E2 ubiquitin-conjugating enzyme that accepts ubiquitin from an E1 ubiquitin-activating protein, and catalyzes its covalent attachment to other proteins by an E3 ubiquitin-protein ligase complex (PubMed:10329681, PubMed:17588522, PubMed:20061386, PubMed:38326650). In vitro catalyzes 'Lys-48'-linked polyubiquitination (PubMed:22496338). Cooperates with the E2 UBCH5C and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation (PubMed:10329681, PubMed:10918611, PubMed:17698585). Performs ubiquitin chain elongation building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. UBE2D3 acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin. Cooperates with the SCF(SKP2) E3 ligase complex to regulate cell proliferation through ubiquitination and degradation of MYBL2 and KIP1 (PubMed:10871850, PubMed:15652359, PubMed:19112177). Involved in ubiquitin conjugation and degradation of CREM isoform ICERIIgamma and ATF15 resulting in abrogation of ICERIIgamma- and ATF5-mediated repression of cAMP-induced transcription during both meiotic and mitotic cell cycles. Involved in the regulation of the cell cycle G2/M phase through its targeting of the WEE1 kinase for ubiquitination and degradation (PubMed:19126550). Also involved in the degradation of beta-catenin (PubMed:12037680). Is target of human herpes virus 1 protein ICP0, leading to ICP0-dependent dynamic interaction with proteasomes (PubMed:11805320, PubMed:12060736). {ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:10871850, ECO:0000269|PubMed:10918611, ECO:0000269|PubMed:11805320, ECO:0000269|PubMed:12037680, ECO:0000269|PubMed:12060736, ECO:0000269|PubMed:15652359, ECO:0000269|PubMed:17588522, ECO:0000269|PubMed:17698585, ECO:0000269|PubMed:19112177, ECO:0000269|PubMed:19126550, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:22496338, ECO:0000269|PubMed:38326650}. This is the function of CDC34 (cell division cycle 34, ubiquitin conjugating enzyme, ENSG00000099804).