These results indicated that UL44 possesses multiple SUMO target lysines that are located throughout the protein, in accordance with the observation that Ubc9 could bind to both N-and C-terminal portions of UL44 ( Fig. 1D and Fig. S1 ). Mutagenesis of several of these lysines in combination caused a strong decrease of UL44 expression (data not shown), likely due to protein misfolding and/or instability, making impossible to analyze the sumoylation state of the mutated protein and to compare it to that of wild-type UL44.