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Protein

Ubiquitin-conjugating enzyme E2 R1

Gene

CDC34

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. 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.13 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 + N(6)-monoubiquitinyl-[acceptor protein]-L-lysine.1 Publication

Enzyme 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

    • cellular protein modification process Source: UniProtKB
    • cellular response to interferon-beta Source: UniProtKB
    • DNA replication initiation Source: UniProtKB
    • G1/S transition of mitotic cell cycle Source: UniProtKB
    • negative regulation of cAMP-mediated signaling Source: UniProtKB
    • positive regulation of inclusion body assembly Source: Ensembl
    • positive regulation of neuron apoptotic process Source: Ensembl
    • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
    • protein K48-linked ubiquitination Source: UniProtKB
    • protein polyubiquitination Source: UniProtKB
    • protein ubiquitination Source: UniProtKB
    • response to growth factor Source: Ensembl
    Complete GO annotation...

    Keywords - Molecular functioni

    Transferase

    Keywords - Biological processi

    Cell cycle, Ubl conjugation pathway

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciZFISH:HS01911-MONOMER.
    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.
    UniPathwayiUPA00143.

    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

    HGNCiHGNC:1734. CDC34.

    Subcellular locationi

    • Cytoplasm
    • Nucleus

    • Note: The phosphorylation of the C-terminal tail plays an important role in mediating nuclear localization. Colocalizes with beta-tubulin on mitotic spindles in anaphase.

    GO - Cellular componenti

    • cytoplasm Source: HPA
    • nucleoplasm Source: HPA
    • nucleus Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    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
    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. Autoubiquitination is promoted by the human herpes virus 1 protein ICP0 and leads to degradation by the Ubiquitin-proteasomal pathway.2 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.

    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.
    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. When phosphorylated, interacts with beta-TrCP (BTRC). Interacts with human herpes virus 1 protein ICP0 and associates with the proteasome for degradation. Interacts with casein kinase subunit CSNK2B.11 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CUL1Q136163EBI-975634,EBI-359390
    SDCBPO005605EBI-975634,EBI-727004
    SIAH1Q8IUQ43EBI-975634,EBI-747107

    GO - Molecular functioni

    Protein-protein interaction databases

    BioGridi107432. 58 interactors.
    DIPiDIP-37783N.
    IntActiP49427. 17 interactors.
    MINTiMINT-238910.
    STRINGi9606.ENSP00000215574.

    Structurei

    Secondary structure

    1236
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi8 – 22Combined sources15
    Beta strandi28 – 32Combined sources5
    Beta strandi40 – 46Combined sources7
    Turni52 – 55Combined sources4
    Beta strandi57 – 63Combined sources7
    Turni66 – 69Combined sources4
    Beta strandi74 – 79Combined sources6
    Beta strandi90 – 92Combined sources3
    Helixi94 – 97Combined sources4
    Helixi120 – 132Combined sources13
    Helixi142 – 153Combined sources12
    Turni154 – 156Combined sources3
    Helixi160 – 178Combined sources19

    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...

    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.
    OMAiCFGEDED.
    OrthoDBiEOG091G0O9F.
    PhylomeDBiP49427.
    TreeFamiTF101107.

    Family and domain databases

    Gene3Di3.10.110.10. 1 hit.
    InterProiIPR000608. UBQ-conjugat_E2.
    IPR023313. UBQ-conjugating_AS.
    IPR016135. UBQ-conjugating_enzyme/RWD.
    [Graphical view]
    PfamiPF00179. UQ_con. 1 hit.
    [Graphical view]
    SUPFAMiSSF54495. SSF54495. 1 hit.
    PROSITEiPS00183. UBIQUITIN_CONJUGAT_1. 1 hit.
    PS50127. UBIQUITIN_CONJUGAT_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    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

    Sequence cautioni

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

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_021277227D → H.1 PublicationCorresponds to variant rs16990650dbSNPEnsembl.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

    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. 58 interactors.
    DIPiDIP-37783N.
    IntActiP49427. 17 interactors.
    MINTiMINT-238910.
    STRINGi9606.ENSP00000215574.

    PTM databases

    iPTMnetiP49427.
    PhosphoSitePlusiP49427.

    Polymorphism and mutation databases

    BioMutaiCDC34.
    DMDMi2507505.

    Proteomic databases

    EPDiP49427.
    MaxQBiP49427.
    PaxDbiP49427.
    PeptideAtlasiP49427.
    PRIDEiP49427.

    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.
    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.
    OMAiCFGEDED.
    OrthoDBiEOG091G0O9F.
    PhylomeDBiP49427.
    TreeFamiTF101107.

    Enzyme and pathway databases

    UniPathwayiUPA00143.
    BioCyciZFISH:HS01911-MONOMER.
    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

    EvolutionaryTraceiP49427.
    GeneWikiiCDC34.
    GenomeRNAii997.
    PROiP49427.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000099804.
    CleanExiHS_CDC34.
    ExpressionAtlasiP49427. baseline and differential.
    GenevisibleiP49427. HS.

    Family and domain databases

    Gene3Di3.10.110.10. 1 hit.
    InterProiIPR000608. UBQ-conjugat_E2.
    IPR023313. UBQ-conjugating_AS.
    IPR016135. UBQ-conjugating_enzyme/RWD.
    [Graphical view]
    PfamiPF00179. UQ_con. 1 hit.
    [Graphical view]
    SUPFAMiSSF54495. SSF54495. 1 hit.
    PROSITEiPS00183. UBIQUITIN_CONJUGAT_1. 1 hit.
    PS50127. UBIQUITIN_CONJUGAT_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiUB2R1_HUMAN
    AccessioniPrimary (citable) accession number: P49427
    Secondary accession number(s): A8K689
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: November 1, 1997
    Last modified: November 30, 2016
    This is version 163 of the entry and version 2 of the sequence. [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. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.