Skip to main content
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
. 1985 Feb;82(3):708–712. doi: 10.1073/pnas.82.3.708

Human complement component C3: cDNA coding sequence and derived primary structure.

M H de Bruijn, G H Fey
PMCID: PMC397115  PMID: 2579379

Abstract

The complete cDNA coding sequence and derived amino acid sequence of human complement component C3 are presented. The encoded precursor molecule contains a signal peptide of 22 amino acid residues, the beta chain (645 residues), and the alpha chain (992 residues). The two chains are joined by four arginine residues not present in the mature protein. Several functionally important sites have been localized, such as the thiolester site, the cleavage site liberating the anaphylatoxin, and two sites of cleavage by the serine protease factor I, as well as a peptide fragment with leukocyte mobilizing activity. At least two carbohydrate attachment sites, one on each chain, have been identified. Human C3 has 79% identity to mouse C3 at the nucleotide level and 77% identity at the amino acid level. The protease alpha 2-macroglobulin and complement component C4 show considerable homology to C3, suggesting that the three proteins have evolved from a common ancestor.

Full text

PDF
708

Selected References

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

  1. Alexander J. W., Ogle C. K., Stinnett J. D., Macmillan B. G. A sequential, prospective analysis of immunologic abnormalities and infection following severe thermal injury. Ann Surg. 1978 Dec;188(6):809–816. doi: 10.1097/00000658-197812000-00016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alper C. A., Colten H. R., Gear J. S., Rabson A. R., Rosen F. S. Homozygous human C3 deficiency. The role of C3 in antibody production, C-1s-induced vasopermeability, and cobra venom-induced passive hemolysis. J Clin Invest. 1976 Jan;57(1):222–229. doi: 10.1172/JCI108263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Alper C. A., Johnson A. M., Birtch A. G., Moore F. D. Human C'3: evidence for the liver as the primary site of synthesis. Science. 1969 Jan 17;163(3864):286–288. doi: 10.1126/science.163.3864.286. [DOI] [PubMed] [Google Scholar]
  4. Belt K. T., Carroll M. C., Porter R. R. The structural basis of the multiple forms of human complement component C4. Cell. 1984 Apr;36(4):907–914. doi: 10.1016/0092-8674(84)90040-0. [DOI] [PubMed] [Google Scholar]
  5. Bentley D. R., Porter R. R. Isolation of cDNA clones for human complement component C2. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1212–1215. doi: 10.1073/pnas.81.4.1212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Bokisch V. A., Müller-Eberhard H. J., Cochrane C. G. Isolation of a fragment (C3a) of the third component of human complement containing anaphylatoxin and chemotactic activity and description of an anaphylatoxin inactivator of human serum. J Exp Med. 1969 May 1;129(5):1109–1130. doi: 10.1084/jem.129.5.1109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Davis A. E., 3rd, Harrison R. A., Lachmann P. J. Physiologic inactivation of fluid phase C3b: isolation and structural analysis of C3c, C3d,g (alpha 2D), and C3g. J Immunol. 1984 Apr;132(4):1960–1966. [PubMed] [Google Scholar]
  9. Davis A. E., 3rd, Harrison R. A. Structural characterization of factor I mediated cleavage of the third component of complement. Biochemistry. 1982 Nov 9;21(23):5745–5749. doi: 10.1021/bi00266a003. [DOI] [PubMed] [Google Scholar]
  10. Domdey H., Wiebauer K., Kazmaier M., Müller V., Odink K., Fey G. Characterization of the mRNA and cloned cDNA specifying the third component of mouse complement. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7619–7623. doi: 10.1073/pnas.79.24.7619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fey G. H., Lundwall A., Wetsel R. A., Tack B. F., de Bruijn M. H., Domdey H. Nucleotide sequence of complementary DNA and derived amino acid sequence of murine complement protein C3. Philos Trans R Soc Lond B Biol Sci. 1984 Sep 6;306(1129):333–344. doi: 10.1098/rstb.1984.0094. [DOI] [PubMed] [Google Scholar]
  12. Hanahan D., Meselson M. Plasmid screening at high colony density. Gene. 1980 Jun;10(1):63–67. doi: 10.1016/0378-1119(80)90144-4. [DOI] [PubMed] [Google Scholar]
  13. Hugli T. E. Human anaphylatoxin (C3a) from the third component of complement. Primary structure. J Biol Chem. 1975 Nov 10;250(21):8293–8301. [PubMed] [Google Scholar]
  14. Hugli T. E. The structural basis for anaphylatoxin and chemotactic functions of C3a, C4a, and C5a. Crit Rev Immunol. 1981 Feb;1(4):321–366. [PubMed] [Google Scholar]
