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Gene Review

RNASE2  -  ribonuclease, RNase A family, 2 (liver,...

Homo sapiens

Synonyms: EDN, Eosinophil-derived neurotoxin, Non-secretory ribonuclease, RAF3, RNS2, ...
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Disease relevance of RNASE2


High impact information on RNASE2


Chemical compound and disease context of RNASE2

  • In rats subjected to chronic hypoxia (10% O2) for up to 10 wk, the two electrophysiological abnormalities had developed by 4 wk and were very similar in degree to those seen in EDN and EGN [10].
  • The cardinal electrophysiological abnormalities in experimental diabetic (EDN) and experimental galactose (EGN) neuropathy, models in which endoneurial hypoxia has been demonstrated, are a slowing in nerve conduction velocity (NCV) and a resistance to ischemic conduction block (RICB) [10].

Biological context of RNASE2

  • We mutated two human ribonucleases-pancreatic RNase (hRNAse) and eosinophil-derived neurotoxin (EDN)-to incorporate cysteine residues at putative sites of close contact to RI, but distant from the catalytic sites [1].
  • Amino acid sequence analyses showed that ECP-1 and ECP-2 are identical from residue 1 through residue 59 and that the sequences of EDN and ECP are highly homologous (37 of 55 residues identical) [11].
  • Neurologic abnormalities of onconase-treated animals were indistinguishable from those of EDN-treated animals, and histology showed dramatic Purkinje cell loss in the brains of onconase-treated animals [12].
  • In contrast, the homologous bovine pancreatic RNase A injected intraventricularly at a dose 5000 times greater than the LD50 dose of EDN or onconase is not toxic and does not cause the Gordon phenomenon [12].
  • We have previously shown that optimal expression of the EDN gene is dependent on an interaction between an intronic enhancer element or elements and the 5' promoter region [13].

Anatomical context of RNASE2


Associations of RNASE2 with chemical compounds


Physical interactions of RNASE2

  • Simultaneous substitutions of three neighboring tryptophans (261, 263, and 318) on RI attenuate affinity even more dramatically (by 4900-fold), indicating that the interactions of this RI region also contribute a considerable amount of the binding energy for the EDN complex [18].

Regulatory relationships of RNASE2


Other interactions of RNASE2

  • Coupling of Cys89 of RNase and Cys87 of EDN to proteins at these sites via a thioether bond produced enzymatically active conjugates that were resistant to RI [1].
  • Radioimmunoassay, using monoclonal antibodies, of fractions from the heparin-Sepharose chromatography showed one peak of EDN activity and two peaks of ECP activity (termed ECP-1 and ECP-2) [11].
  • The uneventful trends observed for RNase k6 serve to spotlight the unique nature of EDN and ECP and the unusual evolutionary constraints to which these two ribonuclease genes must be responding [24].
  • Expression of chimeras of RNase 2 and nonglycosylated RNase 4 and deletion mutants in HEK293 cells identified residues 1-13 to be sufficient for C-mannosylation [14].
  • We conclude that ECP and EPX/EDN may be used to monitor antiinflammatory treatment in asthmatic patients, and that smoking asthmatic subjects are resistant to inhaled corticosteroids [25].

