Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Full Paper
  • Published:

hIan5: the human ortholog to the rat Ian4/Iddm1/lyp is a new member of the Ian family that is overexpressed in B-cell lymphoid malignancies

Genes & Immunity volume 5, pages 109–116 (2004)Cite this article

Abstract

The family of immune associated nucleotide binding proteins (Ian) is a distinct family of GTP-binding proteins conserved in plants, mice, rats and humans that are associated with immune functions, suggesting involvement in conserved defense mechanisms. Recently, the rat Ian4 (rIan4) was cloned and it appears to be identical to the gene Iddm1/lyp responsible for severe lymphopenia and the development of insulin-dependent diabetes in the BB-DP rat. Here we describe the characterization of a new human member of the Ian family: hIan5. hIan5 is highly homologous to rIan4, has a predicted molecular weight of 35 kDa and contains distinct G motifs of GTP-binding proteins (G-1 to G-4) in the N-terminus. Human Ian5 is anchored to the mitochondria by the hydrophobic COOH-terminal domain. Human Ian5 is highly expressed in lymph node and spleen. Different blood fractions show high hIan5 expression in CD4- and CD8-positive T cells and monocytes, but not in B lymphocytes. In contrast, in B-CLL (chronic lymphocytic leukemia) and mantle cell lymphoma samples, hIan5 mRNA was upregulated. The current data underline the role of hIan5 in T-lymphocyte development and function, and for the first time suggest that upregulation of Ian proteins is associated with B-cell malignancy, possibly by inhibiting apoptosis.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Beutler B, Rehli M . Evolution of the TIR, tolls and TLRs: functional inferences from computational biology. Curr Top Microbiol Immunol 2002; 270: 1–21.

    CAS  PubMed  Google Scholar 

  2. Cohn J, Sessa G, Martin GB . Innate immunity in plants. Curr Opin Immunol 2001; 13: 55–62.

    Article  CAS  Google Scholar 

  3. Reuber TL, Ansubel FM . Isolation of Arabidopsis genes that differentiation between resistance responses mediated by the RP3 and RPM1 disease resistance genes. Plant Cell 1996; 8: 241–245.

    Article  CAS  Google Scholar 

  4. Staskawicz BJ, Ausubel FM, Baker BJ, Ellis JG, Jones JD . The molecular genetics of plant disease resistance. Science 1995; 268: 661–667.

    Article  CAS  Google Scholar 

  5. Poirier GM, Anderson G, Huvar A et al. Immune-associated nucleotide-1 (IAN-1) is a thymic selection marker and defines a novel gene family conserved in plants. J Immunol 1999; 163: 4960–4969.

    CAS  PubMed  Google Scholar 

  6. Daheron L, Zenz T, Siracusa LD, Brenner C, Calabretta B . Molecular cloning of Ian4: a BCR/ABL-induced gene that encodes an outer membrane mitochondrial protein with GTP-binding activity. Nucleic Acids Res 2001; 29: 1308–1316.

    Article  CAS  Google Scholar 

  7. Kruecken J, Schmitt-Wrede H-P, Markmann-Mulish U, Wunderlich F . Novel gene expressed in spleen cells mediating acquired testerone-resistant immunity to plasmodium chabaudi malaria. Biochem Biophys Res Commun 1997; 230: 167–170.

    Article  CAS  Google Scholar 

  8. Krucken J, Stamm O, Schmitt-Wrede HP, Mincheva A, Lichter P, Wunderlich F . Spleen-specific expression of the malaria-inducible intronless mouse gene imap38. J Biol Chem 1999; 274: 24383–24391.

    Article  CAS  Google Scholar 

  9. MacMurray AJ, Moralejo DH, Kwitek AE et al. Lymphopenia in the BB rat model of type 1 diabetes is due to a mutation in a novel immune-associated nucleotide (Ian)-related gene. Genome Res 2002; 12: 1029–1039.

    Article  CAS  Google Scholar 

  10. Hornum L, Romer J, Markholst H . The diabetes-prone BB rat carries a frameshift mutation in Ian4, a positional candidate of Iddm1. Diabetes 2002; 51: 1972–1979.

    Article  CAS  Google Scholar 

  11. Pandarpurkar M, Wilson-Fritch L, Corvera S et al. Ian4 is required for mitochondrial integrity and T cell survival. Proc Natl Acad Sci USA 2003; 100: 10382–10387.

    Article  CAS  Google Scholar 

  12. Stamm O, Krucken J, Schmitt-Wrede HP, Benten WP, Wunderlich F . Human ortholog to mouse gene imap38 encoding an ER-localizable G-protein belongs to a gene family clustered on chromosome 7q32–36. Gene 2002; 282: 159–167.

