NEDD8-conjugating enzyme UBE2F

UBE2F (NEDD8-conjugating enzyme UBE2F) is an E2 ubiquitin-like conjugating enzyme that accepts NEDD8 from the UBA3-NAE1 E1 complex and catalyzes its covalent attachment to target proteins (UniProt: Q969M7). Working with the E3 ligase RNF7/RBX2, UBE2F specifically neddylates cullin-5 (CUL5) and the CUL9-RBX1 complex, but not other cullins. The protein also participates in HIV-1 pathogenesis by mediating neddylation of CUL5 during APOBEC3G degradation following viral infection (UniProt: Q969M7).

UBE2F functions within the NEDD8 conjugation pathway, which regulates protein stability and cellular signaling through cullin-RING ligase (CRL) complexes. No Mendelian disease associations are documented in UniProt for this gene.

In Alzheimer's Disease, UBE2F shows ambiguous regulation across brain subcellular fractions, with a mean log2 fold-change of −0.209 relative to age-matched controls in post-mortem AD brain proteomics (Chaparral AD proteomics). This modest, inconsistent change across fractions suggests UBE2F expression is largely preserved in AD pathology, though its role in cullin-mediated protein degradation warrants further investigation in neurodegeneration contexts.