The type-2 N-end rule peptide recognition activity of Ubr11 ubiquitin ligase is required for the expression of peptide transporters

The Ubr1-like canonical N-recognins, widely conserved ubiquitin ligases in eukaryotes, play a role in the N-end rule pathway-mediated degradation of substrates harboring basic (type-1) or bulky hydrophobic (type-2) amino acids at the N-terminus. In this study, the roles of conserved domains were studied in the Schizosaccharomyces pombe Ubr11 protein. Mutations in the UBR box and the autoinhibitory domain blocked degradation of both type-1 and type-2 substrates, expression of peptide transporter genes, and the uptake of oligopeptides. An N-domain mutant was normal for the type-1-related function, but nevertheless failed to express peptide transporters. These data suggest the importance of the type-2-related activity of Ubr11 for its in vivo function.

► The UBR box and N-domain are conserved in all canonical Ubr N-recognins. ► Ubr11 is essential for expression of peptide transporters in Schizosaccharomyces pombe. ► Peptide uptake is completely abrogated in N-domain and UBR box mutants of Ubr11. ► An N-domain mutant can recognize peptides with an N-terminal basic (type-1) residue. ► Recognition of type-1 peptides by Ubr11 is insufficient for peptide transporter expression.