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Gene Review

Ubr5  -  ubiquitin protein ligase E3 component n...

Rattus norvegicus

Synonyms: 100 kDa protein, Dd5, E3 ubiquitin-protein ligase UBR5, E3 ubiquitin-protein ligase, HECT domain-containing 1, Edd, ...
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Disease relevance of Dd5

  • Addition of GTP or its analogs to the binding reaction, exposure of intact cells to pertussis toxin prior to irradiation, or treatment of irradiated membranes with N-ethylmaleimide did not change the target size (approximately equal to 100 kDa) for opioid receptors in NG 108-15 cells and rat brain [1].
  • Furthermore, both the abnormal mature 130-kDa and precursor 100-kDa beta 1-subunits were detected on the surface of Zajdela hepatoma cells, associated with the alpha 5-subunit [2].
  • Tetanus toxin is composed of a heavy chain (100 kDa) and a light chain (50 kDa) held together by a single interchain disulfide bridge [3].
  • The nature and subcellular localization of the enzymic activities responsible for the production of the 20 kDa protein betagranin from its 100 kDa chromogranin-A-like precursor was investigated in transplantable insulinoma tissue [4].
  • Utilization of heme-hemopexin as a source of heme by Haemophilus influenzae type b is dependent on expression by this bacterium of the 100-kDa HxuA protein, which is both present on the bacterial cell surface and released into the culture supernatant (L. D. Cope, R. Yogev, U. Muller-Eberhard, and E. J. Hansen, J. Bacteriol. 177:2644-2653, 1995) [5].

High impact information on Dd5

  • Gi-mediated activation of the Ras/MAP kinase pathway involves a 100 kDa tyrosine-phosphorylated Grb2 SH3 binding protein, but not Src nor Shc [6].
  • The pore-forming toxin streptolysin O (SLO) can be used to reversibly permeabilize adherent and nonadherent cells, allowing delivery of molecules with up to 100 kDa mass to the cytosol [7].
  • Preliminary analysis of key activity present in BSN-CM indicates that it is a heat-sensitive, heparin-binding factor with a probable molecular mass greater than 100 kDa [8].
  • Dynamin is a 100-kDa microtubule-activated GTPase originally isolated from mammalian brain that has been proposed to be crucial in the early steps of endocytosis [9].
  • In adult rat brain, the microtubule-associated protein dynamin is composed of a closely spaced polypeptide doublet of approximately 100 kDa [10].

Chemical compound and disease context of Dd5

  • The protein quantity and activity of this 100-kDa src-related protein tyrosine kinase significantly increased with the progress of chronic hepatitis to hepatocellular carcinoma, especially in the tumorous portion of the liver [11].
  • Here, the crystallization in the absence of Ca(2+) of an inactive mutant hybrid calpain (MW approximately 100 kDa), which contains 85% of the rat mu-calpain sequence and is well expressed in Escherichia coli, is described [12].
  • The 45, 55, 65 and 100 kDa ATP-binding proteinases (ATP-BPases) of the heat-shocked (44 degrees C for 30 min, recovery for 12 h) rat C6 glioma cells were purified by DEAE-ionexchange and ATP-affinity chromatography [13].
  • The ability of RU486 to counteract progestin-induced lordosis was assessed by infusing 10 micrograms of this agent into the VMHN along with any of the progestins [14].
  • CONCLUSIONS: The infusion of the beta-amylase fraction containing a 100-kDa glycoprotein from IMLNS patients in relapse induced proteinuria and effacement of foot processes in the rat [15].

Biological context of Dd5


Anatomical context of Dd5

  • A cDNA has been isolated from a rat testis library which encodes a novel protein of 100 kDa that contains domains found in two different proteins involved in the processing of pre-mRNAs [17].
  • Protein kinase C agonists (phorbol ester and diacylglycerol) and agonist precursor (myoinositol) reversed the Na+ pump lesion, suggesting that protein kinase C-dependent phosphorylation of the 100-kDa subunit regulates Na+ pump activity and that insulin can influence erythrocyte protein kinase C activity [20].
  • Polyclonal antibodies, raised against the purified 100-kDa protein, recognized the protein in a variety of mammalian tissues and cell lines [21].
  • A major substrate, Mr 100,00 (100 kDa), for a Ca2+/calmodulin (CaM)-dependent protein kinase found in many mammalian tissues has been purified from rat pancreas [21].
  • Immunoblot analysis of crude liver membranes revealed a single band at 100 kDa [19].

Associations of Dd5 with chemical compounds


Physical interactions of Dd5


Enzymatic interactions of Dd5

  • Instead, we detect a 100 kDa tyrosine-phosphorylated protein (p100) that binds to the C-terminal SH3 domain of Grb2 in a strictly Gi- and agonist-dependent manner [6].
  • Only CaM kinase III was able to phosphorylate the 100-kDa protein; synapsin I, phosphorylase b, myosin light chain, and histone were poor substrates for this enzyme [21].

