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Gene Review

BRB  -  brain ribonuclease

Bos taurus

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Disease relevance of BRB


High impact information on BRB

  • However, only one of them, Asp-435, was equally important for binding of Ang; the Ki increases produced by mutations of the others were 20- to 93-fold smaller for Ang than for RNase A [6].
  • Crystallography and mutagenesis of human Ang have previously shown that its pyrimidine binding site is obstructed by Gln-117, implying that a conformational change is a key part of the mechanism of Ang action [7].
  • The capacity of angiogenin (Ang) to induce blood vessel growth is critically dependent on its ribonucleolytic activity [7].
  • The Arg-Gly-Asp segment of this site in bovine Ang, which is replaced by Arg-Glu-Asn in human Ang, does not have a conformation typical of an integrin recognition site [7].
  • Nuclear translocation of angiogenin in proliferating endothelial cells is essential to its angiogenic activity [8].

Chemical compound and disease context of BRB

  • Bovine adrenal zona glomerulosa cells were stimulated with angiotensin II (ANG II) or adenosine 3',5'-cyclic monophosphate under room air control (21% O2-0% CO2), CO2 per se (21% O2-10% CO2), hypoxia per se (10% O2-0% CO2), and the combination of CO2 and hypoxia (10% O2-10% CO2) [9].
  • The mitogenic effect of ANG II was not inhibited by pretreatment with pertussis toxin and was mediated by AT1 receptors as indicated by its sensitivity to the subtype-selective antagonist DuP-753 [10].

Biological context of BRB


Anatomical context of BRB


Associations of BRB with chemical compounds

  • With high molecular weight wheat germ RNA and tRNA, ARH-I is 660- and 300-fold more active than angiogenin, respectively, while with poly(uridylic acid), poly(cytidylic acid), cytidylyl(3'----5')adenosine (CpA), and uridylyl(3'----5')adenosine (UpA) activity is enhanced by about 200-fold [12].
  • The effects of Phe versus Ala substitutions show that the key residue Tyr434 interacts with both ligands primarily through its phenyl ring; for Tyr437, the OH group forms the important contacts with RNase A, whereas the phenyl group interacts with Ang [17].
  • Retinoic acid and monensin potentiate the cytotoxicity of bovine seminal RNase, Onconase, angiogenin, and human ribonuclease A 100 times or more [18].
  • (ii) The structure of T80A-Ang supports the view that Thr80 plays little role in maintaining the obstructive conformation of the C-terminus and that its participation in a hydrogen bond with Thr44 selectively weakens the interaction between Thr44 and N3 of cytosine [19].
  • (i) The structure of T44D-Ang indicates that Asp44 can participate directly in pyrimidine binding and that the intrinsic hydrogen-bonding capability of this residue largely governs the pyrimidine specificity of this variant [19].

Physical interactions of BRB

  • Binding of angiogenin to its cell-surface binding protein (actin) followed by dissociation of the angiogenin-actin complex from the cell surface and subsequent activation of tissue-type plasminogen activator/plasmin are likely steps involved in the processes of endothelial cell invasion and angiogenesis [20].

Enzymatic interactions of BRB

  • Angiogenin catalyzes limited cleavage of 18S and 28S ribosomal RNA and is several orders of magnitude less potent than RNase A toward conventional substrates [12].

