Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1986 Jun;83(12):4199–4203. doi: 10.1073/pnas.83.12.4199

Primary structure of bovine vitamin K-dependent protein S.

B Dahlbäck, A Lundwall, J Stenflo
PMCID: PMC323699  PMID: 2940598

Abstract

Protein S is a vitamin K-dependent plasma protein that functions as a cofactor to activated protein C in the inactivation of coagulation factors Va and VIIIa. The nucleotide sequence of a full-length cDNA clone, obtained from a bovine liver library, was determined and the amino acid sequence was deduced. In addition, 95% of the structure was determined by protein sequencing. Protein S consists of 634 amino acids in a single polypeptide chain and has one asparagine-linked carbohydrate side chain. The cDNA sequence showed that the protein has a leader sequence, 41 amino acid residues long. The amino-terminal part of the molecule containing gamma-carboxyglutamic acid is followed by a region, residues 42-75, with two peptide bonds that are very sensitive to cleavage by thrombin. Residues 76-244 have four cysteinerich repeat sequences, each about 40 residues long, that are homologous to the precursor of mouse epidermal growth factor. In contrast to the other vitamin K-dependent plasma proteins, the carboxyl-terminal part of protein S is not homologous to the serine proteases.

Full text

PDF
4200

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Biggin M. D., Gibson T. J., Hong G. F. Buffer gradient gels and 35S label as an aid to rapid DNA sequence determination. Proc Natl Acad Sci U S A. 1983 Jul;80(13):3963–3965. doi: 10.1073/pnas.80.13.3963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Comp P. C., Nixon R. R., Cooper M. R., Esmon C. T. Familial protein S deficiency is associated with recurrent thrombosis. J Clin Invest. 1984 Dec;74(6):2082–2088. doi: 10.1172/JCI111632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dahlbäck B., Hildebrand B. Degradation of human complement component C4b in the presence of the C4b-binding protein-protein S complex. Biochem J. 1983 Mar 1;209(3):857–863. doi: 10.1042/bj2090857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dahlbäck B., Lundwall A., Stenflo J. Localization of thrombin cleavage sites in the amino-terminal region of bovine protein S. J Biol Chem. 1986 Apr 15;261(11):5111–5115. [PubMed] [Google Scholar]
  5. Dahlbäck B. Purification of human C4b-binding protein and formation of its complex with vitamin K-dependent protein S. Biochem J. 1983 Mar 1;209(3):847–856. doi: 10.1042/bj2090847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dahlbäck B. Purification of human vitamin K-dependent protein S and its limited proteolysis by thrombin. Biochem J. 1983 Mar 1;209(3):837–846. doi: 10.1042/bj2090837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dahlbäck B., Stenflo J. High molecular weight complex in human plasma between vitamin K-dependent protein S and complement component C4b-binding protein. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2512–2516. doi: 10.1073/pnas.78.4.2512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dayhoff M. O., Barker W. C., Hunt L. T. Establishing homologies in protein sequences. Methods Enzymol. 1983;91:524–545. doi: 10.1016/s0076-6879(83)91049-2. [DOI] [PubMed] [Google Scholar]
  9. Di Scipio R. G., Hermodson M. A., Yates S. G., Davie E. W. A comparison of human prothrombin, factor IX (Christmas factor), factor X (Stuart factor), and protein S. Biochemistry. 1977 Feb 22;16(4):698–706. doi: 10.1021/bi00623a022. [DOI] [PubMed] [Google Scholar]
  10. DiScipio R. G., Davie E. W. Characterization of protein S, a gamma-carboxyglutamic acid containing protein from bovine and human plasma. Biochemistry. 1979 Mar 6;18(5):899–904. doi: 10.1021/bi00572a026. [DOI] [PubMed] [Google Scholar]
