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Protein

Ubiquitin-conjugating enzyme E2 N

Gene

UBE2N

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 (By similarity). 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 (By similarity).By similarity

Catalytic activityi

ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine.PROSITE-ProRule annotation

Enzyme regulationi

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

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei87 – 871Glycyl thioester intermediate

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. ligase activity Source: UniProtKB-KW
  3. poly(A) RNA binding Source: Ensembl
  4. ubiquitin-like protein transferase activity Source: GO_Central
  5. ubiquitin protein ligase activity Source: GO_Central
  6. ubiquitin protein ligase binding Source: GO_Central
  7. ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

  1. DNA double-strand break processing Source: Ensembl
  2. double-strand break repair via homologous recombination Source: Ensembl
  3. histone ubiquitination Source: Ensembl
  4. positive regulation of DNA repair Source: Ensembl
  5. positive regulation of histone modification Source: Ensembl
  6. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  7. positive regulation of NF-kappaB transcription factor activity Source: Ensembl
  8. positive regulation of ubiquitin-protein transferase activity Source: Ensembl
  9. postreplication repair Source: GO_Central
  10. protein K63-linked ubiquitination Source: UniProtKB
  11. regulation of histone ubiquitination Source: Ensembl
  12. T cell receptor signaling pathway Source: Ensembl
  13. ubiquitin-dependent protein catabolic process Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

DNA damage, DNA repair, Ubl conjugation pathway

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_278715. ISG15 antiviral mechanism.
REACT_279280. Downstream TCR signaling.
REACT_285661. FCERI mediated NF-kB activation.
REACT_286248. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
REACT_321905. Interleukin-1 signaling.
REACT_335623. IRAK1 recruits IKK complex.
REACT_336915. NOD1/2 Signaling Pathway.
REACT_343577. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin-conjugating enzyme E2 N (EC:6.3.2.19)
Alternative name(s):
Ubiquitin carrier protein N
Ubiquitin-protein ligase N
Gene namesi
Name:UBE2N
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
ProteomesiUP000009136 Componenti: Chromosome 5

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: GO_Central
  2. extracellular vesicular exosome Source: Ensembl
  3. nucleus Source: GO_Central
  4. UBC13-MMS2 complex Source: Ensembl
  5. UBC13-UEV1A complex Source: UniProtKB
  6. ubiquitin ligase complex Source: UniProtKB
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 152152Ubiquitin-conjugating enzyme E2 NPRO_0000278832Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei82 – 821N6-acetyllysineBy similarity
Cross-linki92 – 92Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)By similarity

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Isopeptide bond, Ubl conjugation

Proteomic databases

PaxDbiQ0P5K3.
PRIDEiQ0P5K3.

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 (By similarity).By similarity

Structurei

3D structure databases

ProteinModelPortaliQ0P5K3.
SMRiQ0P5K3. Positions 3-152.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiCOG5078.
GeneTreeiENSGT00540000070023.
HOGENOMiHOG000233455.
HOVERGENiHBG063308.
InParanoidiQ0P5K3.
KOiK10580.
OMAiYFDVEIH.
OrthoDBiEOG7XWPQB.
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.

Q0P5K3-1 [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:September 18, 2006 - v1
Checksum:iFACD84D883D77407
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC119931 mRNA. Translation: AAI19932.1.
RefSeqiNP_001069726.1. NM_001076258.1.
UniGeneiBt.22061.

Genome annotation databases

EnsembliENSBTAT00000052393; ENSBTAP00000052296; ENSBTAG00000021767.
GeneIDi541130.
KEGGibta:541130.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC119931 mRNA. Translation: AAI19932.1.
RefSeqiNP_001069726.1. NM_001076258.1.
UniGeneiBt.22061.

3D structure databases

ProteinModelPortaliQ0P5K3.
SMRiQ0P5K3. Positions 3-152.
ModBaseiSearch...
MobiDBiSearch...

Chemistry

BindingDBiQ0P5K3.

Proteomic databases

PaxDbiQ0P5K3.
PRIDEiQ0P5K3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000052393; ENSBTAP00000052296; ENSBTAG00000021767.
GeneIDi541130.
KEGGibta:541130.

Organism-specific databases

CTDi7334.

Phylogenomic databases

eggNOGiCOG5078.
GeneTreeiENSGT00540000070023.
HOGENOMiHOG000233455.
HOVERGENiHBG063308.
InParanoidiQ0P5K3.
KOiK10580.
OMAiYFDVEIH.
OrthoDBiEOG7XWPQB.
TreeFamiTF101126.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiREACT_278715. ISG15 antiviral mechanism.
REACT_279280. Downstream TCR signaling.
REACT_285661. FCERI mediated NF-kB activation.
REACT_286248. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
REACT_321905. Interleukin-1 signaling.
REACT_335623. IRAK1 recruits IKK complex.
REACT_336915. NOD1/2 Signaling Pathway.
REACT_343577. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.

Miscellaneous databases

NextBioi20879024.

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...

Publicationsi

  1. NIH - Mammalian Gene Collection (MGC) project
    Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Hereford.
    Tissue: Fetal skin.

Entry informationi

Entry nameiUBE2N_BOVIN
AccessioniPrimary (citable) accession number: Q0P5K3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 5, 2007
Last sequence update: September 18, 2006
Last modified: March 31, 2015
This is version 78 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.