Affinage

MX1

Interferon-induced GTP-binding protein Mx1 · UniProt P20591

Length
662 aa
Mass
75.5 kDa
Annotated
2026-06-10
100 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MX1 (MxA) is an interferon-induced, dynamin-superfamily GTPase that acts as a broad cytoplasmic antiviral effector, restricting RNA and some DNA viruses by recognizing and sequestering their nucleocapsid structures (PMID:2161946, PMID:1657964, PMID:11880649). It possesses intrinsic, Mg2+-dependent GTPase activity localized to an N-terminal domain whose mutation abolishes catalysis, and it binds GTP with higher affinity than GDP (PMID:1629950, PMID:7539429, PMID:7507489). MxA self-assembles into oligomeric horseshoe, ring, and helical polymers, an assembly that is remodeled by guanine nucleotides; crystallography of the oligomerized stalk and GTPase effector domain (GED) defines this architecture and its capacity to tubulate liposomes (PMID:8325879, PMID:11847228, PMID:20538602). Single-molecule analysis shows that GTP loading drives conformational shifts between the GTPase domain and the bundle-signaling element, generating torque within the polymer that underlies a mechanochemical mode of action (PMID:28548099). Antiviral target recognition is mediated by the C-terminal GED: MxA binds the nucleocapsid proteins of La Crosse, Crimean-Congo hemorrhagic fever, influenza A, and VSV and sequesters them into perinuclear complexes, and the C-terminal E645R mutation abolishes both target binding and restriction (PMID:11880649, PMID:15047845, PMID:26507657). GTP binding rather than hydrolysis is required for antiviral activity, and MxA monomers/dimers extracted from the oligomeric pool are the active species, with dimers forming the stable nucleoprotein-binding unit (PMID:7831809, PMID:10933733, PMID:26507657). Through this mechanism MxA blocks viral replication at an early step preceding primary transcription, acting against influenza A, VSV, Thogoto, Bunyaviridae, Semliki Forest virus, and African swine fever virus (PMID:2161946, PMID:8551631, PMID:9445055, PMID:19109387, PMID:23152507). Beyond direct antiviral defense MxA engages cellular partners including the RNA helicases UAP56/URH49, tubulin, and TRPC channels, and it inhibits tumor cell motility in a GTPase-dependent manner (PMID:15757897, PMID:19297326, PMID:21859714). Rare heterozygous dominant-negative MX1 variants that abolish antiviral activity increase human susceptibility to zoonotic H7N9 influenza, confirming its essential role in innate antiviral immunity (PMID:34413236).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1990 High

    Established that MxA is a specific antiviral effector by showing it confers cytoplasmic resistance to defined virus families but not others, distinguishing it functionally from MxB.

    Evidence Stable transfection of 3T3 cells with MxA or MxB cDNA followed by viral yield assays

    PMID:2161946

    Open questions at the time
    • Did not define the molecular target or mechanism of restriction
    • Basis of virus-family specificity unknown
  2. 1991 High

    Placed Mx proteins in the dynamin superfamily and showed they are GTP-hydrolyzing enzymes, providing the biochemical framework for their mechanism.

    Evidence Recombinant mouse Mx1 purified from E. coli, in vitro GTPase assay, site-directed mutagenesis of the GTP-binding motif

    PMID:1657964

    Open questions at the time
    • Did not connect GTPase activity to antiviral function
    • No structural model
  3. 1992 High

    Defined GTPase catalysis and the C-terminal region as separable determinants, with the C-terminus controlling antiviral specificity and subcellular site of inhibition.

    Evidence GTPase assays on immunoprecipitated MxA with mutagenesis; nuclear-targeted MxA(R645) and viral RNA accumulation assays

    PMID:1314172 PMID:1629950

    Open questions at the time
    • Did not identify the C-terminal binding partner
    • Mechanism linking localization to inhibition step unresolved
  4. 1995 High

    Demonstrated that purified MxA directly inhibits viral RNP transcription and that GTP binding, not hydrolysis, is the requirement, dissociating catalytic turnover from antiviral output.

    Evidence In vitro VSV transcription assays with purified His-MxA, GTP analog experiments, and the E645R mutant; fluorescent nucleotide binding kinetics

    PMID:7539429 PMID:7745744 PMID:7831809

    Open questions at the time
    • The direct viral target structure not yet physically identified
    • How GTP-bound MxA interferes with initiation mechanistically unclear
  5. 1993 High

    Showed MxA/Mx1 self-assembly into polymers is nucleotide-responsive, mapping a conserved N-terminal self-assembly motif and revealing GTP-driven conformational reorganization.

    Evidence Gel filtration, negative-stain EM, and deletion/point mutagenesis of purified Mx protein; intramolecular fold-back mapping by yeast two-hybrid

    PMID:11847228 PMID:8325879 PMID:9774462

    Open questions at the time
    • Functional role of oligomers vs. monomers in restriction unsettled
    • Polymer geometry not defined at atomic resolution
  6. 1996 High

    Broadened the antiviral spectrum to all Bunyaviridae genera and positive-strand togaviruses, showing MxA blocks an early replication step prior to transcript accumulation.

