ID ANGI_HUMAN Reviewed; 147 AA. AC P03950; Q05CV1; Q53X86; Q6P5T2; Q8WXE7; DT 23-OCT-1986, integrated into UniProtKB/Swiss-Prot. DT 23-OCT-1986, sequence version 1. DT 28-JAN-2026, entry version 253. DE RecName: Full=Angiogenin {ECO:0000303|PubMed:2866795}; DE EC=3.1.27.- {ECO:0000269|PubMed:1400510, ECO:0000269|PubMed:21855800, ECO:0000269|PubMed:2424496, ECO:0000269|PubMed:2459697, ECO:0000269|PubMed:28176817, ECO:0000269|PubMed:38718836}; DE AltName: Full=Ribonuclease 5; DE Short=RNase 5; DE Flags: Precursor; GN Name=ANG {ECO:0000303|PubMed:11919285, ECO:0000312|HGNC:HGNC:483}; GN Synonyms=RNASE5; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2866795; DOI=10.1021/bi00341a032; RA Kurachi K., Davie E.W., Strydom D.J., Riordan J.F., Vallee B.L.; RT "Sequence of the cDNA and gene for angiogenin, a human angiogenesis RT factor."; RL Biochemistry 24:5494-5499(1985). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLU-84. RX PubMed=11919285; DOI=10.1093/oxfordjournals.molbev.a004099; RA Zhang J., Rosenberg H.F.; RT "Diversifying selection of the tumor-growth promoter angiogenin in primate RT evolution."; RL Mol. Biol. Evol. 19:438-445(2002). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Li J., Wang H.; RL Submitted (SEP-2008) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Small intestine; RA Wakamatsu A., Yamamoto J., Kimura K., Kaida T., Tsuchiya K., Iida Y., RA Takayama Y., Murakawa K., Kanehori K., Andoh T., Kagawa N., Sato R., RA Kawamura Y., Tanaka S., Kisu Y., Sugano S., Goshima N., Nomura N., RA Isogai T.; RT "NEDO functional analysis of protein and research application project."; RL Submitted (JAN-2008) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Liver; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP PROTEIN SEQUENCE OF 25-147, PYROGLUTAMATE FORMATION AT GLN-25, AND RP DISULFIDE BONDS. RX PubMed=2866794; DOI=10.1021/bi00341a031; RA Strydom D.J., Fett J.W., Lobb R.R., Alderman E.M., Bethune J.L., RA Riordan J.F., Vallee B.L.; RT "Amino acid sequence of human tumor derived angiogenin."; RL Biochemistry 24:5486-5494(1985). RN [9] RP FUNCTION. RX PubMed=4074709; DOI=10.1021/bi00341a030; RA Fett J.W., Strydom D.J., Lobb R.R., Alderman E.M., Bethune J.L., RA Riordan J.F., Vallee B.L.; RT "Isolation and characterization of angiogenin, an angiogenic protein from RT human carcinoma cells."; RL Biochemistry 24:5480-5486(1985). RN [10] RP SUBCELLULAR LOCATION. RX PubMed=3663649; DOI=10.1021/bi00390a037; RA Shapiro R., Strydom D.J., Olson K.A., Vallee B.L.; RT "Isolation of angiogenin from normal human plasma."; RL Biochemistry 26:5141-5146(1987). RN [11] RP FUNCTION. RX PubMed=2424496; DOI=10.1021/bi00360a008; RA Shapiro R., Riordan J.F., Vallee B.L.; RT "Characteristic ribonucleolytic activity of human angiogenin."; RL Biochemistry 25:3527-3532(1986). RN [12] RP FUNCTION. RX PubMed=3122207; DOI=10.1073/pnas.84.24.8783; RA Shapiro R., Weremowicz S., Riordan J.F., Vallee B.L.; RT "Ribonucleolytic activity of angiogenin: essential histidine, lysine, and RT arginine residues."; RL Proc. Natl. Acad. Sci. U.S.A. 84:8783-8787(1987). RN [13] RP TISSUE SPECIFICITY. RX PubMed=2440105; DOI=10.1126/science.2440105; RA Weiner H.L., Weiner L.H., Swain J.L.; RT "Tissue