MX2 explained

Interferon-induced GTP-binding protein Mx2 is a protein that in humans is encoded by the MX2 gene.^{[1] [2] [3]}

The protein encoded by this gene has a nuclear and a cytoplasmic form and is a member of both the dynamin family and the family of large GTPases. The nuclear form is localized in a granular pattern in the heterochromatin region beneath the nuclear envelope. A nuclear localization signal (NLS) is present at the amino terminal end of the nuclear form but is lacking in the cytoplasmic form due to use of an alternate translation start codon.

Antiviral activity

This protein is upregulated by interferon-alpha but does not contain the antiviral activity of a similar myxovirus resistance protein 1.

MX2/MXB has antiviral activity against HIV-1.^{[4] [5] [6] [7] [8] [9] [10]} MXB is also a restriction factor for herpesviruses, which acts at a very early stage of the replication cycle and MX2/MXB restriction of herpesvirus requires GTPase activity.^{[11] [12] [13] [14]}

Further reading

• Horisberger MA, McMaster GK, Zeller H, Wathelet MG, Dellis J, Content J . Cloning and sequence analyses of cDNAs for interferon- and virus-induced human Mx proteins reveal that they contain putative guanine nucleotide-binding sites: functional study of the corresponding gene promoter . Journal of Virology . 64 . 3 . 1171–81 . March 1990 . 2154602 . 249231 . 10.1128/JVI.64.3.1171-1181.1990 .
• Horisberger MA, Wathelet M, Szpirer J, Szpirer C, Islam Q, Levan G, Huez G, Content J . 6 . cDNA cloning and assignment to chromosome 21 of IFI-78K gene, the human equivalent of murine Mx gene . Somatic Cell and Molecular Genetics . 14 . 2 . 123–31 . March 1988 . 3162334 . 10.1007/BF01534397 . 31805827 .
• al-Masri AN, Werfel T, Jakschies D, von Wussow P . Intracellular staining of Mx proteins in cells from peripheral blood, bone marrow and skin . Molecular Pathology . 50 . 1 . 9–14 . February 1997 . 9208807 . 379572 . 10.1136/mp.50.1.9 .
• Melén K, Julkunen I . Nuclear cotransport mechanism of cytoplasmic human MxB protein . The Journal of Biological Chemistry . 272 . 51 . 32353–9 . December 1997 . 9405443 . 10.1074/jbc.272.51.32353 . free .
• Hattori M, Fujiyama A, Taylor TD, Watanabe H, Yada T, Park HS, Toyoda A, Ishii K, Totoki Y, Choi DK, Groner Y, Soeda E, Ohki M, Takagi T, Sakaki Y, Taudien S, Blechschmidt K, Polley A, Menzel U, Delabar J, Kumpf K, Lehmann R, Patterson D, Reichwald K, Rump A, Schillhabel M, Schudy A, Zimmermann W, Rosenthal A, Kudoh J, Schibuya K, Kawasaki K, Asakawa S, Shintani A, Sasaki T, Nagamine K, Mitsuyama S, Antonarakis SE, Minoshima S, Shimizu N, Nordsiek G, Hornischer K, Brant P, Scharfe M, Schon O, Desario A, Reichelt J, Kauer G, Blocker H, Ramser J, Beck A, Klages S, Hennig S, Riesselmann L, Dagand E, Haaf T, Wehrmeyer S, Borzym K, Gardiner K, Nizetic D, Francis F, Lehrach H, Reinhardt R, Yaspo ML . 6 . The DNA sequence of human chromosome 21 . Nature . 405 . 6784 . 311–9 . May 2000 . 10830953 . 10.1038/35012518 . free . 2000Natur.405..311H .
• Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Marra MA . 6 . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proceedings of the National Academy of Sciences of the United States of America . 99 . 26 . 16899–903 . December 2002 . 12477932 . 139241 . 10.1073/pnas.242603899 . 2002PNAS...9916899M . free .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . 6 . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 4427026 . 2005Natur.437.1173R .
• Tanaka S, Honda Y, Honda M . Identification of differentially expressed genes in blood cells of narcolepsy patients . Sleep . 30 . 8 . 974–9 . August 2007 . 17702266 . 1978392 . 10.1093/sleep/30.8.974 .

