The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

UBC4  -  E2 ubiquitin-conjugating protein UBC4

Saccharomyces cerevisiae S288c

Synonyms: Ubiquitin carrier protein 4, Ubiquitin-conjugating enzyme E2 4, Ubiquitin-protein ligase 4, YBR0745, YBR082C
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of UBC4

  • A catalytically inactive derivative of Ubc4 (Ubc4(C86A)), which causes toxicity in yeast cells, can also bind the proteasome [1].
  • Significantly, the interaction between Ubc4 and the proteasome is strongly induced by heat stress, consistent with the requirement for this E2 for efficient stress tolerance [1].

High impact information on UBC4

  • We find that UBC4 and at least one other ubiquitin-conjugating enzyme can support cyclin B ubiquitination [2].
  • UBC4 and UBC5 are individually dispensable class I E2 enzymes involved in the degradation of short-lived and abnormal proteins [3].
  • Ste6 is a very unstable protein (half-life 13 min) which is stabilized approximately 3-fold in a ubc4 ubc5 mutant, implicating the ubiquitin system in the degradation of Ste6 [4].
  • Loss of UBC4 and UBC5 activity impairs cell growth, leads to inviability at elevated temperatures or in the presence of an amino acid analog, and induces the stress response [5].
  • In Xenopus and clam oocytes, the ubiquitin-conjugating enzymes that function with APC/C have been identified as two proteins, UBC4 and UBCx/E2-C [6].

Biological context of UBC4

  • Using oligonucleotides derived from the S. cerevisiae UBC4 sequence as primers in a PCR reaction with rat muscle cDNA as a template, a 390 bp DNA fragment was amplified which predicted an amino acid sequence that was 83% identical to yeast UBC4 [7].
  • Surprisingly, the structure of this E2 was markedly more similar to the Saccharomyces cerevisiae DNA repair gene RAD6, than to the S. cerevisiae UBC4/UBC5 genes which are required for the degradation of short-lived proteins and support much of the ubiquitination of yeast proteins [7].
  • We have disrupted the UBC11 gene and found it is not essential for yeast cell viability even when combined with deletion of UBC4, a gene that has also been implicated in mitotic cyclin destruction [8].
  • This RAD6 derivative carries out the stress-related function of UBC4 and the cell cycle function of CDC34 while maintaining its own DNA repair function [9].
  • From enzymatic analysis of the UBC1 and UBC4 gene products mutagenized in vitro, we have identified several domains important for E2 function, including the active site cysteine and N-terminal and C-terminal domains [10].

Anatomical context of UBC4

  • We cloned rabbit reticulocyte E217K because unlike the similarly sized class I E2s, E214K and UBC4, it is unable to support ubiquitin-protein ligase (E3)-dependent conjugation to endogenous proteins [11].
  • However, Ubc4p is not required for Pex5p ubiquitination in wild type cells, and cells lacking Ubc4p are not affected in peroxisome biogenesis [12].

Associations of UBC4 with chemical compounds

  • Overexpression of UBC4 and of UBC7, two other genes for ubiquitin-conjugating enzymes, also conferred resistance to methylmercury [13].
  • Whereas the UBC1 gene product does not require its additional cysteine residue at position 116 for thiol ester formation, alteration of cysteine 143 in the UBC4 gene product greatly diminishes this ability [10].
  • A second lysine within UBC4 (K64) was also identified whose mutation resulted in the loss of ubiquitination at K144 [14].
  • Analysis of the mutant ubc4 allele identified a single base pair mutation within the UBC4 coding region, which would generate a glutamic acid to lysine amino acid substitution within a region of conserved tertiary structure located within the first alpha-helix of Ubc4p [15].

Regulatory relationships of UBC4

  • However, Ubc4 levels in the proteasome were reduced significantly in a strain that expressed a mutant Rpt1 subunit [16].

Other interactions of UBC4

  • Expression of UBC4 and UBC5 genes is heat inducible [5].
  • Surprisingly, the E2(14k)) sequence is markedly more similar to Saccharomyces cerevisiae RAD6 (69% identity) than to its proposed homologs UBC4/UBC5 (38% identity) [17].
  • Ubiquitin-conjugating enzymes UBC4 and UBC5 mediate selective degradation of short-lived and abnormal proteins [5].
  • UBC1, UBC4 and UBC5 are functionally overlapping and constitute an enzyme family essential for cell growth and viability [18].
  • Finally, we provide evidence that the proteasome is involved in the turnover of Pex5p in wild type yeast cells, a process that requires Ubc4p and occurs at the peroxisomal membrane [19].


