FIBA_HUMAN
ID FIBA_HUMAN Reviewed; 866 AA.
AC P02671; A8K3E4; D3DP14; D3DP15; Q4QQH7; Q9BX62; Q9UCH2;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 256.
DE RecName: Full=Fibrinogen alpha chain;
DE Contains:
DE RecName: Full=Fibrinopeptide A;
DE Contains:
DE RecName: Full=Fibrinogen alpha chain;
DE Flags: Precursor;
GN Name=FGA;
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 [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORMS 1 AND
RP 2).
RX PubMed=1457396; DOI=10.1021/bi00163a002;
RA Fu Y., Weissbach L., Plant P.W., Oddoux C., Cao Y., Liang T.J., Roy S.N.,
RA Redman C.M., Grieninger G.;
RT "Carboxy-terminal-extended variant of the human fibrinogen alpha subunit: a
RT novel exon conferring marked homology to beta and gamma subunits.";
RL Biochemistry 31:11968-11972(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1).
RA Chung D.W., Grieninger G.;
RT "Fibrinogen DNA and protein sequences.";
RL (In) Ebert R.F. (eds.);
RL Index of variant human fibrinogens, pp.13-24, CRC Press, Boca Raton (1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-6; ALA-331 AND ALA-456.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT ALA-331.
RC TISSUE=Heart;
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 [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [7]
RP NUCLEOTIDE SEQUENCE OF 1-655 (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=2102623; DOI=10.1007/978-1-4615-3806-6_3;
RA Chung D.W., Harris J.E., Davie E.W.;
RT "Nucleotide sequences of the three genes coding for human fibrinogen.";
RL Adv. Exp. Med. Biol. 281:39-48(1990).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=6575389; DOI=10.1073/pnas.80.13.3953;
RA Kant J.A., Lord S.T., Crabtree G.R.;
RT "Partial mRNA sequences for human A alpha, B beta, and gamma fibrinogen
RT chains: evolutionary and functional implications.";
RL Proc. Natl. Acad. Sci. U.S.A. 80:3953-3957(1983).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-629.
RX PubMed=6688355; DOI=10.1021/bi00282a031;
RA Rixon M.W., Chan W.-Y., Davie E.W., Chung D.W.;
RT "Characterization of a complementary deoxyribonucleic acid coding for the
RT alpha chain of human fibrinogen.";
RL Biochemistry 22:3237-3244(1983).
RN [10]
RP PROTEIN SEQUENCE OF 20-629.
RA Henschen A., Lottspeich F., Southan C., Topfer-Petersen E.;
RT "Human fibrinogen: sequence, sulfur bridges, glycosylation and some
RT structural variants.";
RL (In) Peeters H. (eds.);
RL Protides of the biological fluids, Proc. 28th colloquium, pp.51-56,
RL Pergamon Press, Oxford (1980).
RN [11]
RP PROTEIN SEQUENCE OF 20-629, DISULFIDE BONDS, AND SUBUNIT.
RX PubMed=518846; DOI=10.1021/bi00591a024;
RA Watt K.W.K., Cottrell B.A., Strong D.D., Doolittle R.F.;
RT "Amino acid sequence studies on the alpha chain of human fibrinogen.
RT Overlapping sequences providing the complete sequence.";
RL Biochemistry 18:5410-5416(1979).
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 110-156.
RX PubMed=6689067; DOI=10.1093/nar/11.21.7427;
RA Imam A.M.A., Eaton M.A.W., Williamson R., Humphries S.;
RT "Isolation and characterisation of cDNA clones for the A alpha- and gamma-
RT chains of human fibrinogen.";
RL Nucleic Acids Res. 11:7427-7434(1983).
RN [13]
RP NUCLEOTIDE SEQUENCE OF 605-644 (ISOFORM 2).
RX PubMed=6575700; DOI=10.1111/j.1749-6632.1983.tb23265.x;
RA Chung D.W., Rixon M.W., Que B.G., Davie E.W.;
RT "Cloning of fibrinogen genes and their cDNA.";
RL Ann. N. Y. Acad. Sci. 408:449-456(1983).
RN [14]
RP PROTEIN SEQUENCE OF 20-35.
RA Blombaeck B., Blombaeck M., Grondahl N.J., Guthrie C., Hinton M.;
RT "Studies on fibrinopeptides from primates.";
RL Acta Chem. Scand. 19:1788-1789(1965).
RN [15]
RP DISULFIDE BONDS, AND SUBUNIT.
RX PubMed=741445; DOI=10.1016/0049-3848(78)90142-1;
RA Bouma H., Takagi T., Doolittle R.F.;
RT "The arrangement of disulfide bonds in fragment D from human fibrinogen.";
RL Thromb. Res. 13:557-562(1978).
RN [16]
RP CROSS-LINKING ACCEPTOR SITES.
RX PubMed=518845; DOI=10.1021/bi00591a023;
RA Cottrell B.A., Strong D.D., Watt K.W.K., Doolittle R.F.;
RT "Amino acid sequence studies on the alpha chain of human fibrinogen. Exact
RT location of cross-linking acceptor sites.";
RL Biochemistry 18:5405-5410(1979).
RN [17]
RP CROSS-LINKING ACCEPTOR SITES.
RX PubMed=632262; DOI=10.1016/s0021-9258(17)38057-2;
RA Fretto L.J., Ferguson E.W., Steinman H.M., McKee P.A.;
RT "Localization of the alpha-chain cross-link acceptor sites of human
RT fibrin.";
RL J. Biol. Chem. 253:2184-2195(1978).
RN [18]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-686.
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., Moore R.J.,
RA 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 [19]
RP DISULFIDE BONDS, AND SUBUNIT.
RX PubMed=936108; DOI=10.1016/0049-3848(76)90245-0;
RA Blombaeck B., Hessel B., Hogg D.;
RT "Disulfide bridges in NH2-terminal part of human fibrinogen.";
RL Thromb. Res. 8:639-658(1976).
RN [20]
RP REVIEW, ELECTRON MICROSCOPY, POLYMERIZATION, AND LIGANDS.
RX PubMed=6383194; DOI=10.1146/annurev.bi.53.070184.001211;
RA Doolittle R.F.;
RT "Fibrinogen and fibrin.";
RL Annu. Rev. Biochem. 53:195-229(1984).
RN [21]
RP CROSS-LINKING SITE FOR ALPHA-2-PLASMIN INHIBITOR.
RX PubMed=2877981; DOI=10.1016/s0021-9258(18)66755-9;
RA Kimura S., Aoki N.;
RT "Cross-linking site in fibrinogen for alpha 2-plasmin inhibitor.";
RL J. Biol. Chem. 261:15591-15595(1986).
RN [22]
RP PHOSPHORYLATION.
RX PubMed=6318767; DOI=10.1016/0006-291x(83)91247-0;
RA Itarte E., Plana M., Guasch M.D., Martos C.;
RT "Phosphorylation of fibrinogen by casein kinase 1.";
RL Biochem. Biophys. Res. Commun. 117:631-636(1983).
RN [23]
RP INTERACTION WITH STAPHYLOCOCCUS AUREUS PROTEIN FIB (MICROBIAL INFECTION).
