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Basic Characteristics of Mutations
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Mutation Site
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Y206A |
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Mutation Site Sentence
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MCV LT alanine substitution mutants, GST.LT(1-258).R204A, T205A, Y206A, G207A, T208A, and W209A were generated using the QuikChange Lighting Site-directed Mutagenesis Kit (Agilent) using GST. |
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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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Large T |
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Standardized Encoding Gene
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MCPyV_gp3
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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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VPS39
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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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21454559
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Title
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Merkel cell polyomavirus large T antigen disrupts lysosome clustering by translocating human Vam6p from the cytoplasm to the nucleus
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Author
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Liu X,Hein J,Richardson SC,Basse PH,Toptan T,Moore PS,Gjoerup OV,Chang Y
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Journal
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The Journal of biological chemistry
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Journal Info
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2011 May 13;286(19):17079-90
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Abstract
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Merkel cell polyomavirus (MCV) has been recently described as the cause for most human Merkel cell carcinomas. MCV is similar to simian virus 40 (SV40) and encodes a nuclear large T (LT) oncoprotein that is usually mutated to eliminate viral replication among tumor-derived MCV. We identified the hVam6p cytoplasmic protein involved in lysosomal processing as a novel interactor with MCV LT but not SV40 LT. hVam6p binds through its clathrin heavy chain homology domain to a unique region of MCV LT adjacent to the retinoblastoma binding site. MCV LT translocates hVam6p to the nucleus, sequestering it from involvement in lysosomal trafficking. A naturally occurring, tumor-derived mutant LT (MCV350) lacking a nuclear localization signal binds hVam6p but fails to inhibit hVam6p-induced lysosomal clustering. MCV has evolved a novel mechanism to target hVam6p that may contribute to viral uncoating or egress through lysosomal processing during virus replication.
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Sequence Data
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-
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