ID FA11_HUMAN Reviewed; 625 AA. AC P03951; D3DP64; Q4W5C2; Q9Y495; DT 23-OCT-1986, integrated into UniProtKB/Swiss-Prot. DT 23-OCT-1986, sequence version 1. DT 20-DEC-2017, entry version 211. DE RecName: Full=Coagulation factor XI; DE Short=FXI; DE EC=3.4.21.27; DE AltName: Full=Plasma thromboplastin antecedent; DE Short=PTA; DE Contains: DE RecName: Full=Coagulation factor XIa heavy chain; DE Contains: DE RecName: Full=Coagulation factor XIa light chain; DE Flags: Precursor; GN Name=F11; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=3636155; DOI=10.1021/bi00357a018; RA Fujikawa K., Chung D.W., Hendrickson L.E., Davie E.W.; RT "Amino acid sequence of human factor XI, a blood coagulation factor RT with four tandem repeats that are highly homologous with plasma RT prekallikrein."; RL Biochemistry 25:2417-2424(1986). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RX PubMed=2827746; DOI=10.1021/bi00397a004; RA Asakai R., Davie E.W., Chung D.W.; RT "Organization of the gene for human factor XI."; RL Biochemistry 26:7221-7228(1987). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=9593722; DOI=10.1074/jbc.273.22.13787; RA Hsu T.-C., Shore S.K., Seshsmma T., Bagasra O., Walsh P.N.; RT "Molecular cloning of platelet factor XI, an alternative splicing RT product of the plasma factor XI gene."; RL J. Biol. Chem. 273:13787-13793(1998). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT PHE-339. RG SeattleSNPs variation discovery resource; RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 4."; RL Nature 434:724-731(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP PARTIAL PROTEIN SEQUENCE, AND DISULFIDE BONDS. RX PubMed=1998667; DOI=10.1021/bi00222a008; RA McMullen B.A., Fujikawa K., Davie E.W.; RT "Location of the disulfide bonds in human coagulation factor XI: the RT presence of tandem apple domains."; RL Biochemistry 30:2056-2060(1991). RN [9] RP ENZYME REGULATION, AND HETERODIMER WITH SERPINA5. RX PubMed=2844223; DOI=10.1021/bi00412a005; RA Meijers J.C., Kanters D.H., Vlooswijk R.A., van Erp H.E., Hessing M., RA Bouma B.N.; RT "Inactivation of human plasma kallikrein and factor XIa by protein C RT inhibitor."; RL Biochemistry 27:4231-4237(1988). RN [10] RP HEPARIN-BINDING SITE. RX PubMed=11412111; DOI=10.1021/bi0027433; RA Badellino K.O., Walsh P.N.; RT "Localization of a heparin binding site in the catalytic domain of RT factor XIa."; RL Biochemistry 40:7569-7580(2001). RN [11] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-126; ASN-450 AND ASN-491. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., RA Moore R.J., Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [12] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-450 AND ASN-491. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of RT multiple enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [13] RP GLYCOSYLATION AT ASN-90; ASN-126; ASN-163; ASN-450 AND ASN-491, RP PARTIAL PROTEIN SEQUENCE, IDENTIFICATION BY MASS SPECTROMETRY, AND RP STRUCTURE OF CARBOHYDRATES. RX PubMed=25092234; DOI=10.1002/pmic.201400038; RA Faid V., Denguir N., Chapuis V., Bihoreau N., Chevreux G.; RT "Site-specific N-glycosylation analysis of human factor XI: RT Identification of a noncanonical NXC glycosite."; RL Proteomics 14:2460-2470(2014). RN [14] RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 388-625 IN COMPLEX WITH RP INHIBITOR, AND DISULFIDE BONDS. RX PubMed=18510371; DOI=10.1021/jm800314b; RA Buchanan M.S., Carroll A.R., Wessling D., Jobling M., Avery V.M., RA Davis R.A., Feng Y., Xue Y., Oster L., Fex T., Deinum J., Hooper J.N., RA Quinn R.J.; RT "Clavatadine A, a natural product with selective recognition and RT irreversible inhibition of factor XIa."; RL J. Med. Chem. 51:3583-3587(2008). RN [15] RP VARIANT FA11D LEU-301. RX PubMed=2813350; DOI=10.1073/pnas.86.20.7667; RA Asakai R., Chung D.W., Ratnoff O.D., Davie E.W.; RT "Factor XI (plasma thromboplastin antecedent) deficiency in Ashkenazi RT Jews is a bleeding disorder that can result from three types of point RT mutations."; RL Proc. Natl. Acad. Sci. U.S.A. 86:7667-7671(1989). RN [16] RP VARIANT FA11D LEU-301. RX PubMed=1547342; RA Meijers J.C., Davie E.W., Chung D.W.; RT "Expression of human blood coagulation factor XI: characterization of RT the defect in factor XI type III deficiency."; RL Blood 79:1435-1440(1992). RN [17] RP VARIANTS FA11D HIS-34; PRO-320; ILE-322 AND LYS-341. RX PubMed=7888672; RA Pugh R.E., McVey J.H., Tuddenham E.G., Hancock J.F.; RT "Six point mutations that cause factor XI deficiency."; RL Blood 85:1509-1516(1995). RN [18] RP VARIANT FA11D VAL-460. RX PubMed=7669672; DOI=10.1111/j.1365-2141.1995.tb05215.x; RA Imanaka Y., Lal K., Nishimura T., Bolton-Maggs P.H., Tuddenham E.G., RA McVey J.H.; RT "Identification of two novel mutations in non-Jewish factor XI RT deficiency."; RL Br. J. Haematol. 