Uev1A

UEV1A, also known as UBE2V1, is a ubiquitin-conjugating enzyme variant 1A, a small non-catalytic E2 enzyme in humans. It is part of the ubiquitin signaling system and functions as a cofactor of the E2 enzyme UBE2N (also called Ubc13). The protein forms a heterodimer with UBE2N and promotes formation of Lys63-linked polyubiquitin chains, which regulate signaling pathways rather than targeting proteins for proteasomal degradation.

Biological roles: Lys63-linked chains generated by Ubc13-Uev1A (and Ubc13-MMS2) are involved in activation of NF-κB signaling in response to TNF and IL-1, and in DNA damage tolerance pathways. Uev1A lacks the active-site cysteine necessary for ubiquitin transfer, hence it does not catalyze ubiquitin transfer by itself but modulates chain assembly via the Ubc13 active site.

Genetics and evolution: The gene encoding UEV1A is UBE2V1. It is one of two human UEV family members; the other is UBE2V2 (MMS2). UEV1A is conserved across eukaryotes, with homologs in yeast and other organisms.

Structure and expression: UEV1A is a small cytosolic protein of roughly 150 amino acids, lacking catalytic activity, and is broadly expressed in human tissues.

Clinical and research notes: Dysregulation of Lys63-linked ubiquitination can affect immune signaling and the DNA damage response; UBE2V1/UEV1A has been studied in the context of inflammatory signaling and cancer biology, though it is not currently a standalone therapeutic target.