The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

RNF19A  -  ring finger protein 19A, RBR E3 ubiquitin...

Homo sapiens

Synonyms: DKFZp566B1346, Dorfin, Double ring-finger protein, E3 ubiquitin-protein ligase RNF19A, RING finger protein 19A, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of RNF19


High impact information on RNF19


Chemical compound and disease context of RNF19


Biological context of RNF19


Anatomical context of RNF19


Associations of RNF19 with chemical compounds

  • VCP(K524A), a dominant negative form of VCP, reduced the E3 activity of Dorfin against mutant superoxide dismutase 1, whereas it had no effect on the autoubiquitylation of Parkin [1].
  • Glycerol gradient centrifugation analysis showed that endogenous Dorfin consisted of a 400-600-kDa complex and was co-immunoprecipitated with endogenous VCP [1].
  • Aloe-emodin (40 microM)-induced apoptosis of H460 cells involves modulation of cAMP-dependent protein kinase, protein kinase C, Bcl-2, caspase-3 and p38 protein expression [17].
  • The anticancer agent methyl jasmonate induces activation of stress-regulated c-Jun N-terminal kinase and p38 protein kinase in human lymphoid cells [18].
  • HIV-gp120 enhancement of IL-1beta-induced NO(2)(-) production was blocked by 10 microM of SB-203580 (SB), a selective p38 protein kinase inhibitor (3.6 +/- 0.2 vs. 6.6 +/- 0.6 micromol/1. 25 x 10(5) cells/48 h, IL-1beta + gp120 + SB vs. IL-1beta + gp120, respectively; n = 12, P </= 0.5) [19].

Physical interactions of RNF19

  • In vitro experiments showed that Dorfin interacted directly with VCP through its C-terminal region [1].

Enzymatic interactions of RNF19

  • We have previously reported that in thrombin-stimulated human platelets, cytosolic phospholipase A(2) (cPLA2) is phosphorylated on Ser-505 by p38 protein kinase and on Ser-727 by an unknown kinase [20].

Other interactions of RNF19

  • Dorfin localizes to Lewy bodies and ubiquitylates synphilin-1 [21].
  • High through-put analysis using mass spectrometry identified VCP as a candidate of Dorfin-associated protein [1].
  • However, because we failed to show the direct binding of alpha-synuclein with Dorfin, future investigations into the binding partner(s) of Dorfin will be needed to deepen our understanding of the pathophysiology of alpha-synucleinopathy and ALS [2].
  • There was no activation of JNK or p38 protein kinases [22].
  • Exercise increased total and nuclear p38 phosphorylation and association with MEF-2, without changes in total or nuclear p38 protein abundance [23].

Analytical, diagnostic and therapeutic context of RNF19

  • To improve its stability and enhance its E3 activity, we developed chimeric proteins containing the substrate-binding hydrophobic portion of Dorfin and the U-box domain of the carboxyl terminus of Hsc70-interacting protein (CHIP), which has strong E3 activity through the U-box domain [24].
  • By immunohistochemistry, the expression of all p38 MAPK isoforms was localized to the synovial lining layer as well as to blood vessels [25].
  • This phosphorylation pattern was confirmed in immunoprecipitation studies in which activated p38 MAPK from synovial tissue extracts was identified as p38 MAPKalpha and -gamma but not p38 MAPKbeta or -delta [25].
  • The expression and activation of the alpha, beta, gamma, and delta isoforms of p38 MAPK were examined by immunoblotting, immunoprecipitation, and immunohistochemistry [25].
  • Employing Western blot analysis and immunohistochemical studies, we found that GTP resulted in inhibition of UVB-induced: (i) phosphorylation of extracellular-signal-regulated kinases (ERK1/2), (ii) c-Jun N-terminal kinases, and (iii) p38 protein expression [26].


