MGP Database

MGP003251

UniProt Annotations

Entry Information
Gene Nameubiquitin-conjugating enzyme E2N
Protein EntryUBE2N_HUMAN
UniProt IDP61088
SpeciesHuman
Comments
Comment typeDescription
Catalytic ActivityATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine. {ECO:0000255|PROSITE- ProRule:PRU00388, ECO:0000255|PROSITE-ProRule:PRU10133}.
Enzyme RegulationActivity is inhibited by binding to OTUB1, which prevents 'Lys-63'-linked polyubiquitination. {ECO:0000269|PubMed:20725033, ECO:0000269|PubMed:22325355, ECO:0000269|PubMed:22367539}.
FunctionThe 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 (By similarity). {ECO:0000250}.
InteractionQ13489:BIRC3; NbExp=2; IntAct=EBI-1052908, EBI-517709; Q6UWE0:LRSAM1; NbExp=3; IntAct=EBI-1052908, EBI-720984; Q62925:Map3k1 (xeno); NbExp=44; IntAct=EBI-1052908, EBI-636664; Q9BYM8:RBCK1; NbExp=2; IntAct=EBI-1052908, EBI-2340624; Q6PCD5:RFWD3; NbExp=2; IntAct=EBI-1052908, EBI-2129159; Q9Y3C5:RNF11; NbExp=4; IntAct=EBI-1052908, EBI-396669; O43567:RNF13; NbExp=2; IntAct=EBI-1052908, EBI-2129183; Q8IYW5:RNF168; NbExp=2; IntAct=EBI-1052908, EBI-914207; Q8N6D2:RNF182; NbExp=2; IntAct=EBI-1052908, EBI-2130099; Q9UNE7:STUB1; NbExp=5; IntAct=EBI-1052908, EBI-357085; Q9WUD1:Stub1 (xeno); NbExp=2; IntAct=EBI-1052908, EBI-773027; Q9Y4K3:TRAF6; NbExp=3; IntAct=EBI-1052908, EBI-359276; Q13404:UBE2V1; NbExp=18; IntAct=EBI-1052908, EBI-1050671; Q15819:UBE2V2; NbExp=3; IntAct=EBI-1052908, EBI-714329; P98170:XIAP; NbExp=2; IntAct=EBI-1052908, EBI-517127; Q8ND25:ZNRF1; NbExp=3; IntAct=EBI-1052908, EBI-2129250;
PathwayProtein modification; protein ubiquitination. {ECO:0000255|PROSITE-ProRule:PRU00388}.
PtmConjugation to ISG15 impairs formation of the thioester bond with ubiquitin but not interaction with UBE2V2.
SimilarityBelongs to the ubiquitin-conjugating enzyme family. {ECO:0000255|PROSITE-ProRule:PRU00388}.
Subcellular LocationNucleus {ECO:0000269|PubMed:19340006}. Cytoplasm {ECO:0000269|PubMed:19340006}.
SubunitHeterodimer 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. {ECO:0000269|PubMed:10089880, ECO:0000269|PubMed:11473255, ECO:0000269|PubMed:14562038, ECO:0000269|PubMed:16215985, ECO:0000269|PubMed:16307917, ECO:0000269|PubMed:17108083, ECO:0000269|PubMed:17130289, ECO:0000269|PubMed:18316726, ECO:0000269|PubMed:18615712, ECO:0000269|PubMed:18719106, ECO:0000269|PubMed:19203578, ECO:0000269|PubMed:19340006, ECO:0000269|PubMed:20725033, ECO:0000269|PubMed:22325355, ECO:0000269|PubMed:22367539, ECO:0000269|PubMed:22589545}.
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