Full text data of FGG
FGG
[Confidence: low (only semi-automatic identification from reviews)]
Fibrinogen gamma chain; Flags: Precursor
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Fibrinogen gamma chain; Flags: Precursor
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P02679
ID FIBG_HUMAN Reviewed; 453 AA.
AC P02679; A8K057; P04469; P04470; Q53Y18; Q96A14; Q96KJ3; Q9UC62;
read moreAC Q9UC63; Q9UCF3;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2002, sequence version 3.
DT 22-JAN-2014, entry version 183.
DE RecName: Full=Fibrinogen gamma chain;
DE Flags: Precursor;
GN Name=FGG; ORFNames=PRO2061;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=6688357; DOI=10.1021/bi00282a033;
RA Chung D.W., Chan W.-Y., Davie E.W.;
RT "Characterization of a complementary deoxyribonucleic acid coding for
RT the gamma chain of human fibrinogen.";
RL Biochemistry 22:3250-3256(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS GAMMA-A AND
RP GAMMA-B).
RX PubMed=2990550; DOI=10.1021/bi00329a041;
RA Rixon M.W., Chung D.W., Davie E.W.;
RT "Nucleotide sequence of the gene for the gamma chain of human
RT fibrinogen.";
RL Biochemistry 24:2077-2086(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS GAMMA-A AND GAMMA-B).
RC TISSUE=Liver;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GAMMA-A).
RC TISSUE=Fetal liver;
RA Zhang C., Yu Y., Zhang S., Wei H., Zhou G., Bi J., Zhang Y., Liu M.,
RA He F.;
RT "Functional prediction of the coding sequences of 33 new genes deduced
RT by analysis of cDNA clones from human fetal liver.";
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GAMMA-A).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-140 AND ARG-191.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GAMMA-A).
RC TISSUE=Skeletal muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 27-437.
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 [10]
RP PROTEIN SEQUENCE OF 27-41.
RC TISSUE=Platelet;
RX PubMed=8509453; DOI=10.1083/jcb.121.6.1329;
RA Bertagnolli M.E., Beckerle M.C.;
RT "Evidence for the selective association of a subpopulation of GPIIb-
RT IIIa with the actin cytoskeletons of thrombin-activated platelets.";
RL J. Cell Biol. 121:1329-1342(1993).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 75-286.
RC TISSUE=Liver;
RX PubMed=1685103;
RA Marchetti L., Zanelli T., Malcovati M., Tenchini M.L.;
RT "Polymorphism of the human gamma chain fibrinogen gene.";
RL DNA Seq. 1:419-422(1991).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 209-270.
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
RT gamma-chains of human fibrinogen.";
RL Nucleic Acids Res. 11:7427-7434(1983).
RN [13]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 285-437 (ISOFORMS GAMMA-A AND
RP GAMMA-B).
RX PubMed=6092346;
RA Fornace A.J. Jr., Cummings D.E., Comeau C.M., Kant J.A.,
RA Crabtree G.R.;
RT "Structure of the human gamma-fibrinogen gene. Alternate mRNA splicing
RT near the 3' end of the gene produces gamma A and gamma B forms of
RT gamma-fibrinogen.";
RL J. Biol. Chem. 259:12826-12830(1984).
RN [14]
RP PROTEIN SEQUENCE OF 291-310, AND VARIANTS BARCELONA-3/BARCELONA-4
RP HIS-301 AND VILLAJOYOSA CYS-301.
RC TISSUE=Blood;
RX PubMed=7654933;
RA Borrell M., Gari M., Coll I., Vallve C., Tirado I., Soria J.M.,
RA Sala N., Munoz C., Oliver A., Garcia A.;
RT "Abnormal polymerization and normal binding of plasminogen and t-PA in
RT three new dysfibrinogenaemias: Barcelona III and IV (gamma Arg
RT 275-->His) and Villajoyosa (gamma Arg 275-->Cys).";
RL Blood Coagul. Fibrinolysis 6:198-206(1995).
RN [15]
RP PROTEIN SEQUENCE OF 411-453 (ISOFORM GAMMA-B).
RX PubMed=7306501; DOI=10.1021/bi00524a036;
RA Wolfenstein-Todel C., Mosesson M.W.;
RT "Carboxy-terminal amino acid sequence of a human fibrinogen gamma-
RT chain variant (gamma').";
RL Biochemistry 20:6146-6149(1981).
RN [16]
RP REVIEW, AND DISULFIDE BONDS.
RX PubMed=6575689; DOI=10.1111/j.1749-6632.1983.tb23232.x;
RA Henschen A., Lottspeich F., Kehl M., Southan C.;
RT "Covalent structure of fibrinogen.";
RL Ann. N. Y. Acad. Sci. 408:28-43(1983).
RN [17]
RP DISULFIDE BONDS.
RA Doolittle R.F., Takagi T., Watt K.W.K., Bouma H. III, Cottrell B.A.,
RA Cassman K.G., Goldbaum D.M., Doolittle L.R., Friezner S.J.;
RT "The structures of fibrinogen and fibrin.";
RL (In) Magnusson S., Ottesen M., Foltmann B., Dano K., Neurath H.
RL (eds.);
RL Regulatory proteolytic enzymes and their inhibitors, pp.163-172,
RL Pergamon Press, New York (1978).
RN [18]
RP DISULFIDE BONDS.
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 [19]
RP QUATERNARY STRUCTURE, AND DISULFIDE BONDS.
RX PubMed=6860649; DOI=10.1021/bi00278a003;
RA Hoeprich P.D., Doolittle R.F.;
RT "Dimeric half-molecules of human fibrinogen are joined through
RT disulfide bonds in an antiparallel orientation.";
RL Biochemistry 22:2049-2055(1983).
RN [20]
RP SULFATION.
RX PubMed=1892842; DOI=10.1021/bi00103a004;
RA Farrel D.H., Mulvihill E.R., Huang S., Chung D.W., Davie E.W.;
RT "Recombinant human fibrinogen and sulfation of the gamma' chain.";
RL Biochemistry 30:9414-9420(1991).
RN [21]
RP SULFATION AT TYR-444 AND TYR-448.
RX PubMed=11307817;
RA Meh D.A., Siebenlist K.R., Brennan S.O., Holyst T., Mosesson M.W.;
RT "The amino acid sequence in fibrin responsible for high affinity
RT thrombin binding.";
RL Thromb. Haemost. 85:470-474(2001).
RN [22]
RP REVIEW, ELECTRON MICROSCOPY, POLYMERIZATION, AND LIGANDS.
RX PubMed=6383194;
RA Doolittle R.F.;
RT "Fibrinogen and fibrin.";
RL Annu. Rev. Biochem. 53:195-229(1984).
RN [23]
RP POLYMERIZATION SITE.
RX PubMed=6592597; DOI=10.1073/pnas.81.19.5980;
RA Horwitz B.H., Varadi A., Scheraga H.A.;
RT "Localization of a fibrin gamma-chain polymerization site within
RT segment Thr-374 to Glu-396 of human fibrinogen.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:5980-5984(1984).
RN [24]
RP POLYMERIZATION SITE.
RX PubMed=6451630;
RA Olexa S.A., Budzynski A.Z.;
RT "Localization of a fibrin polymerization site.";
RL J. Biol. Chem. 256:3544-3549(1981).
RN [25]
RP PLATELET AGGREGATION SITE.
RX PubMed=6326808; DOI=10.1021/bi00303a028;
RA Kloczewiak M., Timmons S., Lukas T.J., Hawiger J.;
RT "Platelet receptor recognition site on human fibrinogen. Synthesis and
RT structure-function relationship of peptides corresponding to the
RT carboxy-terminal segment of the gamma chain.";
RL Biochemistry 23:1767-1774(1984).
RN [26]
RP PLATELET AGGREGATION SITE.
RX PubMed=6325435;
RA Plow E.F., Srouji A.H., Meyer D., Marguerie G., Ginsberg M.H.;
RT "Evidence that three adhesive proteins interact with a common
RT recognition site on activated platelets.";
RL J. Biol. Chem. 259:5388-5391(1984).
RN [27]
RP CALCIUM-BINDING SITE.
RX PubMed=3160702;
RA Dang C.V., Ebert R.F., Bell W.R.;
RT "Localization of a fibrinogen calcium binding site between gamma-
RT subunit positions 311 and 336 by terbium fluorescence.";
RL J. Biol. Chem. 260:9713-9719(1985).
RN [28]
RP CHROMATOGRAPHIC COMPARISON OF GAMMA-A AND GAMMA-B CHAINS.
RX PubMed=6933547; DOI=10.1073/pnas.77.9.5069;
RA Wolfenstein-Todel C., Mosesson M.W.;
RT "Human plasma fibrinogen heterogeneity: evidence for an extended
RT carboxyl-terminal sequence in a normal gamma chain variant (gamma').";
RL Proc. Natl. Acad. Sci. U.S.A. 77:5069-5073(1980).
RN [29]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-78, AND MASS SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=14760718; DOI=10.1002/pmic.200300556;
RA Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.;
RT "Screening for N-glycosylated proteins by liquid chromatography mass
RT spectrometry.";
RL Proteomics 4:454-465(2004).
RN [30]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-78, AND MASS SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA Moore R.J., Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [31]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-78, AND MASS SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=16263699; DOI=10.1074/mcp.M500324-MCP200;
RA Lewandrowski U., Moebius J., Walter U., Sickmann A.;
RT "Elucidation of N-glycosylation sites on human platelet proteins: a
RT glycoproteomic approach.";
RL Mol. Cell. Proteomics 5:226-233(2006).
RN [32]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-78, AND MASS SPECTROMETRY.
RC TISSUE=Milk;
RX PubMed=18780401; DOI=10.1002/pmic.200701057;
RA Picariello G., Ferranti P., Mamone G., Roepstorff P., Addeo F.;
RT "Identification of N-linked glycoproteins in human milk by hydrophilic
RT interaction liquid chromatography and mass spectrometry.";
RL Proteomics 8:3833-3847(2008).
RN [33]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-78, AND MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [34]
RP GLYCOSYLATION AT ASN-78.
RX PubMed=19139490; DOI=10.1074/mcp.M800504-MCP200;
RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F.,
RA Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y.,
RA Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core
RT fucosylated glycoproteins.";
RL Mol. Cell. Proteomics 8:913-923(2009).
RN [35]
RP CLEAVAGE BY HEMENTIN AND PLASMIN.
RX PubMed=2143188;
RA Kirschbaum N.E., Budzynski A.Z.;
RT "A unique proteolytic fragment of human fibrinogen containing the A
RT alpha COOH-terminal domain of the native molecule.";
RL J. Biol. Chem. 265:13669-13676(1990).
RN [36]
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.,
RA Buerckstuemmer T., 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 [37]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 169-437.
RX PubMed=9016719; DOI=10.1016/S0969-2126(97)00171-8;
RA Yee V.C., Pratt K.P., Cote H.C.F., le Trong I., Chung D.W.,
RA Davie E.W., Stenkamp R.E., Teller D.C.;
RT "Crystal structure of a 30 kDa C-terminal fragment from the gamma
RT chain of human fibrinogen.";
RL Structure 5:125-138(1997).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 169-437.
RX PubMed=9207064; DOI=10.1073/pnas.94.14.7176;
RA Pratt K.P., Cote H.C.F., Chung D.W., Stenkamp R.E., Davie E.W.;
RT "The primary fibrin polymerization pocket: three-dimensional structure
RT of a 30-kDa C-terminal gamma chain fragment complexed with the peptide
RT Gly-Pro-Arg-Pro.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:7176-7181(1997).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 114-432.
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
RT crosslinked counterpart from fibrin.";
RL Nature 389:455-462(1997).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 114-432.
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 [41]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 114-432.
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
RT fibrin(ogen) upon binding the peptide ligand Gly-His-Arg-Pro-amide.";
RL Biochemistry 38:2941-2946(1999).
RN [42]
RP VARIANT ASAHI THR-336.
RX PubMed=2496144; DOI=10.1172/JCI114056;
RA Yamazumi K., Shimura K., Terukina S., Takahashi N., Matsuda M.;
RT "A gamma methionine-310 to threonine substitution and consequent N-
RT glycosylation at gamma asparagine-308 identified in a congenital
RT dysfibrinogenemia associated with posttraumatic bleeding, fibrinogen
RT Asahi.";
RL J. Clin. Invest. 83:1590-1597(1989).
RN [43]
RP VARIANTS OSAKA-2 CYS-301; KYOTO-1 LYS-334; ASAHI THR-336 AND KYOTO-3
RP TYR-356.
RX PubMed=1421174;
RA Mimuro J., Muramatsu S., Maekawa H., Sakata Y., Kaneko M.,
RA Yoshitake S., Okuma M., Ito Y., Takeda Y., Matsuda M.;
RT "Gene analyses of abnormal fibrinogens with a mutation in the gamma
RT chain.";
RL Int. J. Hematol. 56:129-134(1992).
RN [44]
RP VARIANT BALTIMORE-1 VAL-318.
RX PubMed=2257302;
RA Bantia S., Mane S.M., Bell W.R., Dang C.V.;
RT "Fibrinogen Baltimore I: polymerization defect associated with a gamma
RT 292Gly-->Val (GGC-->GTC) mutation.";
RL Blood 76:2279-2283(1990).
RN [45]
RP VARIANT BALTIMORE-3 ILE-334.
RX PubMed=2328317;
RA Bantia S., Bell W.R., Dang C.V.;
RT "Polymerization defect of fibrinogen Baltimore III due to a gamma
RT Asn308-->Ile mutation.";
RL Blood 75:1659-1663(1990).
RN [46]
RP VARIANT BERN-1 LYS-363.
RX PubMed=8400260;
RA Steinmann C., Reber P., Jungo M., Laemmle B., Heinemann G.,
RA Wermuth B., Furlan M.;
RT "Fibrinogen Bern I: substitution gamma 337 Asn-->Lys is responsible
RT for defective fibrin monomer polymerization.";
RL Blood 82:2104-2108(1993).
RN [47]
RP VARIANT KYOTO-1 LYS-334.
RX PubMed=2971046;
RA Yoshida N., Terukina S., Okuma M., Moroi M., Aoki N., Matsuda M.;
RT "Characterization of an apparently lower molecular weight gamma-chain
RT variant in fibrinogen Kyoto I. The replacement of gamma-asparagine 308
RT by lysine which causes accelerated cleavage of fragment D1 by plasmin
RT and the generation of a new plasmin cleavage site.";
RL J. Biol. Chem. 263:13848-13856(1988).
RN [48]
RP VARIANT KYOTO-3 TYR-356.
RX PubMed=2819242;
RA Terukina S., Yamazumi K., Okamoto K., Yamashita H., Ito Y.,
RA Matsuda M.;
RT "Fibrinogen Kyoto III: a congenital dysfibrinogen with a gamma
RT aspartic acid-330 to tyrosine substitution manifesting impaired fibrin
RT monomer polymerization.";
RL Blood 74:2681-2687(1989).
RN [49]
RP VARIANT MILANO-1 VAL-356.
RX PubMed=3708159;
RA Reber P., Furlan M., Rupp C., Kehl M., Henschen A., Mannucci P.M.,
RA Beck E.A.;
RT "Characterization of fibrinogen Milano I: amino acid exchange gamma
RT 330 Asp-->Val impairs fibrin polymerization.";
RL Blood 67:1751-1756(1986).
RN [50]
RP VARIANT MILANO-5 CYS-301.
RX PubMed=7841300;
RA Steinmann C., Boegli C., Jungo M., Laemmle B., Heinemann G.,
RA Wermuth B., Redaelli R., Baudo F., Furlan M.;
RT "Fibrinogen Milano V: a congenital dysfibrinogenaemia with a gamma 275
RT Arg-->Cys substitution.";
RL Blood Coagul. Fibrinolysis 5:463-471(1994).
RN [51]
RP VARIANT MILANO-7 CYS-384.
RX PubMed=8080993;
RA Steinmann C., Boegli C., Jungo M., Laemmle B., Heinemann G.,
RA Wermuth B., Redaelli R., Baudo F., Furlan M.;
RT "A new substitution, gamma 358 Ser-->Cys, in fibrinogen Milano VII
RT causes defective fibrin polymerization.";
RL Blood 84:1874-1880(1994).
RN [52]
RP VARIANT NAGOYA-1 ARG-355.
RX PubMed=2738036;
RA Miyata T., Furukawa K., Iwanaga S., Takamatsu J., Saito H.;
RT "Fibrinogen Nagoya, a replacement of glutamine-329 by arginine in the
RT gamma-chain that impairs the polymerization of fibrin monomer.";
RL J. Biochem. 105:10-14(1989).
RN [53]
RP VARIANT OSAKA-2 CYS-301.
RX PubMed=2971042;
RA Terukina S., Matsuda M., Hirata H., Takeda Y., Miyata T., Takao T.,
RA Shimonishi Y.;
RT "Substitution of gamma Arg-275 by Cys in an abnormal fibrinogen,
RT 'fibrinogen Osaka II'. Evidence for a unique solitary cystine
RT structure at the mutation site.";
RL J. Biol. Chem. 263:13579-13587(1988).
RN [54]
RP VARIANT OSAKA-3 HIS-301.
RX PubMed=1455400;
RA Yoshida N., Imoka S., Hirata H., Matsuda M., Asakura S.;
RT "Heterozygous abnormal fibrinogen Osaka III with the replacement of
RT gamma arginine-275 by histidine has an apparently higher molecular
RT weight gamma-chain variant.";
RL Thromb. Haemost. 68:534-538(1992).
RN [55]
RP VARIANT OSAKA-5 GLY-401.
RX PubMed=1733971;
RA Yoshida N., Hirata H., Morigami Y., Imaoka S., Matsuda M.,
RA Yamazumi K., Asakura S.;
RT "Characterization of an abnormal fibrinogen Osaka V with the
RT replacement of gamma-arginine 375 by glycine. The lack of high
RT affinity calcium binding to D-domains and the lack of protective
RT effect of calcium on fibrinolysis.";
RL J. Biol. Chem. 267:2753-2759(1992).
RN [56]
RP VARIANT PARIS-1 GLY-377 DELINS
RP VAL-MET-CYS-GLY-GLU-ALA-LEU-PRO-MET-LEU-LYS-ASP-PRO-CYS-TYR-SER.
RX PubMed=8470043;
RA Rosenberg J.B., Newman P.J., Mosesson M.W., Guillin M.-C.,
RA Amrani D.L.;
RT "Paris I dysfibrinogenemia: a point mutation in intron 8 results in
RT insertion of a 15 amino acid sequence in the fibrinogen gamma-chain.";
RL Thromb. Haemost. 69:217-220(1993).
RN [57]
RP VARIANT TOCHIGI CYS-301.
RX PubMed=3337908;
RA Yoshida N., Ota K., Moroi M., Matsuda M.;
RT "An apparently higher molecular weight gamma-chain variant in a new
RT congenital abnormal fibrinogen Tochigi characterized by the
RT replacement of gamma arginine-275 by cysteine.";
RL Blood 71:480-487(1988).
RN [58]
RP VARIANT VLISSINGEN 345-ASN-ASP-346 DEL.
RX PubMed=2071611;
RA Koopman J., Haverkate F., Briet E., Lord S.T.;
RT "A congenitally abnormal fibrinogen (Vlissingen) with a 6-base
RT deletion in the gamma-chain gene, causing defective calcium binding
RT and impaired fibrin polymerization.";
RL J. Biol. Chem. 266:13456-13461(1991).
RN [59]
RP VARIANT BERGAMO-2/ESSEN/HAIFA/PERUGIA HIS-301.
