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Basic Characteristics of Mutations
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Mutation Site
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T100A |
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Mutation Site Sentence
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Notably, mutant ZIKV with T100A alteration in NS2A replicates much weaker than the wild-type virus. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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NS2A |
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Standardized Encoding Gene
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NS2A
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Genotype/Subtype
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Asian |
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Viral Reference
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KX377337
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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KPNA2
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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32924767
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Title
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Zika virus NS2A protein induces the degradation of KPNA2 (karyopherin subunit alpha 2) via chaperone-mediated autophagy
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Author
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He J,Yang L,Chang P,Yang S,Lin S,Tang Q,Wang X,Zhang YJ
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Journal
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Autophagy
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Journal Info
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2020 Dec;16(12):2238-2251
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Abstract
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KPNA2/importin-alpha1 (karyopherin subunit alpha 2) is the primary nucleocytoplasmic transporter for some transcription factors to activate cellular proliferation and differentiation. Aberrant increase of KPNA2 level is identified as a prognostic marker in a variety of cancers. Yet, the turnover mechanism of KPNA2 remains unknown. Here, we demonstrate that KPNA2 is degraded via the chaperone-mediated autophagy (CMA) and that Zika virus (ZIKV) enhances the KPNA2 degradation. KPNA2 contains a CMA motif, which possesses an indispensable residue Gln109 for the CMA-mediated degradation. RNAi-mediated knockdown of LAMP2A, a vital component of the CMA pathway, led to a higher level of KPNA2. Moreover, ZIKV reduced KPNA2 via the viral NS2A protein, which contains an essential residue Thr100 for inducing the CMA-mediated KPNA2 degradation. Notably, mutant ZIKV with T100A alteration in NS2A replicates much weaker than the wild-type virus. Also, knockdown of KPNA2 led to a higher ZIKV viral yield, which indicates that KPNA2 mediates certain antiviral effects. These data provide insights into the KPNA2 turnover and the ZIKV-cell interactions.
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Sequence Data
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-
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