A complete functional map of UBE2I A complete functional map of UBE2I A complete functional map of UBE2I as resulting from the combination of the complementation screen and machine‐learning imputation and refinement. An impact score of 0 (blue) corresponds to a fitness equivalent to the empty vector control. A score of 1 (white) corresponds to a fitness equivalent to the wild‐type control. A score > 1 (red) corresponds to fitness above wild‐type levels. Shown above, for comparison are sequence conservation, secondary structure, solvent accessibility, and burial of the respective amino acid in protein–protein interaction interfaces with covalently and non‐covalently bound SUMO, the E1 UBA2, the sumoylation target RanGAP1, the E3 RanBP2 and UBE2I itself. Hydrogen bonds or salt bridges between residues and the respective interaction partner are marked with red asterisks. Residues buried in both the covalent SUMO and client interfaces are framed with dotted lines, marking the core members of the active site.UBE2I crystal structure with residues colored according to the median mutant fitness. Colors as in (A). The interacting substrate's ΨKxE motif is shown in green stick model; Covalently bound SUMO is shown as a red cartoon model; and non‐covalently bound SUMO is shown in brown cartoon model. The structures shown were obtained by alignment of PDB entries 3UIP and 2PE6.UBE2I crystal structure as in (B), with residues colored according to maximum mutant fitness. Jochen Weile et al. Mol Syst Biol 2017;13:957 © as stated in the article, figure or figure legend