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Gene Review

Mx1  -  MX dynamin-like GTPase 1

Mus musculus

Synonyms: AI893580, Influenza resistance protein, Interferon-induced GTP-binding protein Mx1, Mx, Mx-1, ...
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Disease relevance of Mx1

  • Human cells treated with interferon synthesize two proteins that exhibit high homology to murine Mx1 protein, which has previously been identified as the mediator of interferon-induced cellular resistance of mouse cells against influenza viruses [1].
  • BALB/3T3 fibroblasts expressing stably Mx2 but not Mx1 had an antiviral activity against recombinant vesicular stomatitis virus (VSV) [2].
  • Mx is an interferon (IFN)-inducible intracellular protein found in various vertebrates that mediates resistance against negative-strand RNA viruses [3].
  • The polymeric form of Mx1 from E. coli was observed as "horseshoe"-like structure by negative staining microscopy [4].
  • Moreover, stable lines of transfected mouse 3T3 cells that constitutively express Mx1 protein showed increased resistance to Thogoto virus infection [5].

High impact information on Mx1

  • Mx protein: constitutive expression in 3T3 cells transformed with cloned Mx cDNA confers selective resistance to influenza virus [6].
  • The predicted amino acid sequence includes a guanine nucleotide-binding domain that is homologous with those of a family of antiviral factors, inducible by interferon and known as Mx proteins, and with the product of the essential yeast vacuolar protein sorting gene VPS1 [7].
  • Thus, inborn resistance of radiation chimeras was found to be independent of Mx-gene expression in cells of the hemopoietic system [8].
  • Mice homozygous (A2G) or heterozygous (F1 hybrids between A2G and several susceptible strains) for the gene Mx, shown previously to induce a high level of resistance towards lethal challenge by a number of myxoviruses in vivo, yielded peritoneal macrophages which were not affected by M-TUR [9].
  • Here, we show that overexpression of PML, but not that of Mx1 or MxA, leads to a drastic decrease of a complex retrovirus, the human foamy virus (HFV), gene expression [10].

Biological context of Mx1


Anatomical context of Mx1


Associations of Mx1 with chemical compounds

  • The Mx- phenotype of the Mx RFLP type 3 strain CBA/J is due to a point mutation that converts the lysine codon in position 389 to a termination codon [17].
  • As analyzed, by filter binding assay, Mx1 protein (at 1 microM) showed a relatively high affinity for GDP (Kd = 1.0 x 10(-7) M) and approximately 340-fold lower affinity for guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) (Kd = 3.4 x 10(-5) M) [18].
  • The antiviral activity may be mediated in part by 2',5'-oligoadenylate synthetase, RNA-dependent protein kinase, and Mx protein, which inhibit viral replication or degrade viral components, because limitin induced their mRNA expression and enzyme activity [19].
  • Molecular cloning of double-stranded RNA inducible Mx genes from Atlantic salmon (Salmo salar L.) [20].
  • In this work Mx genes in Atlantic salmon were studied using the double stranded RNA, polyinosinic: polycytidylic acid (poly I:C), to induce interferon production [20].

Regulatory relationships of Mx1

  • Synthesis of the immunoprecipitable 75,000-dalton protein Mx was induced by interferon-alpha/beta but not by interferon-gamma in Mx+ cells of diverse genetic backgrounds [21].

Other interactions of Mx1

  • We isolated clones of the transcripts of a second Mx gene (Mx2) which is closely linked to the well-characterized resistance gene and determined their sequences [22].
  • In particular, PKR, RNase L, and Mx are considered to be the principal proteins through which IFNs mount an antiviral state [23].
  • Furthermore, our results indicate the existence of an interferon-mediated antipoxvirus pathway that operates independently of PKR, Mx1, or the 2-5A/RNase L system [24].
  • In appropriate backcross mice, no linkage was observed between Mx and md, a marker previously mapped close to the centromere of chromosome 16, suggesting a more distal localization of Mx [25].
  • Since the Mx1 promoter is IFN-alpha/beta specific and the Mx1 gene is not inducible directly by IFN-gamma, these data suggest a role of IFN-alpha/beta in the host response to Salmonella infection [26].

