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 27-MAR-2024, entry version 279. 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; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC 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 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., Findeli A., RA Tolstoshev P., Lecocq J.-P.; RT "Isolation of a human anti-haemophilic factor IX cDNA clone using a unique RT 52-base synthetic oligonucleotide probe deduced from the amino acid RT 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; DOI=10.1002/j.1460-2075.1984.tb01926.x; 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 factor RT 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 human RT 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 lacking RT 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., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., 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., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA 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., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., 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., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., 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., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., 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., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., 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., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA 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., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., 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 project: RT 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, FUNCTION, RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND PROTEOLYTIC CLEAVAGE. RX PubMed=8295821; RA de la Salle C., Charmantier J.L., Ravanat C., Ohlmann P., Hartmann M.L., RA Schuhler S., Bischoff R., Ebel C., Roecklin D., 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: identification of RT 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 TISSUE RP SPECIFICITY. RX PubMed=2592373; DOI=10.1016/s0021-9258(19)30074-2; 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 propeptide RT cleavage or acetylation results in a destabilized calcium-induced RT conformation: effects on phospholipid binding and activation by factor RT 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., Wiesel M.L., RA Grunebaum L., Cazenave J.-P.; RT "A deletion located in the 3' non translated part of the factor IX gene RT 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-dependent RT 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; DOI=10.1016/s0021-9258(18)91070-7; RA Morita T., Isaacs B.S., Esmon C.T., Johnson A.E.; RT "Derivatives of blood coagulation factor IX contain a high affinity Ca2+- RT binding site that lacks gamma-carboxyglutamic acid."; RL J. Biol. Chem. 259:5698-5704(1984). RN [22] RP ERRATUM OF PUBMED:6425296. 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; DOI=10.1016/s0021-9258(19)47065-8; 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-Glc) RT O-glycosidically linked to a serine residue in the first epidermal growth RT factor-like domain of human factors VII and IX and protein Z and bovine RT 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; DOI=10.1007/978-1-4615-3806-6_12; 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 first RT 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 IXa RT 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; DOI=10.1016/s0021-9258(19)37073-5; RA Nishimura H., Takao T., Hase S., Shimonishi Y., Iwanaga S.; RT "Human factor IX has a tetrasaccharide O-glycosidically linked to serine 61 RT 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 protein RL 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., Camire R.M., RA Chu K., Fields P.A., Herzog R.W., Couto L.B., Larson P.J., High K.A.; RT "Posttranslational modifications of recombinant myotube-synthesized human RT 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., 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 THR-85; SER-99; SER-107; THR-205; THR-215 AND THR-225, RP PHOSPHORYLATION AT SER-204 AND THR-205, AND IDENTIFICATION BY MASS RP 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., Chen S.H.; RT "Identification of protein O-glycosylation site and corresponding glycans RT using liquid chromatography-tandem mass spectrometry via mapping accurate RT mass and retention time shift."; RL J. Chromatogr. A 1371:136-145(2014). RN [32] 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., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [33] 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 [34] 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 domain RT of factor IX."; RL Biochemistry 34:12126-12137(1995). RN [35] 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., Furie B.; RT "Identification of the phospholipid binding site in the vitamin K-dependent RT blood coagulation protein factor IX."; RL J. Biol. Chem. 271:16227-16236(1996). RN [36] 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 acid RT domain of coagulation factor IX using molecular dynamics simulation with RT initial Ca2+ positions determined by a genetic algorithm."; RL Biochemistry 36:2132-2138(1997). RN [37] 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 location of RT the calcium binding site in the first epidermal growth factor like domain RT of blood coagulation factor IX."; RL Biochemistry 30:7402-7409(1991). RN [38] 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., Tse A.G.D., RA 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 [39] RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 92-130 IN COMPLEX WITH CALCIUM, RP 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 domain: its RT role in protein-protein interactions."; RL Cell 82:131-141(1995). RN [40] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 133-461 IN COMPLEX WITH 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 substrate RT binding."; RL Structure 7:989-996(1999). RN [41] RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 47-91 IN COMPLEX WITH 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 domain RT bound to a conformation-specific anti-factor IX antibody."; RL J. Biol. Chem. 279:14338-14346(2004). RN [42] RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 133-191 AND 227-461 OF MUTANTS RP PHE-305/THR-311/ALA-365/THR-391 IN COMPLEX WITH CALCIUM AND SYNTHETIC RP INHIBITOR, ACTIVE SITE, DISULFIDE BOND, SUBUNIT, AND 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 of RT human coagulation factor IXa."; RL Structure 17:1669-1678(2009). RN [43] RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 133-461 IN COMPLEX WITH CALCIUM, RP 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) inhibitors RT in thrombosis."; RL J. Med. Chem. 53:1465-1472(2010). RN [44] RP X-RAY CRYSTALLOGRAPHY (2.62 ANGSTROMS) OF 133-188 AND 227-461 IN COMPLEX RP WITH CALCIUM, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND 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., Shaikh S., RA Chahwala S., Chander C., Baumgartner C., Holthoff H.P., Murray E., RA Blackney M., Giddings A.; RT "Structure based drug design: development of potent and selective factor RT IXa (FIXa) inhibitors."; RL J. Med. Chem. 53:1473-1482(2010). RN [45] RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 131-188 AND 227-461 IN COMPLEX RP WITH SERPINC1 AND CALCIUM, DISULFIDE BOND, PROTEOLYTIC CLEAVAGE, AND RP 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 [46] RP MOLECULAR PATHOLOGY OF HEMB B. RX PubMed=2743975; DOI=10.1002/j.1460-2075.1989.tb03474.x; 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 [47] RP REVIEW ON HEMB VARIANTS. RX PubMed=1634040; DOI=10.1096/fasebj.6.10.1634040; RA Sommer S.S.; RT "Assessing the underlying pattern of human germline mutations: lessons from RT the factor IX gene."; RL FASEB J. 6:2767-2774(1992). RN [48] 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 [49] 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 [50] 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 [51] 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 [52] 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 (Long RT Beach)."; RL Blood 72:820-822(1988). RN [53] RP VARIANT HEMB VAL-436. RX PubMed=3243764; DOI=10.1093/oxfordjournals.jbchem.a122575; RA Sugimoto M., Miyata T., Kawabata S., Yoshioka A., Fukui H., Takahashi H., RA Iwanaga S.; RT "Blood clotting factor IX Niigata: substitution of alanine-390 by valine in RT the catalytic domain."; RL J. Biochem. 