    Evidence Stable MxA-transfected Vero/HEp-2/U937 cells, plaque assays, replicon transfection, and northern/RT-PCR RNA analysis

    PMID:8551631 PMID:9445055

    Open questions at the time
    • Common molecular target across diverse viruses not yet defined
    • Whether a single mechanism explains all families unknown
  7. 1998 Medium

    Provided the first direct physical evidence that MxA engages a viral RNP target, in a GTP-dependent manner, while clarifying intramolecular versus intermolecular oligomerization surfaces.

    Evidence GTPgammaS-dependent cosedimentation of purified MxA with Thogoto RNP; yeast two-hybrid and mutagenesis of fold-back/leucine-zipper residues

    PMID:9735310 PMID:9774462

    Open questions at the time
    • Cosedimentation from single lab without reciprocal in-cell validation at the time
    • Stoichiometry of the MxA-RNP interaction undefined
  8. 2000 High

    Resolved the active species question by showing GTPase-dead, monomeric MxA(L612K) retains antiviral activity, defining oligomers as a storage pool and monomers as functional.

    Evidence L612K mutagenesis, transient transfection, Thogoto minireplicon assay, and GTPase measurement in Vero cells

    PMID:10933733

    Open questions at the time
    • Apparent tension with later dimer-as-active-unit data
    • How monomer recruitment from oligomer pool is regulated unknown
  9. 2002 High

    Identified the mechanism of restriction as C-terminal GED-mediated capture of viral nucleocapsid protein into perinuclear complexes, blocking virion incorporation.

    Evidence Co-IP, confocal and electron microscopy of MxA-LACV N complexes, with the E645R C-terminal mutant; in vitro filament/ring assembly by EM

    PMID:11847228 PMID:11880649

    Open questions at the time
    • Whether sequestration is the sole mechanism across all viruses unclear
    • Structural basis of N-protein recognition not solved
  10. 2004 High

    Generalized the nucleocapsid-sequestration mechanism to a second nairovirus (CCHFV), confirming the C-terminal GED as the conserved target-recognition determinant.

    Evidence Confocal co-localization, co-IP, plaque assay, and the E645R mutant in CCHFV-infected cells

    PMID:15047845

    Open questions at the time
    • Did not establish whether all sensitive viruses share an identical binding interface
  11. 2010 High

    Provided the structural basis for MxA oligomerization by solving the stalk/GED architecture and demonstrating membrane-tubulating capacity.

    Evidence X-ray crystallography of the oligomerized MxA stalk plus liposome tubulation assays

    PMID:20538602

    Open questions at the time
    • Full-length nucleotide-bound structure not captured
    • Direct structural snapshot of MxA bound to a viral target absent
  12. 2011 Medium

    Expanded the interactome to cellular RNA helicases UAP56/URH49 and the ER chaperone BiP, linking MxA to host RNA processing and ER stress responses during infection.

    Evidence Co-IP, in vitro binding with purified recombinant proteins, confocal co-localization, and ER stress markers in IAV-infected cells

    PMID:21859714 PMID:21992152

    Open questions at the time
    • Functional consequence of helicase binding for restriction not isolated
    • BiP interaction rests on single co-IP
  13. 2012 High

    Confirmed MxA as the effector of IFN-alpha-mediated influenza suppression by loss-of-function and pinpointed the block to a step before primary transcription.

    Evidence siRNA knockdown in IFN-treated primate cells and strand-specific RT-PCR in stable MxA-Vero cells

    PMID:23152507

    Open questions at the time
    • Precise molecular event blocked before transcription not defined
    • Relationship to NP sequestration in this assay not directly shown
  14. 2015 Medium

    Refined the active antiviral unit as the MxA dimer for nucleoprotein capture and linked strain resistance (1918 PR8) to weakened NP binding; established SUMO as a stabilizer of the MxA oligomer pool.

    Evidence GTPgammaS-induced disassembly, analytical ultracentrifugation, co-IP with IAV NP; SUMO co-expression with MxA oligomer analysis and siRNA epistasis

    PMID:25447205 PMID:26507657 PMID:27170750

    Open questions at the time
    • Reconciliation of dimer-active model with earlier monomer-active data incomplete
    • SUMOylation per se shown dispensable, leaving its in vivo role unclear
  15. 2017 High

    Defined the mechanochemical basis of MxA action by showing GTP-driven open/closed conformational cycling generates torque within the helical polymer.

    Evidence Single-molecule FRET with site-specific labeling under different nucleotide states, plus FRAP

    PMID:28548099

    Open questions at the time
    • Direct demonstration that torque disrupts viral RNP not yet shown
    • Link between polymer mechanics and monomer/dimer active units unresolved
  16. 2019 Medium

    Reinterpreted MxA cytoplasmic organization as membraneless, tonicity-responsive condensates that recruit viral nucleocapsid, revising earlier ER/Golgi localization models.

    Evidence Live-cell imaging, FRAP, 1,6-hexanediol and tonicity perturbation, and co-localization with VSV N protein

    PMID:16978069 PMID:31484749

    Open questions at the time
    • Single-lab condensate model conflicts with prior smooth-ER localization data
    • Functional necessity of condensate formation for restriction not isolated
  17. 2021 High

    Established human in vivo relevance by linking dominant-negative MX1 variants to susceptibility to zoonotic H7N9 influenza, confirming MxA as essential for antiviral defense.

