The recognition of ubiquitylated substrates is an essential element of ubiqu-itin⁄26S proteasome-mediated proteolysis (UPP), which is mediated directly by the proteasome subunit RPN10 and⁄or RPN13, or indirectly by ubiquitin receptors containing ubiquitin-like and ubiquitin-associated domains. By pull-down and mutagenesis assays, we detected cross-species divergence of the major recognition pathways.