RX PubMed=11418620; DOI=10.1074/jbc.m104554200;
RA Palma M., Shannon O., Quezada H.C., Berg A., Flock J.I.;
RT "Extracellular fibrinogen-binding protein, Efb, from Staphylococcus aureus
RT blocks platelet aggregation due to its binding to the alpha-chain.";
RL J. Biol. Chem. 276:31691-31697(2001).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Pituitary;
RX PubMed=16807684; DOI=10.1007/s11102-006-8916-x;
RA Beranova-Giorgianni S., Zhao Y., Desiderio D.M., Giorgianni F.;
RT "Phosphoproteomic analysis of the human pituitary.";
RL Pituitary 9:109-120(2006).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-412 AND SER-609, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [26]
RP HYDROXYLATION AT PRO-565.
RX PubMed=19696023; DOI=10.1074/jbc.m109.041749;
RA Ono M., Matsubara J., Honda K., Sakuma T., Hashiguchi T., Nose H.,
RA Nakamori S., Okusaka T., Kosuge T., Sata N., Nagai H., Ioka T., Tanaka S.,
RA Tsuchida A., Aoki T., Shimahara M., Yasunami Y., Itoi T., Moriyasu F.,
RA Negishi A., Kuwabara H., Shoji A., Hirohashi S., Yamada T.;
RT "Prolyl 4-hydroxylation of alpha-fibrinogen: a novel protein modification
RT revealed by plasma proteomics.";
RL J. Biol. Chem. 284:29041-29049(2009).
RN [27]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-686.
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 multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [28]
RP CLEAVAGE BY HEMENTIN AND PLASMIN.
RX PubMed=2143188; DOI=10.1016/s0021-9258(18)77401-2;
RA Kirschbaum N.E., Budzynski A.Z.;
RT "A unique proteolytic fragment of human fibrinogen containing the A alpha
RT COOH-terminal domain of the native molecule.";
RL J. Biol. Chem. 265:13669-13676(1990).
RN [29]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [30]
RP GLYCOSYLATION AT THR-320 AND SER-351.
RX PubMed=23050552; DOI=10.1021/pr3005937;
RA Zauner G., Hoffmann M., Rapp E., Koeleman C.A., Dragan I., Deelder A.M.,
RA Wuhrer M., Hensbergen P.J.;
RT "Glycoproteomic analysis of human fibrinogen reveals novel regions of O-
RT glycosylation.";
RL J. Proteome Res. 11:5804-5814(2012).
RN [31]
RP INTERACTION WITH STAPHYLOCOCCUS AUREUS PROTEIN FIB (MICROBIAL INFECTION).
RX PubMed=24348255; DOI=10.1371/journal.ppat.1003816;
RA Ko Y.P., Kuipers A., Freitag C.M., Jongerius I., Medina E.,
RA van Rooijen W.J., Spaan A.N., van Kessel K.P., Hoeoek M., Rooijakkers S.H.;
RT "Phagocytosis escape by a Staphylococcus aureus protein that connects
RT complement and coagulation proteins at the bacterial surface.";
RL PLoS Pathog. 9:E1003816-E1003816(2013).
RN [32]
RP LACK OF GLYCOSYLATION.
RX PubMed=23151259; DOI=10.1021/pr300813h;
RA Adamczyk B., Struwe W.B., Ercan A., Nigrovic P.A., Rudd P.M.;
RT "Characterization of fibrinogen glycosylation and its importance for
RT serum/plasma N-glycome analysis.";
RL J. Proteome Res. 12:444-454(2013).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45; SER-50; SER-281; SER-291;
RP SER-294; THR-412; SER-451; SER-501; THR-505 AND SER-609, AND IDENTIFICATION
RP 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 [34]
RP PHOSPHORYLATION AT SER-45; SER-56; SER-364; SER-524; SER-560 AND SER-609.
RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT "A single kinase generates the majority of the secreted phosphoproteome.";
RL Cell 161:1619-1632(2015).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 26-39.
RX PubMed=1560020; DOI=10.1016/s0021-9258(18)42599-9;
RA Martin P.D., Robertson W., Turk D., Huber R., Bode W., Edwards B.F.P.;
RT "The structure of residues 7-16 of the A alpha-chain of human fibrinogen
RT bound to bovine thrombin at 2.3-A resolution.";
RL J. Biol. Chem. 267:7911-7920(1992).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 130-216, DISULFIDE BONDS, AND
RP SUBUNIT.
RX PubMed=9333233; DOI=10.1038/38947;
RA Spraggon G., Everse S.J., Doolittle R.F.;
RT "Crystal structures of fragment D from human fibrinogen and its crosslinked
RT counterpart from fibrin.";
RL Nature 389:455-462(1997).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 130-216, SUBUNIT, DISULFIDE BONDS,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND COILED COIL DOMAIN.
RX PubMed=9628725; DOI=10.1021/bi9804129;
RA Everse S.J., Spraggon G., Veerapandian L., Riley M., Doolittle R.F.;
RT "Crystal structure of fragment double-D from human fibrin with two
RT different bound ligands.";
RL Biochemistry 37:8637-8642(1998).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 666-866 IN COMPLEX WITH CALCIUM
RP IONS, GLYCOSYLATION AT ASN-686, DISULFIDE BONDS, AND SUBUNIT.
RX PubMed=9689040; DOI=10.1073/pnas.95.16.9099;
RA Spraggon G., Applegate D., Everse S.J., Zhang J.Z., Veerapandian L.,
RA Redman C., Doolittle R.F., Grieninger G.;
RT "Crystal structure of a recombinant alphaEC domain from human fibrinogen-
RT 420.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:9099-9104(1998).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 130-216, AND DISULFIDE BONDS.
RX PubMed=10074346; DOI=10.1021/bi982626w;
RA Everse S.J., Spraggon G., Veerapandian L., Doolittle R.F.;
RT "Conformational changes in fragments D and double-D from human fibrin(ogen)
RT upon binding the peptide ligand Gly-His-Arg-Pro-amide.";
RL Biochemistry 38:2941-2946(1999).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 20-581, SUBUNIT, DISULFIDE BONDS,
RP COILED COIL DOMAIN, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=19296670; DOI=10.1021/bi802205g;
RA Kollman J.M., Pandi L., Sawaya M.R., Riley M., Doolittle R.F.;
RT "Crystal structure of human fibrinogen.";
RL Biochemistry 48:3877-3886(2009).
RN [41]
RP VARIANT KYOTO-2 LEU-37.
RX PubMed=2070049;
RA Yoshida N., Okuma M., Hirata H., Matsuda M., Yamazumi K., Asakura S.;
RT "Fibrinogen Kyoto II, a new congenitally abnormal molecule, characterized
RT by the replacement of A alpha proline-18 by leucine.";
RL Blood 78:149-153(1991).
RN [42]
RP VARIANT LIMA SER-160.
