Ubiquitin-conjugating enzyme E2 N

UBE2N (ubiquitin-conjugating enzyme E2 N) is a 152-amino acid E2 enzyme that catalyzes the synthesis of non-canonical Lys-63-linked polyubiquitin chains (UniProt: P61088). Operating as a heterodimer with UBE2V1 or UBE2V2, it mediates diverse cellular processes including transcriptional activation, cell-cycle progression, error-free DNA repair following genotoxic stress, and innate immune signaling through NF-κB and MAPK pathways. The enzyme also regulates ERAD and restricts viral capsid entry by promoting TRIM5 activity.

UBE2N participates in critical DNA damage responses, PCNA modification during repair, and inflammatory gene expression via IL-17 and interferon signaling cascades. Its involvement in non-proteasomal ubiquitination links it to cellular signaling rather than protein degradation, positioning it at the intersection of stress responses and immune regulation.

In Alzheimer's Disease, UBE2N is upregulated in post-mortem human brain tissue (mean log2FC +0.4776 across two subcellular fractions) relative to age-matched controls in a TMT-labeled quantitative proteomics study (Chaparral AD proteomics). This elevation suggests altered ubiquitin-signaling activity in AD pathology, potentially reflecting compensatory responses to proteotoxic stress or dysregulated immune activation in the diseased brain.