UBC13

UBC13, commonly referred to as Ubc13 and encoded by the human gene UBE2N, is an E2 ubiquitin-conjugating enzyme that specializes in assembling Lys63-linked polyubiquitin chains. In human cells, Ubc13 functions in partnership with noncatalytic cofactors such as UEV1A (also known as MMS2) or UEV1B to form an active complex that promotes non-proteolytic ubiquitination events. The enzyme is conserved across eukaryotes.

The catalytic cycle begins when E1 activates ubiquitin and transfers it to Ubc13, which then cooperates with a UEV cofactor and an E3 ligase (for example RNF8 or TRAF6) to extend ubiquitin chains on substrate proteins. The UEV proteins lack the active-site cysteine and do not themselves become ubiquitinated; instead they shape the geometry and specificity of Lys63-linked chain formation by the Ubc13–UEV complex.

Biological roles of UBC13 include participation in the DNA damage tolerance pathway, where the Ubc13–UEV1A complex promotes Lys63-linked ubiquitination of PCNA and recruitment of repair factors, enabling error-free bypass of DNA lesions. It also participates in inflammatory signaling through NF-κB activation, where Lys63-linked chains produced by Ubc13–UEV1A/UEV1B serve as scaffolds for kinases such as TAK1 and IKK.

Defects in UBC13-related pathways can impair DNA repair and immune signaling. In model organisms, loss of UBC13 or its cofactors reduces the DNA damage response and immune activity. UBC13 is a subject of study in cancer biology and therapeutic development, with attention to selective inhibitors of Lys63-linked ubiquitination.