RX PubMed=1634621; DOI=10.1172/jci115857;
RA Maekawa H., Yamazumi K., Muramatsu S., Kaneko M., Hirata H., Takahashi N.,
RA Arocha-Pinango C.L., Rodriguez S., Nagy H., Perez-Requejo J.L., Matsuda M.;
RT "Fibrinogen Lima: a homozygous dysfibrinogen with an A alpha-arginine-141
RT to serine substitution associated with extra N-glycosylation at A alpha-
RT asparagine-139. Impaired fibrin gel formation but normal fibrin-facilitated
RT plasminogen activation catalyzed by tissue-type plasminogen activator.";
RL J. Clin. Invest. 90:67-76(1992).
RN [43]
RP GLYCOSYLATION AT ASN-453 (VARIANT ASN-453), AND VARIANT CARACAS-2 ASN-453.
RX PubMed=1675636; DOI=10.1016/s0021-9258(18)98995-7;
RA Maekawa H., Yamazumi K., Muramatsu S., Kaneko M., Hirata H., Takahashi N.,
RA de Bosch N.B., Carvajal Z., Ojeda A., Arocha-Pinango C.L., Matsuda M.;
RT "An A alpha Ser-434 to N-glycosylated Asn substitution in a dysfibrinogen,
RT fibrinogen Caracas II, characterized by impaired fibrin gel formation.";
RL J. Biol. Chem. 266:11575-11581(1991).
RN [44]
RP INVOLVEMENT IN DYSFIBRIN, AND VARIANT DYSFIBRIN CYS-573.
RX PubMed=8473507; DOI=10.1172/jci116371;
RA Koopman J., Haverkate F., Grimbergen J., Lord S.T., Mosesson M.W.,
RA Diorio J.P., Siebenlist K.S., Legrand C., Soria J., Soria C., Caen J.P.;
RT "Molecular basis for fibrinogen Dusart (A alpha 554 Arg-->Cys) and its
RT association with abnormal fibrin polymerization and thrombophilia.";
RL J. Clin. Invest. 91:1637-1643(1993).
RN [45]
RP VARIANT AMYL8 LEU-573.
RX PubMed=8097946; DOI=10.1038/ng0393-252;
RA Benson M.D., Liepnieks J., Uemichi T., Wheeler G., Correa R.;
RT "Hereditary renal amyloidosis associated with a mutant fibrinogen alpha-
RT chain.";
RL Nat. Genet. 3:252-255(1993).
RN [46]
RP VARIANT OSAKA IV HIS-35.
RX PubMed=8461606; DOI=10.1007/bf00308999;
RA Yamazumi K., Terukina S., Matsuda M., Kanbayashi J., Sakon M.,
RA Tsujinaka T.;
RT "Fibrinogen Osaka IV: a congenital dysfibrinogenemia found in a patient
RT originally reported in relation to surgery, now defined to have an A alpha
RT arginine-16 to histidine substitution.";
RL Surg. Today 23:45-50(1993).
RN [47]
RP VARIANT CANTERBURY ASP-39.
RX PubMed=8675656; DOI=10.1172/jci118356;
RA Brennan S.O., Hammonds B., George P.M.;
RT "Aberrant hepatic processing causes removal of activation peptide and
RT primary polymerisation site from fibrinogen Canterbury (A-alpha 20 Val-to-
RT Asp).";
RL J. Clin. Invest. 96:2854-2858(1995).
RN [48]
RP VARIANTS ALA-331 AND GLU-446.
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 [49]
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 [50]
RP INVOLVEMENT IN DYSFIBRIN, AND VARIANT DYSFIBRIN CYS-35.
RX PubMed=16846481; DOI=10.1111/j.1365-2141.2006.06129.x;
RA Flood V.H., Al-Mondhiry H.A., Farrell D.H.;
RT "The fibrinogen Aalpha R16C mutation results in fibrinolytic resistance.";
RL Br. J. Haematol. 134:220-226(2006).
RN [51]
RP INVOLVEMENT IN CAFBN; VARIANTS CAFBN ARG-55; PRO-129 AND TRP-184, AND
RP CHARACTERIZATION OF VARIANTS CAFBN ARG-55; PRO-129 AND TRP-184.
RX PubMed=25427968; DOI=10.1160/th14-07-0629;
RA Asselta R., Plate M., Robusto M., Borhany M., Guella I., Solda G.,
RA Afrasiabi A., Menegatti M., Shamsi T., Peyvandi F., Duga S.;
RT "Clinical and molecular characterisation of 21 patients affected by
RT quantitative fibrinogen deficiency.";
RL Thromb. Haemost. 113:567-576(2015).
CC -!- FUNCTION: Cleaved by the protease thrombin to yield monomers which,
CC together with fibrinogen beta (FGB) and fibrinogen gamma (FGG),
CC polymerize to form an insoluble fibrin matrix. Fibrin has a major
CC function in hemostasis as one of the primary components of blood clots.
CC In addition, functions during the early stages of wound repair to
CC stabilize the lesion and guide cell migration during re-
CC epithelialization. Was originally thought to be essential for platelet
CC aggregation, based on in vitro studies using anticoagulated blood.
CC However, subsequent studies have shown that it is not absolutely
CC required for thrombus formation in vivo. Enhances expression of SELP in
CC activated platelets via an ITGB3-dependent pathway. Maternal fibrinogen
CC is essential for successful pregnancy. Fibrin deposition is also
CC associated with infection, where it protects against IFNG-mediated
CC hemorrhage. May also facilitate the immune response via both innate and
CC T-cell mediated pathways. {ECO:0000250|UniProtKB:E9PV24}.
CC -!- SUBUNIT: Heterohexamer; disulfide linked. Contains 2 sets of 3 non-
CC identical chains (alpha, beta and gamma). The 2 heterotrimers are in
CC head to head conformation with the N-termini in a small central domain.
CC {ECO:0000269|PubMed:518846, ECO:0000269|PubMed:741445,
CC ECO:0000269|PubMed:9333233, ECO:0000269|PubMed:936108,
CC ECO:0000269|PubMed:9628725, ECO:0000269|PubMed:9689040}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Staphylococcus aureus
CC protein Fib; this interaction inhibits fibrinogen-dependent platelet
CC aggregation and protects the bacteria form phagocytosis.
CC {ECO:0000269|PubMed:11418620, ECO:0000269|PubMed:24348255}.
CC -!- INTERACTION:
CC P02671; Q8IXL6: FAM20C; NbExp=2; IntAct=EBI-348571, EBI-7147442;
CC P02671-2; O00471: EXOC5; NbExp=3; IntAct=EBI-9640259, EBI-949824;
CC P02671-2; P13473-2: LAMP2; NbExp=3; IntAct=EBI-9640259, EBI-21591415;
CC P02671-2; Q9Y3L3: SH3BP1; NbExp=3; IntAct=EBI-9640259, EBI-346869;
CC P02671-2; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-9640259, EBI-2623095;
CC P02671-2; P00441: SOD1; NbExp=3; IntAct=EBI-9640259, EBI-990792;
CC P02671-2; P61266: STX1B; NbExp=3; IntAct=EBI-9640259, EBI-9071709;
CC P02671-2; P32856-2: STX2; NbExp=3; IntAct=EBI-9640259, EBI-11956649;
CC P02671-2; Q9UBB9: TFIP11; NbExp=3; IntAct=EBI-9640259, EBI-1105213;
CC P02671-2; Q9BTV4: TMEM43; NbExp=3; IntAct=EBI-9640259, EBI-721293;
CC P02671-2; P09493-10: TPM1; NbExp=3; IntAct=EBI-9640259, EBI-12123928;
CC P02671-2; P06753: TPM3; NbExp=3; IntAct=EBI-9640259, EBI-355607;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:19296670,
CC ECO:0000269|PubMed:9628725}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Alpha-E;
CC IsoId=P02671-1; Sequence=Displayed;
CC Name=2; Synonyms=Alpha;
CC IsoId=P02671-2; Sequence=VSP_001531, VSP_001532;
CC -!- TISSUE SPECIFICITY: Detected in blood plasma (at protein level).
CC {ECO:0000269|PubMed:19296670, ECO:0000269|PubMed:9628725}.
CC -!- DOMAIN: A long coiled coil structure formed by 3 polypeptide chains
CC connects the central nodule to the C-terminal domains (distal nodules).
CC The long C-terminal ends of the alpha chains fold back, contributing a
CC fourth strand to the coiled coil structure.
CC {ECO:0000269|PubMed:19296670, ECO:0000269|PubMed:9628725, ECO:0000305}.
CC -!- PTM: The alpha chain is normally not N-glycosylated (PubMed:23151259),
CC even though glycosylation at Asn-686 was observed when a fragment of
CC the protein was expressed in insect cells (PubMed:9689040). It is well
CC known that heterologous expression of isolated domains can lead to
CC adventitious protein modifications. Besides, glycosylation at Asn-686
CC is supported by large-scale glycoproteomics studies (PubMed:16335952
CC and PubMed:19159218), but the evidence is still quite tenuous. Most
CC likely, Asn-686 is not glycosylated in the healthy human body, or only
CC with low efficiency. {ECO:0000269|PubMed:16335952,
CC ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:23151259,
CC ECO:0000269|PubMed:9689040, ECO:0000305}.
CC -!- PTM: O-glycosylated. {ECO:0000269|PubMed:23050552}.
CC -!- PTM: Forms F13A-mediated cross-links between a glutamine and the
CC epsilon-amino group of a lysine residue, forming fibronectin-fibrinogen
CC heteropolymers.
CC -!- PTM: About one-third of the alpha chains in the molecules in blood were
CC found to be phosphorylated.
CC -!- PTM: Conversion of fibrinogen to fibrin is triggered by thrombin, which
CC cleaves fibrinopeptides A and B from alpha and beta chains, and thus
CC exposes the N-terminal polymerization sites responsible for the
CC formation of the soft clot. The soft clot is converted into the hard
CC clot by factor XIIIA which catalyzes the epsilon-(gamma-glutamyl)lysine
CC cross-linking between gamma chains (stronger) and between alpha chains
CC (weaker) of different monomers. {ECO:0000269|PubMed:2143188}.
CC -!- PTM: Phosphorylated by FAM20C in the extracellular medium.
CC {ECO:0000269|PubMed:26091039}.
CC -!- DISEASE: Congenital afibrinogenemia (CAFBN) [MIM:202400]: Rare
CC autosomal recessive disorder is characterized by bleeding that varies
CC from mild to severe and by complete absence or extremely low levels of
CC plasma and platelet fibrinogen. {ECO:0000269|PubMed:25427968}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry. The majority of cases of afibrinogenemia are due to truncating
CC mutations. Variations in position Arg-35 (the site of cleavage of
CC fibrinopeptide a by thrombin) leads to alpha-dysfibrinogenemias.
CC -!- DISEASE: Amyloidosis 8 (AMYL8) [MIM:105200]: A form of hereditary
CC generalized amyloidosis. Clinical features include extensive visceral
CC amyloid deposits, renal amyloidosis resulting in nephrotic syndrome,
CC arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin
CC rash. There is no involvement of the nervous system.
CC {ECO:0000269|PubMed:8097946}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Dysfibrinogenemia, congenital (DYSFIBRIN) [MIM:616004]: A
CC disorder characterized by qualitative abnormalities (dysfibrinogenemia)
CC of the circulating fibrinogen. Affected individuals are frequently
CC asymptomatic, but some patients have bleeding diathesis, thromboembolic
CC complications, or both. In some cases, dysfibrinogenemia is associated
CC with low circulating fibrinogen levels (hypodysfibrinogenemia).
CC {ECO:0000269|PubMed:16846481, ECO:0000269|PubMed:8473507}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Fibrinogen entry;
CC URL="https://en.wikipedia.org/wiki/Fibrinogen";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/fga/";
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DR EMBL; M64982; AAA17056.1; -; Genomic_DNA.
DR EMBL; M64982; AAA17055.1; -; Genomic_DNA.
DR EMBL; M58569; AAC97142.1; -; Transcribed_RNA.
DR EMBL; M58569; AAC97143.1; -; Transcribed_RNA.
DR EMBL; AF361104; AAK31372.1; -; Genomic_DNA.
DR EMBL; AF361104; AAK31373.1; -; Genomic_DNA.
DR EMBL; AK290559; BAF83248.1; -; mRNA.
DR EMBL; CH471056; EAX04925.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX04926.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX04927.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX04928.1; -; Genomic_DNA.
DR EMBL; BC098280; AAH98280.1; -; mRNA.
DR EMBL; BC099706; AAH99706.1; -; mRNA.
DR EMBL; BC099720; AAH99720.1; -; mRNA.
DR EMBL; BC101935; AAI01936.1; -; mRNA.
DR EMBL; J00128; AAA52427.1; -; mRNA.
DR EMBL; J00127; AAA52426.1; -; mRNA.
DR EMBL; K02272; AAA52428.1; -; mRNA.
DR EMBL; M26878; AAA52444.1; -; mRNA.
DR CCDS; CCDS3787.1; -. [P02671-1]
DR CCDS; CCDS47152.1; -. [P02671-2]
DR PIR; A93956; FGHUA.
DR PIR; D44234; D44234.
DR RefSeq; NP_000499.1; NM_000508.4. [P02671-1]
DR RefSeq; NP_068657.1; NM_021871.3. [P02671-2]
DR PDB; 1BBR; X-ray; 2.30 A; F/G/I=26-35.
DR PDB; 1DM4; X-ray; 2.50 A; C=26-35.
DR PDB; 1FPH; X-ray; 2.50 A; F=26-35.
DR PDB; 1FZA; X-ray; 2.90 A; A/D=130-216.
DR PDB; 1FZB; X-ray; 2.90 A; A/D=130-216.
DR PDB; 1FZC; X-ray; 2.30 A; A/D=130-216.
DR PDB; 1FZD; X-ray; 2.10 A; A/B/C/D/E/F/G/H=666-866.
DR PDB; 1FZE; X-ray; 3.00 A; A/D=130-216.
DR PDB; 1FZF; X-ray; 2.70 A; A/D=130-216.
DR PDB; 1FZG; X-ray; 2.50 A; A/D=130-216.
