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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
. 1987 Jul;84(14):4846–4850. doi: 10.1073/pnas.84.14.4846

Complete cDNA and derived amino acid sequence of human factor V.

R J Jenny, D D Pittman, J J Toole, R W Kriz, R A Aldape, R M Hewick, R J Kaufman, K G Mann
PMCID: PMC305202  PMID: 3110773

Abstract

cDNA clones encoding human factor V have been isolated from an oligo(dT)-primed human fetal liver cDNA library prepared with vector Charon 21A. The cDNA sequence of factor V from three overlapping clones includes a 6672-base-pair (bp) coding region, a 90-bp 5' untranslated region, and a 163-bp 3' untranslated region within which is a poly(A) tail. The deduced amino acid sequence consists of 2224 amino acids inclusive of a 28-amino acid leader peptide. Direct comparison with human factor VIII reveals considerable homology between proteins in amino acid sequence and domain structure: a triplicated A domain and duplicated C domain show approximately equal to 40% identity with the corresponding domains in factor VIII. As in factor VIII, the A domains of factor V share approximately 40% amino acid-sequence homology with the three highly conserved domains in ceruloplasmin. The B domain of factor V contains 35 tandem and approximately 9 additional semiconserved repeats of nine amino acids of the form Asp-Leu-Ser-Gln-Thr-Thr/Asn-Leu-Ser-Pro and 2 additional semiconserved repeats of 17 amino acids. Factor V contains 37 potential N-linked glycosylation sites, 25 of which are in the B domain, and a total of 19 cysteine residues.

