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Protein

Ubiquitin-conjugating enzyme E2 N

Gene

UBE2N

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

The UBE2V1-UBE2N and UBE2V2-UBE2N heterodimers catalyze the synthesis of non-canonical 'Lys-63'-linked polyubiquitin chains. This type of polyubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Acts together with the E3 ligases, HLTF and SHPRH, in the 'Lys-63'-linked poly-ubiquitination of PCNA upon genotoxic stress, which is required for DNA repair. Appears to act together with E3 ligase RNF5 in the 'Lys-63'-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes.5 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 annotation1 Publication

Enzyme regulationi

Activity is inhibited by binding to OTUB1, which prevents 'Lys-63'-linked polyubiquitination.3 Publications

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 sitei87Glycyl thioester intermediate1

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • poly(A) RNA binding Source: UniProtKB
  • ubiquitin binding Source: HGNC
  • ubiquitin conjugating enzyme activity Source: Ensembl
  • ubiquitin protein ligase activity Source: GO_Central
  • ubiquitin protein ligase binding Source: GO_Central
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

  • cellular protein modification process Source: ProtInc
  • DNA double-strand break processing Source: HGNC
  • double-strand break repair via homologous recombination Source: HGNC
  • double-strand break repair via nonhomologous end joining Source: Reactome
  • Fc-epsilon receptor signaling pathway Source: Reactome
  • global genome nucleotide-excision repair Source: Reactome
  • histone ubiquitination Source: HGNC
  • nucleotide-binding oligomerization domain containing signaling pathway Source: Reactome
  • positive regulation of DNA repair Source: HGNC
  • positive regulation of histone modification Source: HGNC
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: HGNC
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of ubiquitin-protein transferase activity Source: HGNC
  • postreplication repair Source: HGNC
  • protein K63-linked ubiquitination Source: UniProtKB
  • protein ubiquitination Source: HGNC
  • proteolysis Source: ProtInc
  • regulation of DNA repair Source: ProtInc
  • regulation of histone ubiquitination Source: HGNC
  • stimulatory C-type lectin receptor signaling pathway Source: Reactome
  • T cell receptor signaling pathway Source: UniProtKB
  • ubiquitin-dependent protein catabolic process Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

DNA damage, DNA repair, Ubl conjugation pathway

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS11278-MONOMER.
BRENDAi2.3.2.B6. 2681.
ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-168638. NOD1/2 Signaling Pathway.
R-HSA-202424. Downstream TCR signaling.
R-HSA-2871837. FCERI mediated NF-kB activation.
R-HSA-446652. Interleukin-1 signaling.
R-HSA-5607764. CLEC7A (Dectin-1) signaling.
R-HSA-5693565. Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
R-HSA-5693571. Nonhomologous End-Joining (NHEJ).
R-HSA-5693607. Processing of DNA double-strand break ends.
R-HSA-5696395. Formation of Incision Complex in GG-NER.
R-HSA-69473. G2/M DNA damage checkpoint.
R-HSA-937039. IRAK1 recruits IKK complex.
R-HSA-937041. IKK complex recruitment mediated by RIP1.
R-HSA-975110. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
R-HSA-975144. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiP61088.
SIGNORiP61088.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin-conjugating enzyme E2 N (EC:2.3.2.231 Publication)
Alternative name(s):
Bendless-like ubiquitin-conjugating enzyme
E2 ubiquitin-conjugating enzyme N
Ubc13
UbcH13
Ubiquitin carrier protein N
Ubiquitin-protein ligase N
Gene namesi
Name:UBE2N
Synonyms:BLU
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:12492. UBE2N.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • nucleolus Source: HPA
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • protein complex Source: MGI
  • UBC13-MMS2 complex Source: HGNC
  • UBC13-UEV1A complex Source: UniProtKB
  • ubiquitin ligase complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi87C → A: Loss of polyubiquitination of PCNA. Impairs interaction with SHPRH. 2 Publications1
Mutagenesisi92K → R: No ISGylation. 2 Publications1
Mutagenesisi94K → R: No effect on ISGylation. 1 Publication1

Organism-specific databases

DisGeNETi7334.
OpenTargetsiENSG00000177889.
PharmGKBiPA37141.