104:878-880(1988). RN [54] 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 factor RT IX Hilo."; RL Blood 73:1540-1544(1989). RN [55] 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., Goossens M.; RT "Mutations in the catalytic domain of human coagulation factor IX: rapid RT characterization by direct genomic sequencing of DNA fragments displaying RT an altered melting behavior."; RL Genomics 4:266-272(1989). RN [56] RP VARIANTS HEMB GLN-75; ASP-79; TRP-268; THR-279; SER-306; MET-342; ARG-357 RP 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 of RT polymorphism and a high rate of mutation in the dinucleotide CpG."; RL Am. J. Hum. Genet. 45:448-457(1989). RN [57] 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 position RT 145."; RL Br. J. Haematol. 72:556-560(1989). RN [58] RP VARIANT HEMB PHE-228. RX PubMed=2753873; DOI=10.1093/oxfordjournals.jbchem.a122740; 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 valine-182 RT by phenylalanine."; RL J. Biochem. 105:756-759(1989). RN [59] RP VARIANT HEMB GLN-43. RX PubMed=2738071; DOI=10.1016/s0021-9258(18)60478-8; RA Ware J., Diuguid D.L., Liebman H.A., Rabiet M.J., Kasper C.K., Furie B.C., RA Furie B., Stafford D.W.; RT "Factor IX San Dimas. Substitution of glutamine for Arg-4 in the propeptide RT leads to incomplete gamma-carboxylation and altered phospholipid binding RT properties."; RL J. Biol. Chem. 264:11401-11406(1989). RN [60] 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 epitopes in RT their hemophilic proteins."; RL J. Clin. Invest. 84:113-118(1989). RN [61] 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 [62] 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 182 to RT leucine) results in mild haemophilia Bm."; RL Br. J. Haematol. 75:217-221(1990). RN [63] RP VARIANTS HEMB GLN-226; TRP-226; PHE-227 AND THR-414. RX PubMed=2162822; DOI=10.1016/s0021-9258(19)38528-x; 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 in RT the catalytic domain of factor IX."; RL J. Biol. Chem. 265:10876-10883(1990). RN [64] 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 in RT the loss of both coagulant and esterase activities."; RL Biochemistry 30:11286-11291(1991). RN [65] 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 B."; RL Nucleic Acids Res. 19:1165-1165(1991). RN [66] 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 [67] RP VARIANT HEMB SER-252. RX PubMed=1615485; RA Taylor S.A., Duffin J., Cameron C., Teitel J., Garvey B., 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 [68] RP VARIANTS HEMB ARG-253; GLN-294; GLN-379; PRO-426 AND ILE-TYR-THR-445 INS. RX PubMed=8257988; DOI=10.1002/humu.1380020506; RA David D., Rosa H.A.V., Pemberton S., Diniz M.J., Campos M., Lavinha J.; RT "Single-strand conformation polymorphism (SSCP) analysis of the molecular RT pathology of hemophilia B."; RL Hum. Mutat. 2:355-361(1993). RN [69] 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., Demaille J., RA Claustres M.; RT "Factor IX gene mutations causing haemophilia B: comparison of SSC RT screening versus systematic DNA sequencing and diagnostic applications."; RL Hum. Genet. 94:287-290(1994). RN [70] 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., Demaille J., RA Claustres M.; RT "A novel mutation (Val-373 to Glu) in the catalytic domain of factor IX, RT resulting in moderately/severe hemophilia B in a southern French patient."; RL Hum. Mutat. 3:156-158(1994). RN [71] 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 [72] 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 [73] RP VARIANT WARFS THR-37, AND CHARACTERIZATION OF VARIANT WARFS 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 sensitivity by RT a novel mechanism."; RL J. Clin. Invest. 98:1619-1625(1996). RN [74] RP VARIANTS WARFS THR-37 AND VAL-37. RX PubMed=9233593; DOI=10.1046/j.1365-2141.1997.2213036.x; RA Oldenburg J., Quenzel E.M., Harbrecht U., Fregin A., Kress W., RA Mueller C.R., Hertfelder H.J., Schwaab R., Brackmann H.H., Hanfland P.; RT "Missense mutations at ALA-10 in the factor IX propeptide: an insignificant RT variant in normal life but a decisive cause of bleeding during oral RT anticoagulant therapy."; RL Br. J. Haematol. 98:240-244(1997). 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>3.0.co;2-x; 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 normal RT X-chromosome."; RL Am. J. Hematol. 58:72-76(1998). RN [77] RP VARIANTS HEMB ARG-119 AND THR-454. RX PubMed=9452115; DOI=10.1002/humu.1380110194; 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; GLN-379; RP 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 the RT 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 SSCP RT 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 of RT human genes."; RL Nat. Genet. 22:231-238(1999). RN [82] RP ERRATUM OF PUBMED:10391209. 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 for RT 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; TYR-134; RP GLN-226; GLY-226; TRP-226; LYS-241; TYR-252; GLN-294; PHE-316; ARG-318; RP GLY-379; ILE-383; PHE-383; ILE-395; PHE-396; ARG-407 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: identification RT of a large deletion and 33 independent point 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; MET-342; RP 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 new RT 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, FUNCTION, RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=19846852; DOI=10.1056/nejmoa0904377; RA Simioni P., Tormene D., Tognin G., Gavasso S., Bulato C., Iacobelli N.P., RA 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., Sauna Z.E.; RT "Genetic determinants of immunogenicity to factor IX during the treatment RT 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 families RT with haemophilia B: characterization of five novel mutations."; RL Haemophilia 20:859-865(2014). RN [89] RP VARIANTS WARFS THR-37 AND VAL-37, AND CHARACTERIZATION OF VARIANTS WARFS RP THR-37 AND VAL-37. RX PubMed=29450643; DOI=10.1007/s00277-018-3264-2; RA Pezeshkpoor B., Czogalla K.J., Caspers M., Berkemeier A.C., Liphardt K., RA Ghosh S., Kellner M., Ulrich S., Pavlova A., Oldenburg J.; RT "Variants in FIX propeptide associated with vitamin K antagonist RT hypersensitivity: functional analysis and additional data confirming the RT common founder mutations."; RL Ann. Hematol. 97:1061-1069(2018). 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+) ions, CC phospholipids, and factor VIIIa. {ECO:0000269|PubMed:1730085, CC ECO:0000269|PubMed:19846852, ECO:0000269|PubMed:20121197, CC ECO:0000269|PubMed:20121198, ECO:0000269|PubMed:2592373, CC 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; disulfide- CC linked (PubMed:20121198, PubMed:20121197, PubMed:20080729). Interacts CC with SERPINC1. {ECO:0000269|PubMed:20004170, CC ECO:0000269|PubMed:20080729, ECO:0000269|PubMed:20121197, CC ECO:0000269|PubMed:20121198, ECO:0000269|PubMed:2592373}. CC -!