RX PubMed=3563970;
RA Reber P., Furlan M., Henschen A., Kaudewitz H., Barbui T., Hilgard P.,
RA Nenci G.G., Berrettini M., Beck E.A.;
RT "Three abnormal fibrinogen variants with the same amino acid
RT substitution (gamma 275 Arg-->His): fibrinogens Bergamo II, Essen and
RT Perugia.";
RL Thromb. Haemost. 56:401-406(1986).
RN [60]
RP VARIANT SAGA HIS-301.
RX PubMed=2976995;
RA Yamazumi K., Terukina S., Onohara S., Matsuda M.;
RT "Normal plasmic cleavage of the gamma-chain variant of 'fibrinogen
RT Saga' with an Arg-275 to His substitution.";
RL Thromb. Haemost. 60:476-480(1988).
RN [61]
RP VARIANT MILANO-12 ARG-191.
RX PubMed=11435303; DOI=10.1182/blood.V98.2.351;
RA Bolliger-Stucki B., Lord S.T., Furlan M.;
RT "Fibrinogen Milano XII: a dysfunctional variant containing 2 amino
RT acid substitutions, A-alpha R16C and gamma G165R.";
RL Blood 98:351-357(2001).
RN [62]
RP VARIANTS ARG-191 AND VAL-410.
RX PubMed=10391209; DOI=10.1038/10290;
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RT "Characterization of single-nucleotide polymorphisms in coding regions
RT of human genes.";
RL Nat. Genet. 22:231-238(1999).
RN [63]
RP ERRATUM.
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RL Nat. Genet. 23:373-373(1999).
RN [64]
RP VARIANT HILLSBOROUGH ASP-335.
RX PubMed=11986213; DOI=10.1182/blood.V99.10.3597;
RA Mullin J.L., Brennan S.O., Ganly P.S., George P.M.;
RT "Fibrinogen Hillsborough: a novel gamma-gly309asp dysfibrinogen with
RT impaired clotting.";
RL Blood 99:3597-3601(2002).
CC -!- FUNCTION: Fibrinogen has a double function: yielding monomers that
CC polymerize into fibrin and acting as a cofactor in platelet
CC aggregation.
CC -!- SUBUNIT: Heterohexamer; disulfide linked. Contains 2 sets of 3
CC non-identical chains (alpha, beta and gamma). The 2 heterotrimers
CC are in head to head conformation with the N-termini in a small
CC central domain (By similarity).
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Gamma-B; Synonyms=Gamma';
CC IsoId=P02679-1; Sequence=Displayed;
CC Note=Present in about 10% of the fibrinogen molecules in plasma
CC but absent from those in the platelets;
CC Name=Gamma-A;
CC IsoId=P02679-2; Sequence=VSP_001537;
CC -!- DOMAIN: A long coiled coil structure formed by 3 polypeptide
CC chains connects the central nodule to the C-terminal domains
CC (distal nodules). The long C-terminal ends of the alpha chains
CC fold back, contributing a fourth strand to the coiled coil
CC structure.
CC -!- PTM: Conversion of fibrinogen to fibrin is triggered by thrombin,
CC which cleaves fibrinopeptides A and B from alpha and beta chains,
CC and thus exposes the N-terminal polymerization sites responsible
CC for the formation of the soft clot. The soft clot is converted
CC into the hard clot by factor XIIIA which catalyzes the epsilon-
CC (gamma-glutamyl)lysine cross-linking between gamma chains
CC (stronger) and between alpha chains (weaker) of different
CC monomers.
CC -!- PTM: Sulfation of C-terminal tyrosines increases affinity for
CC thrombin.
CC -!- DISEASE: Congenital afibrinogenemia (CAFBN) [MIM:202400]: Rare
CC autosomal recessive disorder is characterized by bleeding that
CC varies from mild to severe and by complete absence or extremely
CC low levels of plasma and platelet fibrinogen. Note=The disease is
CC caused by mutations affecting the gene represented in this entry.
CC Patients with congenital fibrinogen abnormalities can manifest
CC different clinical pictures. Some cases are clinically silent,
CC some show a tendency toward bleeding and some show a
CC predisposition for thrombosis with or without bleeding.
CC -!- MISCELLANEOUS: The gamma-chain carries the main binding site for
CC the platelet receptor.
CC -!- SIMILARITY: Contains 1 fibrinogen C-terminal domain.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/FGG";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Fibrinogen entry;
CC URL="http://en.wikipedia.org/wiki/Fibrinogen";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/fgg/";
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DR EMBL; M10014; AAB59530.1; -; Genomic_DNA.
DR EMBL; M10014; AAB59531.1; -; Genomic_DNA.
DR EMBL; AF118092; AAF22036.1; -; mRNA.
DR EMBL; AF350254; AAK19751.2; -; Genomic_DNA.
DR EMBL; AF350254; AAK19752.2; -; Genomic_DNA.
DR EMBL; AK289422; BAF82111.1; -; mRNA.
DR EMBL; AK290824; BAF83513.1; -; mRNA.
DR EMBL; BT007081; AAP35744.1; -; mRNA.
DR EMBL; CH471056; EAX04917.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX04919.1; -; Genomic_DNA.
DR EMBL; BC007044; AAH07044.1; -; mRNA.
DR EMBL; BC021674; AAH21674.1; -; mRNA.
DR EMBL; X51473; CAA35837.1; -; mRNA.
DR EMBL; X00086; CAA24944.1; -; mRNA.
DR EMBL; K02569; AAA52430.1; -; Genomic_DNA.
DR EMBL; K02569; AAA52431.1; -; Genomic_DNA.
DR PIR; A90470; FGHUG.
DR PIR; A90494; FGHUGB.
DR RefSeq; NP_000500.2; NM_000509.4.
DR RefSeq; NP_068656.2; NM_021870.2.
DR UniGene; Hs.727584; -.
DR PDB; 1DUG; X-ray; 1.80 A; A/B=424-433.
DR PDB; 1FIB; X-ray; 2.10 A; A=169-433.
DR PDB; 1FIC; X-ray; 2.50 A; A/B=169-433.
DR PDB; 1FID; X-ray; 2.10 A; A=169-433.
DR PDB; 1FZA; X-ray; 2.90 A; C/F=114-432.
DR PDB; 1FZB; X-ray; 2.90 A; C/F=114-432.
DR PDB; 1FZC; X-ray; 2.30 A; C/F=114-432.
DR PDB; 1FZE; X-ray; 3.00 A; C/F=114-432.
DR PDB; 1FZF; X-ray; 2.70 A; C/F=114-432.
DR PDB; 1FZG; X-ray; 2.50 A; C/F=114-432.
DR PDB; 1LT9; X-ray; 2.80 A; C/F=122-432.
DR PDB; 1LTJ; X-ray; 2.80 A; C/F=122-432.
DR PDB; 1N86; X-ray; 3.20 A; C/F=114-433.
DR PDB; 1N8E; X-ray; 4.50 A; C/F=114-433.
DR PDB; 1RE3; X-ray; 2.45 A; C/F=122-432.
DR PDB; 1RE4; X-ray; 2.70 A; C/F=122-432.
DR PDB; 1RF0; X-ray; 2.81 A; C/F=122-432.
DR PDB; 1RF1; X-ray; 2.53 A; C/F=122-432.
DR PDB; 2A45; X-ray; 3.65 A; I/L=27-71.
DR PDB; 2FFD; X-ray; 2.89 A; C/F=122-432.
DR PDB; 2FIB; X-ray; 2.01 A; A=169-433.
DR PDB; 2H43; X-ray; 2.70 A; C/F=115-433.
DR PDB; 2HLO; X-ray; 2.60 A; C/F=114-433.
DR PDB; 2HOD; X-ray; 2.90 A; C/F/I/L=115-433.
DR PDB; 2HPC; X-ray; 2.90 A; C/F/I/L=115-433.
DR PDB; 2HWL; X-ray; 2.40 A; P=439-452.
DR PDB; 2OYH; X-ray; 2.40 A; C/F=122-432.
DR PDB; 2OYI; X-ray; 2.70 A; C/F=122-432.
DR PDB; 2Q9I; X-ray; 2.80 A; C/F=114-433.
DR PDB; 2VDO; X-ray; 2.51 A; C=426-433.
DR PDB; 2VDP; X-ray; 2.80 A; C=428-433.
DR PDB; 2VDQ; X-ray; 2.59 A; C=426-433.
DR PDB; 2VDR; X-ray; 2.40 A; C=428-433.
DR PDB; 2VR3; X-ray; 1.95 A; C/D=425-433.
DR PDB; 2XNX; X-ray; 3.30 A; C/F/I/L=114-432.
DR PDB; 2XNY; X-ray; 7.50 A; C/F=114-432.
DR PDB; 2Y7L; X-ray; 1.49 A; B=421-433.
DR PDB; 2Z4E; X-ray; 2.70 A; C/F=114-433.
DR PDB; 3BVH; X-ray; 2.60 A; C/F=128-420.
DR PDB; 3E1I; X-ray; 2.30 A; C/F=114-432.
DR PDB; 3FIB; X-ray; 2.10 A; A=170-418.
DR PDB; 3GHG; X-ray; 2.90 A; C/F/I/L=27-433.
DR PDB; 3H32; X-ray; 3.60 A; C/F=121-433.
DR PDB; 3HUS; X-ray; 3.04 A; C/F=122-432.
DR PDB; 4B60; X-ray; 1.83 A; C/D=421-433.
DR PDBsum; 1DUG; -.
DR PDBsum; 1FIB; -.
DR PDBsum; 1FIC; -.
DR PDBsum; 1FID; -.
DR PDBsum; 1FZA; -.
DR PDBsum; 1FZB; -.
DR PDBsum; 1FZC; -.
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; 2A45; -.
DR PDBsum; 2FFD; -.
DR PDBsum; 2FIB; -.
DR PDBsum; 2H43; -.
DR PDBsum; 2HLO; -.
DR PDBsum; 2HOD; -.
DR PDBsum; 2HPC; -.
DR PDBsum; 2HWL; -.
DR PDBsum; 2OYH; -.
DR PDBsum; 2OYI; -.
DR PDBsum; 2Q9I; -.
DR PDBsum; 2VDO; -.
DR PDBsum; 2VDP; -.
DR PDBsum; 2VDQ; -.
DR PDBsum; 2VDR; -.
DR PDBsum; 2VR3; -.
DR PDBsum; 2XNX; -.
DR PDBsum; 2XNY; -.
DR PDBsum; 2Y7L; -.
DR PDBsum; 2Z4E; -.
DR PDBsum; 3BVH; -.
DR PDBsum; 3E1I; -.
DR PDBsum; 3FIB; -.
DR PDBsum; 3GHG; -.
DR PDBsum; 3H32; -.
DR PDBsum; 3HUS; -.
DR PDBsum; 4B60; -.
DR ProteinModelPortal; P02679; -.
DR SMR; P02679; 28-421.
DR DIP; DIP-29644N; -.
DR IntAct; P02679; 1.
DR MINT; MINT-5004002; -.
DR BindingDB; P02679; -.
DR ChEMBL; CHEMBL2364709; -.
DR DrugBank; DB00364; Sucralfate.
DR PhosphoSite; P02679; -.
DR DMDM; 20178280; -.
DR DOSAC-COBS-2DPAGE; P02679; -.
DR OGP; P02679; -.
DR REPRODUCTION-2DPAGE; IPI00219713; -.
DR REPRODUCTION-2DPAGE; P02679; -.
DR SWISS-2DPAGE; P02679; -.
DR PaxDb; P02679; -.
DR PeptideAtlas; P02679; -.
DR PRIDE; P02679; -.
DR DNASU; 2266; -.
DR Ensembl; ENST00000336098; ENSP00000336829; ENSG00000171557.
DR Ensembl; ENST00000404648; ENSP00000384860; ENSG00000171557.
DR GeneID; 2266; -.
DR KEGG; hsa:2266; -.
DR UCSC; uc003ioj.3; human.
DR CTD; 2266; -.
DR GeneCards; GC04M155525; -.
DR HGNC; HGNC:3694; FGG.
DR HPA; HPA027529; -.
DR MIM; 134850; gene.
DR MIM; 202400; phenotype.
DR neXtProt; NX_P02679; -.
DR Orphanet; 98880; Familial afibrinogenemia.
DR Orphanet; 98881; Familial dysfibrinogenemia.
DR Orphanet; 248408; Familial hypodysfibrinogenemia.
DR Orphanet; 101041; Familial hypofibrinogenemia.
DR PharmGKB; PA430; -.
DR eggNOG; NOG269667; -.
DR HOVERGEN; HBG099783; -.
DR KO; K03905; -.
DR OrthoDB; EOG7X9G60; -.
DR PhylomeDB; P02679; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR Reactome; REACT_604; Hemostasis.
DR ChiTaRS; FGG; human.
DR EvolutionaryTrace; P02679; -.
DR GeneWiki; FGG; -.
DR GenomeRNAi; 2266; -.
DR NextBio; 9205; -.
DR PMAP-CutDB; P02679; -.
DR PRO; PR:P02679; -.
DR ArrayExpress; P02679; -.
DR Bgee; P02679; -.
DR CleanEx; HS_FGG; -.
DR Genevestigator; P02679; -.
DR GO; GO:0072562; C:blood microparticle; IEA:Ensembl.
DR GO; GO:0005938; C:cell cortex; IEA:Ensembl.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005577; C:fibrinogen complex; TAS:ProtInc.
DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome.
DR GO; GO:0051258; P:protein polymerization; IEA:InterPro.
DR GO; GO:0051592; P:response to calcium ion; IDA:BHF-UCL.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR Gene3D; 3.90.215.10; -; 1.
DR Gene3D; 4.10.530.10; -; 1.
DR InterPro; IPR014716; Fibrinogen_a/b/g_C_1.
DR InterPro; IPR014715; Fibrinogen_a/b/g_C_2.
DR InterPro; IPR002181; Fibrinogen_a/b/g_C_dom.
DR InterPro; IPR012290; Fibrinogen_a/b/g_coil_dom.
DR InterPro; IPR020837; Fibrinogen_CS.
DR Pfam; PF08702; Fib_alpha; 1.
DR Pfam; PF00147; Fibrinogen_C; 1.
DR SMART; SM00186; FBG; 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; Alternative splicing; Blood coagulation; Calcium;
KW Coiled coil; Complete proteome; Direct protein sequencing;
KW Disease mutation; Disulfide bond; Glycoprotein; Hemostasis;
KW Isopeptide bond; Metal-binding; Polymorphism; Reference proteome;
KW Secreted; Signal; Sulfation.
FT SIGNAL 1 26
FT CHAIN 27 453 Fibrinogen gamma chain.
FT /FTId=PRO_0000009099.
FT DOMAIN 170 416 Fibrinogen C-terminal.
FT CA_BIND 341 355
FT REGION 400 422 Gamma-chain polymerization, binding amino
FT end of another fibrin alpha chain.
FT REGION 423 437 Platelet aggregation and Staphylococcus
FT clumping.
FT SITE 84 85 Cleavage; by plasmin; to break down
FT fibrin clots.
FT SITE 88 89 Cleavage; by plasmin; to break down
FT fibrin clots.
FT SITE 102 103 Cleavage; by hementin; to prevent blood
FT coagulation.
FT MOD_RES 444 444 Sulfotyrosine.
FT MOD_RES 448 448 Sulfotyrosine.
FT CARBOHYD 78 78 N-linked (GlcNAc...) (complex).
FT CARBOHYD 334 334 N-linked (GlcNAc...); in variant Asahi.
FT DISULFID 34 34 Interchain (with C-35).
FT DISULFID 35 35 Interchain (with C-34).
FT DISULFID 45 45 Interchain (with C-110 in beta chain).
FT DISULFID 49 49 Interchain (with C-64 in alpha chain).
FT DISULFID 161 161 Interchain (with C-227 in beta chain).
FT DISULFID 165 165 Interchain (with C-180 in alpha chain).
FT DISULFID 179 208
FT DISULFID 352 365
FT CROSSLNK 424 424 Isoglutamyl lysine isopeptide (Gln-Lys)
FT (interchain with K-432).
FT CROSSLNK 432 432 Isoglutamyl lysine isopeptide (Lys-Gln)
FT (interchain with Q-424).
FT VAR_SEQ 434 453 VRPEHPAETEYDSLYPEDDL -> AGDV (in isoform
FT Gamma-A).
FT /FTId=VSP_001537.
FT VARIANT 77 77 E -> G (in dbSNP:rs11551835).
FT /FTId=VAR_049066.
FT VARIANT 140 140 Y -> H (in dbSNP:rs2066870).
FT /FTId=VAR_033930.
FT VARIANT 191 191 G -> R (in Milano-12; dbSNP:rs6063).
FT /FTId=VAR_014170.
FT VARIANT 301 301 R -> C (in Tochigi/Osaka-2/Milano-5/
FT Villajoyosa).
FT /FTId=VAR_002409.
FT VARIANT 301 301 R -> H (in Bergamo-2/Essen/Haifa/Osaka-3/
FT Perugia/Saga/Barcelona-3/Barcelona-4).
FT /FTId=VAR_002410.
FT VARIANT 318 318 G -> V (in Baltimore-1; impaired
FT polymerization).
FT /FTId=VAR_002411.
FT VARIANT 334 334 N -> I (in Baltimore-3; impaired
FT polymerization; dbSNP:rs121913090).
FT /FTId=VAR_002413.
FT VARIANT 334 334 N -> K (in Kyoto-1; causes accelerated
FT cleavage by plasmin).
FT /FTId=VAR_002412.
FT VARIANT 335 335 G -> D (in Hillsborough; prolonged
FT thrombin clotting time).
FT /FTId=VAR_015853.
FT VARIANT 336 336 M -> T (in Asahi; impaired
FT polymerization).
FT /FTId=VAR_002414.
FT VARIANT 345 346 Missing (in Vlissingen; defective calcium
FT binding and impaired polymerization).
FT /FTId=VAR_002415.
FT VARIANT 355 355 Q -> R (in Nagoya-1; impaired
FT polymerization).
FT /FTId=VAR_002416.
FT VARIANT 356 356 D -> V (in Milano-1; impaired
FT polymerization).
FT /FTId=VAR_002418.
FT VARIANT 356 356 D -> Y (in Kyoto-3; impaired
FT polymerization).
FT /FTId=VAR_002417.
FT VARIANT 363 363 N -> K (in Bern-1; impaired
FT polymerization).
FT /FTId=VAR_002419.
FT VARIANT 377 377 G -> VMCGEALPMLKDPCYS (in Paris-1;
FT impaired polymerization).
FT /FTId=VAR_002420.
FT VARIANT 384 384 S -> C (in Milano-7; impaired
FT polymerization).
FT /FTId=VAR_002421.
FT VARIANT 401 401 R -> G (in Osaka-5).
FT /FTId=VAR_002422.
FT VARIANT 410 410 M -> V (in dbSNP:rs6061).
FT /FTId=VAR_014171.
FT CONFLICT 114 114 K -> I (in Ref. 2; AAB59530/AAB59531).
FT CONFLICT 435 435 R -> Y (in Ref. 15; AA sequence).
FT CONFLICT 448 448 Y -> R (in Ref. 15; AA sequence).