Chemistry databases

ChEMBLiCHEMBL6089.

Polymorphism and mutation databases

BioMutaiUBE2N.
DMDMi46577660.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000825021 – 152Ubiquitin-conjugating enzyme E2 NAdd BLAST152

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei82N6-acetyllysineCombined sources1
Disulfide bondi87Interchain (with C-78 in ISG15)1 Publication
Cross-linki92Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)2 Publications

Post-translational modificationi

Conjugation to ISG15 impairs formation of the thioester bond with ubiquitin but not interaction with UBE2V2.1 Publication

Keywords - PTMi

Acetylation, Disulfide bond, Isopeptide bond, Ubl conjugation

Proteomic databases

EPDiP61088.
PaxDbiP61088.
PeptideAtlasiP61088.
PRIDEiP61088.
TopDownProteomicsiP61088.

2D gel databases

OGPiQ16781.
REPRODUCTION-2DPAGEIPI00003949.

PTM databases

iPTMnetiP61088.
PhosphoSitePlusiP61088.
SwissPalmiP61088.

Expressioni

Gene expression databases

BgeeiENSG00000177889.
CleanExiHS_UBE2N.
ExpressionAtlasiP61088. baseline and differential.
GenevisibleiP61088. HS.

Organism-specific databases

HPAiHPA003962.
HPA044976.

Interactioni

Subunit structurei

Heterodimer with UBE2V2. Interacts (UBE2V2-UBE2N heterodimer) with the E3 ligase STUB1 (via the U-box domain); the complex has a specific 'Lys-63'-linked polyubiquitination activity. Interacts with RNF8 and RNF168. Interacts with RNF11. Interacts with the E3 ligases, HLTF and SHPRH; the interactions promote the 'Lys-63'-linked polyubiquitination of PCNA upon genotoxic stress and lead to DNA repair. Interacts with ARIH2 (via RING-type 2). Interacts with OTUB1; leading to inhibit E2-conjugating activity.16 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BIRC3Q134892EBI-1052908,EBI-517709
LRSAM1Q6UWE03EBI-1052908,EBI-720984
Map3k1Q6292544EBI-1052908,EBI-636664From a different organism.
RBCK1Q9BYM82EBI-1052908,EBI-2340624
RFWD3Q6PCD52EBI-1052908,EBI-2129159
RNF11Q9Y3C54EBI-1052908,EBI-396669
RNF13O435672EBI-1052908,EBI-2129183
RNF168Q8IYW52EBI-1052908,EBI-914207
RNF182Q8N6D22EBI-1052908,EBI-2130099
STUB1Q9UNE75EBI-1052908,EBI-357085
Stub1Q9WUD12EBI-1052908,EBI-773027From a different organism.
TRAF6Q9Y4K34EBI-1052908,EBI-359276
TRIM32Q130493EBI-1052908,EBI-742790
UBE2V1Q1340418EBI-1052908,EBI-1050671
UBE2V2Q158194EBI-1052908,EBI-714329
XIAPP981702EBI-1052908,EBI-517127
ZNRF1Q8ND254EBI-1052908,EBI-2129250

GO - Molecular functioni

  • ubiquitin binding Source: HGNC
  • ubiquitin protein ligase binding Source: GO_Central

Protein-protein interaction databases

BioGridi113182. 162 interactors.
DIPiDIP-29829N.
IntActiP61088. 134 interactors.
MINTiMINT-5001139.
STRINGi9606.ENSP00000316176.

Chemistry databases

BindingDBiP61088.