90:916-920(1995). RN [19] RP VARIANT FA11D ASN-404. RX PubMed=9401068; DOI=10.1046/j.1365-2141.1997.4343244.x; RA Wistinghausen B., Reischer A., Oddoux C., Ostrer H., Nardi M., RA Karpatkin M.; RT "Severe factor XI deficiency in an Arab family associated with a novel RT mutation in exon 11."; RL Br. J. Haematol. 99:575-577(1997). RN [20] RP VARIANT FA11D ASN-266, AND VARIANT ARG-244. RX PubMed=9787168; RA Martincic D., Zimmerman S.A., Ware R.E., Sun M.-F., Whitlock J.A., RA Gailani D.; RT "Identification of mutations and polymorphisms in the factor XI genes RT of an African American family by dideoxyfingerprinting."; RL Blood 92:3309-3317(1998). RN [21] RP ERRATUM. RA Martincic D., Zimmerman S.A., Ware R.E., Sun M.-F., Whitlock J.A., RA Gailani D.; RL Blood 93:1786-1786(1999). RN [22] RP VARIANT FA11D CYS-246. RX PubMed=10027710; DOI=10.1046/j.1365-2141.1999.01150.x; RA Alhaq A., Mitchell M., Sethi M., Rahman S., Flynn G., Boulton P., RA Caeno G., Smith M., Savidge G.; RT "Identification of a novel mutation in a non-Jewish factor XI RT deficient kindred."; RL Br. J. Haematol. 104:44-49(1999). RN [23] RP VARIANTS FA11D CYS-326; VAL-430 ILE-493 AND ARG-594. RX PubMed=10606881; DOI=10.1046/j.1365-2141.1999.01769.x; RA Mitchell M., Cutler J., Thompson S., Moore G., Jenkins Ap Rees E., RA Smith M., Savidge G., Alhaq A.; RT "Heterozygous factor XI deficiency associated with three novel RT mutations."; RL Br. J. Haematol. 107:763-765(1999). RN [24] RP VARIANTS LEU-66; ARG-244; PHE-308 AND PHE-339. RX PubMed=10391209; DOI=10.1038/10290; RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RT "Characterization of single-nucleotide polymorphisms in coding regions RT of human genes."; RL Nat. Genet. 22:231-238(1999). RN [25] RP ERRATUM. RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RL Nat. Genet. 23:373-373(1999). RN [26] RP VARIANTS FA11D ARG-56; TYR-255 AND HIS-511, VARIANT PHE-339, AND RP CHARACTERIZATION OF VARIANTS FA11D ARG-56; TYR-255 AND HIS-511. RX PubMed=11895778; DOI=10.1182/blood.V99.7.2448; RA Zivelin A., Bauduer F., Ducout L., Peretz H., Rosenberg N., Yatuv R., RA Seligsohn U.; RT "Factor XI deficiency in French Basques is caused predominantly by an RT ancestral Cys38Arg mutation in the factor XI gene."; RL Blood 99:2448-2454(2002). RN [27] RP VARIANTS FA11D VAL-418 AND SER-587, AND CHARACTERIZATION OF VARIANTS RP FA11D VAL-418 AND SER-587. RX PubMed=15026311; DOI=10.1182/blood-2003-10-3530; RA Kravtsov D.V., Wu W., Meijers J.C.M., Sun M.-F., Blinder M.A., RA Dang T.P., Wang H., Gailani D.; RT "Dominant factor XI deficiency caused by mutations in the factor XI RT catalytic domain."; RL Blood 104:128-134(2004). RN [28] RP VARIANT FA11D ILE-270, AND CHARACTERIZATION OF VARIANT F11 DEFICIENCY RP ILE-270. RX PubMed=15180874; DOI=10.1111/j.1365-2141.2004.04979.x; RA Dai L., Mitchell M., Carson P., Creagh D., Cutler J., Savidge G., RA Alhaq A.; RT "Severe factor XI deficiency caused by compound heterozygosity."; RL Br. J. Haematol. 125:817-818(2004). RN [29] RP VARIANTS FA11D PHE-46; ARG-101; CYS-151; GLU-263; VAL-430; LEU-538; RP LYS-565 AND SER-618. RX PubMed=15953011; DOI=10.1111/j.1365-2141.2005.05536.x; RA Hill M., McLeod F., Franks H., Gordon B., Dolan G.; RT "Genetic analysis in FXI deficiency: six novel mutations and the use RT of a polymerase chain reaction-based test to define a whole gene RT deletion."; RL Br. J. Haematol. 129:825-829(2005). RN [30] RP VARIANTS FA11D TYR-140; LYS-315 AND LYS-597. RX PubMed=16607084; DOI=10.1097/01.mbc.0000198054.50257.96; RA Quelin F., Mathonnet F., Potentini-Esnault C., Trigui N., Peynet J., RA Bastenaire B., Guillon L., Bigel M.L., Sauger A., Mazurier C., RA de Mazancourt P.; RT "Identification of five novel mutations in the factor XI gene (F11) of RT patients with factor XI deficiency."; RL Blood Coagul. Fibrinolysis 17:69-73(2006). RN [31] RP VARIANTS FA11D ILE-51; PRO-51; ILE-331; PRO-360; PRO-503 AND HIS-608. RX PubMed=18005151; DOI=10.1111/j.1365-2516.2007.01593.x; RA Fard-Esfahani P., Lari G.R., Ravanbod S., Mirkhani F., Allahyari M., RA Rassoulzadegan M., Ala F.; RT "Seven novel point mutations in the F11 gene in Iranian FXI-deficient RT patients."; RL Haemophilia 14:91-95(2008). RN [32] RP VARIANTS FA11D ARG-32; GLN-53; THR-252; ARG-401 AND GLU-526. RX PubMed=21668437; DOI=10.1111/j.1399-0004.2011.01732.x; RA Kim J., Song J., Lyu C., Kim Y., Oh S., Choi Y., Yoo J., Choi J., RA Kim H., Lee K.A.; RT "Population-specific spectrum of the F11 mutations in Koreans: RT evidence for a founder effect."; RL Clin. Genet. 