Alignment of key functional domains of MCPyV, JC, and SV40 large T antigens. At the top is a cartoon of the protein structure of the predicted MCPyV large T antigen, based on its homology to the well-characterized SV40 large T antigen (modified from ). Underneath are expanded alignments for the Hsc70-binding motif and the pRb-binding motif, comparing the putative MCPyV large T antigen with the JC and SV40 large T antigens. Importantly, as indicated by the bold underlines below the zoom-ins, both the HPDK Hsc70-binding motif and the LxCxEx Rb-binding motifs are preserved in the predicted MCPyV large T antigen. Noted on the cartoon are the locations of the premature stop (MCV350) and frameshift (MCV339) mutations of the two known MCPyV genomes . These predicted truncated proteins potentially preserve some of the cell-cycle progression activities of the amino terminus of large T but prevent cell-lethal genomic instability related to the replicative functions of the carboxyl terminus.