Structurei

Secondary structure

1152
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi6 – 17Combined sources12
Beta strandi23 – 27Combined sources5
Beta strandi34 – 40Combined sources7
Turni46 – 49Combined sources4
Beta strandi51 – 57Combined sources7
Turni60 – 64Combined sources5
Beta strandi68 – 71Combined sources4
Beta strandi78 – 80Combined sources3
Helixi89 – 91Combined sources3
Turni92 – 94Combined sources3
Helixi101 – 113Combined sources13
Beta strandi121 – 123Combined sources3
Helixi124 – 131Combined sources8
Helixi133 – 147Combined sources15
Beta strandi148 – 150Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1J7DX-ray1.85B1-152[»]
2C2VX-ray2.90B/E/H/K2-152[»]
3HCTX-ray2.10B1-152[»]
3HCUX-ray2.60B/D1-152[»]
3VONX-ray3.15C/E/G/J/L/N/Q/S/U/X/Z/b/e/g/i/l/n/p3-150[»]
3W31X-ray2.96B1-152[»]
4DHIX-ray1.80D1-152[»]
4DHJX-ray2.35C/G/K/N1-152[»]
4DHZX-ray3.11F1-152[»]
4IP3X-ray2.30B1-152[»]
4NR3X-ray1.80B2-150[»]
4NRGX-ray1.95B1-152[»]
4NRIX-ray2.30B3-150[»]
4ONLX-ray1.35B1-152[»]
4ONMX-ray1.35B1-152[»]
4ONNX-ray1.50B1-152[»]
4ORHX-ray4.80B/F/J1-152[»]
4TKPX-ray2.08A2-152[»]
4WHVX-ray8.30B/E/H/K1-152[»]
5AITX-ray3.40B/E1-152[»]
5AIUX-ray2.21B/E1-152[»]
5EYAX-ray2.40A/B1-152[»]
ProteinModelPortaliP61088.
SMRiP61088.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP61088.

Family & Domainsi

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0417. Eukaryota.
COG5078. LUCA.
GeneTreeiENSGT00540000070023.
HOGENOMiHOG000233455.
HOVERGENiHBG063308.
InParanoidiP61088.
KOiK10580.
OMAiIDKWSPA.
PhylomeDBiP61088.
TreeFamiTF101126.

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.

P61088-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAGLPRRIIK ETQRLLAEPV PGIKAEPDES NARYFHVVIA GPQDSPFEGG
60 70 80 90 100
TFKLELFLPE EYPMAAPKVR FMTKIYHPNV DKLGRICLDI LKDKWSPALQ
110 120 130 140 150
IRTVLLSIQA LLSAPNPDDP LANDVAEQWK TNEAQAIETA RAWTRLYAMN

NI
Length:152
Mass (Da):17,138
Last modified:April 26, 2004 - v1
Checksum:iFACD84D883D77407
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D83004 mRNA. Translation: BAA11675.1.
BT006873 mRNA. Translation: AAP35519.1.
BC000396 mRNA. Translation: AAH00396.1.
BC003365 mRNA. Translation: AAH03365.1.
BC108704 mRNA. Translation: AAI08705.1.
CCDSiCCDS31875.1.
PIRiJC4894.
RefSeqiNP_003339.1. NM_003348.3.
UniGeneiHs.524630.

