Fetuin pp 1-10 | Cite as


  • Katarzyna M. Dziegielewska
  • William M. Brown
Part of the Molecular Biology Intelligence Unit book series (MBIU)


Fetuin was discovered in 1944 because of its behavior in the ultracentrifuge.1 In his historical review of fetuin, Kai Pedersen, the original discoverer of the protein, wrote,

“it (fetuin) was quite different from other serum proteins previously studied. It precipitated abundantly in an ammonium sulphate concentration range in which earlier only 7s and 20s components had been observed. Its molecular weight, 50,000, was the lowest observed for a serum protein; it was very asymmetrical; its partial specific volume was quite low—0.70; the nitrogen content was low, 13g N/100g protein; the isoelectric point was low, pH 3.5. The cause of the low nitrogen value was the high carbohydrate content of fetuin, 23%. The name fetuin (Latin; fetus) was proposed because this protein was the predominating component in the fetal serum, rapidly decreased, and finally disappeared in the newborn calf.”


Fetal Serum Fetal Plasma Partial Specific Volume Free Sulfhydryl Group Insulin Receptor Tyrosine Kinase 
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  1. 1.
    Pedersen KO. Fetuin, a new globulin isolated from serum. Nature 1944; 154: 575.CrossRefGoogle Scholar
  2. 2.
    Deutsch HF. Fetuin: the mucoprotein of fetal calf serum. J Biol Chem 1954; 208: 669–678.PubMedGoogle Scholar
  3. 3.
    Bergstand CG, Czar B. Demonstration of new protein fraction in serum from human fetus. Scand. J Clin Lab Med 1956; 8: 174.CrossRefGoogle Scholar
  4. 4.
    Christie DL, Dziegielewska KM, Hill RM et al. Fetuin: the bovine homologue of human a2-HS glycoprotein. FEBS Letts 1987; 214: 45–49.CrossRefGoogle Scholar
  5. 5.
    Dziegielewska KM, Mellgârd K, Reynolds ML et al. A fetuin-related glycoprotein (a2-HS) in human embryonic and fetal development. Cell Tiss Res 1987; 248: 33–41.CrossRefGoogle Scholar
  6. 6.
    Dziegielewska KM, Brown WM, Casey SJ et al. The complete cDNA and amino acid sequence of bovine fetuin. Its homology with a2-HS glycoprotein and relation to other members of the cystatin superfamily. J Biol Chem 1990; 265: 4354–7.PubMedGoogle Scholar
  7. 7.
    Fisher HW, O’Brien D, Puck TT. The hydrolytic products of fetuin. Arch Biochem Biophys 1962; 99: 241–248.PubMedCrossRefGoogle Scholar
  8. 8.
    Puck TT, Waldren CA, Jones C. Mammalian cell growth proteins. I. Growth stimulation of fetuin. Proc Natl Acad Sci USA 1968; 59: 192–199.PubMedCrossRefGoogle Scholar
  9. 9.
    Spiro RG. Studies on fetuin, a glycoprotein of fetal serum. I. isolation, chemical composition, and physicochemical properties. J Biol Chem 1960; 235: 2860–2869.Google Scholar
  10. 10.
    Spiro MJ, Spiro RG. Composition of the peptide portion of fetuin. J Biol Chem 1962; 237: 1507–1510.PubMedGoogle Scholar
  11. 11.
    Spiro RG. Studies on fetuin, a glycoprotein of fetal serum. II. Nature of the carbohydrate units. J Biol Chem 1962; 237: 382–388.Google Scholar
  12. 12.
    Spiro RG. Studies on the monosaccharide sequence of the serum glycoprotein fetuin. J Biol Chem 1962; 237: 646–652.PubMedGoogle Scholar
  13. 13.
    Spiro RG. Demonstration of a single peptide chain in the glycoprotein fetuin: terminal amino acid analyses and studies of the oxidized and reduced alkylated preparations. J Biol Chem 1963; 238: 644–649.PubMedGoogle Scholar
  14. 14.
