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Gene Review

UBR5  -  ubiquitin protein ligase E3 component n...

Homo sapiens

Synonyms: DD5, E3 ubiquitin-protein ligase UBR5, E3 ubiquitin-protein ligase, HECT domain-containing 1, EDD, EDD1, ...
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Disease relevance of EDD1


Psychiatry related information on EDD1

  • Plasma concentrations of BUP were time dependent, as were withdrawal symptoms, carbon dioxide sensitivity and extent of HYD blockade [5].

High impact information on EDD1

  • Preliminary evidence for the biological significance of this PR signaling pathway through regulatory SH3 domains was shown with respect to an influence on progestin-induced growth arrest of breast epithelial cells and induction of Xenopus oocyte maturation [6].
  • Brachial artery diameter was measured at rest, during increased flow (causing endothelium-dependent dilation, EDD) and after sublingual glyceryl trinitrate (causing endothelium-independent dilation) [7].
  • Dietary supplementation with L-arginine significantly improves EDD in hypercholesterolemic young adults, and this may impact favorably on the atherogenic process [7].
  • Expression of the progestin-induced fatty acid synthetase in benign mastopathies and breast cancer as measured by RNA in situ hybridization [8].
  • Sequence profile searches and comparative protein structure modeling identified a small ORF from the Arabidopsis thaliana genome that encodes a structurally similar but distantly related PABP/HYD domain [9].

Chemical compound and disease context of EDD1


Biological context of EDD1


Anatomical context of EDD1


Associations of EDD1 with chemical compounds


Physical interactions of EDD1


Enzymatic interactions of EDD1

  • To further validate the method, we present data that confirm that ERK2 phosphorylates EDD in vitro and in vivo [26].

Regulatory relationships of EDD1


Other interactions of EDD1


Analytical, diagnostic and therapeutic context of EDD1

  • Multivariate analysis confirmed homocysteine level as the strongest predictor for impaired EDD, independent of age, sex, body mass index, or blood pressure, folate, vitamin B12, and cholesterol levels [21].
  • METHODS: Availability of muOR (measured with positron emission tomography and [(11)C]-carfentanil), plasma BUP concentration, opioid withdrawal symptoms, and blockade of hydromorphone (HYD; heroin-like agonist) effects were measured at 4, 28, 52, and 76 hours after omitting the 16 mg/d dose of BUP in a study reported elsewhere [5].
  • Measurements of left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), stroke dimension (SD = LVEDD-LVESD), fractional shortening (FS = SD/EDD) and posterior wall thickness (PWT) were obtained from continuous 2-D targeted on M-mode echocardiography [31].
  • In normal subjects, EPSS was 2.5 +/- 1.7 mm and "normalized" EPSS, that is, the ratio of EPSS to end-diastolic dimension (EPSS/EDD), was 0.08 +/- 0.06 (mean +/- standard deviation); there was no correlation between either of these indexes and age, body surface area, height or weight [20].
  • Materials and methods Blood was drawn on the third and sixth days after progestin-induced withdrawal bleeding in 20 young non-diabetic women with PCOS and once between the third and sixth days of the menstrual cycle in 21 age-matched lean healthy control women during a 75-g oral glucose tolerance test (oGTT) [32].


