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. 1988 Jan 15;249(2):593–602. doi: 10.1042/bj2490593

The complete amino acid sequence of human complement factor H.

J Ripoche 1, A J Day 1, T J Harris 1, R B Sim 1
PMCID: PMC1148743  PMID: 2963625

Abstract

The complete amino acid sequence of the human complement system regulatory protein, factor H, has been derived from sequencing three overlapping cDNA clones. The sequence consists of 1213 amino acids arranged in 20 homologous units, each about 60 amino acids long, and an 18-residue leader sequence. The 60-amino-acid-long repetitive units are homologous with those found in a large number of other complement and non-complement proteins. Two basic C-terminal residues, deduced from the cDNA sequence, are absent from factor H isolated from outdated plasma. A tyrosine/histidine polymorphism was observed within the seventh homologous repeat unit of factor H. This is likely to represent a difference between the two major allelic variants of factor H. The nature of the cDNA clones indicates that there is likely to be an alternative splicing mechanism, resulting in the formation of at least two species of factor H mRNA.

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Selected References

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

  1. Alsenz J., Schulz T. F., Lambris J. D., Sim R. B., Dierich M. P. Structural and functional analysis of the complement component factor H with the use of different enzymes and monoclonal antibodies to factor H. Biochem J. 1985 Dec 15;232(3):841–850. doi: 10.1042/bj2320841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Bentley D. R. Primary structure of human complement component C2. Homology to two unrelated protein families. Biochem J. 1986 Oct 15;239(2):339–345. doi: 10.1042/bj2390339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. Christie D. L., Gagnon J. Isolation, characterization and N-terminal sequences of the CNBr-cleavage peptides from human complement Factor B. Localization of a free thiol group and a sequence defining the site cleaved by factor D. Biochem J. 1982 Mar 1;201(3):555–567. doi: 10.1042/bj2010555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Day A. J., Ripoche J., Lyons A., McIntosh B., Harris T. J., Sim R. B. Sequence analysis of a cDNA clone encoding the C-terminal end of human complement factor H. Biosci Rep. 1987 Mar;7(3):201–207. doi: 10.1007/BF01124790. [DOI] [PubMed] [Google Scholar]
  9. Erdei A., Sim R. B. Complement factor H-binding protein of Raji cells and tonsil B lymphocytes. Biochem J. 1987 Aug 15;246(1):149–156. doi: 10.1042/bj2460149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gardner R. C., Howarth A. J., Messing J., Shepherd R. J. Cloning and sequencing of restriction fragments generated by Eco RI*. DNA. 1982;1(2):109–115. doi: 10.1089/dna.1.1982.1.109. [DOI] [PubMed] [Google Scholar]
  11. Grosveld F. G., Dahl H. H., de Boer E., Flavell R. A. Isolation of beta-globin-related genes from a human cosmid library. Gene. 1981 Apr;13(3):227–237. doi: 10.1016/0378-1119(81)90028-7. [DOI] [PubMed] [Google Scholar]
  12. Hagenbüchle O., Bovey R., Young R. A. Tissue-specific expression of mouse-alpha-amylase genes: nucleotide sequence of isoenzyme mRNAs from pancreas and salivary gland. Cell. 1980 Aug;21(1):179–187. doi: 10.1016/0092-8674(80)90125-7. [DOI] [PubMed] [Google Scholar]
  13. Klickstein L. B., Wong W. W., Smith J. A., Weis J. H., Wilson J. G., Fearon D. T. Human C3b/C4b receptor (CR1). Demonstration of long homologous repeating domains that are composed of the short consensus repeats characteristics of C3/C4 binding proteins. J Exp Med. 1987 Apr 1;165(4):1095–1112. doi: 10.1084/jem.165.4.1095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kristensen T., Tack B. F. Murine protein H is comprised of 20 repeating units, 61 amino acids in length. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3963–3967. doi: 10.1073/pnas.83.11.3963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kristensen T., Wetsel R. A., Tack B. F. Structural analysis of human complement protein H: homology with C4b binding protein, beta 2-glycoprotein I, and the Ba fragment of B2. J Immunol. 1986 May 1;136(9):3407–3411. [PubMed] [Google Scholar]