Other interactions of Dd5


Analytical, diagnostic and therapeutic context of Dd5

  • The NTF and CTF eluted from a gel filtration column at an estimated mass of over 100 kDa, suggesting that these fragments exist as an oligomerized species [34].
  • Immunoassay revealed that the 100-kDa protein made up 0.3-1.7% of the total cytosolic protein in these samples [21].
  • Western immunoblots of ER proteins probed with polyclonal antibodies raised against the 100-kDa SR Ca-ATPase of rabbit skeletal muscle identified a single reactive protein of 100 kDa [35].
  • Insulin-activated ribosomal S6 kinases were resolved into two major peaks by Mono Q chromatography, the latter of which contained a 100-kDa isoform of p90rsk as revealed by immunoblotting with an anti-rsk-peptide antibody [36].
  • Insulin- and Ox-Hb-hydrolyzing activity was also inhibited following immunoprecipitation of the 100-kDa metalloinsulinase [37].


  1. Sodium modulates opioid receptors through a membrane component different from G-proteins. Demonstration by target size analysis. Ott, S., Costa, T., Herz, A. J. Biol. Chem. (1988) [Pubmed]
  2. Biosynthesis, surface expression and function of the fibronectin receptor after rat liver cell transformation to tumorigenicity. Decastel, M., Doyennette-Moyne, M.A., Gouet, E., Aubery, M., Codogno, P. Biochem. J. (1993) [Pubmed]
  3. An intact interchain disulfide bond is required for the neurotoxicity of tetanus toxin. Schiavo, G., Papini, E., Genna, G., Montecucco, C. Infect. Immun. (1990) [Pubmed]
  4. Proteolytic processing of chromogranin A in purified insulin granules. Formation of a 20 kDa N-terminal fragment (betagranin) by the concerted action of a Ca2+-dependent endopeptidase and carboxypeptidase H (EC Hutton, J.C., Davidson, H.W., Peshavaria, M. Biochem. J. (1987) [Pubmed]
  5. Binding of heme-hemopexin complexes by soluble HxuA protein allows utilization of this complexed heme by Haemophilus influenzae. Cope, L.D., Thomas, S.E., Hrkal, Z., Hansen, E.J. Infect. Immun. (1998) [Pubmed]
  6. Gi-mediated activation of the Ras/MAP kinase pathway involves a 100 kDa tyrosine-phosphorylated Grb2 SH3 binding protein, but not Src nor Shc. Kranenburg, O., Verlaan, I., Hordijk, P.L., Moolenaar, W.H. EMBO J. (1997) [Pubmed]
  7. Delivery of proteins into living cells by reversible membrane permeabilization with streptolysin-O. Walev, I., Bhakdi, S.C., Hofmann, F., Djonder, N., Valeva, A., Aktories, K., Bhakdi, S. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  8. Branching morphogenesis independent of mesenchymal-epithelial contact in the developing kidney. Qiao, J., Sakurai, H., Nigam, S.K. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  9. Identification of dynamin 2, an isoform ubiquitously expressed in rat tissues. Cook, T.A., Urrutia, R., McNiven, M.A. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  10. Analysis of dynamin isoforms in mammalian brain: dynamin-1 expression is spatially and temporally regulated during postnatal development. Faire, K., Trent, F., Tepper, J.M., Bonder, E.M. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  11. A possible novel src-related tyrosine kinase in cancer cells of LEC rats that develop hepatocellular carcinoma. Masaki, T., Tokuda, M., Shiratori, Y., Shirai, M., Matsumoto, K., Nishioka, M., Omata, M. J. Hepatol. (2000) [Pubmed]
  12. Purification, crystallization and preliminary X-ray analysis of a mu-like calpain. Pal, G.P., DeVeyra, T., Elce, J.S., Jia, Z. Acta Crystallogr. D Biol. Crystallogr. (2003) [Pubmed]
  13. Heat shock induction of a 65 kDa ATP-binding proteinase in rat C6 glioma cells. Xu, C.S., Zhang, W.M., Techel, D., Meyer, M., Li, Y.Z., Rensing, L. Cell Res. (1999) [Pubmed]
  14. Intrahypothalamic injection of RU486 antagonizes the lordosis induced by ring A-reduced progestins. González-Mariscal, G., González-Flores, O., Beyer, C. Physiol. Behav. (1989) [Pubmed]
  15. Proteinuria and fusion of podocyte foot processes in rats after infusion of cytokine from patients with idiopathic minimal lesion nephrotic syndrome. Garin, E.H., Laflam, P.F., Muffly, K. Nephron Exp. Nephrol. (2006) [Pubmed]
  16. 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]
  17. Molecular characterization of a novel rat protein structurally related to poly(A) binding proteins and the 70K protein of the U1 small nuclear ribonucleoprotein particle (snRNP). Müller, D., Rehbein, M., Baumeister, H., Richter, D. Nucleic Acids Res. (1992) [Pubmed]
