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:29779948, PubMed:29775578). 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:9122164, PubMed:10973499, PubMed:11384984, PubMed:12609982, PubMed:24076655). 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:9122164, PubMed:10973499, PubMed:26138980, PubMed:29779948, PubMed:29775578). ECS(VHL) mediates the ubiquitination of hypoxia-inducible factor (HIF) (PubMed:9122164, PubMed:10973499). 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:29779948, PubMed:29775578). ECS complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:27565346). Protein modification; protein ubiquitination. Component of multiple ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes formed of CUL2, Elongin BC (ELOB and ELOC), RBX1 and a variable substrate-specific adapter (PubMed:9122164, PubMed:10973499, PubMed:11384984, PubMed:26138980, PubMed:29779948, PubMed:29775578). Component of the ECS(VHL) or CBC(VHL) complex containing VHL (PubMed:9122164, PubMed:10973499, PubMed:11384984). Component of the ECS(MED8) complex with the probable substrate recognition component MED8 (PubMed:12149480). Component of multiple ECS complexes part of the DesCEND (destruction via C-end degrons) pathway, which contain either KLHDC2, KLHDC3, KLHDC10, APPBP2, FEM1A, FEM1B or FEM1C as substrate-recognition component (PubMed:23102700, PubMed:26138980, PubMed:29779948, PubMed:29775578). Component of the ECS(LRR1) complex with the probable substrate recognition component LRR1 (PubMed:15601820). Component of a probable ECS E3 ubiquitin-protein ligase complex containing CUL2, RBX1, ELOB, ELOC and FEM1B (PubMed:15601820). Part of an E3 ubiquitin-protein ligase complex including ZYG11B, CUL2 and Elongin BC (PubMed:17304241). Part of an E3 ubiquitin-protein ligase complex including ZER1, CUL2 and Elongin BC (PubMed:17304241). Interacts with RBX1, RNF7, FEM1B and TIP120A/CAND1 (PubMed:10230407, PubMed:12609982). Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, ELOB and CUL2 (PubMed:22286099). Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1 (PubMed:24076655, PubMed:27565346). Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions promote the cullin neddylation (PubMed:23401859, PubMed:23201271, PubMed:24192928, PubMed:26906416). Component of VCB (elongins BC/CUL2/VHL) complex that contains at least DCUN1D1, CUL2 and VHL; this complex triggers CUL2 neddylation and consequently cullin ring ligase (CRL) substrates polyubiquitylation (PubMed:23401859). (Microbial infection) Interacts with human respiratory syncytial virus (HRSV) protein NS1. Neddylated; which enhances the ubiquitination activity of ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes. CBC(VHL) complex formation seems to promote neddylation. Deneddylated via its interaction with the COP9 signalosome (CSN) complex (By similarity). Belongs to the cullin family.