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Gene Review

RNF2  -  ring finger protein 2

Homo sapiens

Synonyms: BAP-1, BAP1, DING, E3 ubiquitin-protein ligase RING2, HIP2-interacting protein 3, ...
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Disease relevance of RNF2

  • Changes in expression associated with tumoral transformation have been found for BMI1 and RNF2, which exhibited increased expression in a large series of tumors, including gastrointestinal tumors, pituitary and parathyroid adenomas, and lymphomas, compared with their expression in normal-cell counterparts [1].
  • Confocal microscopy showed the presence of RNF2 in the cytoplasm of the Pgp-negative, drug-sensitive MCF-7 breast cancer cells [2].
  • Further, mutations in the RING-IBR-RING of Parkin cause a rare form of Parkinsonism and these studies provide an explanation for those mutations that occur in its RING2 [3].
  • These data indicate that patients with a flexible annuloplasty ring have better left ventricular systolic function than patients with a rigid annuloplasty ring 2 to 3 months after mitral valve reconstruction for chronic mitral regurgitation secondary to degenerative disease of the mitral valve [4].
  • To study the clinical effects of Da Ding Feng Zhu ([symbol: see text]) Decoction on liver fibrosis [5].

Psychiatry related information on RNF2

  • Nicotine dependence was measured by adapting the Fagerstrom Tolerance Questionnaire (FTQ; Prokhorov, Pallonen, Fava, Ding, & Niaura, 1996), and by a 6-item withdrawal symptom scale [6].

High impact information on RNF2

  • A variant tandemly repeated nucleotide sequence in Balbiani ring 2 of Chironomus tentans [7].
  • A hierarchic arrangement of the repetitive sequences in the Balbiani ring 2 gene of Chironomus tentans [8].
  • Furthermore, parallel repression of sp-Ib and sp-Id synthesis by galactose led us to hypothesize that both of their genes exist within Balbiani ring 2 [9].
  • We show that A. vinelandii has two clusters of rnf-like genes: rnf1, whose expression is nif-regulated, and rnf2, which is expressed independently of the nitrogen source in the medium [10].
  • (Chen, Y., Lu, J., Pan, H., Zhang, Y., Wu, H., Xu, K., Liu, X., Jiang, Y., Bao, X., Yao, Z., Ding, K., Lo, W. H., Qiang, B., Chan, P., Shen, Y., and Wu, X. (2003) Ann. Neurol. 54, 239-243) 12 missense mutations were identified in the CACNA1H (Ca(v)3.2) gene in 14 of 118 patients with CAE but not in 230 control individuals [11].

Biological context of RNF2

  • Interestingly, the RNF2-S6' interaction increases the ATP hydrolysis activity of the S6' protein [12].
  • We suggest that RNF2 regulates the cellular abundance of Pgp, and plays a key role in the development of cancer drug resistance through its own down-regulation [2].
  • During this cloning we found that HNK-1ST and other Golgi-associated sulfotransferases cloned before share homologous sequences including the RDP motif (Ong, E., Yeh, J.-C., Ding, Y., Hindsgaul, O., and Fukuda, M. (1998) J. Biol. Chem. 223, 5190-5195) [13].
  • Additionally, this RING2 topology is novel, bearing slight resemblance to zinc-ribbon motifs around the zinc site and is different from the topologies of the zinc binding sites found in RING and PHDs [3].
  • The injection of [11C]thymidine labeled in the ring-2 position or [11C]acetate labeled in the carboxylate position resulted in the production of large amounts of labeled CO2 with the exhalation of about 47% and 23%, respectively, of the injected label over 60 min [14].

Anatomical context of RNF2

  • Reducing the expression of Ring2 results in a dramatic decrease in the level of ubiquitinated H2A in HeLa cells [15].
  • We have evidence that the limulus (Tachypleus tri-dentatus) hemocyte transglutaminase (TGase) has a molecular mass of 86 kDa and properties of the mammalian type II TGase-like enzyme (Tokunaga, F., Yamada, M., Miyata, T., Ding, Y.-L., Hiranaga-Kawabata, M., Muta, T., Iwanaga, S., Ichinose, A., and Davie, E.W. (1993) J. Biol. Chem. 268, 252-261) [16].
  • The former used the mouse mammary carcinoma cell line GZHI, which expresses the human MUC-1 gene (L. Ding, E.N. Lalani, M. Reddish, R. Koganty, T. Wong, J. Samuel, M.B. Yacyshyn, A. Meikle, P.Y.S. Fung, J. Taylor-Papadimitriou, B.M. Longenecker, Cancer Immunol. Immunother. 36 (1993) 9--17) [17].