  11. Doolittle R. F., Feng D. F., Johnson M. S. Computer-based characterization of epidermal growth factor precursor. Nature. 1984 Feb 9;307(5951):558–560. doi: 10.1038/307558a0. [DOI] [PubMed] [Google Scholar]
  12. Drakenberg T., Fernlund P., Roepstorff P., Stenflo J. beta-Hydroxyaspartic acid in vitamin K-dependent protein C. Proc Natl Acad Sci U S A. 1983 Apr;80(7):1802–1806. doi: 10.1073/pnas.80.7.1802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fernlund P., Stenflo J. Beta-hydroxyaspartic acid in vitamin K-dependent proteins. J Biol Chem. 1983 Oct 25;258(20):12509–12512. [PubMed] [Google Scholar]
  14. Foster D. C., Yoshitake S., Davie E. W. The nucleotide sequence of the gene for human protein C. Proc Natl Acad Sci U S A. 1985 Jul;82(14):4673–4677. doi: 10.1073/pnas.82.14.4673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fung M. R., Hay C. W., MacGillivray R. T. Characterization of an almost full-length cDNA coding for human blood coagulation factor X. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3591–3595. doi: 10.1073/pnas.82.11.3591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Højrup P., Jensen M. S., Petersen T. E. Amino acid sequence of bovine protein Z: a vitamin K-dependent serine protease homolog. FEBS Lett. 1985 May 20;184(2):333–338. doi: 10.1016/0014-5793(85)80633-5. [DOI] [PubMed] [Google Scholar]
  17. Jackson C. M., Nemerson Y. Blood coagulation. Annu Rev Biochem. 1980;49:765–811. doi: 10.1146/annurev.bi.49.070180.004001. [DOI] [PubMed] [Google Scholar]
  18. Long G. L., Belagaje R. M., MacGillivray R. T. Cloning and sequencing of liver cDNA coding for bovine protein C. Proc Natl Acad Sci U S A. 1984 Sep;81(18):5653–5656. doi: 10.1073/pnas.81.18.5653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schwarz H. P., Fischer M., Hopmeier P., Batard M. A., Griffin J. H. Plasma protein S deficiency in familial thrombotic disease. Blood. 1984 Dec;64(6):1297–1300. [PubMed] [Google Scholar]
  20. Staden R. An interactive graphics program for comparing and aligning nucleic acid and amino acid sequences. Nucleic Acids Res. 1982 May 11;10(9):2951–2961. doi: 10.1093/nar/10.9.2951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Staden R. Automation of the computer handling of gel reading data produced by the shotgun method of DNA sequencing. Nucleic Acids Res. 1982 Aug 11;10(15):4731–4751. doi: 10.1093/nar/10.15.4731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Stenflo J., Jönsson M. Protein S, a new vitamin K-dependent protein from bovine plasma. FEBS Lett. 1979 May 15;101(2):377–381. doi: 10.1016/0014-5793(79)81048-0. [DOI] [PubMed] [Google Scholar]
  23. Sugo T., Dahlbäck B., Holmgren A., Stenflo J. Calcium binding of bovine protein S. Effect of thrombin cleavage and removal of the gamma-carboxyglutamic acid-containing region. J Biol Chem. 1986 Apr 15;261(11):5116–5120. [PubMed] [Google Scholar]
  24. Walker F. J. Regulation of activated protein C by protein S. The role of phospholipid in factor Va inactivation. J Biol Chem. 1981 Nov 10;256(21):11128–11131. [PubMed] [Google Scholar]
  25. Walker F. J. Regulation of vitamin K-dependent protein S. Inactivation by thrombin. J Biol Chem. 1984 Aug 25;259(16):10335–10339. [PubMed] [Google Scholar]
  26. Woods D. E., Markham A. F., Ricker A. T., Goldberger G., Colten H. R. Isolation of cDNA clones for the human complement protein factor B, a class III major histocompatibility complex gene product. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5661–5665. doi: 10.1073/pnas.79.18.5661. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES