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Gene Review

FGG  -  fibrinogen gamma chain

Homo sapiens

Synonyms: Fibrinogen gamma chain, PRO2061
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Disease relevance of FGG

  • Expression and analysis of a split premature termination codon in FGG responsible for congenital afibrinogenemia: escape from RNA surveillance mechanisms in transfected cells [1].
  • No fibrin degradation product was observed in plasma samples, however, high amounts of fibrinogen gamma-chain dimer crosslinked by transglutaminase were detected in plasma from tumor patients, but not in plasma from controls and patients suffering acute infections and/or inflammations [2].
  • In conclusion, fibrinogen FGG and FGA gene haplotypes are not associated with coronary events, coronary atherosclerosis or extracoronary atherosclerosis [3].
  • The in vitro kinetic parameters of PRT and FGGP (where FGGP is the single polypeptide form of the HIV-1 protease with 2 glycine residues connecting the two subunits) for three peptide substrates are similar [4].
  • Clumping factor A (ClfA) is a surface protein of Staphylococcus aureus bacteria known for its ability to bind the C-terminus of plasma fibrinogen gamma chain, which participates in mediating fibrinogen-platelet interaction and fibrin cross-linking, resulting in thrombus formation [5].

High impact information on FGG

  • Thymus-dependent protein antigens such as fowl gamma globulin (FGG) and dinitrophenylated-human gamma globulin (DNP-HGG), readily induced tolerance of the B cell in the absence of T cells even when these antigens were not deaggregated [6].
  • In the presence of XIIIa, the Dusart fibrinogen gamma chain cross-linking rate was about twice that of normal, but was normalized in proteolytic fibrinogen derivatives lacking the Aalpha chain abnormality, as was reduced plasminogen binding [7].
  • Arginine-glycine-aspartic acid- and fibrinogen gamma-chain carboxyterminal peptides inhibit platelet adherence to arterial subendothelium at high wall shear rates. An effect dissociable from interference with adhesive protein binding [8].
  • The fibrinogen-mediated leukocyte adhesion and transendothelial migration could be inhibited by a peptide from the fibrinogen gamma-chain sequence N117NQKIVNL-KEKVAQLEA133, which blocks the binding of fibrinogen to ICAM-1 [9].
  • We have constructed synthetic peptides modeled on the sequences of (i) Arg-Gly-Asp, present in fibrinogen, fibronectin, and von Willebrand factor, and of (ii) the fibrinogen gamma chain (gamma 400-411) His-His-Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val [10].

Biological context of FGG

  • The disease is caused by mutations in 1 of the 3 fibrinogen genes FGG, FGA, and FGB, clustered on the long arm of human chromosome 4 [1].
  • Expression studies in COS-7 cells demonstrated that the Arg134Xaa codon, which is encoded by adjacent exons (TG-intron 4-A) affected neither mRNA splicing nor stability, but led to the production of an unstable, severely truncated fibrinogen gamma chain that is not incorporated into a functional fibrinogen hexamer [1].
  • The FGG-FGA*4 haplotype, composed of the minor FGG 9340C and FGA 2224A alleles, had similar effects, supporting its reported protective role in relation to MI [11].
  • Sixty controls were selected according to FGG 9340T > C [rs1049636] genotype for studies on fibrin clot structure using the liquid permeation method [11].
  • Supplementing data suggest that FGG is distal to MNSs on the long arm of chromosome 4 [12].