Notes and References

1. Aebi M, Fäh J, Hurt N, Samuel CE, Thomis D, Bazzigher L, Pavlovic J, Haller O, Staeheli P . 6 . cDNA structures and regulation of two interferon-induced human Mx proteins . Molecular and Cellular Biology . 9 . 11 . 5062–72 . November 1989 . 2481229 . 363658 . 10.1128/mcb.9.11.5062 .
2. Melén K, Keskinen P, Ronni T, Sareneva T, Lounatmaa K, Julkunen I . Human MxB protein, an interferon-alpha-inducible GTPase, contains a nuclear targeting signal and is localized in the heterochromatin region beneath the nuclear envelope . The Journal of Biological Chemistry . 271 . 38 . 23478–86 . September 1996 . 8798556 . 10.1074/jbc.271.38.23478 . free .
3. Web site: Entrez Gene: MX2 myxovirus (influenza virus) resistance 2 (mouse).
4. Liu Z, Pan Q, Ding S, Qian J, Xu F, Zhou J, Cen S, Guo F, Liang C . 6 . The interferon-inducible MxB protein inhibits HIV-1 infection . Cell Host & Microbe . 14 . 4 . 398–410 . October 2013 . 24055605 . 10.1016/j.chom.2013.08.015 . free .
5. Kane M, Yadav SS, Bitzegeio J, Kutluay SB, Zang T, Wilson SJ, Schoggins JW, Rice CM, Yamashita M, Hatziioannou T, Bieniasz PD . 6 . MX2 is an interferon-induced inhibitor of HIV-1 infection . Nature . 502 . 7472 . 563–6 . October 2013 . 24121441 . 3912734 . 10.1038/nature12653 . 2013Natur.502..563K .
6. Goujon C, Moncorgé O, Bauby H, Doyle T, Ward CC, Schaller T, Hué S, Barclay WS, Schulz R, Malim MH . 6 . Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection . Nature . 502 . 7472 . 559–62 . October 2013 . 24048477 . 3808269 . 10.1038/nature12542 . 2013Natur.502..559G .
7. Alvarez FJ, He S, Perilla JR, Jang S, Schulten K, Engelman AN, Scheres SH, Zhang P . 6 . CryoEM structure of MxB reveals a novel oligomerization interface critical for HIV restriction . Science Advances . 3 . 9 . e1701264 . September 2017 . 28929138 . 5600524 . 10.1126/sciadv.1701264 . 2017SciA....3E1264A .
8. Merindol N, Berthoux L . Restriction Factors in HIV-1 Disease Progression . Current HIV Research . 13 . 6 . 448–61 . 2015 . 26051387 . 10.2174/1570162x13666150608104412 .
9. Haller O, Staeheli P, Schwemmle M, Kochs G . Mx GTPases: dynamin-like antiviral machines of innate immunity . Trends in Microbiology . 23 . 3 . 154–63 . March 2015 . 25572883 . 10.1016/j.tim.2014.12.003 .
10. Chintala K, Mohareer K, Banerjee S . Dodging the Host Interferon-Stimulated Gene Mediated Innate Immunity by HIV-1: A Brief Update on Intrinsic Mechanisms and Counter-Mechanisms . Frontiers in Immunology . 12 . 716927 . 2021 . 34394123 . 8358655 . 10.3389/fimmu.2021.716927 . free .
11. Crameri M, Bauer M, Caduff N, Walker R, Steiner F, Franzoso FD, Gujer C, Boucke K, Kucera T, Zbinden A, Münz C, Fraefel C, Greber UF, Pavlovic J . 6 . MxB is an interferon-induced restriction factor of human herpesviruses . Nature Communications . 9 . 1 . 1980 . May 2018 . 29773792 . 5958057 . 10.1038/s41467-018-04379-2 . 2018NatCo...9.1980C .
12. Schilling M, Bulli L, Weigang S, Graf L, Naumann S, Patzina C, Wagner V, Bauersfeld L, Goujon C, Hengel H, Halenius A, Ruzsics Z, Schaller T, Kochs G . 6 . Human MxB Protein Is a Pan-herpesvirus Restriction Factor . Journal of Virology . 92 . 17 . e01056–18, /jvi/92/17/e01056–18.atom . September 2018 . 29950411 . 6096802 . 10.1128/JVI.01056-18 . Sandri-Goldin RM .
13. Jaguva Vasudevan AA, Bähr A, Grothmann R, Singer A, Häussinger D, Zimmermann A, Münk C . MXB inhibits murine cytomegalovirus . Virology . 522 . 158–167 . September 2018 . 30032029 . 10.1016/j.virol.2018.07.017 . free .
14. Staeheli P, Haller O . Human MX2/MxB: a Potent Interferon-Induced Postentry Inhibitor of Herpesviruses and HIV-1 . Journal of Virology . 92 . 24 . e00709–18, /jvi/92/24/e00709–18.atom . December 2018 . 30258007 . 6258936 . 10.1128/JVI.00709-18 . Ulrike Gack MU .