- INTERACTION: CC P00740; PRO_0000002968 [P00451]: F8; NbExp=2; IntAct=EBI-9640450, EBI-11621603; CC P00740; 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 in CC plasma. {ECO:0000269|PubMed:19846852, ECO:0000269|PubMed:2592373, CC ECO:0000269|PubMed:3857619}. CC -!- DOMAIN: Calcium binds to the gamma-carboxyglutamic acid (Gla) residues CC in the Gla domain. Calcium can also bind, with stronger affinity, to CC another site beyond the Gla domain (PubMed:6425296). Under CC physiological ion concentrations, Ca(2+) is displaced by Mg(2+) from CC some of the gammaglutamate residues in the N-terminal Gla domain. This CC leads to a subtle conformation change that may affect the interaction CC 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 removed by CC snake venom protease (PubMed:20004170, PubMed:20080729). CC {ECO:0000269|PubMed:1730085, ECO:0000269|PubMed:20004170, CC ECO:0000269|PubMed:20080729, ECO:0000269|PubMed:2592373, CC ECO:0000269|PubMed:8295821, ECO:0000269|PubMed:9169594}. CC -!- PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate CC and asparagine is (R) stereospecific within EGF domains. CC {ECO:0000269|PubMed:6688526}. 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 similar CC to hemophilia A, but patients present with fewer symptoms. Many CC patients are asymptomatic until the hemostatic system is stressed by CC 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 variants CC affecting the gene represented in this entry. CC -!- DISEASE: Note=Mutations in position 43 (Oxford-3, San Dimas) and 46 CC (Cambridge) prevents cleavage of the propeptide (PubMed:12588353, CC PubMed:2738071, PubMed:3009023, PubMed:8295821, PubMed:9169594, CC PubMed:9600455, PubMed:25251685). Mutation in position 93 (Alabama) CC probably fails to bind to cell membranes (PubMed:3790720). Mutation in CC position 191 (Chapel-Hill) or in position 226 (Nagoya or Hilo) prevent CC cleavage of the activation peptide (PubMed:6603618, PubMed:8076946, CC PubMed:12588353, 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 caused CC by variants affecting the gene represented in this entry. CC -!- DISEASE: Warfarin sensitivity, X-linked (WARFS) [MIM:301052]: A CC condition characterized by sensitivity to warfarin, a drugs used as CC anti-coagulants for the prevention of thromboembolic diseases in CC subjects with deep vein thrombosis, atrial fibrillation, or mechanical CC heart valve replacement. Warfarin sensitive individuals develop CC bleeding complications when they are given warfarin within the CC therapeutic ranges. {ECO:0000269|PubMed:29450643, CC ECO:0000269|PubMed:8833911, ECO:0000269|PubMed:9233593}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- PHARMACEUTICAL: Available under the name BeneFix (Baxter and American CC Home Products). Used to treat hemophilia B. CC -!- MISCELLANEOUS: In 1952, one of the earliest researchers of the disease, CC Dr. R.G. Macfarlane used the patient's surname, Christmas, to refer to CC the disease and also to refer to the clotting factor which he called CC the 'Christmas Factor'. At the time, Stephen Christmas was a 5-year-old CC boy. He died in 1993 at the age of 46 from acquired immunodeficiency CC syndrome contracted through treatment with blood products. CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE- CC 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 - Issue CC 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 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 PDB; 6MV4; X-ray; 1.37 A; H=227-461, L=132-185. DR PDB; 6RFK; X-ray; 1.60 A; E=130-191, S=227-461. DR PDB; 6X5J; X-ray; 2.51 A; A=227-461, B=130-191. DR PDB; 6X5L; X-ray; 2.25 A; A=227-460, B=130-191. DR PDB; 6X5P; X-ray; 2.00 A; A=227-461, B=130-191. DR PDB; 7AHV; X-ray; 3.11 A; H=227-461, L=130-188. DR PDB; 8OL9; X-ray; 2.60 A; H=227-461, L=130-188. 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 PDBsum; 6MV4; -. DR PDBsum; 6RFK; -. DR PDBsum; 6X5J; -. DR PDBsum; 6X5L; -. DR PDBsum; 6X5P; -. DR PDBsum; 7AHV; -. DR PDBsum; 8OL9; -. DR AlphaFoldDB; P00740; -. DR SMR; P00740; -. DR BioGRID; 108456; 56. DR ComplexPortal; CPX-4945; Coagulation factor IXa complex. DR DIP; DIP-58520N; -. DR ELM; P00740; -. DR IntAct; P00740; 36. DR MINT; P00740; -. DR STRING; 9606.ENSP00000218099; -. DR BindingDB; P00740; -. DR ChEMBL; CHEMBL2016; -. DR DrugBank; DB13192; Antihemophilic factor human. DR DrugBank; DB00025; Antihemophilic factor, human recombinant. DR DrugBank; DB13150; Coagulation factor VII human. DR DrugBank; DB13923; Emicizumab. DR DrugBank; DB09332; Kappadione. DR DrugBank; DB13998; Lonoctocog alfa. DR DrugBank; DB00170; Menadione. DR DrugBank; DB13999; Moroctocog alfa. DR DrugBank; DB05131; TTP889. DR DrugBank; DB09109; Turoctocog alfa. DR DrugBank; DB14738; Turoctocog alfa pegol. DR GuidetoPHARMACOLOGY; 2364; -. DR Allergome; 9616; Hom s Factor IX. DR MEROPS; S01.214; -. DR GlyConnect; 96; 13 N-Linked glycans, 1 O-Fuc glycan (1 site), 2 O-Glc glycans (1 site), 9 O-Linked glycans (6 sites). DR GlyCosmos; P00740; 9 sites, 41 glycans. DR GlyGen; P00740; 10 sites, 23 N-linked glycans (1 site), 18 O-linked glycans (8 sites). DR iPTMnet; P00740; -. DR PhosphoSitePlus; P00740; -. DR BioMuta; F9; -. DR CPTAC; non-CPTAC-2647; -. DR jPOST; P00740; -. DR MassIVE; P00740; -. DR PaxDb; 9606-ENSP00000218099; -. DR PeptideAtlas; P00740; -. DR ProteomicsDB; 51274; -. [P00740-1] DR ABCD; P00740; 2 sequenced antibodies. DR Antibodypedia; 367; 963 antibodies from 39 providers. DR DNASU; 2158; -. DR Ensembl; ENST00000218099.7; ENSP00000218099.2; ENSG00000101981.12. [P00740-1] DR Ensembl; ENST00000394090.2; ENSP00000377650.2; ENSG00000101981.12. [P00740-2] DR GeneID; 2158; -. DR KEGG; hsa:2158; -. DR MANE-Select; ENST00000218099.7; ENSP00000218099.2; NM_000133.4; NP_000124.1. DR UCSC; uc004fas.2; human. [P00740-1] DR AGR; HGNC:3551; -. DR CTD; 2158; -. DR DisGeNET; 2158; -. DR GeneCards; F9; -. DR GeneReviews; F9; -. DR HGNC; HGNC:3551; F9. DR HPA; ENSG00000101981; Tissue enriched (liver). DR MalaCards; F9; -. DR MIM; 300746; gene. DR MIM; 300807; phenotype. DR MIM; 301052; phenotype. DR MIM; 306900; phenotype. DR neXtProt; NX_P00740; -. DR OpenTargets; ENSG00000101981; -. DR Orphanet; 177929; Bleeding disorder in hemophilia B carriers. DR Orphanet; 169799; Mild hemophilia B. DR Orphanet; 169796; Moderate hemophilia B. DR Orphanet; 169793; Severe hemophilia B. DR PharmGKB; PA27954; -. DR VEuPathDB; HostDB:ENSG00000101981; -. DR eggNOG; ENOG502QUEV; Eukaryota. DR GeneTree; ENSGT00940000159516; -. DR HOGENOM; CLU_006842_19_5_1; -. DR InParanoid; P00740; -. DR OMA; VICSCTE; -. DR OrthoDB; 4629979at2759; -. DR PhylomeDB; P00740; -. DR TreeFam; TF327329; -. DR BioCyc; MetaCyc:HS02329-MONOMER; -. DR BRENDA; 3.4.21.22; 2681. DR PathwayCommons; P00740; -. 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 Reactome; R-HSA-9629569; Protein hydroxylation. DR Reactome; R-HSA-9672383; Defective factor IX causes thrombophilia. DR Reactome; R-HSA-9672396; Defective cofactor function of FVIIIa variant. DR Reactome; R-HSA-9673202; Defective F9 variant does not activate FX. DR Reactome; R-HSA-9673218; Defective F9 secretion. DR Reactome; R-HSA-9673221; Defective F9 activation. DR Reactome; R-HSA-9673240; Defective gamma-carboxylation of F9. DR SABIO-RK; P00740; -. DR SignaLink; P00740; -. DR SIGNOR; P00740; -. DR BioGRID-ORCS; 2158; 30 hits in 776 CRISPR screens. DR EvolutionaryTrace; P00740; -. DR GeneWiki; Factor_IX; -. DR GenomeRNAi; 2158; -. DR Pharos; P00740; Tchem. DR PRO; PR:P00740; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; P00740; Protein. DR Bgee; ENSG00000101981; Expressed in right lobe of liver and 42 other cell types or tissues. 