Anatomical context of FGG


Associations of FGG with chemical compounds


Other interactions of FGG


Analytical, diagnostic and therapeutic context of FGG


  1. Expression and analysis of a split premature termination codon in FGG responsible for congenital afibrinogenemia: escape from RNA surveillance mechanisms in transfected cells. Neerman-Arbez, M., Germanos-Haddad, M., Tzanidakis, K., Vu, D., Deutsch, S., David, A., Morris, M.A., de Moerloose, P. Blood (2004) [Pubmed]
  2. Elevated plasma levels of crosslinked fibrinogen gamma-chain dimer indicate cancer-related fibrin deposition and fibrinolysis. Gerner, C., Steinkellner, W., Holzmann, K., Gsur, A., Grimm, R., Ensinger, C., Obrist, P., Sauermann, G. Thromb. Haemost. (2001) [Pubmed]
  3. Fibrinogen gene haplotypes in relation to risk of coronary events and coronary and extracoronary atherosclerosis: The Rotterdam Study. Kardys, I., Uitterlinden, A.G., Hofman, A., Witteman, J.C., de Maat, M.P. Thromb. Haemost. (2007) [Pubmed]
  4. Characterization of an active single polypeptide form of the human immunodeficiency virus type 1 protease. DiIanni, C.L., Davis, L.J., Holloway, M.K., Herber, W.K., Darke, P.L., Kohl, N.E., Dixon, R.A. J. Biol. Chem. (1990) [Pubmed]
  5. ClfA(221-550), a fibrinogen-binding segment of Staphylococcus aureus clumping factor A, disrupts fibrinogen function. Liu, C.Z., Shih, M.H., Tsai, P.J. Thromb. Haemost. (2005) [Pubmed]
  6. Tolerance induction in B lymphocytes but thymus-dependent antigens. T cells may abrogate B-cell tolerance induction by prevent an antibody response. Schrader, J.W. J. Exp. Med. (1975) [Pubmed]
  7. The relationship between the fibrinogen D domain self-association/cross-linking site (gammaXL) and the fibrinogen Dusart abnormality (Aalpha R554C-albumin): clues to thrombophilia in the "Dusart syndrome". Mosesson, M.W., Siebenlist, K.R., Hainfeld, J., Wall, J.S., Soria, J., Soria, C., Caen, J.P. J. Clin. Invest. (1996) [Pubmed]
  8. Arginine-glycine-aspartic acid- and fibrinogen gamma-chain carboxyterminal peptides inhibit platelet adherence to arterial subendothelium at high wall shear rates. An effect dissociable from interference with adhesive protein binding. Lawrence, J.B., Kramer, W.S., McKeown, L.P., Williams, S.B., Gralnick, H.R. J. Clin. Invest. (1990) [Pubmed]
  9. Regulation of leukocyte-endothelium interaction and leukocyte transendothelial migration by intercellular adhesion molecule 1-fibrinogen recognition. Languino, L.R., Duperray, A., Joganic, K.J., Fornaro, M., Thornton, G.B., Altieri, D.C. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  10. Inhibition of platelet function with synthetic peptides designed to be high-affinity antagonists of fibrinogen binding to platelets. Ruggeri, Z.M., Houghten, R.A., Russell, S.R., Zimmerman, T.S. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  11. Epistatic and pleiotropic effects of polymorphisms in the fibrinogen and coagulation factor XIII genes on plasma fibrinogen concentration, fibrin gel structure and risk of myocardial infarction. Mannila, M.N., Eriksson, P., Ericsson, C.G., Hamsten, A., Silveira, A. Thromb. Haemost. (2006) [Pubmed]
  12. Fibrinogen gamma chain locus is on chromosome 4 in man. Olaisen, B., Teisberg, P., Gedde-Dahl, T. Hum. Genet. (1982) [Pubmed]
  13. Megakaryocyte and hepatocyte origins of human fibrinogen biosynthesis exhibit hepatocyte-specific expression of gamma chain-variant polypeptides. Haidaris, P.J., Francis, C.W., Sporn, L.A., Arvan, D.S., Collichio, F.A., Marder, V.J. Blood (1989) [Pubmed]
  14. Extrahepatic expression of fibrinogen by granulosa cells: potential role in ovulation. Parrott, J.A., Whaley, P.D., Skinner, M.K. Endocrinology (1993) [Pubmed]