distribution and developmental expression of the messenger RNA RT encoding angiogenin."; RL Science 237:280-282(1987). RN [14] RP FUNCTION. RX PubMed=3289612; DOI=10.1021/bi00407a007; RA Rybak S.M., Vallee B.L.; RT "Base cleavage specificity of angiogenin with Saccharomyces cerevisiae and RT Escherichia coli 5S RNAs."; RL Biochemistry 27:2288-2294(1988). RN [15] RP ACTIVITY REGULATION. RX PubMed=3243277; DOI=10.1002/j.1460-2075.1988.tb03310.x; RA Schneider R., Schneider-Scherzer E., Thurnher M., Auer B., Schweiger M.; RT "The primary structure of human ribonuclease/angiogenin inhibitor (RAI) RT discloses a novel highly diversified protein superfamily with a common RT repetitive module."; RL EMBO J. 7:4151-4156(1988). RN [16] RP FUNCTION, AND MUTAGENESIS OF ASP-140. RX PubMed=2459697; DOI=10.1073/pnas.85.19.7139; RA Harper J.W., Vallee B.L.; RT "Mutagenesis of aspartic acid-116 enhances the ribonucleolytic activity and RT angiogenic potency of angiogenin."; RL Proc. Natl. Acad. Sci. U.S.A. 85:7139-7143(1988). RN [17] RP FUNCTION. RX PubMed=2730651; DOI=10.1016/0006-291x(89)91569-6; RA Lee F.S., Vallee B.L.; RT "Characterization of ribonucleolytic activity of angiogenin towards tRNA."; RL Biochem. Biophys. Res. Commun. 161:121-126(1989). RN [18] RP FUNCTION. RX PubMed=1400510; DOI=10.1016/s0021-9258(19)36710-9; RA Saxena S.K., Rybak S.M., Davey R.T. Jr., Youle R.J., Ackerman E.J.; RT "Angiogenin is a cytotoxic, tRNA-specific ribonuclease in the RNase A RT superfamily."; RL J. Biol. Chem. 267:21982-21986(1992). RN [19] RP FUNCTION. RX PubMed=8448182; DOI=10.1016/0167-4838(93)90145-h; RA Bond M.D., Strydom D.J., Vallee B.L.; RT "Characterization and sequencing of rabbit, pig and mouse angiogenins: RT discernment of functionally important residues and regions."; RL Biochim. Biophys. Acta 1162:177-186(1993). RN [20] RP SUBCELLULAR LOCATION, AND NUCLEOLAR LOCALIZATION SIGNAL. RX PubMed=7945327; DOI=10.1006/bbrc.1994.2391; RA Moroianu J., Riordan J.F.; RT "Identification of the nucleolar targeting signal of human angiogenin."; RL Biochem. Biophys. Res. Commun. 203:1765-1772(1994). RN [21] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=8127865; DOI=10.1073/pnas.91.5.1677; RA Moroianu J., Riordan J.F.; RT "Nuclear translocation of angiogenin in proliferating endothelial cells is RT essential to its angiogenic activity."; RL Proc. Natl. Acad. Sci. U.S.A. 91:1677-1681(1994). RN [22] RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF 140-ASP-GLN-141 AND RP GLN-141. RX PubMed=8159680; DOI=10.1073/pnas.91.8.2920; RA Russo N., Shapiro R., Acharya K.R., Riordan J.F., Vallee B.L.; RT "Role of glutamine-117 in the ribonucleolytic activity of human RT angiogenin."; RL Proc. Natl. Acad. Sci. U.S.A. 91:2920-2924(1994). RN [23] RP FUNCTION, AND MUTAGENESIS OF ARG-29. RX PubMed=8570639; DOI=10.1073/pnas.93.2.804; RA Russo N., Acharya K.R., Vallee B.L., Shapiro R.; RT "A combined kinetic and modeling study of the catalytic center subsites of RT human angiogenin."; RL Proc. Natl. Acad. Sci. U.S.A. 93:804-808(1996). RN [24] RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF 143-ILE-PHE-144. RX PubMed=8622921; DOI=10.1073/pnas.93.8.3243; RA Russo N., Nobile V., Di Donato A., Riordan J.F., Vallee