB; 5EGM; X-ray; 1.84 A; A=227-461, B=131-191. DR PDB; 5F84; X-ray; 2.50 A; B=92-130. DR PDB; 5F85; X-ray; 2.15 A; B=92-130. DR PDB; 5F86; X-ray; 1.90 A; B=92-130. DR PDB; 5JB8; X-ray; 1.45 A; E=134-191, S=227-461. DR PDB; 5JB9; X-ray; 1.30 A; E=134-191, S=227-461. DR PDB; 5JBA; X-ray; 1.40 A; E=134-191, S=227-461. DR PDB; 5JBB; X-ray; 1.56 A; E=134-191, S=227-461. DR PDB; 5JBC; X-ray; 1.90 A; E=134-191, S=227-461. DR PDB; 5TNO; X-ray; 1.54 A; A=227-461, B=130-191. DR PDB; 5TNT; X-ray; 1.40 A; A=227-461, B=130-191. DR PDB; 5VYG; X-ray; 2.20 A; A/B/C=92-130. DR PDBsum; 1CFH; -. DR PDBsum; 1CFI; -. DR PDBsum; 1EDM; -. DR PDBsum; 1IXA; -. DR PDBsum; 1MGX; -. DR PDBsum; 1NL0; -. DR PDBsum; 1RFN; -. DR PDBsum; 2WPH; -. DR PDBsum; 2WPI; -. DR PDBsum; 2WPJ; -. DR PDBsum; 2WPK; -. DR PDBsum; 2WPL; -. DR PDBsum; 2WPM; -. DR PDBsum; 3KCG; -. DR PDBsum; 3LC3; -. DR PDBsum; 3LC5; -. DR PDBsum; 4WM0; -. DR PDBsum; 4WMA; -. DR PDBsum; 4WMB; -. DR PDBsum; 4WMI; -. DR PDBsum; 4WMK; -. DR PDBsum; 4WN2; -. DR PDBsum; 4WNH; -. DR PDBsum; 4YZU; -. DR PDBsum; 4Z0K; -. DR PDBsum; 4ZAE; -. DR PDBsum; 5EGM; -. DR PDBsum; 5F84; -. DR PDBsum; 5F85; -. DR PDBsum; 5F86; -. DR PDBsum; 5JB8; -. DR PDBsum; 5JB9; -. DR PDBsum; 5JBA; -. DR PDBsum; 5JBB; -. DR PDBsum; 5JBC; -. DR PDBsum; 5TNO; -. DR PDBsum; 5TNT; -. DR PDBsum; 5VYG; -. DR ProteinModelPortal; P00740; -. DR SMR; P00740; -. DR BioGrid; 108456; 39. DR DIP; DIP-58520N; -. DR ELM; P00740; -. DR IntAct; P00740; 4. DR MINT; P00740; -. DR STRING; 9606.ENSP00000218099; -. DR BindingDB; P00740; -. DR ChEMBL; CHEMBL2016; -. DR DrugBank; DB00025; Antihemophilic Factor (Recombinant). DR DrugBank; DB13150; Coagulation factor VII human. DR DrugBank; DB00170; Menadione. DR DrugBank; DB05131; TTP889. DR GuidetoPHARMACOLOGY; 2364; -. DR Allergome; 9616; Hom s Factor IX. DR MEROPS; S01.214; -. DR GlyConnect; 96; -. DR iPTMnet; P00740; -. DR PhosphoSitePlus; P00740; -. DR UniCarbKB; P00740; -. DR BioMuta; F9; -. DR jPOST; P00740; -. DR PaxDb; P00740; -. DR PeptideAtlas; P00740; -. DR PRIDE; P00740; -. DR ProteomicsDB; 51274; -. DR DNASU; 2158; -. DR Ensembl; ENST00000218099; ENSP00000218099; ENSG00000101981. [P00740-1] DR Ensembl; ENST00000394090; ENSP00000377650; ENSG00000101981. [P00740-2] DR GeneID; 2158; -. DR KEGG; hsa:2158; -. DR UCSC; uc004fas.2; human. [P00740-1] DR CTD; 2158; -. DR DisGeNET; 2158; -. DR EuPathDB; HostDB:ENSG00000101981.10; -. DR GeneCards; F9; -. DR GeneReviews; F9; -. DR HGNC; HGNC:3551; F9. DR MalaCards; F9; -. DR MIM; 300746; gene. DR MIM; 300807; phenotype. DR MIM; 306900; phenotype. DR neXtProt; NX_P00740; -. DR OpenTargets; ENSG00000101981; -. DR Orphanet; 169799; Mild hemophilia B. DR Orphanet; 169796; Moderately severe hemophilia B. DR Orphanet; 169793; Severe hemophilia B. DR Orphanet; 177929; Symptomatic form of hemophilia B in female carriers. DR PharmGKB; PA27954; -. DR eggNOG; ENOG410IGPV; Eukaryota. DR eggNOG; COG5640; LUCA. DR GeneTree; ENSGT00940000159516; -. DR HOGENOM; HOG000251821; -. DR HOVERGEN; HBG013304; -. DR InParanoid; P00740; -. DR KO; K01321; -. DR OMA; SYECWCQ; -. DR OrthoDB; 1314811at2759; -. DR PhylomeDB; P00740; -. DR TreeFam; TF327329; -. DR BRENDA; 3.4.21.22; 2681. DR Reactome; R-HSA-140834; Extrinsic Pathway of Fibrin Clot Formation. DR Reactome; R-HSA-140837; Intrinsic Pathway of Fibrin Clot Formation. DR Reactome; R-HSA-159740; Gamma-carboxylation of protein precursors. DR Reactome; R-HSA-159763; Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus. DR Reactome; R-HSA-159782; Removal of aminoterminal propeptides from gamma-carboxylated proteins. DR SABIO-RK; P00740; -. DR SIGNOR; P00740; -. DR EvolutionaryTrace; P00740; -. DR GeneWiki; Factor_IX; -. DR GenomeRNAi; 2158; -. DR PMAP-CutDB; P00740; -. DR PRO; PR:P00740; -. DR Proteomes; UP000005640; Chromosome X. DR Bgee; ENSG00000101981; Expressed in 31 organ(s), highest expression level in liver. DR Genevisible; P00740; HS. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB. DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB. DR GO; GO:0004252; F:serine-type endopeptidase activity; NAS:BHF-UCL. DR GO; GO:0007596; P:blood coagulation; IDA:UniProtKB. DR GO; GO:0007597; P:blood coagulation, intrinsic pathway; TAS:Reactome. DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; TAS:Reactome. DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB. DR GO; GO:0031638; P:zymogen activation; IDA:UniProtKB. DR CDD; cd00190; Tryp_SPc; 1. DR Gene3D; 4.10.740.10; -; 1. DR InterPro; IPR017857; Coagulation_fac-like_Gla_dom. DR InterPro; IPR035694; Coagulation_factor_IX. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR013032; EGF-like_CS. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site. DR InterPro; IPR018097; EGF_Ca-bd_CS. DR InterPro; IPR035972; GLA-like_dom_SF. DR InterPro; IPR000294; GLA_domain. DR InterPro; IPR012224; Pept_S1A_FX. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR001314; Peptidase_S1A. DR InterPro; IPR001254; Trypsin_dom. DR InterPro; IPR018114; TRYPSIN_HIS. DR InterPro; IPR033116; TRYPSIN_SER. DR PANTHER; PTHR44064:SF4; PTHR44064:SF4; 1. DR Pfam; PF00008; EGF; 1. DR Pfam; PF00594; Gla; 1. DR Pfam; PF00089; Trypsin; 1. DR PIRSF; PIRSF001143; Factor_X; 1. DR PRINTS; PR00722; CHYMOTRYPSIN. DR PRINTS; PR00001; GLABLOOD. DR SMART; SM00181; EGF; 2. DR SMART; SM00179; EGF_CA; 1. DR SMART; SM00069; GLA; 1. DR SMART; SM00020; Tryp_SPc; 1. DR SUPFAM; SSF50494; SSF50494; 1. DR SUPFAM; SSF57630; SSF57630; 1. DR PROSITE; PS00010; ASX_HYDROXYL; 1. DR PROSITE; PS00022; EGF_1; 1. DR PROSITE; PS01186; EGF_2; 2. DR PROSITE; PS50026; EGF_3; 1. DR PROSITE; PS01187; EGF_CA; 1. DR PROSITE; PS00011; GLA_1; 1. DR PROSITE; PS50998; GLA_2; 1. DR PROSITE; PS50240; TRYPSIN_DOM; 1. DR PROSITE; PS00134; TRYPSIN_HIS; 1. DR PROSITE; PS00135; TRYPSIN_SER; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Blood coagulation; Calcium; KW Cleavage on pair of basic residues; Complete proteome; KW Direct protein sequencing; Disease mutation; Disulfide bond; KW EGF-like domain; Gamma-carboxyglutamic acid; Glycoprotein; Hemophilia; KW Hemostasis; Hydrolase; Hydroxylation; Magnesium; Metal-binding; KW Pharmaceutical; Phosphoprotein; Polymorphism; Protease; KW Reference proteome; Repeat; Secreted; Serine protease; Signal; KW Sulfation; Thrombophilia; Zymogen. FT SIGNAL 1 28 {ECO:0000255}. FT PROPEP 29 46 {ECO:0000269|PubMed:2592373}. FT /FTId=PRO_0000027755. FT CHAIN 47 461 Coagulation factor IX. FT /FTId=PRO_0000027756. FT CHAIN 47 191 Coagulation factor IXa light chain. FT /FTId=PRO_0000027757. FT PROPEP 192 226 Activation peptide. FT /FTId=PRO_0000027758. FT CHAIN 227 461 Coagulation factor IXa heavy chain. FT /FTId=PRO_0000027759. FT DOMAIN 47 92 Gla. {ECO:0000255|PROSITE- FT ProRule:PRU00463}. FT DOMAIN 93 129 EGF-like 1; calcium-binding. FT {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DOMAIN 130 171 EGF-like 2. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 227 459 Peptidase S1. {ECO:0000255|PROSITE- FT ProRule:PRU00274}. FT ACT_SITE 267 267 Charge relay system. FT {ECO:0000269|PubMed:20004170, FT ECO:0000269|PubMed:659613}. FT ACT_SITE 315 315 Charge relay system. FT {ECO:0000269|PubMed:659613}. FT ACT_SITE 411 411 Charge relay system. FT {ECO:0000269|PubMed:20004170, FT ECO:0000269|PubMed:659613}. FT METAL 47 47 Calcium 1; via carbonyl oxygen. FT {ECO:0000244|PDB:1NL0, FT ECO:0000269|PubMed:14722079}. FT METAL 48 48 Calcium 2. {ECO:0000244|PDB:1NL0, FT ECO:0000269|PubMed:14722079}. FT METAL 53 53 Calcium 1; via 4-carboxyglutamate. FT {ECO:0000244|PDB:1NL0, FT ECO:0000305|PubMed:14722079}. FT METAL 53 53 Calcium 2; via 4-carboxyglutamate. FT {ECO:0000244|PDB:1NL0, FT ECO:0000305|PubMed:14722079}. FT METAL 54 54 Calcium 2; via 4-carboxyglutamate. FT {ECO:0000244|PDB:1NL0, FT ECO:0000305|PubMed:14722079}. FT METAL 54 54 Calcium 3; via 4-carboxyglutamate. FT {ECO:0000244|PDB:1NL0, FT ECO:0000305|PubMed:14722079}. FT METAL 61 61 Calcium 4 or magnesium 1; via 4- FT carboxyglutamate. {ECO:0000244|PDB:1NL0, FT ECO:0000250|UniProtKB:P00741, FT ECO:0000305|PubMed:14722079}. FT METAL 63 63 Calcium 1; via 4-carboxyglutamate. FT {ECO:0000244|PDB:1NL0, FT ECO:0000305|PubMed:14722079}. FT METAL 63 63 Calcium 2; via 4-carboxyglutamate. FT {ECO:0000244|PDB:1NL0, FT ECO:0000305|PubMed:14722079}. FT METAL 63 63 Calcium 3; via 4-carboxyglutamate. FT {ECO:0000244|PDB:1NL0, FT ECO:0000305|PubMed:14722079}. FT METAL 66 66 Calcium 4 or magnesium 1; via 4- FT carboxyglutamate. {ECO:0000244|PDB:1NL0, FT ECO:0000250|UniProtKB:P00741, FT ECO:0000305|PubMed:14722079}. FT METAL 67 67 Calcium 1; via 4-carboxyglutamate. FT {ECO:0000244|PDB:1NL0, FT ECO:0000305|PubMed:14722079}. FT METAL 72 72 Calcium 5 or magnesium 2; via 4- FT carboxyglutamate. {ECO:0000244|PDB:1NL0, FT ECO:0000250|UniProtKB:P00741, FT ECO:0000305|PubMed:14722079}. FT METAL 73 73 Calcium 2; via 4-carboxyglutamate. FT {ECO:0000244|PDB:1NL0, FT ECO:0000305|PubMed:14722079}. FT METAL 73 73 Calcium 3; via 4-carboxyglutamate. FT {ECO:0000244|PDB:1NL0, FT ECO:0000305|PubMed:14722079}. FT METAL 76 76 Calcium 3; via 4-carboxyglutamate. FT {ECO:0000244|PDB:1NL0, FT ECO:0000305|PubMed:14722079}. FT METAL 76 76 Calcium 5 or magnesium 2; via 4- FT carboxyglutamate. {ECO:0000244|PDB:1NL0, FT ECO:0000305|PubMed:14722079}. FT METAL 76 76 Calcium 5; via 4-carboxyglutamate. FT {ECO:0000244|PDB:1NL0, FT ECO:0000305|PubMed:14722079}. FT METAL 82 82 Calcium 6 or magnesium 3; via 4- FT carboxyglutamate. FT {ECO:0000250|UniProtKB:P00741}. FT METAL 86 86 Calcium 6 or magnesium 3; via 4- FT carboxyglutamate. FT {ECO:0000250|UniProtKB:P00741}. FT METAL 93 93 Calcium 7. {ECO:0000244|PDB:1EDM, FT ECO:0000269|PubMed:7606779}. FT METAL 94 94 Calcium 7; via carbonyl