82:180-186(2012). RN [33] RP VARIANTS FA11D THR-43; LEU-241 AND MET-403, AND CHARACTERIZATION OF RP VARIANTS FA11D THR-43; LEU-241 AND MET-403. RX PubMed=21457405; DOI=10.1111/j.1365-2516.2011.02519.x; RA Dai L., Rangarajan S., Mitchell M.; RT "Three dominant-negative mutations in factor XI-deficient patients."; RL Haemophilia 17:E919-E922(2011). RN [34] RP VARIANT FA11D GLY-506. RX PubMed=22016685; DOI=10.3343/kjlm.2011.31.4.290; RA Lee J.H., Cho H.S., Hyun M.S., Kim H.Y., Kim H.J.; RT "A novel missense mutation Asp506Gly in exon 13 of the F11 gene in an RT asymptomatic Korean woman with mild factor XI deficiency."; RL Korean J. Lab. Med. 31:290-293(2011). RN [35] RP VARIANT FA11D SER-481. RX PubMed=22322133; DOI=10.1097/MBC.0b013e32834ea02a; RA Tirefort Y., Uhr M.R., Neerman-Arbez M., de Moerloose P.; RT "Identification of a novel F11 missense mutation (Ile463Ser) in a RT family with congenital factor XI deficiency."; RL Blood Coagul. Fibrinolysis 23:251-252(2012). RN [36] RP VARIANT FA11D LYS-454. RX PubMed=21999818; DOI=10.1111/j.1600-0609.2011.01723.x; RA Girolami A., Scarparo P., Bonamigo E., Santarossa L., Cristiani A., RA Moro S., Lombardi A.M.; RT "A cluster of factor XI-deficient patients due to a new mutation (Ile RT 436 Lys) in northeastern Italy."; RL Eur. J. Haematol. 88:229-236(2012). RN [37] RP VARIANTS FA11D PRO-51; ARG-56; VAL-63; TYR-222; GLN-228; CYS-276; RP ASP-277; PHE-514; LEU-575 AND LYS-597. RX PubMed=22159456; DOI=10.1160/TH11-06-0415; RA Gueguen P., Chauvin A., Quemener-Redon S., Pan-Petesch B., Ferec C., RA Abgrall J.F., Le Marechal C.; RT "Revisiting the molecular epidemiology of factor XI deficiency: nine RT new mutations and an original large 4qTer deletion in western Brittany RT (France)."; RL Thromb. Haemost. 107:44-50(2012). RN [38] RP VARIANTS FA11D SER-30; THR-109; ASN-216; LYS-315; LYS-543 AND ARG-552. RX PubMed=25158988; DOI=10.1097/MBC.0000000000000185; RA Keskin E.Y., Guersel T., Kaya Z., Dai L., Kocak U., Yenicesu I., RA Belen F.B., Mitchell M.; RT "Molecular basis and bleeding manifestations of factor XI deficiency RT in 11 Turkish families."; RL Blood Coagul. Fibrinolysis 26:63-68(2015). CC -!- FUNCTION: Factor XI triggers the middle phase of the intrinsic CC pathway of blood coagulation by activating factor IX. CC -!- CATALYTIC ACTIVITY: Selective cleavage of Arg-|-Ala and Arg-|-Val CC bonds in factor IX to form factor IXa. CC -!- ENZYME REGULATION: Inhibited by SERPINA5. CC {ECO:0000269|PubMed:2844223}. CC -!- SUBUNIT: Homodimer; disulfide-linked. Forms a heterodimer with CC SERPINA5. After activation the heavy and light chains are also CC linked by a disulfide bond. {ECO:0000269|PubMed:18510371, CC ECO:0000269|PubMed:1998667}. CC -!- INTERACTION: CC P23827:eco (xeno); NbExp=3; IntAct=EBI-1041019, EBI-1029159; CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P03951-1; Sequence=Displayed; CC Name=2; Synonyms=Platelet; CC IsoId=P03951-2; Sequence=VSP_005388; CC -!- TISSUE SPECIFICITY: Isoform 2 is produced by platelets and CC megakaryocytes but absent from other blood cells. CC -!- PTM: N-glycosylated on both chains. N-glycosylated sites mainly CC consist of nonfucosylated sialylated biantennary (in high CC abundance) and/or triantennary (in low abundance) complex CC structures. Glycosylation at Asn-163 uses a rare non-canonical CC Asn-X-Cys glycosite. {ECO:0000269|PubMed:25092234}. CC -!- PTM: Activated by factor XIIa (or XII), which cleaves each CC polypeptide after Arg-387 into the light chain, which contains the CC active site, and the heavy chain, which associates with high CC molecular weight (HMW) kininogen. CC -!- DISEASE: Factor XI deficiency (FA11D) [MIM:612416]: A hemorrhagic CC disease characterized by reduced levels and activity of factor XI CC resulting in moderate bleeding symptoms, usually occurring after CC trauma or surgery. Patients usually do not present spontaneous CC bleeding but women can present with menorrhagia. Hemorrhages are CC usually moderate. {ECO:0000269|PubMed:10027710, CC ECO:0000269|PubMed:10606881, ECO:0000269|PubMed:11895778, CC ECO:0000269|PubMed:15026311, ECO:0000269|PubMed:15180874, CC ECO:0000269|PubMed:1547342, ECO:0000269|PubMed:15953011, CC ECO:0000269|PubMed:16607084, ECO:0000269|PubMed:18005151, CC ECO:0000269|PubMed:21457405, ECO:0000269|PubMed:21668437, CC ECO:0000269|PubMed:21999818, ECO:0000269|PubMed:22016685, CC ECO:0000269|PubMed:22159456, ECO:0000269|PubMed:22322133, CC ECO:0000269|PubMed:25158988, ECO:0000269|PubMed:2813350, CC ECO:0000269|PubMed:7669672, ECO:0000269|PubMed:7888672, CC ECO:0000269|PubMed:9401068, ECO:0000269|PubMed:9787168}. Note=The CC disease is caused by mutations affecting the gene represented in CC this entry. CC -!