Associations of RNF2 with chemical compounds

  • During intracellular recycling of glypican-1, there is an NO-dependent deaminative cleavage of heparan sulfate at these glucosamine units, which would eliminate the positive charges (Ding, K., Sandgren, S., Mani, K., Belting, M., and Fransson, L.-A. (2001) J. Biol. Chem. 276, 46779-46791) [18].
  • To study the coupling between voltage sensors and gates, we immobilize the voltage sensors, using a bifunctional photo-cross-linking reagent that can be attached to an introduced cysteine, and observe the consequences for gate movement [Horn, R., Ding, S., and Gruber, H. J. (2000) J. Gen. Physiol. 116, 461-475] [19].
  • We recently identified a non-peptide small-molecule IR activator (compound 2), which induced human IR tyrosine kinase activity in Chinese-hamster ovary cells expressing human IR [Qureshi, Ding, Li, Szalkowski, Biazzo-Ashnault, Xie, Saperstein, Brady, Huskey, Shen et al. (2000) J. Biol. Chem. 275, 36590-36595] [20].
  • The DNA of Balbiani ring 2, which is the most active puff in larvae, is transcribed into large RNA molecules of about 22 X 10(6) D which resist degradation by heating, formamide or urea treatment [21].
  • [14C]Bromomisonidazole was prepared by direct bromination of [ring-2] [14C]misonidazole in dioxane [22].

Physical interactions of RNF2

  • 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 [23].

Other interactions of RNF2

  • The interaction of Hip-2 with RNF2, one of the clones, was further confirmed through in vitro and in vivo experiments [23].

Analytical, diagnostic and therapeutic context of RNF2

  • Our sequence analysis of the C-terminal RING (RING2) from this motif show that several metal ligating and hydrophobic residues critical for the formation of a classical RING cross-brace structure are not present [3].
  • Antibacterial activity of the Chinese traditional medicine, Zi Hua Di Ding [24].
  • 56 patients with liver fibrosis due to chronic hepatitis B were randomly divided into a treatment group (30 cases treated with Da Ding Feng Zhu Decoction) and a control group (26 cases treated with colchicine) [5].