oxygen. FT {ECO:0000244|PDB:1EDM, FT ECO:0000269|PubMed:7606779}. FT METAL 96 96 Calcium 7. {ECO:0000244|PDB:1EDM, FT ECO:0000269|PubMed:7606779}. FT METAL 110 110 Calcium 7. {ECO:0000244|PDB:1EDM, FT ECO:0000269|PubMed:7606779}. FT METAL 111 111 Calcium 7; via carbonyl oxygen. FT {ECO:0000244|PDB:1EDM, FT ECO:0000269|PubMed:7606779}. FT METAL 281 281 Calcium 8. {ECO:0000244|PDB:1RFN, FT ECO:0000244|PDB:2WPH, FT ECO:0000244|PDB:2WPI, FT ECO:0000244|PDB:2WPJ, FT ECO:0000244|PDB:2WPK, FT ECO:0000244|PDB:2WPM, FT ECO:0000244|PDB:3KCG, FT ECO:0000244|PDB:3LC3, FT ECO:0000244|PDB:3LC5, FT ECO:0000269|PubMed:10467148, FT ECO:0000269|PubMed:20004170, FT ECO:0000269|PubMed:20080729, FT ECO:0000269|PubMed:20121197, FT ECO:0000269|PubMed:20121198}. FT METAL 283 283 Calcium 8; via carbonyl oxygen. FT {ECO:0000244|PDB:1RFN, FT ECO:0000244|PDB:2WPH, FT ECO:0000244|PDB:2WPI, FT ECO:0000244|PDB:2WPJ, FT ECO:0000244|PDB:2WPK, FT ECO:0000244|PDB:2WPM, FT ECO:0000244|PDB:3KCG, FT ECO:0000244|PDB:3LC3, FT ECO:0000244|PDB:3LC5, FT ECO:0000269|PubMed:10467148, FT ECO:0000269|PubMed:20004170, FT ECO:0000269|PubMed:20080729, FT ECO:0000269|PubMed:20121197, FT ECO:0000269|PubMed:20121198}. FT METAL 286 286 Calcium 8; via carbonyl oxygen. FT {ECO:0000244|PDB:1RFN, FT ECO:0000244|PDB:2WPH, FT ECO:0000244|PDB:2WPI, FT ECO:0000244|PDB:2WPJ, FT ECO:0000244|PDB:2WPK, FT ECO:0000244|PDB:2WPM, FT ECO:0000244|PDB:3KCG, FT ECO:0000244|PDB:3LC3, FT ECO:0000244|PDB:3LC5, FT ECO:0000269|PubMed:10467148, FT ECO:0000269|PubMed:20004170, FT ECO:0000269|PubMed:20080729, FT ECO:0000269|PubMed:20121197, FT ECO:0000269|PubMed:20121198}. FT METAL 288 288 Calcium 8. {ECO:0000244|PDB:1RFN, FT ECO:0000244|PDB:2WPH, FT ECO:0000244|PDB:2WPI, FT ECO:0000244|PDB:2WPJ, FT ECO:0000244|PDB:2WPK, FT ECO:0000244|PDB:2WPM, FT ECO:0000244|PDB:3KCG, FT ECO:0000244|PDB:3LC3, FT ECO:0000244|PDB:3LC5, FT ECO:0000269|PubMed:10467148, FT ECO:0000269|PubMed:20004170, FT ECO:0000269|PubMed:20080729, FT ECO:0000269|PubMed:20121197, FT ECO:0000269|PubMed:20121198}. FT METAL 291 291 Calcium 8. {ECO:0000244|PDB:2WPH, FT ECO:0000244|PDB:2WPI, FT ECO:0000244|PDB:2WPJ, FT ECO:0000244|PDB:2WPK, FT ECO:0000244|PDB:2WPM, FT ECO:0000244|PDB:3KCG, FT ECO:0000244|PDB:3LC3, FT ECO:0000244|PDB:3LC5, FT ECO:0000269|PubMed:10467148, FT ECO:0000269|PubMed:20004170, FT ECO:0000269|PubMed:20080729, FT ECO:0000269|PubMed:20121197, FT ECO:0000269|PubMed:20121198}. FT SITE 191 192 Cleavage; by factor XIa. FT SITE 226 227 Cleavage; by factor XIa. FT MOD_RES 53 53 4-carboxyglutamate. FT {ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463}. FT MOD_RES 54 54 4-carboxyglutamate. FT {ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463}. FT MOD_RES 61 61 4-carboxyglutamate. FT {ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463}. FT MOD_RES 63 63 4-carboxyglutamate. FT {ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463}. FT MOD_RES 66 66 4-carboxyglutamate. FT {ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463}. FT MOD_RES 67 67 4-carboxyglutamate. FT {ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463}. FT MOD_RES 72 72 4-carboxyglutamate. FT {ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463}. FT MOD_RES 73 73 4-carboxyglutamate. FT {ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463}. FT MOD_RES 76 76 4-carboxyglutamate. FT {ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463}. FT MOD_RES 79 79 4-carboxyglutamate. FT {ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463}. FT MOD_RES 82 82 4-carboxyglutamate. FT {ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463}. FT MOD_RES 86 86 4-carboxyglutamate. FT {ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463}. FT MOD_RES 110 110 (3R)-3-hydroxyaspartate. FT {ECO:0000269|PubMed:6688526}. FT MOD_RES 114 114 Phosphoserine. {ECO:0000269|Ref.28}. FT MOD_RES 201 201 Sulfotyrosine. FT {ECO:0000269|PubMed:11133752}. FT MOD_RES 204 204 Phosphoserine. FT {ECO:0000269|PubMed:11133752, FT ECO:0000269|PubMed:25456591}. FT MOD_RES 205 205 Phosphothreonine; alternate. FT {ECO:0000269|PubMed:25456591}. FT CARBOHYD 85 85 O-linked (GalNAc...) threonine. FT {ECO:0000269|PubMed:25456591}. FT CARBOHYD 99 99 O-linked (Glc...) serine; alternate. FT {ECO:0000269|PubMed:2129367, FT ECO:0000269|PubMed:21949356, FT ECO:0000269|PubMed:2511201, FT ECO:0000269|PubMed:25456591}. FT /FTId=CAR_000009. FT CARBOHYD 99 99 O-linked (Xyl...) serine; alternate. FT {ECO:0000269|PubMed:2129367, FT ECO:0000269|PubMed:21949356, FT ECO:0000269|PubMed:2511201}. FT CARBOHYD 107 107 O-linked (Fuc...) serine. FT {ECO:0000269|PubMed:1517205, FT ECO:0000269|PubMed:25456591}. FT /FTId=CAR_000010. FT CARBOHYD 203 203 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 205 205 O-linked (GalNAc...) threonine; FT alternate. {ECO:0000269|PubMed:25456591, FT ECO:0000269|PubMed:8172892}. FT