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Basic Characteristics of Mutations
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Mutation Site
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V121A |
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Mutation Site Sentence
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A NS5A V121A mutation disrupted the NS5A-HNF-1alpha interaction as well as the degradation of HNF-1alpha. |
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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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NS5A |
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Standardized Encoding Gene
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NS5A
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Genotype/Subtype
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- |
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Viral Reference
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-
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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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-
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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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25957097
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Title
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A single-amino-acid mutation in hepatitis C virus NS5A disrupts physical and functional interaction with the transcription factor HNF-1alpha
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Author
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Matsui C,Rosalyn Sianipar I,Minami N,Deng L,Hotta H,Shoji I
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Journal
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The Journal of general virology
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Journal Info
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2015 Aug;96(8):2200-2205
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Abstract
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Hepatitis C virus (HCV) infection often causes extrahepatic manifestations, such as type 2 diabetes. We previously reported that HCV infection induces the lysosomal degradation of the transcription factor HNF-1alpha via an interaction with viral NS5A, thereby suppressing GLUT2 gene expression. However, the molecular mechanism of NS5A-induced degradation of HNF-1alpha is largely unknown. We aimed to identify the determinants necessary for the degradation of HNF-1alpha induced by NS5A. Coimmunoprecipitation analysis revealed that the POU specific (POUs) domain spanning from aa 91 to 181 of HNF-1alpha is responsible for the interaction of NS5A. We also found that the region from aa 121 to 126 of NS5A, which is known as the binding motif of the HCV replication factor FKBP8, is important for the degradation of HNF-1alpha. A NS5A V121A mutation disrupted the NS5A-HNF-1alpha interaction as well as the degradation of HNF-1alpha. Our findings suggest that NS5A Val121 is crucial for viral pathogenesis.
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Sequence Data
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-
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