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:0046872; F:metal ion binding; EXP:DisProt. DR GO; GO:0004252; F:serine-type endopeptidase activity; NAS:BHF-UCL. DR GO; GO:0007596; P:blood coagulation; IDA:UniProtKB. DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB. DR GO; GO:0031638; P:zymogen activation; IDA:UniProtKB. DR CDD; cd00054; EGF_CA; 1. DR CDD; cd00190; Tryp_SPc; 1. DR Gene3D; 4.10.740.10; Coagulation Factor IX; 1. DR Gene3D; 2.10.25.10; Laminin; 2. DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2. DR InterPro; IPR017857; Coagulation_fac-like_Gla_dom. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. 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; IPR043504; Peptidase_S1_PA_chymotrypsin. DR InterPro; IPR001314; Peptidase_S1A. DR InterPro; IPR001254; Trypsin_dom. DR InterPro; IPR018114; TRYPSIN_HIS. DR InterPro; IPR033116; TRYPSIN_SER. DR PANTHER; PTHR24278; COAGULATION FACTOR; 1. DR PANTHER; PTHR24278:SF31; COAGULATION FACTOR IX; 1. DR Pfam; PF00008; EGF; 1. DR Pfam; PF14670; FXa_inhibition; 1. DR Pfam; PF00594; Gla; 1. DR Pfam; PF00089; Trypsin; 1. DR PIRSF; PIRSF001143; Factor_X; 1. DR PRINTS; PR00722; CHYMOTRYPSIN. DR PRINTS; PR00010; EGFBLOOD. 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; SSF57196; EGF/Laminin; 1. DR SUPFAM; SSF57630; GLA-domain; 1. DR SUPFAM; SSF50494; Trypsin-like serine proteases; 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. DR Genevisible; P00740; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Blood coagulation; Calcium; KW Cleavage on pair of basic residues; Direct protein sequencing; KW Disease variant; Disulfide bond; EGF-like domain; KW Gamma-carboxyglutamic acid; Glycoprotein; Hemophilia; Hemostasis; KW Hydrolase; Hydroxylation; Magnesium; Metal-binding; Pharmaceutical; KW Phosphoprotein; Protease; Reference proteome; Repeat; Secreted; KW Serine protease; Signal; Sulfation; Thrombophilia; Zymogen. FT SIGNAL 1..28 FT /evidence="ECO:0000255" FT PROPEP 29..46 FT /evidence="ECO:0000269|PubMed:2592373" FT /id="PRO_0000027755" FT CHAIN 47..461 FT /note="Coagulation factor IX" FT /id="PRO_0000027756" FT CHAIN 47..191 FT /note="Coagulation factor IXa light chain" FT /id="PRO_0000027757" FT PROPEP 192..226 FT /note="Activation peptide" FT /id="PRO_0000027758" FT CHAIN 227..461 FT /note="Coagulation factor IXa heavy chain" FT /id="PRO_0000027759" FT DOMAIN 47..92 FT /note="Gla" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463" FT DOMAIN 93..129 FT /note="EGF-like 1; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 130..171 FT /note="EGF-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 227..459 FT /note="Peptidase S1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT ACT_SITE 267 FT /note="Charge relay system" FT /evidence="ECO:0000269|PubMed:20004170, FT ECO:0000269|PubMed:659613" FT ACT_SITE 315 FT /note="Charge relay system" FT /evidence="ECO:0000269|PubMed:659613" FT ACT_SITE 411 FT /note="Charge relay system" FT /evidence="ECO:0000269|PubMed:20004170, FT ECO:0000269|PubMed:659613" FT BINDING 47 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:14722079, FT ECO:0007744|PDB:1NL0" FT BINDING 48 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:14722079, FT ECO:0007744|PDB:1NL0" FT BINDING 53 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /note="via 4-carboxyglutamate" FT /evidence="ECO:0000305|PubMed:14722079, FT ECO:0007744|PDB:1NL0" FT BINDING 53 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /note="via 4-carboxyglutamate" FT /evidence="ECO:0000305|PubMed:14722079, FT ECO:0007744|PDB:1NL0" FT BINDING 54 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /note="via 4-carboxyglutamate" FT /evidence="ECO:0000305|PubMed:14722079, FT ECO:0007744|PDB:1NL0" FT BINDING 54 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /note="via 4-carboxyglutamate" FT /evidence="ECO:0000305|PubMed:14722079, FT ECO:0007744|PDB:1NL0" FT BINDING 61 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /note="via 4-carboxyglutamate" FT /evidence="ECO:0000305|PubMed:14722079, FT ECO:0007744|PDB:1NL0" FT BINDING 61 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /note="via 4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00741" FT BINDING 63 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /note="via 4-carboxyglutamate" FT /evidence="ECO:0000305|PubMed:14722079, FT ECO:0007744|PDB:1NL0" FT BINDING 63 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /note="via 4-carboxyglutamate" FT /evidence="ECO:0000305|PubMed:14722079, FT ECO:0007744|PDB:1NL0" FT BINDING 63 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /note="via 4-carboxyglutamate" FT /evidence="ECO:0000305|PubMed:14722079, FT ECO:0007744|PDB:1NL0" FT BINDING 66 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /note="via 4-carboxyglutamate" FT /evidence="ECO:0000305|PubMed:14722079, FT ECO:0007744|PDB:1NL0" FT BINDING 66 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /note="via 4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00741" FT BINDING 67 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /note="via 4-carboxyglutamate" FT /evidence="ECO:0000305|PubMed:14722079, FT ECO:0007744|PDB:1NL0" FT BINDING 72 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /note="via 4-carboxyglutamate" FT /evidence="ECO:0000305|PubMed:14722079, FT ECO:0007744|PDB:1NL0" FT BINDING 72 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /note="via 4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00741" FT BINDING 73 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /note="via 4-carboxyglutamate" FT /evidence="ECO:0000305|PubMed:14722079, FT ECO:0007744|PDB:1NL0" FT BINDING 73 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /note="via 4-carboxyglutamate" FT /evidence="ECO:0000305|PubMed:14722079, FT ECO:0007744|PDB:1NL0" FT BINDING 76 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /note="via 4-carboxyglutamate" FT /evidence="ECO:0000305|PubMed:14722079, FT ECO:0007744|PDB:1NL0" FT BINDING 76 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /note="via 4-carboxyglutamate" FT /evidence="ECO:0000305|PubMed:14722079, FT ECO:0007744|PDB:1NL0" FT BINDING 76 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /note="via 4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00741" FT BINDING 82 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /note="via 4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00741" FT BINDING 82 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="3" FT /note="via 4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00741" FT BINDING 86 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /note="via 4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00741" FT BINDING 86 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="3" FT /note="via 4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00741" FT BINDING 93 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="7" FT /evidence="ECO:0000269|PubMed:7606779, FT ECO:0007744|PDB:1EDM" FT BINDING 94 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="7" FT /evidence="ECO:0000269|PubMed:7606779, FT ECO:0007744|PDB:1EDM" FT BINDING 96 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="7" FT /evidence="ECO:0000269|PubMed:7606779, FT ECO:0007744|PDB:1EDM" FT BINDING 110 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="7" FT /evidence="ECO:0000269|PubMed:7606779, FT ECO:0007744|PDB:1EDM" FT BINDING 111 