- SIMILARITY: Belongs to the peptidase S1 family. Plasma kallikrein CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00274}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Factor XI entry; CC URL="https://en.wikipedia.org/wiki/Factor_XI"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/f11/"; CC -!- WEB RESOURCE: Name=Mendelian genes Coagulation factor XI (F11); CC Note=Leiden Open Variation Database (LOVD); CC URL="http://www.lovd.nl/F11"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M13142; AAA52487.1; -; mRNA. DR EMBL; M20218; AAA51985.1; -; Genomic_DNA. DR EMBL; M18296; AAA51985.1; JOINED; Genomic_DNA. DR EMBL; M21184; AAA51985.1; JOINED; Genomic_DNA. DR EMBL; M18298; AAA51985.1; JOINED; Genomic_DNA. DR EMBL; M18299; AAA51985.1; JOINED; Genomic_DNA. DR EMBL; M18300; AAA51985.1; JOINED; Genomic_DNA. DR EMBL; M18301; AAA51985.1; JOINED; Genomic_DNA. DR EMBL; M18302; AAA51985.1; JOINED; Genomic_DNA. DR EMBL; M18303; AAA51985.1; JOINED; Genomic_DNA. DR EMBL; M18304; AAA51985.1; JOINED; Genomic_DNA. DR EMBL; M19417; AAA51985.1; JOINED; Genomic_DNA. DR EMBL; M20217; AAA51985.1; JOINED; Genomic_DNA. DR EMBL; AF045649; AAC24506.1; -; mRNA. DR EMBL; AY191837; AAN85554.1; -; Genomic_DNA. DR EMBL; AC110771; AAY40901.1; -; Genomic_DNA. DR EMBL; CH471056; EAX04621.1; -; Genomic_DNA. DR EMBL; BC119014; AAI19015.1; -; mRNA. DR EMBL; BC122863; AAI22864.1; -; mRNA. DR CCDS; CCDS3847.1; -. [P03951-1] DR PIR; A27431; KFHU1. DR RefSeq; NP_000119.1; NM_000128.3. [P03951-1] DR UniGene; Hs.1430; -. DR PDB; 1XX9; X-ray; 2.20 A; A/B=388-625. DR PDB; 1XXD; X-ray; 2.91 A; A/B=388-625. DR PDB; 1XXF; X-ray; 2.60 A; A/B=388-625. DR PDB; 1ZHM; X-ray; 1.96 A; A=388-624. DR PDB; 1ZHP; X-ray; 2.70 A; A=388-625. DR PDB; 1ZHR; X-ray; 1.73 A; A=388-625. DR PDB; 1ZJD; X-ray; 2.60 A; A=388-624. DR PDB; 1ZLR; X-ray; 2.50 A; A=388-624. DR PDB; 1ZMJ; X-ray; 2.00 A; A=388-624. DR PDB; 1ZML; X-ray; 2.25 A; A=388-625. DR PDB; 1ZMN; X-ray; 2.05 A; A=388-625. DR PDB; 1ZOM; X-ray; 2.25 A; A=388-624. DR PDB; 1ZPB; X-ray; 2.10 A; A=388-624. DR PDB; 1ZPC; X-ray; 2.60 A; A=388-624. DR PDB; 1ZPZ; X-ray; 2.50 A; A=388-625. DR PDB; 1ZRK; X-ray; 2.30 A; A=388-625. DR PDB; 1ZSJ; X-ray; 1.90 A; A=388-625. DR PDB; 1ZSK; X-ray; 1.90 A; A=388-625. DR PDB; 1ZSL; X-ray; 2.05 A; A=388-625. DR PDB; 1ZTJ; X-ray; 2.05 A; A=388-624. DR PDB; 1ZTK; X-ray; 2.50 A; A=388-624. DR PDB; 1ZTL; X-ray; 2.60 A; A=388-624. DR PDB; 2F83; X-ray; 2.87 A; A=1-625. DR PDB; 2FDA; X-ray; 2.00 A; A=388-625. DR PDB; 2J8J; NMR; -; A/B=290-379. DR PDB; 2J8L; NMR; -; A/B=290-379. DR PDB; 3BG8; X-ray; 1.60 A; A=388-625. DR PDB; 3SOR; X-ray; 1.80 A; A=388-625. DR PDB; 3SOS; X-ray; 2.58 A; A=388-625. DR PDB; 4CR5; X-ray; 2.00 A; A=388-625. DR PDB; 4CR9; X-ray; 1.70 A; A=388-625. DR PDB; 4CRA; X-ray; 1.80 A; A=388-625. DR PDB; 4CRB; X-ray; 1.85 A; A=388-625. DR PDB; 4CRC; X-ray; 1.60 A; A=388-625. DR PDB; 4CRD; X-ray; 2.10 A; A=388-625. DR PDB; 4CRE; X-ray; 1.73 A; A=388-625. DR PDB; 4CRF; X-ray; 2.30 A; A=388-625. DR PDB; 4CRG; X-ray; 1.25 A; A=388-625. DR PDB; 4D76; X-ray; 1.77 A; A=388-625. DR PDB; 4D7F; X-ray; 1.62 A; A=388-625. DR PDB; 4D7G; X-ray; 2.33 A; A=388-625. DR PDB; 4NA7; X-ray; 2.80 A; A=388-625. DR PDB; 4NA8; X-ray; 2.30 A; A=388-625. DR PDB; 4TY6; X-ray; 1.85 A; A=388-625, H=375-387. DR PDB; 4TY7; X-ray; 2.09 A; A=388-625. DR PDB; 4WXI; X-ray; 2.60 A; A=388-625. DR PDB; 4X6M; X-ray; 2.40 A; A=388-625. DR PDB; 4X6N; X-ray; 2.10 A; A=388-625, H=375-387. DR PDB; 4X6O; X-ray; 2.10 A; A=388-625. DR PDB; 4X6P; X-ray; 1.93 A; A/B=388-625. DR PDB; 4Y8X; X-ray; 1.90 A; A=388-625. DR PDB; 4Y8Y; X-ray; 2.60 A; A=388-625. DR PDB; 4Y8Z; X-ray; 2.20 A; A=388-625. DR PDB; 5E2O; X-ray; 2.08 A; A=388-625. DR PDB; 5E2P; X-ray; 2.11 A; A=388-625. DR PDB; 5EOD; X-ray; 3.10 A; A=20-625. DR PDB; 5EOK; X-ray; 2.80 A; A=20-625. DR PDB; 5EXL; X-ray; 2.30 A; A=388-625. DR PDB; 5EXM; X-ray; 2.09 A; A=388-625. DR PDB; 5EXN; X-ray; 1.49 A; A=388-625. DR PDB; 5I25; X-ray; 2.85 A; A=19-625. DR PDB; 5Q0D; X-ray; 2.12 A; A=388-625. DR PDB; 5Q0E; X-ray; 2.12 A; A=388-625. DR PDB; 5Q0F; X-ray; 2.12 A; A=388-625. DR PDB; 5Q0G; X-ray; 2.60 A; A=388-625. DR PDB; 5Q0H; X-ray; 2.50 A; A=388-625. DR PDB; 5QCK; X-ray; 2.64 A; A=388-625. DR PDB; 5QCL; X-ray; 2.11 A; A=388-625. DR PDB; 5QCM; X-ray; 2.20 A; A=388-625. DR PDB; 5QCN; X-ray; 2.30 A; A=388-625. DR PDB; 5TKS; X-ray; 1.55 A; A=388-625. DR PDB; 5TKT; X-ray; 2.12 A; A=388-625. DR PDB; 5TKU; X-ray; 2.12 A; A=388-625. DR PDB; 5WB6; X-ray; 2.35 A; A=388-625. DR PDBsum; 1XX9; -. DR PDBsum; 1XXD; -. DR PDBsum; 1XXF; -. DR PDBsum; 1ZHM; -. DR PDBsum; 1ZHP; -. DR PDBsum; 1ZHR; -. DR PDBsum; 1ZJD; -. DR PDBsum; 1ZLR; -. DR PDBsum; 1ZMJ; -. DR PDBsum; 1ZML; -. DR PDBsum; 1ZMN; -. DR PDBsum; 1ZOM; -. DR PDBsum; 1ZPB; -. DR PDBsum; 1ZPC; -. DR