Annotation for mutations in human mitochondrial ERS. (A) Frequency distribution of residues at sites of ERS mutations. The distribution was calculated based on top 100 mammalian homologous sequences identified using BLAST. A ‘-’ represents frequency for gaps in the alignment. (B) Sequence alignment of mitochondrial ERS (UniProt ID Q5JPH6) and T. maritima ERS where substitutions in human protein are shown in boxes. Residues in T. maritima ERS that interact with ATP/analogue and tRNA are underlined in black and red respectively. Structural conservation for T. maritima ERS is graded in four categories <40%, 40-60%, 60-80%, and >80% which are highlighted as magenta, blue, green and red respectively. (C) Mutations (in parentheses) in human ERS mapped on to the crystal structure of T. maritima ERS where mutation in tRNA-binding interface is highlighted with boxed labels.