CARBOHYD 213 213 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 215 215 O-linked (GalNAc...) threonine. FT {ECO:0000269|PubMed:25456591, FT ECO:0000269|PubMed:8172892}. FT CARBOHYD 225 225 O-linked (GalNAc...) threonine. FT {ECO:0000269|PubMed:25456591}. FT DISULFID 64 69 {ECO:0000250|UniProtKB:P00741}. FT DISULFID 97 108 {ECO:0000244|PDB:1EDM, FT ECO:0000244|PDB:1IXA, FT ECO:0000269|PubMed:1304885, FT ECO:0000269|PubMed:7606779}. FT DISULFID 102 117 {ECO:0000244|PDB:1EDM, FT ECO:0000244|PDB:1IXA, FT ECO:0000269|PubMed:1304885, FT ECO:0000269|PubMed:7606779}. FT DISULFID 119 128 {ECO:0000244|PDB:1EDM, FT ECO:0000244|PDB:1IXA, FT ECO:0000269|PubMed:1304885, FT ECO:0000269|PubMed:7606779}. FT DISULFID 134 145 {ECO:0000244|PDB:1RFN, FT ECO:0000244|PDB:2WPH, FT ECO:0000244|PDB:2WPI, FT ECO:0000244|PDB:2WPJ, FT ECO:0000244|PDB:2WPK, FT ECO:0000244|PDB:2WPL, FT ECO:0000244|PDB:2WPM, FT ECO:0000244|PDB:3KCG, FT ECO:0000244|PDB:3LC3, FT ECO:0000244|PDB:3LC5, FT ECO:0000269|PubMed:20004170, FT ECO:0000269|PubMed:20080729, FT ECO:0000269|PubMed:20121197, FT ECO:0000269|PubMed:20121198}. FT DISULFID 141 155 {ECO:0000244|PDB:1RFN, FT ECO:0000244|PDB:2WPH, FT ECO:0000244|PDB:2WPI, FT ECO:0000244|PDB:2WPJ, FT ECO:0000244|PDB:2WPK, FT ECO:0000244|PDB:2WPL, FT ECO:0000244|PDB:2WPM, FT ECO:0000244|PDB:3KCG, FT ECO:0000244|PDB:3LC3, FT ECO:0000244|PDB:3LC5, FT ECO:0000269|PubMed:20004170, FT ECO:0000269|PubMed:20080729, FT ECO:0000269|PubMed:20121197, FT ECO:0000269|PubMed:20121198}. FT DISULFID 157 170 {ECO:0000244|PDB:1RFN, FT ECO:0000244|PDB:2WPH, FT ECO:0000244|PDB:2WPI, FT ECO:0000244|PDB:2WPJ, FT ECO:0000244|PDB:2WPK, FT ECO:0000244|PDB:2WPL, FT ECO:0000244|PDB:2WPM, FT ECO:0000244|PDB:3KCG, FT ECO:0000244|PDB:3LC3, FT ECO:0000244|PDB:3LC5, FT ECO:0000269|PubMed:20004170, FT ECO:0000269|PubMed:20080729, FT ECO:0000269|PubMed:20121197, FT ECO:0000269|PubMed:20121198}. FT DISULFID 178 335 Interchain (between light and heavy FT chains). {ECO:0000244|PDB:1RFN, FT ECO:0000244|PDB:2WPH, FT ECO:0000244|PDB:2WPI, FT ECO:0000244|PDB:2WPJ, FT ECO:0000244|PDB:2WPK, FT ECO:0000244|PDB:2WPL, FT ECO:0000244|PDB:2WPM, FT ECO:0000244|PDB:3KCG, FT ECO:0000244|PDB:3LC3, FT ECO:0000244|PDB:3LC5, FT ECO:0000269|PubMed:20004170, FT ECO:0000269|PubMed:20080729, FT ECO:0000269|PubMed:20121197, FT ECO:0000269|PubMed:20121198}. FT DISULFID 252 268 {ECO:0000244|PDB:1RFN, FT ECO:0000244|PDB:2WPH, FT ECO:0000244|PDB:2WPI, FT ECO:0000244|PDB:2WPJ, FT ECO:0000244|PDB:2WPK, FT ECO:0000244|PDB:2WPL, FT ECO:0000244|PDB:2WPM, FT ECO:0000244|PDB:3KCG, FT ECO:0000244|PDB:3LC3, FT ECO:0000244|PDB:3LC5, FT ECO:0000269|PubMed:20004170, FT ECO:0000269|PubMed:20080729, FT ECO:0000269|PubMed:20121197, FT ECO:0000269|PubMed:20121198}. FT DISULFID 382 396 {ECO:0000244|PDB:1RFN, FT ECO:0000244|PDB:2WPH, FT ECO:0000244|PDB:2WPI, FT ECO:0000244|PDB:2WPJ, FT ECO:0000244|PDB:2WPK, FT ECO:0000244|PDB:2WPL, FT ECO:0000244|PDB:2WPM, FT ECO:0000244|PDB:3KCG, FT ECO:0000244|PDB:3LC3, FT ECO:0000244|PDB:3LC5, FT ECO:0000269|PubMed:20004170, FT ECO:0000269|PubMed:20080729, FT ECO:0000269|PubMed:20121197, FT ECO:0000269|PubMed:20121198}. FT DISULFID 407 435 {ECO:0000244|PDB:1RFN, FT ECO:0000244|PDB:2WPH, FT ECO:0000244|PDB:2WPI, FT ECO:0000244|PDB:2WPJ, FT ECO:0000244|PDB:2WPK, FT ECO:0000244|PDB:2WPL, FT ECO:0000244|PDB:2WPM, FT ECO:0000244|PDB:3KCG, FT ECO:0000244|PDB:3LC3, FT ECO:0000244|PDB:3LC5, FT ECO:0000269|PubMed:20004170, FT ECO:0000269|PubMed:20080729, FT ECO:0000269|PubMed:20121197, FT ECO:0000269|PubMed:20121198}. FT VAR_SEQ 93 130 Missing (in isoform 2). FT {ECO:0000303|Ref.6}. FT /FTId=VSP_047689. FT VARIANT 7 7 I -> F (in dbSNP:rs150190385). FT {ECO:0000269|PubMed:2773937}. FT /FTId=VAR_006520. FT VARIANT 17 17 I -> N (in HEMB; severe; UK 22). FT /FTId=VAR_006521. FT VARIANT 20 20 L -> S (in HEMB; unknown pathological FT significance; decreased protein FT abundance; decreased function in blood FT coagulation). FT {ECO:0000269|PubMed:25251685}. FT /FTId=VAR_073975. FT VARIANT 28 28 C -> R (in HEMB; moderate; HB130; FT dbSNP:rs387906481). FT /FTId=VAR_006522. FT VARIANT 28 28 C -> Y (in HEMB; decreased protein FT abundance; decreased function in blood FT coagulation). FT {ECO:0000269|PubMed:12588353, FT ECO:0000269|PubMed:25251685}. FT /FTId=VAR_017343. FT VARIANT 30 30 V -> I (in HEMB). FT /FTId=VAR_006523. FT VARIANT 37 37 A -> T (in warfarin sensitivity; reduced FT affinity of the glutamate carboxylase for FT the factor IX precursor; FT dbSNP:rs367569299). FT {ECO:0000269|PubMed:8833911}. FT /FTId=VAR_017307. FT VARIANT 43 43 R -> L (in HEMB; severe; Bendorf, Beuten, FT Gleiwitz; impairs removal of propeptide; FT dbSNP:rs1275708479). FT {ECO:0000269|PubMed:12588353, FT ECO:0000269|PubMed:9169594}. FT /FTId=VAR_006525. FT VARIANT 43 43 R -> Q (in HEMB; severe; San Dimas, FT Oxford-3, Strasbourg-2; impairs