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. 1990 Jun;87(12):4529–4532. doi: 10.1073/pnas.87.12.4529

Human genes for the alpha and beta chains of complement C4b-binding protein are closely linked in a head-to-tail arrangement.

F Pardo-Manuel 1, J Rey-Campos 1, A Hillarp 1, B Dahlbäck 1, S Rodriguez de Cordoba 1
PMCID: PMC54149  PMID: 2352933

Abstract

C4b-binding protein (C4BP) is an important component in the regulation of the complement system and also binds the anticoagulant vitamin K-dependent protein S. These activities are performed by distinct, although structurally related, polypeptides of 70 kDa (alpha chain) and 45 kDa (beta chain), respectively. In this report we have investigated the genetic relationships between these polypeptides. Using pulsed field gel electrophoresis analysis we demonstrate that the genes coding for the alpha (C4BP alpha) and beta (C4BP beta) chains are closely linked within the regulator of complement activation gene cluster. In addition, we have determined that the 3' end of the C4BP beta gene lies 3.5-5 kilobases from the 5' end of the C4BP alpha gene. These findings support the concept that the C4BP alpha and C4BP beta genes are the result of a gene duplication event.

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Selected References

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

  1. Bora N. S., Lublin D. M., Kumar B. V., Hockett R. D., Holers V. M., Atkinson J. P. Structural gene for human membrane cofactor protein (MCP) of complement maps to within 100 kb of the 3' end of the C3b/C4b receptor gene. J Exp Med. 1989 Feb 1;169(2):597–602. doi: 10.1084/jem.169.2.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Caras I. W., Davitz M. A., Rhee L., Weddell G., Martin D. W., Jr, Nussenzweig V. Cloning of decay-accelerating factor suggests novel use of splicing to generate two proteins. Nature. 1987 Feb 5;325(6104):545–549. doi: 10.1038/325545a0. [DOI] [PubMed] [Google Scholar]
  3. Carroll M. C., Alicot E. M., Katzman P. J., Klickstein L. B., Smith J. A., Fearon D. T. Organization of the genes encoding complement receptors type 1 and 2, decay-accelerating factor, and C4-binding protein in the RCA locus on human chromosome 1. J Exp Med. 1988 Apr 1;167(4):1271–1280. doi: 10.1084/jem.167.4.1271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chu G., Vollrath D., Davis R. W. Separation of large DNA molecules by contour-clamped homogeneous electric fields. Science. 1986 Dec 19;234(4783):1582–1585. doi: 10.1126/science.3538420. [DOI] [PubMed] [Google Scholar]
  5. Chung L. P., Bentley D. R., Reid K. B. Molecular cloning and characterization of the cDNA coding for C4b-binding protein, a regulatory protein of the classical pathway of the human complement system. Biochem J. 1985 Aug 15;230(1):133–141. doi: 10.1042/bj2300133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dahlbäck B., Smith C. A., Müller-Eberhard H. J. Visualization of human C4b-binding protein and its complexes with vitamin K-dependent protein S and complement protein C4b. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3461–3465. doi: 10.1073/pnas.80.11.3461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  8. Fujita T., Gigli I., Nussenzweig V. Human C4-binding protein. II. Role in proteolysis of C4b by C3b-inactivator. J Exp Med. 1978 Oct 1;148(4):1044–1051. doi: 10.1084/jem.148.4.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fujita T., Nussenzweig V. The role of C4-binding protein and beta 1H in proteolysis of C4b and C3b. J Exp Med. 1979 Aug 1;150(2):267–276. doi: 10.1084/jem.150.2.267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gigli I., Fujita T., Nussenzweig V. Modulation of the classical pathway C3 convertase by plasma proteins C4 binding protein and C3b inactivator. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6596–6600. doi: 10.1073/pnas.76.12.6596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hillarp A., Dahlbäck B. Cloning of cDNA coding for the beta chain of human complement component C4b-binding protein: sequence homology with the alpha chain. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1183–1187. doi: 10.1073/pnas.87.3.1183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hillarp A., Dahlbäck B. Novel subunit in C4b-binding protein required for protein S binding. J Biol Chem. 1988 Sep 5;263(25):12759–12764. [PubMed] [Google Scholar]
