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Protein

Ubiquitin-conjugating enzyme E2 N

Gene

UBE2N

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Activity regulationi

Activity is inhibited by binding to OTUB1, which prevents 'Lys-63'-linked polyubiquitination (PubMed:20725033, PubMed:22325355, PubMed:22367539). Activity is inhibited by GPS2, leading to prevent 'Lys-63'-linked polyubiquitination (By similarity).By similarity3 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

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processDNA damage, DNA repair, Ubl conjugation pathway
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.3.2.B6 2681
ReactomeiR-HSA-1169408 ISG15 antiviral mechanism
R-HSA-168638 NOD1/2 Signaling Pathway
R-HSA-168927 TICAM1, RIP1-mediated IKK complex recruitment
R-HSA-202424 Downstream TCR signaling
R-HSA-2871837 FCERI mediated NF-kB activation
R-HSA-445989 TAK1 activates NFkB by phosphorylation and activation of IKKs complex
R-HSA-450302 activated TAK1 mediates p38 MAPK activation
R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
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-8866654 E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-9020702 Interleukin-1 signaling
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
UniPathwayi
UPA00143

Protein family/group databases

MoonDBiP61088 Predicted

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

EuPathDBiHostDB:ENSG00000177889.9
HGNCiHGNC:12492 UBE2N
MIMi603679 gene
neXtProtiNX_P61088

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
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
ProteomicsDBi57264
TopDownProteomicsiP61088

2D gel databases

OGPiQ16781
REPRODUCTION-2DPAGEiIPI00003949

PTM databases

iPTMnetiP61088
PhosphoSitePlusiP61088
SwissPalmiP61088

Expressioni

Gene expression databases

BgeeiENSG00000177889 Expressed in 244 organ(s), highest expression level in right testis
CleanExiHS_UBE2N
ExpressionAtlasiP61088 baseline and differential
GenevisibleiP61088 HS

Organism-specific databases

HPAiHPA044976

Interactioni

Subunit structurei

Heterodimer with UBE2V2 (PubMed:10089880, PubMed:11473255, PubMed:14562038, PubMed:16307917, PubMed:16307917). Interacts (UBE2V2-UBE2N heterodimer) with the E3 ligase STUB1 (via the U-box domain); the complex has a specific 'Lys-63'-linked polyubiquitination activity (PubMed:16307917). Interacts with RNF8 and RNF168 (PubMed:16215985, PubMed:19203578). Interacts with RNF11 (PubMed:18615712). 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 (PubMed:17108083, PubMed:17130289, PubMed:18316726, PubMed:18719106). Interacts with ARIH2 (via RING-type 2) (PubMed:19340006). Interacts with OTUB1; leading to inhibit E2-conjugating activity (PubMed:20725033, PubMed:22325355, PubMed:22367539). Interacts with GPS2; leading to inhibit E2-conjugating activity (By similarity).By similarity16 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113182, 217 interactors
ComplexPortaliCPX-485 UBC13-UEV1A ubiquitin-conjugating enzyme E2 complex
CPX-530 UBC13-MMS2 ubiquitin-conjugating enzyme E2 complex
CORUMiP61088
DIPiDIP-29829N
IntActiP61088, 140 interactors
MINTiP61088
STRINGi9606.ENSP00000316176

Chemistry databases

BindingDBiP61088

Structurei

Secondary structure

1152
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

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 4 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8VV71F8VV71_HUMAN
Ubiquitin-conjugating enzyme E2 N
UBE2N
152Annotation score:
F8VSD4F8VSD4_HUMAN
Ubiquitin-conjugating enzyme E2 N
UBE2N
105Annotation score:
F8VQQ8F8VQQ8_HUMAN
Ubiquitin-conjugating enzyme E2 N
UBE2N
89Annotation score:
F8VZ29F8VZ29_HUMAN
Ubiquitin-conjugating enzyme E2 N
UBE2N
87Annotation score:

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

Similar proteinsi

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[»]
5H7SX-ray3.49A/C1-152[»]
5VNZX-ray3.41B/E1-152[»]
5VO0X-ray3.90B/E1-152[»]
5YWRX-ray1.47A1-152[»]
ProteinModelPortaliP61088
SMRiP61088
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113182, 217 interactors
ComplexPortaliCPX-485 UBC13-UEV1A ubiquitin-conjugating enzyme E2 complex
CPX-530 UBC13-MMS2 ubiquitin-conjugating enzyme E2 complex
CORUMiP61088
DIPiDIP-29829N
IntActiP61088, 140 interactors
MINTiP61088
STRINGi9606.ENSP00000316176

Chemistry databases

BindingDBiP61088
ChEMBLiCHEMBL6089

Protein family/group databases

MoonDBiP61088 Predicted

PTM databases

iPTMnetiP61088
PhosphoSitePlusiP61088
SwissPalmiP61088

Polymorphism and mutation databases

BioMutaiUBE2N
DMDMi46577660

2D gel databases

OGPiQ16781
REPRODUCTION-2DPAGEiIPI00003949

Proteomic databases

EPDiP61088
PaxDbiP61088
PeptideAtlasiP61088
PRIDEiP61088
ProteomicsDBi57264
TopDownProteomicsiP61088

Protocols and materials databases

DNASUi7334
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000318066; ENSP00000316176; ENSG00000177889
GeneIDi7334
KEGGihsa:7334

Organism-specific databases

CTDi7334
DisGeNETi7334
EuPathDBiHostDB:ENSG00000177889.9
GeneCardsiUBE2N
HGNCiHGNC:12492 UBE2N
HPAiHPA044976
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

UniPathwayi
UPA00143

BRENDAi2.3.2.B6 2681
ReactomeiR-HSA-1169408 ISG15 antiviral mechanism
R-HSA-168638 NOD1/2 Signaling Pathway
R-HSA-168927 TICAM1, RIP1-mediated IKK complex recruitment
R-HSA-202424 Downstream TCR signaling
R-HSA-2871837 FCERI mediated NF-kB activation
R-HSA-445989 TAK1 activates NFkB by phosphorylation and activation of IKKs complex
R-HSA-450302 activated TAK1 mediates p38 MAPK activation
R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
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-8866654 E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-9020702 Interleukin-1 signaling
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
PROiPR:P61088
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000177889 Expressed in 244 organ(s), highest expression level in right testis
CleanExiHS_UBE2N
ExpressionAtlasiP61088 baseline and differential
GenevisibleiP61088 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 nameiUBE2N_HUMAN
AccessioniPrimary (citable) accession number: P61088
Secondary accession number(s): Q16781, Q53Y81
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: April 26, 2004
Last modified: September 12, 2018
This is version 178 of the entry and version 1 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, Direct protein sequencing, Reference proteome

Documents

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