B.L.; RT "The C-terminal region of human angiogenin has a dual role in enzymatic RT activity."; RL Proc. Natl. Acad. Sci. U.S.A. 93:3243-3247(1996). RN [25] RP MUTAGENESIS OF HIS-32; GLN-36; LYS-64; ASN-92 AND GLU-132. RX PubMed=9050852; DOI=10.1073/pnas.94.5.1761; RA Chen C.Z., Shapiro R.; RT "Site-specific mutagenesis reveals differences in the structural bases for RT tight binding of RNase inhibitor to angiogenin and RNase A."; RL Proc. Natl. Acad. Sci. U.S.A. 94:1761-1766(1997). RN [26] RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF THR-68 AND THR-104. RX PubMed=9578571; DOI=10.1021/bi9800146; RA Shapiro R.; RT "Structural features that determine the enzymatic potency and specificity RT of human angiogenin: threonine-80 and residues 58-70 and 116-123."; RL Biochemistry 37:6847-6856(1998). RN [27] RP INTERACTION WITH RNH1, AND MUTAGENESIS OF ARG-29 AND LYS-64. RX PubMed=10413501; DOI=10.1021/bi990762a; RA Chen C.Z., Shapiro R.; RT "Superadditive and subadditive effects of 'hot spot' mutations within the RT interfaces of placental ribonuclease inhibitor with angiogenin and RT ribonuclease A."; RL Biochemistry 38:9273-9285(1999). RN [28] RP FUNCTION, SUBCELLULAR LOCATION, AND DNA-BINDING. RX PubMed=12051708; DOI=10.1016/s0006-291x(02)00479-5; RA Xu Z.P., Tsuji T., Riordan J.F., Hu G.F.; RT "The nuclear function of angiogenin in endothelial cells is related to rRNA RT production."; RL Biochem. Biophys. Res. Commun. 294:287-292(2002). RN [29] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=15735021; DOI=10.1158/0008-5472.can-04-2058; RA Tsuji T., Sun Y., Kishimoto K., Olson K.A., Liu S., Hirukawa S., Hu G.F.; RT "Angiogenin is translocated to the nucleus of HeLa cells and is involved in RT ribosomal RNA transcription and cell proliferation."; RL Cancer Res. 65:1352-1360(2005). RN [30] RP FUNCTION, ACTIVITY REGULATION, INTERACTION WITH RNH1, AND MUTAGENESIS OF RP 109-GLY-GLY-110. RX PubMed=19354288; DOI=10.1021/bi9005094; RA Dickson K.A., Kang D.K., Kwon Y.S., Kim J.C., Leland P.A., Kim B.M., RA Chang S.I., Raines R.T.; RT "Ribonuclease inhibitor regulates neovascularization by human angiogenin."; RL Biochemistry 48:3804-3806(2009). RN [31] RP FUNCTION, INTERACTION WITH RNH1, AND ACTIVITY REGULATION. RX PubMed=19332886; DOI=10.1083/jcb.200811106; RA Yamasaki S., Ivanov P., Hu G.F., Anderson P.; RT "Angiogenin cleaves tRNA and promotes stress-induced translational RT repression."; RL J. Cell Biol. 185:35-42(2009). RN [32] RP FUNCTION. RX PubMed=20129916; DOI=10.1074/jbc.m109.077560; RA Emara M.M., Ivanov P., Hickman T., Dawra N., Tisdale S., Kedersha N., RA Hu G.F., Anderson P.; RT "Angiogenin-induced tRNA-derived stress-induced RNAs promote stress-induced RT stress granule assembly."; RL J. Biol. Chem. 285:10959-10968(2010). RN [33] RP FUNCTION. RX PubMed=21855800; DOI=10.1016/j.molcel.2011.06.022; RA Ivanov P., Emara M.M., Villen J., Gygi S.P., Anderson P.; RT "Angiogenin-induced tRNA fragments inhibit translation initiation."; RL Mol. Cell 43:613-623(2011). RN [34] RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND INTERACTION WITH RP RNH1. RX PubMed=23843625; DOI=10.1242/jcs.134551; RA Pizzo E., Sarcinelli C., Sheng J., Fusco S., Formiggini F., Netti P., RA Yu