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Details on Person UniProt:P49427 CDC34

Class:IdReferenceGeneProduct:66737
_chainChangeLogchain:1-236 added on Fri February 6 2015
_displayNameUniProt:P49427 CDC34
_timestamp2025-02-21 19:44:35
chainchain:1-236
checksum258960666B589DB3
commentFUNCTION 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).CATALYTIC ACTIVITY S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine.CATALYTIC ACTIVITY S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E1 ubiquitin-activating enzyme]-L-cysteine + N(6)-monoubiquitinyl-[acceptor protein]-L-lysine.ACTIVITY REGULATION CDC34-catalyzed polyubiquitin chain assembly activity is stimulated by the conjugation of NEDD8 to the CUL1 SCF E3 ligase complex subunit.BIOPHYSICOCHEMICAL PROPERTIES Measured for E2-E3 complex composed of neddylated UBE2R1 and the CRL2(FEM1C) complex, using an 'Arg-48' donor ubiquitin.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Interacts with multiple Cul1-RING E3 ubiquitin-protein ligase complexes, also known as SCF (SKP1-CUL1-F-box protein) complexes (PubMed:10918611, PubMed:11675391, PubMed:18851830, PubMed:19112177, PubMed:19945379, PubMed:24316736). Identified in a SCF E3 ubiquitin ligase complex together with HINT1 and RBX1 (PubMed:19112177). When cullin is neddylated, the interaction between the E2 and the SCF complex is strengthened (PubMed:10918611, PubMed:11675391, PubMed:18851830, PubMed:19112177, PubMed:19945379, PubMed:24316736). Interacts with multiple Cul2-RING (CRL2) E3 ubiquitin-protein ligase complexes, also known as ECS (Elongin BC-CUL2/5-SOCS-box protein) complexes (PubMed:38326650). When phosphorylated, interacts with beta-TrCP (BTRC) (PubMed:12037680). Interacts with human herpes virus 1 protein ICP0 and associates with the proteasome for degradation (PubMed:11447293, PubMed:11805320, PubMed:12060736). Interacts with casein kinase subunit CSNK2B (PubMed:11546811). Interacts with CNTD1; this interaction regulates the cell-cycle progression (By similarity).INTERACTION The phosphorylation of the C-terminal tail plays an important role in mediating nuclear localization. Colocalizes with beta-tubulin on mitotic spindles in anaphase.TISSUE SPECIFICITY Expressed in testes during spermatogenesis to regulate repression of cAMP-induced transcription.INDUCTION Negatively regulated by the let-7 microRNA.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.PTM 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).PTM Phosphorylated by CK2. Phosphorylation of the C-terminal tail by CK2 controls the nuclear localization.SIMILARITY Belongs to the ubiquitin-conjugating enzyme family.
descriptionrecommendedName: Ubiquitin-conjugating enzyme E2 R1 ecNumber evidence="14 19 24 25 28"2.3.2.23 alternativeName: (E3-independent) E2 ubiquitin-conjugating enzyme R1 ecNumber evidence="18"2.3.2.24 alternativeName: E2 ubiquitin-conjugating enzyme R1 alternativeName: Ubiquitin-conjugating enzyme E2-32 kDa complementing alternativeName: Ubiquitin-conjugating enzyme E2-CDC34 alternativeName: Ubiquitin-protein ligase R1
geneNameCDC34
UBCH3
UBE2R1
identifierP49427
isSequenceChangedFALSE
keyword3D-structure
ATP-binding
Cell cycle
Cytoplasm
Nucleotide-binding
Nucleus
Phosphoprotein
Proteomics identification
Reference proteome
Transferase
Ubl conjugation
Ubl conjugation pathway
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
nameCDC34
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8993975] ENSEMBL:ENSG00000099804 CDC34 [Homo sapiens]
secondaryIdentifierUB2R1_HUMAN
A8K689
sequenceLength236
species[Species:48887] Homo sapiens
(referenceEntity)[EntityWithAccessionedSequence:947621] CDC34 [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:2022820] CDC34 [nucleoplasm] [Homo sapiens]
[EntityWithAccessionedSequence:8852125] CDC34 [nucleoplasm] [Homo sapiens]
[EntityWithAccessionedSequence:8864170] Ub-C93-CDC34 [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:8864204] Ub-C93-CDC34 [nucleoplasm] [Homo sapiens]
(referenceSequence)[ModifiedResidue:8864196] S-(glycyl)-L-cysteine (Cys-Gly) at 93
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No pathways have been reviewed or authored by UniProt:P49427 CDC34 (66737)