  1. Evidence for an interaction between ubiquitin-conjugating enzymes and the 26S proteasome. Tongaonkar, P., Chen, L., Lambertson, D., Ko, B., Madura, K. Mol. Cell. Biol. (2000) [Pubmed]
  2. A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B. King, R.W., Peters, J.M., Tugendreich, S., Rolfe, M., Hieter, P., Kirschner, M.W. Cell (1995) [Pubmed]
  3. An essential ubiquitin-conjugating enzyme with tissue and developmental specificity in th nematode Caenorhabditis elegans. Zhen, M., Schein, J.E., Baillie, D.L., Candido, E.P. EMBO J. (1996) [Pubmed]
  4. The ABC-transporter Ste6 accumulates in the plasma membrane in a ubiquitinated form in endocytosis mutants. Kölling, R., Hollenberg, C.P. EMBO J. (1994) [Pubmed]
  5. Ubiquitin-conjugating enzymes UBC4 and UBC5 mediate selective degradation of short-lived and abnormal proteins. Seufert, W., Jentsch, S. EMBO J. (1990) [Pubmed]
  6. Two ubiquitin-conjugating enzymes, UbcP1/Ubc4 and UbcP4/Ubc11, have distinct functions for ubiquitination of mitotic cyclin. Seino, H., Kishi, T., Nishitani, H., Yamao, F. Mol. Cell. Biol. (2003) [Pubmed]
  7. Molecular cloning, expression and characterization of a ubiquitin conjugation enzyme (E2(17)kB) highly expressed in rat testis. Wing, S.S., Jain, P. Biochem. J. (1995) [Pubmed]
  8. Functional analysis of the Saccharomyces cerevisiae UBC11 gene. Townsley, F.M., Ruderman, J.V. Yeast (1998) [Pubmed]
  9. Creation of a pluripotent ubiquitin-conjugating enzyme. Ptak, C., Gwozd, C., Huzil, J.T., Gwozd, T.J., Garen, G., Ellison, M.J. Mol. Cell. Biol. (2001) [Pubmed]
  10. Cloning of a 16-kDa ubiquitin carrier protein from wheat and Arabidopsis thaliana. Identification of functional domains by in vitro mutagenesis. Sullivan, M.L., Vierstra, R.D. J. Biol. Chem. (1991) [Pubmed]
  11. Identification of rabbit reticulocyte E217K as a UBC7 homologue and functional characterization of its core domain loop. Lin, H., Wing, S.S. J. Biol. Chem. (1999) [Pubmed]
  12. The Saccharomyces cerevisiae peroxisomal import receptor Pex5p is monoubiquitinated in wild type cells. Kragt, A., Voorn-Brouwer, T., van den Berg, M., Distel, B. J. Biol. Chem. (2005) [Pubmed]
  13. Overexpression of the ubiquitin-conjugating enzyme Cdc34 confers resistance to methylmercury in Saccharomyces cerevisiae. Furuchi, T., Hwang, G.W., Naganuma, A. Mol. Pharmacol. (2002) [Pubmed]
  14. The yeast UBC4 ubiquitin conjugating enzyme monoubiquitinates itself in vivo: evidence for an E2-E2 homointeraction. Gwozd, C.S., Arnason, T.G., Cook, W.J., Chau, V., Ellison, M.J. Biochemistry (1995) [Pubmed]
  15. Yeast 2 microm plasmid copy number is elevated by a mutation in the nuclear gene UBC4. Sleep, D., Finnis, C., Turner, A., Evans, L. Yeast (2001) [Pubmed]
  16. Saccharomyces cerevisiae Ub-conjugating enzyme Ubc4 binds the proteasome in the presence of translationally damaged proteins. Chuang, S.M., Madura, K. Genetics (2005) [Pubmed]
  17. A rabbit reticulocyte ubiquitin carrier protein that supports ubiquitin-dependent proteolysis (E214k) is homologous to the yeast DNA repair gene RAD6. Wing, S.S., Dumas, F., Banville, D. J. Biol. Chem. (1992) [Pubmed]
  18. UBC1 encodes a novel member of an essential subfamily of yeast ubiquitin-conjugating enzymes involved in protein degradation. Seufert, W., McGrath, J.P., Jentsch, S. EMBO J. (1990) [Pubmed]
  19. Ubiquitination of the peroxisomal targeting signal type 1 receptor, Pex5p, suggests the presence of a quality control mechanism during peroxisomal matrix protein import. Kiel, J.A., Emmrich, K., Meyer, H.E., Kunau, W.H. J. Biol. Chem. (2005) [Pubmed]
WikiGenes - Universities