    Evidence Whole-genome sequencing case-control study with cell-based functional and dominant-negative co-expression assays of variant MxA

    PMID:34413236

    Open questions at the time
    • Penetrance and contribution to seasonal influenza not addressed
    • Mechanism of dominant-negative interference at the polymer level not detailed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GTP-driven polymer mechanics, the monomer/dimer active species, and condensate formation integrate into a single physical mechanism for disrupting viral RNPs remains unresolved.
  • No atomic-resolution structure of MxA bound to a viral nucleocapsid
  • Unified reconciliation of monomer-, dimer-, and condensate-based models lacking
  • Functional roles of TRPC, tubulin, and SUMO interactions in physiology vs. antiviral defense undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 4 GO:0140313 molecular sequestering activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005829 cytosol 4 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3
Partners
BIPTRPC6TUBULINUAP56UBC9URH49

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 Constitutive expression of human MxA in transfected 3T3 cells conferred resistance to influenza A virus and vesicular stomatitis virus (VSV), but not to picornaviruses, togavirus, or herpes simplex virus type 1, establishing MxA as a specific cytoplasmic antiviral effector. The related MxB protein failed to confer resistance, confirming specificity. Stable transfection of 3T3 cells with MxA or MxB cDNA, followed by viral infection and yield assays Journal of virology High 2161946
1992 MxA protein has intrinsic GTPase activity (hydrolyzes GTP→GDP with Km ~0.1 mM, requires Mg2+, ~70 GTP molecules/min/molecule); amino acid substitution within the GTP-binding domain abolished activity. MxA also transiently binds cytoskeletal components including actin and tubulins. Immunoprecipitation of native MxA with polyclonal antibodies followed by GTPase activity assay; site-directed mutagenesis in transfected CHO cells Journal of virology High 1629950
1992 MxA mutant MxA(R645), carrying a Glu→Arg substitution near the carboxy terminus, retains anti-influenza activity but loses anti-VSV activity, defining the C-terminal region as a determinant of antiviral specificity. When relocated to the nucleus, MxA(R645) blocked influenza primary transcription like murine Mx1, demonstrating that nuclear localization shifts the step of inhibition. Site-directed mutagenesis; nuclear targeting with heterologous NLS; viral RNA accumulation assays The EMBO journal High 1314172
1991 Mouse Mx1 protein purified from E. coli has GTPase activity; amino acid substitution within the GTP-binding motif reduced activity. Mx1 is homologous to dynamin and yeast Vps1 not only in the GTPase motif but also over ~300 N-terminal amino acids, placing Mx proteins in the dynamin superfamily. Purification of recombinant Mx1 from E. coli; in vitro GTPase assay; site-directed mutagenesis The Journal of biological chemistry High 1657964
1993 Mouse Mx1 self-assembles into polymeric 'horseshoe'-like structures in vitro; GTP treatment induces conversion to larger tightly stacked helical forms. The main self-assembly motif maps to residues 51–99, conserved across Mx family and Mx-related proteins. Gel filtration; negative-stain electron microscopy of purified Mx1; deletion mutagenesis The Journal of biological chemistry High 8325879
1995 Purified recombinant His-MxA directly inhibited VSV in vitro transcription catalyzed by viral RNP complexes; inhibition of both leader RNA and mRNA synthesis indicates interference with transcription initiation. GTP binding (not hydrolysis) was required for anti-VSV activity, as GTP analogs non-hydrolyzable by MxA still abolished VSV inhibition. The C-terminal mutant MxA(E645R), despite normal GTPase activity, showed no inhibition of VSV in vitro transcription. In vitro VSV transcription assay with purified His-MxA; GTP analog experiments; mutant MxA proteins Virology High 7831809
1995 MxA expressed in the cytoplasm inhibits Thogoto virus accumulation of viral RNA and proteins; MxA(R645) remains active against Thogoto virus from both cytoplasm and nucleus, indicating a nuclear step is targeted. MxB had no antiviral activity against Thogoto or Dhori virus. Dhori virus is uniquely resistant to MxA but sensitive to murine Mx1. Stable transfection with MxA, MxA(R645), or MxB; viral RNA/protein accumulation assays; nuclear-targeted mutant Journal of virology High 7745744
1995 MxA GTPase activity has Km ~260 µM for GTP with turnover ~27 min⁻¹; MxA binds GTP with higher affinity (Kd ~20 µM) than GDP (Kd ~100 µM), suggesting a high proportion of GTP-loaded MxA in vivo. Guanine nucleotides do not co-purify with MxA, and it forms high-molecular-weight oligomers in solution. Recombinant His-MxA expressed in E. coli; fluorescent nucleotide binding assays; gel filtration The Journal of biological chemistry High 7539429
1996 MxA inhibits representative members of all four genera of Bunyaviridae (Hantaan virus, La Crosse virus, Rift Valley fever virus, sandfly fever virus) by interfering with an early step in virus replication, preventing accumulation of viral transcripts and proteins; viral titers were reduced up to 10⁴-fold. Stable transfection of Vero cells with MxA cDNA; viral RNA/protein detection; plaque assays Journal of virology High 8551631
1998 MxA interacts with Thogoto virus RNP complexes in a GTPγS-dependent cosedimentation assay, demonstrating the first direct physical interaction between MxA GTPase and a viral target structure. MxA also forms oligomers in vivo as shown by nuclear translocation assay in mammalian cells. In vitro cosedimentation assay with purified MxA and viral RNP; nuclear translocation assay in intact cells Methods (San Diego, Calif.) Medium 9735310
