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Gene Review

MX1  -  MX dynamin-like GTPase 1

Homo sapiens

Synonyms: IFI-78K, IFI78, Interferon-induced GTP-binding protein Mx1, Interferon-induced protein p78, Interferon-regulated resistance GTP-binding protein MxA, ...
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Disease relevance of MX1


Psychiatry related information on MX1

  • The localization of alpha-interferon (alpha-IFN) and its induced protein, MxA, was examined in human brain tissues from neurologically normal, Alzheimer's disease (AD) and Parkinson's disease (PD) cases [3].

High impact information on MX1

  • This activation results not only in increased antigen presentation and T cell stimulatory capacity, but also in resistance to the cytopathic effect of the virus, mediated by the production of type I interferon, and upregulation of MxA [4].
  • Forced expression of MxA in Hep3B cells enhances their sensitivity to mitomycin C and induces apoptosis, similar to the FA phenotype [5].
  • MxA overexpression reveals a common genetic link in four Fanconi anemia complementation groups [5].
  • Our results thus define an MxA region that determines antiviral specificity and further demonstrate that nuclear forms of MxA can mimic the action of mouse Mx1 whose natural location is the cell nucleus [6].
  • Haplotype frequencies of the MX1 locus of chromosome 21 distinguish Koyas and Chenchus, along with Indian caste groups, from European and eastern Asian populations [7].

Chemical compound and disease context of MX1


Biological context of MX1

  • A minimum tiling path (MTP) was subsequently defined that consists of 20 PACs, 2 BACs, and 5 cosmids covering 3 Mb between D21S3 and MX1 [13].
  • Treatment of MxA-expressing cells with antibodies to mouse alpha-beta interferon did not abolish the resistance phenotype [1].
  • We observed that in HepG2 and HuH7 cells IFN-inducible genes were upregulated by IFNs, but relatively high concentrations of IFN-alpha were needed to turn on MxA (an antiviral gene) and MxB gene expression [14].
  • METHODS: HepG2 cells were transfected with the plasmid pHCV-Co, and, after treatment with IFN-alpha , levels of MxA, protein kinase R (PKR), and 2'-5' oligoadenylate synthetase (2'-5'OAS) mRNA were determined [15].
  • RESULTS: Levels of MxA mRNA in pHCV-Co-transfected cells decreased in a dose-dependent manner, by down-regulation of the MxA gene promoter [15].

Anatomical context of MX1


Associations of MX1 with chemical compounds

  • Substitutions were made for highly conserved arginine residues in either the LLP-1 or LLP-2 domain (MX1 or MX2, respectively) or in both domains (MX4) [20].
  • MxA protein is a member of the dynamin superfamily of large guanosine triphosphatases [21].
  • It is concluded that pretreatment hepatocellular MxA expression may become a useful predictor of response to combination treatment with IFN-alpha and ribavirin [22].
  • Using cisplatin and a new porphyrin-derived compound TMPyP4, we showed that our model was able to detect a down-regulation of the telomerase activity in MCF7 cells in culture and in a human MX1 tumour xenografts [23].
  • Tumor growth delays were obtained in the MX1 human breast carcinoma xenograft treated with various combinations of Adriamycin (doxorubicin), Fluosol-DA, and carbogen breathing (95% oxygen/5% carbon dioxide) [24].

Physical interactions of MX1

  • Using a yeast two-hybrid interaction assay, we found that the second ankyrin-like repeat domain of TRPC6 interacted with MxA, a member of the dynamin superfamily [25].
  • We studied prospectively the induction of MxA protein and the development of binding (BAb) and neutralising antibodies (NAb) in nine relapsing-remitting MS (RRMS) patients during one year of intramuscular IFNbeta -1a (Avonex((R))) treatment [26].