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Selected References

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  1. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  2. Church W. R., Jernigan R. L., Toole J., Hewick R. M., Knopf J., Knutson G. J., Nesheim M. E., Mann K. G., Fass D. N. Coagulation factors V and VIII and ceruloplasmin constitute a family of structurally related proteins. Proc Natl Acad Sci U S A. 1984 Nov;81(22):6934–6937. doi: 10.1073/pnas.81.22.6934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dahlbäck B., Stenflo J. Binding of bovine coagulation factor Xa to platelets. Biochemistry. 1978 Nov 14;17(23):4938–4945. doi: 10.1021/bi00616a013. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Derman E., Krauter K., Walling L., Weinberger C., Ray M., Darnell J. E., Jr Transcriptional control in the production of liver-specific mRNAs. Cell. 1981 Mar;23(3):731–739. doi: 10.1016/0092-8674(81)90436-0. [DOI] [PubMed] [Google Scholar]
  6. Esmon C. T. The subunit structure of thrombin-activated factor V. Isolation of activated factor V, separation of subunits, and reconstitution of biological activity. J Biol Chem. 1979 Feb 10;254(3):964–973. [PubMed] [Google Scholar]
  7. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  8. Francis R. T., McDonagh J., Mann K. G. Factor V is a substrate for the transamidase factor XIIIa. J Biol Chem. 1986 Jul 25;261(21):9787–9792. [PubMed] [Google Scholar]
  9. Gitschier J., Wood W. I., Goralka T. M., Wion K. L., Chen E. Y., Eaton D. H., Vehar G. A., Capon D. J., Lawn R. M. Characterization of the human factor VIII gene. Nature. 1984 Nov 22;312(5992):326–330. doi: 10.1038/312326a0. [DOI] [PubMed] [Google Scholar]
  10. Hastie N. D., Held W. A., Toole J. J. Multiple genes coding for the androgen-regulated major urinary proteins of the mouse. Cell. 1979 Jun;17(2):449–457. doi: 10.1016/0092-8674(79)90171-5. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Kane W. H., Davie E. W. Cloning of a cDNA coding for human factor V, a blood coagulation factor homologous to factor VIII and ceruloplasmin. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6800–6804. doi: 10.1073/pnas.83.18.6800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kane W. H., Majerus P. W. Purification and characterization of human coagulation factor V. J Biol Chem. 1981 Jan 25;256(2):1002–1007. [PubMed] [Google Scholar]
  14. Katzmann J. A., Nesheim M. E., Hibbard L. S., Mann K. G. Isolation of functional human coagulation factor V by using a hybridoma antibody. Proc Natl Acad Sci U S A. 1981 Jan;78(1):162–166. doi: 10.1073/pnas.78.1.162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Koschinsky M. L., Funk W. D., van Oost B. A., MacGillivray R. T. Complete cDNA sequence of human preceruloplasmin. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5086–5090. doi: 10.1073/pnas.83.14.5086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Krishnaswamy S., Church W. R., Nesheim M. E., Mann K. G. Activation of human prothrombin by human prothrombinase. Influence of factor Va on the reaction mechanism. J Biol Chem. 1987 Mar 5;262(7):3291–3299. [PubMed] [Google Scholar]
  17. Lindhout T., Govers-Riemslag J. W., van de Waart P., Hemker H. C., Rosing J. Factor Va-factor Xa interaction. Effects of phospholipid vesicles of varying composition. Biochemistry. 1982 Oct 26;21(22):5494–5502. doi: 10.1021/bi00265a018. [DOI] [PubMed] [Google Scholar]
  18. Messing J., Vieira J. A new pair of M13 vectors for selecting either DNA strand of double-digest restriction fragments. Gene. 1982 Oct;19(3):269–276. doi: 10.1016/0378-1119(82)90016-6. [DOI] [PubMed] [Google Scholar]
  19. Miletich J. P., Jackson C. M., Majerus P. W. Properties of the factor Xa binding site on human platelets. J Biol Chem. 1978 Oct 10;253(19):6908–6916. [PubMed] [Google Scholar]
  20. Nesheim M. E., Katzmann J. A., Tracy P. B., Mann K. G. Factor V. Methods Enzymol. 1981;80(Pt 100):249–274. doi: 10.1016/s0076-6879(81)80023-7. [DOI] [PubMed] [Google Scholar]
  21. Nesheim M. E., Kettner C., Shaw E., Mann K. G. Cofactor dependence of factor Xa incorporation into the prothrombinase complex. J Biol Chem. 1981 Jul 10;256(13):6537–6540. [PubMed] [Google Scholar]
  22. Nesheim M. E., Mann K. G. Thrombin-catalyzed activation of single chain bovine factor V. J Biol Chem. 1979 Feb 25;254(4):1326–1334. [PubMed] [Google Scholar]
  23. Nesheim M. E., Taswell J. B., Mann K. G. The contribution of bovine Factor V and Factor Va to the activity of prothrombinase. J Biol Chem. 1979 Nov 10;254(21):10952–10962. [PubMed] [Google Scholar]
  24. Poncz M., Solowiejczyk D., Ballantine M., Schwartz E., Surrey S. "Nonrandom" DNA sequence analysis in bacteriophage M13 by the dideoxy chain-termination method. Proc Natl Acad Sci U S A. 1982 Jul;79(14):4298–4302. doi: 10.1073/pnas.79.14.4298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Poole S., Firtel R. A., Lamar E., Rowekamp W. Sequence and expression of the discoidin I gene family in Dictyostelium discoideum. J Mol Biol. 1981 Dec 5;153(2):273–289. doi: 10.1016/0022-2836(81)90278-3. [DOI] [PubMed] [Google Scholar]
  26. Proudfoot N. J., Brownlee G. G. 3' non-coding region sequences in eukaryotic messenger RNA. Nature. 1976 Sep 16;263(5574):211–214. doi: 10.1038/263211a0. [DOI] [PubMed] [Google Scholar]
  27. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Suzuki K., Dahlbäck B., Stenflo J. Thrombin-catalyzed activation of human coagulation factor V. J Biol Chem. 1982 Jun 10;257(11):6556–6564. [PubMed] [Google Scholar]
  29. Takahashi N., Ortel T. L., Putnam F. W. Single-chain structure of human ceruloplasmin: the complete amino acid sequence of the whole molecule. Proc Natl Acad Sci U S A. 1984 Jan;81(2):390–394. doi: 10.1073/pnas.81.2.390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Toole J. J., Knopf J. L., Wozney J. M., Sultzman L. A., Buecker J. L., Pittman D. D., Kaufman R. J., Brown E., Shoemaker C., Orr E. C. Molecular cloning of a cDNA encoding human antihaemophilic factor. Nature. 1984 Nov 22;312(5992):342–347. doi: 10.1038/312342a0. [DOI] [PubMed] [Google Scholar]
  31. Tracy P. B., Eide L. L., Mann K. G. Human prothrombinase complex assembly and function on isolated peripheral blood cell populations. J Biol Chem. 1985 Feb 25;260(4):2119–2124. [PubMed] [Google Scholar]
  32. Tracy P. B., Nesheim M. E., Mann K. G. Coordinate binding of factor Va and factor Xa to the unstimulated platelet. J Biol Chem. 1981 Jan 25;256(2):743–751. [PubMed] [Google Scholar]
  33. Vehar G. A., Keyt B., Eaton D., Rodriguez H., O'Brien D. P., Rotblat F., Oppermann H., Keck R., Wood W. I., Harkins R. N. Structure of human factor VIII. Nature. 1984 Nov 22;312(5992):337–342. doi: 10.1038/312337a0. [DOI] [PubMed] [Google Scholar]
  34. Watson M. E. Compilation of published signal sequences. Nucleic Acids Res. 1984 Jul 11;12(13):5145–5164. doi: 10.1093/nar/12.13.5145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. von Heijne G. Patterns of amino acids near signal-sequence cleavage sites. Eur J Biochem. 1983 Jun 1;133(1):17–21. doi: 10.1111/j.1432-1033.1983.tb07424.x. [DOI] [PubMed] [Google Scholar]
  36. von Heijne G. Signal sequences are not uniformly hydrophobic. J Mol Biol. 1982 Aug 15;159(3):537–541. doi: 10.1016/0022-2836(82)90300-x. [DOI] [PubMed] [Google Scholar]

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