  1. Physical and functional interaction between Dorfin and Valosin-containing protein that are colocalized in ubiquitylated inclusions in neurodegenerative disorders. Ishigaki, S., Hishikawa, N., Niwa, J., Iemura, S., Natsume, T., Hori, S., Kakizuka, A., Tanaka, K., Sobue, G. J. Biol. Chem. (2004) [Pubmed]
  2. Dorfin localizes to the ubiquitylated inclusions in Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and amyotrophic lateral sclerosis. Hishikawa, N., Niwa, J., Doyu, M., Ito, T., Ishigaki, S., Hashizume, Y., Sobue, G. Am. J. Pathol. (2003) [Pubmed]
  3. Diverse effects of pathogenic mutations of Parkin that catalyze multiple monoubiquitylation in vitro. Matsuda, N., Kitami, T., Suzuki, T., Mizuno, Y., Hattori, N., Tanaka, K. J. Biol. Chem. (2006) [Pubmed]
  4. Macromolecular assemblage of aminoacyl-tRNA synthetases: quantitative analysis of protein-protein interactions and mechanism of complex assembly. Robinson, J.C., Kerjan, P., Mirande, M. J. Mol. Biol. (2000) [Pubmed]
  5. Peroxisome proliferator-activated receptor gamma as a molecular target of resveratrol-induced modulation of polyamine metabolism. Ulrich, S., Loitsch, S.M., Rau, O., von Knethen, A., Brüne, B., Schubert-Zsilavecz, M., Stein, J.M. Cancer Res. (2006) [Pubmed]
  6. Phenethyl isothiocyanate-induced apoptosis in p53-deficient PC-3 human prostate cancer cell line is mediated by extracellular signal-regulated kinases. Xiao, D., Singh, S.V. Cancer Res. (2002) [Pubmed]
  7. NK lytic-associated molecule, involved in NK cytotoxic function, is an E3 ligase. Fortier, J.M., Kornbluth, J. J. Immunol. (2006) [Pubmed]
  8. Calcium-sensing Receptor Ubiquitination and Degradation Mediated by the E3 Ubiquitin Ligase Dorfin. Huang, Y., Niwa, J., Sobue, G., Breitwieser, G.E. J. Biol. Chem. (2006) [Pubmed]
  9. Role of stress-activated MAP kinase P38 in cisplatin- and DTT-induced apoptosis of the esophageal carcinoma cell line Eca109. Zhang, Q.X., Feng, R., Zhang, W., Ding, Y., Yang, J.Y., Liu, G.H. World J. Gastroenterol. (2005) [Pubmed]
  10. Dorfin prevents cell death by reducing mitochondrial localizing mutant superoxide dismutase 1 in a neuronal cell model of familial amyotrophic lateral sclerosis. Takeuchi, H., Niwa, J., Hishikawa, N., Ishigaki, S., Tanaka, F., Doyu, M., Sobue, G. J. Neurochem. (2004) [Pubmed]
  11. Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of protein-protein interactions and characterization of a core protein. Quevillon, S., Robinson, J.C., Berthonneau, E., Siatecka, M., Mirande, M. J. Mol. Biol. (1999) [Pubmed]
  12. Role of reactive oxygen species and MAPKs in vanadate-induced G(2)/M phase arrest. Zhang, Z., Leonard, S.S., Huang, C., Vallyathan, V., Castranova, V., Shi, X. Free Radic. Biol. Med. (2003) [Pubmed]
  13. Detection of JNK and p38 activation by flow cytometry analysis. Bou, G., Villasis-Keever, A., Paya, C.V. Anal. Biochem. (2003) [Pubmed]
  14. Identification of brain proteins that interact with 2-methylnorharman. An analog of the parkinsonian-inducing toxin, MPP+. Gearhart, D.A., Toole, P.F., Warren Beach, J. Neurosci. Res. (2002) [Pubmed]
  15. A novel centrosomal ring-finger protein, dorfin, mediates ubiquitin ligase activity. Niwa , J., Ishigaki, S., Doyu, M., Suzuki, T., Tanaka, K., Sobue, G. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  16. Dorfin ubiquitylates mutant SOD1 and prevents mutant SOD1-mediated neurotoxicity. Niwa, J., Ishigaki, S., Hishikawa, N., Yamamoto, M., Doyu, M., Murata, S., Tanaka, K., Taniguchi, N., Sobue, G. J. Biol. Chem. (2002) [Pubmed]
  17. Signaling pathway for aloe-emodin-induced apoptosis in human H460 lung nonsmall carcinoma cell. Yeh, F.T., Wu, C.H., Lee, H.Z. Int. J. Cancer (2003) [Pubmed]
  18. The anticancer agent methyl jasmonate induces activation of stress-regulated c-Jun N-terminal kinase and p38 protein kinase in human lymphoid cells. Rotem, R., Fingrut, O., Moskovitz, J., Flescher, E. Leukemia (2003) [Pubmed]
  19. HIV gp120 enhances NO production by cardiac myocytes through p38 MAP kinase-mediated NF-kappaB activation. Kan, H., Xie, Z., Finkel, M.S. Am. J. Physiol. Heart Circ. Physiol. (2000) [Pubmed]
  20. Serine 727 phosphorylation and activation of cytosolic phospholipase A2 by MNK1-related protein kinases. Hefner, Y., Borsch-Haubold, A.G., Murakami, M., Wilde, J.I., Pasquet, S., Schieltz, D., Ghomashchi, F., Yates, J.R., Armstrong, C.G., Paterson, A., Cohen, P., Fukunaga, R., Hunter, T., Kudo, I., Watson, S.P., Gelb, M.H. J. Biol. Chem. (2000) [Pubmed]
  21. Dorfin localizes to Lewy bodies and ubiquitylates synphilin-1. Ito, T., Niwa, J., Hishikawa, N., Ishigaki, S., Doyu, M., Sobue, G. J. Biol. Chem. (2003) [Pubmed]
  22. Role of ERK activation in growth and erythroid differentiation of K562 cells. Woessmann, W., Mivechi, N.F. Exp. Cell Res. (2001) [Pubmed]
  23. Exercise and myocyte enhancer factor 2 regulation in human skeletal muscle. McGee, S.L., Hargreaves, M. Diabetes (2004) [Pubmed]
  24. Dorfin-CHIP chimeric proteins potently ubiquitylate and degrade familial ALS-related mutant SOD1 proteins and reduce their cellular toxicity. Ishigaki, S., Niwa, J., Yamada, S., Takahashi, M., Ito, T., Sone, J., Doyu, M., Urano, F., Sobue, G. Neurobiol. Dis. (2007) [Pubmed]
  25. Differential tissue expression and activation of p38 MAPK alpha, beta, gamma, and delta isoforms in rheumatoid arthritis. Korb, A., Tohidast-Akrad, M., Cetin, E., Axmann, R., Smolen, J., Schett, G. Arthritis Rheum. (2006) [Pubmed]
  26. Suppression of UVB-induced phosphorylation of mitogen-activated protein kinases and nuclear factor kappa B by green tea polyphenol in SKH-1 hairless mice. Afaq, F., Ahmad, N., Mukhtar, H. Oncogene (2003) [Pubmed]
WikiGenes - Universities