removal FT of propeptide; dbSNP:rs1275708479). FT {ECO:0000269|PubMed:12588353, FT ECO:0000269|PubMed:2738071, FT ECO:0000269|PubMed:3009023, FT ECO:0000269|PubMed:8295821, FT ECO:0000269|PubMed:9169594, FT ECO:0000269|PubMed:9600455}. FT /FTId=VAR_006524. FT VARIANT 43 43 R -> W (in HEMB; severe; Boxtel, Heiden, FT Lienen; impairs removal of propeptide). FT {ECO:0000269|PubMed:12604421, FT ECO:0000269|PubMed:9169594, FT ECO:0000269|PubMed:9600455}. FT /FTId=VAR_006526. FT VARIANT 45 45 K -> N (in HEMB; severe; Seattle E). FT /FTId=VAR_006527. FT VARIANT 46 46 R -> S (in HEMB; severe; Cambridge; FT impaired processing of the propeptide; FT impaired gamma-carboxylation; decreased FT protein abundance; loss of function in FT blood coagulation). FT {ECO:0000269|PubMed:25251685}. FT /FTId=VAR_006528. FT VARIANT 46 46 R -> T (in HEMB; severe). FT {ECO:0000269|PubMed:9600455}. FT /FTId=VAR_006529. FT VARIANT 48 48 N -> I (in HEMB; severe; Calgary-16). FT /FTId=VAR_006530. FT VARIANT 49 49 S -> P (in HEMB). FT /FTId=VAR_006531. FT VARIANT 52 52 L -> S (in HEMB; severe; Gla mutant). FT {ECO:0000269|PubMed:12588353}. FT /FTId=VAR_017344. FT VARIANT 53 53 E -> A (in HEMB; severe; Oxford-B2; Gla FT mutant). FT /FTId=VAR_006532. FT VARIANT 54 54 E -> D (in HEMB; unknown pathological FT significance; no effect on protein FT abundance; loss of function in blood FT coagulation). FT {ECO:0000269|PubMed:25251685}. FT /FTId=VAR_073976. FT VARIANT 54 54 E -> G (in HEMB; severe; HB151; Gla FT mutant). FT /FTId=VAR_006533. FT VARIANT 55 55 F -> C (in HEMB). FT /FTId=VAR_006534. FT VARIANT 58 58 G -> A (in HEMB; severe; Hong Kong-1). FT /FTId=VAR_006535. FT VARIANT 58 58 G -> E (in HEMB; unknown pathological FT significance; no effect on protein FT abundance; loss of function in blood FT coagulation). FT {ECO:0000269|PubMed:25251685}. FT /FTId=VAR_073977. FT VARIANT 58 58 G -> R (in HEMB; severe; Los Angeles-4). FT /FTId=VAR_006536. FT VARIANT 62 63 Missing (in HEMB; severe). FT /FTId=VAR_006537. FT VARIANT 66 66 E -> V (in HEMB; moderate). FT /FTId=VAR_006538. FT VARIANT 67 67 E -> K (in HEMB; severe; Nagoya-4; Gla FT mutant; dbSNP:rs1410080079). FT /FTId=VAR_006539. FT VARIANT 71 71 F -> S (in HEMB; severe). FT /FTId=VAR_006540. FT VARIANT 73 73 E -> K (in HEMB; severe; Seattle-3; Gla FT mutant; dbSNP:rs137852225). FT {ECO:0000269|PubMed:2472424}. FT /FTId=VAR_006541. FT VARIANT 73 73 E -> V (in HEMB; severe; Chongqing; Gla FT mutant; dbSNP:rs137852226). FT {ECO:0000269|PubMed:2339358}. FT /FTId=VAR_006542. FT VARIANT 75 75 R -> Q (in HEMB; mild; FT dbSNP:rs137852228). FT {ECO:0000269|PubMed:2773937}. FT /FTId=VAR_017308. FT VARIANT 79 79 E -> D (in HEMB; dbSNP:rs137852229). FT {ECO:0000269|PubMed:2773937}. FT /FTId=VAR_017309. FT VARIANT 84 84 T -> R (in HEMB; decreased protein FT abundance; loss of function in blood FT coagulation). FT {ECO:0000269|PubMed:12604421, FT ECO:0000269|PubMed:25251685}. FT /FTId=VAR_017345. FT VARIANT 91 91 Y -> C (in HEMB; moderate). FT /FTId=VAR_006543. FT VARIANT 93 93 D -> G (in HEMB; moderate; Alabama; FT dbSNP:rs137852230). FT {ECO:0000269|PubMed:3790720}. FT /FTId=VAR_006544. FT VARIANT 96 96 Q -> P (in HEMB; severe; New London; FT dbSNP:rs137852231). FT /FTId=VAR_006545. FT VARIANT 97 97 C -> S (in HEMB). FT /FTId=VAR_006546. FT VARIANT 101 101 P -> R (in HEMB). FT /FTId=VAR_006547. FT VARIANT 102 102 C -> R (in HEMB; severe; Basel). FT /FTId=VAR_006548. FT VARIANT 106 106 G -> D (in HEMB). FT {ECO:0000269|PubMed:12588353}. FT /FTId=VAR_017346. FT VARIANT 106 106 G -> S (in HEMB; mild; Durham; FT dbSNP:rs137852233). FT {ECO:0000269|PubMed:2472424, FT ECO:0000269|PubMed:9600455}. FT /FTId=VAR_006549. FT VARIANT 108 108 C -> S (in HEMB). FT /FTId=VAR_006550. FT VARIANT 110 110 D -> N (in HEMB; severe; Oxford-D1; FT dbSNP:rs137852274). FT /FTId=VAR_006551. FT VARIANT 112 112 I -> S (in HEMB). FT /FTId=VAR_006552. FT VARIANT 113 113 N -> K (in HEMB; mild). FT {ECO:0000269|PubMed:9222764}. FT /FTId=VAR_006553. FT VARIANT 115 115 Y -> C (in HEMB; severe). FT {ECO:0000269|PubMed:9600455}. FT /FTId=VAR_006554. FT VARIANT 119 119 C -> F (in HEMB; severe). FT /FTId=VAR_006555. FT VARIANT 119 119 C -> R (in HEMB; Iran). FT {ECO:0000269|PubMed:9452115}. FT /FTId=VAR_006556. FT VARIANT 124 124 E -> K (in HEMB). FT {ECO:0000269|PubMed:12588353}. FT /FTId=VAR_017347. FT VARIANT 125 125 G -> E (in HEMB). FT /FTId=VAR_006557. FT VARIANT 125 125 G -> R (in HEMB). FT {ECO:0000269|PubMed:12604421}. FT /FTId=VAR_017348. FT VARIANT 125 125 G -> V (in HEMB). FT {ECO:0000269|PubMed:12604421}. FT /FTId=VAR_006558. FT VARIANT 129 130 Missing (in HEMB). FT /FTId=VAR_006559. FT VARIANT 134 134 C -> Y (in HEMB). FT {ECO:0000269|PubMed:12588353}. FT /FTId=VAR_017349. FT VARIANT 136 136 I -> T (in HEMB; mild). FT /FTId=VAR_006560. FT VARIANT 138 138 N -> H (in HEMB; unknown