    Article  CAS  Google Scholar 

  13. Cambot M, Aresta S, Kahn-Perles B, de Gunzburg J, Romeo PH . Human immune associated nucleotide 1: a member of a new guanosine triphosphatase family expressed in resting T and B cells. Blood 2002; 99: 3293–3301.

    Article  CAS  Google Scholar 

  14. Sandal T, Aumo L, Hedin L, Gjertsen BT, Doskeland SO . Irod/Ian5: an inhibitor of gamma-radiation- and okadaic acid-induced apoptosis. Mol Biol Cell 2003; 14: 3292–3304.

    Article  CAS  Google Scholar 

  15. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ . Basic local alignment search tool. J Mol Biol 1990; 215: 403–410.

    Article  CAS  Google Scholar 

  16. Walker JE, Saraste M, Runswick MJ, Gay NJ . Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold. EMBO J 1982; 1: 945–951.

    Article  CAS  Google Scholar 

  17. Dohner K, Brown J, Hehmann U et al. Molecular cytogenetic characterization of a critical region in bands 7q35–36 commonly deleted in malignant myeloid disorders. Blood 1998; 92: 4031–4035.

    CAS  PubMed  Google Scholar 

  18. Cserzo M, Wallin E, Simon I, von Heijne G, Elofsson A . Prediction of transmembrane alpha-helices in procariotic membrane proteins: the dense alignment surface method. Prot Eng 1997; 10: 673–676.

    Article  CAS  Google Scholar 

  19. Viardot A, Moller P, Hogel J et al. Clinicopathologic correlations of genomic gains and losses in follicular lymphoma. J Clin Oncol 2002; 20: 4523–4530.

    Article  Google Scholar 

  20. Hales KG, Fuller MT . Developmentally regulated mitochondrial fusion mediated by a conserved, novel, predicted GTPase. Cell 1997; 90: 121–129.

    Article  CAS  Google Scholar 

  21. Santel A, Fuller MT . Control of mitochondrial morphology by a human mitofusin. J Cell Sci 2001; 114: 867–874.

    CAS  PubMed  Google Scholar 

  22. Thomson M . What are guanosine triphosphate-binding proteins doing in mitochondria? Biochim Biophys Acta 1998; 1403: 211–218.

    Article  CAS  Google Scholar 

  23. Kessler F, Blobel G, Patel HV, Schnell DJ . Identification of two GTP-binding proteins in the chloroplast protein import machinery. Science 1994; 266: 1035–1039.

    Article  CAS  Google Scholar 

  24. Schneider E, Hunke S . ATP binding cassette (ABC) transport systems: functional and structuralaaspects of the ATP hydrolyzing subunits/domains. FEMS Microbiol Rev 1998; 22: 1–20.

    Article  CAS  Google Scholar 

  25. Hogue DL, Liu L, Ling V . Identification and characterization of a mammalian mitochondrial ATP-binding cassette membrane protein. J Mol Biol 1999; 285: 379–389.

    Article  CAS  Google Scholar 

  26. Castedo M, Kroemer G . The beauty of death. Trends Cell Biol 2002; 12: 446.

    Article  Google Scholar 

  27. Iwakoshi NN, Goldschneider I, Tausche F, Mordes JP, Rossini AA, Greiner DL . High frequency apoptosis of recent thymic emigrants in the liver of lymphopenic diabetes-prone BioBreeding rats. J Immunol 1998; 160: 5838–5850.

    CAS  PubMed  Google Scholar 

  28. Schattner EJ . Apoptosis in lymphocytic leukemias and lymphomas. Cancer Invest 2002; 20: 737–748.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Thorsten Zenz was supported by a fellowship from the ‘Dr Mildred Scheel Stiftung fuer Krebsforschung’, Bonn, Germany. L Dahéron was in part supported by a fellowship of ‘La ligue contre le Cancer des Deux-Sevres’. This work was, in part, supported by NIH grants to BC. We are grateful to S Stilgenbauer for supplying patient material.

Author information

Authors and Affiliations

  1. Department of Medicine III, University Hospital Ulm, Ulm, Germany

    T Zenz, A Roessner, S Fröhling & H Döhner

  2. Department of Medicine I, University Hospital Freiburg, Freiburg, Germany

    A Thomas

  3. Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA, USA

    B Calabretta

  4. Whitehead Institute for Biomedical Research, MIT, Cambridge, MA, USA

    L Dahéron

Authors
  1. T Zenz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A Roessner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Fröhling
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H Döhner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. B Calabretta
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. L Dahéron
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T Zenz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zenz, T., Roessner, A., Thomas, A. et al. hIan5: the human ortholog to the rat Ian4/Iddm1/lyp is a new member of the Ian family that is overexpressed in B-cell lymphoid malignancies. Genes Immun 5, 109–116 (2004). https://doi.org/10.1038/sj.gene.6364044

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gene.6364044

Keywords

This article is cited by

Search

Advanced search

Quick links