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 27-NOV-2024, entry version 268. 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 AMYLD2 LEU-573, AND INVOLVEMENT IN AMYLD2. 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; P27348: YWHAQ; NbExp=2; IntAct=EBI-348571, EBI-359854; 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 PubMed:19159218), but the evidence is still quite tenuous. Most likely, CC Asn-686 is not glycosylated in the healthy human body, or only with low CC efficiency. {ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218, CC ECO:0000269|PubMed:23151259, 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, hereditary systemic 2 (AMYLD2) [MIM:105200]: A CC form of hereditary systemic amyloidosis, a disorder characterized by CC amyloid deposition in multiple tissues resulting in a wide clinical CC spectrum. AMYLD2 is an autosomal dominant form characterized by CC deposition of amyloid preferentially in the glomeruli of the kidney. It CC clinically presents with hypertension, proteinuria, and finally CC azotemia. Involvement of liver and spleen may be seen in advanced CC cases, but heavy glomerular deposition without significant medium sized CC vessel involvement is characteristic of the disease. 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 --------------------------------------------------------------------------- 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; 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; 103. DR ComplexPortal; CPX-1922; Fibrinogen complex. DR ComplexPortal; CPX-6225; Fibrin complex. DR CORUM; P02671; -. DR DIP; DIP-29643N; -. DR IntAct; P02671; 72. DR MINT; P02671; -. DR STRING; 9606.ENSP00000498441; -. 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 UniLectin; P02671; -. DR CarbonylDB; P02671; -. DR GlyConnect; 1238; 3 N-Linked glycans (1 site). DR GlyConnect; 157; 4 N-Linked glycans. DR GlyCosmos; P02671; 23 sites, 14 glycans. DR GlyGen; P02671; 29 sites, 14 N-linked glycans (2 sites), 5 O-linked glycans (27 sites). DR iPTMnet; P02671; -. DR PhosphoSitePlus; P02671; -. DR SwissPalm; P02671; -. DR BioMuta; FGA; -. DR DMDM; 1706799; -. DR OGP; P02671; -. DR CPTAC; non-CPTAC-1117; -. DR CPTAC; non-CPTAC-1118; -. DR jPOST; P02671; -. DR MassIVE; P02671; -. DR PaxDb; 9606-ENSP00000306361; -. DR PeptideAtlas; P02671; -. DR ProteomicsDB; 51542; -. [P02671-1] DR ProteomicsDB; 51543; -. [P02671-2] DR Pumba; P02671; -. DR ABCD; P02671; 6 sequenced antibodies. DR Antibodypedia; 3395; 1075 antibodies from 45 providers. DR DNASU; 2243; -. DR Ensembl; ENST00000403106.8; ENSP00000385981.3; ENSG00000171560.18. [P02671-2] DR Ensembl; ENST00000651975.2; ENSP00000498441.1; ENSG00000171560.18. [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 AGR; HGNC:3661; -. 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. 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; PRIVEHM; -. DR OrthoDB; 3134470at2759; -. DR PhylomeDB; P02671; -. DR TreeFam; TF351984; -. DR BioCyc; MetaCyc:ENSG00000171560-MONOMER; -. 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 1158 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 113 other cell types or tissues. DR ExpressionAtlas; P02671; baseline and differential. 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:0030674; F:protein-macromolecule adaptor activity; IBA:GO_Central. 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:UniProtKB. 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: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 FunFam; 1.20.5.50:FF:000006; Fibrinogen alpha chain; 1. DR FunFam; 3.90.215.10:FF:000009; Fibrinogen alpha chain; 1. DR FunFam; 4.10.530.10:FF:000002; Fibrinogen gamma chain; 1. DR Gene3D; 1.20.5.50; -; 1. DR Gene3D; 3.90.215.10; Gamma Fibrinogen, chain A, domain 1; 1. DR Gene3D; 4.10.530.10; Gamma-fibrinogen Carboxyl Terminal Fragment, domain 2; 1. DR InterPro; IPR037579; Fibrinogen. 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; IPR020837; Fibrinogen_CS. DR NCBIfam; NF040941; GGGWT_bact; 1. DR PANTHER; PTHR47221; FIBRINOGEN ALPHA CHAIN; 1. DR PANTHER; PTHR47221:SF3; FIBRINOGEN ALPHA CHAIN; 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; Fibrinogen C-terminal domain-like; 1. DR SUPFAM; SSF58010; Fibrinogen coiled-coil and central regions; 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; Proteomics identification; KW 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; dbSNP:rs1730757828)" 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 AMYLD2; 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 AMYLD2; 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 //