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
. 1985 Sep;82(17):5895–5899. doi: 10.1073/pnas.82.17.5895

Complete cDNA sequence of the fourth component of murine complement.

D S Sepich, D J Noonan, R T Ogata
PMCID: PMC390660  PMID: 3862104

Abstract

We have used the method of Okayama and Berg to construct cDNA clones that span the entire length of the fourth component of murine complement (C4) from mouse strain B10.WR. The cDNA sequence spans 5372 nucleotides and encodes a pre-pro-C4 molecule 1738 amino acids in length; it includes 56 and 99 untranslated bases at the 5' and 3' ends, respectively, of the C4 mRNA. The deduced pre-pro-C4 molecule includes a 19 amino acid signal peptide and two highly basic interchain regions that presumably are excised during maturation of the protein. The nucleotide sequence shows 79% identity with the human C4 cDNA sequence over the length of the protein-coding region. A comparison of the B10.WR C4 sequence with those of C4 and sex-limited protein (Slp) from mouse strain FM (i) suggests that the difference in hemolytic activity between the C4 proteins from B10.WR and FM is due to structural changes distant from both the C1 cleavage site and the internal thioester site and (ii) raises the possibility that the C4 gene from B10.WR has undergone genetic exchange with its adjoining Slp genes.

Full text

PDF
5899

Selected References

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

  1. Atkinson J. P., McGinnis K., Brown L., Peterein J., Shreffler D. A murine C4 molecule with reduced hemolytic efficiency. J Exp Med. 1980 Feb 1;151(2):492–497. doi: 10.1084/jem.151.2.492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Battula N., Loeb L. A. On the fidelity of DNA replication. Characterization of polynucleotides with errors in base-pairing synthesized by avian myeloblastosis virus deoxyribonucleic acid polymerase. J Biol Chem. 1975 Jun 25;250(12):4405–4409. [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. Brown L. J., Shreffler D. C. Female expression of the H-2-linked sex-limited protein (Slp) due to non-H-2 genes. Immunogenetics. 1980;10(1):19–29. doi: 10.1007/BF01561549. [DOI] [PubMed] [Google Scholar]
  6. Casadaban M. J., Cohen S. N. Analysis of gene control signals by DNA fusion and cloning in Escherichia coli. J Mol Biol. 1980 Apr;138(2):179–207. doi: 10.1016/0022-2836(80)90283-1. [DOI] [PubMed] [Google Scholar]
  7. Chaplin D. D., Sackstein R., Perlmutter D. H., Weis J. H., Kruse T. A., Coligan J., Colten H. R., Seidman J. G. Expression of hemolytically active murine fourth component of complement in transfected L cells. Cell. 1984 Jun;37(2):569–576. doi: 10.1016/0092-8674(84)90387-8. [DOI] [PubMed] [Google Scholar]
  8. Chaplin D. D., Woods D. E., Whitehead A. S., Goldberger G., Colten H. R., Seidman J. G. Molecular map of the murine S region. Proc Natl Acad Sci U S A. 1983 Nov;80(22):6947–6951. doi: 10.1073/pnas.80.22.6947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dretzen G., Bellard M., Sassone-Corsi P., Chambon P. A reliable method for the recovery of DNA fragments from agarose and acrylamide gels. Anal Biochem. 1981 Apr;112(2):295–298. doi: 10.1016/0003-2697(81)90296-7. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Karp D. R., Atkinson J. P., Shreffler D. C. Genetic variation in glycosylation of the fourth component of murine complement. Association with hemolytic activity. J Biol Chem. 1982 Jul 10;257(13):7330–7335. [PubMed] [Google Scholar]
  12. Karp D. R., Capra J. D., Atkinson J. P., Shreffler D. C. Structural and functional characterization of an incompletely processed form of murine C4 and Slp. J Immunol. 1982 May;128(5):2336–2341. [PubMed] [Google Scholar]
  13. Karp D. R., Parker K. L., Shreffler D. C., Slaughter C., Capra J. D. Amino acid sequence homologies and glycosylation differences between the fourth component of murine complement and sex-limited protein. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6347–6349. doi: 10.1073/pnas.79.20.6347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Karp D. R., Shreffler D. C. S region genetic control of murine C4 biosynthesis: analysis of pro-C4 cleavage. Immunogenetics. 1982;16(2):171–176. doi: 10.1007/BF00364403. [DOI] [PubMed] [Google Scholar]
  15. Karp D. R. Variation in the glycosylation of the murine sex-limited protein: comparison with the fourth component of murine complement. J Immunol. 1983 Sep;131(3):1405–1410. [PubMed] [Google Scholar]
  16. Kozak M. Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs. Nucleic Acids Res. 1984 Jan 25;12(2):857–872. doi: 10.1093/nar/12.2.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kreil G. Transfer of proteins across membranes. Annu Rev Biochem. 1981;50:317–348. doi: 10.1146/annurev.bi.50.070181.001533. [DOI] [PubMed] [Google Scholar]