1998 MxA C-terminus (downstream of aa 564) folds back to interact with an internal domain (aa 372–540); this intramolecular interaction requires Phe382 and Leu612 (part of a leucine zipper). Intermolecular oligomerization uses the same interaction surfaces; the outcome (monomer vs. oligomer) depends on whether the interaction is intra- or intermolecular. Yeast two-hybrid mapping; mammalian nuclear transport assay; site-directed mutagenesis of Phe382 and Leu612 The Journal of biological chemistry High 9774462
1998 Human MxA confers resistance to Semliki Forest virus (SFV), a positive-strand RNA togavirus, reducing viral yield up to 1,700-fold. MxA inhibited accumulation of 49S and 26S SFV RNA, indicating block early in replication. MxA inhibited an SFV replicon lacking structural proteins, showing the target is among viral nonstructural components. Stable MxA-transfected HEp-2 and U937 cells; SFV replicon transfection; viral RNA northern blot Journal of virology High 9445055
2000 Monomeric MxA(L612K), which lacks GTPase activity and fails to oligomerize, retains antiviral activity against Thogoto virus and VSV in transient transfection. This indicates that GTP hydrolysis is not required for antiviral function and that MxA monomers are antivirally active. Wild-type MxA high-molecular-weight oligomers serve as a stable intracellular pool from which active monomers are recruited. Site-directed mutagenesis (L612K); transient transfection in Vero cells; Thogoto minireplicon assay; GTPase activity measurement Journal of virology High 10933733
2002 MxA binds to the La Crosse virus (LACV) nucleocapsid (N) protein via its C-terminal GTPase effector domain (carboxy terminus), sequesters it into perinuclear fibrillary complexes visible by electron microscopy, and thereby prevents incorporation into new virions. The C-terminal mutant MxA(E645R) neither binds N protein nor causes complex formation. Co-immunoprecipitation; confocal microscopy co-localization; electron microscopy; C-terminal point mutant MxA(E645R) Proceedings of the National Academy of Sciences of the United States of America High 11880649
2002 Recombinant MxA protein assembles in vitro at physiological salt into ~20 nm-diameter filamentous structures; in the presence of guanosine nucleotides these rearrange into rings and compact helical arrays, indicating that GTP binding/hydrolysis drives conformational changes critical for antiviral function. Recombinant MxA production; sedimentation assay; negative-stain electron microscopy; nucleotide titration The Journal of biological chemistry High 11847228
2004 MxA colocalizes with and co-immunoprecipitates the nucleocapsid protein (NP) of Crimean-Congo hemorrhagic fever virus (CCHFV) in perinuclear regions; the E645R mutation in the C-terminal domain abolishes both antiviral activity and NP interaction, confirming C-terminal GED mediates target recognition. Confocal microscopy; co-immunoprecipitation; C-terminal mutant MxA(E645R); plaque assay Journal of virology High 15047845
2005 MxA physically interacts with the second ankyrin-like repeat domain of TRPC channels (TRPC1, -3, -4, -5, -6, -7) in yeast two-hybrid, GST pull-down, and co-immunoprecipitation assays. Co-expression of MxA with TRPC6 enhances agonist/OAG-induced Ca²⁺ entry; GTP binding (not hydrolysis) is required for this potentiation. Endogenous MxA upregulated by IFN-α also regulated TRPC6 activity. Yeast two-hybrid; GST pull-down; co-immunoprecipitation; Ca²⁺ imaging in HEK293T cells; GTP-binding mutants The Journal of biological chemistry Medium 15757897
2006 MxA localizes to a subcompartment of the smooth endoplasmic reticulum positive for Syntaxin17; overexpression causes redistribution of Hook3, mannose-6-phosphate receptor, and Lamp-1 to this MxA-positive compartment, but does not functionally affect endocytosis or the secretory pathway. Immunofluorescence co-localization with ER/Golgi markers; functional endocytosis assays; live-cell imaging Journal of interferon & cytokine research Medium 16978069
2008 Human MxA inhibits African swine fever virus (ASFV), a large double-stranded DNA virus, reducing replication 100-fold. MxA was recruited to perinuclear ASFV assembly sites surrounding virus factories, and a C-terminal MxA mutant lost this activity, extending MxA's known antiviral range to large dsDNA viruses. Stable MxA-transfected Vero cells; plaque assay; immunofluorescence co-localization with viral assembly sites; mutant MxA Journal of virology Medium 19109387
2009 MxA inhibits tumor cell motility and invasion in a GTPase-dependent manner. Co-immunoprecipitation showed MxA associates with tubulin, and a GTPase-inactivating mutation abolished both tubulin association and anti-motility activity. In vivo expression reduced hepatic metastases. Stable MxA expression in PC-3M and LOX cells; in vitro motility/invasion assays; co-immunoprecipitation with tubulin; GTPase mutant; intrasplenic injection mouse model The Journal of biological chemistry Medium 19297326
2010 MxA belongs to the dynamin superfamily: crystal structures of its oligomerized stalk (middle domain + GTPase effector domain) revealed the architecture of MxA oligomers and provided structural basis for antiviral function, including formation of ring-like structures around liposomes and liposome tubulation. Crystal structure determination (X-ray crystallography); liposome tubulation assay The Journal of biological chemistry High 20538602
