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Protein

Ubiquitin-conjugating enzyme E2 R1

Gene

CDC34

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. 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. 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. 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. Also involved in the degradation of beta-catenin. Is target of human herpes virus 1 protein ICP0, leading to ICP0-dependent dynamic interaction with proteasomes (PubMed:10329681, PubMed:10373550, PubMed:10871850, PubMed:11675391, PubMed:12037680, PubMed:15652359, PubMed:17461777, PubMed:17698585, PubMed:19112177, PubMed:19126550, PubMed:19945379, PubMed:20061386, PubMed:20347421).14 Publications

Catalytic activityi

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.PROSITE-ProRule annotation4 Publications
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E1 ubiquitin-activating enzyme]-L-cysteine + N6-monoubiquitinyl-[acceptor protein]-L-lysine.1 Publication

Activity regulationi

CDC34-catalyzed polyubiquitin chain assembly activity is stimulated by the conjugation of NEDD8 to the CUL1 SCF E3 ligase complex subunit.1 Publication

Kineticsi

  1. KM=0.11 µM for beta-catenin-monoubiquin1 Publication

    Pathwayi: protein ubiquitination

    This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.PROSITE-ProRule annotation
    View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei93Glycyl thioester intermediate1

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionTransferase
    Biological processCell cycle, Ubl conjugation pathway
    LigandATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.3.2.B6 2681
    ReactomeiR-HSA-202424 Downstream TCR signaling
    R-HSA-2871837 FCERI mediated NF-kB activation
    R-HSA-5607764 CLEC7A (Dectin-1) signaling
    R-HSA-8866652 Synthesis of active ubiquitin: roles of E1 and E2 enzymes
    R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
    SignaLinkiP49427
    SIGNORiP49427
    UniPathwayi
    UPA00143

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Ubiquitin-conjugating enzyme E2 R1 (EC:2.3.2.234 Publications)
    Alternative name(s):
    (E3-independent) E2 ubiquitin-conjugating enzyme R1 (EC:2.3.2.241 Publication)
    E2 ubiquitin-conjugating enzyme R1
    Ubiquitin-conjugating enzyme E2-32 kDa complementing
    Ubiquitin-conjugating enzyme E2-CDC34
    Ubiquitin-protein ligase R1
    Gene namesi
    Name:CDC34
    Synonyms:UBCH3, UBE2R1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 19

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000099804.8
    HGNCiHGNC:1734 CDC34
    MIMi116948 gene
    neXtProtiNX_P49427

