Figure 1. The mammalian Arg/N-end rule pathway and missense mutations in human UBR1 that underlie specific cases of the Johanson-Blizzard syndrome (JBS).

(A) The mammalian N-end rule pathway. N-terminal residues are indicated by single-letter abbreviations for amino acids. Yellow ovals denote the rest of a protein substrate. ‘Primary’, ‘secondary’ and ‘tertiary’ denote mechanistically distinct subsets of destabilizing N-terminal residues (see Introduction). C* denotes oxidized Cys, either Cys-sulfinate or Cys-sulfonate. MetAPs, Met-aminopeptidases. (B) Single-residue mutations in the UBR1 proteins of JBS patients #1 and #2. The positions of mutant residues are indicated both for the original mutations in human UBR1 and for their mimics in S. cerevisiae. (C) Same as in B but the mutation in UBR1 of patient #3 (see Results).