|
Basic Characteristics of Mutations
|
|
Mutation Site
|
E216K |
|
Mutation Site Sentence
|
As seen in Fig. 6, substitution of lysine for glutamate at position 216 (LT.LXCXK),disrupts Rb interactions with LT (Fig. 6A) but has no effect on the hVam6p interaction with LT (Fig. 6B). |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
Large T |
|
Standardized Encoding Gene
|
MCPyV_gp3
|
|
Genotype/Subtype
|
- |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
Cell line
|
|
Immune
|
- |
|
Target Gene
|
VPS39
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
- |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
21454559
|
|
Title
|
Merkel cell polyomavirus large T antigen disrupts lysosome clustering by translocating human Vam6p from the cytoplasm to the nucleus
|
|
Author
|
Liu X,Hein J,Richardson SC,Basse PH,Toptan T,Moore PS,Gjoerup OV,Chang Y
|
|
Journal
|
The Journal of biological chemistry
|
|
Journal Info
|
2011 May 13;286(19):17079-90
|
|
Abstract
|
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.
|
|
Sequence Data
|
-
|