2011 MxA directly interacts with cellular RNA helicases UAP56 and URH49 via in vitro binding with purified recombinant proteins; the MxA–UAP56/URH49 complex localizes to the perinuclear region in the cytoplasm. Mouse Mx1 also binds UAP56 and URH49, with the complex forming in distinct nuclear dots. These helicases are required for efficient IAV replication. Co-immunoprecipitation; in vitro binding with purified recombinant proteins; confocal microscopy co-localization The Journal of biological chemistry High 21859714
2011 MxA enhances ER stress signaling in influenza virus-infected cells and promotes tunicamycin-induced cell death. MxA interacts with the ER chaperone BiP, and BiP overexpression reduces MxA-promoted ER stress signaling. Co-immunoprecipitation of MxA with BiP; ER stress markers (BiP mRNA, XBP1 splicing); cell death assay with tunicamycin Journal of interferon & cytokine research Medium 21992152
2012 siRNA knockdown of MxA in IFN-α-treated primate cells abolished IFN-α-mediated suppression of influenza A virus replication. In MxA-stable Vero cells, strand-specific RT-PCR showed that MxA blocked viral replication at a step prior to primary transcription of gRNA into mRNA (suppressed mRNA, cRNA, and gRNA accumulation at 8 h post-infection). siRNA knockdown of MxA in A549 and LLC-MK2 cells; stable MxA-Vero cells; strand-specific RT-PCR; plaque assay Journal of virology High 23152507
2014 MxA is SUMOylated at Lys48 by SUMO2/3; it also interacts with SUMO1 via its CID-GED domain in a SIM-independent manner and with the SUMO E2 enzyme Ubc9 via its GTPase domain. Mutation of putative SIM motifs (SIMa, SIMb) reduced MxA antiviral activity. However, the SUMOylation-deficient mutant MxA(K48R) retained full antiviral activity against VSV and IAV, indicating SUMOylation itself is not required for antiviral function. Yeast two-hybrid screen; co-immunoprecipitation; confocal co-localization; site-directed mutagenesis; antiviral activity assays Experimental cell research Medium 25447205
2015 SUMO expression stabilizes MxA protein and increases the level of MxA oligomers in cells, providing a larger intracellular pool of MxA. Depletion of MxA in SUMO-expressing cells abolished SUMO-mediated resistance to VSV, demonstrating that MxA mediates SUMO-induced intrinsic anti-VSV resistance. Stable SUMO expression; MxA depletion by siRNA; MxA oligomer analysis; VSV replication assay Journal of virology Medium 27170750
2015 Dimeric MxA (produced by GTPγS-induced disassembly of oligomers) forms stable complexes with influenza A virus nucleoprotein (NP). Dimeric MxA binds NP from MxA-sensitive IAV strains but interacts much more weakly with NP from the MxA-resistant H1N1/1918 PR8 strain. Monomeric MxA restricted IAV replication but could not form stable NP complexes, suggesting dimers are the active NP-binding unit. GTPγS-induced MxA disassembly; native gel and analytical ultracentrifugation for stoichiometry; co-immunoprecipitation of MxA with viral NP; influenza infection assays The Journal of biological chemistry High 26507657
2017 Single-molecule FRET revealed that MxA GTPase domain–BSE can adopt 'open' or 'closed' conformations; GTP loading shifts preference to the 'closed' state and activates domain movement. Frequent movements between BSE and stalk via hinge 1 occur during GTP hydrolysis cycles, generating torque in the MxA helical polymer that may underlie its mechanochemical antiviral mechanism. Single-molecule FRET (smFRET) with MxA labeled at defined positions; nucleotide-loading experiments; FRAP Nature communications High 28548099
2019 MxA forms membraneless metastable cytoplasmic condensates (not ER/Golgi-associated membranes as previously believed); condensates undergo rapid reversible disassembly/reassembly driven by changes in extracellular tonicity. VSV nucleocapsid (N) protein associates with GFP-MxA condensates in infected cells showing antiviral effect. FRAP showed a mobile fraction of ~0.24, consistent with a higher-order network. Live-cell fluorescence microscopy; FRAP; 1,6-hexanediol treatment; tonicity manipulation; co-localization with VSV N protein Journal of virology Medium 31484749
2021 Rare heterozygous single-nucleotide variants in MX1 were strongly associated with human susceptibility to zoonotic H7N9 influenza. Most identified MxA variants lost antiviral activity against avian IAVs, and nearly all exerted dominant-negative effects on wild-type MxA function, indicating an effective MxA null phenotype in heterozygous carriers. Whole-genome sequencing case-control study; functional assays in transfected human cell lines with wild-type and variant MxA; dominant-negative co-expression experiments Science High 34413236
1994 Insect cell-purified murine Mx1 and human MxA both hydrolyze GTP with Km ~65 µM (Mx1) and ~62 µM (MxA); activity is strictly Mg2+-dependent and specific for guanine nucleotides. Mx1 is thermolabile at 10°C lower than MxA, and Mx1 shows ~340-fold higher affinity for GTPγS than GDP while MxA shows only ~30-fold difference, indicating distinct enzymatic properties. Purification of baculovirus-expressed Mx1 and MxA; GTPase kinetics; filter-binding nucleotide affinity assay The Journal of biological chemistry High 7507489
2015 IFNλ induces MxA expression in primary human dermal fibroblasts via a MAPK-dependent (p38 and p42/44) but STAT1-independent mechanism; inhibition of MAPK blocked MxA induction in fibroblasts but not in keratinocytes. This defines a cell-type-specific signaling pathway for MxA induction. IFNλ stimulation of primary dermal fibroblasts and keratinocytes; MAPK inhibitors (p38, MEK); STAT1 phosphorylation western blot; MxA western blot The Journal of investigative dermatology Medium 26288353

