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Gene Review

UBE2K  -  ubiquitin-conjugating enzyme E2K

Homo sapiens

Synonyms: E2-25K, HIP-2, HIP2, HYPG, Huntingtin-interacting protein 2, ...
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Disease relevance of HIP2


High impact information on HIP2

  • UCP level correlates inversely with pVHL level in most tumor cell lines [3].
  • The human ubiquitin carrier protein E2(Mr = 17,000) is homologous to the yeast DNA repair gene RAD6 [5].
  • DNA LIG k becomes adenylated in reactions with ATP, and the adenylate moiety is removed by incubation with pyrophosphate or nicked DNA [6].
  • 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) [7].
  • Intact UCRP supports a low rate of ubiquitin-activating enzyme (E1)-dependent ATP:PPi exchange but fails to form a stoichiometric E1-UCRP thiol ester or undergo transfer to ubiquitin carrier protein (E2) [8].

Chemical compound and disease context of HIP2


Biological context of HIP2

  • Ubiquitination of multiple intracellular proteins was observed in agLDL-treated macrophages, which coincided with upregulation of LIG [12].
  • The dominant-negative cullin 5 protein stabilized p53 and the MRN complex, indicating that it inhibited the viral ubiquitin-protein ligase but had no effect on viral early mRNA synthesis, early protein synthesis, or viral DNA replication [1].
  • This unique post-translational modification is thought to be distinct from similar cytosolic reactions in requiring ubiquitin-activating enzyme (E1) and one or more putative ubiquitin carrier proteins (E2) but not isopeptide ligase (E3) [13].
  • The patterns of extracellular enzyme activities and mnp and cbh gene expression are similar whereas LIG gene expression can be detected when no corresponding enzyme activity is observed in the extracellular supernatant [14].
  • 3. The combined mean values (microgram/l) for maternal serum retinol for all gestational ages were 193 for LIG and 261 for HIG [4].

Anatomical context of HIP2


Associations of HIP2 with chemical compounds

  • In this study, we investigated the effects of the Class Ic antiarrhythmic agent flecainide (FLEC) on ionic current (I(HERG)) mediated by cloned HERG channels at 37 degrees C. We also compared the inhibitory potency of FLEC with other Class I agents: quinidine (QUIN, Class Ia); lignocaine (LIG, Class Ib) and propafenone (PROPAF, Class Ic) [18].
  • 2. In the case of full-term infants, the mean values for maternal serum vitamin E (mg/l) for LIG (n 73) and HIG (n 43) were 9.9 (SE 0.4) and 11.6 (SE 0.5) [9].
  • 4. Fetal liver retinol concentrations were much lower than those reported for healthy Thai subjects by Montreewasuwat & Olson (1979) in early pregnancy but showed complete 'catch up' in late pregnancy for HIG and to a considerable extent for LIG [4].
  • Trabeculae were isolated from rabbits with coronary ligation-induced heart failure (LIG, n = 11), sham operated controls (SH, n = 10), isoprenaline-infused rabbits (ISO, 7 days mini-osmotic pump 100 micrograms/kg.h; n = 7) and saline-infused controls (SAL, n = 7) [19].
  • By either transient or stable transfection of Chinese hamster ovary (CHO) Tet-On cells, we successfully expressed, detected, and immobilized biotinylated human Itch, a pleiotropic multi-domain ubiquitin-protein ligase, as well as Gla-RTK, a putative vitamin K-dependent receptor tyrosine kinase [20].

Physical interactions of HIP2

  • Mutations in the RING domain of RNF2 prevented the clone from binding to Hip-2, an indication that the RING domain is the binding determinant [21].

Enzymatic interactions of HIP2


Other interactions of HIP2


Analytical, diagnostic and therapeutic context of HIP2

  • Sequence analyses showed that, with one exception, all Hip-2-interacting proteins contained the RING finger motifs [21].
  • The results, before and after adjustment of physical characteristics, showed that anthropometry, body composition, and lung functions were significantly higher in HIG compared to MIG and LIG children, while in girls, no differences were observed in physical characteristics after adjustments [26].
  • In a multi-center pilot study 37 immunodeficiency patients with chronic diarrhoea [29 HIV-infected patients, 2 patients with common variable immunodeficiency (CVID), one unidentified immunodeficiency, five patients with graft versus host disease (GvHD) following bone marrow transplantation] were treated with oral LIG (10 g/day for 10 days) [17].
  • 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 [27].