  1. Progestin-induced caveolin-1 expression mediates breast cancer cell proliferation. Salatino, M., Beguelin, W., Peters, M.G., Carnevale, R., Proietti, C.J., Galigniana, M.D., Vedoy, C.G., Schillaci, R., Charreau, E.H., Sogayar, M.C., Elizalde, P.V. Oncogene (2006) [Pubmed]
  2. EDD, the human orthologue of the hyperplastic discs tumour suppressor gene, is amplified and overexpressed in cancer. Clancy, J.L., Henderson, M.J., Russell, A.J., Anderson, D.W., Bova, R.J., Campbell, I.G., Choong, D.Y., Macdonald, G.A., Mann, G.J., Nolan, T., Brady, G., Olopade, O.I., Woollatt, E., Davies, M.J., Segara, D., Hacker, N.F., Henshall, S.M., Sutherland, R.L., Watts, C.K. Oncogene (2003) [Pubmed]
  3. Increase of estrogen dose deteriorates mood during progestin phase in sequential hormonal therapy. Björn, I., Sundström-Poromaa, I., Bixo, M., Nyberg, S., Bäckström, G., Bäckström, T. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  4. Mannose-binding lectin-2 genetic variation and stomach cancer risk. Baccarelli, A., Hou, L., Chen, J., Lissowska, J., El-Omar, E.M., Grillo, P., Giacomini, S.M., Yaeger, M., Bernig, T., Zatonski, W., Fraumeni, J.F., Chanock, S.J., Chow, W.H. Int. J. Cancer (2006) [Pubmed]
  5. Buprenorphine Duration of Action: Mu-opioid Receptor Availability and Pharmacokinetic and Behavioral Indices. Greenwald, M., Johanson, C.E., Bueller, J., Chang, Y., Moody, D.E., Kilbourn, M., Koeppe, R., Zubieta, J.K. Biol. Psychiatry (2007) [Pubmed]
  6. Progesterone receptor contains a proline-rich motif that directly interacts with SH3 domains and activates c-Src family tyrosine kinases. Boonyaratanakornkit, V., Scott, M.P., Ribon, V., Sherman, L., Anderson, S.M., Maller, J.L., Miller, W.T., Edwards, D.P. Mol. Cell (2001) [Pubmed]
  7. Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults. Clarkson, P., Adams, M.R., Powe, A.J., Donald, A.E., McCredie, R., Robinson, J., McCarthy, S.N., Keech, A., Celermajer, D.S., Deanfield, J.E. J. Clin. Invest. (1996) [Pubmed]
  8. Expression of the progestin-induced fatty acid synthetase in benign mastopathies and breast cancer as measured by RNA in situ hybridization. Chalbos, D., Escot, C., Joyeux, C., Tissot-Carayon, M.J., Pages, A., Rochefort, H. J. Natl. Cancer Inst. (1990) [Pubmed]
  9. X-ray structure of the human hyperplastic discs protein: an ortholog of the C-terminal domain of poly(A)-binding protein. Deo, R.C., Sonenberg, N., Burley, S.K. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  10. Identification of a human HECT family protein with homology to the Drosophila tumor suppressor gene hyperplastic discs. Callaghan, M.J., Russell, A.J., Woollatt, E., Sutherland, G.R., Sutherland, R.L., Watts, C.K. Oncogene (1998) [Pubmed]
  11. Estrogen, androgen, glucocorticoid, and progesterone receptors in progestin-induced regression of human breast cancer. Teulings, F.A., van Gilse, H.A., Henkelman, M.S., Portengen, H., Alexieva-Figusch, J. Cancer Res. (1980) [Pubmed]
  12. Endothelial dysfunction in renal transplant patients is closely related to serum cyclosporine levels. Mercanoglu, F., Turkmen, A., Kocaman, O., Pinarbasi, B., Dursun, M., Selcukbiricik, F., Sever, M.S. Transplant. Proc. (2004) [Pubmed]
  13. Cooperation of HECT-domain ubiquitin ligase hHYD and DNA topoisomerase II-binding protein for DNA damage response. Honda, Y., Tojo, M., Matsuzaki, K., Anan, T., Matsumoto, M., Ando, M., Saya, H., Nakao, M. J. Biol. Chem. (2002) [Pubmed]
  14. Phosphorylation of human progesterone receptors at serine-294 by mitogen-activated protein kinase signals their degradation by the 26S proteasome. Lange, C.A., Shen, T., Horwitz, K.B. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  15. EDD, the human hyperplastic discs protein, has a role in progesterone receptor coactivation and potential involvement in DNA damage response. Henderson, M.J., Russell, A.J., Hird, S., Muñoz, M., Clancy, J.L., Lehrbach, G.M., Calanni, S.T., Jans, D.A., Sutherland, R.L., Watts, C.K. J. Biol. Chem. (2002) [Pubmed]
