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). CUL2 may serve as a rigid scaffold in the complex and may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme (PubMed:10973499, PubMed:11384984, PubMed:12609982, PubMed:24076655, PubMed:9122164). 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). The functional specificity of the ECS complex depends on the substrate recognition component (PubMed:10973499, PubMed:26138980, PubMed:29775578, PubMed:29779948, PubMed:9122164). 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).
