UBE2V2: Proteins and Enzymes

Ubiquitin-conjugating Enzyme E2 Variant 2 (UBE2V2), also known as MMS2 and UEV2, is a 145 amino acid (aa) Ubiquitin-conjugating (E2) enzyme variant with a predicted molecular weight of approximately 16.5 kDa. The human protein shares 98% and 99% aa sequence identity with the mouse and rat orthologs, respectively. The E2 catalytic core domain of UBE2V2 lacks an active site cysteine residue, rendering it catalytically inactive. However, UBE2V2 can form a catalytically active complex with UBE2N/Ubc13 and this complex specifically catalyzes the formation of Lys63-linked poly-Ubiquitin chains. This complex forms foci in the nucleus following DNA damage and functions in multiple DNA repair pathways. The UBE2N/Ubc13-UBE2V2 complex interacts with the SHPRH and HLTF Ubiquitin ligases (E3s) to promote the poly-ubiquitination of PCNA, a key step in the postreplication repair pathway. Additionally, it functions with the RNF8 E3 to poly-ubiquitinate Histone H2A and Histone H2AX near DNA double-stranded breaks, which is required for the recruitment of DNA repair effector proteins.