  13. Hillarp A., Hessing M., Dahlbäck B. Protein S binding in relation to the subunit composition of human C4b-binding protein. FEBS Lett. 1989 Dec 18;259(1):53–56. doi: 10.1016/0014-5793(89)81492-9. [DOI] [PubMed] [Google Scholar]
  14. Hourcade D., Miesner D. R., Atkinson J. P., Holers V. M. Identification of an alternative polyadenylation site in the human C3b/C4b receptor (complement receptor type 1) transcriptional unit and prediction of a secreted form of complement receptor type 1. J Exp Med. 1988 Oct 1;168(4):1255–1270. doi: 10.1084/jem.168.4.1255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kenwrick S., Patterson M., Speer A., Fischbeck K., Davies K. Molecular analysis of the Duchenne muscular dystrophy region using pulsed field gel electrophoresis. Cell. 1987 Jan 30;48(2):351–357. doi: 10.1016/0092-8674(87)90438-7. [DOI] [PubMed] [Google Scholar]
  16. Kristensen T., Ogata R. T., Chung L. P., Reid K. B., Tack B. F. cDNA structure of murine C4b-binding protein, a regulatory component of the serum complement system. Biochemistry. 1987 Jul 28;26(15):4668–4674. doi: 10.1021/bi00389a012. [DOI] [PubMed] [Google Scholar]
  17. Kurtz C. B., Paul M. S., Aegerter M., Weis J. J., Weis J. H. Murine complement receptor gene family. II. Identification and characterization of the murine homolog (Cr2) to human CR2 and its molecular linkage to Crry. J Immunol. 1989 Sep 15;143(6):2058–2067. [PubMed] [Google Scholar]
  18. Lublin D. M., Lemons R. S., Le Beau M. M., Holers V. M., Tykocinski M. L., Medof M. E., Atkinson J. P. The gene encoding decay-accelerating factor (DAF) is located in the complement-regulatory locus on the long arm of chromosome 1. J Exp Med. 1987 Jun 1;165(6):1731–1736. doi: 10.1084/jem.165.6.1731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nagasawa S., Stroud R. M. Purification and characterization of a macromolecular weight cofactor for C3b-inactivator, C4bC3bINA-cofactor, of human plasma. Mol Immunol. 1980 Nov;17(11):1365–1372. doi: 10.1016/0161-5890(80)90005-x. [DOI] [PubMed] [Google Scholar]
  20. Rey-Campos J., Rubinstein P., Rodriguez de Cordoba S. A physical map of the human regulator of complement activation gene cluster linking the complement genes CR1, CR2, DAF, and C4BP. J Exp Med. 1988 Feb 1;167(2):664–669. doi: 10.1084/jem.167.2.664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rey-Campos J., Rubinstein P., Rodriguez de Cordoba S. Decay-accelerating factor. Genetic polymorphism and linkage to the RCA (regulator of complement activation) gene cluster in humans. J Exp Med. 1987 Jul 1;166(1):246–252. doi: 10.1084/jem.166.1.246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rodriguez de Cordoba S., Lublin D. M., Rubinstein P., Atkinson J. P. Human genes for three complement components that regulate the activation of C3 are tightly linked. J Exp Med. 1985 May 1;161(5):1189–1195. doi: 10.1084/jem.161.5.1189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Scharfstein J., Ferreira A., Gigli I., Nussenzweig V. Human C4-binding protein. I. Isolation and characterization. J Exp Med. 1978 Jul 1;148(1):207–222. doi: 10.1084/jem.148.1.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Weis J. H., Morton C. C., Bruns G. A., Weis J. J., Klickstein L. B., Wong W. W., Fearon D. T. A complement receptor locus: genes encoding C3b/C4b receptor and C3d/Epstein-Barr virus receptor map to 1q32. J Immunol. 1987 Jan 1;138(1):312–315. [PubMed] [Google Scholar]
  25. Weis J. J., Toothaker L. E., Smith J. A., Weis J. H., Fearon D. T. Structure of the human B lymphocyte receptor for C3d and the Epstein-Barr virus and relatedness to other members of the family of C3/C4 binding proteins. J Exp Med. 1988 Mar 1;167(3):1047–1066. doi: 10.1084/jem.167.3.1047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wong W. W., Cahill J. M., Rosen M. D., Kennedy C. A., Bonaccio E. T., Morris M. J., Wilson J. G., Klickstein L. B., Fearon D. T. Structure of the human CR1 gene. Molecular basis of the structural and quantitative polymorphisms and identification of a new CR1-like allele. J Exp Med. 1989 Mar 1;169(3):847–863. doi: 10.1084/jem.169.3.847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wu L. C., Morley B. J., Campbell R. D. Cell-specific expression of the human complement protein factor B gene: evidence for the role of two distinct 5'-flanking elements. Cell. 1987 Jan 30;48(2):331–342. doi: 10.1016/0092-8674(87)90436-3. [DOI] [PubMed] [Google Scholar]

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