W., D'Alessio G., Hu G.F.; RT "Ribonuclease/angiogenin inhibitor 1 regulates stress-induced subcellular RT localization of angiogenin to control growth and survival."; RL J. Cell Sci. 126:4308-4319(2013). RN [35] RP FUNCTION, INTERACTION WITH RNH1, AND SUBCELLULAR LOCATION. RX PubMed=27518564; DOI=10.1016/j.cell.2016.06.042; RA Goncalves K.A., Silberstein L., Li S., Severe N., Hu M.G., Yang H., RA Scadden D.T., Hu G.F.; RT "Angiogenin promotes hematopoietic regeneration by dichotomously regulating RT quiescence of stem and progenitor cells."; RL Cell 166:894-906(2016). RN [36] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF HIS-37; ARG-90 AND RP ASN-92. RX PubMed=29100074; DOI=10.1016/j.cell.2017.10.005; RA Yu W., Goncalves K.A., Li S., Kishikawa H., Sun G., Yang H., Vanli N., RA Wu Y., Jiang Y., Hu M.G., Friedel R.H., Hu G.F.; RT "Plexin-B2 mediates physiologic and pathologic functions of angiogenin."; RL Cell 171:849-864(2017). RN [37] RP FUNCTION, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANT ALS9 RP LEU-136. RX PubMed=29748193; DOI=10.1261/rna.065516.117; RA Thomas S.P., Hoang T.T., Ressler V.T., Raines R.T.; RT "Human angiogenin is a potent cytotoxin in the absence of ribonuclease RT inhibitor."; RL RNA 24:1018-1027(2018). RN [38] RP FUNCTION. RX PubMed=31582561; DOI=10.1074/jbc.ra119.009272; RA Su Z., Kuscu C., Malik A., Shibata E., Dutta A.; RT "Angiogenin generates specific stress-induced tRNA halves and is not RT involved in tRF-3-mediated gene silencing."; RL J. Biol. Chem. 294:16930-16941(2019). RN [39] RP FUNCTION, ACTIVITY REGULATION, AND INTERACTION WITH RNH1. RX PubMed=32510170; DOI=10.15252/embj.2019103325; RA Bai R., Sun D., Chen M., Shi X., Luo L., Yao Z., Liu Y., Ge X., Gao X., RA Hu G.F., Zhou W., Sheng J., Xu Z.; RT "Myeloid cells protect intestinal epithelial barrier integrity through the RT angiogenin/plexin-B2 axis."; RL EMBO J. 39:e103325-e103325(2020). RN [40] RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 25-147, AND DISULFIDE BONDS. RX PubMed=8159679; DOI=10.1073/pnas.91.8.2915; RA Acharya K.R., Shapiro R., Allen S.C., Riordan J.F., Vallee B.L.; RT "Crystal structure of human angiogenin reveals the structural basis for its RT functional divergence from ribonuclease."; RL Proc. Natl. Acad. Sci. U.S.A. 91:2915-2919(1994). RN [41] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 25-147 IN COMPLEX WITH RNH1, RP DISULFIDE BONDS, AND SUBUNIT. RX PubMed=9311977; DOI=10.1093/emboj/16.17.5162; RA Papageorgiou A.C., Shapiro R., Acharya K.R.; RT "Molecular recognition of human angiogenin by placental ribonuclease RT inhibitor -- an X-ray crystallographic study at 2.0-A resolution."; RL EMBO J. 16:5162-5177(1997). RN [42] RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 26-147, ACTIVE SITES, AND RP DISULFIDE BONDS. RX PubMed=9918722; DOI=10.1006/jmbi.1998.2378; RA Leonidas D.D., Shapiro R., Allen S.C., Subbarao G.V., Veluraja K., RA Acharya K.R.; RT "Refined crystal structures of native human angiogenin and two active site RT variants: implications for the unique functional properties of an enzyme RT involved in neovascularisation during tumour growth."; RL J. Mol. Biol. 285:1209-1233(1999). RN [43] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 