Skip to main content
SpringerLink
Log in

Two factor H-related proteins from the mouse: expression analysis and functional characterization

  • Original Paper
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

Complement factor H-related (FHR) proteins display structural and functional similarities to each other and to the complement regulator factor H (FH). FHRs have been identified in various species, including human, rat, and the fish barred sand bass. As mice provide a useful model system to study the physiological role of FHRs in vivo, we aimed at characterizing murine FHR proteins. Two putative FHRs of approximately 100 and 38 kDa were detected in mouse plasma using FH-specific antiserum. In a liver cDNA library, three murine FHR-encoding transcripts were identified. Two clones code for related FHR proteins termed FHR-C and FHR-C_v1, which in secreted form are composed of 14 and 13 short consensus repeat (SCR) domains, homologous to SCRs 6–17 and 19–20 of FH. The third transcript, FHR-B, is derived from a separate gene and codes for a secreted protein composed of five SCR domains. FHR-B displays homology to SCRs 5–7 and 19–20 of FH. Expression of FHR-B in various tissues was analyzed by real-time polymerase chain reaction and was identified at high levels in liver, kidney and heart. In liver, FHR-B transcript level was even higher than that of FH. In addition, FHR-B was expressed as a recombinant 37-kDa protein, and this recombinant FHR-B interacted with the ligands heparin and human C3b. Using mouse plasma, the native presumptive FHR proteins were also analyzed in binding assays. In summary, we identify two FHR proteins in mice and for the first time characterize a murine FHR as a heparin- and C3b-binding protein.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Cheng ZZ, Hellwage J, Seeberger H, Zipfel PF, Meri S, Jokiranta TS (2006) Comparison of surface recognition and C3b binding properties of mouse and human complement factor H. Mol Immunol 43:972–979

    Article  PubMed  CAS  Google Scholar 

  • Dahmen A, Kaidoh T, Zipfel PF, Gigli I (1994) Cloning and characterization of a cDNA representing a putative complement-regulatory plasma protein from barred sand bass (Parablax neblifer). Biochem J 301:391–397

    PubMed  CAS  Google Scholar 

  • Demberg T, Pollok-Kopp B, Gerke D, Götze O, Schlaf G (2002) Rat complement factor H: molecular cloning, sequencing and quantification with a newly established ELISA. Scand J Immunol 56:149–160

    Article  PubMed  CAS  Google Scholar 

  • Díaz-Guillén MA, Rodríguez de Córdoba S, Heine-Suner D (1999) A radiation hybrid map of complement factor H and factor H-related genes. Immunogenetics 49:549–552

    Article  PubMed  Google Scholar 

  • Estaller C, Schwaeble W, Dierich MP, Weiss EH (1991) Human complement factor H: two factor H serum proteins are derived from alternatively spliced transcripts. Eur J Immunol 21:799–802

    PubMed  CAS  Google Scholar 

  • Friese MA, Hellwage J, Jokiranta TS, Meri S, Peter HH, Eibel H, Zipfel PF (1999) FHL-1/reconectin and factor H: two human complement regulators which are encoded by the same gene are differently expressed and regulated. Mol Immunol 36:809–818

    Article  PubMed  CAS  Google Scholar 

  • Hellwage J, Skerka C, Zipfel PF (1997) Biochemical and functional characterization of the factor-H-related protein 4 (FHR-4). Immunopharmacology 38:149–157

    Article  PubMed  CAS  Google Scholar 

  • Hellwage J, Jokiranta TS, Koistinen V, Vaarala O, Meri S, Zipfel PF (1999) Functional properties of complement factor H-related proteins FHR-3 and FHR-4: binding to the C3d region of C3b and differential regulation by heparin. FEBS Lett 462:345–352

    Article  PubMed  CAS  Google Scholar 

  • Hogasen K, Jansen JH, Mollnes TE, Hovdenes J, Harboe M (1995) Hereditary porcine membranoproliferative glomerulonephritis type II is caused by factor H deficiency. J Clin Invest 95:1054–1061

    Article  PubMed  CAS  Google Scholar 

  • Józsi M, Richter H, Löschmann I, Skerka C, Buck F, Beisiegel U, Erdei A, Zipfel PF (2005) FHR-4A: a new factor H-related protein is encoded by the human FHR-4 gene. Eur J Hum Genet 13:321–329

    Article  PubMed  CAS  Google Scholar 

  • Kemper C, Zipfel PF, Gigli I (1998) The complement cofactor protein (SBP1) from the barred sand bass (Paralabrax nebulifer) mediates overlapping regulatory activities of both human C4b binding protein and factor H. J Biol Chem 273:19398–19404