  1. Adenovirus ubiquitin-protein ligase stimulates viral late mRNA nuclear export. Woo, J.L., Berk, A.J. J. Virol. (2007) [Pubmed]
  2. Expression of Pirh2, a newly identified ubiquitin protein ligase, in lung cancer. Duan, W., Gao, L., Druhan, L.J., Zhu, W.G., Morrison, C., Otterson, G.A., Villalona-Calero, M.A. J. Natl. Cancer Inst. (2004) [Pubmed]
  3. 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]
  4. Liver stores of vitamin A in human fetuses in relation to gestational age, fetal size and maternal nutritional status. Shah, R.S., Rajalakshmi, R., Bhatt, R.V., Hazra, M.N., Patel, B.C., Swamy, N.B., Patel, T.V. Br. J. Nutr. (1987) [Pubmed]
  5. 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]
  6. Mitochondrial DNA ligase in Crithidia fasciculata. Sinha, K.M., Hines, J.C., Downey, N., Ray, D.S. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  7. 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]
  8. Conjugation of the 15-kDa interferon-induced ubiquitin homolog is distinct from that of ubiquitin. Narasimhan, J., Potter, J.L., Haas, A.L. J. Biol. Chem. (1996) [Pubmed]
  9. Vitamin E status of the newborn in relation to gestational age, birth weight and maternal vitamin E status. Shah, R.S., Rajalakshmi, R., Bhatt, R.V., Hazra, M.N., Patel, B.C., Swamy, N.B., Patel, T.V. Br. J. Nutr. (1987) [Pubmed]
  10. Ubiquitin-protein ligase parkin and its role in the development of Parkinson's disease. Buneeva, O.A., Medvedev, A.E. Biochemistry Mosc. (2006) [Pubmed]
  11. Multivariate statistics of the pyrolysis products of high molecular components in pulping wastewaters to explain their toxicity. Paasivirta, J., Kukkola, J., Knuutinen, J., Pessala, P., Schultz, E., Herve, S. Environmental science and pollution research international. (2005) [Pubmed]
  12. Regulation of macrophage-specific gene expression by degenerated lipoproteins. Furukawa, Y., Kubo, N., Kikuchi, J., Tokura, A., Fujita, N., Sakurabayashi, I. Electrophoresis (2000) [Pubmed]
  13. Functional diversity among putative E2 isozymes in the mechanism of ubiquitin-histone ligation. Haas, A.L., Bright, P.M., Jackson, V.E. J. Biol. Chem. (1988) [Pubmed]
  14. PCR-mediated analysis of lignocellulolytic gene transcription by Phanerochaete chrysosporium: substrate-dependent differential expression within gene families. Broda, P., Birch, P.R., Brooks, P.R., Sims, P.F. Appl. Environ. Microbiol. (1995) [Pubmed]
  15. Ubiquitin-conjugating enzyme E2-25K increases aggregate formation and cell death in polyglutamine diseases. de Pril, R., Fischer, D.F., Roos, R.A., van Leeuwen, F.W. Mol. Cell. Neurosci. (2007) [Pubmed]
  16. 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]
  17. Treatment of diarrhoea in human immunodeficiency virus-infected patients with immunoglobulins from bovine colostrum. Rump, J.A., Arndt, R., Arnold, A., Bendick, C., Dichtelmüller, H., Franke, M., Helm, E.B., Jäger, H., Kampmann, B., Kolb, P. The Clinical investigator. (1992) [Pubmed]
  18. Inhibition of the current of heterologously expressed HERG potassium channels by flecainide and comparison with quinidine, propafenone and lignocaine. Paul, A.A., Witchel, H.J., Hancox, J.C. Br. J. Pharmacol. (2002) [Pubmed]
  19. Effects of cyclic adenosine monophosphate (cAMP) on sarcoplasmic reticulum Ca(2+)-loading in failing rabbit and human cardiac trabeculae. Denvir, M.A., MacFarlane, N.G., Miller, D.J., Cobbe, S.M. Basic Res. Cardiol. (1998) [Pubmed]
  20. 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]
  21. E3 ligase activity of RING finger proteins that interact with Hip-2, a human ubiquitin-conjugating enzyme. Lee, S.J., Choi, J.Y., Sung, Y.M., Park, H., Rhim, H., Kang, S. FEBS Lett. (2001) [Pubmed]
  22. Beta-arrestin and Mdm2, unsuspected partners in signaling from the cell surface. Strous, G.J., Schantl, J.A. Sci. STKE (2001) [Pubmed]
  23. Differential response between the p53 ubiquitin-protein ligases Pirh2 and MdM2 following DNA damage in human cancer cells. Duan, W., Gao, L., Wu, X., Zhang, Y., Otterson, G.A., Villalona-Calero, M.A. Exp. Cell Res. (2006) [Pubmed]
  24. The ubiquitin-protein ligase activity of Hdm2 is inhibited by nucleic acids. Linares, L.K., Scheffner, M. FEBS Lett. (2003) [Pubmed]
  25. Novel mutations of ubiquitin protein ligase 3A gene in Italian patients with Angelman syndrome. Russo, S., Cogliati, F., Viri, M., Cavalleri, F., Selicorni, A., Turolla, L., Belli, S., Romeo, A., Larizza, L. Hum. Mutat. (2000) [Pubmed]
  26. Influence of socioeconomic status on lung function and prediction equations in Indian children. Raju, P.S., Prasad, K.V., Ramana, Y.V., Balakrishna, N., Murthy, K.J. Pediatr. Pulmonol. (2005) [Pubmed]
  27. pVHL's kryptonite: E2-EPF UCP. Ohh, M. Cancer Cell (2006) [Pubmed]
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