  16. Lambris J. D., Ross G. D. Characterization of the lymphocyte membrane receptor for factor H (beta 1H-globulin) with an antibody to anti-factor H idiotype. J Exp Med. 1982 May 1;155(5):1400–1411. doi: 10.1084/jem.155.5.1400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Low M. G. Biochemistry of the glycosyl-phosphatidylinositol membrane protein anchors. Biochem J. 1987 May 15;244(1):1–13. doi: 10.1042/bj2440001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Malhotra V., Sim R. B. Expression of complement factor H on the cell surface of the human monocytic cell line U937. Eur J Immunol. 1985 Sep;15(9):935–941. doi: 10.1002/eji.1830150913. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Ripoche J., Al Salihi A., Rousseaux J., Fontaine M. Isolation of two molecular populations of human complement factor H by hydrophobic affinity chromatography. Biochem J. 1984 Jul 1;221(1):89–96. doi: 10.1042/bj2210089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ripoche J., Day A. J., Willis A. C., Belt K. T., Campbell R. D., Sim R. B. Partial characterization of human complement factor H by protein and cDNA sequencing: homology with other complement and non-complement proteins. Biosci Rep. 1986 Jan;6(1):65–72. doi: 10.1007/BF01145180. [DOI] [PubMed] [Google Scholar]
  22. Rodriguez de Cordoba S., Rubinstein P. New alleles of C4-binding protein and factor H and further linkage data in the regulator of complement activation (RCA) gene cluster in man. Immunogenetics. 1987;25(4):267–268. doi: 10.1007/BF00404698. [DOI] [PubMed] [Google Scholar]
  23. Rodriguez de Cordoba S., Rubinstein P. Quantitative variations of the C3b/C4b receptor (CR1) in human erythrocytes are controlled by genes within the regulator of complement activation (RCA) gene cluster. J Exp Med. 1986 Oct 1;164(4):1274–1283. doi: 10.1084/jem.164.4.1274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Schulz T. F., Scheiner O., Alsenz J., Lambris J. D., Dierich M. P. Use of monoclonal antibodies against factor H to investigate the role of a membrane-associated protein antigenically related to H in C3b-receptor function. J Immunol. 1984 Jan;132(1):392–398. [PubMed] [Google Scholar]
  26. Schulz T. F., Schwäble W., Stanley K. K., Weiss E., Dierich M. P. Human complement factor H: isolation of cDNA clones and partial cDNA sequence of the 38-kDa tryptic fragment containing the binding site for C3b. Eur J Immunol. 1986 Nov;16(11):1351–1355. doi: 10.1002/eji.1830161107. [DOI] [PubMed] [Google Scholar]
  27. Sim E., Palmer M. S., Puklavec M., Sim R. B. Monoclonal antibodies against the complement control protein factor H (beta 1 H). Biosci Rep. 1983 Dec;3(12):1119–1131. doi: 10.1007/BF01120205. [DOI] [PubMed] [Google Scholar]
  28. Sim R. B., DiScipio R. G. Purification and structural studies on the complement-system control protein beta 1H (Factor H). Biochem J. 1982 Aug 1;205(2):285–293. doi: 10.1042/bj2050285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sim R. B., Malhotra V., Day A. J., Erdei A. Structure and specificity of complement receptors. Immunol Lett. 1987 Feb;14(3):183–190. doi: 10.1016/0165-2478(87)90099-x. [DOI] [PubMed] [Google Scholar]
  30. Sim R. B., Malhotra V., Ripoche J., Day A. J., Micklem K. J., Sim E. Complement receptors and related complement control proteins. Biochem Soc Symp. 1986;51:83–96. [PubMed] [Google Scholar]
  31. 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]
  32. Weiler J. M., Daha M. R., Austen K. F., Fearon D. T. Control of the amplification convertase of complement by the plasma protein beta1H. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3268–3272. doi: 10.1073/pnas.73.9.3268. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. Yoon S. H., Fearon D. T. Characterization of a soluble form of the C3b/C4b receptor (CR1) in human plasma. J Immunol. 1985 May;134(5):3332–3338. [PubMed] [Google Scholar]
  35. von Heijne G. Analysis of the distribution of charged residues in the N-terminal region of signal sequences: implications for protein export in prokaryotic and eukaryotic cells. EMBO J. 1984 Oct;3(10):2315–2318. doi: 10.1002/j.1460-2075.1984.tb02132.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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