    Spiro RG, Bhoyroo VD. Structure of the 0-glycosidically linked carbohydrate units of fetuin. J Biol Chem 1974; 249: 5704–17.PubMedGoogle Scholar
  15. 15.
    Oshiro Y, Eylar EH. Physical and chemical studies on glycoproteins. III. The microheterogeneity of fetuin, a fetal calf serum glycoprotein. Arch Biochem Biophys 1968; 127: 476–489.PubMedCrossRefGoogle Scholar
  16. 16.
    Oshiro Y, Eylar EH. Physical and chemical studies on glycoproteins. 4. The influence of sialic acid on the conformation of fetuin. Arch Biochem Biophys 1969; 130: 227–234.PubMedCrossRefGoogle Scholar
  17. 17.
    Page M. Demonstration of the microheterogeneity of fetuin by electrofocusing. Biochim Biophys Acta 1971; 236: 571–577.PubMedCrossRefGoogle Scholar
  18. 18.
    Marti J, Bonfils C, Moretti J. Microheterogeneity of lamb fetuin. [French]. Biochimie 1974; 56: 873–880.PubMedCrossRefGoogle Scholar
  19. 19.
    Begbie R. Studies on fetuin from foetal bovine serum. The composition and amino acid sequences of glycopeptides from fetuin. Biochim Biophys Acta 1974; 371: 549–576.PubMedCrossRefGoogle Scholar
  20. 20.
    Begbie R. Some studies on the structure of bovine fetuin. Protides Biol Fluids 1976; 24: 245–248.Google Scholar
  21. 21.
    Gorin MB, Cooper DL, Eifermann F et al. The evolution of alpha-fetoprotein and albumin. I. A comparison of the primary amino acid sequences of mammalian a-fetoprotein and albumin. J Biol Chem 1981; 256: 1954–1959.PubMedGoogle Scholar
  22. 22.
    Kioussis D, Eiferman F, van de Rijn P et al. The evolution of the a-fetoprotein and albumin. II. The structures of the a-fetoprotein and albumin genes in the mouse. J Biol Chem 1981; 256: 1960–1967.PubMedGoogle Scholar
  23. 23.
    Alexander F, Young PR, Tilghman SM. Evolution of the albumin: a-fetoprotein gene from the amplification of a 27 nucleotide sequence. J Mol Biol 1984; 173: 159–176.PubMedCrossRefGoogle Scholar
  24. 24.
    Dugaiczyk A, Ruffner DE, Minghetti PP et al. Structure and evolution of the serum albumin gene family. Protides Biol Fluids 1985; 35: 27–30.Google Scholar
  25. 25.
    Yang F, Brune JL, Naylor SL et al. Human group-specific component (Gc) is a member of the albumin family. Proc Natl Acad Sci USA 1985; 82: 7994–7998.PubMedCrossRefGoogle Scholar
  26. 26.
    Yang F, Luna VJ, McAnelly RD et al. Evolutionary and structural relationships among group-specific component, albumin and a-fetoprotein. Nucleic Acids Res 1985; 13: 8007–8017.PubMedCrossRefGoogle Scholar
  27. 27.
    Brown WM. The plasma protein fetuin: common structural features of the mammalian fetuin family. PhD thesis, University of Southampton, UK; 1991.Google Scholar
  28. 28.
    Falquerho L, Patey G, Paquereau L et al. Primary structure of the rat gene encoding an inhibitor of the insulin receptor tyrosine kinase. Gene 1991; 98: 209–216.PubMedCrossRefGoogle Scholar
  29. 29.
    Eiberg H, Mohr J, Nielsen LS. a2-HS: new methods of phenotyping and analysis of linkage relations: assignment to chromosome 3. Cytogenet Cell Genet 1984; 37: 461.Google Scholar
  30. 30.