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi70Y → R: Loss of RBX1-binding. 1 Publication1
    Mutagenesisi85N → Q: Inhibits both mono and polyubiquitination of NFKBIA. 1 Publication1
    Mutagenesisi87Y → A: Decreases polyubiquitination of NFKBIA. 1 Publication1
    Mutagenesisi93C → S or A: Loss of function. 2 Publications1
    Mutagenesisi95S → D: Inhibits both mono and polyubiquitination of NFKBIA. 1 Publication1
    Mutagenesisi97L → S: Loss of function. 1 Publication1
    Mutagenesisi102D → A: Inhibits polyubiquitination of NFKBIA; when associated with A-103. 1 Publication1
    Mutagenesisi103D → A: Inhibits polyubiquitination of NFKBIA; when associated with A-102. 1 Publication1
    Mutagenesisi108E → A: Inhibits both mono and polyubiquitination of NFKBIA; when associated with A-112. 1 Publication1
    Mutagenesisi112E → A: Inhibits both mono andpolyubiquitination of NFKBIA; when associated with A-108. 1 Publication1
    Mutagenesisi117T → E: Loss of RBX1-binding. 1 Publication1
    Mutagenesisi129S → L: No effect on activity, when assayed in a Sic1-SCF-cdc4 ubiquitination assay. 1 Publication1
    Mutagenesisi129S → R: Complete loss of activity, when assayed in a Sic1-SCF-cdc4 ubiquitination assay. 1 Publication1
    Mutagenesisi133E → R: No effect on activity, when assayed in a Sic1-SCF-cdc4 ubiquitination assay. 1 Publication1
    Mutagenesisi138S → A: Decreases monoubiquitination of NFKBIA and inhibits polyubiquitination of NFKBIA. 1 Publication1
    Mutagenesisi143D → A: Inhibits polyubiquitination of NFKBIA; when associated with A-147; A-149; A-150 and A-153. 1 Publication1
    Mutagenesisi147M → A: Inhibits polyubiquitination of NFKBIA; when associated with A-143; A-149; A-150 and A-153. 1 Publication1
    Mutagenesisi149R → A: Inhibits polyubiquitination of NFKBIA; when associated with A-147; A-147; A-150 and A-153. 1 Publication1
    Mutagenesisi150K → A: Inhibits polyubiquitination of NFKBIA; when associated with A-143; A-147; A-149 and A-153. 1 Publication1
    Mutagenesisi153E → A: Inhibits polyubiquitination of NFKBIA; when associated with A-143; A-147; A-149 and A-150. 1 Publication1
    Mutagenesisi203S → A: Abolishes phosphorylation by CK2. Impairs nuclear localization; when associated with A-222; A-231; A-233 and A-236. 1 Publication1
    Mutagenesisi222S → A: Abolishes phosphorylation by CK2. Impairs nuclear localization; when associated with A-203; A-231; A-233 and A-236. 1 Publication1
    Mutagenesisi231S → A: Abolishes phosphorylation by CK2. Impairs nuclear localization; when associated with A-203; A-222; A-233 and A-236. 2 Publications1
    Mutagenesisi233T → A: Abolishes phosphorylation by CK2. Impairs nuclear localization; when associated with A-203; A-222; A-231 and A-236. 1 Publication1
    Mutagenesisi236S → A: Abolishes phosphorylation by CK2. Impairs nuclear localization; when associated with A-203; A-222; A-231 and A-233. 1 Publication1

    Organism-specific databases

    DisGeNETi997
    OpenTargetsiENSG00000099804
    PharmGKBiPA26265

    Polymorphism and mutation databases

    BioMutaiCDC34
    DMDMi2507505

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000824511 – 236Ubiquitin-conjugating enzyme E2 R1Add BLAST236

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei203Phosphoserine; by CK22 Publications1
    Modified residuei222Phosphoserine; by CK22 Publications1
    Modified residuei231Phosphoserine; by CK23 Publications1
    Modified residuei233Phosphothreonine; by CK21 Publication1
    Modified residuei236Phosphoserine; by CK21 Publication1

    Post-translational modificationi

    Autoubiquitinated (PubMed:22496338, PubMed:11805320, PubMed:12060736). Autoubiquitination is promoted by the human herpes virus 1 protein ICP0 and leads to degradation by the Ubiquitin-proteasomal pathway (PubMed:11805320, PubMed:12060736).3 Publications
    Phosphorylated by CK2. Phosphorylation of the C-terminal tail by CK2 controles the nuclear localization.3 Publications

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    EPDiP49427
    MaxQBiP49427
    PaxDbiP49427
    PeptideAtlasiP49427
    PRIDEiP49427
    ProteomicsDBi56009

    PTM databases

    iPTMnetiP49427
    PhosphoSitePlusiP49427

    Expressioni

    Tissue specificityi

    Expressed in testes during spermatogenesis to regulate repression of cAMP-induced transcription.1 Publication

    Inductioni

    Negatively regulated by the let-7 microRNA.1 Publication

    Gene expression databases

    BgeeiENSG00000099804 Expressed in 214 organ(s), highest expression level in testis
    CleanExiHS_CDC34
    ExpressionAtlasiP49427 baseline and differential
    GenevisibleiP49427 HS

    Organism-specific databases

    HPAiCAB005109
    CAB047311
    HPA002382

    Interactioni

    Subunit structurei

    Interacts with SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex. Identified in a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex together with HINT1 and RBX1. When cullin is neddylated, the interaction between the E2 and the SCF complex is strengthened (PubMed:10918611, PubMed:11675391, PubMed:18851830, PubMed:19945379, PubMed:19112177, PubMed:24316736). 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).11 Publications