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1990 Resistance to influenza virus and vesicular stomatitis virus conferred by expression of human MxA protein. Journal of virology 374 2161946
2010 Human MxA protein: an interferon-induced dynamin-like GTPase with broad antiviral activity. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 294 21166595
1996 Inhibition of bunyaviruses, phleboviruses, and hantaviruses by human MxA protein. Journal of virology 193 8551631
2002 Antivirally active MxA protein sequesters La Crosse virus nucleocapsid protein into perinuclear complexes. Proceedings of the National Academy of Sciences of the United States of America 161 11880649
2019 Identification of Functionally Distinct Mx1+αSMA+ Periosteal Skeletal Stem Cells. Cell stem cell 156 31809737
1992 Interferon-induced human protein MxA is a GTPase which binds transiently to cellular proteins. Journal of virology 141 1629950
2016 Sarcoplasmic MxA expression: A valuable marker of dermatomyositis. Neurology 134 28039312
1992 Mechanism of human MxA protein action: variants with changed antiviral properties. The EMBO journal 127 1314172
1999 Human MxA protein protects mice lacking a functional alpha/beta interferon system against La crosse virus and other lethal viral infections. Journal of virology 124 10400797
1995 Human MxA protein inhibits tick-borne Thogoto virus but not Dhori virus. Journal of virology 122 7745744
1994 Cell type-specific MxA-mediated inhibition of measles virus transcription in human brain cells. Journal of virology 122 7933071
1998 Human MxA protein confers resistance to Semliki Forest virus and inhibits the amplification of a Semliki Forest virus-based replicon in the absence of viral structural proteins. Journal of virology 119 9445055
2001 The rainbow trout (Oncorhynchus mykiss) Mx1 promoter. Structural and functional characterization. European journal of biochemistry 108 11248675
2004 Human MxA protein inhibits the replication of Crimean-Congo hemorrhagic fever virus. Journal of virology 101 15047845
2016 Host genetics of severe influenza: from mouse Mx1 to human IRF7. Current opinion in immunology 100 26761402
1995 Expression of MxA protein in inflammatory dermatoses. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 93 7822763
2010 Dynamin-like MxA GTPase: structural insights into oligomerization and implications for antiviral activity. The Journal of biological chemistry 91 20538602
2020 SARS-CoV-2 Infection Boosts MX1 Antiviral Effector in COVID-19 Patients. iScience 84 32989429
2009 Hepatitis delta virus proteins repress hepatitis B virus enhancers and activate the alpha/beta interferon-inducible MxA gene. The Journal of general virology 83 19625466
1991 Interferon-inducible mouse Mx1 protein that confers resistance to influenza virus is GTPase. The Journal of biological chemistry 83 1657964
1996 Inhibition of puumala and tula hantaviruses in Vero cells by MxA protein. Virology 82 8862399
2002 Self-assembly of human MxA GTPase into highly ordered dynamin-like oligomers. The Journal of biological chemistry 79 11847228
1989 Regulation of the interferon-inducible IFI-78K gene, the human equivalent of the murine Mx gene, by interferons, double-stranded RNA, certain cytokines, and viruses. Journal of virology 79 2542574
1998 The MxA protein levels in whole blood lysates of patients with various viral infections. Journal of virological methods 77 9562412
1995 Vesicular stomatitis virus transcription inhibited by purified MxA protein. Virology 76 7831809
2008 Inhibition of a large double-stranded DNA virus by MxA protein. Journal of virology 74 19109387
2015 Diagnosis of viral infections using myxovirus resistance protein A (MxA). Pediatrics 71 25802344
2009 Epigenetic silencing of CRABP2 and MX1 in head and neck tumors. Neoplasia (New York, N.Y.) 68 20019841
2000 A monomeric GTPase-negative MxA mutant with antiviral activity. Journal of virology 68 10933733
1995 Interferon-induced MxA protein. GTP binding and GTP hydrolysis properties. The Journal of biological chemistry 68 7539429
1988 cDNA cloning and assignment to chromosome 21 of IFI-78K gene, the human equivalent of murine Mx gene. Somatic cell and molecular genetics 68 3162334
2021 Rare variant MX1 alleles increase human susceptibility to zoonotic H7N9 influenza virus. Science (New York, N.Y.) 66 34413236
2015 Oligomerization and GTP-binding Requirements of MxA for Viral Target Recognition and Antiviral Activity against Influenza A Virus. The Journal of biological chemistry 66 26507657
2006 Interferon-induced, antiviral human MxA protein localizes to a distinct subcompartment of the smooth endoplasmic reticulum. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 66 16978069
