Ubiquitin-conjugating enzyme E2 D2 (UBE2D2)
The protein contains 147 amino acids for an estimated molecular weight of 16735 Da.
Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-linked polyubiquitination. Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and autoubiquitination of STUB1 and TRAF6. Involved in the signal-induced conjugation and subsequent degradation of NFKBIA, FBXW2-mediated GCM1 ubiquitination and degradation, MDM2-dependent degradation of p53/TP53 and the activation of MAVS in the mitochondria by DDX58/RIG-I in response to viral infection. Essential for viral activation of IRF3. (updated: Sept. 12, 2018)
Protein identification was indicated in the following studies:
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
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
Cellular protein modification process
MyD88-independent toll-like receptor signaling pathway
Protein autoubiquitination
Protein K48-linked ubiquitination
Protein localization
Protein polyubiquitination
Protein targeting to peroxisome
Protein ubiquitination
TRIF-dependent toll-like receptor signaling pathway
Ubiquitin-dependent protein catabolic process
Cellular Component
Cytosol
Extracellular exosome
Nucleoplasm
Nucleus
Protein-containing complex
Ubiquitin ligase complex
The reference OMIM entry for this protein is 602962
Ubiquitin-conjugating enzyme e2d 2; ube2d2
Ubc4/5, s. cerevisiae, homolog of
Ubiquitin-conjugating enzyme ubch5b; ubch5b
Ubc4
See UBE2D1 (602961) for general information about ubiquitination and the UBC4/5 subfamily of E2 enzymes.
CLONING
By PCR using degenerate oligonucleotides corresponding to conserved regions of S. cerevisiae UBC5 and the related Drosophila UbcD1, Jensen et al. (1995) identified a human peripheral blood lymphocyte cDNA encoding UBCH5B, or UBE2D2. The predicted 147-amino acid UBCH5B and UBCH5C (UBE2D3; 602963) proteins have only 4 amino acid differences, 3 of which are conservative changes; the nucleotide sequences of their cDNAs are 87% identical within the coding region and 23% conserved within the 3-prime untranslated region. The UBCH5B protein has 95% sequence identity with the Drosophila UbcD1 protein, 93% identity with C. elegans ubc2, 89% identity with human UBCH5A (UBE2D1), and 79% identity with S. cerevisiae UBC4 and UBC5, and Arabidopsis thaliana UBC8 and UBC9. Recombinant UBCH5B expressed in E. coli had a molecular mass of 16 kD by SDS-PAGE. Quantitative PCR detected UBCH5B expression in all human tissues examined. Independently, Rolfe et al. (1995) isolated a HeLa cell cDNA encoding UBE2D2, which they called UBC4. Jensen et al. (1995) noted that the coding sequences of this UBC4 cDNA and the UBCH5B cDNA isolated by them have 3 nucleotide differences, 1 of which results in an amino acid substitution.GENE FUNCTION
Jensen et al. (1995) demonstrated that UBCH5B could conjugate ubiquitin to target proteins in an E6AP (UBE3A; 601623)-dependent manner. Rolfe et al. (1995) showed that UBC4 specifically ubiquitinated E6AP and that in vivo inhibition of UBC4 led to inhibition of E6-stimulated p53 (TP53; 191170) degradation. Kim et al. (2005) noted that the ubiquitin-conjugating (E2) enzyme UBCH5B is part of a ubiquitin-ligating (E3) complex with CULLIN1 (CUL1; 603134), SKP1 (601434), ROC1 (RBX1; 603814), and BTRC (603482). By yeast 2-hybrid, coimmunoprecipitation, and Western blot analyses, Kim et al. (2005) found that the Shigella flexneri effector protein OspG interacted with a number of E2 enzymes, including UBCH5B. Transfection experiments showed that OspG prevented phosphorylated IKBA (NFKBIA; 164008) degradation and NFKB (164011) activation mediated by the UBCH5B-containing E3 complex. Inactivation of OspG, on the other hand, increased IKBA degradation in infected epithelial cells and increased the inflammatory response in vivo. Kim et al. (2005) concluded that OspG negatively controls the host innate immune response induced by S. flexneri invasion of the epithelium. ... More on the omim web site
July 1, 2020: Protein entry updated
Automatic update: OMIM entry 602962 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).