DR PDB; 1LT9; X-ray; 2.80 A; A/D=145-210.
DR PDB; 1LTJ; X-ray; 2.80 A; A/D=145-210.
DR PDB; 1N86; X-ray; 3.20 A; A/D=130-216.
DR PDB; 1N8E; X-ray; 4.50 A; A/D=130-218.
DR PDB; 1RE3; X-ray; 2.45 A; A/D=145-210.
DR PDB; 1RE4; X-ray; 2.70 A; A/D=145-210.
DR PDB; 1RF0; X-ray; 2.81 A; A/D=145-210.
DR PDB; 1RF1; X-ray; 2.53 A; A/D=145-210.
DR PDB; 1YCP; X-ray; 2.50 A; F/N=20-42.
DR PDB; 2A45; X-ray; 3.65 A; G/J=36-92.
DR PDB; 2FFD; X-ray; 2.89 A; A/D=145-210.
DR PDB; 2H43; X-ray; 2.70 A; A/D=130-216.
DR PDB; 2HLO; X-ray; 2.60 A; A/D=130-216.
DR PDB; 2HOD; X-ray; 2.90 A; A/D/G/J=130-216.
DR PDB; 2HPC; X-ray; 2.90 A; A/D/G/J=130-216.
DR PDB; 2OYH; X-ray; 2.40 A; A/D=145-210.
DR PDB; 2OYI; X-ray; 2.70 A; A/D=145-210.
DR PDB; 2Q9I; X-ray; 2.80 A; A/D=130-216.
DR PDB; 2XNX; X-ray; 3.30 A; A/D/G/J=130-216.
DR PDB; 2XNY; X-ray; 7.50 A; A/D=130-216.
DR PDB; 2Z4E; X-ray; 2.70 A; A/D=130-216.
DR PDB; 3AT0; X-ray; 2.50 A; B=332-347.
DR PDB; 3BVH; X-ray; 2.60 A; A/D=148-209.
DR PDB; 3E1I; X-ray; 2.30 A; A/D=130-216.
DR PDB; 3GHG; X-ray; 2.90 A; A/D/G/J=20-581.
DR PDB; 3H32; X-ray; 3.60 A; A/D=20-216.
DR PDB; 3HUS; X-ray; 3.04 A; A/D=145-210.
DR PDB; 4F27; X-ray; 1.92 A; Q=336-347.
DR PDB; 5CFA; X-ray; 1.45 A; C/D=580-594.
DR PDBsum; 1BBR; -.
DR PDBsum; 1DM4; -.
DR PDBsum; 1FPH; -.
DR PDBsum; 1FZA; -.
DR PDBsum; 1FZB; -.
DR PDBsum; 1FZC; -.
DR PDBsum; 1FZD; -.
DR PDBsum; 1FZE; -.
DR PDBsum; 1FZF; -.
DR PDBsum; 1FZG; -.
DR PDBsum; 1LT9; -.
DR PDBsum; 1LTJ; -.
DR PDBsum; 1N86; -.
DR PDBsum; 1N8E; -.
DR PDBsum; 1RE3; -.
DR PDBsum; 1RE4; -.
DR PDBsum; 1RF0; -.
DR PDBsum; 1RF1; -.
DR PDBsum; 1YCP; -.
DR PDBsum; 2A45; -.
DR PDBsum; 2FFD; -.
DR PDBsum; 2H43; -.
DR PDBsum; 2HLO; -.
DR PDBsum; 2HOD; -.
DR PDBsum; 2HPC; -.
DR PDBsum; 2OYH; -.
DR PDBsum; 2OYI; -.
DR PDBsum; 2Q9I; -.
DR PDBsum; 2XNX; -.
DR PDBsum; 2XNY; -.
DR PDBsum; 2Z4E; -.
DR PDBsum; 3AT0; -.
DR PDBsum; 3BVH; -.
DR PDBsum; 3E1I; -.
DR PDBsum; 3GHG; -.
DR PDBsum; 3H32; -.
DR PDBsum; 3HUS; -.
DR PDBsum; 4F27; -.
DR PDBsum; 5CFA; -.
DR AlphaFoldDB; P02671; -.
DR SMR; P02671; -.
DR BioGRID; 108534; 95.
DR ComplexPortal; CPX-1922; Fibrinogen complex.
DR ComplexPortal; CPX-6225; Fibrin complex.
DR CORUM; P02671; -.
DR DIP; DIP-29643N; -.
DR IntAct; P02671; 41.
DR MINT; P02671; -.
DR STRING; 9606.ENSP00000306361; -.
DR ChEMBL; CHEMBL2364709; -.
DR DrugBank; DB04919; Alfimeprase.
DR DrugBank; DB00009; Alteplase.
DR DrugBank; DB05099; Ancrod.
DR DrugBank; DB00029; Anistreplase.
DR DrugBank; DB13151; Anti-inhibitor coagulant complex.
DR DrugBank; DB05675; EP-2104R.
DR DrugBank; DB11571; Human thrombin.
DR DrugBank; DB06245; Lanoteplase.
DR DrugBank; DB11311; Prothrombin.
DR DrugBank; DB00015; Reteplase.
DR DrugBank; DB00364; Sucralfate.
DR DrugBank; DB00031; Tenecteplase.
DR DrugBank; DB11300; Thrombin.
DR DrugBank; DB11572; Thrombin alfa.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR CarbonylDB; P02671; -.
DR GlyConnect; 1238; 3 N-Linked glycans (1 site).
DR GlyConnect; 157; 4 N-Linked glycans.
DR GlyGen; P02671; 24 sites, 10 N-linked glycans (2 sites), 4 O-linked glycans (21 sites).
DR iPTMnet; P02671; -.
DR PhosphoSitePlus; P02671; -.
DR SwissPalm; P02671; -.
DR BioMuta; FGA; -.
DR DMDM; 1706799; -.
DR OGP; P02671; -.
DR SWISS-2DPAGE; P02671; -.
DR CPTAC; non-CPTAC-1117; -.
DR CPTAC; non-CPTAC-1118; -.
DR jPOST; P02671; -.
DR MassIVE; P02671; -.
DR MaxQB; P02671; -.
DR PaxDb; P02671; -.
DR PeptideAtlas; P02671; -.
DR PRIDE; P02671; -.
DR ProteomicsDB; 51542; -. [P02671-1]
DR ProteomicsDB; 51543; -. [P02671-2]
DR ABCD; P02671; 6 sequenced antibodies.
DR Antibodypedia; 3395; 1039 antibodies from 42 providers.
DR DNASU; 2243; -.
DR Ensembl; ENST00000403106.8; ENSP00000385981.3; ENSG00000171560.17. [P02671-2]
DR Ensembl; ENST00000651975.1; ENSP00000498441.1; ENSG00000171560.17. [P02671-1]
DR GeneID; 2243; -.
DR KEGG; hsa:2243; -.
DR MANE-Select; ENST00000403106.8; ENSP00000385981.3; NM_021871.4; NP_068657.1. [P02671-2]
DR UCSC; uc003iod.2; human. [P02671-1]
DR CTD; 2243; -.