  15. Law S. K., Levine R. P. Interaction between the third complement protein and cell surface macromolecules. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2701–2705. doi: 10.1073/pnas.74.7.2701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Leytus S. P., Chung D. W., Kisiel W., Kurachi K., Davie E. W. Characterization of a cDNA coding for human factor X. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3699–3702. doi: 10.1073/pnas.81.12.3699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Marshall R. D. Glycoproteins. Annu Rev Biochem. 1972;41:673–702. doi: 10.1146/annurev.bi.41.070172.003325. [DOI] [PubMed] [Google Scholar]
  18. Medof M. E., Iida K., Mold C., Nussenzweig V. Unique role of the complement receptor CR1 in the degradation of C3b associated with immune complexes. J Exp Med. 1982 Dec 1;156(6):1739–1754. doi: 10.1084/jem.156.6.1739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Meuth J. L., Morgan E. L., DiSipio R. G., Hugli T. E. Suppression of T lymphocyte functions by human C3 fragments. I. Inhibition of human T cell proliferative responses by a kallikrein cleavage fragment of human iC3b. J Immunol. 1983 Jun;130(6):2605–2611. [PubMed] [Google Scholar]
  20. Morris K. M., Goldberger G., Colten H. R., Aden D. P., Knowles B. B. Biosynthesis and processing of a human precursor complement protein, pro-C3, in a hepatoma-derived cell line. Science. 1982 Jan 22;215(4531):399–400. doi: 10.1126/science.7199205. [DOI] [PubMed] [Google Scholar]
  21. Müller-Eberhard H. J., Schreiber R. D. Molecular biology and chemistry of the alternative pathway of complement. Adv Immunol. 1980;29:1–53. doi: 10.1016/s0065-2776(08)60042-5. [DOI] [PubMed] [Google Scholar]
  22. Ogata R. T., Shreffler D. C., Sepich D. S., Lilly S. P. cDNA clone spanning the alpha-gamma subunit junction in the precursor of the murine fourth complement component (C4). Proc Natl Acad Sci U S A. 1983 Aug;80(16):5061–5065. doi: 10.1073/pnas.80.16.5061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Reid K. B., Porter R. R. The proteolytic activation systems of complement. Annu Rev Biochem. 1981;50:433–464. doi: 10.1146/annurev.bi.50.070181.002245. [DOI] [PubMed] [Google Scholar]
  24. Roord J. J., Daha M., Kuis W., Verbrugh H. A., Verhoef J., Zegers B. J., Stoop J. W. Inherited deficiency of the third component of complement associated with recurrent pyogenic infections, circulating immune complexes, and vasculitis in a Dutch family. Pediatrics. 1983 Jan;71(1):81–87. [PubMed] [Google Scholar]
  25. Ross G. D., Lambris J. D., Cain J. A., Newman S. L. Generation of three different fragments of bound C3 with purified factor I or serum. I. Requirements for factor H vs CR1 cofactor activity. J Immunol. 1982 Nov;129(5):2051–2060. [PubMed] [Google Scholar]
  26. Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
  27. Schreiber R. D. The chemistry and biology of complement receptors. Springer Semin Immunopathol. 1984;7(2-3):221–249. doi: 10.1007/BF01893021. [DOI] [PubMed] [Google Scholar]
  28. Sottrup-Jensen L., Stepanik T. M., Kristensen T., Lønblad P. B., Jones C. M., Wierzbicki D. M., Magnusson S., Domdey H., Wetsel R. A., Lundwall A. Common evolutionary origin of alpha 2-macroglobulin and complement components C3 and C4. Proc Natl Acad Sci U S A. 1985 Jan;82(1):9–13. doi: 10.1073/pnas.82.1.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. 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]
  31. Staden R. Graphic methods to determine the function of nucleic acid sequences. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 2):521–538. doi: 10.1093/nar/12.1part2.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Tack B. F., Harrison R. A., Janatova J., Thomas M. L., Prahl J. W. Evidence for presence of an internal thiolester bond in third component of human complement. Proc Natl Acad Sci U S A. 1980 Oct;77(10):5764–5768. doi: 10.1073/pnas.77.10.5764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Tack B. F., Morris S. C., Prahl J. W. Third component of human complement: structural analysis of the polypeptide chains of C3 and C3b. Biochemistry. 1979 Apr 17;18(8):1497–1503. doi: 10.1021/bi00575a017. [DOI] [PubMed] [Google Scholar]
  34. Tack B. F. The beta-Cys-gamma-Glu thiolester bond in human C3, C4, and alpha 2-macroglobulin. Springer Semin Immunopathol. 1983;6(4):259–282. doi: 10.1007/BF02116276. [DOI] [PubMed] [Google Scholar]
  35. Taylor J. C., Crawford I. P., Hugli T. E. Limited degradation of the third component (C3) of human complement by human leukocyte elastase (HLE): partial characterization of C3 fragments. Biochemistry. 1977 Jul 26;16(15):3390–3396. doi: 10.1021/bi00634a016. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. Whaley K., Ruddy S. Modulation of the alternative complement pathways by beta 1 H globulin. J Exp Med. 1976 Nov 2;144(5):1147–1163. doi: 10.1084/jem.144.5.1147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Whitehead A. S., Solomon E., Chambers S., Bodmer W. F., Povey S., Fey G. Assignment of the structural gene for the third component of human complement to chromosome 19. Proc Natl Acad Sci U S A. 1982 Aug;79(16):5021–5025. doi: 10.1073/pnas.79.16.5021. [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