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="7" FT /evidence="ECO:0000269|PubMed:7606779, FT ECO:0007744|PDB:1EDM" FT BINDING 281 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="8" FT /evidence="ECO:0000269|PubMed:10467148, FT ECO:0000269|PubMed:20004170, ECO:0000269|PubMed:20080729, FT ECO:0000269|PubMed:20121197, ECO:0000269|PubMed:20121198, FT ECO:0007744|PDB:1RFN, ECO:0007744|PDB:2WPH, FT ECO:0007744|PDB:2WPI, ECO:0007744|PDB:2WPJ, FT ECO:0007744|PDB:2WPK, ECO:0007744|PDB:2WPM, FT ECO:0007744|PDB:3KCG, ECO:0007744|PDB:3LC3, FT ECO:0007744|PDB:3LC5" FT BINDING 283 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="8" FT /evidence="ECO:0000269|PubMed:10467148, FT ECO:0000269|PubMed:20004170, ECO:0000269|PubMed:20080729, FT ECO:0000269|PubMed:20121197, ECO:0000269|PubMed:20121198, FT ECO:0007744|PDB:1RFN, ECO:0007744|PDB:2WPH, FT ECO:0007744|PDB:2WPI, ECO:0007744|PDB:2WPJ, FT ECO:0007744|PDB:2WPK, ECO:0007744|PDB:2WPM, FT ECO:0007744|PDB:3KCG, ECO:0007744|PDB:3LC3, FT ECO:0007744|PDB:3LC5" FT BINDING 286 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="8" FT /evidence="ECO:0000269|PubMed:10467148, FT ECO:0000269|PubMed:20004170, ECO:0000269|PubMed:20080729, FT ECO:0000269|PubMed:20121197, ECO:0000269|PubMed:20121198, FT ECO:0007744|PDB:1RFN, ECO:0007744|PDB:2WPH, FT ECO:0007744|PDB:2WPI, ECO:0007744|PDB:2WPJ, FT ECO:0007744|PDB:2WPK, ECO:0007744|PDB:2WPM, FT ECO:0007744|PDB:3KCG, ECO:0007744|PDB:3LC3, FT ECO:0007744|PDB:3LC5" FT BINDING 288 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="8" FT /evidence="ECO:0000269|PubMed:10467148, FT ECO:0000269|PubMed:20004170, ECO:0000269|PubMed:20080729, FT ECO:0000269|PubMed:20121197, ECO:0000269|PubMed:20121198, FT ECO:0007744|PDB:1RFN, ECO:0007744|PDB:2WPH, FT ECO:0007744|PDB:2WPI, ECO:0007744|PDB:2WPJ, FT ECO:0007744|PDB:2WPK, ECO:0007744|PDB:2WPM, FT ECO:0007744|PDB:3KCG, ECO:0007744|PDB:3LC3, FT ECO:0007744|PDB:3LC5" FT BINDING 291 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="8" FT /evidence="ECO:0000269|PubMed:10467148, FT ECO:0000269|PubMed:20004170, ECO:0000269|PubMed:20080729, FT ECO:0000269|PubMed:20121197, ECO:0000269|PubMed:20121198, FT ECO:0007744|PDB:2WPH, ECO:0007744|PDB:2WPI, FT ECO:0007744|PDB:2WPJ, ECO:0007744|PDB:2WPK, FT ECO:0007744|PDB:2WPM, ECO:0007744|PDB:3KCG, FT ECO:0007744|PDB:3LC3, ECO:0007744|PDB:3LC5" FT SITE 191..192 FT /note="Cleavage; by factor XIa" FT SITE 226..227 FT /note="Cleavage; by factor XIa" FT MOD_RES 53 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463" FT MOD_RES 54 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463" FT MOD_RES 61 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463" FT MOD_RES 63 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463" FT MOD_RES 66 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463" FT MOD_RES 67 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463" FT MOD_RES 72 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463" FT MOD_RES 73 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463" FT MOD_RES 76 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463" FT MOD_RES 79 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463" FT MOD_RES 82 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463" FT MOD_RES 86 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00741, FT ECO:0000255|PROSITE-ProRule:PRU00463" FT MOD_RES 110 FT /note="(3R)-3-hydroxyaspartate" FT /evidence="ECO:0000269|PubMed:6688526" FT MOD_RES 114 FT /note="Phosphoserine" FT /evidence="ECO:0000269|Ref.28" FT MOD_RES 201 FT /note="Sulfotyrosine" FT /evidence="ECO:0000269|PubMed:11133752" FT MOD_RES 204 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11133752, FT ECO:0000269|PubMed:25456591" FT MOD_RES 205 FT /note="Phosphothreonine; alternate" FT /evidence="ECO:0000269|PubMed:25456591" FT CARBOHYD 85 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000269|PubMed:25456591" FT CARBOHYD 99 FT /note="O-linked (Glc...) serine" FT /evidence="ECO:0000269|PubMed:2129367, FT ECO:0000269|PubMed:2511201, ECO:0000269|PubMed:25456591" FT /id="CAR_000009" FT CARBOHYD 107 FT /note="O-linked (Fuc...) serine" FT /evidence="ECO:0000269|PubMed:1517205, FT ECO:0000269|PubMed:25456591" FT /id="CAR_000010" FT CARBOHYD 203 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 205 FT /note="O-linked (GalNAc...) threonine; alternate" FT /evidence="ECO:0000269|PubMed:25456591, FT ECO:0000269|PubMed:8172892" FT CARBOHYD 213 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 215 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000269|PubMed:25456591, FT ECO:0000269|PubMed:8172892" FT CARBOHYD 225 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000269|PubMed:25456591" FT DISULFID 64..69 FT /evidence="ECO:0000250|UniProtKB:P00741" FT DISULFID 97..108 FT /evidence="ECO:0000269|PubMed:1304885, FT ECO:0000269|PubMed:7606779, ECO:0007744|PDB:1EDM, FT ECO:0007744|PDB:1IXA" FT DISULFID 102..117 FT /evidence="ECO:0000269|PubMed:1304885, FT ECO:0000269|PubMed:7606779, ECO:0007744|PDB:1EDM, FT ECO:0007744|PDB:1IXA" FT DISULFID 119..128 FT /evidence="ECO:0000269|PubMed:1304885, FT ECO:0000269|PubMed:7606779, ECO:0007744|PDB:1EDM, FT ECO:0007744|PDB:1IXA" FT DISULFID 134..145 FT /evidence="ECO:0000269|PubMed:20004170, FT ECO:0000269|PubMed:20080729, ECO:0000269|PubMed:20121197, FT ECO:0000269|PubMed:20121198, ECO:0007744|PDB:1RFN, FT ECO:0007744|PDB:2WPH, ECO:0007744|PDB:2WPI, FT ECO:0007744|PDB:2WPJ, ECO:0007744|PDB:2WPK, FT ECO:0007744|PDB:2WPL, ECO:0007744|PDB:2WPM, FT ECO:0007744|PDB:3KCG, ECO:0007744|PDB:3LC3, FT ECO:0007744|PDB:3LC5" FT DISULFID 141..155 FT /evidence="ECO:0000269|PubMed:20004170, FT ECO:0000269|PubMed:20080729, ECO:0000269|PubMed:20121197, FT ECO:0000269|PubMed:20121198, ECO:0007744|PDB:1RFN, FT ECO:0007744|PDB:2WPH, ECO:0007744|PDB:2WPI, FT ECO:0007744|PDB:2WPJ, ECO:0007744|PDB:2WPK, FT ECO:0007744|PDB:2WPL, ECO:0007744|PDB:2WPM, FT ECO:0007744|PDB:3KCG, ECO:0007744|PDB:3LC3, FT ECO:0007744|PDB:3LC5" FT DISULFID 157..170 FT /evidence="ECO:0000269|PubMed:20004170, FT ECO:0000269|PubMed:20080729, ECO:0000269|PubMed:20121197, FT ECO:0000269|PubMed:20121198, ECO:0007744|PDB:1RFN, FT ECO:0007744|PDB:2WPH, ECO:0007744|PDB:2WPI, FT ECO:0007744|PDB:2WPJ, ECO:0007744|PDB:2WPK, FT ECO:0007744|PDB:2WPL, ECO:0007744|PDB:2WPM, FT ECO:0007744|PDB:3KCG, ECO:0007744|PDB:3LC3, FT ECO:0007744|PDB:3LC5" FT DISULFID 178..335 FT /note="Interchain (between light and heavy chains)" FT /evidence="ECO:0000269|PubMed:20004170, FT ECO:0000269|PubMed:20080729, ECO:0000269|PubMed:20121197, FT ECO:0000269|PubMed:20121198, ECO:0007744|PDB:1RFN, FT ECO:0007744|PDB:2WPH, ECO:0007744|PDB:2WPI, FT ECO:0007744|PDB:2WPJ, ECO:0007744|PDB:2WPK, FT ECO:0007744|PDB:2WPL, ECO:0007744|PDB:2WPM, FT ECO:0007744|PDB:3KCG, ECO:0007744|PDB:3LC3, FT ECO:0007744|PDB:3LC5" FT DISULFID 252..268 FT /evidence="ECO:0000269|PubMed:20004170, FT ECO:0000269|PubMed:20080729, ECO:0000269|PubMed:20121197, FT ECO:0000269|PubMed:20121198, ECO:0007744|PDB:1RFN, FT ECO:0007744|PDB:2WPH, ECO:0007744|PDB:2WPI, FT ECO:0007744|PDB:2WPJ, ECO:0007744|PDB:2WPK, FT ECO:0007744|PDB:2WPL, ECO:0007744|PDB:2WPM, FT ECO:0007744|PDB:3KCG, ECO:0007744|PDB:3LC3, FT ECO:0007744|PDB:3LC5" FT DISULFID 382..396 FT /evidence="ECO:0000269|PubMed:20004170, FT ECO:0000269|PubMed:20080729, ECO:0000269|PubMed:20121197, FT ECO:0000269|PubMed:20121198, ECO:0007744|PDB:1RFN, FT ECO:0007744|PDB:2WPH, ECO:0007744|PDB:2WPI, FT ECO:0007744|PDB:2WPJ, ECO:0007744|PDB:2WPK, FT ECO:0007744|PDB:2WPL, ECO:0007744|PDB:2WPM, FT ECO:0007744|PDB:3KCG, ECO:0007744|PDB:3LC3, FT ECO:0007744|PDB:3LC5" FT DISULFID 407..435 FT /evidence="ECO:0000269|PubMed:20004170, FT ECO:0000269|PubMed:20080729, ECO:0000269|PubMed:20121197, FT