    Cox DW, Francke U. Direct assignment of orosomucoid to human chromosome 9 and a2-HS glycoprotein to chromosome 3 using human fetal liver x rat hepatoma hybrids. Hum Genet 1985; 70: 109–115.PubMedCrossRefGoogle Scholar
  31. 31.
    Arnaud P, Mietz JA, Grossman Z et al. Isolation and characteristics of a cDNA clone for human a2-HS-glycoprotein. Protides Biol Fluids 1987; 35: 135–138.Google Scholar
  32. 32.
    Magnuson VL, McCombs JL, Lee CC et al. Human a2-HS-glycoprotein localized to 3g27, 29 by in situ hybridization. Cytogenet Cell Genet 1988; 47: 72–74.CrossRefGoogle Scholar
  33. 33.
    Murray JC, Watanabe K, Tamaoki T et al. RFLP’s for human a-fetoprotein (AFP) at 4g11–4g13. Nucleic Acids Res 1985; 13: 6794.PubMedCrossRefGoogle Scholar
  34. 34.
    Harper ME, Dugaiczyk A. Linkage of the evolutionarily-related serum albumin and a-fetoprotein genes within q11–22 of human chromosome 4. Am J Hum Genet 1983; 35: 565–572.PubMedGoogle Scholar
  35. 35.
    Marti J, Aliau S, Bonfils C et al. Preparation, physical constants and chemical composition of lamb fetuin. [French]. Biochim Biophys Acta 1973; 303: 348–359.PubMedCrossRefGoogle Scholar
  36. 36.
    Bergmann FH, Levine L, Spiro RG. Fetuin: immunochemistry and quantitative estimation in serum. Biochim Biophys Acta 1962; 58: 41–51.PubMedCrossRefGoogle Scholar
  37. 37.
    Barboriak JJ, Meschia G, Barron DH et al. Blood plasma proteins in fetal goats and sheep. Proc Soc Exptl Biol 1958; 99: 635–637.Google Scholar
  38. 38.
    Jalanko H, Ruoslahti E. Lack of human material inhibitory in fetuin radioimmunoassay. Contribution of carbohydrate moiety to fetuin antigenicity. Protides Biol Fluids 1976; 24: 303–306.Google Scholar
  39. 39.
    Coste J, Bali JP, Aliau S et al. Immunological studies on ovine fetuin: radioimmunoassay and comparison with related antigens. Int J Biochem 1980; 11: 183–187.PubMedCrossRefGoogle Scholar
  40. 40.
    Dziegielewska KM, Kocsis KC, Saunders NR. Identification of fetuin and other proteins in cerebrospinal fluid and plasma of fetal pigs during development. Comp Biochem Physiol 1980; B66: 535–541.Google Scholar
  41. 41.
    Dziegielewska KM. Proteins in fetal CSF and plasma. PhD thesis University of London, UK; 1982.Google Scholar
  42. 42.
    Waymouth C. Nutritional requirements of cells in culture with special reference to neural cells. In “Tissue and Organ Culture in Neurobiology.” Eds. S Federoff and L Hertz. New York: Academic Press; 1977: 631–648.Google Scholar
  43. 43.
    Dziegielewska KM, Bock E, Cornelis ME et al. Identification of fetuin in human and rat fetuses and in other species. Comp Biochem Physiol A 1983; 76: 241–245.PubMedCrossRefGoogle Scholar
  44. 44.
    Mollgârd K, Reynolds ML, Jacobsen M et al. Differential immunocytochemical staining for fetuin and transferrin in the developing cortical plate. J Neurocytol 1984; 13: 497–502.PubMedCrossRefGoogle Scholar
  45. 45.
    Kellermann J, Haupt H, Auerswald EA et al. The arrangement of disulfide loops in human a2-HS glycoprotein. Similarity to the disulfide bridge structures of cystatins and kininogens. J Biol Chem 1989; 264: 14121–14128.PubMedGoogle Scholar
  46. 46.