1993 Structure of mouse Mx1 protein. Molecular assembly and GTP-dependent conformational change. The Journal of biological chemistry 66 8325879
2019 Long Noncoding RNA Lnc-MxA Inhibits Beta Interferon Transcription by Forming RNA-DNA Triplexes at Its Promoter. Journal of virology 64 31434735
2003 Measurement of MxA mRNA or protein as a biomarker of IFNbeta bioactivity: detection of antibody-mediated decreased bioactivity (ADB). Neurology 63 14610107
2005 MxA, a member of the dynamin superfamily, interacts with the ankyrin-like repeat domain of TRPC. The Journal of biological chemistry 59 15757897
2013 An evolutionary perspective on the broad antiviral specificity of MxA. Current opinion in microbiology 56 23725670
1991 Molecular and functional analysis of the virus- and interferon-inducible human MxA promoter. Archives of virology 54 1706589
1998 Domains mediating intramolecular folding and oligomerization of MxA GTPase. The Journal of biological chemistry 51 9774462
1997 Expression of MxA protein in blood lymphocytes discriminates between viral and bacterial infections in febrile children. Pediatric research 51 9128286
2006 Expression of toll-like receptors and type 1 interferon specific protein MxA in biliary atresia. Laboratory investigation; a journal of technical methods and pathology 46 17075576
2009 Inhibition of tumor cell motility by the interferon-inducible GTPase MxA. The Journal of biological chemistry 44 19297326
1998 Characterization and expression of the Mx1 gene in wild mouse species. Biochemical genetics 44 9919357
2002 Polymorphisms and the antiviral property of porcine Mx1 protein. The Journal of veterinary medical science 43 12520098
2015 Mx1 and Mx2 key antiviral proteins are surprisingly lost in toothed whales. Proceedings of the National Academy of Sciences of the United States of America 42 26080416
2014 Blood MxA protein as a marker for respiratory virus infections in young children. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 42 25542463
2017 Conformational dynamics of dynamin-like MxA revealed by single-molecule FRET. Nature communications 39 28548099
2012 Myxovirus resistance gene A (MxA) expression suppresses influenza A virus replication in alpha interferon-treated primate cells. Journal of virology 39 23152507
1995 Mx1 but not MxA confers resistance against tick-borne Dhori virus in mice. Virology 37 7645224
2012 Type 1 IFN-induced protein MxA and plasmacytoid dendritic cells in lesions of morphea. Experimental dermatology 36 22507598
2013 Bat Mx1 and Oas1, but not Pkr are highly induced by bat interferon and viral infection. Developmental and comparative immunology 35 23541614
2011 Interferon-induced antiviral protein MxA interacts with the cellular RNA helicases UAP56 and URH49. The Journal of biological chemistry 35 21859714
2002 Promoted cell death of cells expressing human MxA by influenza virus infection. Microbiology and immunology 35 11911186
2019 Human Antiviral Protein MxA Forms Novel Metastable Membraneless Cytoplasmic Condensates Exhibiting Rapid Reversible Tonicity-Driven Phase Transitions. Journal of virology 32 31484749
2020 Myxovirus resistance 1 (MX1) is an independent predictor of poor outcome in invasive breast cancer. Breast cancer research and treatment 30 32350677
1994 Enzymatic characterization of interferon-induced antiviral GTPases murine Mx1 and human MxA proteins. The Journal of biological chemistry 30 7507489
2019 Mx1 in Hematopoietic Cells Protects against Thogoto Virus Infection. Journal of virology 28 31092574
1998 MxA GTPase: oligomerization and GTP-dependent interaction with viral RNP target structures. Methods (San Diego, Calif.) 28 9735310
2018 Porcine Mx1 Protein Inhibits Classical Swine Fever Virus Replication by Targeting Nonstructural Protein NS5B. Journal of virology 26 29343573
2011 Interferon-inducible antiviral protein MxA enhances cell death triggered by endoplasmic reticulum stress. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 26 21992152
2004 Genomic structure, organisation, and promoter analysis of the bovine (Bos taurus) Mx1 gene. Gene 26 14729264
1996 MxA protein in infants and children with respiratory tract infection. Acta paediatrica (Oslo, Norway : 1992) 26 8640043
2019 Cell-Penetrating Mx1 Enhances Anti-Viral Resistance against Mucosal Influenza Viral Infection. Viruses 25 30696001
2023 Influenza a virus regulates interferon signaling and its associated genes; MxA and STAT3 by cellular miR-141 to ensure viral replication. Virology journal 24 37596622
2004 Inhibition of Dugbe nairovirus replication by human MxA protein. Virus research 24 14687945
2004 Expression of interferon-alpha and Mx1 protein in pigs acutely infected with porcine reproductive and respiratory syndrome virus (PRRSV). Journal of comparative pathology 24 15053933