ECO:0000269|PubMed:20121198, ECO:0007744|PDB:1RFN, FT ECO:0007744|PDB:2WPH, ECO:0007744|PDB:2WPI, FT ECO:0007744|PDB:2WPJ, ECO:0007744|PDB:2WPK, FT ECO:0007744|PDB:2WPL, ECO:0007744|PDB:2WPM, FT ECO:0007744|PDB:3KCG, ECO:0007744|PDB:3LC3, FT ECO:0007744|PDB:3LC5" FT VAR_SEQ 93..130 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.6" FT /id="VSP_047689" FT VARIANT 7 FT /note="I -> F (in dbSNP:rs150190385)" FT /evidence="ECO:0000269|PubMed:2773937" FT /id="VAR_006520" FT VARIANT 17 FT /note="I -> N (in HEMB; severe; UK 22)" FT /id="VAR_006521" FT VARIANT 20 FT /note="L -> S (in HEMB; uncertain significance; decreased FT protein abundance; decreased function in blood FT coagulation)" FT /evidence="ECO:0000269|PubMed:25251685" FT /id="VAR_073975" FT VARIANT 28 FT /note="C -> R (in HEMB; moderate; HB130; FT dbSNP:rs387906481)" FT /id="VAR_006522" FT VARIANT 28 FT /note="C -> Y (in HEMB; decreased protein abundance; FT decreased function in blood coagulation)" FT /evidence="ECO:0000269|PubMed:12588353, FT ECO:0000269|PubMed:25251685" FT /id="VAR_017343" FT VARIANT 30 FT /note="V -> I (in HEMB)" FT /id="VAR_006523" FT VARIANT 37 FT /note="A -> T (in WARFS; reduced affinity of the glutamate FT carboxylase for the factor IX precursor; 4.4-fold decreased FT in the EC(50) for warfarin; dbSNP:rs367569299)" FT /evidence="ECO:0000269|PubMed:29450643, FT ECO:0000269|PubMed:8833911, ECO:0000269|PubMed:9233593" FT /id="VAR_017307" FT VARIANT 37 FT /note="A -> V (in WARFS; 2.5-fold decreased in the EC(50) FT for warfarin; dbSNP:rs1327097914)" FT /evidence="ECO:0000269|PubMed:29450643, FT ECO:0000269|PubMed:9233593" FT /id="VAR_083981" FT VARIANT 43 FT /note="R -> L (in HEMB; severe; Bendorf, Beuten, Gleiwitz; FT impairs removal of propeptide; dbSNP:rs1275708479)" FT /evidence="ECO:0000269|PubMed:12588353, FT ECO:0000269|PubMed:9169594" FT /id="VAR_006525" FT VARIANT 43 FT /note="R -> Q (in HEMB; severe; San Dimas, Oxford-3, FT Strasbourg-2; impairs removal of propeptide; FT dbSNP:rs1275708479)" FT /evidence="ECO:0000269|PubMed:12588353, FT ECO:0000269|PubMed:2738071, ECO:0000269|PubMed:3009023, FT ECO:0000269|PubMed:8295821, ECO:0000269|PubMed:9169594, FT ECO:0000269|PubMed:9600455" FT /id="VAR_006524" FT VARIANT 43 FT /note="R -> W (in HEMB; severe; Boxtel, Heiden, Lienen; FT impairs removal of propeptide; dbSNP:rs1603264205)" FT /evidence="ECO:0000269|PubMed:12604421, FT ECO:0000269|PubMed:9169594, ECO:0000269|PubMed:9600455" FT /id="VAR_006526" FT VARIANT 45 FT /note="K -> N (in HEMB; severe; Seattle E)" FT /id="VAR_006527" FT VARIANT 46 FT /note="R -> S (in HEMB; severe; Cambridge; impaired FT processing of the propeptide; impaired gamma-carboxylation; FT decreased protein abundance; loss of function in blood FT coagulation)" FT /evidence="ECO:0000269|PubMed:25251685" FT /id="VAR_006528" FT VARIANT 46 FT /note="R -> T (in HEMB; severe)" FT /evidence="ECO:0000269|PubMed:9600455" FT /id="VAR_006529" FT VARIANT 48 FT /note="N -> I (in HEMB; severe; Calgary-16)" FT /id="VAR_006530" FT VARIANT 49 FT /note="S -> P (in HEMB)" FT /id="VAR_006531" FT VARIANT 52 FT /note="L -> S (in HEMB; severe; Gla mutant)" FT /evidence="ECO:0000269|PubMed:12588353" FT /id="VAR_017344" FT VARIANT 53 FT /note="E -> A (in HEMB; severe; Oxford-B2; Gla mutant)" FT /id="VAR_006532" FT VARIANT 54 FT /note="E -> D (in HEMB; uncertain significance; no effect FT on protein abundance; loss of function in blood FT coagulation)" FT /evidence="ECO:0000269|PubMed:25251685" FT /id="VAR_073976" FT VARIANT 54 FT /note="E -> G (in HEMB; severe; HB151; Gla mutant)" FT /id="VAR_006533" FT VARIANT 55 FT /note="F -> C (in HEMB)" FT /id="VAR_006534" FT VARIANT 58 FT /note="G -> A (in HEMB; severe; Hong Kong-1)" FT /id="VAR_006535" FT VARIANT 58 FT /note="G -> E (in HEMB; uncertain significance; no effect FT on protein abundance; loss of function in blood FT coagulation)" FT /evidence="ECO:0000269|PubMed:25251685" FT /id="VAR_073977" FT VARIANT 58 FT /note="G -> R (in HEMB; severe; Los Angeles-4)" FT /id="VAR_006536" FT VARIANT 62..63 FT /note="Missing (in HEMB; severe)" FT /id="VAR_006537" FT VARIANT 66 FT /note="E -> V (in HEMB; moderate)" FT /id="VAR_006538" FT VARIANT 67 FT /note="E -> K (in HEMB; severe; Nagoya-4; Gla mutant; FT dbSNP:rs1410080079)" FT /id="VAR_006539" FT VARIANT 71 FT /note="F -> S (in HEMB; severe)" FT /id="VAR_006540" FT VARIANT 73 FT /note="E -> K (in HEMB; severe; Seattle-3; Gla mutant; FT dbSNP:rs137852225)" FT /evidence="ECO:0000269|PubMed:2472424" FT /id="VAR_006541" FT VARIANT 73 FT /note="E -> V (in HEMB; severe; Chongqing; Gla mutant; FT dbSNP:rs137852226)" FT /evidence="ECO:0000269|PubMed:2339358" FT /id="VAR_006542" FT VARIANT 75 FT /note="R -> Q (in HEMB; mild; dbSNP:rs137852228)" FT /evidence="ECO:0000269|PubMed:2773937" FT /id="VAR_017308" FT VARIANT 79 FT /note="E -> D (in HEMB; dbSNP:rs137852229)" FT /evidence="ECO:0000269|PubMed:2773937" FT /id="VAR_017309" FT VARIANT 84 FT /note="T -> R (in HEMB; decreased protein abundance; loss FT of function in blood coagulation)" FT /evidence="ECO:0000269|PubMed:12604421, FT ECO:0000269|PubMed:25251685" FT /id="VAR_017345" FT VARIANT 91 FT /note="Y -> C (in HEMB; moderate)" FT /id="VAR_006543" FT VARIANT 93 FT /note="D -> G (in HEMB; moderate; Alabama; FT dbSNP:rs137852230)" FT /evidence="ECO:0000269|PubMed:3790720" FT /id="VAR_006544" FT VARIANT 96 FT /note="Q -> P (in HEMB; severe; New London; FT dbSNP:rs137852231)" FT /id="VAR_006545" FT VARIANT 97 FT /note="C -> S (in HEMB)" FT /id="VAR_006546" FT VARIANT 101 FT /note="P -> R (in HEMB)" FT /id="VAR_006547" FT VARIANT 102 FT /note="C -> R (in HEMB; severe; Basel; dbSNP:rs1603264719)" FT /id="VAR_006548" FT VARIANT 106 FT /note="G -> D (in HEMB)" FT /evidence="ECO:0000269|PubMed:12588353" FT /id="VAR_017346" FT VARIANT 106 FT /note="G -> S (in HEMB; mild; Durham; dbSNP:rs137852233)" FT /evidence="ECO:0000269|PubMed:2472424, FT ECO:0000269|PubMed:9600455" FT /id="VAR_006549" FT VARIANT 108 FT /note="C -> S (in HEMB)" FT /id="VAR_006550" FT VARIANT 110 FT /note="D -> N (in HEMB; severe; Oxford-D1; FT dbSNP:rs137852274)" FT /id="VAR_006551" FT VARIANT 112 FT /note="I -> S (in HEMB)" FT /id="VAR_006552" FT VARIANT 113 FT /note="N -> K (in HEMB; mild)" FT /evidence="ECO:0000269|PubMed:9222764" FT /id="VAR_006553" FT VARIANT 115 FT /note="Y -> C (in HEMB; severe; dbSNP:rs1603264727)" FT /evidence="ECO:0000269|PubMed:9600455" FT /id="VAR_006554" FT VARIANT 119 FT /note="C -> F (in HEMB; severe)" FT /id="VAR_006555" FT VARIANT 119 FT /note="C -> R (in HEMB; Iran)" FT /evidence="ECO:0000269|PubMed:9452115" FT /id="VAR_006556" FT VARIANT 124 FT /note="E -> K (in HEMB)" FT /evidence="ECO:0000269|PubMed:12588353" FT /id="VAR_017347" FT VARIANT 125 FT /note="G -> E (in HEMB)" FT /id="VAR_006557" FT VARIANT 125 FT /note="G -> R (in HEMB)" FT /evidence="ECO:0000269|PubMed:12604421" FT /id="VAR_017348" FT VARIANT 125 FT /note="G -> V (in HEMB)" FT /evidence="ECO:0000269|PubMed:12604421" FT /id="VAR_006558" FT VARIANT 129..130 FT /note="Missing (in HEMB)" FT /id="VAR_006559" FT VARIANT 134 FT /note="C -> Y (in HEMB)" FT /evidence="ECO:0000269|PubMed:12588353" FT /id="VAR_017349" FT VARIANT 136 FT /note="I -> T (in HEMB; mild; dbSNP:rs1603265481)" FT /id="VAR_006560" FT VARIANT 138 FT /note="N -> H (in HEMB; uncertain significance; decreased FT protein abundance; decreased function in blood FT coagulation)" FT /evidence="ECO:0000269|PubMed:25251685" FT /id="VAR_073978" FT VARIANT 139 FT /note="G -> D (in HEMB; severe; dbSNP:rs1216516070)" FT /id="VAR_006561" FT VARIANT 139 FT /note="G -> S (in HEMB)" FT /id="VAR_006562" FT VARIANT 155 FT /note="C -> F (in HEMB; severe; dbSNP:rs1330705989)" FT /evidence="ECO:0000269|PubMed:9600455" FT /id="VAR_006563" FT VARIANT 160 FT /note="G -> E (in HEMB; mild)" FT /id="VAR_006564" FT VARIANT 167 FT /note="Q -> H (in HEMB; mild)" FT /id="VAR_006565" FT VARIANT 169 FT /note="S -> C (in HEMB)" FT /evidence="ECO:0000269|PubMed:11122099" FT /id="VAR_017350" FT VARIANT 170 FT /note="C -> F (in HEMB)" FT /evidence="ECO:0000269|PubMed:12604421" FT /id="VAR_017351" FT VARIANT 178 FT /note="C -> R (in HEMB)" FT /id="VAR_006566" FT VARIANT 178 FT /note="C -> W (in HEMB; severe)" FT /id="VAR_006567" FT VARIANT 191 FT /note="R -> C (in HEMB; moderate; Albuquerque, Cardiff-1; FT dbSNP:rs137852237)" FT /evidence="ECO:0000269|PubMed:2775660" FT /id="VAR_006569" FT VARIANT 191 FT /note="R -> H (in HEMB; moderate; Chapel-Hill, Chicago-2; FT dbSNP:rs137852238)" FT /evidence="ECO:0000269|PubMed:6603618, FT ECO:0000269|PubMed:8076946" FT /id="VAR_006568" FT VARIANT 194 FT /note="T -> A (in dbSNP:rs6048)" FT /evidence="ECO:0000269|PubMed:10391209, FT ECO:0000269|PubMed:25470321, ECO:0000269|PubMed:2994716, FT ECO:0000269|PubMed:3857619, ECO:0000269|PubMed:6329734" FT /id="VAR_011773" FT VARIANT 226 FT /note="R -> G (in HEMB; severe; Madrid)" FT /evidence="ECO:0000269|PubMed:12588353, FT ECO:0000269|PubMed:8076946" FT /id="VAR_006571" FT VARIANT 226 FT /note="R -> Q (in HEMB; severe; Hilo and Novara; no effect FT on protein abundance; loss of function in blood FT coagulation; dbSNP:rs137852241)" FT /evidence="ECO:0000269|PubMed:12588353, FT ECO:0000269|PubMed:2162822, ECO:0000269|PubMed:25251685, FT ECO:0000269|PubMed:2713493" FT /id="VAR_006572" FT VARIANT 226 FT /note="R -> W (in HEMB; severe; Nagoya-1, Dernbach, FT Deventer, Idaho; dbSNP:rs137852240)" FT /evidence="ECO:0000269|PubMed:12588353, FT ECO:0000269|PubMed:2162822, ECO:0000269|PubMed:2592373" FT /id="VAR_006570" FT VARIANT 227 FT /note="V -> D (in HEMB; mild)" FT /id="VAR_006573" FT VARIANT 227 FT /note="V -> F (in HEMB; Milano; dbSNP:rs137852242)" FT /evidence="ECO:0000269|PubMed:2162822" FT /id="VAR_017310" FT VARIANT 228 FT /note="V -> F (in HEMB; severe; Kashihara; FT dbSNP:rs137852243)" FT /evidence="ECO:0000269|PubMed:2753873" FT /id="VAR_017311" FT VARIANT 228 FT /note="V -> L (in HEMB; mild; Cardiff-2; FT dbSNP:rs137852243)" FT /evidence="ECO:0000269|PubMed:2372509" FT /id="VAR_006574" FT VARIANT 241 FT /note="Q -> H (in HEMB; dbSNP:rs1182648920)" FT /evidence="ECO:0000269|PubMed:25470321" FT /id="VAR_006575" FT VARIANT 241 FT /note="Q -> K (in HEMB)" FT /evidence="ECO:0000269|PubMed:12588353" FT /id="VAR_017352" FT VARIANT 252 FT /note="C -> S (in HEMB; severe; dbSNP:rs267606792)" FT /evidence="ECO:0000269|PubMed:1615485" FT /id="VAR_017312" FT VARIANT 252 FT /note="C -> Y (in HEMB)" FT /evidence="ECO:0000269|PubMed:12588353" FT /id="VAR_017353" FT VARIANT 253 FT /note="G -> E (in HEMB; severe)" FT /id="VAR_006576" FT VARIANT 253 FT /note="G -> R (in HEMB; severe; Luanda; FT dbSNP:rs1603267181)" FT /evidence="ECO:0000269|PubMed:8257988" FT /id="VAR_006577" FT VARIANT 265 FT /note="A -> T (in HEMB; mild)" FT /id="VAR_006578" FT VARIANT 268 FT /note="C -> W (in HEMB; moderate; dbSNP:rs137852246)" FT /evidence="ECO:0000269|PubMed:2773937" FT /id="VAR_017313" FT VARIANT 279 FT /note="A -> T (in HEMB; mild; dbSNP:rs137852247)" FT /evidence="ECO:0000269|PubMed:2773937, FT ECO:0000269|PubMed:8076946" FT /id="VAR_006579" FT VARIANT 283 FT /note="N -> D (in HEMB; severe)" FT /id="VAR_006580" FT VARIANT 284 FT /note="Missing (in HEMB; severe; decreased protein FT abundance; loss of function in blood coagulation)" FT /evidence="ECO:0000269|PubMed:25251685" FT /id="VAR_073979" FT VARIANT 286 FT /note="Missing (in HEMB; severe)" FT /id="VAR_006581" FT VARIANT 291 FT /note="E -> V (in HEMB; Monschau; dbSNP:rs137852279)" FT /evidence="ECO:0000269|PubMed:1346975" FT /id="VAR_017314" FT VARIANT 294 FT /note="R -> G (in HEMB; severe)" FT /id="VAR_006582" FT VARIANT 294 FT /note="R -> Q (in HEMB; mild to moderate; Dreihacken, FT Penafiel and Seattle-4; dbSNP:rs137852249)" FT /evidence="ECO:0000269|PubMed:12588353, FT ECO:0000269|PubMed:1346975, ECO:0000269|PubMed:2472424, FT ECO:0000269|PubMed:7981722, ECO:0000269|PubMed:8257988" FT /id="VAR_006583" FT VARIANT 296 FT /note="V -> M (in HEMB; uncertain significance; decreased FT protein abundance; decreased function in blood FT coagulation)" FT /evidence="ECO:0000269|PubMed:25251685" FT /id="VAR_073980" FT VARIANT 302 FT /note="H -> R (in HEMB)" FT /evidence="ECO:0000269|PubMed:12604421" FT /id="VAR_006584" FT VARIANT 306 FT /note="N -> S (in HEMB; mild; dbSNP:rs137852251)" FT /evidence="ECO:0000269|PubMed:2773937" FT /id="VAR_017315" FT VARIANT 316 FT /note="I -> F (in HEMB)" FT /evidence="ECO:0000269|PubMed:12588353" FT /id="VAR_006585" FT VARIANT 318 FT /note="L -> R (in HEMB; dbSNP:rs1222227572)" FT /evidence="ECO:0000269|PubMed:12588353" FT /id="VAR_017354" FT VARIANT 321 FT /note="L -> Q (in HEMB; severe)" FT /id="VAR_006586" FT VARIANT 328 FT /note="N -> K (in HEMB; uncertain significance; decreased FT protein abundance; decreased function in blood FT coagulation)" FT /evidence="ECO:0000269|PubMed:25251685" FT /id="VAR_073981" FT VARIANT 328 FT /note="N -> Y (in HEMB; moderate; decreased protein FT abundance; decreased function in blood coagulation)" FT /evidence="ECO:0000269|PubMed:25251685" FT /id="VAR_073982" FT VARIANT 333 FT /note="P -> H (in HEMB; severe)" FT /id="VAR_006587" FT VARIANT 333 FT /note="P -> T (in HEMB)" FT /evidence="ECO:0000269|PubMed:11122099" FT /id="VAR_017355" FT VARIANT 342 FT /note="T -> K (in HEMB; mild)" FT /id="VAR_006588" FT VARIANT 342 FT /note="T -> M (in HEMB; moderate; dbSNP:rs137852254)" FT /evidence="ECO:0000269|PubMed:12604421, FT ECO:0000269|PubMed:2773937, ECO:0000269|PubMed:9222764" FT /id="VAR_006589" FT VARIANT 344 FT /note="I -> L (in HEMB)" FT /evidence="ECO:0000269|PubMed:12604421" FT /id="VAR_017356" FT VARIANT 351 FT /note="G -> D (in HEMB)" FT /id="VAR_006590" FT VARIANT 356 FT /note="W -> C (in HEMB; severe)" FT /id="VAR_006591" FT VARIANT 357 FT /note="G -> E (in HEMB; severe; Amagasaki; FT dbSNP:rs137852275)" FT /evidence="ECO:0000269|PubMed:1958666" FT /id="VAR_006592" FT VARIANT 357 FT /note="G -> R (in HEMB; dbSNP:rs137852257)" FT /evidence="ECO:0000269|PubMed:2773937" FT /id="VAR_017316" FT VARIANT 362 FT /note="K -> E (in HEMB; moderate)" FT /id="VAR_006593" FT VARIANT 363 FT /note="G -> W (in HEMB)" FT /id="VAR_006594" FT VARIANT 366 FT /note="A -> D (in HEMB)" FT /id="VAR_006595" FT VARIANT 379 FT /note="R -> G (in HEMB; moderate; dbSNP:rs137852258)" FT /evidence="ECO:0000269|PubMed:12588353" FT /id="VAR_006596" FT VARIANT 379 FT /note="R -> Q (in HEMB; severe; Iceland-1, London and FT Sesimbra; dbSNP:rs137852259)" FT /evidence="ECO:0000269|PubMed:8076946, FT ECO:0000269|PubMed:8257988, ECO:0000269|PubMed:9600455" FT /id="VAR_006597" FT VARIANT 382 FT /note="C -> Y (in HEMB; dbSNP:rs1303221289)" FT /id="VAR_006598" FT VARIANT 383 FT /note="L -> F (in HEMB)" FT /evidence="ECO:0000269|PubMed:12588353" FT /id="VAR_017358" FT VARIANT 383 FT /note="L -> I (in HEMB)" FT /evidence="ECO:0000269|PubMed:12588353" FT /id="VAR_017357" FT VARIANT 384 FT /note="R -> L (in THPH8; factor IXPadua; higher specific FT activity than wild-type; dbSNP:rs137852283)" FT /evidence="ECO:0000269|PubMed:19846852" FT /id="VAR_062999" FT VARIANT 387 FT /note="K -> E (in HEMB; mild)" FT /evidence="ECO:0000269|PubMed:9600455" FT /id="VAR_006599" FT VARIANT 390 FT /note="I -> F (in HEMB; severe)" FT /id="VAR_006600" FT VARIANT 394 FT /note="M -> K (in HEMB)" FT /id="VAR_006601" FT VARIANT 395 FT /note="F -> I (in HEMB; dbSNP:rs1175050951)" FT /evidence="ECO:0000269|PubMed:12588353" FT /id="VAR_017359" FT VARIANT 395 FT /note="F -> L (in HEMB; dbSNP:rs1175050951)" FT /evidence="ECO:0000269|PubMed:12604421" FT /id="VAR_017360" FT VARIANT 396 FT /note="C -> F (in HEMB)" FT /evidence="ECO:0000269|PubMed:12588353" FT /id="VAR_017361" FT VARIANT 396 FT /note="C -> S (in HEMB; severe; dbSNP:rs137852273)" FT /id="VAR_006602" FT VARIANT 397 FT /note="A -> P (in HEMB; mild; Hong Kong-11; FT dbSNP:rs137852281)" FT /evidence="ECO:0000269|PubMed:9590153" FT /id="VAR_017317" FT VARIANT 404 FT /note="R -> T (in HEMB)" FT /id="VAR_006603" FT VARIANT 407 FT /note="C -> R (in HEMB)" FT /evidence="ECO:0000269|PubMed:12588353" FT /id="VAR_017362" FT VARIANT 407 FT /note="C -> S (in HEMB; severe)" FT /id="VAR_006604" FT VARIANT 410 FT /note="D -> H (in HEMB; Mechtal; dbSNP:rs137852278)" FT /evidence="ECO:0000269|PubMed:1346975" FT /id="VAR_017318" FT VARIANT 411 FT /note="S -> G (in HEMB; Varel; dbSNP:rs137852277)" FT /evidence="ECO:0000269|PubMed:1346975" FT /id="VAR_017320" FT VARIANT 411 FT /note="S -> I (in HEMB; Schmallenberg; dbSNP:rs137852276)" FT /evidence="ECO:0000269|PubMed:1346975" FT /id="VAR_017319" FT VARIANT 412 FT /note="G -> E (in HEMB; dbSNP:rs1233706534)" FT /evidence="ECO:0000269|PubMed:12588353" FT /id="VAR_017363" FT VARIANT 413 FT /note="G -> R (in HEMB; moderate to severe; FT dbSNP:rs1306658513)" FT /evidence="ECO:0000269|PubMed:7981722, FT ECO:0000269|PubMed:9222764" FT /id="VAR_006605" FT VARIANT 414 FT /note="P -> T (in HEMB; Bergamo; increased protein FT abundance; loss of function in blood coagulation; FT dbSNP:rs137852265)" FT /evidence="ECO:0000269|PubMed:12604421, FT ECO:0000269|PubMed:2162822, ECO:0000269|PubMed:25251685" FT /id="VAR_017321" FT VARIANT 419 FT /note="V -> E (in HEMB; moderately severe; FT dbSNP:rs137852280)" FT /evidence="ECO:0000269|PubMed:8076946, FT ECO:0000269|PubMed:8199596" FT /id="VAR_006606" FT VARIANT 424 FT /note="F -> V (in HEMB)" FT /evidence="ECO:0000269|PubMed:9222764" FT /id="VAR_006607" FT VARIANT 426 FT /note="T -> P (in HEMB; severe; Barcelos; FT dbSNP:rs1928129466)" FT /evidence="ECO:0000269|PubMed:8257988" FT /id="VAR_006608" FT VARIANT 430 FT /note="S -> T (in HEMB)" FT /id="VAR_006609" FT VARIANT 431 FT /note="W -> G (in HEMB)" FT /id="VAR_006610" FT VARIANT 431 FT /note="W -> R (in HEMB; moderate)" FT /id="VAR_006611" FT VARIANT 432 FT /note="G -> S (in HEMB; severe; dbSNP:rs1170838100)" FT /id="VAR_006612" FT VARIANT 432 FT /note="G -> V (in HEMB; severe)" FT /evidence="ECO:0000269|PubMed:9600455" FT /id="VAR_006613" FT VARIANT 433 FT /note="E -> A (in HEMB)" FT /id="VAR_006614" FT VARIANT 433 FT /note="E -> K (in HEMB; dbSNP:rs767828752)" FT /id="VAR_006615" FT VARIANT 435 FT /note="C -> Y (in HEMB; dbSNP:rs1385141619)" FT /evidence="ECO:0000269|PubMed:12604421" FT /id="VAR_017364" FT VARIANT 436 FT /note="A -> V (in HEMB; moderately severe; Niigata; FT dbSNP:rs137852266)" FT /evidence="ECO:0000269|PubMed:3243764" FT /id="VAR_006616" FT VARIANT 442 FT /note="G -> E (in HEMB; dbSNP:rs1603267474)" FT /evidence="ECO:0000269|PubMed:12604421" FT /id="VAR_017365" FT VARIANT 442 FT /note="G -> R (in HEMB; severe; Angers; dbSNP:rs137852267)" FT /evidence="ECO:0000269|PubMed:2714791" FT /id="VAR_017322" FT VARIANT 443 FT /note="I -> T (in HEMB; moderately severe; Long Beach, Los FT Angeles and Vancouver; dbSNP:rs137852268)" FT /evidence="ECO:0000269|PubMed:1902289, FT ECO:0000269|PubMed:3401602" FT /id="VAR_017323" FT VARIANT 445 FT /note="T -> TIYT (in HEMB; severe; Lousada)" FT /id="VAR_006617" FT VARIANT 447 FT /note="V -> VYTKV (in HEMB; reduced protein abundance; loss FT of function in blood coagulation)" FT /evidence="ECO:0000269|PubMed:25251685" FT /id="VAR_073983" FT VARIANT 449 FT /note="R -> Q (in HEMB; mild; dbSNP:rs143018900)" FT /evidence="ECO:0000269|PubMed:8076946" FT /id="VAR_006618" FT VARIANT 449 FT /note="R -> W (in HEMB; mild; dbSNP:rs757996262)" FT /evidence="ECO:0000269|PubMed:12604421" FT /id="VAR_006619" FT VARIANT 450 FT /note="Y -> C (in HEMB; severe; dbSNP:rs1243180674)" FT /evidence="ECO:0000269|PubMed:9600455" FT /id="VAR_006620" FT VARIANT 453 FT /note="W -> R (in HEMB; dbSNP:rs137852269)" FT /evidence="ECO:0000269|PubMed:2773937" FT /id="VAR_017324" FT VARIANT 454 FT /note="I -> T (in HEMB; Italy; dbSNP:rs1603267486)" FT /evidence="ECO:0000269|PubMed:9452115" FT /id="VAR_006621" FT VARIANT 461 FT /note="T -> P (in dbSNP:rs4149751)" FT /evidence="ECO:0000269|Ref.7" FT /id="VAR_014308" FT MUTAGEN 305 FT /note="Y->F: Strongly increases enzyme activity with a FT synthetic peptide substrate; when associated with T-311; FT A-365 and T-391." FT /evidence="ECO:0000269|PubMed:12444082" FT MUTAGEN 311 FT /note="K->T: Strongly increases enzyme activity with a FT synthetic peptide substrate; when associated with F-305; FT A-365 and T-391." FT /evidence="ECO:0000269|PubMed:12444082" FT MUTAGEN 312 FT /note="Y->A: Strongly decreases enzyme activity with a FT synthetic peptide substrate." FT /evidence="ECO:0000269|PubMed:12444082" FT MUTAGEN 391 FT /note="Y->T: Strongly increases enzyme activity with a FT synthetic peptide substrate; when associated with F-305; FT T-311 and A-365." FT /evidence="ECO:0000269|PubMed:12444082" FT STRAND 50..52 FT /evidence="ECO:0007829|PDB:1NL0" FT HELIX 60..64 FT /evidence="ECO:0007829|PDB:1NL0" FT STRAND 65..67 FT /evidence="ECO:0007829|PDB:1CFH" FT HELIX 71..75 FT /evidence="ECO:0007829|PDB:1NL0" FT STRAND 78..80 FT /evidence="ECO:0007829|PDB:1NL0" FT HELIX 81..90 FT /evidence="ECO:0007829|PDB:1NL0" FT TURN 96..99 FT /evidence="ECO:0007829|PDB:1EDM" FT STRAND 102..105 FT /evidence="ECO:0007829|PDB:4WMA" FT STRAND 107..111 FT /evidence="ECO:0007829|PDB:1EDM" FT STRAND 114..118 FT /evidence="ECO:0007829|PDB:1EDM" FT TURN 125..128 FT /evidence="ECO:0007829|PDB:4WMA" FT TURN 134..136 FT /evidence="ECO:0007829|PDB:6MV4" FT HELIX 137..140 FT /evidence="ECO:0007829|PDB:5JB9" FT STRAND 142..148 FT /evidence="ECO:0007829|PDB:5JB9" FT TURN 149..151 FT /evidence="ECO:0007829|PDB:5JB9" FT STRAND 152..156 FT /evidence="ECO:0007829|PDB:5JB9" FT STRAND 161..163 FT /evidence="ECO:0007829|PDB:5JB9" FT STRAND 165..168 FT /evidence="ECO:0007829|PDB:2WPI" FT STRAND 170..172 FT /evidence="ECO:0007829|PDB:5JB9" FT STRAND 174..176 FT /evidence="ECO:0007829|PDB:5JB9" FT STRAND 187..189 FT /evidence="ECO:0007829|PDB:2WPJ" FT STRAND 241..248 FT /evidence="ECO:0007829|PDB:5JB9" FT STRAND 252..258 FT /evidence="ECO:0007829|PDB:5JB9" FT STRAND 261..264 FT /evidence="ECO:0007829|PDB:5JB9" FT HELIX 266..268 FT /evidence="ECO:0007829|PDB:5JB9" FT STRAND 269..271 FT /evidence="ECO:0007829|PDB:5JB9" FT STRAND 276..280 FT /evidence="ECO:0007829|PDB:5JB9" FT STRAND 282..286 FT /evidence="ECO:0007829|PDB:6MV4" FT STRAND 292..301 FT /evidence="ECO:0007829|PDB:5JB9" FT TURN 303..306 FT /evidence="ECO:0007829|PDB:5JB9" FT STRAND 307..310 FT /evidence="ECO:0007829|PDB:5JB9" FT TURN 311..314 FT /evidence="ECO:0007829|PDB:5TNT" FT STRAND 317..323 FT /evidence="ECO:0007829|PDB:5JB9" FT STRAND 328..331 FT /evidence="ECO:0007829|PDB:6X5P" FT HELIX 339..347 FT /evidence="ECO:0007829|PDB:5JB9" FT STRAND 350..360 FT /evidence="ECO:0007829|PDB:5JB9" FT STRAND 370..377 FT /evidence="ECO:0007829|PDB:5JB9" FT HELIX 379..384 FT /evidence="ECO:0007829|PDB:5JB9" FT STRAND 394..398 FT /evidence="ECO:0007829|PDB:5JB9" FT STRAND 400..403 FT /evidence="ECO:0007829|PDB:6MV4" FT STRAND 414..419 FT /evidence="ECO:0007829|PDB:5JB9" FT STRAND 422..431 FT /evidence="ECO:0007829|PDB:5JB9" FT STRAND 433..436 FT /evidence="ECO:0007829|PDB:5JB9" FT STRAND 442..446 FT /evidence="ECO:0007829|PDB:5JB9" FT HELIX 447..450 FT /evidence="ECO:0007829|PDB:5JB9" FT HELIX 451..457 FT /evidence="ECO:0007829|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 //