pathological FT significance; decreased protein FT abundance; decreased function in blood FT coagulation). FT {ECO:0000269|PubMed:25251685}. FT /FTId=VAR_073978. FT VARIANT 139 139 G -> D (in HEMB; severe; FT dbSNP:rs1216516070). FT /FTId=VAR_006561. FT VARIANT 139 139 G -> S (in HEMB). FT /FTId=VAR_006562. FT VARIANT 155 155 C -> F (in HEMB; severe; FT dbSNP:rs1330705989). FT {ECO:0000269|PubMed:9600455}. FT /FTId=VAR_006563. FT VARIANT 160 160 G -> E (in HEMB; mild). FT /FTId=VAR_006564. FT VARIANT 167 167 Q -> H (in HEMB; mild). FT /FTId=VAR_006565. FT VARIANT 169 169 S -> C (in HEMB). FT {ECO:0000269|PubMed:11122099}. FT /FTId=VAR_017350. FT VARIANT 170 170 C -> F (in HEMB). FT {ECO:0000269|PubMed:12604421}. FT /FTId=VAR_017351. FT VARIANT 178 178 C -> R (in HEMB). FT /FTId=VAR_006566. FT VARIANT 178 178 C -> W (in HEMB; severe). FT /FTId=VAR_006567. FT VARIANT 191 191 R -> C (in HEMB; moderate; Albuquerque, FT Cardiff-1; dbSNP:rs137852237). FT {ECO:0000269|PubMed:2775660}. FT /FTId=VAR_006569. FT VARIANT 191 191 R -> H (in HEMB; moderate; Chapel-Hill, FT Chicago-2; dbSNP:rs137852238). FT {ECO:0000269|PubMed:6603618, FT ECO:0000269|PubMed:8076946}. FT /FTId=VAR_006568. FT VARIANT 194 194 T -> A (in dbSNP:rs6048). FT {ECO:0000269|PubMed:10391209, FT ECO:0000269|PubMed:25470321, FT ECO:0000269|PubMed:2994716, FT ECO:0000269|PubMed:3857619, FT ECO:0000269|PubMed:6329734}. FT /FTId=VAR_011773. FT VARIANT 226 226 R -> G (in HEMB; severe; Madrid). FT {ECO:0000269|PubMed:12588353, FT ECO:0000269|PubMed:8076946}. FT /FTId=VAR_006571. FT VARIANT 226 226 R -> Q (in HEMB; severe; Hilo and Novara; FT no effect on protein abundance; loss of FT function in blood coagulation; FT dbSNP:rs137852241). FT {ECO:0000269|PubMed:12588353, FT ECO:0000269|PubMed:2162822, FT ECO:0000269|PubMed:25251685, FT ECO:0000269|PubMed:2713493}. FT /FTId=VAR_006572. FT VARIANT 226 226 R -> W (in HEMB; severe; Nagoya-1, FT Dernbach, Deventer, Idaho; FT dbSNP:rs137852240). FT {ECO:0000269|PubMed:12588353, FT ECO:0000269|PubMed:2162822, FT ECO:0000269|PubMed:2592373}. FT /FTId=VAR_006570. FT VARIANT 227 227 V -> D (in HEMB; mild). FT /FTId=VAR_006573. FT VARIANT 227 227 V -> F (in HEMB; Milano; FT dbSNP:rs137852242). FT {ECO:0000269|PubMed:2162822}. FT /FTId=VAR_017310. FT VARIANT 228 228 V -> F (in HEMB; severe; Kashihara; FT dbSNP:rs137852243). FT {ECO:0000269|PubMed:2753873}. FT /FTId=VAR_017311. FT VARIANT 228 228 V -> L (in HEMB; mild; Cardiff-2; FT dbSNP:rs137852243). FT {ECO:0000269|PubMed:2372509}. FT /FTId=VAR_006574. FT VARIANT 241 241 Q -> H (in HEMB; dbSNP:rs1182648920). FT {ECO:0000269|PubMed:25470321}. FT /FTId=VAR_006575. FT VARIANT 241 241 Q -> K (in HEMB). FT {ECO:0000269|PubMed:12588353}. FT /FTId=VAR_017352. FT VARIANT 252 252 C -> S (in HEMB; severe; FT dbSNP:rs267606792). FT {ECO:0000269|PubMed:1615485}. FT /FTId=VAR_017312. FT VARIANT 252 252 C -> Y (in HEMB). FT {ECO:0000269|PubMed:12588353}. FT /FTId=VAR_017353. FT VARIANT 253 253 G -> E (in HEMB; severe). FT /FTId=VAR_006576. FT VARIANT 253 253 G -> R (in HEMB; severe; Luanda). FT {ECO:0000269|PubMed:8257988}. FT /FTId=VAR_006577. FT VARIANT 265 265 A -> T (in HEMB; mild). FT /FTId=VAR_006578. FT VARIANT 268 268 C -> W (in HEMB; moderate; FT dbSNP:rs137852246). FT {ECO:0000269|PubMed:2773937}. FT /FTId=VAR_017313. FT VARIANT 279 279 A -> T (in HEMB; mild; FT dbSNP:rs137852247). FT {ECO:0000269|PubMed:2773937, FT ECO:0000269|PubMed:8076946}. FT /FTId=VAR_006579. FT VARIANT 283 283 N -> D (in HEMB; severe). FT /FTId=VAR_006580. FT VARIANT 284 284 Missing (in HEMB; severe; decreased FT protein abundance; loss of function in FT blood coagulation). FT {ECO:0000269|PubMed:25251685}. FT /FTId=VAR_073979. FT VARIANT 286 286 Missing (in HEMB; severe). FT /FTId=VAR_006581. FT VARIANT 291 291 E -> V (in HEMB; Monschau; FT dbSNP:rs137852279). FT {ECO:0000269|PubMed:1346975}. FT /FTId=VAR_017314. FT VARIANT 294 294 R -> G (in HEMB; severe). FT /FTId=VAR_006582. FT VARIANT 294 294 R -> Q (in HEMB; mild to moderate; FT Dreihacken, Penafiel and Seattle-4; FT dbSNP:rs137852249). FT {ECO:0000269|PubMed:12588353, FT ECO:0000269|PubMed:1346975, FT ECO:0000269|PubMed:2472424, FT ECO:0000269|PubMed:7981722, FT ECO:0000269|PubMed:8257988}. FT /FTId=VAR_006583. FT VARIANT 296 296 V -> M (in HEMB; unknown pathological FT significance; decreased protein FT abundance; decreased function in blood FT coagulation). FT {ECO:0000269|PubMed:25251685}. FT /FTId=VAR_073980. FT VARIANT 302 302 H -> R (in HEMB). FT {ECO:0000269|PubMed:12604421}. FT /FTId=VAR_006584. FT VARIANT 306 306 N -> S (in HEMB; mild; FT dbSNP:rs137852251). FT {ECO:0000269|PubMed:2773937}. FT /FTId=VAR_017315. FT VARIANT 316 316 I -> F (in HEMB). FT {ECO:0000269|PubMed:12588353}. FT /FTId=VAR_006585. FT VARIANT 318 318 L -> R (in HEMB; dbSNP:rs1222227572). FT {ECO:0000269|PubMed:12588353}. FT /FTId=VAR_017354. FT VARIANT 321 321 L -> Q (in HEMB; severe). FT /FTId=VAR_006586. FT VARIANT 328 328 N -> K (in HEMB; unknown pathological FT significance; decreased protein FT abundance; decreased function in blood FT coagulation). FT {ECO:0000269|PubMed:25251685}. FT /FTId=VAR_073981. FT VARIANT 328 328 N -> Y (in HEMB; moderate; decreased FT protein abundance; decreased function in FT blood coagulation). FT {ECO:0000269|PubMed:25251685}. FT /FTId=VAR_073982. FT VARIANT 333 333 P -> H (in HEMB; severe). FT /FTId=VAR_006587. FT VARIANT 333 333 P -> T (in HEMB). FT {ECO:0000269|PubMed:11122099}. FT /FTId=VAR_017355. FT VARIANT 342 342 T -> K (in HEMB; mild). FT /FTId=VAR_006588. FT VARIANT 342 342 T -> M (in HEMB; moderate; FT dbSNP:rs137852254). FT {ECO:0000269|PubMed:12604421, FT ECO:0000269|PubMed:2773937, FT ECO:0000269|PubMed:9222764}. FT /FTId=VAR_006589. FT VARIANT 344 344 I -> L (in HEMB). FT {ECO:0000269|PubMed:12604421}. FT /FTId=VAR_017356. FT VARIANT 351 351 G -> D (in HEMB). FT /FTId=VAR_006590. FT VARIANT 356 356 W -> C (in HEMB; severe). FT /FTId=VAR_006591. FT VARIANT 357 357 G -> E (in HEMB; severe; Amagasaki; FT dbSNP:rs137852275). FT {ECO:0000269|PubMed:1958666}. FT /FTId=VAR_006592. FT VARIANT 357 357 G -> R (in HEMB; dbSNP:rs137852257). FT {ECO:0000269|PubMed:2773937}. FT /FTId=VAR_017316. FT VARIANT 362 362 K -> E (in HEMB; moderate). FT /FTId=VAR_006593. FT VARIANT 363 363 G -> W (in HEMB). FT /FTId=VAR_006594. FT VARIANT 366 366 A -> D (in HEMB). FT /FTId=VAR_006595. FT VARIANT 379 379 R -> G (in HEMB; moderate; FT dbSNP:rs137852258). FT {ECO:0000269|PubMed:12588353}. FT /FTId=VAR_006596. FT VARIANT 379 379 R -> Q (in HEMB; severe; Iceland-1, FT London and Sesimbra; dbSNP:rs137852259). FT {ECO:0000269|PubMed:8076946, FT ECO:0000269|PubMed:8257988, FT ECO:0000269|PubMed:9600455}. FT /FTId=VAR_006597. FT VARIANT 382 382 C -> Y (in HEMB; dbSNP:rs1303221289). FT /FTId=VAR_006598. FT VARIANT 383 383 L -> F (in HEMB). FT {ECO:0000269|PubMed:12588353}. FT /FTId=VAR_017358. FT VARIANT 383 383 L -> I (in HEMB). FT {ECO:0000269|PubMed:12588353}. FT /FTId=VAR_017357. FT VARIANT 384 384 R -> L (in THPH8; factor IX Padua; higher FT specific activity than wild-type; FT dbSNP:rs137852283). FT {ECO:0000269|PubMed:19846852}. FT /FTId=VAR_062999. FT VARIANT 387 387 K -> E (in HEMB; mild). FT {ECO:0000269|PubMed:9600455}. FT /FTId=VAR_006599. FT VARIANT 390 390 I -> F (in HEMB; severe). FT /FTId=VAR_006600. FT VARIANT 394 394 M -> K (in HEMB). FT /FTId=VAR_006601. FT VARIANT 395 395 F -> I (in HEMB; dbSNP:rs1175050951). FT {ECO:0000269|PubMed:12588353}. FT /FTId=VAR_017359. FT VARIANT 395 395 F -> L (in HEMB; dbSNP:rs1175050951). FT {ECO:0000269|PubMed:12604421}. FT /FTId=VAR_017360. FT VARIANT 396 396 C -> F (in HEMB). FT {ECO:0000269|PubMed:12588353}. FT /FTId=VAR_017361. FT VARIANT 396 396 C -> S (in HEMB; severe; FT dbSNP:rs137852273). FT /FTId=VAR_006602. FT VARIANT 397 397 A -> P (in HEMB; mild; Hong Kong-11; FT dbSNP:rs137852281). FT {ECO:0000269|PubMed:9590153}. FT /FTId=VAR_017317. FT VARIANT 404 404 R -> T (in HEMB). FT /FTId=VAR_006603. FT VARIANT 407 407 C -> R (in HEMB). FT {ECO:0000269|PubMed:12588353}. FT /FTId=VAR_017362. FT VARIANT 407 407 C -> S (in HEMB; severe). FT /FTId=VAR_006604. FT VARIANT 410 410 D -> H (in HEMB; Mechtal; FT dbSNP:rs137852278). FT {ECO:0000269|PubMed:1346975}. FT /FTId=VAR_017318. FT VARIANT 411 411 S -> G (in HEMB; Varel; FT dbSNP:rs137852277). FT {ECO:0000269|PubMed:1346975}. FT /FTId=VAR_017320. FT VARIANT 411 411 S -> I (in HEMB; Schmallenberg; FT dbSNP:rs137852276). FT {ECO:0000269|PubMed:1346975}. FT /FTId=VAR_017319. FT VARIANT 412 412 G -> E (in HEMB; dbSNP:rs1233706534). FT {ECO:0000269|PubMed:12588353}. FT /FTId=VAR_017363. FT VARIANT 413 413 G -> R (in HEMB; moderate to severe; FT dbSNP:rs1306658513). FT {ECO:0000269|PubMed:7981722, FT ECO:0000269|PubMed:9222764}. FT /FTId=VAR_006605. FT VARIANT 414 414 P -> T (in HEMB; Bergamo; increased FT protein abundance; loss of function in FT blood coagulation; dbSNP:rs137852265). FT {ECO:0000269|PubMed:12604421, FT ECO:0000269|PubMed:2162822, FT ECO:0000269|PubMed:25251685}. FT /FTId=VAR_017321. FT VARIANT 419 419 V -> E (in HEMB; moderately severe; FT dbSNP:rs137852280). FT {ECO:0000269|PubMed:8076946, FT ECO:0000269|PubMed:8199596}. FT /FTId=VAR_006606. FT VARIANT 424 424 F -> V (in HEMB). FT {ECO:0000269|PubMed:9222764}. FT /FTId=VAR_006607. FT VARIANT 426 426 T -> P (in HEMB; severe; Barcelos). FT {ECO:0000269|PubMed:8257988}. FT /FTId=VAR_006608. FT VARIANT 430 430 S -> T (in HEMB). FT /FTId=VAR_006609. FT VARIANT 431 431 W -> G (in HEMB). FT /FTId=VAR_006610. FT VARIANT 431 431 W -> R (in HEMB; moderate). FT /FTId=VAR_006611. FT VARIANT 432 432 G -> S (in HEMB; severe; FT dbSNP:rs1170838100). FT /FTId=VAR_006612. FT VARIANT 432 432 G -> V (in HEMB; severe). FT {ECO:0000269|PubMed:9600455}. FT /FTId=VAR_006613. FT VARIANT 433 433 E -> A (in HEMB). FT /FTId=VAR_006614. FT VARIANT 433 433 E -> K (in HEMB; dbSNP:rs767828752). FT /FTId=VAR_006615. FT VARIANT 435 435 C -> Y (in HEMB; dbSNP:rs1385141619). FT {ECO:0000269|PubMed:12604421}. FT /FTId=VAR_017364. FT VARIANT 436 436 A -> V (in HEMB; moderately severe; FT Niigata; dbSNP:rs137852266). FT {ECO:0000269|PubMed:3243764}. FT /FTId=VAR_006616. FT VARIANT 442 442 G -> E (in HEMB). FT {ECO:0000269|PubMed:12604421}. FT /FTId=VAR_017365. FT VARIANT 442 442 G -> R (in HEMB; severe; Angers; FT dbSNP:rs137852267). FT {ECO:0000269|PubMed:2714791}. FT /FTId=VAR_017322. FT VARIANT 443 443 I -> T (in HEMB; moderately severe; Long FT Beach, Los Angeles and Vancouver; FT dbSNP:rs137852268). FT {ECO:0000269|PubMed:1902289, FT ECO:0000269|PubMed:3401602}. FT /FTId=VAR_017323. FT VARIANT 445 445 T -> TIYT (in HEMB; severe; Lousada). FT /FTId=VAR_006617. FT VARIANT 447 447 V -> VYTKV (in HEMB; reduced protein FT abundance; loss of function in blood FT coagulation). FT {ECO:0000269|PubMed:25251685}. FT /FTId=VAR_073983. FT VARIANT 449 449 R -> Q (in HEMB; mild; FT dbSNP:rs143018900). FT {ECO:0000269|PubMed:8076946}. FT /FTId=VAR_006618. FT VARIANT 449 449 R -> W (in HEMB; mild; FT dbSNP:rs757996262). FT {ECO:0000269|PubMed:12604421}. FT /FTId=VAR_006619. FT VARIANT 450 450 Y -> C (in HEMB; severe; FT dbSNP:rs1243180674). FT {ECO:0000269|PubMed:9600455}. FT /FTId=VAR_006620. FT VARIANT 453 453 W -> R (in HEMB; dbSNP:rs137852269). FT {ECO:0000269|PubMed:2773937}. FT /FTId=VAR_017324. FT VARIANT 454 454 I -> T (in HEMB; Italy). FT {ECO:0000269|PubMed:9452115}. FT /FTId=VAR_006621. FT VARIANT 461 461 T -> P (in dbSNP:rs4149751). FT {ECO:0000269|Ref.7}. FT /FTId=VAR_014308. FT MUTAGEN 305 305 Y->F: Strongly increases enzyme activity FT with a synthetic peptide substrate; when FT associated with T-311; A-365 and T-391. FT {ECO:0000269|PubMed:12444082}. FT MUTAGEN 311 311 K->T: Strongly increases enzyme activity FT with a synthetic peptide substrate; when FT associated with F-305; A-365 and T-391. FT {ECO:0000269|PubMed:12444082}. FT MUTAGEN 312 312 Y->A: Strongly decreases enzyme activity FT with a synthetic peptide substrate. FT {ECO:0000269|PubMed:12444082}. FT MUTAGEN 391 391 Y->T: Strongly increases enzyme activity FT with a synthetic peptide substrate; when FT associated with F-305; T-311 and A-365. FT {ECO:0000269|PubMed:12444082}. FT STRAND 50 52 {ECO:0000244|PDB:1NL0}. FT HELIX 60 64 {ECO:0000244|PDB:1NL0}. FT STRAND 65 67 {ECO:0000244|PDB:1CFH}. FT HELIX 71 75 {ECO:0000244|PDB:1NL0}. FT STRAND 78 80 {ECO:0000244|PDB:1NL0}. FT HELIX 81 90 {ECO:0000244|PDB:1NL0}. FT TURN 96 99 {ECO:0000244|PDB:1EDM}. FT STRAND 102 105 {ECO:0000244|PDB:4WMA}. FT STRAND 107 111 {ECO:0000244|PDB:1EDM}. FT STRAND 114 118 {ECO:0000244|PDB:1EDM}. FT TURN 125 128 {ECO:0000244|PDB:4WMA}. FT TURN 134 136 {ECO:0000244|PDB:2WPH}. FT HELIX 137 140 {ECO:0000244|PDB:5JB9}. FT STRAND 142 148 {ECO:0000244|PDB:5JB9}. FT TURN 149 151 {ECO:0000244|PDB:5JB9}. FT STRAND 152 156 {ECO:0000244|PDB:5JB9}. FT STRAND 161 163 {ECO:0000244|PDB:5JB9}. FT STRAND 165 168 {ECO:0000244|PDB:2WPI}. FT STRAND 170 172 {ECO:0000244|PDB:5JB9}. FT STRAND 174 176 {ECO:0000244|PDB:5JB9}. FT STRAND 187 189 {ECO:0000244|PDB:2WPJ}. FT STRAND 241 248 {ECO:0000244|PDB:5JB9}. FT STRAND 252 258 {ECO:0000244|PDB:5JB9}. FT STRAND 261 264 {ECO:0000244|PDB:5JB9}. FT HELIX 266 268 {ECO:0000244|PDB:5JB9}. FT STRAND 269 271 {ECO:0000244|PDB:5JB9}. FT STRAND 276 280 {ECO:0000244|PDB:5JB9}. FT STRAND 282 286 {ECO:0000244|PDB:1RFN}. FT STRAND 292 301 {ECO:0000244|PDB:5JB9}. FT TURN 303 306 {ECO:0000244|PDB:5JB9}. FT STRAND 307 310 {ECO:0000244|PDB:5JB9}. FT TURN 311 314 {ECO:0000244|PDB:5TNT}. FT STRAND 317 323 {ECO:0000244|PDB:5JB9}. FT HELIX 339 347 {ECO:0000244|PDB:5JB9}. FT STRAND 350 360 {ECO:0000244|PDB:5JB9}. FT STRAND 370 377 {ECO:0000244|PDB:5JB9}. FT HELIX 379 384 {ECO:0000244|PDB:5JB9}. FT STRAND 394 398 {ECO:0000244|PDB:5JB9}. FT STRAND 414 419 {ECO:0000244|PDB:5JB9}. FT STRAND 422 431 {ECO:0000244|PDB:5JB9}. FT STRAND 433 436 {ECO:0000244|PDB:5JB9}. FT STRAND 442 446 {ECO:0000244|PDB:5JB9}. FT HELIX 447 450 {ECO:0000244|PDB:5JB9}. FT HELIX 451 457 {ECO:0000244|PDB:5JB9}. SQ SEQUENCE 461 AA; 51778 MW; C4720C1234477EF5 CRC64; MQRVNMIMAE SPGLITICLL GYLLSAECTV FLDHENANKI LNRPKRYNSG KLEEFVQGNL ERECMEEKCS FEEAREVFEN TERTTEFWKQ YVDGDQCESN PCLNGGSCKD DINSYECWCP FGFEGKNCEL DVTCNIKNGR CEQFCKNSAD NKVVCSCTEG YRLAENQKSC EPAVPFPCGR VSVSQTSKLT RAETVFPDVD YVNSTEAETI LDNITQSTQS FNDFTRVVGG EDAKPGQFPW QVVLNGKVDA FCGGSIVNEK WIVTAAHCVE TGVKITVVAG EHNIEETEHT EQKRNVIRII PHHNYNAAIN KYNHDIALLE LDEPLVLNSY VTPICIADKE YTNIFLKFGS GYVSGWGRVF HKGRSALVLQ YLRVPLVDRA TCLRSTKFTI YNNMFCAGFH EGGRDSCQGD SGGPHVTEVE GTSFLTGIIS WGEECAMKGK YGIYTKVSRY VNWIKEKTKL T //