Online Mendelian Inheritance in Man (OMIM) (original) (raw)

* 602962

UBIQUITIN-CONJUGATING ENZYME E2 D2; UBE2D2

Alternative titles; symbols

UBIQUITIN-CONJUGATING ENZYME E2D 2

UBC4/5, S. CEREVISIAE, HOMOLOG OF
UBIQUITIN-CONJUGATING ENZYME UBCH5B; UBCH5B
UBC4

HGNC Approved Gene Symbol: UBE2D2

Cytogenetic location: 5q31.2 Genomic coordinates (GRCh38) : 5:139,526,240-139,628,434 (from NCBI)

TEXT

Description

See UBE2D1 (602961) for general information about ubiquitination and the UBC4/5 subfamily of E2 enzymes.

Members of the UBE2D family, including UBE2D2, are E2 ubiquitin-conjugating enzymes that form a complex with the RING domain E3 ubiquitin ligase IDOL (MYLIP; 610082). The UBE2D-IDOL complex mediates sterol-dependent degradation of low density lipoprotein receptor (LDLR; 606945) (Zhang et al., 2011).

Cloning and Expression

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.

By immunoprecipitation analysis in HEK293 cells, Zhang et al. (2011) showed that human UBE2D family proteins, including UBE2D2, interacted with human IDOL. By interacting with IDOL, the UBE2D proteins promoted autoubiquitination of IDOL and ubiquitination and degradation of LDLR. Analysis with UBE2D1 suggested that the RING domain of IDOL interacted directly with the UBE2D proteins.

Using RT-PCR and Western blot analyses, Lee et al. (2016) showed that cadmium exposure induced p53 accumulation via suppression of UBE2D2 and UBE2D4 (621515) expression in HK-2 human proximal tubular cells. Further analysis revealed that cadmium suppressed UBE2D2 and UBE2D4 transcription by inhibiting activity of the transcription factors YY1 (600013) and FOXF1 (601089). Overaccumulation of p53 due to cadmium exposure led to apoptosis in HK-2 cells. Mice exposed to cadmium for 6 months also exhibited increased p53 levels and induction of apoptosis in proximal tubular cells.

REFERENCES

  1. 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\]
  2. 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\]
  3. Lee, J. Y., Tokumoto, M., Fujiwara, Y., Hasegawa, T., Seko, Y., Shimada, A., Satoh, M.Accumulation of p53 via down-regulation of UBE2D family genes is a critical pathway for cadmium-induced renal toxicity. Sci. Rep. 6: 21968, 2016. [PubMed: 26912277] [Full Text: https://doi.org/10.1038/srep21968\]
  4. 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\]
  5. Zhang, L., Fairall, L., Goult, B. T., Calkin, A. C., Hong, C., Millard, C. J., Tontonoz, P., Schwabe, J. W.The IDOL-UBE2D complex mediates sterol-dependent degradation of the LDL receptor. Genes Dev. 25: 1262-1274, 2011. [PubMed: 21685362] [Full Text: https://doi.org/10.1101/gad.2056211\]

Contributors:

Bao Lige - updated : 02/23/2026
Paul J. Converse - updated : 4/3/2006

Creation Date:

Patti M. Sherman : 8/12/1998

Edit History:

mgross : 02/23/2026
mgross : 04/18/2022
wwang : 12/17/2008
mgross : 4/4/2006
terry : 4/3/2006
psherman : 9/4/1998
alopez : 9/3/1998
psherman : 8/13/1998