PDBsum; 1ZPZ; -. DR PDBsum; 1ZRK; -. DR PDBsum; 1ZSJ; -. DR PDBsum; 1ZSK; -. DR PDBsum; 1ZSL; -. DR PDBsum; 1ZTJ; -. DR PDBsum; 1ZTK; -. DR PDBsum; 1ZTL; -. DR PDBsum; 2F83; -. DR PDBsum; 2FDA; -. DR PDBsum; 2J8J; -. DR PDBsum; 2J8L; -. DR PDBsum; 3BG8; -. DR PDBsum; 3SOR; -. DR PDBsum; 3SOS; -. DR PDBsum; 4CR5; -. DR PDBsum; 4CR9; -. DR PDBsum; 4CRA; -. DR PDBsum; 4CRB; -. DR PDBsum; 4CRC; -. DR PDBsum; 4CRD; -. DR PDBsum; 4CRE; -. DR PDBsum; 4CRF; -. DR PDBsum; 4CRG; -. DR PDBsum; 4D76; -. DR PDBsum; 4D7F; -. DR PDBsum; 4D7G; -. DR PDBsum; 4NA7; -. DR PDBsum; 4NA8; -. DR PDBsum; 4TY6; -. DR PDBsum; 4TY7; -. DR PDBsum; 4WXI; -. DR PDBsum; 4X6M; -. DR PDBsum; 4X6N; -. DR PDBsum; 4X6O; -. DR PDBsum; 4X6P; -. DR PDBsum; 4Y8X; -. DR PDBsum; 4Y8Y; -. DR PDBsum; 4Y8Z; -. DR PDBsum; 5E2O; -. DR PDBsum; 5E2P; -. DR PDBsum; 5EOD; -. DR PDBsum; 5EOK; -. DR PDBsum; 5EXL; -. DR PDBsum; 5EXM; -. DR PDBsum; 5EXN; -. DR PDBsum; 5I25; -. DR PDBsum; 5Q0D; -. DR PDBsum; 5Q0E; -. DR PDBsum; 5Q0F; -. DR PDBsum; 5Q0G; -. DR PDBsum; 5Q0H; -. DR PDBsum; 5QCK; -. DR PDBsum; 5QCL; -. DR PDBsum; 5QCM; -. DR PDBsum; 5QCN; -. DR PDBsum; 5TKS; -. DR PDBsum; 5TKT; -. DR PDBsum; 5TKU; -. DR PDBsum; 5WB6; -. DR ProteinModelPortal; P03951; -. DR SMR; P03951; -. DR BioGrid; 108458; 6. DR DIP; DIP-29085N; -. DR IntAct; P03951; 1. DR STRING; 9606.ENSP00000384957; -. DR BindingDB; P03951; -. DR ChEMBL; CHEMBL2820; -. DR DrugBank; DB07022; 3-HYDROXYPROPYL 3-[({7-[AMINO(IMINO)METHYL]-1-NAPHTHYL}AMINO)CARBONYL]BENZENESULFONATE. DR DrugBank; DB07299; 4-METHYL-PENTANOIC ACID {1-[4-GUANIDINO-1-(THIAZOLE-2-CARBONYL)-BUTYLCARBAMOYL]-2-METHYL-PROPYL}-AMIDE. DR DrugBank; DB07074; 6-CARBAMIMIDOYL-4-(3-HYDROXY-2-METHYL-BENZOYLAMINO)-NAPHTHALENE-2-CARBOXYLIC ACID METHYL ESTER. DR DrugBank; DB06404; C1 Esterase Inhibitor (Human). DR DrugBank; DB09228; C1 Esterase Inhibitor (Recombinant). DR DrugBank; DB00100; Coagulation Factor IX (Recombinant). DR DrugBank; DB07212; N-(7-CARBAMIMIDOYL-NAPHTHALEN-1-YL)-3-HYDROXY-2-METHYL-BENZAMIDE. DR GuidetoPHARMACOLOGY; 2360; -. DR MEROPS; S01.213; -. DR iPTMnet; P03951; -. DR PhosphoSitePlus; P03951; -. DR BioMuta; F11; -. DR DMDM; 119762; -. DR PaxDb; P03951; -. DR PeptideAtlas; P03951; -. DR PRIDE; P03951; -. DR Ensembl; ENST00000264692; ENSP00000264692; ENSG00000088926. [P03951-2] DR Ensembl; ENST00000403665; ENSP00000384957; ENSG00000088926. [P03951-1] DR GeneID; 2160; -. DR KEGG; hsa:2160; -. DR UCSC; uc003iza.2; human. [P03951-1] DR CTD; 2160; -. DR DisGeNET; 2160; -. DR EuPathDB; HostDB:ENSG00000088926.13; -. DR GeneCards; F11; -. DR HGNC; HGNC:3529; F11. DR HPA; HPA039808; -. DR MalaCards; F11; -. DR MIM; 264900; gene. DR MIM; 612416; phenotype. DR neXtProt; NX_P03951; -. DR OpenTargets; ENSG00000088926; -. DR Orphanet; 329; Congenital factor XI deficiency. DR PharmGKB; PA27941; -. DR eggNOG; KOG3627; Eukaryota. DR eggNOG; COG5640; LUCA. DR GeneTree; ENSGT00760000118962; -. DR HOGENOM; HOG000112467; -. DR HOVERGEN; HBG000399; -. DR InParanoid; P03951; -. DR KO; K01323; -. DR OMA; GWGYRKL; -. DR OrthoDB; EOG091G0AH5; -. DR PhylomeDB; P03951; -. DR TreeFam; TF343687; -. DR BRENDA; 3.4.21.27; 2681. DR Reactome; R-HSA-140837; Intrinsic Pathway of Fibrin Clot Formation. DR SABIO-RK; P03951; -. DR ChiTaRS; F11; human. DR EvolutionaryTrace; P03951; -. DR GeneWiki; Factor_XI; -. DR GenomeRNAi; 2160; -. DR PMAP-CutDB; P03951; -. DR PRO; PR:P03951; -. DR Proteomes; UP000005640; Chromosome 4. DR Bgee; ENSG00000088926; -. DR CleanEx; HS_F11; -. DR ExpressionAtlas; P03951; baseline and differential. DR Genevisible; P03951; HS. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL. DR GO; GO:0016020; C:membrane; NAS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0070009; F:serine-type aminopeptidase activity; IEA:Ensembl. DR GO; GO:0004252; F:serine-type endopeptidase activity; TAS:ProtInc. DR GO; GO:0007596; P:blood coagulation; IDA:BHF-UCL. DR GO; GO:0007597; P:blood coagulation, intrinsic pathway; TAS:Reactome. DR GO; GO:0031639; P:plasminogen activation; IDA:BHF-UCL. DR GO; GO:0051919; P:positive regulation of fibrinolysis; IDA:BHF-UCL. DR CDD; cd00190; Tryp_SPc; 1. DR InterPro; IPR000177; Apple. DR InterPro; IPR035696; Coagulation_factor_XI. DR InterPro; IPR003609; Pan_app. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR001314; Peptidase_S1A. DR InterPro; IPR001254; Trypsin_dom. DR InterPro; IPR018114; TRYPSIN_HIS. DR InterPro; IPR033116; TRYPSIN_SER. DR PANTHER; PTHR44459:SF1; PTHR44459:SF1; 1. DR Pfam; PF00024; PAN_1; 4. DR Pfam; PF00089; Trypsin; 1. DR PRINTS; PR00005; APPLEDOMAIN. DR PRINTS; PR00722; CHYMOTRYPSIN. DR SMART; SM00223; APPLE; 4. DR SMART; SM00020; Tryp_SPc; 1. DR SUPFAM; SSF50494; SSF50494; 1. DR PROSITE; PS00495; APPLE; 4. DR PROSITE; PS50948; PAN; 4. 