DR DisGeNET; 2243; -.
DR GeneCards; FGA; -.
DR HGNC; HGNC:3661; FGA.
DR HPA; ENSG00000171560; Tissue enriched (liver).
DR MalaCards; FGA; -.
DR MIM; 105200; phenotype.
DR MIM; 134820; gene+phenotype.
DR MIM; 202400; phenotype.
DR MIM; 616004; phenotype.
DR neXtProt; NX_P02671; -.
DR OpenTargets; ENSG00000171560; -.
DR Orphanet; 93562; AFib amyloidosis.
DR Orphanet; 98880; Familial afibrinogenemia.
DR Orphanet; 98881; Familial dysfibrinogenemia.
DR Orphanet; 248408; Familial hypodysfibrinogenemia.
DR Orphanet; 101041; Familial hypofibrinogenemia.
DR PharmGKB; PA429; -.
DR VEuPathDB; HostDB:ENSG00000171560; -.
DR eggNOG; KOG2579; Eukaryota.
DR GeneTree; ENSGT00940000155946; -.
DR HOGENOM; CLU_013807_0_0_1; -.
DR InParanoid; P02671; -.
DR OMA; WVSFRGA; -.
DR OrthoDB; 363208at2759; -.
DR PhylomeDB; P02671; -.
DR TreeFam; TF351984; -.
DR PathwayCommons; P02671; -.
DR Reactome; R-HSA-114608; Platelet degranulation.
DR Reactome; R-HSA-1236974; ER-Phagosome pathway.
DR Reactome; R-HSA-140875; Common Pathway of Fibrin Clot Formation.
DR Reactome; R-HSA-166058; MyD88:MAL(TIRAP) cascade initiated on plasma membrane.
DR Reactome; R-HSA-216083; Integrin cell surface interactions.
DR Reactome; R-HSA-354192; Integrin signaling.
DR Reactome; R-HSA-354194; GRB2:SOS provides linkage to MAPK signaling for Integrins.
DR Reactome; R-HSA-372708; p130Cas linkage to MAPK signaling for integrins.
DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-HSA-5602498; MyD88 deficiency (TLR2/4).
DR Reactome; R-HSA-5603041; IRAK4 deficiency (TLR2/4).
DR Reactome; R-HSA-5674135; MAP2K and MAPK activation.
DR Reactome; R-HSA-5686938; Regulation of TLR by endogenous ligand.
DR Reactome; R-HSA-6802946; Signaling by moderate kinase activity BRAF mutants.
DR Reactome; R-HSA-6802948; Signaling by high-kinase activity BRAF mutants.
DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions.
DR Reactome; R-HSA-6802955; Paradoxical activation of RAF signaling by kinase inactive BRAF.
DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR Reactome; R-HSA-9649948; Signaling downstream of RAS mutants.
DR Reactome; R-HSA-9656223; Signaling by RAF1 mutants.
DR Reactome; R-HSA-977225; Amyloid fiber formation.
DR SignaLink; P02671; -.
DR SIGNOR; P02671; -.
DR BioGRID-ORCS; 2243; 10 hits in 1072 CRISPR screens.
DR ChiTaRS; FGA; human.
DR EvolutionaryTrace; P02671; -.
DR GeneWiki; Fibrinogen_alpha_chain; -.
DR GenomeRNAi; 2243; -.
DR Pharos; P02671; Tbio.
DR PRO; PR:P02671; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P02671; protein.
DR Bgee; ENSG00000171560; Expressed in right lobe of liver and 111 other tissues.
DR ExpressionAtlas; P02671; baseline and differential.
DR Genevisible; P02671; HS.
DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:BHF-UCL.
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:BHF-UCL.
DR GO; GO:1903561; C:extracellular vesicle; HDA:UniProtKB.
DR GO; GO:0005577; C:fibrinogen complex; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0031091; C:platelet alpha granule; IDA:BHF-UCL.
DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome.
DR GO; GO:0005201; F:extracellular matrix structural constituent; HDA:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005102; F:signaling receptor binding; IEA:InterPro.
DR GO; GO:0005198; F:structural molecule activity; IDA:BHF-UCL.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0072377; P:blood coagulation, common pathway; IMP:BHF-UCL.
DR GO; GO:0072378; P:blood coagulation, fibrin clot formation; IDA:ComplexPortal.
DR GO; GO:0007160; P:cell-matrix adhesion; IDA:BHF-UCL.
DR GO; GO:0042730; P:fibrinolysis; IDA:UniProtKB.
DR GO; GO:0043152; P:induction of bacterial agglutination; IDA:CACAO.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:2000261; P:negative regulation of blood coagulation, common pathway; TAS:BHF-UCL.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; IDA:BHF-UCL.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; IDA:BHF-UCL.
DR GO; GO:0031639; P:plasminogen activation; IDA:UniProtKB.
DR GO; GO:0070527; P:platelet aggregation; IDA:BHF-UCL.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:BHF-UCL.
DR GO; GO:0045921; P:positive regulation of exocytosis; IDA:BHF-UCL.
DR GO; GO:0034116; P:positive regulation of heterotypic cell-cell adhesion; IDA:BHF-UCL.
DR GO; GO:0090277; P:positive regulation of peptide hormone secretion; IDA:BHF-UCL.
DR GO; GO:0050714; P:positive regulation of protein secretion; IDA:BHF-UCL.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; NAS:BHF-UCL.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; IDA:BHF-UCL.
DR GO; GO:0051258; P:protein polymerization; IDA:BHF-UCL.
DR GO; GO:0065003; P:protein-containing complex assembly; IDA:BHF-UCL.
DR GO; GO:0051592; P:response to calcium ion; IDA:BHF-UCL.
DR CDD; cd00087; FReD; 1.
DR Gene3D; 3.90.215.10; -; 1.
DR InterPro; IPR036056; Fibrinogen-like_C.
DR InterPro; IPR014716; Fibrinogen_a/b/g_C_1.
DR InterPro; IPR002181; Fibrinogen_a/b/g_C_dom.
DR InterPro; IPR012290; Fibrinogen_a/b/g_coil_dom.
DR InterPro; IPR021996; Fibrinogen_aC.
DR InterPro; IPR037579; Fibrinogen_alpha.
DR InterPro; IPR020837; Fibrinogen_CS.
DR PANTHER; PTHR47221; PTHR47221; 1.
DR Pfam; PF08702; Fib_alpha; 1.
DR Pfam; PF12160; Fibrinogen_aC; 1.
DR Pfam; PF00147; Fibrinogen_C; 1.
DR SMART; SM00186; FBG; 1.
DR SMART; SM01212; Fib_alpha; 1.
DR SUPFAM; SSF56496; SSF56496; 1.
DR PROSITE; PS00514; FIBRINOGEN_C_1; 1.
