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Gene Review

UBE2S  -  ubiquitin-conjugating enzyme E2S

Homo sapiens

Synonyms: E2-EPF, E2EPF, EPF5, OK/SW-cl.73, Ubiquitin carrier protein S, ...
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Disease relevance of UBE2S


High impact information on UBE2S

  • E2-EPF UCP targets pVHL for degradation and associates with tumor growth and metastasis [2].
  • UCP level correlates inversely with pVHL level in most tumor cell lines [2].
  • The human ubiquitin carrier protein E2(Mr = 17,000) is homologous to the yeast DNA repair gene RAD6 [4].
  • UBE3A encodes a ubiquitin-protein ligase and shows brain-specific imprinting [5].
  • The role of ER stress in dopaminergic neuronal vulnerability was highlighted by their decreased survival in mice deficient in the ubiquitin-protein ligase Parkin and the ER chaperone ORP150 (150 kDa oxygen-regulated protein) [6].

Biological context of UBE2S


Anatomical context of UBE2S

  • The keratinocyte ubiquitin carrier protein expressed in bacteria, and isolated either intact or as a glutathione S-transferase fusion protein, exhibited the ability to form a thiol ester linkage with ubiquitin in a ubiquitin activating enzyme (E1)-dependent manner, a characteristic property of ubiquitin carrier proteins [1].
  • Using a rabbit reticulocyte lysate system, E2EPF was shown to support the degradation of a model substrate in an ATP- and ubiquitin-dependent fashion [9].
  • Suppression of Nedd4 expression with siRNA resulted in an accumulation of gap junction plaques at the plasma membrane, suggesting an involvement of the ubiquitin protein ligase Nedd4 in gap junction internalization [10].

Associations of UBE2S with chemical compounds

  • In contrast to a previous study which showed that selective protein degradation in one system is dependent upon multiubiquitination via the lysine 48 residue of ubiquitin, multiubiquitination, and proteolytic targeting by E2EPF was shown here to be independent of the lysine 48 multiubiquitin linkage [9].
  • In a recent report published in Nature Medicine, Jung et al. identified von Hippel-Lindau (VHL) tumor suppressor protein, which targets the alpha subunit of hypoxia-inducible factor (HIF) for ubiquitin-mediated destruction, as a bona fide substrate of UCP and demonstrated a potential pVHL-HIF pathway-dependent role for UCP in cancer development [11].

Analytical, diagnostic and therapeutic context of UBE2S

  • E2-EPF ubiquitin carrier protein (UCP) is a member of an E2 family of enzymes that catalyzes the ligation of ubiquitin to proteins targeted for destruction by the proteasome [11].


  1. cDNA cloning of a novel human ubiquitin carrier protein. An antigenic domain specifically recognized by endemic pemphigus foliaceus autoantibodies is encoded in a secondary reading frame of this human epidermal transcript. Liu, Z., Diaz, L.A., Haas, A.L., Giudice, G.J. J. Biol. Chem. (1992) [Pubmed]
  2. E2-EPF UCP targets pVHL for degradation and associates with tumor growth and metastasis. Jung, C.R., Hwang, K.S., Yoo, J., Cho, W.K., Kim, J.M., Kim, W.H., Im, D.S. Nat. Med. (2006) [Pubmed]
  3. Ubiquitin-protein ligase parkin and its role in the development of Parkinson's disease. Buneeva, O.A., Medvedev, A.E. Biochemistry Mosc. (2006) [Pubmed]
  4. The human ubiquitin carrier protein E2(Mr = 17,000) is homologous to the yeast DNA repair gene RAD6. Schneider, R., Eckerskorn, C., Lottspeich, F., Schweiger, M. EMBO J. (1990) [Pubmed]
  5. Mutation analysis of UBE3A in Angelman syndrome patients. Malzac, P., Webber, H., Moncla, A., Graham, J.M., Kukolich, M., Williams, C., Pagon, R.A., Ramsdell, L.A., Kishino, T., Wagstaff, J. Am. J. Hum. Genet. (1998) [Pubmed]
  6. Pael receptor induces death of dopaminergic neurons in the substantia nigra via endoplasmic reticulum stress and dopamine toxicity, which is enhanced under condition of parkin inactivation. Kitao, Y., Imai, Y., Ozawa, K., Kataoka, A., Ikeda, T., Soda, M., Nakimawa, K., Kiyama, H., Stern, D.M., Hori, O., Wakamatsu, K., Ito, S., Itohara, S., Takahashi, R., Ogawa, S. Hum. Mol. Genet. (2007) [Pubmed]
  7. A versatile system for site-specific enzymatic biotinylation and regulated expression of proteins in cultured mammalian cells. Kulman, J.D., Satake, M., Harris, J.E. Protein Expr. Purif. (2007) [Pubmed]
  8. The ubiquitin-protein ligase Nedd4 targets Notch1 in skeletal muscle and distinguishes the subset of atrophies caused by reduced muscle tension. Koncarevic, A., Jackman, R.W., Kandarian, S.C. FASEB J. (2007) [Pubmed]
  9. Characterization of a novel keratinocyte ubiquitin carrier protein. Liu, Z., Haas, A.L., Diaz, L.A., Conrad, C.A., Gíudice, G.J. J. Biol. Chem. (1996) [Pubmed]
  10. Ubiquitin protein ligase Nedd4 binds to connexin43 by a phosphorylation-modulated process. Leykauf, K., Salek, M., Bomke, J., Frech, M., Lehmann, W.D., Dürst, M., Alonso, A. J. Cell. Sci. (2006) [Pubmed]
  11. pVHL's kryptonite: E2-EPF UCP. Ohh, M. Cancer Cell (2006) [Pubmed]
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