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Gene Review

HUWE1  -  HECT, UBA and WWE domain containing 1, E3...

Homo sapiens

Synonyms: ARF-BP1, ARF-binding protein 1, E3 ubiquitin-protein ligase HUWE1, HECT, UBA and WWE domain-containing protein 1, HECTH9, ...
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Disease relevance of HUWE1


High impact information on HUWE1

  • In this issue of Cell, and describe a new E3 ligase, ARF-BP1/Mule, which targets two very different substrates, p53 and Mcl-1, with completely different cellular outcomes [5].
  • Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis [6].
  • Elimination of Mule expression by RNA interference stabilizes Mcl-1 protein, resulting in an attenuation of the apoptosis induced by DNA-damage agents [6].
  • Mass spectrometry and size analysis by gel filtration and glycerol gradient centrifugation suggested that E3Histone is a monomer of LASU1 [7].
  • This GLUT4 trafficking to the plasma membrane in the absence of golgin-160 was independent of TGN/Golgi sorting, because it was no longer inhibited by the expression of a dominant-interfering Golgi-localized, gamma-ear-containing ARF-binding protein mutant and displayed reduced binding to the lectin wheat germ agglutinin [8].

Chemical compound and disease context of HUWE1

  • The aim of this study was to assess the effect of partial replacement of dietary glucose provided by corn starch with fructose on metabolism and fatty liver production in the Mule ducks [9].

Biological context of HUWE1


Anatomical context of HUWE1

  • A competing BH3-ligand derived from Bim interacted with Mcl-1 and prevented its interaction with LASU1 in HeLa cells, causing elevation of the steady-state levels of Mcl-1 [12].
  • In particular, all essential cysteine residues, the transmembrane domain as well as the cytoplasmic tail residues harbouring the signals for endocytosis and Golgi-localizing, gamma-ear-containing, ARF-binding protein (GGA)-mediated sorting at the trans-Golgi network, are highly conserved [13].
  • 5. Mule drakes have strong sexual drives as a result of high concentrations of testosterone, but, because spermatogenesis is incomplete, their semen had no sperm [14].
  • With similar food intake, Mule ducks (moderately overfed) showed global blood insulin lower than that of Pekin ducks (intensively overfed) despite similar blood sugar levels, suggesting a trend towards reduced pancreas response to glucose in Mule ducks [15].
  • This study provides evidence that overfeeding with a carbohydrate-rich corn-based diet induces a de novo hepatic lipogenesis in Mule duck which predominates over dietary lipid intake to change the lipid composition of the hepatocyte plasma membrane [16].

Associations of HUWE1 with chemical compounds

  • Of note, the BH3 domain of LASU1 interacted with Mcl-1 but not with Bcl-2 or Bcl-Xl [12].
  • These results suggest that a GK-like enzyme may actively contribute to glucose disposal throughout the overfeeding period in Mule ducks fed a carbohydrate-rich diet [17].