Analytical, diagnostic and therapeutic context of Mx1


  1. cDNA structures and regulation of two interferon-induced human Mx proteins. Aebi, M., Fäh, J., Hurt, N., Samuel, C.E., Thomis, D., Bazzigher, L., Pavlovic, J., Haller, O., Staeheli, P. Mol. Cell. Biol. (1989) [Pubmed]
  2. Intracellular localization and antiviral property of canine Mx proteins. Nakamura, T., Asano, A., Okano, S., Ko, J.H., Kon, Y., Watanabe, T., Agui, T. J. Interferon Cytokine Res. (2005) [Pubmed]
  3. Mouse Mx2 gene: organization, mRNA expression and the role of the interferon-response promoter in its regulation. Asano, A., Jin, H.K., Watanabe, T. Gene (2003) [Pubmed]
  4. Structure of mouse Mx1 protein. Molecular assembly and GTP-dependent conformational change. Nakayama, M., Yazaki, K., Kusano, A., Nagata, K., Hanai, N., Ishihama, A. J. Biol. Chem. (1993) [Pubmed]
  5. Tick-borne thogoto virus infection in mice is inhibited by the orthomyxovirus resistance gene product Mx1. Haller, O., Frese, M., Rost, D., Nuttall, P.A., Kochs, G. J. Virol. (1995) [Pubmed]
  6. Mx protein: constitutive expression in 3T3 cells transformed with cloned Mx cDNA confers selective resistance to influenza virus. Staeheli, P., Haller, O., Boll, W., Lindenmann, J., Weissmann, C. Cell (1986) [Pubmed]
  7. Molecular cloning of the microtubule-associated mechanochemical enzyme dynamin reveals homology with a new family of GTP-binding proteins. Obar, R.A., Collins, C.A., Hammarback, J.A., Shpetner, H.S., Vallee, R.B. Nature (1990) [Pubmed]
  8. Natural, genetically determined resistance toward influenza virus in hemopoietic mouse chimeras. Role of mononuclear phagocytes. Haller, O., Arnheiter, H., Lindenmann, J. J. Exp. Med. (1979) [Pubmed]
  9. Inborn resistance of mice to myxoviruses: macrophages express phenotype in vitro. Lindenmann, J., Deuel, E., Fanconi, S., Haller, O. J. Exp. Med. (1978) [Pubmed]
  10. PML mediates the interferon-induced antiviral state against a complex retrovirus via its association with the viral transactivator. Regad, T., Saib, A., Lallemand-Breitenbach, V., Pandolfi, P.P., de Thé, H., Chelbi-Alix, M.K. EMBO J. (2001) [Pubmed]
  11. Mouse Mx2 protein inhibits vesicular stomatitis virus but not influenza virus. Zürcher, T., Pavlovic, J., Staeheli, P. Virology (1992) [Pubmed]
  12. Interferon-inducible Mx gene expression in cotton rats: cloning, characterization, and expression during influenza viral infection. Pletneva, L.M., Haller, O., Porter, D.D., Prince, G.A., Blanco, J.C. J. Interferon Cytokine Res. (2006) [Pubmed]
  13. Nuclear localization of mouse Mx1 protein is necessary for inhibition of influenza virus. Zürcher, T., Pavlovic, J., Staeheli, P. J. Virol. (1992) [Pubmed]
  14. Mx1 but not MxA confers resistance against tick-borne Dhori virus in mice. Thimme, R., Frese, M., Kochs, G., Haller, O. Virology (1995) [Pubmed]
  15. Mutational analysis of murine Mx1 protein: GTP binding core domain is essential for anti-influenza A activity. Melén, K., Julkunen, I. Virology (1994) [Pubmed]
