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NameAngiogenin
Synonyms
  • 3.1.27.-
  • Ribonuclease 5
  • RNase 5
  • RNASE5
Gene NameANG
OrganismHuman
Amino acid sequence
>lcl|BSEQ0002349|Angiogenin
MVMGLGVLLLVFVLGLGLTPPTLAQDNSRYTHFLTQHYDAKPQGRDDRYCESIMRRRGLT
SPCKDINTFIHGNKRSIKAICENKNGNPHRENLRISKSSFQVTTCKLHGGSPWPPCQYRA
TAGFRNVVVACENGLPVHLDQSIFRRP
Number of residues147
Molecular Weight16549.95
Theoretical pI10.09
GO Classification
Functions
  • heparin binding
  • protein homodimerization activity
  • copper ion binding
  • rRNA binding
  • DNA binding
  • peptide binding
  • receptor binding
  • endonuclease activity
  • ribonuclease activity
  • actin binding
Processes
  • actin filament polymerization
  • adherens junction organization
  • activation of protein kinase B activity
  • placenta development
  • cell junction assembly
  • response to yeast
  • cell-cell junction organization
  • diacylglycerol biosynthetic process
  • positive regulation of protein secretion
  • homeostatic process
  • negative regulation of smooth muscle cell proliferation
  • cell migration
  • positive regulation of phosphorylation
  • cell communication
  • ovarian follicle development
  • innate immune response
  • rRNA transcription
  • nucleic acid phosphodiester bond hydrolysis
  • oocyte maturation
  • response to hypoxia
  • antibacterial humoral response
  • defense response to Gram-positive bacterium
  • angiogenesis
  • RNA phosphodiester bond hydrolysis
  • negative regulation of translation
  • activation of phospholipase C activity
  • antifungal humoral response
  • positive regulation of endothelial cell proliferation
  • activation of phospholipase A2 activity
  • response to hormone
Components
  • extracellular exosome
  • basal lamina
  • nucleolus
  • extracellular region
  • nucleus
  • growth cone
  • extracellular space
  • neuronal cell body
  • angiogenin-PRI complex
General FunctionRrna binding
Specific FunctionBinds 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 RegionsNot Available
GenBank Protein ID178250
UniProtKB IDP03950
UniProtKB Entry NameANGI_HUMAN
Cellular LocationCytoplasmic vesicle
Gene sequence
>lcl|BSEQ0010823|Angiogenin (ANG)
ATGGTGATGGGCCTGGGCGTTTTGTTGTTGGTCTTCGTGCTGGGTCTGGGTCTGACCCCA
CCGACCCTGGCTCAGGATAACTCCAGGTACACACACTTCCTGACCCAGCACTATGATGCC
AAACCACAGGGCCGGGATGACAGATACTGTGAAAGCATCATGAGGAGACGGGGCCTGACC
TCACCCTGCAAAGACATCAACACATTTATTCATGGCAACAAGCGCAGCATCAAGGCCATC
TGTGAAAACAAGAATGGAAACCCTCACAGAGAAAACCTAAGAATAAGCAAGTCTTCTTTC
CAGGTCACCACTTGCAAGCTACATGGAGGTTCCCCCTGGCCTCCATGCCAGTACCGAGCC
ACAGCGGGGTTCAGAAACGTTGTTGTTGCTTGTGAAAATGGCTTACCTGTCCACTTGGAT
CAGTCAATTTTCCGTCGTCCGTAA
GenBank Gene IDM11567
GeneCard IDNot Available
GenAtlas IDANG
HGNC IDHGNC:483
Chromosome Location14
Locus14q11.1-q11.2
References
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  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. 11919285
  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. 15489334
  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. 2866794
  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. 2440105
  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. 1400510
  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. 7945327
  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. 9050852
  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. 10413501
  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. 12051708
  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. 19354288
  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. 21855800
  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. 8159679
  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. 9311977
  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. 9918722
  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. 11468363
  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. 11851402
  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. 12842050
  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. 14756559
  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. 9461294
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  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. 15557516
  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. 16501576
  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. 17886298
  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. 17900154
  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. 18087731
  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. 17703939
  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. 22292843
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