  18. Protein kinase C as a component of a nerve growth factor-sensitive phosphorylation system in PC12 cells. Hama, T., Huang, K.P., Guroff, G. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  19. Endopeptidase from rat liver membranes, which generates miniglucagon from glucagon. Blache, P., Kervran, A., Le-Nguyen, D., Dufour, M., Cohen-Solal, A., Duckworth, W., Bataille, D. J. Biol. Chem. (1993) [Pubmed]
  20. Reversible sodium pump defect and swelling in the diabetic rat erythrocyte: effects on filterability and implications for microangiopathy. Kowluru, R., Bitensky, M.W., Kowluru, A., Dembo, M., Keaton, P.A., Buican, T. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  21. Identification of calmodulin-dependent protein kinase III and its major Mr 100,000 substrate in mammalian tissues. Nairn, A.C., Bhagat, B., Palfrey, H.C. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  22. Functional reconstitution of the canalicular bile salt transport system of rat liver. Ruetz, S., Hugentobler, G., Meier, P.J. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  23. Human anti-endoplasmic reticulum antibodies in sera of patients with halothane-induced hepatitis are directed against a trifluoroacetylated carboxylesterase. Satoh, H., Martin, B.M., Schulick, A.H., Christ, D.D., Kenna, J.G., Pohl, L.R. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  24. Biochemical characterization of the mammalian stress proteins and identification of two stress proteins as glucose- and Ca2+-ionophore-regulated proteins. Welch, W.J., Garrels, J.I., Thomas, G.P., Lin, J.J., Feramisco, J.R. J. Biol. Chem. (1983) [Pubmed]
  25. Evidence for structural and functional diversity among SDS-resistant SNARE complexes in neuroendocrine cells. Kubista, H., Edelbauer, H., Boehm, S. J. Cell. Sci. (2004) [Pubmed]
  26. Growth promotion by insulin-like growth factor I in hypophysectomized and diabetic rats. Zapf, J. Mol. Cell. Endocrinol. (1998) [Pubmed]
  27. Gi-mediated tyrosine phosphorylation of Grb2 (growth-factor-receptor-bound protein 2)-bound dynamin-II by lysophosphatidic acid. Kranenburg, O., Verlaan, I., Moolenaar, W.H. Biochem. J. (1999) [Pubmed]
  28. Localization and subcellular distribution of SH-PTP2, a protein-tyrosine phosphatase with Src homology-2 domains, in rat brain. Suzuki, T., Matozaki, T., Mizoguchi, A., Kasuga, M. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  29. Follicle-stimulating hormone activates extracellular signal-regulated kinase but not extracellular signal-regulated kinase kinase through a 100-kDa phosphotyrosine phosphatase. Cottom, J., Salvador, L.M., Maizels, E.T., Reierstad, S., Park, Y., Carr, D.W., Davare, M.A., Hell, J.W., Palmer, S.S., Dent, P., Kawakatsu, H., Ogata, M., Hunzicker-Dunn, M. J. Biol. Chem. (2003) [Pubmed]
  30. Complete amino acid sequence of rat brain hexokinase, deduced from the cloned cDNA, and proposed structure of a mammalian hexokinase. Schwab, D.A., Wilson, J.E. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  31. Phosphatidylinositol 3-kinase regulates nuclear translocation of NF-E2-related factor 2 through actin rearrangement in response to oxidative stress. Kang, K.W., Lee, S.J., Park, J.W., Kim, S.G. Mol. Pharmacol. (2002) [Pubmed]
  32. Phosphorylation and inactivation of HMG-CoA reductase at the AMP-activated protein kinase site in response to fructose treatment of isolated rat hepatocytes. Gillespie, J.G., Hardie, D.G. FEBS Lett. (1992) [Pubmed]
  33. Contribution of a time-dependent and hyperpolarization-activated chloride conductance to currents of resting and hypotonically shocked rat hepatocytes. Lan, W.Z., Abbas, H., Lam, H.D., Lemay, A.M., Hill, C.E. Am. J. Physiol. Gastrointest. Liver Physiol. (2005) [Pubmed]
  34. Evidence for phosphorylation and oligomeric assembly of presenilin 1. Seeger, M., Nordstedt, C., Petanceska, S., Kovacs, D.M., Gouras, G.K., Hahne, S., Fraser, P., Levesque, L., Czernik, A.J., George-Hyslop, P.S., Sisodia, S.S., Thinakaran, G., Tanzi, R.E., Greengard, P., Gandy, S. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  35. Endoplasmic reticulum of rat liver contains two proteins closely related to skeletal sarcoplasmic reticulum Ca-ATPase and calsequestrin. Damiani, E., Spamer, C., Heilmann, C., Salvatori, S., Margreth, A. J. Biol. Chem. (1988) [Pubmed]
  36. Characterization of insulin-stimulated seryl/threonyl protein kinases in rat skeletal muscle. Hei, Y.J., McNeill, J.H., Sanghera, J.S., Diamond, J., Bryer-Ash, M., Pelech, S.L. J. Biol. Chem. (1993) [Pubmed]
  37. The ATP-independent pathway in red blood cells that degrades oxidant-damaged hemoglobin. Fagan, J.M., Waxman, L. J. Biol. Chem. (1992) [Pubmed]
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