1999 MxA protein in capillary blood of children with viral infections. Journal of medical virology 24 10534740
2016 MxA Mediates SUMO-Induced Resistance to Vesicular Stomatitis Virus. Journal of virology 23 27170750
2016 Mx1 of black carp functions importantly in the antiviral innate immune response. Fish & shellfish immunology 23 27717902
2014 Interferon inducible antiviral MxA is inversely associated with prostate cancer and regulates cell cycle, invasion and Docetaxel induced apoptosis. The Prostate 23 25327819
2017 MxA is a positive regulator of type I IFN signaling in HCV infection. Journal of medical virology 22 28561372
2020 MxA suppresses TAK1-IKKα/β-NF-κB mediated inflammatory cytokine production to facilitate Mycobacterium tuberculosis infection. The Journal of infection 21 32445727
2015 IFNλ Stimulates MxA Production in Human Dermal Fibroblasts via a MAPK-Dependent STAT1-Independent Mechanism. The Journal of investigative dermatology 21 26288353
2014 Production of transgenic pigs over-expressing the antiviral gene Mx1. Cell regeneration (London, England) 21 25408889
2013 Mx1-cre mediated Rgs12 conditional knockout mice exhibit increased bone mass phenotype. Genesis (New York, N.Y. : 2000) 21 23349096
2018 SMARCA2-regulated host cell factors are required for MxA restriction of influenza A viruses. Scientific reports 20 29391557
2014 MxA interacts with and is modified by the SUMOylation machinery. Experimental cell research 20 25447205
2019 Effect of CRISPR/Cas9-mediated knockout of either Mx1 or ISG15 gene in EPC cells on resistance against VHSV infection. Fish & shellfish immunology 19 31465870
2010 IL-29 and IFN-α regulate the expression of MxA, 2',5'-OAS and PKR genes in association with the activation of Raf-MEK-ERK and PI3K-AKT signal pathways in HepG2.2.15 cells. Molecular biology reports 19 20309637
2007 Human MxA protein confers resistance to double-stranded RNA viruses of two virus families. The Journal of general virology 19 17374778
2013 Association of functional polymorphisms in the MxA gene with susceptibility to enterovirus 71 infection. Human genetics 18 24085612
2001 Intrahepatic MxA expression is correlated with interferon-alpha expression in chronic and fulminant hepatitis. The Journal of pathology 18 11523057
2006 Genomic structure, promoter analysis, and expression of the porcine (Sus scrofa) Mx1 gene. Immunogenetics 17 16738935
2019 Distinguishing pustular psoriasis and acute generalized exanthematous pustulosis on the basis of plasmacytoid dendritic cells and MxA protein. Journal of cutaneous pathology 16 30667074
2024 Bat-borne H9N2 influenza virus evades MxA restriction and exhibits efficient replication and transmission in ferrets. Nature communications 15 38664395
2006 Mx1 and IP-10: biomarkers to measure IFN-beta activity in mice following gene-based delivery. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 15 17032164
2001 Expression of human MxA protein in mosquito cells interferes with LaCrosse virus replication. Journal of virology 15 11222725
1996 Expression of the human MxA protein is associated with hyperphosphorylation of VSV P protein in human neural Cells. Virology 15 8659121
2020 Effects of early pregnancy on expression of interferon-stimulated gene 15, STAT1, OAS1, MX1, and IP-10 in ovine liver. Animal science journal = Nihon chikusan Gakkaiho 14 32329195
2015 Co-immunoprecipitation of the Mouse Mx1 Protein with the Influenza A Virus Nucleoprotein. Journal of visualized experiments : JoVE 14 25938860
2015 Structural analysis of tumor-related single amino acid mutations in human MxA protein. Chinese journal of cancer 14 26411585
2014 Cloning and characterization of the Mx1, Mx2 and Mx3 promoters from gilthead seabream (Sparus aurata). Fish & shellfish immunology 14 24704419
2014 MxA mRNA quantification and disability progression in interferon beta-treated multiple sclerosis patients. PloS one 14 24733382
2006 Single nucleotide polymorphisms and functional analysis of MxA promoter region in multiple sclerosis. Journal of the neurological sciences 14 16843495
2004 Genetic polymorphisms and antiviral activity in the bovine MX1 gene. Animal genetics 14 15147388
2019 MicroRNA-29b variants and MxA expression change during interferon beta therapy in patients with relapsing-remitting multiple sclerosis. Multiple sclerosis and related disorders 13 31421628
2013 Expression of bovine Mx1 protein inhibits the replication of foot-and-mouth disease virus in BHK-21 cells. Acta virologica 13 24294956
2003 MxA expression in patients with viral infection after allogeneic stem cell transplantation. Bone marrow transplantation 13 12858204

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