Alternative titles; symbols
HGNC Approved Gene Symbol: UBE2D2
Cytogenetic location: 5q31.2 Genomic coordinates (GRCh38): 5:139,526,240-139,628,434 (from NCBI)
See UBE2D1 (602961) for general information about ubiquitination and the UBC4/5 subfamily of E2 enzymes.
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.
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.
Jensen, J. P., Bates, P. W., Yang, M., Vierstra, R. A., Weissman, A. M. Identification of a family of closely related human ubiquitin conjugating enzymes. J. Biol. Chem. 270: 30408-30414, 1995. [PubMed: 8530467] [Full Text: https://doi.org/10.1074/jbc.270.51.30408]
Kim, D. W., Lenzen, G., Page, A.-L., Legrain, P., Sansonetti, P. J., Parsot, C. The Shigella flexneri effector OspG interferes with innate immune responses by targeting ubiquitin-conjugating enzymes. Proc. Nat. Acad. Sci. 102: 14046-14051, 2005. [PubMed: 16162672] [Full Text: https://doi.org/10.1073/pnas.0504466102]
Rolfe, M., Beer-Romero, P., Glass, S., Eckstein, J., Berdo, I., Theodoras, A., Pagano, M., Draetta, G. Reconstitution of p53-ubiquitylation reactions from purified components: the role of human ubiquitin-conjugating enzyme UBC4 and E6-associated protein (E6AP). Proc. Nat. Acad. Sci. 92: 3264-3268, 1995. [PubMed: 7724550] [Full Text: https://doi.org/10.1073/pnas.92.8.3264]