Cullin-2

Cullin-2 (CUL2) is a core scaffolding component of ElonginB/C-CUL2-SOCS-box protein (ECS) E3 ubiquitin-protein ligase complexes that mediate substrate ubiquitination and degradation (UniProt: Q13617). These complexes depend on CUL2 neddylation for catalytic activity and participate in diverse pathways including hypoxia response and the DesCEND pathway, which targets proteins bearing C-terminal degrons. CUL2 positions substrates and E2 enzymes to facilitate the ubiquitination reaction.

CUL2 is broadly expressed across tissues and participates in fundamental cellular degradation pathways including proteasomal protein turnover and replisome disassembly during DNA replication (UniProt: Q13617). No canonical disease associations are documented in UniProt records.

CUL2 is tagged as relevant to Alzheimer's Disease; however, proteomics evidence from human post-mortem AD brain shows ambiguous direction across subcellular fractions, with a mean log2 fold-change of −0.003 relative to age-matched controls (Chaparral AD proteomics). This near-zero change suggests minimal overall dysregulation of CUL2 protein abundance in AD pathology, though fraction-specific alterations cannot be excluded.