    Article  PubMed  CAS  Google Scholar 

  • McRae JL, Duthy TG, Griggs KM, Ormsby RJ, Cowan PJ, Cromer BA, McKinstry WJ, Parker MW, Murphy BF, Gordon DL (2005) Human factor H-related protein 5 has cofactor activity, inhibits C3 convertase activity, binds heparin and C-reactive protein, and associates with lipoprotein. J Immunol 174:6250–6256

    PubMed  CAS  Google Scholar 

  • Murphy B, Georgiou T, Machet D, Hill P, McRae J (2002) Factor H-related protein-5: a novel component of human glomerular immune deposits. Am J Kidney Dis 39:24–27

    Article  PubMed  CAS  Google Scholar 

  • Park CT, Wright SD (1996) Plasma lipopolysaccharide-binding protein is found associated with a particle containing apolipoprotein A-I, phospholipid, and factor H-related proteins. J Biol Chem 271:18054–18060

    Article  PubMed  CAS  Google Scholar 

  • Pickering MC, Cook HT, Warren J, Bygrave AE, Moss J, Walport MJ, Botto M (2002) Uncontrolled C3 activation causes membranoproliferative glomerulonephritis in mice deficient in complement factor H. Nat Genet 31:424–428

    PubMed  CAS  Google Scholar 

  • Ren G, Doshi M, Hack BK, Alexander JJ, Quigg RJ (2002) Isolation and characterization of a novel rat factor H-related protein that is up-regulated in glomeruli under complement attack. J Biol Chem 277:48351–48358

    Article  PubMed  CAS  Google Scholar 

  • Skerka C, Hellwage J, Weber W, Tilkorn A, Buck F, Marti T, Kampen E, Beisiegel U, Zipfel PF (1997) The human factor H-related protein 4 (FHR-4). A novel short consensus repeat-containing protein is associated with human triglyceride-rich lipoproteins. J Biol Chem 272:5627–5634

    Article  PubMed  CAS  Google Scholar 

  • Vik DP, Munoz-Canoves P, Kozono H, Martin LG, Tack BF, Chaplin DD (1990) Identification and sequence analysis of four complement factor H-related transcripts in mouse liver. J Biol Chem 265:3193–3201

    PubMed  CAS  Google Scholar 

  • Zipfel PF, Kemper C, Dahmen A, Gigli I (1996) Cloning and recombinant expression of a barred sand bass (Paralabrax nebulifer) cDNA. The encoded protein displays structural homology and immunological crossreactivity to human complement/cofactor related plasma proteins. Dev Comp Immunol 20:407–416

    Article  PubMed  CAS  Google Scholar 

  • Zipfel PF, Skerka C, Hellwage J, Jokiranta ST, Meri S, Brade V, Kraiczy P, Noris M, Remuzzi G (2002) Factor H family proteins: on complement, microbes and human diseases. Biochem Soc Trans 30:971–978

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank Ina Löschmann for sequencing the clones and Gerlinde Heckrodt and Andrea Hartmann for their excellent technical assistance. We thank Prof. Marina Botto for providing the FH−/− mice. This work was supported by grant from the Deutsche Forschungsgemeinschaft (Zi 432). T.S.J. is supported by the Academy of Finland (#201506 and #1110367), the Helsinki University Central Hospital Funds and the Finnish Cultural Foundation.

Author information

Author notes

  1. Jens Hellwage

    Present address: , 4-Antibody AG, Winzerlaer Str. 2, 07745, Jena, Germany

Authors and Affiliations

  1. Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute, Jena, Germany

    Jens Hellwage, Florian Eberle, Tanja Babuke, Harald Seeberger, Heiko Richter, Anja Kunert, Albert Härtl, Peter F. Zipfel & Mihály Józsi

  2. Friedrich Schiller University, Jena, Germany

    Peter F. Zipfel

  3. Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland

    T. Sakari Jokiranta

  4. HUSLAB, Helsinki University Central Hospital, Helsinki, Finland

    T. Sakari Jokiranta

  5. Cellular Immunology Group, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute, Beutenbergstr. 11a, 07745, Jena, Germany

    Mihály Józsi

Authors
  1. Jens Hellwage
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Florian Eberle
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tanja Babuke
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Harald Seeberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Heiko Richter
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anja Kunert
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Albert Härtl
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Peter F. Zipfel
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. T. Sakari Jokiranta
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mihály Józsi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mihály Józsi.

Additional information

Nucleotide sequence data reported are available in the EMBL database under the following accession numbers: AJ565908 (FHR-B), AJ871401 (FHR-C), AJ871402 (FHR-C_v1).

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hellwage, J., Eberle, F., Babuke, T. et al. Two factor H-related proteins from the mouse: expression analysis and functional characterization. Immunogenetics 58, 883–893 (2006). https://doi.org/10.1007/s00251-006-0153-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00251-006-0153-y

Keywords

Search

Navigation