    Binary interactionsi

    Protein-protein interaction databases

    BioGridi107432, 66 interactors
    CORUMiP49427
    DIPiDIP-37783N
    IntActiP49427, 19 interactors
    MINTiP49427
    STRINGi9606.ENSP00000215574

    Structurei

    Secondary structure

    1236
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliP49427
    SMRiP49427
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP49427

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni190 – 236SCF-bindingAdd BLAST47

    Compositional bias

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Compositional biasi200 – 236Asp/Glu-rich (acidic)Add BLAST37

    Domaini

    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.2 Publications

    Sequence similaritiesi

    Belongs to the ubiquitin-conjugating enzyme family.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiKOG0425 Eukaryota
    COG5078 LUCA
    GeneTreeiENSGT00730000110436
    HOGENOMiHOG000233454
    HOVERGENiHBG063308
    InParanoidiP49427
    KOiK02207
    OMAiCVKTKTP
    OrthoDBiEOG091G0O9F
    PhylomeDBiP49427
    TreeFamiTF101107

    Family and domain databases

    CDDicd00195 UBCc, 1 hit
    Gene3Di3.10.110.10, 1 hit
    InterProiView protein in InterPro
    IPR000608 UBQ-conjugat_E2
    IPR023313 UBQ-conjugating_AS
    IPR016135 UBQ-conjugating_enzyme/RWD
    PfamiView protein in Pfam
    PF00179 UQ_con, 1 hit
    SUPFAMiSSF54495 SSF54495, 1 hit
    PROSITEiView protein in PROSITE
    PS00183 UBIQUITIN_CONJUGAT_1, 1 hit
    PS50127 UBIQUITIN_CONJUGAT_2, 1 hit

    Sequence (1+)i

    Sequence statusi: Complete.

    This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

    P49427-1 [UniParc]FASTAAdd to basket
    « Hide
            10         20         30         40         50
    MARPLVPSSQ KALLLELKGL QEEPVEGFRV TLVDEGDLYN WEVAIFGPPN
    60 70 80 90 100
    TYYEGGYFKA RLKFPIDYPY SPPAFRFLTK MWHPNIYETG DVCISILHPP
    110 120 130 140 150
    VDDPQSGELP SERWNPTQNV RTILLSVISL LNEPNTFSPA NVDASVMYRK
    160 170 180 190 200
    WKESKGKDRE YTDIIRKQVL GTKVDAERDG VKVPTTLAEY CVKTKAPAPD
    210 220 230
    EGSDLFYDDY YEDGEVEEEA DSCFGDDEDD SGTEES
    Length:236
    Mass (Da):26,737
    Last modified:November 1, 1997 - v2
    Checksum:i258960666B589DB3
    GO

    Computationally mapped potential isoform sequencesi

    There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    U3KQ77U3KQ77_HUMAN
    Ubiquitin-conjugating enzyme E2 R1
    CDC34
    119Annotation score:
    U3KPV8U3KPV8_HUMAN
    Ubiquitin-conjugating enzyme E2 R1
    CDC34
    146Annotation score:
    U3KQP9U3KQP9_HUMAN
    Ubiquitin-conjugating enzyme E2 R1
    CDC34
    107Annotation score:

    Sequence cautioni

    The sequence AAC37534 differs from that shown. Reason: Erroneous initiation.Curated

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_021277227D → H1 PublicationCorresponds to variant dbSNP:rs16990650Ensembl.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    L22005 mRNA Translation: AAC37534.1 Different initiation.
    BT006659 mRNA Translation: AAP35305.1
    AY650399 Genomic DNA Translation: AAT46688.1
    AK291554 mRNA Translation: BAF84243.1
    CH471242 Genomic DNA Translation: EAW61190.1
    BC009850 mRNA Translation: AAH09850.1
    BC018143 mRNA Translation: AAH18143.1
    BC023979 mRNA Translation: AAH23979.1
    CCDSiCCDS12030.1
    PIRiA49630
    RefSeqiNP_004350.1, NM_004359.1
    UniGeneiHs.514997

    Genome annotation databases

    EnsembliENST00000215574; ENSP00000215574; ENSG00000099804
    GeneIDi997
    KEGGihsa:997
    UCSCiuc002lov.4 human

