CDC34
Domain
The C-terminal acidic tail is required for nuclear localization and is involved in the binding to SCF E3 ligase complexes, and more specifically with the CUL1 subunit.
Function
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).
Pathway
Protein modification; protein ubiquitination.
Post-translational modifications
Autoubiquitinated (PubMed:11805320, PubMed:12060736, PubMed:22496338). Autoubiquitination is promoted by the human herpes virus 1 protein ICP0 and leads to degradation by the Ubiquitin-proteasomal pathway (PubMed:11805320, PubMed:12060736).
Phosphorylated by CK2. Phosphorylation of the C-terminal tail by CK2 controls the nuclear localization.
Sequence Similarities
Belongs to the ubiquitin-conjugating enzyme family.
Tissue Specificity
Expressed in testes during spermatogenesis to regulate repression of cAMP-induced transcription.
Cellular localization
- Cytoplasm
- Nucleus
- The phosphorylation of the C-terminal tail plays an important role in mediating nuclear localization. Colocalizes with beta-tubulin on mitotic spindles in anaphase.
Alternative names
UBCH3, UBE2R1, CDC34, Ubiquitin-conjugating enzyme E2 R1, (E3-independent) E2 ubiquitin-conjugating enzyme R1, E2 ubiquitin-conjugating enzyme R1, Ubiquitin-conjugating enzyme E2-32 kDa complementing, Ubiquitin-conjugating enzyme E2-CDC34, Ubiquitin-protein ligase R1