DR PROSITE; PS51406; FIBRINOGEN_C_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; Amyloid;
KW Amyloidosis; Blood coagulation; Calcium; Coiled coil;
KW Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein;
KW Hemostasis; Hydroxylation; Immunity; Innate immunity; Isopeptide bond;
KW Metal-binding; Phosphoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:518846, ECO:0000269|Ref.10,
FT ECO:0000269|Ref.14"
FT PEPTIDE 20..35
FT /note="Fibrinopeptide A"
FT /id="PRO_0000009021"
FT CHAIN 36..866
FT /note="Fibrinogen alpha chain"
FT /id="PRO_0000009022"
FT DOMAIN 623..864
FT /note="Fibrinogen C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT REGION 36..38
FT /note="Alpha-chain polymerization, binding distal domain of
FT another fibrin gamma chain"
FT REGION 262..460
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 543..638
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 68..631
FT /evidence="ECO:0000305|PubMed:19296670"
FT COMPBIAS 269..419
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 425..447
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 544..563
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 573..597
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 598..634
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 791
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:9689040,
FT ECO:0007744|PDB:1FZD"
FT BINDING 793
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:9689040,
FT ECO:0007744|PDB:1FZD"
FT BINDING 795
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:9689040,
FT ECO:0007744|PDB:1FZD"
FT BINDING 797
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:9689040,
FT ECO:0007744|PDB:1FZD"
FT SITE 35..36
FT /note="Cleavage; by thrombin; to release fibrinopeptide A"
FT SITE 100..101
FT /note="Cleavage; by plasmin; to break down fibrin clots"
FT SITE 121..122
FT /note="Cleavage; by hementin; to prevent blood coagulation"
FT SITE 123..124
FT /note="Cleavage; by plasmin; to break down fibrin clots"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16807684"
FT MOD_RES 45
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 50
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 56
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 281
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 291
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 294
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 364
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 412
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 451
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 501
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 505
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 524
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 560
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 565
FT /note="4-hydroxyproline; by P4HA1"
FT /evidence="ECO:0000269|PubMed:19696023"
FT MOD_RES 609
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039,
FT ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:24275569"
FT CARBOHYD 320
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:23050552"
FT CARBOHYD 351
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|PubMed:23050552"
FT CARBOHYD 453
FT /note="N-linked (GlcNAc...) asparagine; in variant Caracas-
FT 2"
FT /evidence="ECO:0000269|PubMed:1675636"
FT CARBOHYD 686
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:9689040"
FT DISULFID 47
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:19296670"
FT DISULFID 55
FT /note="Interchain (with C-95 in beta chain)"
FT /evidence="ECO:0000269|PubMed:19296670"
FT DISULFID 64
FT /note="Interchain (with C-49 in gamma chain)"
FT /evidence="ECO:0000269|PubMed:19296670"
FT DISULFID 68
FT /note="Interchain (with C-106 in beta chain)"
FT /evidence="ECO:0000269|PubMed:19296670"
FT DISULFID 180
FT /note="Interchain (with C-165 in gamma chain)"
FT /evidence="ECO:0000269|PubMed:19296670,
FT ECO:0000269|PubMed:741445, ECO:0000269|PubMed:9333233,
FT ECO:0000269|PubMed:9628725"
FT DISULFID 184
FT /note="Interchain (with C-223 in beta chain)"
FT /evidence="ECO:0000269|PubMed:19296670,
FT ECO:0000269|PubMed:741445, ECO:0000269|PubMed:9333233,
FT ECO:0000269|PubMed:9628725"
FT DISULFID 461..491
FT /evidence="ECO:0000250|UniProtKB:P02672"
FT DISULFID 799..812
FT /evidence="ECO:0000269|PubMed:9689040,
FT ECO:0007744|PDB:1FZD"
FT CROSSLNK 322
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-41 in alpha-2-antiplasmin)"
FT CROSSLNK 347
FT /note="Isoglutamyl lysine isopeptide (Gln-Lys) (interchain
FT with K-?)"
FT CROSSLNK 385
FT /note="Isoglutamyl lysine isopeptide (Gln-Lys) (interchain
FT with K-?)"
FT CROSSLNK 527
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-?)"
FT /evidence="ECO:0000255"
FT CROSSLNK 558
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-?)"
FT /evidence="ECO:0000255"
FT CROSSLNK 575
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-?)"
FT /evidence="ECO:0000255"
FT CROSSLNK 581
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-?)"
FT /evidence="ECO:0000255"
FT CROSSLNK 599
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-?)"
FT /evidence="ECO:0000255"
FT VAR_SEQ 631..644
FT /note="DCDDVLQTHPSGTQ -> GIHTSPLGKPSLSP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:6575389"
FT /id="VSP_001531"
FT VAR_SEQ 645..866
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:6575389"
FT /id="VSP_001532"
FT VARIANT 6
FT /note="I -> V (in dbSNP:rs2070025)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_011609"
FT VARIANT 26
FT /note="D -> N (in Lille-1; dbSNP:rs121909604)"
FT /id="VAR_002390"
FT VARIANT 31
FT /note="G -> V (in Rouen-1; dbSNP:rs121909605)"
FT /id="VAR_002391"
FT VARIANT 35
FT /note="R -> C (in DYSFIBRIN; fibrinogen Metz 1/Hershey III;
FT dbSNP:rs121909606)"
