UBE2N (UBC13) Recombinant Protein

The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. Studies in mouse suggest that this protein plays a role in DNA postreplication repair. [provided by RefSeq, Jul 2008]

Function: 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

By similarity. Ref.6 Ref.7 Ref.16 Ref.20 Ref.23

Catalytic activity: ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine.

Enzyme regulation: Activity is inhibited by binding to OTUB1, which prevents 'Lys-63'-linked polyubiquitination. Ref.21 Ref.29 Ref.30

Pathway: Protein modification; protein ubiquitination.

Subunit structure: 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. Ref.6 Ref.7 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14 Ref.15 Ref.17 Ref.18 Ref.21 Ref.29 Ref.30

Subcellular location: Nucleus. Cytoplasm Ref.17.

Post-translational modification: Conjugation to ISG15 impairs formation of the thioester bond with ubiquitin but not interaction with UBE2V2.

Sequence similarities: Belongs to the ubiquitin-conjugating enzyme family.