FA9_HUMAN
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 03-AUG-2022, entry version 270.
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 ---------------------------------------------------------------------------
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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 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 AlphaFoldDB; P00740; -.
DR SMR; P00740; -.
DR BioGRID; 108456; 55.
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, 12 O-Linked glycans (6 sites).
DR GlyGen; P00740; 10 sites, 23 N-linked glycans (1 site), 16 O-linked glycans (7 sites).
DR iPTMnet; P00740; -.
DR PhosphoSitePlus; P00740; -.
DR BioMuta; F9; -.
DR CPTAC; non-CPTAC-2647; -.
DR jPOST; P00740; -.
DR MassIVE; P00740; -.
DR PaxDb; P00740; -.
DR PeptideAtlas; P00740; -.
DR PRIDE; P00740; -.
DR ProteomicsDB; 51274; -. [P00740-1]
DR ABCD; P00740; 2 sequenced antibodies.
DR Antibodypedia; 367; 852 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 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; SCTEGYQ; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; P00740; -.
DR TreeFam; TF327329; -.
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-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; 28 hits in 696 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 41 other tissues.
DR Genevisible; P00740; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0016020; C:membrane; IDA:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0032991; C:protein-containing complex; IPI:ComplexPortal.
DR GO; GO:1905370; C:serine-type endopeptidase complex; IC:ComplexPortal.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; NAS:BHF-UCL.
DR GO; GO:0007596; P:blood coagulation; IDA:UniProtKB.
DR GO; GO:0007597; P:blood coagulation, intrinsic pathway; IDA:ComplexPortal.
DR GO; GO:0006508; P:proteolysis; IDA:ComplexPortal.
DR GO; GO:0031638; P:zymogen activation; IDA:ComplexPortal.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 4.10.740.10; -; 1.
DR InterPro; IPR017857; Coagulation_fac-like_Gla_dom.
DR InterPro; IPR035694; Coagulation_factor_IX.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; 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:SF31; PTHR24278:SF31; 1.
DR Pfam; PF00008; EGF; 1.
DR Pfam; PF00594; Gla; 1.
DR Pfam; PF00089; Trypsin; 1.
DR PIRSF; PIRSF001143; Factor_X; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR PRINTS; PR00001; GLABLOOD.
DR SMART; SM00181; EGF; 2.
DR SMART; SM00179; EGF_CA; 1.
DR SMART; SM00069; GLA; 1.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF57630; SSF57630; 1.
DR PROSITE; PS00010; ASX_HYDROXYL; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 2.
DR PROSITE; PS50026; EGF_3; 1.
DR PROSITE; PS01187; EGF_CA; 1.
DR PROSITE; PS00011; GLA_1; 1.
DR PROSITE; PS50998; GLA_2; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Blood coagulation; Calcium;
KW Cleavage on pair of basic residues; 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; unknown pathological significance;
FT decreased 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; unknown pathological significance;
FT no effect 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; unknown pathological significance;
FT no effect 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; unknown pathological significance;
FT decreased 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; unknown pathological significance;
FT decreased 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; unknown pathological significance;
FT decreased 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 IX Padua; 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 /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; A-
FT 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; A-
FT 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; T-
FT 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
