CDC34 UniProt P49427
2 alternative isoforms · canonical 236 aa · nucleus; cytosol; cytoskeleton
CDC34 (UBE2R1/Ubc3) is a ubiquitin-conjugating enzyme (E2) that drives the G1-to-S cell cycle transition by assembling K48-linked polyubiquitin chains on regulatory substrates marked for proteasomal degradation [PMID:2842867, PMID:1848239]. Catalysis proceeds through a thioester at the active-site Cys95, and a dominant-negative C95S mutant blocks both growth and substrate ubiquitination, establishing the catalytic center [PMID:7592826]. CDC34 shows intrinsic kinetic selectivity for processive K48-linked multiubiquitination [PMID:1848239], with chain processivity and linkage specificity governed by a conserved acidic loop and catalytic-core residues that position the donor ubiquitin and lower the pKa of the attacking acceptor lysine [PMID:16360039, PMID:17698585, PMID:21474069, PMID:24129577]. CDC34 functions as the obligate E2 for SCF (Skp1–Cullin/Cdc53–F-box) cullin-RING ligases: Cdc53 scaffolds independent binding sites for CDC34 and Skp1, the RING subunit Hrt1/ROC1 stimulates activity, and the disordered acidic C-terminal tail mediates high-affinity electrostatic binding to the SCF basic canyon while also directly promoting ubiquitin transfer [PMID:9499404, PMID:10385629, PMID:19875449, PMID:25425648]. Through SCF complexes it ubiquitinates cell cycle regulators including Sic1, Swe1/Wee1, and p27Kip1 to license replication and mitotic entry [PMID:9285816, PMID:9716410, PMID:9836638, PMID:15652359], and acts with SCF(βTrCP) on phospho-IκBα in a UbcH5/CDC34 handoff in which a priming E2 attaches the first ubiquitin and CDC34 elongates the K48 chain [PMID:10918611, PMID:20347421]. CDC34 also mediates degradation of additional substrates (ATF5, hICERIIγ, B-Myb, c-Ski) and, in the case of Met4, catalyzes a non-proteolytic ubiquitination that inactivates a transcription factor without destroying it [PMID:10373550, PMID:10975521, PMID:10871850, PMID:15122324]. Its activity is tuned by CK2 phosphorylation of both the catalytic domain and acidic tail, which stimulates ubiquitin charging and accelerates cell cycle progression [PMID:17461777, PMID:18418079]. CDC34 is itself a substrate for autoubiquitination and SCF(βTrCP)-mediated turnover, from which the COP9 signalosome protects it [PMID:8383676, PMID:20378537].
Isoform tracks
Protein-residue axis (canonical frame). Top bar = canonical; each bar below is an isoform aligned on its shared region — extensions reach left of residue 1 (green), the lost region of a truncation is shaded on the canonical bar (red). Variant rows sit above (ClinVar/gnomAD/COSMIC, red = pathogenic, one row per consequence); below the bars are InterPro domains, disorder / coiled-coil / motifs, and per-cell-line initiation efficiency (dot size). Features are deduplicated across isoforms; hover any glyph for detail.