26-147 OF MUTANT GLY-141 IN RP COMPLEX WITH PHOSPHATE AND PYROPHOSPHATE, ACTIVE SITES, AND DISULFIDE RP BONDS. RX PubMed=11468363; DOI=10.1110/ps.13601; RA Leonidas D.D., Chavali G.B., Jardine A.M., Li S., Shapiro R., Acharya K.R.; RT "Binding of phosphate and pyrophosphate ions at the active site of human RT angiogenin as revealed by X-ray crystallography."; RL Protein Sci. 10:1669-1676(2001). RN [44] RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 26-147, DISULFIDE BONDS, AND RP MUTAGENESIS OF ASP-140; GLN-141 AND 143-ILE-PHE-144. RX PubMed=11851402; DOI=10.1021/bi015768q; RA Leonidas D.D., Shapiro R., Subbarao G.V., Russo A., Acharya K.R.; RT "Crystallographic studies on the role of the C-terminal segment of human RT angiogenin in defining enzymatic potency."; RL Biochemistry 41:2552-2562(2002). RN [45] RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 26-147, AND DISULFIDE BONDS. RX PubMed=12842050; DOI=10.1016/s0969-2126(03)00131-x; RA Chavali G.B., Papageorgiou A.C., Olson K.A., Fett J.W., Hu G., Shapiro R., RA Acharya K.R.; RT "The crystal structure of human angiogenin in complex with an antitumor RT neutralizing antibody."; RL Structure 11:875-885(2003). RN [46] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF MUTANTS ASP-68 AND ALA-104, AND RP DISULFIDE BONDS. RX PubMed=14756559; DOI=10.1021/bi035654+; RA Holloway D.E., Chavali G.B., Hares M.C., Baker M.D., Subbarao G.V., RA Shapiro R., Acharya K.R.; RT "Crystallographic studies on structural features that determine the RT enzymatic specificity and potency of human angiogenin: Thr44, Thr80, and RT residues 38-41."; RL Biochemistry 43:1230-1241(2004). RN [47] RP STRUCTURE BY NMR, AND DISULFIDE BONDS. RX PubMed=9461294; DOI=10.1111/j.1432-1033.1997.00712.x; RA Lequin O., Thuering H., Robin M., Lallemand J.-Y.; RT "Three-dimensional solution structure of human angiogenin determined by RT 1H,15N-NMR spectroscopy -- characterization of histidine protonation states RT and pKa values."; RL Eur. J. Biochem. 250:712-726(1997). RN [48] {ECO:0007744|PDB:4AHD, ECO:0007744|PDB:4AHE, ECO:0007744|PDB:4AHF, ECO:0007744|PDB:4AHG, ECO:0007744|PDB:4AHH, ECO:0007744|PDB:4AHI, ECO:0007744|PDB:4AHJ, ECO:0007744|PDB:4AHK, ECO:0007744|PDB:4AHL, ECO:0007744|PDB:4AHM, ECO:0007744|PDB:4AHN} RP X-RAY CRYSTALLOGRAPHY (1.04 ANGSTROMS) OF 24-147, FUNCTION, AND SUBCELLULAR RP LOCATION. RX PubMed=23047679; DOI=10.1038/ncomms2126; RA Thiyagarajan N., Ferguson R., Subramanian V., Acharya K.R.; RT "Structural and molecular insights into the mechanism of action of human RT angiogenin-ALS variants in neurons."; RL Nat. Commun. 3:1121-1121(2012). RN [49] RP 3D-STRUCTURE MODELING. RX PubMed=22384259; DOI=10.1371/journal.pone.0032479; RA Padhi A.K., Kumar H., Vasaikar S.V., Jayaram B., Gomes J.; RT "Mechanisms of loss of functions of human angiogenin variants implicated in RT amyotrophic lateral sclerosis."; RL PLoS ONE 7:E32479-E32479(2012). RN [50] {ECO:0007744|PDB:5M9A, ECO:0007744|PDB:5M9C, ECO:0007744|PDB:5M9G, ECO:0007744|PDB:5M9J, ECO:0007744|PDB:5M9M, ECO:0007744|PDB:5M9P, ECO:0007744|PDB:5M9Q, ECO:0007744|PDB:5M9R, ECO:0007744|PDB:5M9S, ECO:0007744|PDB:5M9T, ECO:0007744|PDB:5M9V} RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 