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; KW Complete proteome; Direct protein sequencing; Disease mutation; KW Disulfide bond; Glycoprotein; Hemostasis; Heparin-binding; Hydrolase; KW Polymorphism; Protease; Reference proteome; Repeat; Secreted; KW Serine protease; Signal. FT SIGNAL 1 18 FT CHAIN 19 387 Coagulation factor XIa heavy chain. FT /FTId=PRO_0000027825. FT CHAIN 388 625 Coagulation factor XIa light chain. FT /FTId=PRO_0000027826. FT DOMAIN 20 103 Apple 1. {ECO:0000255|PROSITE- FT ProRule:PRU00315}. FT DOMAIN 110 193 Apple 2. {ECO:0000255|PROSITE- FT ProRule:PRU00315}. FT DOMAIN 200 283 Apple 3. {ECO:0000255|PROSITE- FT ProRule:PRU00315}. FT DOMAIN 291 374 Apple 4. {ECO:0000255|PROSITE- FT ProRule:PRU00315}. FT DOMAIN 388 623 Peptidase S1. {ECO:0000255|PROSITE- FT ProRule:PRU00274}. FT REGION 547 550 Heparin-binding. FT ACT_SITE 431 431 Charge relay system. FT ACT_SITE 480 480 Charge relay system. FT ACT_SITE 575 575 Charge relay system. FT CARBOHYD 90 90 N-linked (GlcNAc...) (complex) FT asparagine. FT {ECO:0000269|PubMed:25092234}. FT CARBOHYD 126 126 N-linked (GlcNAc...) (complex) FT asparagine. {ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:25092234}. FT CARBOHYD 163 163 N-linked (GlcNAc...) (complex) FT asparagine; atypical. FT {ECO:0000269|PubMed:25092234}. FT CARBOHYD 353 353 N-linked (GlcNAc...) asparagine. FT CARBOHYD 450 450 N-linked (GlcNAc...) (complex) FT asparagine. {ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:25092234}. FT CARBOHYD 491 491 N-linked (GlcNAc...) (complex) FT asparagine. {ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:1998667, FT ECO:0000269|PubMed:25092234}. FT DISULFID 20 103 {ECO:0000255}. FT DISULFID 29 29 Interchain. FT DISULFID 46 76 {ECO:0000269|PubMed:1998667}. FT DISULFID 50 56 {ECO:0000269|PubMed:1998667}. FT DISULFID 110 193 {ECO:0000269|PubMed:1998667}. FT DISULFID 136 165 {ECO:0000269|PubMed:1998667}. FT DISULFID 140 146 {ECO:0000269|PubMed:1998667}. FT DISULFID 200 283 FT DISULFID 226 255 {ECO:0000269|PubMed:1998667}. FT DISULFID 230 236 {ECO:0000269|PubMed:1998667}. FT DISULFID 291 374 {ECO:0000269|PubMed:1998667}. FT DISULFID 317 346 {ECO:0000269|PubMed:1998667}. FT DISULFID 321 327 {ECO:0000269|PubMed:1998667}. FT DISULFID 339 339 Interchain. {ECO:0000255}. FT DISULFID 380 500 Interchain (between heavy and light FT chains). FT DISULFID 416 432 {ECO:0000269|PubMed:1998667}. FT DISULFID 514 581 FT DISULFID 545 560 {ECO:0000269|PubMed:1998667}. FT DISULFID 571 599 FT VAR_SEQ 109 162 Missing (in isoform 2). FT {ECO:0000303|PubMed:9593722}. FT /FTId=VSP_005388. FT VARIANT 30 30 F -> S (in FA11D). FT {ECO:0000269|PubMed:25158988}. FT /FTId=VAR_076515. FT VARIANT 32 32 G -> R (in FA11D; dbSNP:rs281875259). FT {ECO:0000269|PubMed:21668437}. FT /FTId=VAR_067929. FT VARIANT 34 34 D -> H (in FA11D; dbSNP:rs281875267). FT {ECO:0000269|PubMed:7888672}. FT /FTId=VAR_012085. FT VARIANT 43 43 A -> T (in FA11D; dominant-negative FT mutation that results in severely FT decreased protein secretion; FT dbSNP:rs281875264). FT {ECO:0000269|PubMed:21457405}. FT /FTId=VAR_067930. FT VARIANT 46 46 C -> F (in FA11D; dbSNP:rs281875271). FT {ECO:0000269|PubMed:15953011}. FT /FTId=VAR_054894. FT VARIANT 51 51 T -> I (in FA11D; dbSNP:rs281875252). FT {ECO:0000269|PubMed:18005151}. FT /FTId=VAR_067931. FT VARIANT 51 51 T -> P (in FA11D; dbSNP:rs281875243). FT {ECO:0000269|PubMed:18005151, FT ECO:0000269|PubMed:22159456}. FT /FTId=VAR_067932. FT VARIANT 53 53 H -> Q (in FA11D; dbSNP:rs281875261). FT {ECO:0000269|PubMed:21668437}. FT /FTId=VAR_067933. FT VARIANT 56 56 C -> R (in FA11D; secretion of the mutant FT protein is impaired; dbSNP:rs121965069). FT {ECO:0000269|PubMed:11895778, FT ECO:0000269|PubMed:22159456}. FT /FTId=VAR_054895. FT VARIANT 63 63 A -> V (in FA11D; dbSNP:rs281875244). FT {ECO:0000269|PubMed:22159456}. FT /FTId=VAR_067934. FT VARIANT 66 66 P -> L (in dbSNP:rs5968). FT {ECO:0000269|PubMed:10391209}. FT /FTId=VAR_011774. FT VARIANT 101 101 K -> R (in FA11D; dbSNP:rs281875272). FT {ECO:0000269|PubMed:15953011}. FT /FTId=VAR_054896. FT VARIANT 109 109 A -> T (in FA11D; dbSNP:rs768474112). FT {ECO:0000269|PubMed:25158988}. FT /FTId=VAR_076516. FT VARIANT 140 140 C -> Y (in FA11D; dbSNP:rs281875256). FT {ECO:0000269|PubMed:16607084}. FT /FTId=VAR_067935. FT VARIANT 151 151 Y -> C (in FA11D; dbSNP:rs281875273). FT {ECO:0000269|PubMed:15953011}. FT /FTId=VAR_054897. FT VARIANT 216 216 D -> N (in FA11D). FT {ECO:0000269|PubMed:25158988}. FT /FTId=VAR_076517. FT VARIANT 222 222 D -> Y (in FA11D; dbSNP:rs281875245). FT {ECO:0000269|PubMed:22159456}. FT /FTId=VAR_067936. FT VARIANT 228 228 R -> Q (in FA11D; dbSNP:rs281875246). FT {ECO:0000269|PubMed:22159456}. FT /FTId=VAR_067937. FT VARIANT 241 241 F -> L (in FA11D; dominant-negative FT mutation that results in severely FT decreased protein secretion; FT dbSNP:rs281875265). FT {ECO:0000269|PubMed:21457405}. FT /FTId=VAR_067938. FT VARIANT 244 244 Q -> R (found in a patient with factor XI FT deficiency that also carries mutation N- FT 266; dbSNP:rs5969). FT {ECO:0000269|PubMed:10391209, FT ECO:0000269|PubMed:9787168}. FT /FTId=VAR_011775. FT VARIANT 246 246 W -> C (in FA11D; dbSNP:rs281875279). FT {ECO:0000269|PubMed:10027710}. FT /FTId=VAR_012086. FT VARIANT 252 252 R -> T (in FA11D; dbSNP:rs281875260). FT {ECO:0000269|PubMed:21668437}. FT /FTId=VAR_067939. FT VARIANT 255 255 C -> Y (in FA11D; secretion of the mutant FT protein is impaired; dbSNP:rs281875277). FT {ECO:0000269|PubMed:11895778}. FT /FTId=VAR_054898. FT VARIANT 263 263 G -> E (in FA11D; dbSNP:rs281875274). FT {ECO:0000269|PubMed:15953011}. FT /FTId=VAR_054899. FT VARIANT 266 266 S -> N (in FA11D; dbSNP:rs145168351). FT {ECO:0000269|PubMed:9787168}. FT /FTId=VAR_012087. FT VARIANT 270 270 K -> I (in FA11D; although the mutant FT protein is synthesized the secretion is FT reduced; dbSNP:rs121965070). FT {ECO:0000269|PubMed:15180874}. FT /FTId=VAR_054900. FT VARIANT 276 276 S -> C (in FA11D; dbSNP:rs281875247). FT {ECO:0000269|PubMed:22159456}. FT /FTId=VAR_067940. FT VARIANT 277 277 G -> D (in FA11D; dbSNP:rs281875248). FT {ECO:0000269|PubMed:22159456}. FT /FTId=VAR_067941. FT VARIANT 301 301 F -> L (in FA11D; dbSNP:rs121965064). FT {ECO:0000269|PubMed:1547342, FT ECO:0000269|PubMed:2813350}. FT /FTId=VAR_006622. FT VARIANT 308 308 I -> F (in dbSNP:rs5972). FT {ECO:0000269|PubMed:10391209}. FT /FTId=VAR_011776. FT VARIANT 315 315 E -> K (in FA11D; dbSNP:rs281875257). FT {ECO:0000269|PubMed:16607084, FT ECO:0000269|PubMed:25158988}. FT /FTId=VAR_067942. FT VARIANT 320 320 L -> P (in FA11D; dbSNP:rs281875268). FT {ECO:0000269|PubMed:7888672}. FT /FTId=VAR_012088. FT VARIANT 322 322 T -> I (in FA11D; dbSNP:rs281875269). FT {ECO:0000269|PubMed:7888672}. FT /FTId=VAR_012089. FT VARIANT 326 326 R -> C (in FA11D; dbSNP:rs28934608). FT {ECO:0000269|PubMed:10606881}. FT /FTId=VAR_012090. FT VARIANT 331 331 T -> I (in FA11D; dbSNP:rs281875253). FT {ECO:0000269|PubMed:18005151}. FT /FTId=VAR_067943. FT VARIANT 339 339 C -> F (in dbSNP:rs5967). FT {ECO:0000269|PubMed:10391209, FT ECO:0000269|PubMed:11895778, FT ECO:0000269|Ref.4}. FT /FTId=VAR_011777. FT VARIANT 341 341 E -> K (in FA11D; dbSNP:rs281875270). FT {ECO:0000269|PubMed:7888672}. FT /FTId=VAR_012091. FT VARIANT 360 360 L -> P (in FA11D; dbSNP:rs281875254). FT {ECO:0000269|PubMed:18005151}. FT /FTId=VAR_067944. FT VARIANT 399 399 W -> R (in dbSNP:rs1800439). FT /FTId=VAR_011778. FT VARIANT 401 401 W -> R (in FA11D; dbSNP:rs281875262). FT {ECO:0000269|PubMed:21668437}. FT /FTId=VAR_067945. FT VARIANT 403 403 V -> M (in FA11D; dominant-negative FT mutation that results in severely FT decreased protein secretion; FT dbSNP:rs281875266). FT {ECO:0000269|PubMed:21457405}. FT /FTId=VAR_067946. FT VARIANT 404 404 T -> N (in FA11D; dbSNP:rs121965067). FT {ECO:0000269|PubMed:9401068}. FT /FTId=VAR_012092. FT VARIANT 418 418 G -> V (in FA11D; mutant is not secreted FT by transfected fibroblasts; dominant- FT negative effect; dbSNP:rs121965071). FT {ECO:0000269|PubMed:15026311}. FT /FTId=VAR_054901. FT VARIANT 430 430 A -> V (in FA11D; dbSNP:rs121965068). FT {ECO:0000269|PubMed:15953011}. FT /FTId=VAR_012093. FT VARIANT 454 454 I -> K (in FA11D; dbSNP:rs281875241). FT {ECO:0000269|PubMed:21999818}. FT /FTId=VAR_067947. FT VARIANT 460 460 F -> V (in FA11D; dbSNP:rs121965065). FT {ECO:0000269|PubMed:7669672}. FT /FTId=VAR_012094. FT VARIANT 481 481 I -> S (in FA11D; dbSNP:rs281875242). FT {ECO:0000269|PubMed:22322133}. FT /FTId=VAR_067948. FT VARIANT 493 493 T -> I (in FA11D). FT {ECO:0000269|PubMed:10606881}. FT /FTId=VAR_012095. FT VARIANT 503 503 S -> P (in FA11D; dbSNP:rs140068026). FT {ECO:0000269|PubMed:18005151}. FT /FTId=VAR_067949. FT VARIANT 506 506 D -> G (in FA11D; mild phenotype; FT dbSNP:rs281875258). FT {ECO:0000269|PubMed:22016685}. FT /FTId=VAR_067950. FT VARIANT 511 511 Y -> H (in FA11D; transfected cells FT contain reduced amount of mutant protein FT and display decreased secretion; FT dbSNP:rs281875278). FT {ECO:0000269|PubMed:11895778}. FT /FTId=VAR_054902. FT VARIANT 514 514 C -> F (in FA11D; dbSNP:rs281875249). FT {ECO:0000269|PubMed:22159456}. FT /FTId=VAR_067951. FT VARIANT 526 526 D -> E (in FA11D; dbSNP:rs281875263). FT {ECO:0000269|PubMed:21668437}. FT /FTId=VAR_067952. FT VARIANT 538 538 P -> L (in FA11D; dbSNP:rs139695003). FT {ECO:0000269|PubMed:15953011}. FT /FTId=VAR_054903. FT VARIANT 543 543 