• 3.1.27.-
  • Ribonuclease 5
  • RNase 5
  • RNASE5
Gene Name
Amino acid sequence
Number of residues
Molecular Weight
Theoretical pI
GO Classification
actin binding / copper ion binding / DNA binding / endonuclease activity / heparin binding / peptide binding / protein homodimerization activity / receptor binding / ribonuclease activity / rRNA binding
actin filament polymerization / activation of phospholipase A2 activity / activation of phospholipase C activity / activation of protein kinase B activity / adherens junction organization / angiogenesis / antibacterial humoral response / antifungal humoral response / cell communication / cell junction assembly / cell migration / cell-cell junction organization / defense response to Gram-positive bacterium / diacylglycerol biosynthetic process / homeostatic process / innate immune response / negative regulation of smooth muscle cell proliferation / negative regulation of translation / nucleic acid phosphodiester bond hydrolysis / oocyte maturation / ovarian follicle development / placenta development / positive regulation of endothelial cell proliferation / positive regulation of phosphorylation / positive regulation of protein secretion / response to hormone / response to hypoxia / response to yeast / RNA phosphodiester bond hydrolysis / rRNA transcription
angiogenin-PRI complex / basal lamina / extracellular exosome / extracellular region / extracellular space / growth cone / neuronal cell body / nucleolus / nucleus
General Function
Rrna binding
Specific Function
Binds to actin on the surface of endothelial cells; once bound, angiogenin is endocytosed and translocated to the nucleus. Stimulates ribosomal RNA synthesis including that containing the initiation site sequences of 45S rRNA. Cleaves tRNA within anticodon loops to produce tRNA-derived stress-induced fragments (tiRNAs) which inhibit protein synthesis and triggers the assembly of stress granules (SGs). Angiogenin induces vascularization of normal and malignant tissues. Angiogenic activity is regulated by interaction with RNH1 in vivo.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasmic vesicle
Gene sequence
>lcl|BSEQ0010823|Angiogenin (ANG)
Chromosome Location
External Identifiers
UniProtKB IDP03950
UniProtKB Entry NameANGI_HUMAN
GenBank Protein ID178250
GenBank Gene IDM11567
GenAtlas IDANG
General References
  1. Kurachi K, Davie EW, Strydom DJ, Riordan JF, Vallee BL: Sequence of the cDNA and gene for angiogenin, a human angiogenesis factor. Biochemistry. 1985 Sep 24;24(20):5494-9. [Article]
  2. Zhang J, Rosenberg HF: Diversifying selection of the tumor-growth promoter angiogenin in primate evolution. Mol Biol Evol. 2002 Apr;19(4):438-45. [Article]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  4. Strydom DJ, Fett JW, Lobb RR, Alderman EM, Bethune JL, Riordan JF, Vallee BL: Amino acid sequence of human tumor derived angiogenin. Biochemistry. 1985 Sep 24;24(20):5486-94. [Article]
  5. Weiner HL, Weiner LH, Swain JL: Tissue distribution and developmental expression of the messenger RNA encoding angiogenin. Science. 1987 Jul 17;237(4812):280-2. [Article]
  6. Saxena SK, Rybak SM, Davey RT Jr, Youle RJ, Ackerman EJ: Angiogenin is a cytotoxic, tRNA-specific ribonuclease in the RNase A superfamily. J Biol Chem. 1992 Oct 25;267(30):21982-6. [Article]
  7. Moroianu J, Riordan JF: Identification of the nucleolar targeting signal of human angiogenin. Biochem Biophys Res Commun. 1994 Sep 30;203(3):1765-72. [Article]
  8. Chen CZ, Shapiro R: Site-specific mutagenesis reveals differences in the structural bases for tight binding of RNase inhibitor to angiogenin and RNase A. Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1761-6. [Article]
  9. Chen CZ, Shapiro R: Superadditive and subadditive effects of "hot spot" mutations within the interfaces of placental ribonuclease inhibitor with angiogenin and ribonuclease A. Biochemistry. 1999 Jul 20;38(29):9273-85. [Article]
  10. Xu ZP, Tsuji T, Riordan JF, Hu GF: The nuclear function of angiogenin in endothelial cells is related to rRNA production. Biochem Biophys Res Commun. 2002 Jun 7;294(2):287-92. [Article]
  11. Dickson KA, Kang DK, Kwon YS, Kim JC, Leland PA, Kim BM, Chang SI, Raines RT: Ribonuclease inhibitor regulates neovascularization by human angiogenin. Biochemistry. 2009 May 12;48(18):3804-6. doi: 10.1021/bi9005094. [Article]
  12. Ivanov P, Emara MM, Villen J, Gygi SP, Anderson P: Angiogenin-induced tRNA fragments inhibit translation initiation. Mol Cell. 2011 Aug 19;43(4):613-23. doi: 10.1016/j.molcel.2011.06.022. [Article]