    Yoshioka Y, Gejyo F, Marti T et al. The complete amino acid sequence of the A-chain of human a2-HS-glycoprotein. J Biol Chem 1986; 261: 1665–1676.PubMedGoogle Scholar
  47. 47.
    Lee CC, Bowman BH, Yang FM. Human a2-HS-glycoprotein: the A and B chains with a connecting sequence are encoded by a single mRNA transcript. Proc Natl Acad Sci USA 1987; 84: 4403–4407.PubMedCrossRefGoogle Scholar
  48. 48.
    Elzanowski A, Barker WC; Hunt LT et al. Cystatin domains in a2-HSglycoprotein and fetuin. FEBS Letts 1988; 227: 167–70.CrossRefGoogle Scholar
  49. 49.
    Barrett AJ. Cystatin, the egg white inhibitor of cysteine proteinases. Meths Enzymol 1981; 80: 771–778.CrossRefGoogle Scholar
  50. 50.
    Turk V, Brzin J, Longer M et al. Protein inhibitors of cysteine proteinases. III. Amino-acid sequence of cystatin from chicken egg white. Hoppe Seylers Z Physiol Chem 1983; 364: 1487–96.PubMedCrossRefGoogle Scholar
  51. 51.
    Schwabe C, Anastasi A, Crow H et al. Cystatin. Amino acid sequence and possible secondary structure. Biochem J 1984; 217: 813–817.PubMedGoogle Scholar
  52. 52.
    Colella R, Sakaguchi Y, Nagase H et al. Chicken egg white cystatin. Molecular cloning, nucleotide sequence, and tissue distribution. J Biol Chem 1989; 264: 17164–9.PubMedGoogle Scholar
  53. 53.
    Colella R, Bird JW. Isolation and characterization of the chicken cystatinencoding gene: mapping transcription start point and polyadenylation sites. Gene 1993; 130: 175–81.PubMedCrossRefGoogle Scholar
  54. 54.
    Grubb A, Lofberg H, Barrett AJ. The disulphide bridges of human cystatin C (gamma trace) and chicken cystatin. FEBS Letts. 1984; 170: 370–374.CrossRefGoogle Scholar
  55. 55.
    Turk V, Brzin J, Kotnik M et al. Human cysteine proteinases and their protein inhibitors stefins, cystatins and kininogens. Biomed Biochim Acta 1986; 45: 1375–84.PubMedGoogle Scholar
  56. 56.
    Barrett AJ. The cystatins: a new class of peptidase inhibitors. Trends Biochem Sci 1987; 12: 193–196.CrossRefGoogle Scholar
  57. 57.
    Rawlings ND, Barrett AJ. Evolution of proteins of the cystatin superfamily. J Mol Evol 1990; 30: 60–71.PubMedCrossRefGoogle Scholar
  58. 58.
    Turk V, Bode W. The cystatins: protein inhibitors of cysteine proteinases. FEBS Letts 1991; 285: 213–9.CrossRefGoogle Scholar
  59. 59.
    Ohkubo I, Kurachi K, Takasawa T et al. Isolation of a human cDNA for a2-thiol proteinase inhibitor and its identity with low molecular weight kininogen. Biochemistry 1984; 23: 5691–7.PubMedCrossRefGoogle Scholar
  60. 60.
    Hamberg U, Elg P, Nissinen E et al. Purification and heterogeneity of human kininogen. Use of DEAE-chromatography, molecular sieving and antibody specific immunosorbents. Int J Pept Protein Res 1975; 7: 261–80.PubMedCrossRefGoogle Scholar
  61. 61.
    Araki T, Yoshioka Y, Schmid K. The position of the disulfide bonds in human plasma a2-HS-glycoprotein and the repeating double disulfide bonds in the domain structure. Biochim Biophys Acta 1989; 994: 195–199.PubMedCrossRefGoogle Scholar
  62. 62.