Analytical, diagnostic and therapeutic context of RNASE2


  1. Engineering receptor-mediated cytotoxicity into human ribonucleases by steric blockade of inhibitor interaction. Suzuki, M., Saxena, S.K., Boix, E., Prill, R.J., Vasandani, V.M., Ladner, J.E., Sung, C., Youle, R.J. Nat. Biotechnol. (1999) [Pubmed]
  2. Eosinophil-derived neurotoxin (EDN), an antimicrobial protein with chemotactic activities for dendritic cells. Yang, D., Rosenberg, H.F., Chen, Q., Dyer, K.D., Kurosaka, K., Oppenheim, J.J. Blood (2003) [Pubmed]
  3. Mapping the ribonucleolytic active site of eosinophil-derived neurotoxin (EDN). High resolution crystal structures of EDN complexes with adenylic nucleotide inhibitors. Leonidas, D.D., Boix, E., Prill, R., Suzuki, M., Turton, R., Minson, K., Swaminathan, G.J., Youle, R.J., Acharya, K.R. J. Biol. Chem. (2001) [Pubmed]
  4. Molecular cloning of the human eosinophil-derived neurotoxin: a member of the ribonuclease gene family. Rosenberg, H.F., Tenen, D.G., Ackerman, S.J. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  5. Evolution of antiviral activity in the ribonuclease A gene superfamily: evidence for a specific interaction between eosinophil-derived neurotoxin (EDN/RNase 2) and respiratory syncytial virus. Domachowske, J.B., Bonville, C.A., Dyer, K.D., Rosenberg, H.F. Nucleic Acids Res. (1998) [Pubmed]
  6. Rapid evolution of a unique family of primate ribonuclease genes. Rosenberg, H.F., Dyer, K.D., Tiffany, H.L., Gonzalez, M. Nat. Genet. (1995) [Pubmed]
  7. Association of the eosinophilia-myalgia syndrome with the ingestion of tryptophan. Hertzman, P.A., Blevins, W.L., Mayer, J., Greenfield, B., Ting, M., Gleich, G.J. N. Engl. J. Med. (1990) [Pubmed]
  8. Differentiation in vitro of hybrid eosinophil/basophil granulocytes: autocrine function of an eosinophil developmental intermediate. Boyce, J.A., Friend, D., Matsumoto, R., Austen, K.F., Owen, W.F. J. Exp. Med. (1995) [Pubmed]
  9. Human eosinophil cationic protein. Molecular cloning of a cytotoxin and helminthotoxin with ribonuclease activity. Rosenberg, H.F., Ackerman, S.J., Tenen, D.G. J. Exp. Med. (1989) [Pubmed]
  10. Experimental chronic hypoxic neuropathy: relevance to diabetic neuropathy. Low, P.A., Schmelzer, J.D., Ward, K.K., Yao, J.K. Am. J. Physiol. (1986) [Pubmed]
  11. Biochemical and functional similarities between human eosinophil-derived neurotoxin and eosinophil cationic protein: homology with ribonuclease. Gleich, G.J., Loegering, D.A., Bell, M.P., Checkel, J.L., Ackerman, S.J., McKean, D.J. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  12. Toxicity of an antitumor ribonuclease to Purkinje neurons. Newton, D.L., Walbridge, S., Mikulski, S.M., Ardelt, W., Shogen, K., Ackerman, S.J., Rybak, S.M., Youle, R.J. J. Neurosci. (1994) [Pubmed]
  13. Intronic enhancer activity of the eosinophil-derived neurotoxin (RNS2) and eosinophil cationic protein (RNS3) genes is mediated by an NFAT-1 consensus binding sequence. Handen, J.S., Rosenberg, H.F. J. Biol. Chem. (1997) [Pubmed]
  14. Recognition signal for C-mannosylation of Trp-7 in RNase 2 consists of sequence Trp-x-x-Trp. Krieg, J., Hartmann, S., Vicentini, A., Gläsner, W., Hess, D., Hofsteenge, J. Mol. Biol. Cell (1998) [Pubmed]
  15. Calcium ionophore A23187 calcium-dependent cytolytic degranulation in human eosinophils. Fukuda, T., Ackerman, S.J., Reed, C.E., Peters, M.S., Dunnette, S.L., Gleich, G.J. J. Immunol. (1985) [Pubmed]
  16. Characterization of a unique nonsecretory ribonuclease from urine of pregnant women. Sakakibara, R., Hashida, K., Kitahara, T., Ishiguro, M. J. Biochem. (1992) [Pubmed]
  17. Eosinophil-derived neurotoxin and human liver ribonuclease. Identity of structure and linkage of neurotoxicity to nuclease activity. Sorrentino, S., Glitz, D.G., Hamann, K.J., Loegering, D.A., Checkel, J.L., Gleich, G.J. J. Biol. Chem. (1992) [Pubmed]
  18. Mutational analysis of the complex of human RNase inhibitor and human eosinophil-derived neurotoxin (RNase 2). Teufel, D.P., Kao, R.Y., Acharya, K.R., Shapiro, R. Biochemistry (2003) [Pubmed]
  19. Effects of the very late adhesion molecule 4 antagonist WAY103 on human peripheral blood eosinophil vascular cell adhesion molecule 1-dependent functions. Sedgwick, J.B., Jansen, K.J., Kennedy, J.D., Kita, H., Busse, W.W. J. Allergy Clin. Immunol. (2005) [Pubmed]
  20. Chemokines induce eosinophil degranulation through CCR-3. Fujisawa, T., Kato, Y., Nagase, H., Atsuta, J., Terada, A., Iguchi, K., Kamiya, H., Morita, Y., Kitaura, M., Kawasaki, H., Yoshie, O., Hirai, K. J. Allergy Clin. Immunol. (2000) [Pubmed]
  21. Novel co-operation between eotaxin and substance-P in inducing eosinophil-derived neurotoxin release. El-Shazly, A., Ishikawa, T. Mediators of inflammation. (1999) [Pubmed]
  22. The inhibitory receptor IRp60 (CD300a) is expressed and functional on human mast cells. Bachelet, I., Munitz, A., Moretta, A., Moretta, L., Levi-Schaffer, F. J. Immunol. (2005) [Pubmed]
  23. Immobilized lactoferrin is a stimulus for eosinophil activation. Thomas, L.L., Xu, W., Ardon, T.T. J. Immunol. (2002) [Pubmed]
  24. Ribonuclease k6: chromosomal mapping and divergent rates of evolution within the RNase A gene superfamily. Deming, M.S., Dyer, K.D., Bankier, A.T., Piper, M.B., Dear, P.H., Rosenberg, H.F. Genome Res. (1998) [Pubmed]
  25. Eosinophil and neutrophil activity in asthma in a one-year trial with inhaled budesonide. The impact of smoking. Pedersen, B., Dahl, R., Karlström, R., Peterson, C.G., Venge, P. Am. J. Respir. Crit. Care Med. (1996) [Pubmed]
  26. Localization of eosinophil-derived neurotoxin and eosinophil cationic protein in neutrophilic leukocytes. Sur, S., Glitz, D.G., Kita, H., Kujawa, S.M., Peterson, E.A., Weiler, D.A., Kephart, G.M., Wagner, J.M., George, T.J., Gleich, G.J., Leiferman, K.M. J. Leukoc. Biol. (1998) [Pubmed]
  27. Peripheral blood eosinophils from patients with allergic asthma contain increased intracellular eosinophil-derived neurotoxin. Sedgwick, J.B., Vrtis, R.F., Jansen, K.J., Kita, H., Bartemes, K., Busse, W.W. J. Allergy Clin. Immunol. (2004) [Pubmed]
  28. Proteomic-based discovery and characterization of glycosylated eosinophil-derived neurotoxin and COOH-terminal osteopontin fragments for ovarian cancer in urine. Ye, B., Skates, S., Mok, S.C., Horick, N.K., Rosenberg, H.F., Vitonis, A., Edwards, D., Sluss, P., Han, W.K., Berkowitz, R.S., Cramer, D.W. Clin. Cancer Res. (2006) [Pubmed]
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