Regulatory relationships of MX1

  • RESULTS: Pretreatment of Huh-7 cells with 0.5-1 mM H2O2 resulted in the suppression of the IFN-alpha-induced antiviral protein MxA and of IRF-9 mRNA expression [27].
  • Additionally, we showed IL-28A and IL-29 induced reporter genes--protein MxA promoter linked to luciferase, or interferon stimulated response element (ISRE) linked to secreted alkaline phosphatase (SEAP)--more weakly than IFN [28].
  • The addition of antibodies to beta interferon (IFN-beta) blocked interferon-directed MxA induction by >90% and demonstrated that hantavirus infection induces the secretion of IFN-beta from endothelial cells [29].
  • The present findings are consistent with previous data which indicated that cytoplasmic MxA prevents transport of vRNPs into the nucleus, whereas nuclear MxA directly inhibits the viral polymerase activity in the nucleus [30].

Other interactions of MX1

  • Chloramphenycol acethyl transferase (CAT) analysis was performed on cells cotransfected with pHCV-Co and pMx4CAT (containing the MxA gene promoter) and treated with IFN [15].
  • Polymorphisms in the interferon-induced genes, MxA, OAS-1 and PKR appear thus associated with HCV outcome [31].
  • This article describes a bioassay based on the real time PCR measurement of mRNA that results from the induction, in cultured human cells, of the MxA gene by IFNbeta [32].
  • In addition, the assay was robust with respect to number of cells plated (i.e., increasing cell densities from 12x10(3)/well to 384x10(3)/well resulted in 3.03% variability in MxA expression normalized with glyceraldehyde-3 phosphate dehydrogenase) [32].
  • Biological markers of interferon-beta therapy: comparison among interferon-stimulated genes MxA, TRAIL and XAF-1 [2].

Analytical, diagnostic and therapeutic context of MX1

  • There are two commonly employed types of bioassays for the detection of neutralizing antibodies (NAbs) against interferon-beta (IFNbeta): the cytopatic effect assay (CPE), and the MxA (myxovirus resistance protein A) protein assay (MPA) [32].
  • In influenza A virus-infected A549 and HFL1 cells, MxA gene induction was mediated by IFN-alpha/beta released into the cell culture supernatant, and was prevented by anti-type I IFN Abs [8].
  • We show that recombinant MxA protein assembles into long filamentous structures with a diameter of about 20 nm at physiological salt concentration as demonstrated by sedimentation assays and electron microscopy [33].
  • Levels of the antiviral protein MxA and soluble vascular cell adhesion molecule-1 (sVCAM) in the four groups were measured by ELISA [34].
  • METHODS: The authors measured MxA in whole blood by ELISA, and serum-binding antibodies (SBA) by Western blot and ELISA in 134 samples of MS patients on IFNbeta-1b and 54 control subjects, and correlated the MxA levels and SBA titers with the NAB titer [35].