    Chin CC, Wold F. The use of tributylphosphine and 4-(aminosulfonyl)7-fluoro-2,1,3-benzoxadiazole in the study of protein sulfhydryls and disulfides. Anal Biochem 1993; 214: 128–34.PubMedCrossRefGoogle Scholar
  63. 63.
    Yamakawa Y, Omori-Satoh T. Primary structure of the antihemorrhagic factor in serum of the Japanese Habu: a snake venom metalloproteinase inhibitor with a double-headed cystatin domain. J Biochem 1992; 112: 583–589.PubMedGoogle Scholar
  64. 64.
    Smith KM, Lai PCW, Robertson HA et al. Distribution of alphal-fetoprotein in fetal plasma, allantoic fluid, amniotic fluid and maternal plasma of cows. J Reprod Fertil 1979; 57: 235–238.PubMedCrossRefGoogle Scholar
  65. 65.
    Dziegielewska KM, Evans CA, Malinowska DH et al. Blood-cerebrospinal fluid transfer of plasma proteins during fetal development in the sheep. J Physiol 1980; 300: 457–465.PubMedGoogle Scholar
  66. 66.
    Dziegielewska KM, Matthews N, Saunders NR et al. a2-HS-glycoprotein is expressed at high concentration in human fetal plasma and cerebrospinal fluid. Fetal Diagn Ther 1993; 8: 22–27.PubMedCrossRefGoogle Scholar
  67. 67.
    Auberger P, Falquerho L, Contreres JO et al. Characterization of a natural inhibitor of the insulin receptor tyrosine kinase. cDNA cloning, purification, and anti-mitogenic activity. Cell 1989; 58: 631–640.PubMedCrossRefGoogle Scholar
  68. 68.
    Haasemann M, Nawratil P, Müller-Esterl W. Rat tyrosine kinase inhibitor shows sequence similarity to human a2-HS glycoprotein and bovine fetuin. Biochem J 1991; 274: 899–902.PubMedGoogle Scholar
  69. 69.
    Brown WM, Christie DL, Dziegielewska KM et al. The rat protein encoded by clone pp63 is a fetuin/a2-glycoprotein-like molecule, but is it the tyrosine kinase inhibitor PP63. Cell 1992; 68: 7–8.PubMedCrossRefGoogle Scholar
  70. 70.
    Sbraccia P, Goodman PA, Maddux BA et al. Production of inhibitor of insulin-receptor tyrosine kinase in fibroblasts from patients with insulin resistance and NIDDM. Diabetes 1991; 40: 295–299.PubMedCrossRefGoogle Scholar
  71. 71.
    Le Cam A, Auberger P, Falquerho L et al. pp63 is very likely the rat fetuin. Cell 1992; 67: 8.Google Scholar
  72. 72.
    Maddux BA, Sbraccia P, Reaven GM et al. Inhibitors of insulin receptor tyrosine kinase in fibroblasts from diverse patients with impaired insulin action: evidence for a novel mechanism of postreceptor insulin resistance. J Clin Endocrinol Metab 1993; 77: 73–79.PubMedCrossRefGoogle Scholar
  73. 73.
    Srinivas PR, Wagner AS, Reddy LV et al. Serum a2-HS-glycoprotein is an inhibitor of the human insulin receptor at the tyrosine kinase level. Mol Endocrinol 1993; 7: 1445–1455.PubMedCrossRefGoogle Scholar
  74. 74.
    White H, Totty N, Panayotou G. Haemonectin, a granulocytic-cell-binding protein, is related to the plasma glycoprotein fetuin. Eur J Biochem 1993; 213: 523–528.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • Katarzyna M. Dziegielewska
    • 1
  • William M. Brown
    • 2
  1. 1.University of TasmaniaHobartAustralia
  2. 2.Law Firm: Sills, Cummis, Zuckerman, Radin, Tischman, Epstein and GrossNewarkUSA

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