  15. Adhesive interactions of platelets and their blockade. Hawiger, J. Ann. N. Y. Acad. Sci. (1991) [Pubmed]
  16. Fibrinogen gamma375 arg-->trp mutation (fibrinogen aguadilla) causes hereditary hypofibrinogenemia, hepatic endoplasmic reticulum storage disease and cirrhosis. Rubbia-Brandt, L., Neerman-Arbez, M., Rougemont, A.L., Malé, P.J., Spahr, L. Am. J. Surg. Pathol. (2006) [Pubmed]
  17. Human platelet fibrinogen gamma chain structure. Mosesson, M.W., Homandberg, G.A., Amrani, D.L. Blood (1984) [Pubmed]
  18. Proteomic study of plasma from moderate hypercholesterolemic patients. Alonso-Orgaz, S., Moreno, L., Macaya, C., Rico, L., Mateos-Cáceres, P.J., Sacristán, D., Pérez-Vizcaíno, F., Segura, A., Tamargo, J., López-Farré, A. J. Proteome Res. (2006) [Pubmed]
  19. A peptide corresponding to GPIIb alpha 300-312, a presumptive fibrinogen gamma-chain binding site on the platelet integrin GPIIb/IIIa, inhibits the adhesion of platelets to at least four adhesive ligands. Taylor, D.B., Gartner, T.K. J. Biol. Chem. (1992) [Pubmed]
  20. The fibrinogen gamma chain dodecapeptide inhibits agonist-induced aggregation of rabbit platelets and fibrinogen binding to rabbit glycoprotein IIb-IIIa. Rand, M.L., Packham, M.A., Taylor, D.M., Yeo, E.L., Gemmell, C.H., Patil, S., Lam, S.C. Thromb. Haemost. (1999) [Pubmed]
  21. RGD induces conformational transition in purified platelet integrin GPIIb/IIIa-SDS system yielding multiple binding states for fibrinogen gamma-chain C-terminal peptide. Mayo, K.H., Fan, F., Beavers, M.P., Eckardt, A., Keane, P., Hoekstra, W.J., Andrade-Gordon, P. FEBS Lett. (1996) [Pubmed]
  22. Function of fibrinogen gamma-chain dodecapeptide-conjugated latex beads under flow. Takeoka, S., Okamura, Y., Teramura, Y., Watanabe, N., Suzuki, H., Tsuchida, E., Handa, M., Ikeda, Y. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  23. Platelet-fibrinogen interactions. Bennett, J.S. Ann. N. Y. Acad. Sci. (2001) [Pubmed]
  24. Structural recognition of a novel fibrinogen gamma chain sequence (117-133) by intercellular adhesion molecule-1 mediates leukocyte-endothelium interaction. Altieri, D.C., Duperray, A., Plescia, J., Thornton, G.B., Languino, L.R. J. Biol. Chem. (1995) [Pubmed]
  25. Paris I dysfibrinogenemia: a point mutation in intron 8 results in insertion of a 15 amino acid sequence in the fibrinogen gamma-chain. Rosenberg, J.B., Newman, P.J., Mosesson, M.W., Guillin, M.C., Amrani, D.L. Thromb. Haemost. (1993) [Pubmed]
  26. The structural motif glycine 190-valine 202 of the fibrinogen gamma chain interacts with CD11b/CD18 integrin (alpha M beta 2, Mac-1) and promotes leukocyte adhesion. Altieri, D.C., Plescia, J., Plow, E.F. J. Biol. Chem. (1993) [Pubmed]
  27. Design and evaluation of nonpeptide fibrinogen gamma-chain based GPIIb/IIIa antagonists. Hoekstra, W.J., Beavers, M.P., Andrade-Gordon, P., Evangelisto, M.F., Keane, P.M., Press, J.B., Tomko, K.A., Fan, F., Kloczewiak, M., Mayo, K.H. J. Med. Chem. (1995) [Pubmed]
  28. Polymerization defect of fibrinogen Baltimore III due to a gamma Asn308----Ile mutation. Bantia, S., Bell, W.R., Dang, C.V. Blood (1990) [Pubmed]
  29. Fibrinogen coating density affects the conformation of immobilized fibrinogen: implications for platelet adhesion and spreading. Moskowitz, K.A., Kudryk, B., Coller, B.S. Thromb. Haemost. (1998) [Pubmed]
  30. Dissecting clot retraction and platelet aggregation. Clot retraction does not require an intact fibrinogen gamma chain C terminus. Rooney, M.M., Parise, L.V., Lord, S.T. J. Biol. Chem. (1996) [Pubmed]
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