Ubiquitin-conjugating enzyme E2 N (UBE2N)
The protein contains 152 amino acids for an estimated molecular weight of 17138 Da.
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. Together with RNF135 and UB2V1, catalyzes the viral RNA-dependent 'Lys-63'-linked polyubiquitination of RIG-I/DDX58 to activate the downstream signaling pathway that leads to interferon beta production (PubMed:28469175, PubMed:31006531). UBE2V1-UBE2N together with TRAF3IP2 E3 ubiquitin ligase mediate 'Lys-63'-linked polyubiquitination of TRAF6, a component of IL17A-me (updated: Oct. 7, 2020)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Activation of MAPK activity
Aggrephagy
Cellular protein modification process
Cytokine-mediated signaling pathway
DNA double-strand break processing
Double-strand break repair
Double-strand break repair via homologous recombination
Double-strand break repair via nonhomologous end joining
Fc-epsilon receptor signaling pathway
Global genome nucleotide-excision repair
Histone ubiquitination
Innate immune response
Interleukin-1-mediated signaling pathway
JNK cascade
MyD88-dependent toll-like receptor signaling pathway
Nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
Nucleotide-binding oligomerization domain containing signaling pathway
Positive regulation of DNA repair
Positive regulation of histone modification
Positive regulation of I-kappaB kinase/NF-kappaB signaling
Positive regulation of NF-kappaB transcription factor activity
Positive regulation of ubiquitin-protein transferase activity
Postreplication repair
Protein K63-linked ubiquitination
Protein polyubiquitination
Protein ubiquitination
Proteolysis
Regulation of DNA repair
Regulation of histone ubiquitination
Stimulatory C-type lectin receptor signaling pathway
T cell receptor signaling pathway
Toll-like receptor 10 signaling pathway
Toll-like receptor 2 signaling pathway
Toll-like receptor 4 signaling pathway
Toll-like receptor 5 signaling pathway
Toll-like receptor 9 signaling pathway
Toll-like receptor signaling pathway
Toll-like receptor TLR1:TLR2 signaling pathway
Toll-like receptor TLR6:TLR2 signaling pathway
Ubiquitin-dependent protein catabolic process
The reference OMIM entry for this protein is 603679
Ubiquitin-conjugating enzyme e2n; ube2n
Ubiquitin-conjugating enzyme 13, s. cerevisiae, homolog of; ubc13; ubch13
Bendless, drosophila, homolog of; ubchben
CLONING
Yamaguchi et al. (1996) cloned the cDNA encoding UBE2N, a human ubiquitin (191339)-conjugating enzyme, from an epidermoid carcinoma KB cDNA library. The UBE2N gene, which the authors referred to as UBCHBEN, encodes a protein of 152 amino acids with a calculated molecular mass of 17.1 kD. The amino acid sequence shows 80% identity with the Drosophila 'bendless' gene product (ubiquitin-conjugating enzyme E2). Northern blot analysis detected a major 1.4- and a minor 2.4-kb transcript in all tissues examined, with the highest expression in heart, skeletal muscle, and testis.MAPPING
Gross (2014) mapped the UBE2N gene to chromosome 12q22 based on an alignment of the UBE2N sequence (GenBank GENBANK BC000396) with the genomic sequence (GRCh38).GENE FUNCTION
Yamaguchi et al. (1996) found that, when expressed in Escherichia coli, the UBE2N gene product exhibited the ability to form a thiol ester linkage with ubiquitin in a ubiquitin-activating enzyme E1 (314370)-dependent manner. They concluded that the UBE2N gene encodes a novel human E2 that may be involved in protein degradation in the muscles and testis. In yeast, Hofmann and Pickart (1999) showed that UBE2N, which they referred to as UBC13, formed a specific heteromeric complex with MMS2, a ubiquitin-conjugating enzyme variant (UBE2V2; 603001). A ubc13 yeast strain was ultraviolet (UV) sensitive, and single, double, and triple mutants of the UBC13, MMS2, and ubiquitin genes displayed a similar phenotype. These findings supported a model in which an MMS2/UBC13 complex assembles novel polyubiquitin chains for signaling in DNA repair, and suggested that UEV proteins may act to increase diversity and selectivity in ubiquitin conjugation. The RAD6 (179095) pathway is central to postreplicative DNA repair in eukaryotic cells. Two principal elements of this pathway are the ubiquitin-conjugating enzymes RAD6 and the MMS2-UBC13 heterodimer, which are recruited to chromatin by the RING finger proteins RAD18 (605256) and RAD5 (608048), respectively. Hoege et al. (2002) showed that UBC9 (601661), a small ubiquitin-related modifier (SUMO)-conjugating enzyme, is also affiliated with this pathway and that proliferating cell nuclear antigen (PCNA; 176740), a DNA polymerase sliding clamp involved in DNA synthesis and repair, is a substrate. PCNA is monoubiquitinated through RAD6 and RAD18, modified by lys63-linked multiubiquitination, which additionally requires MMS2, UBC13, and RAD5, and is conjugated to SUMO by UBC9. All 3 modifications affect the same lysine residue of PCNA, K164, suggesting that they label PCNA for alternative functions. Hoege et al. (2002) demonstrated that these modifications differentially affect resistance to DNA damage, and that damage-induced PCNA ubiquitination is elementary for DNA repair and occurs at the same conserved residue in yeast and humans. Zhao et al. (2007) found that depletion of UBC13 in chicken and human cells resulted in severe growth defects due to chromosome instability, as well as hypersensitivity to UV and ionizing radiation, consistent with a conserved role for UBC13 in RAD6/RAD18-dependent postreplication repair. UBC13-deficient cells were also compromised for DNA double-strand break repair by homologous recombination. Recruitment and activation of the E3 ubiquitin ligase function of BRCA1 (113705) and subsequent formation of RAD51 (179617) nucleoprotein filaments at double-strand breaks were abolished in UBC13-defic ... More on the omim web site
Oct. 20, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Jan. 22, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for UBE2N
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603679 was added.