CUL2
Domain
The Cullin neddylation domain restrains the RING domain of RBX1 in the E3 ubiquitin-protein ligase complex; this restraint is removed upon neddylation of the cullin.
Function
Core component of multiple cullin-RING-based ECS (ElonginB/C-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of target proteins (PubMed:11384984, PubMed:26138980, PubMed:29775578, PubMed:29779948, PubMed:38326650). CUL2 serves as a rigid scaffold in the complex and may contribute to catalysis through positioning of the substrate and the E2 ubiquitin-conjugating enzyme (PubMed:10973499, PubMed:11384984, PubMed:12609982, PubMed:24076655, PubMed:9122164, PubMed:38326650). The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1 (PubMed:12609982, PubMed:24076655, PubMed:27565346, PubMed:38326650). The functional specificity of the ECS complex depends on the substrate recognition component (PubMed:10973499, PubMed:26138980, PubMed:29775578, PubMed:29779948, PubMed:9122164, PubMed:38326650). ECS(VHL) mediates the ubiquitination of hypoxia-inducible factor (HIF) (PubMed:10973499, PubMed:9122164). A number of ECS complexes (containing either KLHDC2, KLHDC3, KLHDC10, APPBP2, FEM1A, FEM1B or FEM1C as substrate-recognition component) are part of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (PubMed:26138980, PubMed:29775578, PubMed:29779948). ECS complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:27565346). ECS(LRR1) ubiquitinates MCM7 and promotes CMG replisome disassembly by VCP and chromatin extraction during S-phase (By similarity).
Pathway
Protein modification; protein ubiquitination.
Post-translational modifications
Neddylated; which enhances the ubiquitination activity of ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes (PubMed:24076655, PubMed:27565346, PubMed:38326650). Neddylation leads to structural rearrangment in the complex that allows interaction between the E2 ubiquitin-conjugating enzyme and the acceptor ubiquitin (PubMed:38326650). CBC(VHL) complex formation seems to promote neddylation. Deneddylated via its interaction with the COP9 signalosome (CSN) complex (By similarity).
Sequence Similarities
Belongs to the cullin family.
Cellular localization
- Nucleus
Alternative names
Cullin-2, CUL-2, CUL2