FT /evidence="ECO:0000269|PubMed:16846481"
FT /id="VAR_002392"
FT VARIANT 35
FT /note="R -> H (in dbSNP:rs121909607)"
FT /evidence="ECO:0000269|PubMed:8461606"
FT /id="VAR_002393"
FT VARIANT 37
FT /note="P -> L (in Kyoto-2; dbSNP:rs121909609)"
FT /evidence="ECO:0000269|PubMed:2070049"
FT /id="VAR_002394"
FT VARIANT 38
FT /note="R -> G (in Aarhus-1; dbSNP:rs121909608)"
FT /id="VAR_002397"
FT VARIANT 38
FT /note="R -> N (in Munich-1; requires 2 nucleotide
FT substitutions)"
FT /id="VAR_002395"
FT VARIANT 38
FT /note="R -> S (in Detroit-1; dbSNP:rs1403508334)"
FT /id="VAR_002396"
FT VARIANT 39
FT /note="V -> D (in Canterbury; dbSNP:rs121909614)"
FT /evidence="ECO:0000269|PubMed:8675656"
FT /id="VAR_010730"
FT VARIANT 55
FT /note="C -> R (in CAFBN; hypofibrinogenemia; heterozygous;
FT decreased fibrinogen complex assembly; no effect on
FT fibrinogen complex secretion)"
FT /evidence="ECO:0000269|PubMed:25427968"
FT /id="VAR_072721"
FT VARIANT 66
FT /note="S -> T"
FT /id="VAR_002398"
FT VARIANT 129
FT /note="R -> P (in CAFBN; hypofibrinogenemia; heterozygous;
FT no effect on fibrinogen complex assembly; no effect on
FT fibrinogen complex secretion)"
FT /evidence="ECO:0000269|PubMed:25427968"
FT /id="VAR_072722"
FT VARIANT 160
FT /note="R -> S (in Lima)"
FT /evidence="ECO:0000269|PubMed:1634621"
FT /id="VAR_002399"
FT VARIANT 184
FT /note="C -> W (in CAFBN; hypofibrinogenemia; heterozygous;
FT impaired fibrinogen complex assembly)"
FT /evidence="ECO:0000269|PubMed:25427968"
FT /id="VAR_072723"
FT VARIANT 331
FT /note="T -> A (in dbSNP:rs6050)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:14702039, ECO:0000269|Ref.3"
FT /id="VAR_011610"
FT VARIANT 446
FT /note="K -> E (in dbSNP:rs6052)"
FT /evidence="ECO:0000269|PubMed:10391209"
FT /id="VAR_014168"
FT VARIANT 453
FT /note="S -> N (in Caracas-2; dbSNP:rs121909610)"
FT /evidence="ECO:0000269|PubMed:1675636"
FT /id="VAR_002400"
FT VARIANT 456
FT /note="T -> A (in dbSNP:rs2070031)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_011611"
FT VARIANT 545
FT /note="E -> V (in AMYL8; dbSNP:rs121909612)"
FT /id="VAR_010731"
FT VARIANT 573
FT /note="R -> C (in DYSFIBRIN; fibrinogen Dusart/Paris-5;
FT dbSNP:rs121909613)"
FT /evidence="ECO:0000269|PubMed:8473507"
FT /id="VAR_002401"
FT VARIANT 573
FT /note="R -> L (in AMYL8; dbSNP:rs78506343)"
FT /evidence="ECO:0000269|PubMed:8097946"
FT /id="VAR_010732"
FT CONFLICT 177
FT /note="I -> V (in Ref. 4; BAF83248)"
FT /evidence="ECO:0000305"
FT CONFLICT 215..216
FT /note="SR -> RS (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 299
FT /note="S -> G (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 304
FT /note="S -> G (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 317..318
FT /note="GT -> SG (in Ref. 11; AA sequence)"
FT /evidence="ECO:0000305"
FT TURN 27..31
FT /evidence="ECO:0007829|PDB:1BBR"
FT STRAND 57..60
FT /evidence="ECO:0007829|PDB:3GHG"
FT STRAND 63..65
FT /evidence="ECO:0007829|PDB:3GHG"
FT HELIX 67..92
FT /evidence="ECO:0007829|PDB:3GHG"
FT HELIX 94..111
FT /evidence="ECO:0007829|PDB:3GHG"
FT HELIX 116..129
FT /evidence="ECO:0007829|PDB:3GHG"
FT TURN 133..135
FT /evidence="ECO:0007829|PDB:1FZA"
FT TURN 139..141
FT /evidence="ECO:0007829|PDB:1FZC"
FT HELIX 142..178
FT /evidence="ECO:0007829|PDB:1FZC"
FT TURN 179..183
FT /evidence="ECO:0007829|PDB:1FZC"
FT STRAND 184..186
FT /evidence="ECO:0007829|PDB:1RE3"
FT HELIX 195..209
FT /evidence="ECO:0007829|PDB:1FZC"
FT TURN 226..228
FT /evidence="ECO:0007829|PDB:3GHG"
FT STRAND 337..343
FT /evidence="ECO:0007829|PDB:4F27"
FT STRAND 582..587
FT /evidence="ECO:0007829|PDB:5CFA"
FT STRAND 673..681
FT /evidence="ECO:0007829|PDB:1FZD"
FT HELIX 689..694
FT /evidence="ECO:0007829|PDB:1FZD"
FT HELIX 711..718
FT /evidence="ECO:0007829|PDB:1FZD"
FT STRAND 723..729
FT /evidence="ECO:0007829|PDB:1FZD"
FT STRAND 735..744
FT /evidence="ECO:0007829|PDB:1FZD"
FT TURN 747..751
FT /evidence="ECO:0007829|PDB:1FZD"
FT STRAND 753..762
FT /evidence="ECO:0007829|PDB:1FZD"
FT TURN 765..768
FT /evidence="ECO:0007829|PDB:1FZD"
FT TURN 771..773
FT /evidence="ECO:0007829|PDB:1FZD"
FT HELIX 775..778
FT /evidence="ECO:0007829|PDB:1FZD"
FT STRAND 793..797
FT /evidence="ECO:0007829|PDB:1FZD"
FT HELIX 799..803
FT /evidence="ECO:0007829|PDB:1FZD"
FT STRAND 810..812
FT /evidence="ECO:0007829|PDB:1FZD"
FT STRAND 814..816
FT /evidence="ECO:0007829|PDB:1FZD"
FT STRAND 823..826
FT /evidence="ECO:0007829|PDB:1FZD"
FT HELIX 829..831
FT /evidence="ECO:0007829|PDB:1FZD"
FT STRAND 840..843
FT /evidence="ECO:0007829|PDB:1FZD"
FT HELIX 844..847
FT /evidence="ECO:0007829|PDB:1FZD"
FT STRAND 854..861
FT /evidence="ECO:0007829|PDB:1FZD"
FT CONFLICT P02671-2:640..644
FT /note="PSLSP -> LPCPPRLS (in Ref. 3; AAK31372)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 866 AA; 94973 MW; EA73A81204D8AEC4 CRC64;
MFSMRIVCLV LSVVGTAWTA DSGEGDFLAE GGGVRGPRVV ERHQSACKDS DWPFCSDEDW
NYKCPSGCRM KGLIDEVNQD FTNRINKLKN SLFEYQKNNK DSHSLTTNIM EILRGDFSSA
NNRDNTYNRV SEDLRSRIEV LKRKVIEKVQ HIQLLQKNVR AQLVDMKRLE VDIDIKIRSC
RGSCSRALAR EVDLKDYEDQ QKQLEQVIAK DLLPSRDRQH LPLIKMKPVP DLVPGNFKSQ
LQKVPPEWKA LTDMPQMRME LERPGGNEIT RGGSTSYGTG SETESPRNPS SAGSWNSGSS
GPGSTGNRNP GSSGTGGTAT WKPGSSGPGS TGSWNSGSSG TGSTGNQNPG SPRPGSTGTW
NPGSSERGSA GHWTSESSVS GSTGQWHSES GSFRPDSPGS GNARPNNPDW GTFEEVSGNV
SPGTRREYHT EKLVTSKGDK ELRTGKEKVT SGSTTTTRRS CSKTVTKTVI GPDGHKEVTK
EVVTSEDGSD CPEAMDLGTL SGIGTLDGFR HRHPDEAAFF DTASTGKTFP GFFSPMLGEF
VSETESRGSE SGIFTNTKES SSHHPGIAEF PSRGKSSSYS KQFTSSTSYN RGDSTFESKS
YKMADEAGSE ADHEGTHSTK RGHAKSRPVR DCDDVLQTHP SGTQSGIFNI KLPGSSKIFS
VYCDQETSLG GWLLIQQRMD GSLNFNRTWQ DYKRGFGSLN DEGEGEFWLG NDYLHLLTQR
GSVLRVELED WAGNEAYAEY HFRVGSEAEG YALQVSSYEG TAGDALIEGS VEEGAEYTSH
NNMQFSTFDR DADQWEENCA EVYGGGWWYN NCQAANLNGI YYPGGSYDPR NNSPYEIENG
VVWVSFRGAD YSLRAVRMKI RPLVTQ