FT STRAND 44 46
FT HELIX 49 94
FT TURN 96 98
FT TURN 115 118
FT TURN 119 122
FT TURN 124 128
FT HELIX 129 160
FT STRAND 161 163
FT STRAND 166 168
FT STRAND 171 178
FT HELIX 179 184
FT STRAND 191 195
FT TURN 198 200
FT STRAND 204 210
FT STRAND 212 214
FT STRAND 216 226
FT HELIX 234 239
FT STRAND 241 244
FT STRAND 246 248
FT STRAND 252 254
FT HELIX 256 263
FT HELIX 265 267
FT STRAND 270 277
FT STRAND 279 281
FT STRAND 283 290
FT HELIX 296 298
FT STRAND 301 303
FT STRAND 305 309
FT HELIX 315 317
FT STRAND 322 324
FT HELIX 327 331
FT STRAND 341 343
FT STRAND 346 350
FT HELIX 352 356
FT STRAND 358 360
FT STRAND 363 365
FT STRAND 367 369
FT STRAND 370 373
FT STRAND 376 379
FT HELIX 382 384
FT STRAND 385 387
FT STRAND 392 395
FT TURN 396 398
FT STRAND 406 414
FT HELIX 415 417
FT STRAND 420 424
FT STRAND 427 436
SQ SEQUENCE 453 AA; 51512 MW; 1787204904E0D4BB CRC64;
MSWSLHPRNL ILYFYALLFL SSTCVAYVAT RDNCCILDER FGSYCPTTCG IADFLSTYQT
KVDKDLQSLE DILHQVENKT SEVKQLIKAI QLTYNPDESS KPNMIDAATL KSRKMLEEIM
KYEASILTHD SSIRYLQEIY NSNNQKIVNL KEKVAQLEAQ CQEPCKDTVQ IHDITGKDCQ
DIANKGAKQS GLYFIKPLKA NQQFLVYCEI DGSGNGWTVF QKRLDGSVDF KKNWIQYKEG
FGHLSPTGTT EFWLGNEKIH LISTQSAIPY ALRVELEDWN GRTSTADYAM FKVGPEADKY
RLTYAYFAGG DAGDAFDGFD FGDDPSDKFF TSHNGMQFST WDNDNDKFEG NCAEQDGSGW
WMNKCHAGHL NGVYYQGGTY SKASTPNGYD NGIIWATWKT RWYSMKKTTM KIIPFNRLTI
GEGQQHHLGG AKQVRPEHPA ETEYDSLYPE DDL
//
ID FIBG_HUMAN Reviewed; 453 AA.
AC P02679; A8K057; P04469; P04470; Q53Y18; Q96A14; Q96KJ3; Q9UC62;
read moreAC Q9UC63; Q9UCF3;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2002, sequence version 3.
DT 22-JAN-2014, entry version 183.
DE RecName: Full=Fibrinogen gamma chain;
DE Flags: Precursor;
GN Name=FGG; ORFNames=PRO2061;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=6688357; DOI=10.1021/bi00282a033;
RA Chung D.W., Chan W.-Y., Davie E.W.;
RT "Characterization of a complementary deoxyribonucleic acid coding for
RT the gamma chain of human fibrinogen.";
RL Biochemistry 22:3250-3256(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS GAMMA-A AND
RP GAMMA-B).
RX PubMed=2990550; DOI=10.1021/bi00329a041;
RA Rixon M.W., Chung D.W., Davie E.W.;
RT "Nucleotide sequence of the gene for the gamma chain of human
RT fibrinogen.";
RL Biochemistry 24:2077-2086(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS GAMMA-A AND GAMMA-B).
RC TISSUE=Liver;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GAMMA-A).
RC TISSUE=Fetal liver;
RA Zhang C., Yu Y., Zhang S., Wei H., Zhou G., Bi J., Zhang Y., Liu M.,
RA He F.;
RT "Functional prediction of the coding sequences of 33 new genes deduced
RT by analysis of cDNA clones from human fetal liver.";
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GAMMA-A).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-140 AND ARG-191.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GAMMA-A).
RC TISSUE=Skeletal muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 27-437.
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 [10]
RP PROTEIN SEQUENCE OF 27-41.
RC TISSUE=Platelet;
RX PubMed=8509453; DOI=10.1083/jcb.121.6.1329;
RA Bertagnolli M.E., Beckerle M.C.;
RT "Evidence for the selective association of a subpopulation of GPIIb-
RT IIIa with the actin cytoskeletons of thrombin-activated platelets.";
RL J. Cell Biol. 121:1329-1342(1993).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 75-286.
RC TISSUE=Liver;
RX PubMed=1685103;
RA Marchetti L., Zanelli T., Malcovati M., Tenchini M.L.;
RT "Polymorphism of the human gamma chain fibrinogen gene.";
RL DNA Seq. 1:419-422(1991).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 209-270.
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
RT gamma-chains of human fibrinogen.";
RL Nucleic Acids Res. 11:7427-7434(1983).
RN [13]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 285-437 (ISOFORMS GAMMA-A AND
RP GAMMA-B).
RX PubMed=6092346;
RA Fornace A.J. Jr., Cummings D.E., Comeau C.M., Kant J.A.,
RA Crabtree G.R.;
RT "Structure of the human gamma-fibrinogen gene. Alternate mRNA splicing
RT near the 3' end of the gene produces gamma A and gamma B forms of
RT gamma-fibrinogen.";
RL J. Biol. Chem. 259:12826-12830(1984).
RN [14]
RP PROTEIN SEQUENCE OF 291-310, AND VARIANTS BARCELONA-3/BARCELONA-4
RP HIS-301 AND VILLAJOYOSA CYS-301.
RC TISSUE=Blood;
RX PubMed=7654933;
RA Borrell M., Gari M., Coll I., Vallve C., Tirado I., Soria J.M.,
RA Sala N., Munoz C., Oliver A., Garcia A.;
RT "Abnormal polymerization and normal binding of plasminogen and t-PA in
RT three new dysfibrinogenaemias: Barcelona III and IV (gamma Arg
RT 275-->His) and Villajoyosa (gamma Arg 275-->Cys).";
RL Blood Coagul. Fibrinolysis 6:198-206(1995).
RN [15]
RP PROTEIN SEQUENCE OF 411-453 (ISOFORM GAMMA-B).
RX PubMed=7306501; DOI=10.1021/bi00524a036;
RA Wolfenstein-Todel C., Mosesson M.W.;
RT "Carboxy-terminal amino acid sequence of a human fibrinogen gamma-
RT chain variant (gamma').";
RL Biochemistry 20:6146-6149(1981).
RN [16]
RP REVIEW, AND DISULFIDE BONDS.
RX PubMed=6575689; DOI=10.1111/j.1749-6632.1983.tb23232.x;
RA Henschen A., Lottspeich F., Kehl M., Southan C.;
RT "Covalent structure of fibrinogen.";
RL Ann. N. Y. Acad. Sci. 408:28-43(1983).
RN [17]
RP DISULFIDE BONDS.
RA Doolittle R.F., Takagi T., Watt K.W.K., Bouma H. III, Cottrell B.A.,
RA Cassman K.G., Goldbaum D.M., Doolittle L.R., Friezner S.J.;
RT "The structures of fibrinogen and fibrin.";
RL (In) Magnusson S., Ottesen M., Foltmann B., Dano K., Neurath H.
RL (eds.);
RL Regulatory proteolytic enzymes and their inhibitors, pp.163-172,
RL Pergamon Press, New York (1978).
RN [18]
RP DISULFIDE BONDS.
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 [19]
RP QUATERNARY STRUCTURE, AND DISULFIDE BONDS.
RX PubMed=6860649; DOI=10.1021/bi00278a003;
RA Hoeprich P.D., Doolittle R.F.;
RT "Dimeric half-molecules of human fibrinogen are joined through
RT disulfide bonds in an antiparallel orientation.";
RL Biochemistry 22:2049-2055(1983).
RN [20]
RP SULFATION.
RX PubMed=1892842; DOI=10.1021/bi00103a004;
RA Farrel D.H., Mulvihill E.R., Huang S., Chung D.W., Davie E.W.;
RT "Recombinant human fibrinogen and sulfation of the gamma' chain.";
RL Biochemistry 30:9414-9420(1991).
RN [21]
RP SULFATION AT TYR-444 AND TYR-448.
RX PubMed=11307817;
RA Meh D.A., Siebenlist K.R., Brennan S.O., Holyst T., Mosesson M.W.;
RT "The amino acid sequence in fibrin responsible for high affinity
RT thrombin binding.";
RL Thromb. Haemost. 85:470-474(2001).
RN [22]
RP REVIEW, ELECTRON MICROSCOPY, POLYMERIZATION, AND LIGANDS.
RX PubMed=6383194;
RA Doolittle R.F.;
RT "Fibrinogen and fibrin.";
RL Annu. Rev. Biochem. 53:195-229(1984).
RN [23]
RP POLYMERIZATION SITE.
RX PubMed=6592597; DOI=10.1073/pnas.81.19.5980;
RA Horwitz B.H., Varadi A., Scheraga H.A.;
RT "Localization of a fibrin gamma-chain polymerization site within
RT segment Thr-374 to Glu-396 of human fibrinogen.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:5980-5984(1984).
RN [24]
RP POLYMERIZATION SITE.
RX PubMed=6451630;
RA Olexa S.A., Budzynski A.Z.;
RT "Localization of a fibrin polymerization site.";
RL J. Biol. Chem. 256:3544-3549(1981).
RN [25]
RP PLATELET AGGREGATION SITE.
RX PubMed=6326808; DOI=10.1021/bi00303a028;
RA Kloczewiak M., Timmons S., Lukas T.J., Hawiger J.;
RT "Platelet receptor recognition site on human fibrinogen. Synthesis and
RT structure-function relationship of peptides corresponding to the
RT carboxy-terminal segment of the gamma chain.";
RL Biochemistry 23:1767-1774(1984).
RN [26]
RP PLATELET AGGREGATION SITE.
RX PubMed=6325435;
RA Plow E.F., Srouji A.H., Meyer D., Marguerie G., Ginsberg M.H.;
RT "Evidence that three adhesive proteins interact with a common
RT recognition site on activated platelets.";
RL J. Biol. Chem. 259:5388-5391(1984).
RN [27]
RP CALCIUM-BINDING SITE.
RX PubMed=3160702;
RA Dang C.V., Ebert R.F., Bell W.R.;
RT "Localization of a fibrinogen calcium binding site between gamma-
RT subunit positions 311 and 336 by terbium fluorescence.";
RL J. Biol. Chem. 260:9713-9719(1985).
RN [28]
RP CHROMATOGRAPHIC COMPARISON OF GAMMA-A AND GAMMA-B CHAINS.
RX PubMed=6933547; DOI=10.1073/pnas.77.9.5069;
RA Wolfenstein-Todel C., Mosesson M.W.;
RT "Human plasma fibrinogen heterogeneity: evidence for an extended
RT carboxyl-terminal sequence in a normal gamma chain variant (gamma').";
RL Proc. Natl. Acad. Sci. U.S.A. 77:5069-5073(1980).
RN [29]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-78, AND MASS SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=14760718; DOI=10.1002/pmic.200300556;
RA Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.;
RT "Screening for N-glycosylated proteins by liquid chromatography mass
RT spectrometry.";
RL Proteomics 4:454-465(2004).
RN [30]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-78, AND MASS SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA Moore R.J., Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [31]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-78, AND MASS SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=16263699; DOI=10.1074/mcp.M500324-MCP200;
RA Lewandrowski U., Moebius J., Walter U., Sickmann A.;
RT "Elucidation of N-glycosylation sites on human platelet proteins: a
RT glycoproteomic approach.";
RL Mol. Cell. Proteomics 5:226-233(2006).
RN [32]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-78, AND MASS SPECTROMETRY.
RC TISSUE=Milk;
RX PubMed=18780401; DOI=10.1002/pmic.200701057;
RA Picariello G., Ferranti P., Mamone G., Roepstorff P., Addeo F.;
RT "Identification of N-linked glycoproteins in human milk by hydrophilic
RT interaction liquid chromatography and mass spectrometry.";
RL Proteomics 8:3833-3847(2008).
RN [33]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-78, AND MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [34]
RP GLYCOSYLATION AT ASN-78.
RX PubMed=19139490; DOI=10.1074/mcp.M800504-MCP200;
RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F.,
RA Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y.,
RA Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core
RT fucosylated glycoproteins.";
RL Mol. Cell. Proteomics 8:913-923(2009).
RN [35]
RP CLEAVAGE BY HEMENTIN AND PLASMIN.
RX PubMed=2143188;
RA Kirschbaum N.E., Budzynski A.Z.;
RT "A unique proteolytic fragment of human fibrinogen containing the A
RT alpha COOH-terminal domain of the native molecule.";
RL J. Biol. Chem. 265:13669-13676(1990).
RN [36]
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.,
RA Buerckstuemmer T., 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 [37]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 169-437.
RX PubMed=9016719; DOI=10.1016/S0969-2126(97)00171-8;
RA Yee V.C., Pratt K.P., Cote H.C.F., le Trong I., Chung D.W.,
RA Davie E.W., Stenkamp R.E., Teller D.C.;
RT "Crystal structure of a 30 kDa C-terminal fragment from the gamma
RT chain of human fibrinogen.";
RL Structure 5:125-138(1997).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 169-437.
RX PubMed=9207064; DOI=10.1073/pnas.94.14.7176;
RA Pratt K.P., Cote H.C.F., Chung D.W., Stenkamp R.E., Davie E.W.;
RT "The primary fibrin polymerization pocket: three-dimensional structure
RT of a 30-kDa C-terminal gamma chain fragment complexed with the peptide
RT Gly-Pro-Arg-Pro.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:7176-7181(1997).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 114-432.
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
RT crosslinked counterpart from fibrin.";
RL Nature 389:455-462(1997).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 114-432.
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 [41]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 114-432.
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
RT fibrin(ogen) upon binding the peptide ligand Gly-His-Arg-Pro-amide.";
RL Biochemistry 38:2941-2946(1999).
RN [42]
RP VARIANT ASAHI THR-336.
RX PubMed=2496144; DOI=10.1172/JCI114056;
RA Yamazumi K., Shimura K., Terukina S., Takahashi N., Matsuda M.;
RT "A gamma methionine-310 to threonine substitution and consequent N-
RT glycosylation at gamma asparagine-308 identified in a congenital
RT dysfibrinogenemia associated with posttraumatic bleeding, fibrinogen
RT Asahi.";
RL J. Clin. Invest. 83:1590-1597(1989).
RN [43]
RP VARIANTS OSAKA-2 CYS-301; KYOTO-1 LYS-334; ASAHI THR-336 AND KYOTO-3
RP TYR-356.
RX PubMed=1421174;
RA Mimuro J., Muramatsu S., Maekawa H., Sakata Y., Kaneko M.,
RA Yoshitake S., Okuma M., Ito Y., Takeda Y., Matsuda M.;
RT "Gene analyses of abnormal fibrinogens with a mutation in the gamma
RT chain.";
RL Int. J. Hematol. 56:129-134(1992).
RN [44]
RP VARIANT BALTIMORE-1 VAL-318.
RX PubMed=2257302;
RA Bantia S., Mane S.M., Bell W.R., Dang C.V.;
RT "Fibrinogen Baltimore I: polymerization defect associated with a gamma
RT 292Gly-->Val (GGC-->GTC) mutation.";
RL Blood 76:2279-2283(1990).
RN [45]
RP VARIANT BALTIMORE-3 ILE-334.
RX PubMed=2328317;
RA Bantia S., Bell W.R., Dang C.V.;
RT "Polymerization defect of fibrinogen Baltimore III due to a gamma
RT Asn308-->Ile mutation.";
RL Blood 75:1659-1663(1990).
RN [46]
RP VARIANT BERN-1 LYS-363.
RX PubMed=8400260;
RA Steinmann C., Reber P., Jungo M., Laemmle B., Heinemann G.,
RA Wermuth B., Furlan M.;
RT "Fibrinogen Bern I: substitution gamma 337 Asn-->Lys is responsible
RT for defective fibrin monomer polymerization.";
RL Blood 82:2104-2108(1993).
RN [47]
RP VARIANT KYOTO-1 LYS-334.
RX PubMed=2971046;
RA Yoshida N., Terukina S., Okuma M., Moroi M., Aoki N., Matsuda M.;
RT "Characterization of an apparently lower molecular weight gamma-chain
RT variant in fibrinogen Kyoto I. The replacement of gamma-asparagine 308
RT by lysine which causes accelerated cleavage of fragment D1 by plasmin
RT and the generation of a new plasmin cleavage site.";
RL J. Biol. Chem. 263:13848-13856(1988).
RN [48]
RP VARIANT KYOTO-3 TYR-356.
RX PubMed=2819242;
RA Terukina S., Yamazumi K., Okamoto K., Yamashita H., Ito Y.,
RA Matsuda M.;
RT "Fibrinogen Kyoto III: a congenital dysfibrinogen with a gamma
RT aspartic acid-330 to tyrosine substitution manifesting impaired fibrin
RT monomer polymerization.";
RL Blood 74:2681-2687(1989).
RN [49]
RP VARIANT MILANO-1 VAL-356.
RX PubMed=3708159;
RA Reber P., Furlan M., Rupp C., Kehl M., Henschen A., Mannucci P.M.,
RA Beck E.A.;
RT "Characterization of fibrinogen Milano I: amino acid exchange gamma
RT 330 Asp-->Val impairs fibrin polymerization.";
RL Blood 67:1751-1756(1986).
RN [50]
RP VARIANT MILANO-5 CYS-301.
RX PubMed=7841300;
RA Steinmann C., Boegli C., Jungo M., Laemmle B., Heinemann G.,
RA Wermuth B., Redaelli R., Baudo F., Furlan M.;
RT "Fibrinogen Milano V: a congenital dysfibrinogenaemia with a gamma 275
RT Arg-->Cys substitution.";
RL Blood Coagul. Fibrinolysis 5:463-471(1994).
RN [51]
RP VARIANT MILANO-7 CYS-384.
RX PubMed=8080993;
RA Steinmann C., Boegli C., Jungo M., Laemmle B., Heinemann G.,
RA Wermuth B., Redaelli R., Baudo F., Furlan M.;
RT "A new substitution, gamma 358 Ser-->Cys, in fibrinogen Milano VII
RT causes defective fibrin polymerization.";
RL Blood 84:1874-1880(1994).
RN [52]
RP VARIANT NAGOYA-1 ARG-355.
RX PubMed=2738036;
RA Miyata T., Furukawa K., Iwanaga S., Takamatsu J., Saito H.;
RT "Fibrinogen Nagoya, a replacement of glutamine-329 by arginine in the
RT gamma-chain that impairs the polymerization of fibrin monomer.";
RL J. Biochem. 105:10-14(1989).
RN [53]
RP VARIANT OSAKA-2 CYS-301.
RX PubMed=2971042;
RA Terukina S., Matsuda M., Hirata H., Takeda Y., Miyata T., Takao T.,
RA Shimonishi Y.;
RT "Substitution of gamma Arg-275 by Cys in an abnormal fibrinogen,
RT 'fibrinogen Osaka II'. Evidence for a unique solitary cystine
RT structure at the mutation site.";
RL J. Biol. Chem. 263:13579-13587(1988).
RN [54]
RP VARIANT OSAKA-3 HIS-301.
RX PubMed=1455400;
RA Yoshida N., Imoka S., Hirata H., Matsuda M., Asakura S.;
RT "Heterozygous abnormal fibrinogen Osaka III with the replacement of
RT gamma arginine-275 by histidine has an apparently higher molecular
RT weight gamma-chain variant.";
RL Thromb. Haemost. 68:534-538(1992).
RN [55]
RP VARIANT OSAKA-5 GLY-401.
RX PubMed=1733971;
RA Yoshida N., Hirata H., Morigami Y., Imaoka S., Matsuda M.,
RA Yamazumi K., Asakura S.;
RT "Characterization of an abnormal fibrinogen Osaka V with the
RT replacement of gamma-arginine 375 by glycine. The lack of high
RT affinity calcium binding to D-domains and the lack of protective
RT effect of calcium on fibrinolysis.";
RL J. Biol. Chem. 267:2753-2759(1992).
RN [56]
RP VARIANT PARIS-1 GLY-377 DELINS
RP VAL-MET-CYS-GLY-GLU-ALA-LEU-PRO-MET-LEU-LYS-ASP-PRO-CYS-TYR-SER.