Genome annotation databases

EnsembliENST00000318066; ENSP00000316176; ENSG00000177889.
GeneIDi7334.
KEGGihsa:7334.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D83004 mRNA. Translation: BAA11675.1.
BT006873 mRNA. Translation: AAP35519.1.
BC000396 mRNA. Translation: AAH00396.1.
BC003365 mRNA. Translation: AAH03365.1.
BC108704 mRNA. Translation: AAI08705.1.
CCDSiCCDS31875.1.
PIRiJC4894.
RefSeqiNP_003339.1. NM_003348.3.
UniGeneiHs.524630.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1J7DX-ray1.85B1-152[»]
2C2VX-ray2.90B/E/H/K2-152[»]
3HCTX-ray2.10B1-152[»]
3HCUX-ray2.60B/D1-152[»]
3VONX-ray3.15C/E/G/J/L/N/Q/S/U/X/Z/b/e/g/i/l/n/p3-150[»]
3W31X-ray2.96B1-152[»]
4DHIX-ray1.80D1-152[»]
4DHJX-ray2.35C/G/K/N1-152[»]
4DHZX-ray3.11F1-152[»]
4IP3X-ray2.30B1-152[»]
4NR3X-ray1.80B2-150[»]
4NRGX-ray1.95B1-152[»]
4NRIX-ray2.30B3-150[»]
4ONLX-ray1.35B1-152[»]
4ONMX-ray1.35B1-152[»]
4ONNX-ray1.50B1-152[»]
4ORHX-ray4.80B/F/J1-152[»]
4TKPX-ray2.08A2-152[»]
4WHVX-ray8.30B/E/H/K1-152[»]
5AITX-ray3.40B/E1-152[»]
5AIUX-ray2.21B/E1-152[»]
5EYAX-ray2.40A/B1-152[»]
ProteinModelPortaliP61088.
SMRiP61088.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113182. 162 interactors.
DIPiDIP-29829N.
IntActiP61088. 134 interactors.
MINTiMINT-5001139.
STRINGi9606.ENSP00000316176.

Chemistry databases

BindingDBiP61088.
ChEMBLiCHEMBL6089.

PTM databases

iPTMnetiP61088.
PhosphoSitePlusiP61088.
SwissPalmiP61088.

Polymorphism and mutation databases

BioMutaiUBE2N.
DMDMi46577660.

2D gel databases

OGPiQ16781.
REPRODUCTION-2DPAGEIPI00003949.

Proteomic databases

EPDiP61088.
PaxDbiP61088.
PeptideAtlasiP61088.
PRIDEiP61088.
TopDownProteomicsiP61088.

Protocols and materials databases

DNASUi7334.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000318066; ENSP00000316176; ENSG00000177889.
GeneIDi7334.
KEGGihsa:7334.

Organism-specific databases

CTDi7334.
DisGeNETi7334.
GeneCardsiUBE2N.
HGNCiHGNC:12492. UBE2N.
HPAiHPA003962.
HPA044976.
MIMi603679. gene.
neXtProtiNX_P61088.
OpenTargetsiENSG00000177889.
PharmGKBiPA37141.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0417. Eukaryota.
COG5078. LUCA.
GeneTreeiENSGT00540000070023.
HOGENOMiHOG000233455.
HOVERGENiHBG063308.
InParanoidiP61088.
KOiK10580.
OMAiIDKWSPA.
PhylomeDBiP61088.
TreeFamiTF101126.

Enzyme and pathway databases

UniPathwayiUPA00143.
BioCyciZFISH:HS11278-MONOMER.
BRENDAi2.3.2.B6. 2681.
ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-168638. NOD1/2 Signaling Pathway.
R-HSA-202424. Downstream TCR signaling.
R-HSA-2871837. FCERI mediated NF-kB activation.
R-HSA-446652. Interleukin-1 signaling.
R-HSA-5607764. CLEC7A (Dectin-1) signaling.
R-HSA-5693565. Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
R-HSA-5693571. Nonhomologous End-Joining (NHEJ).
R-HSA-5693607. Processing of DNA double-strand break ends.
R-HSA-5696395. Formation of Incision Complex in GG-NER.
R-HSA-69473. G2/M DNA damage checkpoint.
R-HSA-937039. IRAK1 recruits IKK complex.
R-HSA-937041. IKK complex recruitment mediated by RIP1.
R-HSA-975110. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
R-HSA-975144. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiP61088.
SIGNORiP61088.

Miscellaneous databases

ChiTaRSiUBE2N. human.
EvolutionaryTraceiP61088.
GeneWikiiUBE2N.
GenomeRNAii7334.
PROiP61088.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000177889.
CleanExiHS_UBE2N.
ExpressionAtlasiP61088. baseline and differential.
GenevisibleiP61088. 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 nameiUBE2N_HUMAN
AccessioniPrimary (citable) accession number: P61088
Secondary accession number(s): Q16781, Q53Y81
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: April 26, 2004
Last modified: November 30, 2016
This is version 158 of the entry and version 1 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. 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.