  16. Characterization and expression of the Mx1 gene in wild mouse species. Jin, H.K., Yamashita, T., Ochiai, K., Haller, O., Watanabe, T. Biochem. Genet. (1998) [Pubmed]
  17. Influenza virus-susceptible mice carry Mx genes with a large deletion or a nonsense mutation. Staeheli, P., Grob, R., Meier, E., Sutcliffe, J.G., Haller, O. Mol. Cell. Biol. (1988) [Pubmed]
  18. Enzymatic characterization of interferon-induced antiviral GTPases murine Mx1 and human MxA proteins. Melén, K., Ronni, T., Lotta, T., Julkunen, I. J. Biol. Chem. (1994) [Pubmed]
  19. Antiviral activity of limitin against encephalomyocarditis virus, herpes simplex virus, and mouse hepatitis virus: diverse requirements by limitin and alpha interferon for interferon regulatory factor 1. Kawamoto, S., Oritani, K., Asada, H., Takahashi, I., Ishikawa, J., Yoshida, H., Yamada, M., Ishida, N., Ujiie, H., Masaie, H., Tomiyama, Y., Matsuzawa, Y. J. Virol. (2003) [Pubmed]
  20. Molecular cloning of double-stranded RNA inducible Mx genes from Atlantic salmon (Salmo salar L.). Robertsen, B., Trobridge, G., Leong, J.A. Dev. Comp. Immunol. (1997) [Pubmed]
  21. Polyclonal and monoclonal antibodies to the interferon-inducible protein Mx of influenza virus-resistant mice. Staeheli, P., Dreiding, P., Haller, O., Lindenmann, J. J. Biol. Chem. (1985) [Pubmed]
  22. Identification of a second interferon-regulated murine Mx gene. Staeheli, P., Sutcliffe, J.G. Mol. Cell. Biol. (1988) [Pubmed]
  23. Interferon action in triply deficient mice reveals the existence of alternative antiviral pathways. Zhou, A., Paranjape, J.M., Der, S.D., Williams, B.R., Silverman, R.H. Virology (1999) [Pubmed]
  24. Blockade of interferon induction and action by the E3L double-stranded RNA binding proteins of vaccinia virus. Xiang, Y., Condit, R.C., Vijaysri, S., Jacobs, B., Williams, B.R., Silverman, R.H. J. Virol. (2002) [Pubmed]
  25. Interferon-regulated influenza virus resistance gene Mx is localized on mouse chromosome 16. Staeheli, P., Pravtcheva, D., Lundin, L.G., Acklin, M., Ruddle, F., Lindenmann, J., Haller, O. J. Virol. (1986) [Pubmed]
  26. Tissue selectivity of interferon-stimulated gene expression in mice infected with Dam(+) versus Dam(-) Salmonella enterica serovar Typhimurium strains. Shtrichman, R., Heithoff, D.M., Mahan, M.J., Samuel, C.E. Infect. Immun. (2002) [Pubmed]
  27. Interferon-induced antiviral Mx1 GTPase is associated with components of the SUMO-1 system and promyelocytic leukemia protein nuclear bodies. Engelhardt, O.G., Ullrich, E., Kochs, G., Haller, O. Exp. Cell Res. (2001) [Pubmed]
  28. "Endogenous adjuvant" activity of the RNA components of lupus autoantigens Sm/RNP and Ro 60. Kelly, K.M., Zhuang, H., Nacionales, D.C., Scumpia, P.O., Lyons, R., Akaogi, J., Lee, P., Williams, B., Yamamoto, M., Akira, S., Satoh, M., Reeves, W.H. Arthritis Rheum. (2006) [Pubmed]
  29. Function of the mouse Mx1 protein is inhibited by overexpression of the PB2 protein of influenza virus. Stranden, A.M., Staeheli, P., Pavlovic, J. Virology (1993) [Pubmed]
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