  16. Involvement of histone acetylation in ovarian steroid-induced decidualization of human endometrial stromal cells. Sakai, N., Maruyama, T., Sakurai, R., Masuda, H., Yamamoto, Y., Shimizu, A., Kishi, I., Asada, H., Yamagoe, S., Yoshimura, Y. J. Biol. Chem. (2003) [Pubmed]
  17. Expression of the gene encoding growth hormone in the human mammary gland. Mol, J.A., Henzen-Logmans, S.C., Hageman, P., Misdorp, W., Blankenstein, M.A., Rijnberk, A. J. Clin. Endocrinol. Metab. (1995) [Pubmed]
  18. Proliferation of endothelial and tumor epithelial cells by progestin-induced vascular endothelial growth factor from human breast cancer cells: paracrine and autocrine effects. Liang, Y., Hyder, S.M. Endocrinology (2005) [Pubmed]
  19. New insights in the molecular mechanism of progestin-induced proliferation of mammary epithelium: induction of the local biosynthesis of growth hormone (GH) in the mammary glands of dogs, cats and humans. Mol, J.A., van Garderen, E., Rutteman, G.R., Rijnberk, A. J. Steroid Biochem. Mol. Biol. (1996) [Pubmed]
  20. Mitral valve E point to ventricular septal separation in infants and children. Engle, S.J., DiSessa, T.G., Perloff, J.K., Isabel-Jones, J., Leighton, J., Gross, K., Friedman, W.F. Am. J. Cardiol. (1983) [Pubmed]
  21. Hyperhomocyst(e)inemia is a risk factor for arterial endothelial dysfunction in humans. Woo, K.S., Chook, P., Lolin, Y.I., Cheung, A.S., Chan, L.T., Sun, Y.Y., Sanderson, J.E., Metreweli, C., Celermajer, D.S. Circulation (1997) [Pubmed]
  22. Estrogenic potential of progestins in oral contraceptives to stimulate human breast cancer cell proliferation. Jeng, M.H., Parker, C.J., Jordan, V.C. Cancer Res. (1992) [Pubmed]
  23. Interference between progesterone and dioxin signal transduction pathways. Different mechanisms are involved in repression by the progesterone receptor A and B isoforms. Kuil, C.W., Brouwer, A., van der Saag, P.T., van der Burg, B. J. Biol. Chem. (1998) [Pubmed]
  24. EDD mediates DNA damage-induced activation of CHK2. Henderson, M.J., Munoz, M.A., Saunders, D.N., Clancy, J.L., Russell, A.J., Williams, B., Pappin, D., Khanna, K.K., Jackson, S.P., Sutherland, R.L., Watts, C.K. J. Biol. Chem. (2006) [Pubmed]
  25. Ovarian age-related responsiveness to human chorionic gonadotropin in women with polycystic ovary syndrome. Piltonen, T., Koivunen, R., Perheentupa, A., Morin-Papunen, L., Ruokonen, A., Tapanainen, J.S. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  26. Identification of novel ERK2 substrates through use of an engineered kinase and ATP analogs. Eblen, S.T., Kumar, N.V., Shah, K., Henderson, M.J., Watts, C.K., Shokat, K.M., Weber, M.J. J. Biol. Chem. (2003) [Pubmed]
  27. G protein-coupled receptor 30 is critical for a progestin-induced growth inhibition in MCF-7 breast cancer cells. Ahola, T.M., Manninen, T., Alkio, N., Ylikomi, T. Endocrinology (2002) [Pubmed]
  28. Co-operation of progestational steroids with epidermal growth factor in activation of gene expression in mammary tumor cells. Krusekopf, S., Chauchereau, A., Milgrom, E., Henderson, D., Cato, A.C. J. Steroid Biochem. Mol. Biol. (1991) [Pubmed]
  29. Integration of progesterone receptor mediated rapid signaling and nuclear actions in breast cancer cell models: role of mitogen-activated protein kinases and cell cycle regulators. Faivre, E., Skildum, A., Pierson-Mullany, L., Lange, C.A. Steroids (2005) [Pubmed]
  30. Progestin and G protein-coupled receptor 30 inhibit mitogen-activated protein kinase activity in MCF-7 breast cancer cells. Ahola, T.M., Alkio, N., Manninen, T., Ylikomi, T. Endocrinology (2002) [Pubmed]
  31. Cardiovascular response to sudden strenuous exercise: an exercise echocardiographic study. Chesler, R.M., Michielli, D.W., Aron, M., Stein, R.A. Medicine and science in sports and exercise. (1997) [Pubmed]
  32. Women with polycystic ovary syndrome are sensitive to the TNF-alpha-lowering effect of glucose-induced hyperinsulinaemia. Puder, J.J., Varga, S., Nusbaumer, C.P., Zulewski, H., Bilz, S., M??ller, B., Keller, U. Eur. J. Clin. Invest. (2006) [Pubmed]
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