  1. Resistance to influenza virus and vesicular stomatitis virus conferred by expression of human MxA protein. Pavlovic, J., Zürcher, T., Haller, O., Staeheli, P. J. Virol. (1990) [Pubmed]
  2. Biological markers of interferon-beta therapy: comparison among interferon-stimulated genes MxA, TRAIL and XAF-1. Gilli, F., Marnetto, F., Caldano, M., Sala, A., Malucchi, S., Capobianco, M., Bertolotto, A. Mult. Scler. (2006) [Pubmed]
  3. Immunohistochemistry using antibodies to alpha-interferon and its induced protein, MxA, in Alzheimer's and Parkinson's disease brain tissues. Yamada, T., Horisberger, M.A., Kawaguchi, N., Moroo, I., Toyoda, T. Neurosci. Lett. (1994) [Pubmed]
  4. Maturation, activation, and protection of dendritic cells induced by double-stranded RNA. Cella, M., Salio, M., Sakakibara, Y., Langen, H., Julkunen, I., Lanzavecchia, A. J. Exp. Med. (1999) [Pubmed]
  5. MxA overexpression reveals a common genetic link in four Fanconi anemia complementation groups. Li, Y., Youssoufian, H. J. Clin. Invest. (1997) [Pubmed]
  6. Mechanism of human MxA protein action: variants with changed antiviral properties. Zürcher, T., Pavlovic, J., Staeheli, P. EMBO J. (1992) [Pubmed]
  7. The genetic heritage of the earliest settlers persists both in Indian tribal and caste populations. Kivisild, T., Rootsi, S., Metspalu, M., Mastana, S., Kaldma, K., Parik, J., Metspalu, E., Adojaan, M., Tolk, H.V., Stepanov, V., Gölge, M., Usanga, E., Papiha, S.S., Cinnioğlu, C., King, R., Cavalli-Sforza, L., Underhill, P.A., Villems, R. Am. J. Hum. Genet. (2003) [Pubmed]
  8. Regulation of IFN-alpha/beta, MxA, 2',5'-oligoadenylate synthetase, and HLA gene expression in influenza A-infected human lung epithelial cells. Ronni, T., Matikainen, S., Sareneva, T., Melén, K., Pirhonen, J., Keskinen, P., Julkunen, I. J. Immunol. (1997) [Pubmed]
  9. Antiviral effects of geranylgeranylacetone: enhancement of MxA expression and phosphorylation of PKR during influenza virus infection. Unoshima, M., Iwasaka, H., Eto, J., Takita-Sonoda, Y., Noguchi, T., Nishizono, A. Antimicrob. Agents Chemother. (2003) [Pubmed]
  10. Effects of temperature on the therapeutic efficacy and pharmacokinetics of ifosfamide. Wiedemann, G.J., Siemens, H.J., Mentzel, M., Biersack, A., Wössmann, W., Knocks, D., Weiss, C., Wagner, T. Cancer Res. (1993) [Pubmed]
  11. 4-Demethylpenclomedine, an antitumor-active, potentially nonneurotoxic metabolite of penclomedine. Waud, W.R., Tiwari, A., Schmid, S.M., Shih, T.W., Strong, J.M., Hartman, N.R., O'Reilly, S., Struck, R.F. Cancer Res. (1997) [Pubmed]
  12. Prevention of central nervous system toxicity of the antitumor antibiotic acivicin by concomitant infusion of an amino acid mixture. Williams, M.G., Earhart, R.H., Bailey, H., McGovren, J.P. Cancer Res. (1990) [Pubmed]
  13. A contiguous 3-Mb sequence-ready map in the S3-MX region on 21q22.2 based on high- throughput nonisotopic library screenings. Hildmann, T., Kong, X., O'Brien, J., Riesselman, L., Christensen, H.M., Dagand, E., Lehrach, H., Yaspo, M.L. Genome Res. (1999) [Pubmed]
  14. Interferon-induced gene expression and signaling in human hepatoma cell lines. Melén, K., Keskinen, P., Lehtonen, A., Julkunen, I. J. Hepatol. (2000) [Pubmed]
  15. Hepatitis C virus core protein down-regulates transcription of interferon-induced antiviral genes. de Lucas, S., Bartolome, J., Carreno, V. J. Infect. Dis. (2005) [Pubmed]
  16. Increased sensitivity of SARS-coronavirus to a combination of human type I and type II interferons. Scagnolari, C., Vicenzi, E., Bellomi, F., Stillitano, M.G., Pinna, D., Poli, G., Clementi, M., Dianzani, F., Antonelli, G. Antivir. Ther. (Lond.) (2004) [Pubmed]
  17. IFN-alpha subtypes differentially affect human T cell motility. Foster, G.R., Masri, S.H., David, R., Jones, M., Datta, A., Lombardi, G., Runkell, L., de Dios, C., Sizing, I., James, M.J., Marelli-Berg, F.M. J. Immunol. (2004) [Pubmed]
