UEV-1

UEV-1 is a ubiquitin-conjugating enzyme variant, the human UEV1A/MMS2 protein, in which the catalytic cysteine of a canonical E2 has been lost during evolution. Instead of transferring ubiquitin itself, UEV-1 heterodimerizes tightly with UBE2N (UBC13), and the duo synthesizes K63-linked polyubiquitin chains that serve as non-proteolytic signaling scaffolds. These chains activate NF-κB through the TAK1 complex and mediate error-free postreplication DNA repair. UEV1A is expressed in proliferating cells and has been linked to cell cycle progression and tumorigenesis when overexpressed. Recombinant UEV-1 is routinely combined with UBE2N to generate K63 chains for signaling and enzyme studies.