Enzymatic interactions of HUWE1


Other interactions of HUWE1


Analytical, diagnostic and therapeutic context of HUWE1


  1. ARF-BP1 as a potential therapeutic target. Chen, D., Brooks, C.L., Gu, W. Br. J. Cancer (2006) [Pubmed]
  2. Over-expression of human UREB1 in colorectal cancer: HECT domain of human UREB1 inhibits the activity of tumor suppressor p53 protein. Yoon, S.Y., Lee, Y., Kim, J.H., Chung, A.S., Joo, J.H., Kim, C.N., Kim, N.S., Choe, I.S., Kim, J.W. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  3. Hormonal and metabolic responses to overfeeding in three genotypes of ducks. Davail, S., Rideau, N., Guy, G., André, J.M., Hermier, D., Hoo-Paris, R. Comp. Biochem. Physiol., Part A Mol. Integr. Physiol. (2003) [Pubmed]
  4. Submicroscopic duplications of the hydroxysteroid dehydrogenase HSD17B10 and the E3 ubiquitin ligase HUWE1 are associated with mental retardation. Froyen, G., Corbett, M., Vandewalle, J., Jarvela, I., Lawrence, O., Meldrum, C., Bauters, M., Govaerts, K., Vandeleur, L., Van Esch, H., Chelly, J., Sanlaville, D., van Bokhoven, H., Ropers, H.H., Laumonnier, F., Ranieri, E., Schwartz, C.E., Abidi, F., Tarpey, P.S., Futreal, P.A., Whibley, A., Raymond, F.L., Stratton, M.R., Fryns, J.P., Scott, R., Peippo, M., Sipponen, M., Partington, M., Mowat, D., Field, M., Hackett, A., Marynen, P., Turner, G., Gécz, J. Am. J. Hum. Genet. (2008) [Pubmed]
  5. Life, death, and ubiquitin: taming the mule. Shmueli, A., Oren, M. Cell (2005) [Pubmed]
  6. Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis. Zhong, Q., Gao, W., Du, F., Wang, X. Cell (2005) [Pubmed]
  7. Characterization of E3Histone, a novel testis ubiquitin protein ligase which ubiquitinates histones. Liu, Z., Oughtred, R., Wing, S.S. Mol. Cell. Biol. (2005) [Pubmed]
  8. Golgin-160 Is Required for the Golgi Membrane Sorting of the Insulin-responsive Glucose Transporter GLUT4 in Adipocytes. Williams, D., Hicks, S.W., Machamer, C.E., Pessin, J.E. Mol. Biol. Cell (2006) [Pubmed]
  9. Effects of dietary fructose on liver steatosis in overfed mule ducks. Davail, S., Rideau, N., Bernadet, M.D., André, J.M., Guy, G., Hoo-Paris, R. Horm. Metab. Res. (2005) [Pubmed]
  10. UREB1, a tyrosine phosphorylated nuclear protein, inhibits p53 transactivation. Gu, J., Dubner, R., Fornace, A.J., Iadarola, M.J. Oncogene (1995) [Pubmed]
  11. Alternative reading frame protein (ARF)-independent function of CARF (collaborator of ARF) involves its interactions with p53: evidence for a novel p53-activation pathway and its negative feedback control. Hasan, M.K., Yaguchi, T., Minoda, Y., Hirano, T., Taira, K., Wadhwa, R., Kaul, S.C. Biochem. J. (2004) [Pubmed]
  12. BH3-ligand regulates access of MCL-1 to its E3 ligase. Warr, M.R., Acoca, S., Liu, Z., Germain, M., Watson, M., Blanchette, M., Wing, S.S., Shore, G.C. FEBS Lett. (2005) [Pubmed]
  13. The early vertebrate Danio rerio Mr 46000 mannose-6-phosphate receptor: biochemical and functional characterisation. Koduru, S., Vegiraju, S.R., Nadimpalli, S.K., von Figura, K., Pohlmann, R., Dennes, A. Dev. Genes Evol. (2006) [Pubmed]
  14. Testosterone concentrations, testes weight and morphology of mule drakes (Muscovy drake x Khaki Campbell). Snapir, N., Rulf, J., Meltzer, A., Gvaryahu, G., Rozenboim, I., Robinzon, B. Br. Poult. Sci. (1998) [Pubmed]
  15. Pancreatic hormonal and metabolic responses in overfed ducks. Davail, S., Rideau, N., Guy, G., André, J.M., Hoo-Paris, R. Horm. Metab. Res. (2003) [Pubmed]
  16. Changes in lipid composition of hepatocyte plasma membrane induced by overfeeding in duck. Molee, W., Bouillier-Oudot, M., Auvergne, A., Babilé, R. Comp. Biochem. Physiol. B, Biochem. Mol. Biol. (2005) [Pubmed]
  17. A glucokinase-like enzyme induced in Mule duck livers by overfeeding. Berradi, H., Guy, G., Rideau, N. Poult. Sci. (2004) [Pubmed]
  18. A novel ARF-binding protein (LZAP) alters ARF regulation of HDM2. Wang, J., He, X., Luo, Y., Yarbrough, W.G. Biochem. J. (2006) [Pubmed]
  19. Minireview: recent developments in the regulation of glucose transporter-4 traffic: new signals, locations, and partners. Ishiki, M., Klip, A. Endocrinology (2005) [Pubmed]
  20. Artificial insemination and natural mating in the crossbreeding of the Muscovy drake and the Pekin duck. Gvaryahu, G., Robinzon, B., Meltzer, A., Perek, M., Snapir, N. Poult. Sci. (1984) [Pubmed]
  21. Extensive homology between the major immunodominant mitochondrial antigen in primary biliary cirrhosis and Helicobacter pylori does not lead to immunological cross-reactivity. Bogdanos, D.P., Baum, H., Gunsar, F., Arioli, D., Polymeros, D., Ma, Y., Burroughs, A.K., Vergani, D. Scand. J. Gastroenterol. (2004) [Pubmed]
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