  18. The antiviral dynamin family member, MxA, tubulates lipids and localizes to the smooth endoplasmic reticulum. Accola, M.A., Huang, B., Al Masri, A., McNiven, M.A. J. Biol. Chem. (2002) [Pubmed]
  19. Neutralizing antibodies reduce MxA protein induction in interferon-beta-1a-treated MS patients. Vallittu, A.M., Halminen, M., Peltoniemi, J., Ilonen, J., Julkunen, I., Salmi, A., Erälinna, J.P. Neurology (2002) [Pubmed]
  20. Rational site-directed mutations of the LLP-1 and LLP-2 lentivirus lytic peptide domains in the intracytoplasmic tail of human immunodeficiency virus type 1 gp41 indicate common functions in cell-cell fusion but distinct roles in virion envelope incorporation. Kalia, V., Sarkar, S., Gupta, P., Montelaro, R.C. J. Virol. (2003) [Pubmed]
  21. Andes virus stimulates interferon-inducible MxA protein expression in endothelial cells. Khaiboullina, S.F., Rizvanov, A.A., Deyde, V.M., St Jeor, S.C. J. Med. Virol. (2005) [Pubmed]
  22. Intrahepatic MxA and PKR protein expression in chronic hepatitis C virus infection. MacQuillan, G.C., de Boer, W.B., Platten, M.A., McCaul, K.A., Reed, W.D., Jeffrey, G.P., Allan, J.E. J. Med. Virol. (2002) [Pubmed]
  23. A human breast cancer model for the study of telomerase inhibitors based on a new biotinylated-primer extension assay. Raymond, E., Sun, D., Izbicka, E., Mangold, G., Silvas, E., Windle, B., Sharma, S., Soda, H., Laurence, R., Davidson, K., Von Hoff, D.D. Br. J. Cancer (1999) [Pubmed]
  24. Effects of Fluosol-DA and oxygen breathing on adriamycin antitumor activity and cardiac toxicity in mice. Teicher, B.A., Holden, S.A., Crawford, J.M. Cancer (1988) [Pubmed]
  25. MxA, a member of the dynamin superfamily, interacts with the ankyrin-like repeat domain of TRPC. Lussier, M.P., Cayouette, S., Lepage, P.K., Bernier, C.L., Francoeur, N., St-Hilaire, M., Pinard, M., Boulay, G. J. Biol. Chem. (2005) [Pubmed]
  26. MxA protein induction in MS patients treated with intramuscular IFNbeta-1a. Vallittu, A.M., Salmi, A.A., Erälinna, J.P. Neurol. Sci. (2006) [Pubmed]
  27. Oxidative stress inhibits IFN-alpha-induced antiviral gene expression by blocking the JAK-STAT pathway. Di Bona, D., Cippitelli, M., Fionda, C., Cammà, C., Licata, A., Santoni, A., Craxì, A. J. Hepatol. (2006) [Pubmed]
  28. Biological activity of interleukins-28 and -29: comparison with type I interferons. Meager, A., Visvalingam, K., Dilger, P., Bryan, D., Wadhwa, M. Cytokine (2005) [Pubmed]
  29. The Pathogenic NY-1 Hantavirus G1 Cytoplasmic Tail Inhibits RIG-I- and TBK-1-Directed Interferon Responses. Alff, P.J., Gavrilovskaya, I.N., Gorbunova, E., Endriss, K., Chong, Y., Geimonen, E., Sen, N., Reich, N.C., Mackow, E.R. J. Virol. (2006) [Pubmed]
  30. MxA GTPase blocks reporter gene expression of reconstituted Thogoto virus ribonucleoprotein complexes. Weber, F., Haller, O., Kochs, G. J. Virol. (2000) [Pubmed]
  31. Polymorphisms in interferon-induced genes and the outcome of hepatitis C virus infection: roles of MxA, OAS-1 and PKR. Knapp, S., Yee, L.J., Frodsham, A.J., Hennig, B.J., Hellier, S., Zhang, L., Wright, M., Chiaramonte, M., Graves, M., Thomas, H.C., Hill, A.V., Thursz, M.R. Genes Immun. (2003) [Pubmed]
  32. Development and validation of a real time PCR-based bioassay for quantification of neutralizing antibodies against human interferon-beta. Bertolotto, A., Sala, A., Caldano, M., Capobianco, M., Malucchi, S., Marnetto, F., Gilli, F. J. Immunol. Methods (2007) [Pubmed]
  33. Self-assembly of human MxA GTPase into highly ordered dynamin-like oligomers. Kochs, G., Haener, M., Aebi, U., Haller, O. J. Biol. Chem. (2002) [Pubmed]
  34. A comparative study of the relative bioavailability of different interferon beta preparations. Deisenhammer, F., Mayringer, I., Harvey, J., Dilitz, E., Gasse, T., Stadlbauer, D., Reindl, M., Berger, T. Neurology (2000) [Pubmed]
  35. Bioavailability of interferon beta 1b in MS patients with and without neutralizing antibodies. Deisenhammer, F., Reindl, M., Harvey, J., Gasse, T., Dilitz, E., Berger, T. Neurology (1999) [Pubmed]
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