  13. Acharya KR, Shapiro R, Allen SC, Riordan JF, Vallee BL: Crystal structure of human angiogenin reveals the structural basis for its functional divergence from ribonuclease. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):2915-9. [Article]
  14. Papageorgiou AC, Shapiro R, Acharya KR: Molecular recognition of human angiogenin by placental ribonuclease inhibitor--an X-ray crystallographic study at 2.0 A resolution. EMBO J. 1997 Sep 1;16(17):5162-77. [Article]
  15. Leonidas DD, Shapiro R, Allen SC, Subbarao GV, Veluraja K, Acharya KR: Refined crystal structures of native human angiogenin and two active site variants: implications for the unique functional properties of an enzyme involved in neovascularisation during tumour growth. J Mol Biol. 1999 Jan 22;285(3):1209-33. [Article]
  16. Leonidas DD, Chavali GB, Jardine AM, Li S, Shapiro R, Acharya KR: Binding of phosphate and pyrophosphate ions at the active site of human angiogenin as revealed by X-ray crystallography. Protein Sci. 2001 Aug;10(8):1669-76. [Article]
  17. Leonidas DD, Shapiro R, Subbarao GV, Russo A, Acharya KR: Crystallographic studies on the role of the C-terminal segment of human angiogenin in defining enzymatic potency. Biochemistry. 2002 Feb 26;41(8):2552-62. [Article]
  18. Chavali GB, Papageorgiou AC, Olson KA, Fett JW, Hu Gf, Shapiro R, Acharya KR: The crystal structure of human angiogenin in complex with an antitumor neutralizing antibody. Structure. 2003 Jul;11(7):875-85. [Article]
  19. Holloway DE, Chavali GB, Hares MC, Baker MD, Subbarao GV, Shapiro R, Acharya KR: Crystallographic studies on structural features that determine the enzymatic specificity and potency of human angiogenin: Thr44, Thr80, and residues 38-41. Biochemistry. 2004 Feb 10;43(5):1230-41. [Article]
  20. Lequin O, Thuring H, Robin M, Lallemand JY: Three-dimensional solution structure of human angiogenin determined by 1H,15N-NMR spectroscopy--characterization of histidine protonation states and pKa values. Eur J Biochem. 1997 Dec 15;250(3):712-26. [Article]
  21. Padhi AK, Kumar H, Vasaikar SV, Jayaram B, Gomes J: Mechanisms of loss of functions of human angiogenin variants implicated in amyotrophic lateral sclerosis. PLoS One. 2012;7(2):e32479. doi: 10.1371/journal.pone.0032479. Epub 2012 Feb 27. [Article]
  22. Greenway MJ, Alexander MD, Ennis S, Traynor BJ, Corr B, Frost E, Green A, Hardiman O: A novel candidate region for ALS on chromosome 14q11.2. Neurology. 2004 Nov 23;63(10):1936-8. [Article]
  23. Greenway MJ, Andersen PM, Russ C, Ennis S, Cashman S, Donaghy C, Patterson V, Swingler R, Kieran D, Prehn J, Morrison KE, Green A, Acharya KR, Brown RH Jr, Hardiman O: ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis. Nat Genet. 2006 Apr;38(4):411-3. Epub 2006 Feb 26. [Article]
  24. Wu D, Yu W, Kishikawa H, Folkerth RD, Iafrate AJ, Shen Y, Xin W, Sims K, Hu GF: Angiogenin loss-of-function mutations in amyotrophic lateral sclerosis. Ann Neurol. 2007 Dec;62(6):609-17. [Article]
  25. Crabtree B, Thiyagarajan N, Prior SH, Wilson P, Iyer S, Ferns T, Shapiro R, Brew K, Subramanian V, Acharya KR: Characterization of human angiogenin variants implicated in amyotrophic lateral sclerosis. Biochemistry. 2007 Oct 23;46(42):11810-8. Epub 2007 Sep 27. [Article]
  26. Gellera C, Colombrita C, Ticozzi N, Castellotti B, Bragato C, Ratti A, Taroni F, Silani V: Identification of new ANG gene mutations in a large cohort of Italian patients with amyotrophic lateral sclerosis. Neurogenetics. 2008 Feb;9(1):33-40. Epub 2007 Dec 18. [Article]
  27. Conforti FL, Sprovieri T, Mazzei R, Ungaro C, La Bella V, Tessitore A, Patitucci A, Magariello A, Gabriele AL, Tedeschi G, Simone IL, Majorana G, Valentino P, Condino F, Bono F, Monsurro MR, Muglia M, Quattrone A: A novel Angiogenin gene mutation in a sporadic patient with amyotrophic lateral sclerosis from southern Italy. Neuromuscul Disord. 2008 Jan;18(1):68-70. Epub 2007 Aug 20. [Article]
  28. Brown JA, Min J, Staropoli JF, Collin E, Bi S, Feng X, Barone R, Cao Y, O'Malley L, Xin W, Mullen TE, Sims KB: SOD1, ANG, TARDBP and FUS mutations in amyotrophic lateral sclerosis: a United States clinical testing lab experience. Amyotroph Lateral Scler. 2012 Feb;13(2):217-22. doi: 10.3109/17482968.2011.643899. [Article]
  29. Padhi AK, Banerjee K, Gomes J, Banerjee M: Computational and functional characterization of Angiogenin mutations, and correlation with amyotrophic lateral sclerosis. PLoS One. 2014 Nov 5;9(11):e111963. doi: 10.1371/journal.pone.0111963. eCollection 2014. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB09130Copperapproved, investigationalunknowncofactorDetails