E -> K (in FA11D; dbSNP:rs142952627). FT {ECO:0000269|PubMed:25158988}. FT /FTId=VAR_076518. FT VARIANT 552 552 H -> R (in FA11D; dbSNP:rs369935706). FT {ECO:0000269|PubMed:25158988}. FT /FTId=VAR_076519. FT VARIANT 565 565 E -> K (in FA11D; dbSNP:rs281875275). FT {ECO:0000269|PubMed:15953011}. FT /FTId=VAR_054904. FT VARIANT 575 575 S -> L (in FA11D; dbSNP:rs281875250). FT {ECO:0000269|PubMed:22159456}. FT /FTId=VAR_067953. FT VARIANT 587 587 W -> S (in FA11D; mutant is not secreted FT by transfected fibroblasts; dominant- FT negative effect; dbSNP:rs121965072). FT {ECO:0000269|PubMed:15026311}. FT /FTId=VAR_054905. FT VARIANT 594 594 S -> R (in FA11D; dbSNP:rs28934609). FT {ECO:0000269|PubMed:10606881}. FT /FTId=VAR_012096. FT VARIANT 597 597 E -> K (in FA11D; dbSNP:rs281875251). FT {ECO:0000269|PubMed:16607084, FT ECO:0000269|PubMed:22159456}. FT /FTId=VAR_067954. FT VARIANT 608 608 Y -> H (in FA11D; dbSNP:rs281875255). FT {ECO:0000269|PubMed:18005151}. FT /FTId=VAR_067955. FT VARIANT 618 618 I -> S (in FA11D; dbSNP:rs281875276). FT {ECO:0000269|PubMed:15953011}. FT /FTId=VAR_054906. FT CONFLICT 226 226 C -> S (in Ref. 2; AAA51985). FT {ECO:0000305}. FT STRAND 25 30 {ECO:0000244|PDB:5EOK}. FT STRAND 34 39 {ECO:0000244|PDB:5EOK}. FT HELIX 43 52 {ECO:0000244|PDB:5EOK}. FT STRAND 53 55 {ECO:0000244|PDB:5EOK}. FT STRAND 58 62 {ECO:0000244|PDB:5EOK}. FT HELIX 70 72 {ECO:0000244|PDB:5EOK}. FT STRAND 75 79 {ECO:0000244|PDB:5EOK}. FT STRAND 82 84 {ECO:0000244|PDB:5I25}. FT STRAND 88 98 {ECO:0000244|PDB:5EOK}. FT HELIX 100 102 {ECO:0000244|PDB:5EOD}. FT STRAND 114 129 {ECO:0000244|PDB:5EOK}. FT HELIX 133 142 {ECO:0000244|PDB:5EOK}. FT STRAND 143 145 {ECO:0000244|PDB:5I25}. FT STRAND 147 152 {ECO:0000244|PDB:5EOK}. FT TURN 159 163 {ECO:0000244|PDB:5EOK}. FT STRAND 164 169 {ECO:0000244|PDB:5EOK}. FT STRAND 171 174 {ECO:0000244|PDB:5EOK}. FT STRAND 176 188 {ECO:0000244|PDB:5EOK}. FT HELIX 190 192 {ECO:0000244|PDB:5EOK}. FT TURN 193 195 {ECO:0000244|PDB:5EOK}. FT STRAND 205 219 {ECO:0000244|PDB:5EOK}. FT HELIX 223 231 {ECO:0000244|PDB:5EOK}. FT STRAND 237 242 {ECO:0000244|PDB:5EOK}. FT HELIX 249 251 {ECO:0000244|PDB:5EOK}. FT STRAND 254 259 {ECO:0000244|PDB:5EOK}. FT STRAND 261 264 {ECO:0000244|PDB:5EOK}. FT STRAND 266 278 {ECO:0000244|PDB:5EOK}. FT HELIX 281 283 {ECO:0000244|PDB:5EOK}. FT STRAND 294 296 {ECO:0000244|PDB:2J8J}. FT STRAND 299 302 {ECO:0000244|PDB:5EOK}. FT STRAND 304 312 {ECO:0000244|PDB:5EOK}. FT HELIX 314 322 {ECO:0000244|PDB:5EOK}. FT STRAND 329 333 {ECO:0000244|PDB:5EOK}. FT TURN 337 339 {ECO:0000244|PDB:5EOK}. FT STRAND 344 350 {ECO:0000244|PDB:5EOK}. FT STRAND 352 355 {ECO:0000244|PDB:5EOK}. FT STRAND 357 364 {ECO:0000244|PDB:5EOK}. FT STRAND 366 369 {ECO:0000244|PDB:5EOK}. FT HELIX 372 376 {ECO:0000244|PDB:5EOK}. FT HELIX 379 381 {ECO:0000244|PDB:5EOK}. FT STRAND 390 393 {ECO:0000244|PDB:2F83}. FT STRAND 402 407 {ECO:0000244|PDB:4CRG}. FT STRAND 409 411 {ECO:0000244|PDB:4CRG}. FT STRAND 413 422 {ECO:0000244|PDB:4CRG}. FT STRAND 425 428 {ECO:0000244|PDB:4CRG}. FT HELIX 430 433 {ECO:0000244|PDB:4CRG}. FT HELIX 439 441 {ECO:0000244|PDB:4CRG}. FT STRAND 442 445 {ECO:0000244|PDB:4CRG}. FT HELIX 451 453 {ECO:0000244|PDB:4CRG}. FT STRAND 456 458 {ECO:0000244|PDB:1ZTJ}. FT STRAND 461 468 {ECO:0000244|PDB:4CRG}. FT HELIX 475 477 {ECO:0000244|PDB:4CRG}. FT STRAND 482 488 {ECO:0000244|PDB:4CRG}. FT STRAND 494 496 {ECO:0000244|PDB:4X6P}. FT HELIX 504 506 {ECO:0000244|PDB:4CRG}. FT STRAND 507 509 {ECO:0000244|PDB:1ZMJ}. FT STRAND 514 519 {ECO:0000244|PDB:4CRG}. FT STRAND 522 525 {ECO:0000244|PDB:4CRG}. FT STRAND 533 536 {ECO:0000244|PDB:4CRG}. FT HELIX 542 548 {ECO:0000244|PDB:4CRG}. FT TURN 549 551 {ECO:0000244|PDB:4X6P}. FT STRAND 558 561 {ECO:0000244|PDB:4CRG}. FT STRAND 578 583 {ECO:0000244|PDB:4CRG}. FT STRAND 586 595 {ECO:0000244|PDB:4CRG}. FT STRAND 597 600 {ECO:0000244|PDB:4CRG}. FT STRAND 606 610 {ECO:0000244|PDB:4CRG}. FT HELIX 611 614 {ECO:0000244|PDB:4CRG}. FT HELIX 615 622 {ECO:0000244|PDB:4CRG}. SQ SEQUENCE 625 AA; 70109 MW; 147AFA94B7709E8F CRC64; MIFLYQVVHF ILFTSVSGEC VTQLLKDTCF EGGDITTVFT PSAKYCQVVC TYHPRCLLFT FTAESPSEDP TRWFTCVLKD SVTETLPRVN RTAAISGYSF KQCSHQISAC NKDIYVDLDM KGINYNSSVA KSAQECQERC TDDVHCHFFT YATRQFPSLE HRNICLLKHT QTGTPTRITK LDKVVSGFSL KSCALSNLAC IRDIFPNTVF ADSNIDSVMA PDAFVCGRIC THHPGCLFFT FFSQEWPKES QRNLCLLKTS ESGLPSTRIK KSKALSGFSL QSCRHSIPVF CHSSFYHDTD FLGEELDIVA AKSHEACQKL CTNAVRCQFF TYTPAQASCN EGKGKCYLKL SSNGSPTKIL HGRGGISGYT LRLCKMDNEC TTKIKPRIVG GTASVRGEWP WQVTLHTTSP TQRHLCGGSI IGNQWILTAA HCFYGVESPK ILRVYSGILN QSEIKEDTSF FGVQEIIIHD QYKMAESGYD IALLKLETTV NYTDSQRPIC LPSKGDRNVI YTDCWVTGWG YRKLRDKIQN TLQKAKIPLV TNEECQKRYR GHKITHKMIC AGYREGGKDA CKGDSGGPLS CKHNEVWHLV GITSWGEGCA QRERPGVYTN VVEYVDWILE KTQAV //