  18. Lundwall A. B., Wetsel R. A., Kristensen T., Whitehead A. S., Woods D. E., Ogden R. C., Colten H. R., Tack B. F. Isolation and sequence analysis of a cDNA clone encoding the fifth complement component. J Biol Chem. 1985 Feb 25;260(4):2108–2112. [PubMed] [Google Scholar]
  19. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  20. McIntyre K. R., Seidman J. G. Nucleotide sequence of mutant I-A beta bm12 gene is evidence for genetic exchange between mouse immune response genes. Nature. 1984 Apr 5;308(5959):551–553. doi: 10.1038/308551a0. [DOI] [PubMed] [Google Scholar]
  21. Nonaka M., Takahashi M., Natsuume-Sakai S., Nonaka M., Tanaka S., Shimizu A., Honjo T. Isolation of cDNA clones specifying the fourth component of mouse complement and its isotype, sex-limited protein. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6822–6826. doi: 10.1073/pnas.81.21.6822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ogata R. T., Sepich D. S. Genes for murine fourth complement component (C4) and sex-limited protein (Slp) identified by hybridization to C4- and Slp-specific cDNA. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4908–4911. doi: 10.1073/pnas.81.15.4908. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Okayama H., Berg P. A cDNA cloning vector that permits expression of cDNA inserts in mammalian cells. Mol Cell Biol. 1983 Feb;3(2):280–289. doi: 10.1128/mcb.3.2.280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Parker K. L., Roos M. H., Shreffler D. C. Structural characterization of the murine fourth component of complement and sex-limited protein and their precursors: evidence for two loci in the S region of the H-2 complex. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5853–5857. doi: 10.1073/pnas.76.11.5853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Payvar F., Schimke R. T. Methylmercury hydroxide enhancement of translation and transcription of ovalbumin and conalbumin mRNA's. J Biol Chem. 1979 Aug 25;254(16):7636–7642. [PubMed] [Google Scholar]
  27. 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]
  28. 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]
  29. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  30. Roos M. H., Atkinson J. P., Shreffler D. C. Molecular characterization of the Ss and Slp (C4) proteins of the mouse H-2 complex: subunit composition, chain size polymorphism, and an intracellular (PRO-Ss) precursor. J Immunol. 1978 Sep;121(3):1106–1115. [PubMed] [Google Scholar]
  31. Rosa P. A., Sepich D. S., Shreffler D. C., Ogata R. T. Mice constitutive for sex-limited protein (SLP) expression contain multiple Slp gene sequences. J Immunol. 1985 Jul;135(1):627–631. [PubMed] [Google Scholar]
  32. Schulze D. H., Pease L. R., Geier S. S., Reyes A. A., Sarmiento L. A., Wallace R. B., Nathenson S. G. Comparison of the cloned H-2Kbm1 variant gene with the H-2Kb gene shows a cluster of seven nucleotide differences. Proc Natl Acad Sci U S A. 1983 Apr;80(7):2007–2011. doi: 10.1073/pnas.80.7.2007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Shreffler D C, Owen R D. A Serologically Detected Variant in Mouse Serum: Inheritance and Association with the Histocompatibility-2 Locus. Genetics. 1963 Jan;48(1):9–25. doi: 10.1093/genetics/48.1.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Shreffler D. C., Atkinson J. P., Chan A. C., Karp D. R., Killion C. C., Ogata R. T., Rosa P. A. The C4 and Slp genes of the complement region of the murine H-2 major histocompatibility complex. Philos Trans R Soc Lond B Biol Sci. 1984 Sep 6;306(1129):395–403. doi: 10.1098/rstb.1984.0100. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. 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]
  37. 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]
  38. 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]
  39. 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]
  40. Wahli W., Ryffel G. U., Wyler T., Jaggi F. B., Weber R., Dawid I. B. Cloning and characterization of synthetic sequences from the Xenopus iaevis vitellogenin structural gene. Dev Biol. 1978 Dec;67(2):371–383. doi: 10.1016/0012-1606(78)90207-5. [DOI] [PubMed] [Google Scholar]
  41. Weiss E. H., Mellor A., Golden L., Fahrner K., Simpson E., Hurst J., Flavell R. A. The structure of a mutant H-2 gene suggests that the generation of polymorphism in H-2 genes may occur by gene conversion-like events. Nature. 1983 Feb 24;301(5902):671–674. doi: 10.1038/301671a0. [DOI] [PubMed] [Google Scholar]
  42. Whitehead A. S., Goldberger G., Woods D. E., Markham A. F., Colten H. R. Use of a cDNA clone for the fourth component of human complement (C4) for analysis of a genetic deficiency of C4 in guinea pig. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5387–5391. doi: 10.1073/pnas.80.17.5387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. de Bruijn M. H., Fey G. H. Human complement component C3: cDNA coding sequence and derived primary structure. Proc Natl Acad Sci U S A. 1985 Feb;82(3):708–712. doi: 10.1073/pnas.82.3.708. [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