RX PubMed=8470043;
RA Rosenberg J.B., Newman P.J., Mosesson M.W., Guillin M.-C.,
RA Amrani D.L.;
RT "Paris I dysfibrinogenemia: a point mutation in intron 8 results in
RT insertion of a 15 amino acid sequence in the fibrinogen gamma-chain.";
RL Thromb. Haemost. 69:217-220(1993).
RN [57]
RP VARIANT TOCHIGI CYS-301.
RX PubMed=3337908;
RA Yoshida N., Ota K., Moroi M., Matsuda M.;
RT "An apparently higher molecular weight gamma-chain variant in a new
RT congenital abnormal fibrinogen Tochigi characterized by the
RT replacement of gamma arginine-275 by cysteine.";
RL Blood 71:480-487(1988).
RN [58]
RP VARIANT VLISSINGEN 345-ASN-ASP-346 DEL.
RX PubMed=2071611;
RA Koopman J., Haverkate F., Briet E., Lord S.T.;
RT "A congenitally abnormal fibrinogen (Vlissingen) with a 6-base
RT deletion in the gamma-chain gene, causing defective calcium binding
RT and impaired fibrin polymerization.";
RL J. Biol. Chem. 266:13456-13461(1991).
RN [59]
RP VARIANT BERGAMO-2/ESSEN/HAIFA/PERUGIA HIS-301.
RX PubMed=3563970;
RA Reber P., Furlan M., Henschen A., Kaudewitz H., Barbui T., Hilgard P.,
RA Nenci G.G., Berrettini M., Beck E.A.;
RT "Three abnormal fibrinogen variants with the same amino acid
RT substitution (gamma 275 Arg-->His): fibrinogens Bergamo II, Essen and
RT Perugia.";
RL Thromb. Haemost. 56:401-406(1986).
RN [60]
RP VARIANT SAGA HIS-301.
RX PubMed=2976995;
RA Yamazumi K., Terukina S., Onohara S., Matsuda M.;
RT "Normal plasmic cleavage of the gamma-chain variant of 'fibrinogen
RT Saga' with an Arg-275 to His substitution.";
RL Thromb. Haemost. 60:476-480(1988).
RN [61]
RP VARIANT MILANO-12 ARG-191.
RX PubMed=11435303; DOI=10.1182/blood.V98.2.351;
RA Bolliger-Stucki B., Lord S.T., Furlan M.;
RT "Fibrinogen Milano XII: a dysfunctional variant containing 2 amino
RT acid substitutions, A-alpha R16C and gamma G165R.";
RL Blood 98:351-357(2001).
RN [62]
RP VARIANTS ARG-191 AND VAL-410.
RX PubMed=10391209; DOI=10.1038/10290;
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RT "Characterization of single-nucleotide polymorphisms in coding regions
RT of human genes.";
RL Nat. Genet. 22:231-238(1999).
RN [63]
RP ERRATUM.
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RL Nat. Genet. 23:373-373(1999).
RN [64]
RP VARIANT HILLSBOROUGH ASP-335.
RX PubMed=11986213; DOI=10.1182/blood.V99.10.3597;
RA Mullin J.L., Brennan S.O., Ganly P.S., George P.M.;
RT "Fibrinogen Hillsborough: a novel gamma-gly309asp dysfibrinogen with
RT impaired clotting.";
RL Blood 99:3597-3601(2002).
CC -!- FUNCTION: Fibrinogen has a double function: yielding monomers that
CC polymerize into fibrin and acting as a cofactor in platelet
CC aggregation.
CC -!- SUBUNIT: Heterohexamer; disulfide linked. Contains 2 sets of 3
CC non-identical chains (alpha, beta and gamma). The 2 heterotrimers
CC are in head to head conformation with the N-termini in a small
CC central domain (By similarity).
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Gamma-B; Synonyms=Gamma';
CC IsoId=P02679-1; Sequence=Displayed;
CC Note=Present in about 10% of the fibrinogen molecules in plasma
CC but absent from those in the platelets;
CC Name=Gamma-A;
CC IsoId=P02679-2; Sequence=VSP_001537;
CC -!- DOMAIN: A long coiled coil structure formed by 3 polypeptide
CC chains connects the central nodule to the C-terminal domains
CC (distal nodules). The long C-terminal ends of the alpha chains
CC fold back, contributing a fourth strand to the coiled coil
CC structure.
CC -!- PTM: Conversion of fibrinogen to fibrin is triggered by thrombin,
CC which cleaves fibrinopeptides A and B from alpha and beta chains,
CC and thus exposes the N-terminal polymerization sites responsible
CC for the formation of the soft clot. The soft clot is converted
CC into the hard clot by factor XIIIA which catalyzes the epsilon-
CC (gamma-glutamyl)lysine cross-linking between gamma chains
CC (stronger) and between alpha chains (weaker) of different
CC monomers.
CC -!- PTM: Sulfation of C-terminal tyrosines increases affinity for
CC thrombin.
CC -!- DISEASE: Congenital afibrinogenemia (CAFBN) [MIM:202400]: Rare
CC autosomal recessive disorder is characterized by bleeding that
CC varies from mild to severe and by complete absence or extremely
CC low levels of plasma and platelet fibrinogen. Note=The disease is
CC caused by mutations affecting the gene represented in this entry.
CC Patients with congenital fibrinogen abnormalities can manifest
CC different clinical pictures. Some cases are clinically silent,
CC some show a tendency toward bleeding and some show a
CC predisposition for thrombosis with or without bleeding.
CC -!- MISCELLANEOUS: The gamma-chain carries the main binding site for
CC the platelet receptor.
CC -!- SIMILARITY: Contains 1 fibrinogen C-terminal domain.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/FGG";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Fibrinogen entry;
CC URL="http://en.wikipedia.org/wiki/Fibrinogen";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/fgg/";
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DR EMBL; M10014; AAB59530.1; -; Genomic_DNA.
DR EMBL; M10014; AAB59531.1; -; Genomic_DNA.
DR EMBL; AF118092; AAF22036.1; -; mRNA.
DR EMBL; AF350254; AAK19751.2; -; Genomic_DNA.
DR EMBL; AF350254; AAK19752.2; -; Genomic_DNA.
DR EMBL; AK289422; BAF82111.1; -; mRNA.
DR EMBL; AK290824; BAF83513.1; -; mRNA.
DR EMBL; BT007081; AAP35744.1; -; mRNA.
DR EMBL; CH471056; EAX04917.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX04919.1; -; Genomic_DNA.
DR EMBL; BC007044; AAH07044.1; -; mRNA.
DR EMBL; BC021674; AAH21674.1; -; mRNA.
DR EMBL; X51473; CAA35837.1; -; mRNA.
DR EMBL; X00086; CAA24944.1; -; mRNA.
DR EMBL; K02569; AAA52430.1; -; Genomic_DNA.
DR EMBL; K02569; AAA52431.1; -; Genomic_DNA.
DR PIR; A90470; FGHUG.
DR PIR; A90494; FGHUGB.
DR RefSeq; NP_000500.2; NM_000509.4.
DR RefSeq; NP_068656.2; NM_021870.2.
DR UniGene; Hs.727584; -.
DR PDB; 1DUG; X-ray; 1.80 A; A/B=424-433.
DR PDB; 1FIB; X-ray; 2.10 A; A=169-433.
DR PDB; 1FIC; X-ray; 2.50 A; A/B=169-433.
DR PDB; 1FID; X-ray; 2.10 A; A=169-433.
DR PDB; 1FZA; X-ray; 2.90 A; C/F=114-432.
DR PDB; 1FZB; X-ray; 2.90 A; C/F=114-432.
DR PDB; 1FZC; X-ray; 2.30 A; C/F=114-432.
DR PDB; 1FZE; X-ray; 3.00 A; C/F=114-432.
DR PDB; 1FZF; X-ray; 2.70 A; C/F=114-432.
DR PDB; 1FZG; X-ray; 2.50 A; C/F=114-432.
DR PDB; 1LT9; X-ray; 2.80 A; C/F=122-432.
DR PDB; 1LTJ; X-ray; 2.80 A; C/F=122-432.
DR PDB; 1N86; X-ray; 3.20 A; C/F=114-433.
DR PDB; 1N8E; X-ray; 4.50 A; C/F=114-433.
DR PDB; 1RE3; X-ray; 2.45 A; C/F=122-432.
DR PDB; 1RE4; X-ray; 2.70 A; C/F=122-432.
DR PDB; 1RF0; X-ray; 2.81 A; C/F=122-432.
DR PDB; 1RF1; X-ray; 2.53 A; C/F=122-432.
DR PDB; 2A45; X-ray; 3.65 A; I/L=27-71.
DR PDB; 2FFD; X-ray; 2.89 A; C/F=122-432.
DR PDB; 2FIB; X-ray; 2.01 A; A=169-433.
DR PDB; 2H43; X-ray; 2.70 A; C/F=115-433.
DR PDB; 2HLO; X-ray; 2.60 A; C/F=114-433.
DR PDB; 2HOD; X-ray; 2.90 A; C/F/I/L=115-433.
DR PDB; 2HPC; X-ray; 2.90 A; C/F/I/L=115-433.
DR PDB; 2HWL; X-ray; 2.40 A; P=439-452.
DR PDB; 2OYH; X-ray; 2.40 A; C/F=122-432.
DR PDB; 2OYI; X-ray; 2.70 A; C/F=122-432.
DR PDB; 2Q9I; X-ray; 2.80 A; C/F=114-433.
DR PDB; 2VDO; X-ray; 2.51 A; C=426-433.
DR PDB; 2VDP; X-ray; 2.80 A; C=428-433.
DR PDB; 2VDQ; X-ray; 2.59 A; C=426-433.
DR PDB; 2VDR; X-ray; 2.40 A; C=428-433.
DR PDB; 2VR3; X-ray; 1.95 A; C/D=425-433.
DR PDB; 2XNX; X-ray; 3.30 A; C/F/I/L=114-432.
DR PDB; 2XNY; X-ray; 7.50 A; C/F=114-432.
DR PDB; 2Y7L; X-ray; 1.49 A; B=421-433.
DR PDB; 2Z4E; X-ray; 2.70 A; C/F=114-433.
DR PDB; 3BVH; X-ray; 2.60 A; C/F=128-420.
DR PDB; 3E1I; X-ray; 2.30 A; C/F=114-432.
DR PDB; 3FIB; X-ray; 2.10 A; A=170-418.
DR PDB; 3GHG; X-ray; 2.90 A; C/F/I/L=27-433.
DR PDB; 3H32; X-ray; 3.60 A; C/F=121-433.
DR PDB; 3HUS; X-ray; 3.04 A; C/F=122-432.
DR PDB; 4B60; X-ray; 1.83 A; C/D=421-433.
DR PDBsum; 1DUG; -.
DR PDBsum; 1FIB; -.
DR PDBsum; 1FIC; -.
DR PDBsum; 1FID; -.
DR PDBsum; 1FZA; -.
DR PDBsum; 1FZB; -.
DR PDBsum; 1FZC; -.
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; 2A45; -.
DR PDBsum; 2FFD; -.
DR PDBsum; 2FIB; -.
DR PDBsum; 2H43; -.
DR PDBsum; 2HLO; -.
DR PDBsum; 2HOD; -.
DR PDBsum; 2HPC; -.
DR PDBsum; 2HWL; -.
DR PDBsum; 2OYH; -.
DR PDBsum; 2OYI; -.
DR PDBsum; 2Q9I; -.
DR PDBsum; 2VDO; -.
DR PDBsum; 2VDP; -.
DR PDBsum; 2VDQ; -.
DR PDBsum; 2VDR; -.
DR PDBsum; 2VR3; -.
DR PDBsum; 2XNX; -.
DR PDBsum; 2XNY; -.
DR PDBsum; 2Y7L; -.
DR PDBsum; 2Z4E; -.
DR PDBsum; 3BVH; -.
DR PDBsum; 3E1I; -.
DR PDBsum; 3FIB; -.
DR PDBsum; 3GHG; -.
DR PDBsum; 3H32; -.
DR PDBsum; 3HUS; -.
DR PDBsum; 4B60; -.
DR ProteinModelPortal; P02679; -.
DR SMR; P02679; 28-421.
DR DIP; DIP-29644N; -.
DR IntAct; P02679; 1.
DR MINT; MINT-5004002; -.
DR BindingDB; P02679; -.
DR ChEMBL; CHEMBL2364709; -.
DR DrugBank; DB00364; Sucralfate.
DR PhosphoSite; P02679; -.
DR DMDM; 20178280; -.
DR DOSAC-COBS-2DPAGE; P02679; -.
DR OGP; P02679; -.
DR REPRODUCTION-2DPAGE; IPI00219713; -.
DR REPRODUCTION-2DPAGE; P02679; -.
DR SWISS-2DPAGE; P02679; -.
DR PaxDb; P02679; -.
DR PeptideAtlas; P02679; -.
DR PRIDE; P02679; -.
DR DNASU; 2266; -.
DR Ensembl; ENST00000336098; ENSP00000336829; ENSG00000171557.
DR Ensembl; ENST00000404648; ENSP00000384860; ENSG00000171557.
DR GeneID; 2266; -.
DR KEGG; hsa:2266; -.
DR UCSC; uc003ioj.3; human.
DR CTD; 2266; -.
DR GeneCards; GC04M155525; -.
DR HGNC; HGNC:3694; FGG.
DR HPA; HPA027529; -.
DR MIM; 134850; gene.
DR MIM; 202400; phenotype.
DR neXtProt; NX_P02679; -.
DR Orphanet; 98880; Familial afibrinogenemia.
DR Orphanet; 98881; Familial dysfibrinogenemia.
DR Orphanet; 248408; Familial hypodysfibrinogenemia.
DR Orphanet; 101041; Familial hypofibrinogenemia.
DR PharmGKB; PA430; -.
DR eggNOG; NOG269667; -.
DR HOVERGEN; HBG099783; -.
DR KO; K03905; -.
DR OrthoDB; EOG7X9G60; -.
DR PhylomeDB; P02679; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR Reactome; REACT_604; Hemostasis.
DR ChiTaRS; FGG; human.
DR EvolutionaryTrace; P02679; -.
DR GeneWiki; FGG; -.
DR GenomeRNAi; 2266; -.
DR NextBio; 9205; -.
DR PMAP-CutDB; P02679; -.
DR PRO; PR:P02679; -.
DR ArrayExpress; P02679; -.
DR Bgee; P02679; -.
DR CleanEx; HS_FGG; -.
DR Genevestigator; P02679; -.
DR GO; GO:0072562; C:blood microparticle; IEA:Ensembl.
DR GO; GO:0005938; C:cell cortex; IEA:Ensembl.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005577; C:fibrinogen complex; TAS:ProtInc.
DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome.
DR GO; GO:0051258; P:protein polymerization; IEA:InterPro.
DR GO; GO:0051592; P:response to calcium ion; IDA:BHF-UCL.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR Gene3D; 3.90.215.10; -; 1.
DR Gene3D; 4.10.530.10; -; 1.
DR InterPro; IPR014716; Fibrinogen_a/b/g_C_1.
DR InterPro; IPR014715; Fibrinogen_a/b/g_C_2.
DR InterPro; IPR002181; Fibrinogen_a/b/g_C_dom.
DR InterPro; IPR012290; Fibrinogen_a/b/g_coil_dom.
DR InterPro; IPR020837; Fibrinogen_CS.
DR Pfam; PF08702; Fib_alpha; 1.
DR Pfam; PF00147; Fibrinogen_C; 1.
DR SMART; SM00186; FBG; 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; Alternative splicing; Blood coagulation; Calcium;
KW Coiled coil; Complete proteome; Direct protein sequencing;
KW Disease mutation; Disulfide bond; Glycoprotein; Hemostasis;
KW Isopeptide bond; Metal-binding; Polymorphism; Reference proteome;
KW Secreted; Signal; Sulfation.
FT SIGNAL 1 26
FT CHAIN 27 453 Fibrinogen gamma chain.
FT /FTId=PRO_0000009099.
FT DOMAIN 170 416 Fibrinogen C-terminal.
FT CA_BIND 341 355
FT REGION 400 422 Gamma-chain polymerization, binding amino
FT end of another fibrin alpha chain.
FT REGION 423 437 Platelet aggregation and Staphylococcus
FT clumping.
FT SITE 84 85 Cleavage; by plasmin; to break down
FT fibrin clots.
FT SITE 88 89 Cleavage; by plasmin; to break down
FT fibrin clots.
FT SITE 102 103 Cleavage; by hementin; to prevent blood
FT coagulation.
FT MOD_RES 444 444 Sulfotyrosine.
FT MOD_RES 448 448 Sulfotyrosine.
FT CARBOHYD 78 78 N-linked (GlcNAc...) (complex).
FT CARBOHYD 334 334 N-linked (GlcNAc...); in variant Asahi.
FT DISULFID 34 34 Interchain (with C-35).
FT DISULFID 35 35 Interchain (with C-34).
FT DISULFID 45 45 Interchain (with C-110 in beta chain).
FT DISULFID 49 49 Interchain (with C-64 in alpha chain).
FT DISULFID 161 161 Interchain (with C-227 in beta chain).
FT DISULFID 165 165 Interchain (with C-180 in alpha chain).
FT DISULFID 179 208
FT DISULFID 352 365
FT CROSSLNK 424 424 Isoglutamyl lysine isopeptide (Gln-Lys)
FT (interchain with K-432).
FT CROSSLNK 432 432 Isoglutamyl lysine isopeptide (Lys-Gln)
FT (interchain with Q-424).
FT VAR_SEQ 434 453 VRPEHPAETEYDSLYPEDDL -> AGDV (in isoform
FT Gamma-A).
FT /FTId=VSP_001537.
FT VARIANT 77 77 E -> G (in dbSNP:rs11551835).
FT /FTId=VAR_049066.
FT VARIANT 140 140 Y -> H (in dbSNP:rs2066870).
FT /FTId=VAR_033930.
FT VARIANT 191 191 G -> R (in Milano-12; dbSNP:rs6063).
FT /FTId=VAR_014170.
FT VARIANT 301 301 R -> C (in Tochigi/Osaka-2/Milano-5/
FT Villajoyosa).
FT /FTId=VAR_002409.
FT VARIANT 301 301 R -> H (in Bergamo-2/Essen/Haifa/Osaka-3/
FT Perugia/Saga/Barcelona-3/Barcelona-4).
FT /FTId=VAR_002410.
FT VARIANT 318 318 G -> V (in Baltimore-1; impaired
FT polymerization).
FT /FTId=VAR_002411.
FT VARIANT 334 334 N -> I (in Baltimore-3; impaired
FT polymerization; dbSNP:rs121913090).
FT /FTId=VAR_002413.
FT VARIANT 334 334 N -> K (in Kyoto-1; causes accelerated
FT cleavage by plasmin).
FT /FTId=VAR_002412.
FT VARIANT 335 335 G -> D (in Hillsborough; prolonged
FT thrombin clotting time).
FT /FTId=VAR_015853.
FT VARIANT 336 336 M -> T (in Asahi; impaired
FT polymerization).
FT /FTId=VAR_002414.
FT VARIANT 345 346 Missing (in Vlissingen; defective calcium
FT binding and impaired polymerization).
FT /FTId=VAR_002415.
FT VARIANT 355 355 Q -> R (in Nagoya-1; impaired
FT polymerization).
FT /FTId=VAR_002416.
FT VARIANT 356 356 D -> V (in Milano-1; impaired
FT polymerization).
FT /FTId=VAR_002418.
FT VARIANT 356 356 D -> Y (in Kyoto-3; impaired
FT polymerization).
FT /FTId=VAR_002417.
FT VARIANT 363 363 N -> K (in Bern-1; impaired
FT polymerization).
FT /FTId=VAR_002419.