Regulatory relationships of BRB


Other interactions of BRB


Analytical, diagnostic and therapeutic context of BRB


  1. The ribonucleolytic activity of angiogenin. Leland, P.A., Staniszewski, K.E., Park, C., Kelemen, B.R., Raines, R.T. Biochemistry (2002) [Pubmed]
  2. The effect of oxygen on aldosterone release from bovine adrenocortical cells in vitro: PO2 versus steroidogenesis. Raff, H., Kohandarvish, S. Endocrinology (1990) [Pubmed]
  3. Angiotensin II stimulates migration of retinal microvascular pericytes: involvement of TGF-beta and PDGF-BB. Nadal, J.A., Scicli, G.M., Carbini, L.A., Scicli, A.G. Am. J. Physiol. Heart Circ. Physiol. (2002) [Pubmed]
  4. Effect of angiotensin II and III on inositol polyphosphate production in differentiated NG108-15 hybrid cells. Carrithers, M.D., Raman, V.K., Masuda, S., Weyhenmeyer, J.A. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
  5. ANG II stimulates endothelial nitric oxide synthase expression in bovine pulmonary artery endothelium. Olson, S.C., Dowds, T.A., Pino, P.A., Barry, M.T., Burke-Wolin, T. Am. J. Physiol. (1997) [Pubmed]
  6. Site-specific mutagenesis reveals differences in the structural bases for tight binding of RNase inhibitor to angiogenin and RNase A. Chen, C.Z., Shapiro, R. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  7. Crystal structure of bovine angiogenin at 1.5-A resolution. Acharya, K.R., Shapiro, R., Riordan, J.F., Vallee, B.L. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  8. Nuclear translocation of angiogenin in proliferating endothelial cells is essential to its angiogenic activity. Moroianu, J., Riordan, J.F. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  9. Effect of CO2/pH on the aldosterone response to hypoxia in bovine adrenal cells in vitro. Raff, H., Jankowski, B. Am. J. Physiol. (1993) [Pubmed]
  10. Growth responses to angiotensin II in bovine adrenal glomerulosa cells. Tian, Y., Balla, T., Baukal, A.J., Catt, K.J. Am. J. Physiol. (1995) [Pubmed]
  11. Angiogenin is a cytotoxic, tRNA-specific ribonuclease in the RNase A superfamily. Saxena, S.K., Rybak, S.M., Davey, R.T., Youle, R.J., Ackerman, E.J. J. Biol. Chem. (1992) [Pubmed]
  12. A covalent angiogenin/ribonuclease hybrid with a fourth disulfide bond generated by regional mutagenesis. Harper, J.W., Vallee, B.L. Biochemistry (1989) [Pubmed]
  13. A molecular dynamics study based post facto free energy analysis of the binding of bovine angiogenin with UMP and CMP ligands. Madhusudhan, M.S., Vishveshwara, S., Das, A., Kalra, P., Jayaram, B. Indian J. Biochem. Biophys. (2001) [Pubmed]
  14. Replacing a surface loop endows ribonuclease A with angiogenic activity. Raines, R.T., Toscano, M.P., Nierengarten, D.M., Ha, J.H., Auerbach, R. J. Biol. Chem. (1995) [Pubmed]
  15. The angiogenins. Strydom, D.J. Cell. Mol. Life Sci. (1998) [Pubmed]
  16. Immunosuppressive activity of angiogenin in comparison with bovine seminal ribonuclease and pancreatic ribonuclease. Matousek, J., Soucek, J., Ríha, J., Zankel, T.R., Benner, S.A. Comp. Biochem. Physiol. B, Biochem. Mol. Biol. (1995) [Pubmed]
  17. Superadditive and subadditive effects of "hot spot" mutations within the interfaces of placental ribonuclease inhibitor with angiogenin and ribonuclease A. Chen, C.Z., Shapiro, R. Biochemistry (1999) [Pubmed]
  18. A study of the intracellular routing of cytotoxic ribonucleases. Wu, Y., Saxena, S.K., Ardelt, W., Gadina, M., Mikulski, S.M., De Lorenzo, C., D'Alessio, G., Youle, R.J. J. Biol. Chem. (1995) [Pubmed]
  19. Crystallographic studies on structural features that determine the enzymatic specificity and potency of human angiogenin: Thr44, Thr80, and residues 38-41. Holloway, D.E., Chavali, G.B., Hares, M.C., Baker, M.D., Subbarao, G.V., Shapiro, R., Acharya, K.R. Biochemistry (2004) [Pubmed]
  20. Angiogenin promotes invasiveness of cultured endothelial cells by stimulation of cell-associated proteolytic activities. Hu, G., Riordan, J.F., Vallee, B.L. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  21. ANG II AT1 and AT2 receptors both inhibit bFGF-induced proliferation of bovine adrenocortical cells. Liakos, P., Bourmeyster, N., Defaye, G., Chambaz, E.M., Bottari, S.P. Am. J. Physiol. (1997) [Pubmed]
  22. Angiogenin enhances actin acceleration of plasminogen activation. Hu, G.F., Riordan, J.F. Biochem. Biophys. Res. Commun. (1993) [Pubmed]
  23. Effect of ANP on sustained aldosterone secretion stimulated by angiotensin II. Isales, C.M., Bollag, W.B., Kiernan, L.C., Barrett, P.Q. Am. J. Physiol. (1989) [Pubmed]
  24. Binding of phosphate and pyrophosphate ions at the active site of human angiogenin as revealed by X-ray crystallography. Leonidas, D.D., Chavali, G.B., Jardine, A.M., Li, S., Shapiro, R., Acharya, K.R. Protein Sci. (2001) [Pubmed]
  25. Secretion of ribonucleases by normal and immortalized cells grown in serum-free culture conditions. Moenner, M., Hatzi, E., Badet, J. In Vitro Cell. Dev. Biol. Anim. (1997) [Pubmed]
  26. Single K+ channels in adrenal zona glomerulosa cells. II. Inhibition by angiotensin II. Kanazirska, M.V., Vassilev, P.M., Quinn, S.J., Tillotson, D.L., Williams, G.H. Am. J. Physiol. (1992) [Pubmed]
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