25-147, FUNCTION, AND DISULFIDE RP BONDS. RX PubMed=28176817; DOI=10.1038/srep41996; RA Bradshaw W.J., Rehman S., Pham T.T., Thiyagarajan N., Lee R.L., RA Subramanian V., Acharya K.R.; RT "Structural insights into human angiogenin variants implicated in RT Parkinson's disease and Amyotrophic Lateral Sclerosis."; RL Sci. Rep. 7:41996-41996(2017). RN [51] RP STRUCTURE BY NMR. RX PubMed=33535464; DOI=10.3390/ijms22031439; RA Fagagnini A., Garavis M., Gomez-Pinto I., Fasoli S., Gotte G., RA Laurents D.V.; RT "NMR Characterization of Angiogenin Variants and tRNAAla Products Impacting RT Aberrant Protein Oligomerization."; RL Int. J. Mol. Sci. 22:0-0(2021). RN [52] {ECO:0007744|PDB:7PNJ, ECO:0007744|PDB:7PNP, ECO:0007744|PDB:7PNR} RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 25-145, INTERACTION WITH PCNA, RP AND DISULFIDE BONDS. RX PubMed=37218877; DOI=10.1021/acs.biochem.3c00158; RA Papaioannou O.S.E., Tsika A.C., Rovoli M., Papadopoulos G.E., RA Kontopidis G., Spyroulias G.A., Leonidas D.D.; RT "Structural and biochemical characterization of the human angiogenin- RT proliferating cell nuclear antigen interaction."; RL Biochemistry 62:1706-1715(2023). RN [53] RP STRUCTURE BY ELECTRON MICROSCOPY (3.0 ANGSTROMS) IN COMPLEX WITH TRNA AND RP RIBOSOME, ACTIVE SITES, DISULFIDE BONDS, FUNCTION, ACTIVITY REGULATION, RP CHARACTERIZATION OF VARIANT ALS9 GLU-78, AND MUTAGENESIS OF HIS-37. RX PubMed=38718836; DOI=10.1038/s41586-024-07508-8; RA Loveland A.B., Koh C.S., Ganesan R., Jacobson A., Korostelev A.A.; RT "Structural mechanism of angiogenin activation by the ribosome."; RL Nature 630:769-776(2024). RN [54] RP VARIANT ALS9 ILE-64. RX PubMed=15557516; DOI=10.1212/01.wnl.0000144344.39103.f6; RA Greenway M.J., Alexander M.D., Ennis S., Traynor B.J., Corr B., Frost E., RA Green A., Hardiman O.; RT "A novel candidate region for ALS on chromosome 14q11.2."; RL Neurology 63:1936-1938(2004). RN [55] RP VARIANTS ALS9 LEU-36; ILE-41; GLU-41; LYS-55; TRP-63; ILE-64 AND VAL-70. RX PubMed=16501576; DOI=10.1038/ng1742; RA Greenway M.J., Andersen P.M., Russ C., Ennis S., Cashman S., Donaghy C., RA Patterson V., Swingler R., Kieran D., Prehn J., Morrison K.E., Green A., RA Acharya K.R., Brown R.H. Jr., Hardiman O.; RT "ANG mutations segregate with familial and 'sporadic' amyotrophic lateral RT sclerosis."; RL Nat. Genet. 38:411-413(2006). RN [56] RP VARIANTS ALS9 SER-20; ILE-41; ASN-52 AND LEU-136, CHARACTERIZATION OF RP VARIANTS ALS9 ILE-41; ASN-52 AND LEU-136, AND TISSUE SPECIFICITY. RX PubMed=17886298; DOI=10.1002/ana.21221; RA Wu D., Yu W., Kishikawa H., Folkerth R.D., Iafrate A.J., Shen Y., Xin W., RA Sims K., Hu G.-F.; RT "Angiogenin loss-of-function mutations in amyotrophic lateral sclerosis."; RL Ann. Neurol. 62:609-617(2007). RN [57] RP CHARACTERIZATION OF VARIANTS ALS9 LEU-36; ILE-41; GLU-41; LYS-55; TRP-63; RP ILE-64 AND VAL-70, AND CHARACTERIZATION OF VARIANT ALS9 VAL-70. RX PubMed=17900154; DOI=10.1021/bi701333h; RA Crabtree B., Thiyagarajan N., Prior S.H., Wilson P., Iyer S., Ferns T., RA Shapiro R., Brew K., Subramanian V., Acharya K.R.; RT "Characterization of human angiogenin variants implicated in amyotrophic RT lateral sclerosis."; RL Biochemistry 46:11810-11818(2007). RN [58] RP VARIANTS ALS9 VAL-70 AND HIS-145. RX PubMed=18852347; DOI=10.1001/archneur.65.10.1333; RG French Amyotrophic Lateral Sclerosis (ALS) Study Group; RA Paubel A., Violette J., Amy M., Praline J., Meininger V., Camu W., RA Corcia P., Andres C.R., Vourc'h P.; RT "Mutations of the ANG gene in French patients with sporadic amyotrophic RT lateral sclerosis."; RL Arch. Neurol. 