FT VARIANT 377 377 G -> VMCGEALPMLKDPCYS (in Paris-1;
FT impaired polymerization).
FT /FTId=VAR_002420.
FT VARIANT 384 384 S -> C (in Milano-7; impaired
FT polymerization).
FT /FTId=VAR_002421.
FT VARIANT 401 401 R -> G (in Osaka-5).
FT /FTId=VAR_002422.
FT VARIANT 410 410 M -> V (in dbSNP:rs6061).
FT /FTId=VAR_014171.
FT CONFLICT 114 114 K -> I (in Ref. 2; AAB59530/AAB59531).
FT CONFLICT 435 435 R -> Y (in Ref. 15; AA sequence).
FT CONFLICT 448 448 Y -> R (in Ref. 15; AA sequence).
FT STRAND 44 46
FT HELIX 49 94
FT TURN 96 98
FT TURN 115 118
FT TURN 119 122
FT TURN 124 128
FT HELIX 129 160
FT STRAND 161 163
FT STRAND 166 168
FT STRAND 171 178
FT HELIX 179 184
FT STRAND 191 195
FT TURN 198 200
FT STRAND 204 210
FT STRAND 212 214
FT STRAND 216 226
FT HELIX 234 239
FT STRAND 241 244
FT STRAND 246 248
FT STRAND 252 254
FT HELIX 256 263
FT HELIX 265 267
FT STRAND 270 277
FT STRAND 279 281
FT STRAND 283 290
FT HELIX 296 298
FT STRAND 301 303
FT STRAND 305 309
FT HELIX 315 317
FT STRAND 322 324
FT HELIX 327 331
FT STRAND 341 343
FT STRAND 346 350
FT HELIX 352 356
FT STRAND 358 360
FT STRAND 363 365
FT STRAND 367 369
FT STRAND 370 373
FT STRAND 376 379
FT HELIX 382 384
FT STRAND 385 387
FT STRAND 392 395
FT TURN 396 398
FT STRAND 406 414
FT HELIX 415 417
FT STRAND 420 424
FT STRAND 427 436
SQ SEQUENCE 453 AA; 51512 MW; 1787204904E0D4BB CRC64;
MSWSLHPRNL ILYFYALLFL SSTCVAYVAT RDNCCILDER FGSYCPTTCG IADFLSTYQT
KVDKDLQSLE DILHQVENKT SEVKQLIKAI QLTYNPDESS KPNMIDAATL KSRKMLEEIM
KYEASILTHD SSIRYLQEIY NSNNQKIVNL KEKVAQLEAQ CQEPCKDTVQ IHDITGKDCQ
DIANKGAKQS GLYFIKPLKA NQQFLVYCEI DGSGNGWTVF QKRLDGSVDF KKNWIQYKEG
FGHLSPTGTT EFWLGNEKIH LISTQSAIPY ALRVELEDWN GRTSTADYAM FKVGPEADKY
RLTYAYFAGG DAGDAFDGFD FGDDPSDKFF TSHNGMQFST WDNDNDKFEG NCAEQDGSGW
WMNKCHAGHL NGVYYQGGTY SKASTPNGYD NGIIWATWKT RWYSMKKTTM KIIPFNRLTI
GEGQQHHLGG AKQVRPEHPA ETEYDSLYPE DDL
//
MIM
134850
*RECORD*
*FIELD* NO
134850
*FIELD* TI
*134850 FIBRINOGEN, G GAMMA POLYPEPTIDE; FGG
;;FIBRINOGEN--GAMMA POLYPEPTIDE CHAIN
read more*FIELD* TX
See fibrinogen--alpha polypeptide chain (FGA; 134820) and beta chain
(FGB; 134830). In its essential role in the adhesion and aggregation of
platelets, fibrinogen binds to specific receptor sites on platelets.
Hawiger et al. (1982) showed that the gamma and to a lesser extent the
alpha chains carry the main sites for interaction with the platelet
receptor. In a variety of species, including rodents and man, the gamma
chain occurs in 2 forms, called gamma-A and gamma-B, or gamma and
gamma-prime. In the rat, these 2 fibrinogen gamma chains arise by
translation of 2 mRNAs of 1,700 and 2,200 nucleotides, which are
produced from a single gene by alternative splice patterns (Crabtree and
Kant, 1982). The more abundant gamma-A mRNA encodes a protein that is
83% homologous with the human gamma-A chain. The gamma-B mRNA is
identical with the gamma-A sequence with the exception of a 53-bp insert
located 202 bp from the poly(A) extension. This 53-bp insert is
identical to the seventh and final intron of the gamma-A gene and is
located 4 codons before the termination codon for the gamma-A chain.
Translocation into the inserted sequence produces a unique 12 amino acid
C terminus in the rat gamma-B polypeptide that is homologous with the
known C terminus of the human gamma-B chain. The defect in the
dysfibrinogenemia described by Fernandez et al. (1989), fibrinogen
Sevilla, has not been precisely defined. It was found in a 64-year-old
Spanish woman with no history of hemorrhagic or thrombotic diathesis.
The same abnormal fibrinogen was present in a daughter and a grandson,
who also had no clotting abnormality.
Olaisen et al. (1982) assigned the fibrinogen-gamma locus to chromosome
4 by linkage to MN (111300). Using separate DNA clones for each in
hybrid cell studies, Henry et al. (1984) found that all 3 fibrinogen
genes map to chromosome 4.
Ebert (1990) cataloged fibrinogen variants. All dysfibrinogenemias due
to gamma-chain defects have missense mutations except fibrinogen
Vlissingen-1 (134850.0007), which has a 2-amino acid deletion.
Cote et al. (1998) analyzed the molecular structure-function
relationships of naturally occurring mutations in the gamma chain of
human fibrinogen. They tabulated 19 separate mutations, 17 of which were
missense mutations. In general, mutations within the gamma chain of
fibrinogen are not associated with serious bleeding disorders. Two
patients, one with Baltimore 1 (G292V; 134850.0003) and the other with
Giessen 4 (D318G; 134850.0015), who experienced mild bleeding symptoms,
also suffered from thrombotic tendencies. The only
gamma-dysfibrinogenemia associated with a serious bleeding diathesis was
Asahi (M310T; 134850.0006). Cote et al. (1998) suggested that in this
instance bleeding symptoms were probably related to the extra
glycosylation resulting from the M310T substitution. Hypoglycosylation
increases the rate and extent of clotting. Therefore, Cote et al. (1998)
speculated that hyperglycosylation could decrease the clotting rate and
thereby cause a bleeding disorder.
Congenital afibrinogenemia (202400) is a rare autosomal recessive
disorder characterized by complete absence of detectable fibrinogen.
Asselta et al. (2000) and Margaglione et al. (2000) identified mutations
in the FGG gene in patients with afibrinogenemia
(134820.0019-134820.0020).
Liu et al. (2006) studied the mechanical properties of single fibrin
fibers using an atomic force-fluorescence microscopy technique. They
determined the extensibility and elastic limit of fibers formed in the
presence and absence of factor XIIIa (134570). Factor XIIIa induces
covalent crosslinks between gamma chains (along the fiber axis) and
between the alpha (134820) chains. Samples without factor XIIIa showed
no crosslinking. Uncrosslinked fibers extended 226 +/- 52%, and
crosslinked fibers extended 332 +/- 71%, or 4.32 times their original
length. The most extreme fibers could be extended over 6 times their
length. These extensibilities are the largest of any protein fiber. Liu
et al. (2006) tested the elastic limit by stretching fibers to a certain
strain and releasing the applied force. Uncrosslinked fibers could be
stretched 2.2 times their length and recover elastically. Crosslinked
fibers could be stretched over 2.8 times their length (180% strain) and
still recover without permanent damage. Liu et al. (2006) concluded that
the effect of crosslinking is unusual in fibrin. In collagen, spider
silk, and keratin fibers, crosslinking makes fibers stiffer and less
extensible. The increased extensibility and elasticity observed for
crosslinked fibrin indicates the crosslinks are directional, along the
fiber axis. Thus, Liu et al. (2006) concluded that in physiologic
conditions, the fast-forming gamma-gamma crosslinks along the axis may
enhance elasticity and prevent rupture of the nascent fibers. These data
suggested that clot rupture does not arise from the rupture of
individual fibers, as had been assumed; rather, the branch points of the
network forming the clot yield first.
Wassel et al. (2011) used a vascular gene-centric array in 23,634
European Americans and 6,657 African American participants from 6
studies comprising the Candidate Gene Association Resource project to
examine the association of 47,539 common and lower frequency variants
with fibrinogen concentration. Wassel et al. (2011) identified a rare
pro265-to-leu variant in FGB (dbSNP rs6054) associated with lower
fibrinogen. Common fibrinogen gene SNPs FGB dbSNP rs1800787
(134830.0014) and FGG dbSNP rs2066861 significantly associated with
fibrinogen in European Americans were prevalent in African Americans and
showed consistent associations. There were several fibrinogen locus SNPs
associated with lower fibrinogen that were exclusive to African
Americans.
*FIELD* AV
.0001
FIBRINOGEN BALTIMORE 4
FIBRINOGEN MORIOKA 1;;
FIBRINOGEN OSAKA 2;;
FIBRINOGEN TOCHIGI 1;;
FIBRINOGEN TOKYO 2
FGG, ARG275CYS
In 4 persons in 3 generations of a Japanese family ascertained through
routine presurgical coagulation studies which showed markedly prolonged
thrombin time, Matsuda et al. (1983) described an abnormal fibrinogen
tentatively designated 'Tokyo II.' No unusual bleeding or thrombosis was
noted in the family. Another dysfibrinogenemia, fibrinogen Baltimore IV,
was found by Ebert and Bell (1985) in a 56-year-old white man who came
to their attention during routine clinical laboratory assessment prior
to surgery. Despite extensive trauma in the past, he had never
experienced abnormal bleeding and had had no transfusions. The family
history was negative for bleeding diathesis. Clinical laboratory test
showed only a slightly prolonged prothrombin time. Detailed studies
indicated that about half of isolated fibrinogen monomers polymerized
normally whereas the remainder polymerized at about 2% of the normal
rate. Yoshida et al. (1988) found that abnormal fibrinogen Tochigi has a
replacement of arginine at gamma-275 by cysteine. The propositus was
found to have hypofibrinogenemia during routine hematologic study, and
neither he nor his 2 daughters, who had the same abnormal fibrinogen,
had any history of thrombosis or hemorrhage. Terukina et al. (1988)
identified replacement of arginine by cysteine at position 275 of the
gamma chain in fibrinogen Osaka II thus, it is identical to fibrinogen
Tochigi. See Schmelzer et al. (1989) and Terukina et al. (1988).
Mosesson et al. (1995) demonstrated that Tokyo II fibrinogen has a
functionally abnormal D:D self-association site, and that a normal D:D
site interaction is required, in addition to D:E, for normal fibrin or
fibrinogen assembly.
.0002
FIBRINOGEN BERGAMO 2
FIBRINOGEN ESSEN 1;;
FIBRINOGEN HAIFA 1;;
FIBRINOGEN PERUGIA 1;;
FIBRINOGEN SAGA 1;;
FIBRINOGEN OSAKA 3
FGG, ARG275HIS
Reber et al. (1986) described the same substitution, namely,
arginine-to-histidine at gamma-275, in the abnormal fibrinogen from 3
unrelated persons. In 1 family, there was a thrombotic tendency. The
substitution appears to be the same as that in fibrinogen Haifa (Brook
et al., 1983), which was found in a patient with peripheral arterial
thrombosis. See Siebenlist et al. (1989) and Yamazumi et al. (1988).
Yoshida et al. (1992) demonstrated that fibrinogen Osaka III has the
same mutational change.
.0003
FIBRINOGEN BALTIMORE 1
FGG, GLY292VAL
Beck et al. (1965) demonstrated an anomalous fibrinogen in a patient
with increased tendency to thrombosis and, paradoxically, a mild
hemorrhagic diathesis. Three daughters by 2 different husbands were
similarly affected. The group referred to the anomalous protein as
fibrinogen Baltimore. Brown and Crowe (1975) concluded that fibrinogen
Baltimore has a defect in the alpha chain; later work disproved this.
Bantia et al. (1990) demonstrated that glycine-292 in the gamma-chain
was replaced by valine. Direct nucleotide sequencing of a PCR product
containing this portion of the gamma chain demonstrated that the defect
was a change in codon GGC to GTC. The molecular defect of fibrinogen
Baltimore-1 lies in a region of the gamma-chain required for fibrin
polymerization, suggesting that the integrity of gly292 is critical for
fibrin assembly.
.0004
FIBRINOGEN KYOTO 1
FGG, ASN308LYS
In a propositus and his 2 daughters, Yoshida et al. (1986) discovered a
new gamma-chain variant they called fibrinogen Kyoto. All 3 subjects had
hypofibrinogenemia but normal coagulation studies, and the variant
probably had little clinical consequence. Yoshida et al. (1988)
demonstrated replacement of asparagine-308 by lysine in the FGG gene in
fibrinogen Kyoto-1.
.0005
FIBRINOGEN BALTIMORE 3
FGG, ASN308ILE
Ebert and Bell (1988) identified Baltimore-3 as a congenital abnormal
fibrinogen with defective fibrin monomer polymerization. Bantia et al.
(1990) demonstrated an asn308-to-ile mutation. Polymerization is also
affected by asn308-to-lys (Kyoto-1).
.0006
FIBRINOGEN ASAHI
FGG, MET310THR
In an abnormal fibrinogen with severely impaired polymerization of
fibrin monomers, Yamazumi et al. (1989) identified a
methionine-to-threonine substitution at position 310 of the gamma chain.
Furthermore, asparagine at position 308 was found to be N-glycosylated
due to a newly formed consensus sequence,
asparagine(308)-glycine(309)-threonine(310).
.0007
FIBRINOGEN VLISSINGEN 1
FGG, 6-BP DEL, ASN319DEL AND ASP320DEL
Koopman et al. (1989) demonstrated a 6-basepair deletion resulting in
absence of asparagine-319 and aspartic acid-320 and a fibrinogen
molecule with defective interaction with calcium. Koopman et al. (1991)
found this congenitally abnormal fibrinogen in a young woman with
massive pulmonary embolism. In 50% of the fragments corresponding to
exon 8, the 6-bp deletion removed asparagine-319 and aspartic acid-320
from the normal gamma-chain.
.0008
FIBRINOGEN NAGOYA 1
FGG, GLN329ARG
See Miyata et al. (1989).
.0009
FIBRINOGEN KYOTO 3
FGG, ASP330TYR
See Terukina et al. (1989).
.0010
FIBRINOGEN MILANO 1
THROMBOPHILIA, DYSFIBRINOGENEMIC;;
FIBRINOGEN ALES
FGG, ASP330VAL
Reber et al. (1986) found that fibrinogen Milano I has a substitution of
valine for aspartic acid at gamma-330. The variant was discovered in a
father and daughter from northern Italy during routine studies of blood
coagulation. There was no bleeding or thrombosis in either. Fibrin
polymerization was impaired in this mutation.
Lounes et al. (2000) identified the asp330-to-val mutation in the FGG
gene in homozygous state in a case of congenital dysfibrinogenemia,
which they referred to as fibrinogen Ales. The proband had a history of
2 thrombotic strokes before age 30. His hemostatic profile was
characterized by a dramatically prolonged plasma thrombin clotting time,
and no clotting was observed with reptilase. Complete clotting of the
abnormal fibrinogen occurred after a prolonged incubation of plasma with
thrombin. The polymerization defect was characterized by a defective
site 'a,' resulting in an absence of interaction between sites A and a.
The amino acid change resulted from an A-to-T transversion in exon 8 of
the FGG gene. His sister was likewise homozygous for the mutation but
was asymptomatic. The parents were cousins, were heterozygous for the
mutation, and were asymptomatic, as were heterozygotes in the family
reported by Reber et al. (1986). Another mutation in codon 330 is
fibrinogen Kyoto-3 (134850.0009). It is also characterized by impaired
fibrin polymerization.
The proband of Lounes et al. (2000) had been hospitalized in the past
with multiple traumas during which there were no signs of unusual
bleeding or thrombotic tendency. As an explanation for the arterial
thrombosis leading to strokes, the authors suggested that, because
clotting by thrombin was dramatically delayed in the patient, thrombin
was not trapped in fibrin, allowing platelet aggregation to occur.
Thrombophilia in association with congenital dysfibrinogenemia was
reported with fibrinogen Naples (134830.0007), a defect of the beta
chain of fibrinogen. Defective thrombin binding to the clot was
identified in that instance also.
.0011
FIBRINOGEN PARIS 1
FGG, 45-BP INS, IVS8
Menache (1964) described this fibrinogen variant in a father and son.
Budzynski et al. (1974) showed that the gamma polypeptide chain in
fibrinogen Paris I is abnormally long at the C-terminal end. A
terminator mutation, analogous to that found in Hb Constant Spring, was
thought to be responsible for it (Marder, 1974); however, Rosenberg et
al. (1993) demonstrated an A-to-G transition at nucleotide 6588 within
intron 8 of the FGG gene, leading to the insertion of a 45-bp segment
between exons 8 and 9 in the mature FGG mRNA, and a 15-amino acid insert
in the protein after amino acid 350. Alternative splicing of this region
from intron 8 into the mature mRNA also resulted after translation into
a substitution of serine for glycine at position 351. Rosenberg et al.
(1993) concluded that the insertion of this amino acid sequence, with 2
additional cysteines, led to a conformationally altered and
dysfunctional gamma-chain in Paris I fibrinogen. See also Mosesson et
al. (1976).
.0012
FIBRINOGEN OSLO III
FGG,
Rupp and Beck (1984) stated that the gamma chain of fibrinogen Oslo-3 is
elongated at the C-terminal end. The mutation had not been identified.
.0013
FIBRINOGEN OSAKA 5
FGG, ARG375GLY
Heterozygosity for the abnormal fibrinogen Osaka V is characterized by
correction of defective fibrinogen clotting with physiologic
concentrations of calcium; lack of protective effect of calcium on
fibrinogen or crosslinked fibrin against further plasmic digestion; and
defective calcium binding to high affinity sites. Yoshida et al. (1992)
demonstrated substitution of glycine for arginine at position gamma-375,
presumably arising from a CGG-to-GGG change in that codon.
.0014
FIBRINOGEN MATSUMOTO 1
FGG, ASP364HIS
Okumura et al. (1996) identified an asp364-to-his mutation in the gamma
chain of fibrinogen in fibrinogen Matsumoto I, a dysfibrinogen that was
found in a heterozygous individual with a mixture of molecules with
normal and variant gamma chains. Polymerization of fibrinogen Matsumoto
I was markedly delayed and this delay could be partially compensated by
mixing with normal fibrinogen. During blood coagulation, soluble
fibrinogen is converted to fibrin monomers that polymerize to form an
insoluble clot. Polymerization had been described as a 2-step process,
the formation of double-stranded protofibrils and the subsequent lateral
aggregation of protofibrils into fibers. The residues tyr363 and asp364
had been shown to have a significant role in polymerization, most likely
in protofibril formation. Okumura et al. (1997) found that fibrinogen
containing the asp364-to-his mutation showed the same release of
fibrinopeptides A and B as the normal; in contrast, polymerization was
almost nonexistent for the asp364-to-his variant. Clottability of the
his364 variant was substantially reduced, and fibrin gels were not
formed. The data suggested that both protofibril formation and lateral
aggregation were altered by these substitutions, indicating that the
C-terminal domain of the gamma chain has a role in both polymerization
steps.
.0015
FIBRINOGEN GIESSEN 4
FGG, ARG318GLY
See Haverkate and Samama (1995).
