Human Fibrinogen Occurs as Over 1 Million Non-Identical Molecules

  • Agnes H. Henschen-Edman


Traditionally, proteins have been regarded as well-defined, uniform molecules, where one molecule is virtually identical to the next. This notion has been supported by the fact that the highly efficient protein primary structure analysis by prediction from the DNA sequence will result in a well-defined, unique amino acid sequence, containing no direct indication of any kind of modification or processing. However, information is accumulating about protein heterogeneity, co- or post-translational modification and processing as well as about the functional implications of the structural variation (Krishna and Wold, 1993; Graves et al., 1994). Human fibrinogen may serve as an extreme example of a protein existing in a multitude of structural forms, many of which have been demonstrated to differ in functional properties (Henschen and McDonagh, 1986; Henschen, 1993). In the following, the various, so far recognized structural variations and their possible function effects, together with some relevant identification procedures will be described.


Peptide Chain Factor Xiii Methionine Residue Pyroglutamic Acid Human Fibrinogen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Baumann, R.E., and Henschen, A.H., 1993, Human fibrinogen polymorphic site analysis by restriction endonuclease digestion and allele-specific polymerase chain reaction amplification: Identification of polymorphisms at positions Aa312 and Bß448, Blood, 82: 2117–2124.PubMedGoogle Scholar
  2. Baumann, R.E., and Henschen, A.H., 1994, Linkage disequilibrium relationships among four polymorphisms within the human fibrinogen gene cluster, Human Genetics, 94: 165–170.Google Scholar
  3. Blombäck, B., Blombäck, M., Edman, P., and Hessel, B., 1966, Human fibrinopeptides. Isolation, characterization, and structure, Biochim. Biophys. Acta, 115: 371–396.PubMedCrossRefGoogle Scholar
  4. Blombäck, B., Gröndahl, N. J., Hessel, B. Iwanaga, S., and Wallén, P., 1973, Primary structure of human fibrinogen and fibrin. II. Structural studies on NH2-terminal part of y chain, J. Biol. Chem., 248: 5806–5820.PubMedGoogle Scholar
  5. Chen, N. and Henschen, A., 1994, Identification of methionine sulfoxide in native and oxidized fibrinogen, Protein Sci. 3, Suppl. 1: 147.Google Scholar
  6. Chung, D.W., and Davie, E.W., 1984, y and y’ chains of human fibrinogen are produced by alternative mRNA processing, Biochemistry 23: 4232–4236.Google Scholar
  7. Chung, D.W., Harris, J.E., and Davie, E.W., 1990, Nucleotide sequences of the three genes coding for human fibrinogen. In: Fibrinogen, thrombosis, coagulation and fibrinolysis. ( Liu, C.Y., and Chien, S. eds.) Plenum, New York, pp. 39–48.CrossRefGoogle Scholar
  8. Ebert, R.F., 1991, Index of variant human fibrinogens, CRC Press, Boca Raton.Google Scholar
  9. Farrell, D. H., Mulvihill, E.R., Huang, S., Chung, D.W., and Davie, E.W., 1991, Recombinant human fibrinogen and sulfation of the y’ chain, Biochemistry, 30: 9414–9420.PubMedCrossRefGoogle Scholar
  10. Fornace, A.J., Cummings, D.E., Comeau, C.M., Kant, J.A., and Crabtree, G.R., 1984, Structure of the human y-fibrinogen gene. Alternate mRNA splicing near the 3’ end of the gene produces yA and 7B forms of y-fibrinogen, J. Biol. Chem. 259: 12826–12830.PubMedGoogle Scholar
  11. Fu, Y., and Grieninger, G., 1994, Fib 420: a normal human variant of fibrinogen with two extended a chains, Proc. Natl. Acad. Sci. USA 91: 2625–2628.PubMedCrossRefGoogle Scholar
  12. Graves, D. J., Martin, B.L., and Wang, J. H., 1994, Co-and post-translational modification of proteins. Chemical Principles and biological effects. Oxford University, New York. pp. 1–348.Google Scholar
  13. Henschen, A., and Edman, P., 1972, Large scale preparation of S-carboxymethylated chains of human fibrin and fibrinogen and the occurrence of 7-chain variants, Biochim. Biophys. Acta 263: 351–367.PubMedCrossRefGoogle Scholar
  14. Henschen, A., and McDonagh, J., 1986, Fibrinogen, fibrin and factor XIII. In: Blood coagulation. ( Zwaal, R.F.A., and Hemker H.C. eds.) Elsevier, Amsterdam. pp. 171–241.CrossRefGoogle Scholar
  15. Henschen, A.H., 1993, Human fibrinogen - structural variants and functional sites, Thromb. Haem. 70:42–47. Henschen, A.H., 1993, Identification of tyrosine sulfate and tyrosine phosphate residues during sequence analysis, Protein Sci., 2, Suppl. 1: 152.Google Scholar
  16. Henschen, A.H., 1994, Human fibrinogen occurs as over 1 million nonidentical molecules, J. Protein Chem., 13: 504–505.Google Scholar
  17. Henschen, A.H., Theodor, I., and Pirkle, H., 1991, Hydroxyproline, a posttranslational modification of proline, is a constitutent of human fibrinogen, Thromb. Haem. 65: 821.Google Scholar
  18. Humphries, S.E., Cook, M., Dubowitz, M., Stirling, Y., and Meade, T.W., 1987, Role of genetic variation at the fibrinogen locus in determination of plasma fibrinogen concentrations, Lancet. 1452–1455.Google Scholar
  19. Kannel, W.B., D’Agostino, R.B., and Belanger, A.J., 1987, Fibrinogen, cigarette smoking, and risk of cardiovascular disease: Insights from the Framingham Study, Am. Heart J. 113: 1006–1010.PubMedCrossRefGoogle Scholar
  20. Krishna, R.G., and Wold, F., 1993, Post-translational modification of proteins, Adv. Enzymol. Related Areas of Mol. Biol. 67: 265–298.Google Scholar
  21. Müller, E., and Henschen, A., 1988, Isolation and characterization of human plasma fibrinogen molecular-sizevariants by high-performance liquid chromatography and amino acid sequence analysis. In: Fibrinogen. ( Mosesson, M.W., Amrani, D.L., Siebenlist, K.R., and Diorio, J.P. eds.) Elsevier, Amsterdam, pp. 279–282.Google Scholar
  22. Nakashima, A., Sasaki, S., Miyazaki, K., Miyata, T., and Iwanaga, S., 1992, Human fibrinogen heterogeneity: The COOH-terminal residues of defective Act chains of fibrinogen II, Blood Coag. Fibrinol. 3: 361–370.Google Scholar
  23. Seydewitz, H.H., and Witt, I., 1985, Increased phosphorylation of human fibrinopeptide A under acute phase conditions, Thromb. Res. 40: 29–39.PubMedCrossRefGoogle Scholar
  24. Töpfer-Petersen, E., Lottspeich, F., and Henschen, A., 1976, Carbohydrate linkage site in the 0-chain of human fibrin, Hoppe-Seyler’s Z. Physiol Chem. 357: 1509–1513.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Agnes H. Henschen-Edman
    • 1
  1. 1.Department of Molecular Biology and BiochemistryUniversity of California, IrvineIrvineUSA

Personalised recommendations