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    L22005 mRNA Translation: AAC37534.1 Different initiation.
    BT006659 mRNA Translation: AAP35305.1
    AY650399 Genomic DNA Translation: AAT46688.1
    AK291554 mRNA Translation: BAF84243.1
    CH471242 Genomic DNA Translation: EAW61190.1
    BC009850 mRNA Translation: AAH09850.1
    BC018143 mRNA Translation: AAH18143.1
    BC023979 mRNA Translation: AAH23979.1
    CCDSiCCDS12030.1
    PIRiA49630
    RefSeqiNP_004350.1, NM_004359.1
    UniGeneiHs.514997

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2OB4X-ray2.40A7-184[»]
    3RZ3X-ray2.30A/B/C/D7-184[»]
    4MDKX-ray2.61A/B/C/D7-184[»]
    ProteinModelPortaliP49427
    SMRiP49427
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi107432, 66 interactors
    CORUMiP49427
    DIPiDIP-37783N
    IntActiP49427, 19 interactors
    MINTiP49427
    STRINGi9606.ENSP00000215574

    PTM databases

    iPTMnetiP49427
    PhosphoSitePlusiP49427

    Polymorphism and mutation databases

    BioMutaiCDC34
    DMDMi2507505

    Proteomic databases

    EPDiP49427
    MaxQBiP49427
    PaxDbiP49427
    PeptideAtlasiP49427
    PRIDEiP49427
    ProteomicsDBi56009

    Protocols and materials databases

    DNASUi997
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000215574; ENSP00000215574; ENSG00000099804
    GeneIDi997
    KEGGihsa:997
    UCSCiuc002lov.4 human

    Organism-specific databases

    CTDi997
    DisGeNETi997
    EuPathDBiHostDB:ENSG00000099804.8
    GeneCardsiCDC34
    HGNCiHGNC:1734 CDC34
    HPAiCAB005109
    CAB047311
    HPA002382
    MIMi116948 gene
    neXtProtiNX_P49427
    OpenTargetsiENSG00000099804
    PharmGKBiPA26265
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG0425 Eukaryota
    COG5078 LUCA
    GeneTreeiENSGT00730000110436
    HOGENOMiHOG000233454
    HOVERGENiHBG063308
    InParanoidiP49427
    KOiK02207
    OMAiCVKTKTP
    OrthoDBiEOG091G0O9F
    PhylomeDBiP49427
    TreeFamiTF101107

    Enzyme and pathway databases

    UniPathwayi
    UPA00143

    BRENDAi2.3.2.B6 2681
    ReactomeiR-HSA-202424 Downstream TCR signaling
    R-HSA-2871837 FCERI mediated NF-kB activation
    R-HSA-5607764 CLEC7A (Dectin-1) signaling
    R-HSA-8866652 Synthesis of active ubiquitin: roles of E1 and E2 enzymes
    R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
    SignaLinkiP49427
    SIGNORiP49427

    Miscellaneous databases

    ChiTaRSiCDC34 human
    EvolutionaryTraceiP49427
    GeneWikiiCDC34
    GenomeRNAii997
    PROiPR:P49427
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000099804 Expressed in 214 organ(s), highest expression level in testis
    CleanExiHS_CDC34
    ExpressionAtlasiP49427 baseline and differential
    GenevisibleiP49427 HS

    Family and domain databases

    CDDicd00195 UBCc, 1 hit
    Gene3Di3.10.110.10, 1 hit
    InterProiView protein in InterPro
    IPR000608 UBQ-conjugat_E2
    IPR023313 UBQ-conjugating_AS
    IPR016135 UBQ-conjugating_enzyme/RWD
    PfamiView protein in Pfam
    PF00179 UQ_con, 1 hit
    SUPFAMiSSF54495 SSF54495, 1 hit
    PROSITEiView protein in PROSITE
    PS00183 UBIQUITIN_CONJUGAT_1, 1 hit
    PS50127 UBIQUITIN_CONJUGAT_2, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiUB2R1_HUMAN
    AccessioniPrimary (citable) accession number: P49427
    Secondary accession number(s): A8K689
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: November 1, 1997
    Last modified: November 7, 2018
    This is version 177 of the entry and version 2 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    7. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
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