.0016
AFIBRINOGENEMIA, CONGENITAL
FGG, IVS1DS, G-A, +5
Asselta et al. (2000) reported the first example of a mutation in the
gamma-chain gene as the cause of afibrinogenemia (202400). A 3-year-old
Pakistani patient, born of consanguineous parents, had unmeasurable
plasma levels of functional and immunoreactive fibrinogen. Sequencing of
the fibrinogen genes revealed a homozygous G-to-A transition at position
+5 of intron 1 of the gamma-chain gene. The predicted mutant fibrinogen
gamma-chain would contain the signal peptide, followed by a short
stretch of aberrant amino acids, preceding a premature stop codon. No
bleeding complication occurred at birth, but after 3 weeks the child
presented with intracranial bleeding.
.0017
AFIBRINOGENEMIA, CONGENITAL
FGG, IVS3DS, G-A, +5
Margaglione et al. (2000) described congenital afibrinogenemia (202400)
due to an FGG mutation in a 6-year-old girl whose parents were first
cousins. The diagnosis of afibrinogenemia had been made at the age of 1
year because of posttraumatic and life-threatening bleeding. She was
found to be homozygous for a G-to-A mutation at the fifth nucleotide
(nucleotide 2395) of the third intervening sequence of the FGG gene.
Sequencing of the abnormal mRNA showed complete absence of exon 3.
Skipping of exon 3 predicted the deletion of amino acid sequence from
residue 16 to residue 75 and a frameshift at amino acid 76 with a
premature stop codon within exon 4 at position 77. Thus, the truncated
gamma-chain gene product would not interact with other chains to form
the mature fibrinogen molecule.
.0018
FIBRINOGEN MILANO XII, DIGENIC
FGG, GLY165ARG
In an asymptomatic Italian woman whose routine coagulation test results
revealed a prolonged thrombin time, Bolliger-Stucki et al. (2001) found
double heterozygosity for the R16C mutation (134820.0003) in the FGA
gene and a G-to-A transition at nucleotide 4682, resulting in a
gly165-to-arg (G165R) mutation in exon 6 of the FGG gene.
.0019
FIBRINOGEN HILLSBOROUGH
FGG, GLY309ASP
Mullin et al. (2002) discovered a novel gamma-chain dysfibrinogen in a
32-year-old asymptomatic man admitted to the hospital after a car
accident. He presented with a low fibrinogen concentration and a
prolonged thrombin clotting time. Electrophoresis revealed a gamma-chain
variant with an apparently higher molecular weight. DNA sequence
analysis showed a heterozygous mutation of GGC (gly) to GAC (asp) at
codon 309 of the FGG gene.
.0021
AFIBRINOGENEMIA, CONGENITAL
FGG, IVS6AS, A-T, -320
In 2 Italian sibs with congenital afibrinogenemia (202400), previously
reported by Castaman and Rodeghiero, 1992, Spena et al. (2007)
identified a homozygous A-to-T transversion in intron 6 of the FGG gene.
RT-PCR and sequencing analysis showed that the mutation was present in a
cryptic splice site and resulted in an in-frame inclusion of a 75-bp
pseudo-exon carrying a premature stop codon. Circulating fibrinogen was
completely absent in the sibs. Spena et al. (2007) commented on the
unique pathogenic genetic mechanism in this family.
*FIELD* SA
Fornace et al. (1984); Kant et al. (1985); Reber et al. (1986); Rixon
et al. (1985); Yoshida et al. (1992); Yoshida et al. (1988)
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47. Yamazumi, K.; Shimura, K.; Terukina, S.; Takahashi, N.; Matsuda,
M.: A gamma methionine-310 to threonine substitution and consequent
N-glycosylation at gamma asparagine-308 identified in a congenital
dysfibrinogenemia associated with posttraumatic bleeding, fibrinogen
Asahi. J. Clin. Invest. 83: 1590-1597, 1989.
48. Yamazumi, K.; Terukina, S.; Onohara, S.; Matsuda, M.: Normal
plasmic cleavage of the gamma-chain variant of 'fibrinogen Saga' with
an arg275-to-his substitution. Thromb. Haemost. 60: 476-480, 1988.
49. Yoshida, N.; Hirata, H.; Morigami, Y.; Imaoka, S.; Matsuda, M.;
Yamazumi, K.; Asakura, S.: Characterization of an abnormal fibrinogen
Osaka V with the replacement of gamma-arginine 375 by glycine: the
lack of high affinity calcium binding to D-domains and the lack of
protective effect of calcium on fibrinolysis. J. Biol. Chem. 267:
2753-2759, 1992.
50. Yoshida, N.; Imaoka, S.; Hirata, H.; Matsuda, M.; Asakura, S.
: Heterozygous abnormal fibrinogen Osaka III with the replacement
of gamma-arginine-275 by histidine has an apparently higher molecular
weight gamma-chain variant. Thromb. Haemost. 68: 534-538, 1992.
51. Yoshida, N.; Okuma, M.; Moroi, M.; Matsuda, M.: A lower molecular
weight gamma-chain variant in a congenital abnormal fibrinogen (Kyoto). Blood 68:
703-707, 1986.
52. Yoshida, N.; Ota, K.; Moroi, M.; Matsuda, M.: An apparently higher
molecular weight gamma-chain variant in a new congenital abnormal
fibrinogen Tochigi characterized by the replacement of gamma arginine-275
by cysteine. Blood 71: 480-487, 1988.
53. Yoshida, N.; Terukina, S.; Okuma, M.; Moroi, M.; Aoki, N.; Matsuda,
M.: Characterization of an apparently lower molecular weight gamma-chain
variant in fibrinogen Kyoto I: the replacement of gamma-asparagine
308 by lysine which causes accelerated cleavage of fragment D(1) by
plasmin and the generation of a new plasmin cleavage site. J. Biol.
Chem. 263: 13848-13856, 1988.
*FIELD* CN
Ada Hamosh - updated: 10/4/2011
Cassandra L. Kniffin - updated: 3/25/2008
Ada Hamosh - updated: 9/8/2006
Victor A. McKusick - updated: 7/1/2002
Victor A. McKusick - updated: 10/9/2001
Victor A. McKusick - updated: 4/6/2001
Victor A. McKusick - updated: 1/8/2001
Victor A. McKusick - updated: 1/5/2001
Victor A. McKusick - updated: 11/16/1998
Victor A. McKusick - updated: 2/13/1998
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
alopez: 10/11/2011
terry: 10/4/2011
carol: 6/1/2011
wwang: 4/2/2008
ckniffin: 3/25/2008
wwang: 10/3/2006
alopez: 9/8/2006
terry: 9/6/2006
alopez: 9/20/2004
cwells: 7/23/2002
terry: 7/1/2002
carol: 12/5/2001
mcapotos: 10/23/2001
terry: 10/9/2001
carol: 4/16/2001
mcapotos: 4/16/2001
carol: 4/16/2001
mcapotos: 4/16/2001
mcapotos: 4/9/2001
terry: 4/6/2001
mcapotos: 1/17/2001
mcapotos: 1/11/2001
terry: 1/8/2001
terry: 1/5/2001
dkim: 12/2/1998
terry: 11/19/1998
terry: 11/16/1998
dkim: 6/30/1998
dholmes: 3/10/1998
mark: 2/22/1998
terry: 2/13/1998
mark: 8/12/1997
terry: 8/8/1997
alopez: 7/28/1997
mark: 12/26/1996
mark: 11/6/1995
carol: 5/4/1994
mimadm: 4/15/1994
warfield: 4/8/1994
carol: 10/27/1993
carol: 7/22/1993
*RECORD*
*FIELD* NO
134850
*FIELD* TI
*134850 FIBRINOGEN, G GAMMA POLYPEPTIDE; FGG
;;FIBRINOGEN--GAMMA POLYPEPTIDE CHAIN
read more*FIELD* TX
See fibrinogen--alpha polypeptide chain (FGA; 134820) and beta chain
(FGB; 134830). In its essential role in the adhesion and aggregation of
platelets, fibrinogen binds to specific receptor sites on platelets.
Hawiger et al. (1982) showed that the gamma and to a lesser extent the
alpha chains carry the main sites for interaction with the platelet
receptor. In a variety of species, including rodents and man, the gamma
chain occurs in 2 forms, called gamma-A and gamma-B, or gamma and
gamma-prime. In the rat, these 2 fibrinogen gamma chains arise by
translation of 2 mRNAs of 1,700 and 2,200 nucleotides, which are
produced from a single gene by alternative splice patterns (Crabtree and
Kant, 1982). The more abundant gamma-A mRNA encodes a protein that is
83% homologous with the human gamma-A chain. The gamma-B mRNA is
identical with the gamma-A sequence with the exception of a 53-bp insert
located 202 bp from the poly(A) extension. This 53-bp insert is
identical to the seventh and final intron of the gamma-A gene and is
located 4 codons before the termination codon for the gamma-A chain.
Translocation into the inserted sequence produces a unique 12 amino acid
C terminus in the rat gamma-B polypeptide that is homologous with the
known C terminus of the human gamma-B chain. The defect in the
dysfibrinogenemia described by Fernandez et al. (1989), fibrinogen
Sevilla, has not been precisely defined. It was found in a 64-year-old
Spanish woman with no history of hemorrhagic or thrombotic diathesis.
The same abnormal fibrinogen was present in a daughter and a grandson,
who also had no clotting abnormality.
Olaisen et al. (1982) assigned the fibrinogen-gamma locus to chromosome
4 by linkage to MN (111300). Using separate DNA clones for each in
hybrid cell studies, Henry et al. (1984) found that all 3 fibrinogen
genes map to chromosome 4.
Ebert (1990) cataloged fibrinogen variants. All dysfibrinogenemias due
to gamma-chain defects have missense mutations except fibrinogen
Vlissingen-1 (134850.0007), which has a 2-amino acid deletion.
Cote et al. (1998) analyzed the molecular structure-function
relationships of naturally occurring mutations in the gamma chain of
human fibrinogen. They tabulated 19 separate mutations, 17 of which were
missense mutations. In general, mutations within the gamma chain of
fibrinogen are not associated with serious bleeding disorders. Two
patients, one with Baltimore 1 (G292V; 134850.0003) and the other with
Giessen 4 (D318G; 134850.0015), who experienced mild bleeding symptoms,
also suffered from thrombotic tendencies. The only
gamma-dysfibrinogenemia associated with a serious bleeding diathesis was
Asahi (M310T; 134850.0006). Cote et al. (1998) suggested that in this
instance bleeding symptoms were probably related to the extra
glycosylation resulting from the M310T substitution. Hypoglycosylation
increases the rate and extent of clotting. Therefore, Cote et al. (1998)
speculated that hyperglycosylation could decrease the clotting rate and
thereby cause a bleeding disorder.
Congenital afibrinogenemia (202400) is a rare autosomal recessive
disorder characterized by complete absence of detectable fibrinogen.
Asselta et al. (2000) and Margaglione et al. (2000) identified mutations
in the FGG gene in patients with afibrinogenemia
(134820.0019-134820.0020).
Liu et al. (2006) studied the mechanical properties of single fibrin
fibers using an atomic force-fluorescence microscopy technique. They
determined the extensibility and elastic limit of fibers formed in the
presence and absence of factor XIIIa (134570). Factor XIIIa induces
covalent crosslinks between gamma chains (along the fiber axis) and
between the alpha (134820) chains. Samples without factor XIIIa showed
no crosslinking. Uncrosslinked fibers extended 226 +/- 52%, and
crosslinked fibers extended 332 +/- 71%, or 4.32 times their original
length. The most extreme fibers could be extended over 6 times their
length. These extensibilities are the largest of any protein fiber. Liu
et al. (2006) tested the elastic limit by stretching fibers to a certain
strain and releasing the applied force. Uncrosslinked fibers could be
stretched 2.2 times their length and recover elastically. Crosslinked
fibers could be stretched over 2.8 times their length (180% strain) and
still recover without permanent damage. Liu et al. (2006) concluded that
the effect of crosslinking is unusual in fibrin. In collagen, spider
silk, and keratin fibers, crosslinking makes fibers stiffer and less
extensible. The increased extensibility and elasticity observed for
crosslinked fibrin indicates the crosslinks are directional, along the
fiber axis. Thus, Liu et al. (2006) concluded that in physiologic
conditions, the fast-forming gamma-gamma crosslinks along the axis may
enhance elasticity and prevent rupture of the nascent fibers. These data
suggested that clot rupture does not arise from the rupture of
individual fibers, as had been assumed; rather, the branch points of the
network forming the clot yield first.
Wassel et al. (2011) used a vascular gene-centric array in 23,634
European Americans and 6,657 African American participants from 6
studies comprising the Candidate Gene Association Resource project to
examine the association of 47,539 common and lower frequency variants
with fibrinogen concentration. Wassel et al. (2011) identified a rare
pro265-to-leu variant in FGB (dbSNP rs6054) associated with lower
fibrinogen. Common fibrinogen gene SNPs FGB dbSNP rs1800787
(134830.0014) and FGG dbSNP rs2066861 significantly associated with
fibrinogen in European Americans were prevalent in African Americans and
showed consistent associations. There were several fibrinogen locus SNPs
associated with lower fibrinogen that were exclusive to African
Americans.
*FIELD* AV
.0001
FIBRINOGEN BALTIMORE 4
FIBRINOGEN MORIOKA 1;;
FIBRINOGEN OSAKA 2;;
FIBRINOGEN TOCHIGI 1;;
FIBRINOGEN TOKYO 2
FGG, ARG275CYS
In 4 persons in 3 generations of a Japanese family ascertained through
routine presurgical coagulation studies which showed markedly prolonged
thrombin time, Matsuda et al. (1983) described an abnormal fibrinogen
tentatively designated 'Tokyo II.' No unusual bleeding or thrombosis was
noted in the family. Another dysfibrinogenemia, fibrinogen Baltimore IV,
was found by Ebert and Bell (1985) in a 56-year-old white man who came
to their attention during routine clinical laboratory assessment prior
to surgery. Despite extensive trauma in the past, he had never
experienced abnormal bleeding and had had no transfusions. The family
history was negative for bleeding diathesis. Clinical laboratory test
showed only a slightly prolonged prothrombin time. Detailed studies
indicated that about half of isolated fibrinogen monomers polymerized
normally whereas the remainder polymerized at about 2% of the normal
rate. Yoshida et al. (1988) found that abnormal fibrinogen Tochigi has a
replacement of arginine at gamma-275 by cysteine. The propositus was
found to have hypofibrinogenemia during routine hematologic study, and
neither he nor his 2 daughters, who had the same abnormal fibrinogen,
had any history of thrombosis or hemorrhage. Terukina et al. (1988)
identified replacement of arginine by cysteine at position 275 of the
gamma chain in fibrinogen Osaka II thus, it is identical to fibrinogen
Tochigi. See Schmelzer et al. (1989) and Terukina et al. (1988).
Mosesson et al. (1995) demonstrated that Tokyo II fibrinogen has a
functionally abnormal D:D self-association site, and that a normal D:D
site interaction is required, in addition to D:E, for normal fibrin or
fibrinogen assembly.
.0002
FIBRINOGEN BERGAMO 2
FIBRINOGEN ESSEN 1;;
FIBRINOGEN HAIFA 1;;
FIBRINOGEN PERUGIA 1;;
FIBRINOGEN SAGA 1;;
FIBRINOGEN OSAKA 3
FGG, ARG275HIS
Reber et al. (1986) described the same substitution, namely,
arginine-to-histidine at gamma-275, in the abnormal fibrinogen from 3
unrelated persons. In 1 family, there was a thrombotic tendency. The
substitution appears to be the same as that in fibrinogen Haifa (Brook
et al., 1983), which was found in a patient with peripheral arterial
thrombosis. See Siebenlist et al. (1989) and Yamazumi et al. (1988).
Yoshida et al. (1992) demonstrated that fibrinogen Osaka III has the
same mutational change.
.0003
FIBRINOGEN BALTIMORE 1
FGG, GLY292VAL
Beck et al. (1965) demonstrated an anomalous fibrinogen in a patient
with increased tendency to thrombosis and, paradoxically, a mild
hemorrhagic diathesis. Three daughters by 2 different husbands were
similarly affected. The group referred to the anomalous protein as
fibrinogen Baltimore. Brown and Crowe (1975) concluded that fibrinogen
Baltimore has a defect in the alpha chain; later work disproved this.
Bantia et al. (1990) demonstrated that glycine-292 in the gamma-chain
was replaced by valine. Direct nucleotide sequencing of a PCR product
containing this portion of the gamma chain demonstrated that the defect
was a change in codon GGC to GTC. The molecular defect of fibrinogen
Baltimore-1 lies in a region of the gamma-chain required for fibrin
polymerization, suggesting that the integrity of gly292 is critical for
fibrin assembly.
.0004
FIBRINOGEN KYOTO 1
FGG, ASN308LYS
In a propositus and his 2 daughters, Yoshida et al. (1986) discovered a
new gamma-chain variant they called fibrinogen Kyoto. All 3 subjects had
hypofibrinogenemia but normal coagulation studies, and the variant
probably had little clinical consequence. Yoshida et al. (1988)
demonstrated replacement of asparagine-308 by lysine in the FGG gene in
fibrinogen Kyoto-1.
.0005
FIBRINOGEN BALTIMORE 3
FGG, ASN308ILE
Ebert and Bell (1988) identified Baltimore-3 as a congenital abnormal
fibrinogen with defective fibrin monomer polymerization. Bantia et al.
(1990) demonstrated an asn308-to-ile mutation. Polymerization is also
affected by asn308-to-lys (Kyoto-1).
.0006
FIBRINOGEN ASAHI
FGG, MET310THR
In an abnormal fibrinogen with severely impaired polymerization of
fibrin monomers, Yamazumi et al. (1989) identified a
methionine-to-threonine substitution at position 310 of the gamma chain.
Furthermore, asparagine at position 308 was found to be N-glycosylated
due to a newly formed consensus sequence,
asparagine(308)-glycine(309)-threonine(310).
.0007
FIBRINOGEN VLISSINGEN 1
FGG, 6-BP DEL, ASN319DEL AND ASP320DEL
Koopman et al. (1989) demonstrated a 6-basepair deletion resulting in
absence of asparagine-319 and aspartic acid-320 and a fibrinogen
molecule with defective interaction with calcium. Koopman et al. (1991)
found this congenitally abnormal fibrinogen in a young woman with
massive pulmonary embolism. In 50% of the fragments corresponding to
exon 8, the 6-bp deletion removed asparagine-319 and aspartic acid-320
from the normal gamma-chain.
.0008
FIBRINOGEN NAGOYA 1
FGG, GLN329ARG
See Miyata et al. (1989).
.0009
FIBRINOGEN KYOTO 3
FGG, ASP330TYR
See Terukina et al. (1989).
.0010
FIBRINOGEN MILANO 1
THROMBOPHILIA, DYSFIBRINOGENEMIC;;
FIBRINOGEN ALES
FGG, ASP330VAL
Reber et al. (1986) found that fibrinogen Milano I has a substitution of
valine for aspartic acid at gamma-330. The variant was discovered in a
father and daughter from northern Italy during routine studies of blood
coagulation. There was no bleeding or thrombosis in either. Fibrin
polymerization was impaired in this mutation.
Lounes et al. (2000) identified the asp330-to-val mutation in the FGG
gene in homozygous state in a case of congenital dysfibrinogenemia,
which they referred to as fibrinogen Ales. The proband had a history of
2 thrombotic strokes before age 30. His hemostatic profile was
characterized by a dramatically prolonged plasma thrombin clotting time,
and no clotting was observed with reptilase. Complete clotting of the
abnormal fibrinogen occurred after a prolonged incubation of plasma with
thrombin. The polymerization defect was characterized by a defective
site 'a,' resulting in an absence of interaction between sites A and a.