  1. Variability in the expression of polycomb proteins in different normal and tumoral tissues. A pilot study using tissue microarrays. Sánchez-Beato, M., Sánchez, E., González-Carreró, J., Morente, M., Díez, A., Sánchez-Verde, L., Martín, M.C., Cigudosa, J.C., Vidal, M., Piris, M.A. Mod. Pathol. (2006) [Pubmed]
  2. RNF2 interacts with the linker region of the human P-glycoprotein. Rao, P.S., Mallya, K.B., Srivenugopal, K.S., Balaji, K.C., Rao, U.S. Int. J. Oncol. (2006) [Pubmed]
  3. Structure of the C-terminal RING finger from a RING-IBR-RING/TRIAD motif reveals a novel zinc-binding domain distinct from a RING. Capili, A.D., Edghill, E.L., Wu, K., Borden, K.L. J. Mol. Biol. (2004) [Pubmed]
  4. Mitral valve annuloplasty: the effect of the type on left ventricular function. David, T.E., Komeda, M., Pollick, C., Burns, R.J. Ann. Thorac. Surg. (1989) [Pubmed]
  5. Effects of da ding feng zhu decoction in 30 cases of liver fibrosis. Li, W., Wang, C., Zhang, J. Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan / sponsored by All-China Association of Traditional Chinese Medicine, Academy of Traditional Chinese Medicine. (2003) [Pubmed]
  6. An assessment of nicotine dependence among pregnant adolescents. Albrecht, S.A., Cornelius, M.D., Braxter, B., Reynolds, M.D., Stone, C., Cassidy, B. Journal of substance abuse treatment. (1999) [Pubmed]
  7. A variant tandemly repeated nucleotide sequence in Balbiani ring 2 of Chironomus tentans. Case, S.T., Summers, R.L., Jones, A.G. Cell (1983) [Pubmed]
  8. A hierarchic arrangement of the repetitive sequences in the Balbiani ring 2 gene of Chironomus tentans. Sümegi, J., Wieslander, L., Daneholt, B. Cell (1982) [Pubmed]
  9. A novel giant secretion polypeptide in Chironomus salivary glands: implications for another Balbiani ring gene. Kao, W.Y., Case, S.T. J. Cell Biol. (1985) [Pubmed]
  10. Genes required for rapid expression of nitrogenase activity in Azotobacter vinelandii. Curatti, L., Brown, C.S., Ludden, P.W., Rubio, L.M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  11. Gating effects of mutations in the Cav3.2 T-type calcium channel associated with childhood absence epilepsy. Khosravani, H., Altier, C., Simms, B., Hamming, K.S., Snutch, T.P., Mezeyova, J., McRory, J.E., Zamponi, G.W. J. Biol. Chem. (2004) [Pubmed]
  12. E3 ubiquitin ligase RNF2 interacts with the S6' proteasomal ATPase subunit and increases the ATP hydrolysis activity of S6'. Lee, S.J., Choi, D., Rhim, H., Kang, S. Biochem. J. (2005) [Pubmed]
  13. Molecular cloning and expression of two distinct human chondroitin 4-O-sulfotransferases that belong to the HNK-1 sulfotransferase gene family. Hiraoka, N., Nakagawa, H., Ong, E., Akama, T.O., Fukuda, M.N., Fukuda, M. J. Biol. Chem. (2000) [Pubmed]
  14. Contribution of labeled carbon dioxide to PET imaging of carbon-11-labeled compounds. Shields, A.F., Graham, M.M., Kozawa, S.M., Kozell, L.B., Link, J.M., Swenson, E.R., Spence, A.M., Bassingthwaighte, J.B., Krohn, K.A. J. Nucl. Med. (1992) [Pubmed]
  15. Role of histone H2A ubiquitination in Polycomb silencing. Wang, H., Wang, L., Erdjument-Bromage, H., Vidal, M., Tempst, P., Jones, R.S., Zhang, Y. Nature (2004) [Pubmed]
  16. Limulus hemocyte transglutaminase. cDNA cloning, amino acid sequence, and tissue localization. Tokunaga, F., Muta, T., Iwanaga, S., Ichinose, A., Davie, E.W., Kuma, K., Miyata, T. J. Biol. Chem. (1993) [Pubmed]
  17. Anti-MUC-1 immunoliposomal doxorubicin in the treatment of murine models of metastatic breast cancer. Moase, E.H., Qi, W., Ishida, T., Gabos, Z., Longenecker, B.M., Zimmermann, G.L., Ding, L., Krantz, M., Allen, T.M. Biochim. Biophys. Acta (2001) [Pubmed]
  18. Copper-dependent autocleavage of glypican-1 heparan sulfate by nitric oxide derived from intrinsic nitrosothiols. Ding, K., Mani, K., Cheng, F., Belting, M., Fransson, L.A. J. Biol. Chem. (2002) [Pubmed]
  19. Slow photo-cross-linking kinetics of benzophenone-labeled voltage sensors of ion channels. Ding, S., Horn, R. Biochemistry (2001) [Pubmed]
  20. Regulation of insulin signal transduction pathway by a small-molecule insulin receptor activator. Ding, V.D., Qureshi, S.A., Szalkowski, D., Li, Z., Biazzo-Ashnault, D.E., Xie, D., Liu, K., Jones, A.B., Moller, D.E., Zhang, B.B. Biochem. J. (2002) [Pubmed]
  21. The transcripts of Balbiani rings from Chironomus thummi. Giant RNA molecules with messenger characteristics. Serfling, E. Chromosoma (1976) [Pubmed]
  22. Further characterization of 4-bromomisonidazole as a potential detector of hypoxic cells. Rasey, J.S., Krohn, K.A., Grunbaum, Z., Conroy, P.J., Bauer, K., Sutherland, R.M. Radiat. Res. (1985) [Pubmed]
  23. 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]
  24. Antibacterial activity of the Chinese traditional medicine, Zi Hua Di Ding. Xie, C., Kokubun, T., Houghton, P.J., Simmonds, M.S. Phytotherapy research : PTR. (2004) [Pubmed]
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