Uev1a/UBE2V1: Proteins and Enzymes

Ubiquitin-conjugating Enzyme Variant 1a (Uev1a), also known as Ubiquitin-conjugating Enzyme E2 Variant 1 (UBE2V1), is a member of the Ubiquitin-conjugating (E2) enzyme family. Human Uev1a/UBE2V1 and its mouse ortholog have predicted molecular weights of 19 kDa and 16.5 kDa, respectively. The human protein shares 89% amino acid (aa) sequence identity with its mouse ortholog. The E2 catalytic core domain of Uev1a/UBE2V1 lacks an active site cysteine residue, rendering it catalytically inactive on its own. However, in the cytoplasm Uev1a/UBE2V1 is able to form a catalytically active complex with UBE2N/Ubc13, which mediates the synthesis Lys63-linked Ubiquitin chains and is required for NF-kappa B activation. Uev1a/UBE2V1 is required for UBE2N (Ubc13)/Uev1a Complex-dependent Lys63-linked Ubiquitin chain formation. More specifically, Uev1a/UBE2V1 orients the Ubiquitin molecule to favor linkage at Lys63 via a non-covalent interaction with the Ubiquitin molecule. The human protein contains a non-conserved 30 aa N-terminal tail that functionally differentiates it from Mms2, another E2 enzyme variant and UBE2N/Ubc13 binding partner. Pharmacological inhibition of the UBE2N (Ubc13)/Uev1a Complex blocks the proliferation of diffuse large B-cell lymphoma cells, suggesting that this complex may play a role in cancer.