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Basic Characteristics of Mutations
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Mutation Site
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F132A |
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Mutation Site Sentence
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Mutation of this site (F132A) results in defect in Smc5/6 interaction, extrachromosomal reporter transcription, and HBV production both in cells and in mouse model. |
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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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X |
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Standardized Encoding Gene
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X
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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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SMC5
SMC6
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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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36592669
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Title
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Identification of critical residues in the regulatory protein HBx for Smc5/6 interaction and hepatitis B virus production
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Author
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He L,Shen H,Deng H,Zhang X,Xu Y,Shi C,Ouyang Z
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Journal
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Antiviral research
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Journal Info
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2023 Mar;211:105519
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Abstract
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The host structural maintenance of chromosomes 5/6 complex (Smc5/6) is a restriction factor of hepatitis B virus (HBV) that inhibits the transcription of viral ccDNA. HBV antagonizes this restriction by expressing the regulatory X protein (HBx) which targets Smc5/6 for degradation via DNA damage-binding protein 1 (DDB1) E3 ubiquitin ligase. However, the molecular insights into how Smc5/6 interacts with HBx remain elusive. In this study, we systematically investigated the interaction between Smc5/6 and HBx. Smc5/6 interacts with HBx through multiple sites in the absence of DDB1 in the pull-down assay. HBx C-terminal is sufficient for the interaction. Most importantly, residue Phe132, which is strictly conserved in all HBV subtypes, is critical for interaction with Smc5/6 both in vitro and in vivo. Mutation of this site (F132A) results in defect in Smc5/6 interaction, extrachromosomal reporter transcription, and HBV production both in cells and in mouse model. Collectively, our data identifies a key residue on HBx for Smc5/6 interaction and viral production. These results provide valuable information for both basic research and therapeutic drugs targeting HBx.
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Sequence Data
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-
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