The amino acid change resulted from an A-to-T transversion in exon 8 of
the FGG gene. His sister was likewise homozygous for the mutation but
was asymptomatic. The parents were cousins, were heterozygous for the
mutation, and were asymptomatic, as were heterozygotes in the family
reported by Reber et al. (1986). Another mutation in codon 330 is
fibrinogen Kyoto-3 (134850.0009). It is also characterized by impaired
fibrin polymerization.
The proband of Lounes et al. (2000) had been hospitalized in the past
with multiple traumas during which there were no signs of unusual
bleeding or thrombotic tendency. As an explanation for the arterial
thrombosis leading to strokes, the authors suggested that, because
clotting by thrombin was dramatically delayed in the patient, thrombin
was not trapped in fibrin, allowing platelet aggregation to occur.
Thrombophilia in association with congenital dysfibrinogenemia was
reported with fibrinogen Naples (134830.0007), a defect of the beta
chain of fibrinogen. Defective thrombin binding to the clot was
identified in that instance also.
.0011
FIBRINOGEN PARIS 1
FGG, 45-BP INS, IVS8
Menache (1964) described this fibrinogen variant in a father and son.
Budzynski et al. (1974) showed that the gamma polypeptide chain in
fibrinogen Paris I is abnormally long at the C-terminal end. A
terminator mutation, analogous to that found in Hb Constant Spring, was
thought to be responsible for it (Marder, 1974); however, Rosenberg et
al. (1993) demonstrated an A-to-G transition at nucleotide 6588 within
intron 8 of the FGG gene, leading to the insertion of a 45-bp segment
between exons 8 and 9 in the mature FGG mRNA, and a 15-amino acid insert
in the protein after amino acid 350. Alternative splicing of this region
from intron 8 into the mature mRNA also resulted after translation into
a substitution of serine for glycine at position 351. Rosenberg et al.
(1993) concluded that the insertion of this amino acid sequence, with 2
additional cysteines, led to a conformationally altered and
dysfunctional gamma-chain in Paris I fibrinogen. See also Mosesson et
al. (1976).
.0012
FIBRINOGEN OSLO III
FGG,
Rupp and Beck (1984) stated that the gamma chain of fibrinogen Oslo-3 is
elongated at the C-terminal end. The mutation had not been identified.
.0013
FIBRINOGEN OSAKA 5
FGG, ARG375GLY
Heterozygosity for the abnormal fibrinogen Osaka V is characterized by
correction of defective fibrinogen clotting with physiologic
concentrations of calcium; lack of protective effect of calcium on
fibrinogen or crosslinked fibrin against further plasmic digestion; and
defective calcium binding to high affinity sites. Yoshida et al. (1992)
demonstrated substitution of glycine for arginine at position gamma-375,
presumably arising from a CGG-to-GGG change in that codon.
.0014
FIBRINOGEN MATSUMOTO 1
FGG, ASP364HIS
Okumura et al. (1996) identified an asp364-to-his mutation in the gamma
chain of fibrinogen in fibrinogen Matsumoto I, a dysfibrinogen that was
found in a heterozygous individual with a mixture of molecules with
normal and variant gamma chains. Polymerization of fibrinogen Matsumoto
I was markedly delayed and this delay could be partially compensated by
mixing with normal fibrinogen. During blood coagulation, soluble
fibrinogen is converted to fibrin monomers that polymerize to form an
insoluble clot. Polymerization had been described as a 2-step process,
the formation of double-stranded protofibrils and the subsequent lateral
aggregation of protofibrils into fibers. The residues tyr363 and asp364
had been shown to have a significant role in polymerization, most likely
in protofibril formation. Okumura et al. (1997) found that fibrinogen
containing the asp364-to-his mutation showed the same release of
fibrinopeptides A and B as the normal; in contrast, polymerization was
almost nonexistent for the asp364-to-his variant. Clottability of the
his364 variant was substantially reduced, and fibrin gels were not
formed. The data suggested that both protofibril formation and lateral
aggregation were altered by these substitutions, indicating that the
C-terminal domain of the gamma chain has a role in both polymerization
steps.
.0015
FIBRINOGEN GIESSEN 4
FGG, ARG318GLY
See Haverkate and Samama (1995).
.0016
AFIBRINOGENEMIA, CONGENITAL
FGG, IVS1DS, G-A, +5
Asselta et al. (2000) reported the first example of a mutation in the
gamma-chain gene as the cause of afibrinogenemia (202400). A 3-year-old
Pakistani patient, born of consanguineous parents, had unmeasurable
plasma levels of functional and immunoreactive fibrinogen. Sequencing of
the fibrinogen genes revealed a homozygous G-to-A transition at position
+5 of intron 1 of the gamma-chain gene. The predicted mutant fibrinogen
gamma-chain would contain the signal peptide, followed by a short
stretch of aberrant amino acids, preceding a premature stop codon. No
bleeding complication occurred at birth, but after 3 weeks the child
presented with intracranial bleeding.
.0017
AFIBRINOGENEMIA, CONGENITAL
FGG, IVS3DS, G-A, +5
Margaglione et al. (2000) described congenital afibrinogenemia (202400)
due to an FGG mutation in a 6-year-old girl whose parents were first
cousins. The diagnosis of afibrinogenemia had been made at the age of 1
year because of posttraumatic and life-threatening bleeding. She was
found to be homozygous for a G-to-A mutation at the fifth nucleotide
(nucleotide 2395) of the third intervening sequence of the FGG gene.
Sequencing of the abnormal mRNA showed complete absence of exon 3.
Skipping of exon 3 predicted the deletion of amino acid sequence from
residue 16 to residue 75 and a frameshift at amino acid 76 with a
premature stop codon within exon 4 at position 77. Thus, the truncated
gamma-chain gene product would not interact with other chains to form
the mature fibrinogen molecule.
.0018
FIBRINOGEN MILANO XII, DIGENIC
FGG, GLY165ARG
In an asymptomatic Italian woman whose routine coagulation test results
revealed a prolonged thrombin time, Bolliger-Stucki et al. (2001) found
double heterozygosity for the R16C mutation (134820.0003) in the FGA
gene and a G-to-A transition at nucleotide 4682, resulting in a
gly165-to-arg (G165R) mutation in exon 6 of the FGG gene.
.0019
FIBRINOGEN HILLSBOROUGH
FGG, GLY309ASP
Mullin et al. (2002) discovered a novel gamma-chain dysfibrinogen in a
32-year-old asymptomatic man admitted to the hospital after a car
accident. He presented with a low fibrinogen concentration and a
prolonged thrombin clotting time. Electrophoresis revealed a gamma-chain
variant with an apparently higher molecular weight. DNA sequence
analysis showed a heterozygous mutation of GGC (gly) to GAC (asp) at
codon 309 of the FGG gene.
.0021
AFIBRINOGENEMIA, CONGENITAL
FGG, IVS6AS, A-T, -320
In 2 Italian sibs with congenital afibrinogenemia (202400), previously
reported by Castaman and Rodeghiero, 1992, Spena et al. (2007)
identified a homozygous A-to-T transversion in intron 6 of the FGG gene.
RT-PCR and sequencing analysis showed that the mutation was present in a
cryptic splice site and resulted in an in-frame inclusion of a 75-bp
pseudo-exon carrying a premature stop codon. Circulating fibrinogen was
completely absent in the sibs. Spena et al. (2007) commented on the
unique pathogenic genetic mechanism in this family.
*FIELD* SA
Fornace et al. (1984); Kant et al. (1985); Reber et al. (1986); Rixon
et al. (1985); Yoshida et al. (1992); Yoshida et al. (1988)
*FIELD* RF
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E.; Giangrande, P. L. F.; Mannucci, P. M.; Tenchini, M. L.: Afibrinogenemia:
first identification of a splicing mutation in the fibrinogen gamma
chain gene leading to a major gamma chain truncation. Blood 96:
2496-2500, 2000.
2. Bantia, S.; Bell, W. R.; Dang, C. V.: Polymerization defect of
fibrinogen Baltimore III due to a gamma-asn308-to-ile mutation. Blood 75:
1659-1663, 1990.
3. Bantia, S.; Mane, S. M.; Bell, W. R.; Dang, C. V.: Fibrinogen
Baltimore I: polymerization defect associated with a gamma(292)gly-to-val
(GGC-GTC) mutation. Blood 76: 2279-2283, 1990.
4. Beck, E. A.; Charache, P.; Jackson, D. P.: A new inherited coagulation
disorder caused by an abnormal fibrinogen ('fibrinogen Baltimore'). Nature 208:
143-145, 1965.
5. Bolliger-Stucki, B.; Lord, S. T.; Furlan, M.: Fibrinogen Milano
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6. Brook, J. G.; Tabori, S.; Tatarsky, I.; Hashmonai, M.; Schramek,
A.: Fibrinogen 'Haifa'--a new fibrinogen variant: a case report. Haemostasis 13:
277-281, 1983.
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1190-1194, 1975.
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Defect in the gamma polypeptide chain of a congenital abnormal fibrinogen
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prolonged bleeding time of two patients with congenital afibrinogenemia. Thromb.
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2195-2212, 1998.
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gene: alternative mRNA splice patterns produce the gamma-A and gamma-B
(gamma-prime) chains of fibrinogen. Cell 31: 159-166, 1982.
12. Ebert, R. F.: Index of Variant Human Fibrinogens. Rockville,
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dysfibrinogenemia with a shortened gamma-subunit. Thromb. Res. 51:
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15. Fernandez, F. J.; Noguerol, P.; Sosa, R.; Cuesta, B.; Paramo,
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16. Fornace, A. J., Jr.; Cummings, D. E.; Comeau, C. M.; Kant, J.
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alternate mRNA splicing near the 3-prime end of the gene produces
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12826-12830, 1984.
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18. Hawiger, J.; Timmons, S.; Kloczewiak, M.; Strong, D. D.; Doolittle,
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19. Henry, I.; Uzan, G.; Weil, D.; Nicolas, H.; Kaplan, J. C.; Marguerie,
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and gamma chains of fibrinogen are located on chromosome 4. (Abstract) Cytogenet.
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locus on chromosome 4: gene duplication accompanied by transposition
and inversion. Proc. Nat. Acad. Sci. 82: 2344-2348, 1985.
21. Koopman, J.; Haverkate, F.; Briet, E.; Lord, S. T.: A congenitally
abnormal fibrinogen (Vlissingen) with a 6-base deletion in the gamma-chain
gene, causing defective calcium binding and impaired fibrin polymerization. J.
Biol. Chem. 266: 13456-13461, 1991.
22. Koopman, J.; Haverkate, F.; Lord, S.; Caekebeke-Peerlinck, K.;
Brommer, E.; Briet, E.: A six base deletion in the gamma-chain gene
of dysfibrinogen Vlissingen, coding for asn319 and asp320, resulting
in defective interaction with calcium. (Abstract) Thromb. Haemost. 62:
158 only, 1989.
23. Liu, W.; Jawerth, L. M.; Sparks, E. A.; Falvo, M. R.; Hantgan,
R. R.; Superfine, R.; Lord, S. T.; Guthold, M.: Fibrin fibers have
extraordinary extensibility and elasticity. Science 313: 634 only,
2006.
24. Lounes, K. C.; Soria, C.; Mirshahi, S. S.; Desvignes, P.; Mirshahi,
M.; Bertrand, O.; Bonnet, P.; Koopman, J.; Soria, J.: Fibrinogen
Ales: a homozygous case of dysfibrinogenemia (gamma-asp330-to-val)
characterized by a defective fibrin polymerization site 'a'. Blood 96:
3473-3479, 2000.
25. Marder, V. J.: Personal Communication. Philadelphia, Pa. 12/8/1974.
26. Margaglione, M.; Santacroce, R.; Colaizzo, D.; Seripa, D.; Vecchione,
G.; Lupone, M. R.; De Lucia, D.; Fortina, P.; Grandone, E.; Perricone,
C.; Di Minno, G.: A G-to-A mutation in IVS-3 of the human gamma fibrinogen
gene causing afibrinogenemia due to abnormal RNA splicing. Blood 96:
2501-2505, 2000.
27. Matsuda, M.; Baba, M.; Morimoto, K.; Nakamikawa, C.: 'Fibrinogen
Tokyo II': an abnormal fibrinogen with an impaired polymerization
site on the aligned DD domain of fibrin molecules. J. Clin. Invest. 72:
1034-1041, 1983.
28. Menache, D.: Constitutional and familial abnormal fibrinogen. Thromb.
Diath. Haemorrh. 10 (suppl. 13): 173-185, 1964.
29. Miyata, T.; Furukawa, K.; Iwanaga, S.; Takamatsu, J.; Saito, H.
: Fibrinogen Nagoya, a replacement of glutamine-329 by arginine in
the gamma-chain that impairs the polymerization of fibrin monomer. J.
Biochem. 105: 10-14, 1989.
30. Mosesson, M. W.; Amrani, D. L.; Menache, D.: Studies on the structural
abnormality of fibrinogen Paris I. J. Clin. Invest. 57: 782-790,
1976.
31. Mosesson, M. W.; Siebenlist, K. R.; DiOrio, J. P.; Matsuda, M.;
Hainfeld, J. F.; Wall, J. S.: The role of fibrinogen D domain intermolecular
association sites in the polymerization of fibrin and fibrinogen Tokyo
II (gamma-275 Arg-to-Cys). J. Clin. Invest. 96: 1053-1058, 1995.
32. Mullin, J. L.; Brennan, S. O.; Ganly, P. S.; George, P. M.: Fibrinogen
Hillsborough: a novel gamma-gly309asp dysfibrinogen with impaired
clotting. Blood 99: 3597-3601, 2002.
33. Okumura, N.; Furihata, K.; Terasawa, F.; Nagagoshi, R.; Ueno,
I.; Katsuyama, T.: Fibrinogen Matsumoto I: a gamma 364 asp-to-his
(GAT-to-CAT) substitution associated with defective fibrin polymerization. Thromb.
Haemost. 75: 887-891, 1996.
34. Okumura, N.; Gorkun, O. V.; Lord, S. T.: Severely impaired polymerization
of recombinant fibrinogen gamma-364 asp-to-his, the substitution discovered
in a heterozygous individual. J. Biol. Chem. 272: 29596-29601, 1997.
35. Olaisen, B.; Teisberg, P.; Gedde-Dahl, T., Jr.: Fibrinogen gamma
chain locus is on chromosome 4 in man. Hum. Genet. 61: 24-26, 1982.
36. Reber, P.; Furlan, M.; Henschen, A.; Kaudewitz, H.; Barbui, T.;
Hilgard, P.; Nenci, G. G.; Berrettini, M.; Beck, E. A.: Three abnormal
fibrinogen variants with the same amino acid substitution (gamma275
arg-to-his): fibrinogens Bergamo II, Essen and Perugia. Thromb. Haemost. 56:
401-406, 1986.
37. Reber, P.; Furlan, M.; Rupp, C.; Kehl, M.; Henschen, A.; Mannucci,
P. M.; Beck, E. A.: Characterization of fibrinogen Milano I: amino
acid exchange gamma-330 asp-to-val impairs fibrin polymerization. Blood 67:
1751-1756, 1986.
38. Rixon, M. W.; Chung, D. W.; Davie, E. W.: Nucleotide sequence
of the gene for the gamma chain of human fibrinogen. Biochemistry 24:
2077-2086, 1985.
39. Rosenberg, J. B.; Newman, P. J.; Mosesson, M. W.; Guillin, M.-C.;
Amrani, D. L.: Paris I dysfibrinogenemia: a point mutation in intron
8 results in insertion of a 15 amino acid sequence in fibrinogen gamma-chain. Thromb.
Haemost. 69: 217-220, 1993.
40. Rupp, C.; Beck, E. A.: Congenital dysfibrinogenemia.In: Beck,
E. A.; Furlan, M.: Variants of Human Fibrinogen. Berne: Hans Huber
(pub.) 1984. Pp. 65-130.
41. Schmelzer, C. H.; Ebert, R. F.; Bell, W. R.: Fibrinogen Baltimore
IV: congenital dysfibrinogenemia with a gamma-275 (arg-to-cys) substitution. Thromb.
Res. 56: 307-316, 1989.
42. Siebenlist, K. R.; Mosesson, M. W.; Di Orio, J. P.; Tavori, S.;
Tatarsky, I.; Rimon, A.: The polymerization of fibrin prepared from
fibrinogen Haifa (gamma-275-arg-to-his). Thromb. Haemost. 62: 875-879,
1989.
43. Spena, S.; Asselta, R.; Plate, M.; Castaman, G.; Duga, S.; Tenchini,
M. L.: Pseudo-exon activation caused by a deep-intronic mutation
in the fibrinogen gamma-chain gene as a novel mechanism for congenital
afibrinogenaemia. Brit. J. Haemat. 139: 128-132, 2007.
44. Terukina, S.; Matsuda, M.; Hirata, H.; Takeda, Y.; Miyata, T.;
Takao, T.; Shimonishi, Y.: Substitution of gamma-arg-275 by cys in
an abnormal fibrinogen, 'fibrinogen Osaka II': evidence for a unique
solitary cystine structure at the mutation site. J. Biol. Chem. 263:
13579-13587, 1988.
45. Terukina, S.; Yamazumi, K.; Okamoto, K.; Yamashita, H.; Ito, Y.;
Matsuda, M.: Fibrinogen Kyoto III: a congenital dysfibrinogen with
a gamma aspartic acid-330 to tyrosine substitution. Blood 74: 2681-2687,
1989.
46. Wassel, C. L.; Lange, L. A.; Keating, B. J.; Taylor, K. C.; Johnson,
A. D.; Palmer, C.; Ho, L. A.; Smith, N. L.; Lange, E. M.; Li, Y.;
Yang, Q.; Delaney, J. A.; and 11 others: Association of genomic
loci from a cardiovascular gene SNP array with fibrinogen levels in
European Americans and African-Americans from six cohort studies:
the Candidate Gene Association Resource (CARe). Blood 117: 268-275,
2011.
47. Yamazumi, K.; Shimura, K.; Terukina, S.; Takahashi, N.; Matsuda,
M.: A gamma methionine-310 to threonine substitution and consequent
N-glycosylation at gamma asparagine-308 identified in a congenital
dysfibrinogenemia associated with posttraumatic bleeding, fibrinogen
Asahi. J. Clin. Invest. 83: 1590-1597, 1989.
48. Yamazumi, K.; Terukina, S.; Onohara, S.; Matsuda, M.: Normal
plasmic cleavage of the gamma-chain variant of 'fibrinogen Saga' with
an arg275-to-his substitution. Thromb. Haemost. 60: 476-480, 1988.
49. Yoshida, N.; Hirata, H.; Morigami, Y.; Imaoka, S.; Matsuda, M.;
Yamazumi, K.; Asakura, S.: Characterization of an abnormal fibrinogen
Osaka V with the replacement of gamma-arginine 375 by glycine: the
lack of high affinity calcium binding to D-domains and the lack of
protective effect of calcium on fibrinolysis. J. Biol. Chem. 267:
2753-2759, 1992.
50. Yoshida, N.; Imaoka, S.; Hirata, H.; Matsuda, M.; Asakura, S.
: Heterozygous abnormal fibrinogen Osaka III with the replacement
of gamma-arginine-275 by histidine has an apparently higher molecular
weight gamma-chain variant. Thromb. Haemost. 68: 534-538, 1992.
51. Yoshida, N.; Okuma, M.; Moroi, M.; Matsuda, M.: A lower molecular
weight gamma-chain variant in a congenital abnormal fibrinogen (Kyoto). Blood 68:
703-707, 1986.
52. Yoshida, N.; Ota, K.; Moroi, M.; Matsuda, M.: An apparently higher
molecular weight gamma-chain variant in a new congenital abnormal
fibrinogen Tochigi characterized by the replacement of gamma arginine-275
by cysteine. Blood 71: 480-487, 1988.
53. Yoshida, N.; Terukina, S.; Okuma, M.; Moroi, M.; Aoki, N.; Matsuda,
M.: Characterization of an apparently lower molecular weight gamma-chain
variant in fibrinogen Kyoto I: the replacement of gamma-asparagine
308 by lysine which causes accelerated cleavage of fragment D(1) by
plasmin and the generation of a new plasmin cleavage site. J. Biol.
Chem. 263: 13848-13856, 1988.
*FIELD* CN
Ada Hamosh - updated: 10/4/2011
Cassandra L. Kniffin - updated: 3/25/2008
Ada Hamosh - updated: 9/8/2006
Victor A. McKusick - updated: 7/1/2002
Victor A. McKusick - updated: 10/9/2001
Victor A. McKusick - updated: 4/6/2001
Victor A. McKusick - updated: 1/8/2001
Victor A. McKusick - updated: 1/5/2001
Victor A. McKusick - updated: 11/16/1998
Victor A. McKusick - updated: 2/13/1998
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
alopez: 10/11/2011
terry: 10/4/2011
carol: 6/1/2011
wwang: 4/2/2008
ckniffin: 3/25/2008
wwang: 10/3/2006
alopez: 9/8/2006
terry: 9/6/2006
alopez: 9/20/2004
cwells: 7/23/2002
terry: 7/1/2002
carol: 12/5/2001
mcapotos: 10/23/2001
terry: 10/9/2001
carol: 4/16/2001
mcapotos: 4/16/2001
carol: 4/16/2001
mcapotos: 4/16/2001
mcapotos: 4/9/2001
terry: 4/6/2001
mcapotos: 1/17/2001
mcapotos: 1/11/2001
terry: 1/8/2001
terry: 1/5/2001
dkim: 12/2/1998
terry: 11/19/1998
terry: 11/16/1998
dkim: 6/30/1998
dholmes: 3/10/1998
mark: 2/22/1998
terry: 2/13/1998
mark: 8/12/1997
terry: 8/8/1997
alopez: 7/28/1997
mark: 12/26/1996
mark: 11/6/1995
carol: 5/4/1994
mimadm: 4/15/1994
warfield: 4/8/1994
carol: 10/27/1993
carol: 7/22/1993
MIM
202400
*RECORD*
*FIELD* NO
202400
*FIELD* TI
#202400 AFIBRINOGENEMIA, CONGENITAL
HYPOFIBRINOGENEMIA, CONGENITAL, INCLUDED;;
DYSFIBRINOGENEMIA, CONGENITAL, INCLUDED;;
read moreHYPODYSFIBRINOGENEMIA, CONGENITAL, INCLUDED
*FIELD* TX
A number sign (#) is used with this entry because the phenotype is the
result of mutation in one or another of the 3 fibrinogen genes, alpha
(FGA; 134820), beta (FGB; 134830), or gamma (FGG; 134850). Complete
absence of detectable fibrinogen, true congenital afibrinogenemia, was
first demonstrated to be due to a deletion in the FGA gene
(134820.0019). The phenotype has also been associated with missense
mutations in the FGB gene (134830.0009, 134830.0010) that result in
impaired fibrinogen secretion and with mutations in the FGG gene
(134850.0016-134850.0017).
Lefebvre et al. (2004) noted that fibrinogen abnormalities can be
classified according to whether there are low or no circulating levels
of normal protein (hypofibrinogenemia or afibrinogenemia), a mutated
species (dysfibrinogenemia), or a combination (hypodysfibrinogenemia).
Reports (e.g., Haverkate and Samama, 1995) on approximately 350 families
with dysfibrinogenemia revealed that approximately half of cases are
clinically silent, a quarter show a tendency toward bleeding, and
another quarter show a predisposition for thrombosis with or without
bleeding.
Although relatively few cases of congenital afibrinogenemia have been
reported, the high proportion with consanguineous parents and/or
affected sibs makes recessive inheritance very likely. The blood is
completely incoagulable, yet some of the affected persons have
remarkably little trouble with bleeding. In some cases the disorder was
detected at birth because of excess bleeding from the umbilical stump. A
partial deficiency of fibrinogen has been observed in parents and other
heterozygotes. In 2 brothers reported by Lemoine et al. (1963)
congenital afibrinogenemia was associated with osseous and hepatic
lesions, thought to be of hemorrhagic origin. In several Jewish
communities in Israel, the rate of consanguinity and particularly of
uncle-niece marriages is unusually high. Fried and Kaufman (1980)
studied an Iraqi Jewish sibship and a Moroccan Jewish kindred in which
10 of 27 sibs had congenital afibrinogenemia. Death occurred in 6 in
childhood. Two affected sibs were young women. Two died as neonates from
uncontrollable bleeding. Two of the survivors had suffered spontaneous
rupture of the spleen. Fitness seemed to be close to zero. Neerman-Arbez
et al. (1999) reported that patients with afibrinogenemia respond well
to fibrinogen replacement therapy, either prophylactically or on demand.
Neerman-Arbez et al. (2000) pointed out that the overwhelming majority
of cases of afibrinogenemia are due to truncating mutations of the FGA
gene. One of these mutations is a recurrent deletion of approximately 11
kb that probably results from a nonhomologous recombination mediated by
7-bp direct repeats; see 134820.0019. Another common recurrent mutation
occurs at the donor splice site of FGA intron 4 (134820.0020).
*FIELD* SA
Barbui et al. (1972); Bommer et al. (1963); Bronnimann (1954); Egbring
et al. (1971); Elseed and Karrar (1984); Girolami et al. (1971); Lawson
(1953); Montgomery and Natelson (1977); Neerman-Arbez et al. (2001);
Prichard and Vann (1954); Werder (1963)
*FIELD* RF
1. Barbui, T.; Porciello, P. I.; Dini, E.: Coagulation studies in
a case of severe congenital hypofibrinogenemia. Thromb. Diath. Haemorrh. 28:
129-134, 1972.
2. Bommer, W.; Kunzer, W.; Schroer, H.: Kongenitale Afibrinogenaemie. Ann.
Paediat. 200: 46-59, 1963.
3. Bronnimann, R.: Kongenitale Afibrinogenamie. Acta Haemat. 11:
40-51, 1954.
4. Egbring, R.; Andrassey, K.; Egli, H.; Meyer-Linderberg, J.: Diagnostische
und therapeutische Probleme bei congenitaler Afibrinogenaemie. Blut 22:
175-201, 1971.
5. Elseed, F. A.; Karrar, Z. A.: Congenital afibrinogenaemia in a
Saudi family: a case report and family study. Acta Haemat. 71: 388-392,
1984.
6. Fried, K.; Kaufman, S.: Congenital afibrinogenemia in 10 offspring
of uncle-niece marriages. Clin. Genet. 17: 223-227, 1980.
7. Girolami, A.; Zacchello, G.; D'Elia, R.: Congenital afibrinogenemia:
a case report with some considerations on the hereditary transmission
of this disorder. Thromb. Diath. Haemorrh. 25: 460-468, 1971.
8. Haverkate, F.; Samama, M.: Familial dysfibrinogenemia and thrombophilia:
report on a study of the SSC subcommittee on fibrinogen. Thromb.
Haemost. 73: 151-161, 1995.
9. Lawson, H. A.: Congenital afibrinogenemia: report of a case. New
Eng. J. Med. 248: 552-554, 1953.
10. Lefebvre, P.; Velasco, P. T.; Dear, A.; Lounes, K. C.; Lord, S.
T.; Brennan, S. O.; Green, D.; Lorand, L.: Severe hypodysfibrinogenemia
in compound heterozygotes of the fibrinogen A-alpha-IVS4+1G-T mutation
and an A-alpha-gln328 truncation (fibrinogen Keokuk). Blood 103:
2571-2576, 2004.
11. Lemoine, P.; Harousseau, H.; Guimbretiere, J.; Lenne, Y.; Angebaud,
Y.: Afibrinemie congenitale chez deux freres avec lesions osseuses
et hepatiques. Arch. Franc. Pediat. 20: 463-483, 1963.
12. Montgomery, R.; Natelson, S. E.: Afibrinogenemia with intracerebral
hematoma: report of a successfully treated case. Am. J. Dis. Child. 131:
555-556, 1977.
13. Neerman-Arbez, M.; de Moerloose, P.; Bridel, C.; Honsberger, A.;
Schonborner, A.; Rossier, C.; Peerlinck, K.; Claeyssens, S.; Di Michele,
D.; d'Oiron, R.; Dreyfus, M.; Laubriat-Bianchin, M.; Dieval, J.; Antonarakis,
S. E.; Morris, M. A.: Mutations in the fibrinogen A-alpha gene account
for the majority of cases of congenital afibrinogenemia. Blood 96:
149-152, 2000.
14. Neerman-Arbez, M.; de Moerloose, P.; Honsberger, A.; Parlier,
G.; Arnuti, B.; Biron, C.; Borg, J.-Y.; Eber, S.; Meili, E.; Peter-Salonen,
K.; Ripoll, L.; Vervel, C.; d'Oiron, R.; Staeger, P.; Antonarakis,
S. E.; Morris, M. A.: Molecular analysis of the fibrinogen gene cluster
in 16 patients with congenital afibrinogenemia: novel truncating mutations
in the FGA and FGG genes. Hum. Genet. 108: 237-240, 2001.
15. Neerman-Arbez, M.; Honsberger, A.; Antonarakis, S. E.; Morris,
M. A.: Deletion of the fibrinogen alpha-chain gene (FGA) causes congenital
afibrogenemia (sic). J. Clin. Invest. 103: 215-218, 1999. Note:
Erratum: J. Clin. Invest. 103: 759 only, 1999.
16. Prichard, R. W.; Vann, R. L.: Congenital afibrinogenaemia: report
on a child without fibrinogen and review of the literature. Am. J.
Dis. Child. 88: 703-710, 1954.
17. Werder, E. A.: Kongenitale Afibrinogenaemie. Helv. Paediat.
Acta 18: 208-229, 1963.
*FIELD* CS
Abdomen:
Splenic rupture
Heme:
Blood completely incoagulable;
Bleeding mild to severe;
Osseous hemorrhage;
Hepatic hemorrhage
Lab:
Afibrinogenemia
Inheritance:
Autosomal recessive
*FIELD* CN
Anne M. Stumpf - updated: 9/20/2004
Victor A. McKusick - updated: 4/6/2001
Victor A. McKusick - updated: 9/27/2000
Victor A. McKusick - updated: 7/13/2000
Victor A. McKusick - updated: 3/16/1999
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
carol: 12/17/2012
alopez: 9/20/2004
mcapotos: 4/16/2001
mcapotos: 4/9/2001
terry: 4/6/2001
mcapotos: 10/12/2000
mcapotos: 10/10/2000
terry: 9/27/2000
alopez: 7/21/2000
terry: 7/13/2000
carol: 3/16/1999
terry: 3/16/1999
mimadm: 11/12/1995
supermim: 3/16/1992
carol: 1/17/1992
supermim: 3/20/1990
supermim: 2/8/1990
carol: 2/5/1990
*RECORD*
*FIELD* NO
202400
*FIELD* TI
#202400 AFIBRINOGENEMIA, CONGENITAL
HYPOFIBRINOGENEMIA, CONGENITAL, INCLUDED;;
DYSFIBRINOGENEMIA, CONGENITAL, INCLUDED;;
read moreHYPODYSFIBRINOGENEMIA, CONGENITAL, INCLUDED
*FIELD* TX
A number sign (#) is used with this entry because the phenotype is the
result of mutation in one or another of the 3 fibrinogen genes, alpha
(FGA; 134820), beta (FGB; 134830), or gamma (FGG; 134850). Complete
absence of detectable fibrinogen, true congenital afibrinogenemia, was
first demonstrated to be due to a deletion in the FGA gene
(134820.0019). The phenotype has also been associated with missense
mutations in the FGB gene (134830.0009, 134830.0010) that result in
impaired fibrinogen secretion and with mutations in the FGG gene
(134850.0016-134850.0017).
Lefebvre et al. (2004) noted that fibrinogen abnormalities can be
classified according to whether there are low or no circulating levels
of normal protein (hypofibrinogenemia or afibrinogenemia), a mutated
species (dysfibrinogenemia), or a combination (hypodysfibrinogenemia).
Reports (e.g., Haverkate and Samama, 1995) on approximately 350 families
with dysfibrinogenemia revealed that approximately half of cases are
clinically silent, a quarter show a tendency toward bleeding, and
another quarter show a predisposition for thrombosis with or without
bleeding.
Although relatively few cases of congenital afibrinogenemia have been
reported, the high proportion with consanguineous parents and/or
affected sibs makes recessive inheritance very likely. The blood is
completely incoagulable, yet some of the affected persons have
remarkably little trouble with bleeding. In some cases the disorder was
detected at birth because of excess bleeding from the umbilical stump. A
partial deficiency of fibrinogen has been observed in parents and other
heterozygotes. In 2 brothers reported by Lemoine et al. (1963)
congenital afibrinogenemia was associated with osseous and hepatic
lesions, thought to be of hemorrhagic origin. In several Jewish
communities in Israel, the rate of consanguinity and particularly of
uncle-niece marriages is unusually high. Fried and Kaufman (1980)
studied an Iraqi Jewish sibship and a Moroccan Jewish kindred in which
10 of 27 sibs had congenital afibrinogenemia. Death occurred in 6 in
childhood. Two affected sibs were young women. Two died as neonates from
uncontrollable bleeding. Two of the survivors had suffered spontaneous
rupture of the spleen. Fitness seemed to be close to zero. Neerman-Arbez
et al. (1999) reported that patients with afibrinogenemia respond well
to fibrinogen replacement therapy, either prophylactically or on demand.
Neerman-Arbez et al. (2000) pointed out that the overwhelming majority
of cases of afibrinogenemia are due to truncating mutations of the FGA
gene. One of these mutations is a recurrent deletion of approximately 11
kb that probably results from a nonhomologous recombination mediated by
7-bp direct repeats; see 134820.0019. Another common recurrent mutation
occurs at the donor splice site of FGA intron 4 (134820.0020).
*FIELD* SA
Barbui et al. (1972); Bommer et al. (1963); Bronnimann (1954); Egbring
et al. (1971); Elseed and Karrar (1984); Girolami et al. (1971); Lawson
(1953); Montgomery and Natelson (1977); Neerman-Arbez et al. (2001);
Prichard and Vann (1954); Werder (1963)
*FIELD* RF
1. Barbui, T.; Porciello, P. I.; Dini, E.: Coagulation studies in
a case of severe congenital hypofibrinogenemia. Thromb. Diath. Haemorrh. 28:
129-134, 1972.
2. Bommer, W.; Kunzer, W.; Schroer, H.: Kongenitale Afibrinogenaemie. Ann.
Paediat. 200: 46-59, 1963.
3. Bronnimann, R.: Kongenitale Afibrinogenamie. Acta Haemat. 11:
40-51, 1954.
4. Egbring, R.; Andrassey, K.; Egli, H.; Meyer-Linderberg, J.: Diagnostische
und therapeutische Probleme bei congenitaler Afibrinogenaemie. Blut 22:
175-201, 1971.
5. Elseed, F. A.; Karrar, Z. A.: Congenital afibrinogenaemia in a
Saudi family: a case report and family study. Acta Haemat. 71: 388-392,
1984.
6. Fried, K.; Kaufman, S.: Congenital afibrinogenemia in 10 offspring
of uncle-niece marriages. Clin. Genet. 17: 223-227, 1980.
7. Girolami, A.; Zacchello, G.; D'Elia, R.: Congenital afibrinogenemia:
a case report with some considerations on the hereditary transmission
of this disorder. Thromb. Diath. Haemorrh. 25: 460-468, 1971.
8. Haverkate, F.; Samama, M.: Familial dysfibrinogenemia and thrombophilia:
report on a study of the SSC subcommittee on fibrinogen. Thromb.
Haemost. 73: 151-161, 1995.
9. Lawson, H. A.: Congenital afibrinogenemia: report of a case. New
Eng. J. Med. 248: 552-554, 1953.
10. Lefebvre, P.; Velasco, P. T.; Dear, A.; Lounes, K. C.; Lord, S.
T.; Brennan, S. O.; Green, D.; Lorand, L.: Severe hypodysfibrinogenemia
in compound heterozygotes of the fibrinogen A-alpha-IVS4+1G-T mutation
and an A-alpha-gln328 truncation (fibrinogen Keokuk). Blood 103:
2571-2576, 2004.
11. Lemoine, P.; Harousseau, H.; Guimbretiere, J.; Lenne, Y.; Angebaud,
Y.: Afibrinemie congenitale chez deux freres avec lesions osseuses
et hepatiques. Arch. Franc. Pediat. 20: 463-483, 1963.
12. Montgomery, R.; Natelson, S. E.: Afibrinogenemia with intracerebral
hematoma: report of a successfully treated case. Am. J. Dis. Child. 131:
555-556, 1977.
13. Neerman-Arbez, M.; de Moerloose, P.; Bridel, C.; Honsberger, A.;
Schonborner, A.; Rossier, C.; Peerlinck, K.; Claeyssens, S.; Di Michele,
D.; d'Oiron, R.; Dreyfus, M.; Laubriat-Bianchin, M.; Dieval, J.; Antonarakis,
S. E.; Morris, M. A.: Mutations in the fibrinogen A-alpha gene account
for the majority of cases of congenital afibrinogenemia. Blood 96:
149-152, 2000.
14. Neerman-Arbez, M.; de Moerloose, P.; Honsberger, A.; Parlier,
G.; Arnuti, B.; Biron, C.; Borg, J.-Y.; Eber, S.; Meili, E.; Peter-Salonen,
K.; Ripoll, L.; Vervel, C.; d'Oiron, R.; Staeger, P.; Antonarakis,
S. E.; Morris, M. A.: Molecular analysis of the fibrinogen gene cluster
in 16 patients with congenital afibrinogenemia: novel truncating mutations
in the FGA and FGG genes. Hum. Genet. 108: 237-240, 2001.
15. Neerman-Arbez, M.; Honsberger, A.; Antonarakis, S. E.; Morris,
M. A.: Deletion of the fibrinogen alpha-chain gene (FGA) causes congenital
afibrogenemia (sic). J. Clin. Invest. 103: 215-218, 1999. Note:
Erratum: J. Clin. Invest. 103: 759 only, 1999.
16. Prichard, R. W.; Vann, R. L.: Congenital afibrinogenaemia: report
on a child without fibrinogen and review of the literature. Am. J.
Dis. Child. 88: 703-710, 1954.
17. Werder, E. A.: Kongenitale Afibrinogenaemie. Helv. Paediat.
Acta 18: 208-229, 1963.
*FIELD* CS
Abdomen:
Splenic rupture
Heme:
Blood completely incoagulable;
Bleeding mild to severe;
Osseous hemorrhage;
Hepatic hemorrhage
Lab:
Afibrinogenemia
Inheritance:
Autosomal recessive
*FIELD* CN
Anne M. Stumpf - updated: 9/20/2004
Victor A. McKusick - updated: 4/6/2001
Victor A. McKusick - updated: 9/27/2000
Victor A. McKusick - updated: 7/13/2000
Victor A. McKusick - updated: 3/16/1999
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
carol: 12/17/2012
alopez: 9/20/2004
mcapotos: 4/16/2001
mcapotos: 4/9/2001
terry: 4/6/2001
mcapotos: 10/12/2000
mcapotos: 10/10/2000
terry: 9/27/2000
alopez: 7/21/2000
terry: 7/13/2000
carol: 3/16/1999
terry: 3/16/1999
mimadm: 11/12/1995
supermim: 3/16/1992
carol: 1/17/1992
supermim: 3/20/1990
supermim: 2/8/1990
carol: 2/5/1990