65:1333-1336(2008). RN [59] RP VARIANTS ALS9 SER-12; SER-20; VAL-70; ILE-137 AND ARG-138. RX PubMed=18087731; DOI=10.1007/s10048-007-0111-3; RA Gellera C., Colombrita C., Ticozzi N., Castellotti B., Bragato C., RA Ratti A., Taroni F., Silani V.; RT "Identification of new ANG gene mutations in a large cohort of Italian RT patients with amyotrophic lateral sclerosis."; RL Neurogenetics 9:33-40(2008). RN [60] RP VARIANT ALS9 GLU-41. RX PubMed=19153377; DOI=10.1212/01.wnl.0000339487.84908.00; RA van Es M.A., Diekstra F.P., Veldink J.H., Baas F., Bourque P.R., RA Schelhaas H.J., Strengman E., Hennekam E.A., Lindhout D., Ophoff R.A., RA van den Berg L.H.; RT "A case of ALS-FTD in a large FALS pedigree with a K17I ANG mutation."; RL Neurology 72:287-288(2009). RN [61] RP INVOLVEMENT IN ALS9. RX PubMed=17703939; DOI=10.1016/j.nmd.2007.07.003; RA Conforti F.L., Sprovieri T., Mazzei R., Ungaro C., La Bella V., RA Tessitore A., Patitucci A., Magariello A., Gabriele A.L., Tedeschi G., RA Simone I.L., Majorana G., Valentino P., Condino F., Bono F., Monsurro M.R., RA Muglia M., Quattrone A.; RT "A novel angiogenin gene mutation in a sporadic patient with amyotrophic RT lateral sclerosis from southern Italy."; RL Neuromuscul. Disord. 18:68-70(2008). RN [62] RP VARIANTS ALS9 LEU-12 AND GLU-78. RX PubMed=19363631; DOI=10.1007/s00415-009-5124-4; RA Fernandez-Santiago R., Hoenig S., Lichtner P., Sperfeld A.D., Sharma M., RA Berg D., Weichenrieder O., Illig T., Eger K., Meyer T., Anneser J., RA Muench C., Zierz S., Gasser T., Ludolph A.; RT "Identification of novel Angiogenin (ANG) gene missense variants in German RT patients with amyotrophic lateral sclerosis."; RL J. Neurol. 256:1337-1342(2009). RN [63] RP VARIANTS ALS9 LEU-12; SER-12; ASP-15; GLN-20; SER-20; LEU-36; GLU-41; RP ASN-52; LYS-55; TRP-63; ILE-64; GLU-64; SER-104; ILE-124; LEU-136; ILE-137; RP ARG-138 AND HIS-145, AND VARIANTS ALA-13; ASP-17; ARG-37; VAL-46; ARG-78; RP GLN-119 AND CYS-145. RX PubMed=22190368; DOI=10.1002/ana.22611; RA van Es M.A., Schelhaas H.J., van Vught P.W., Ticozzi N., Andersen P.M., RA Groen E.J., Schulte C., Blauw H.M., Koppers M., Diekstra F.P., Fumoto K., RA LeClerc A.L., Keagle P., Bloem B.R., Scheffer H., van Nuenen B.F., RA van Blitterswijk M., van Rheenen W., Wills A.M., Lowe P.P., Hu G.F., Yu W., RA Kishikawa H., Wu D., Folkerth R.D., Mariani C., Goldwurm S., Pezzoli G., RA Van Damme P., Lemmens R., Dahlberg C., Birve A., Fernandez-Santiago R., RA Waibel S., Klein C., Weber M., van der Kooi A.J., de Visser M., Verbaan D., RA van Hilten J.J., Heutink P., Hennekam E.A., Cuppen E., Berg D., RA Brown R.H. Jr., Silani V., Gasser T., Ludolph A.C., Robberecht W., RA Ophoff R.A., Veldink J.H., Pasterkamp R.J., de Bakker P.I., Landers J.E., RA van de Warrenburg B.P., van den Berg L.H.; RT "Angiogenin variants in Parkinson disease and amyotrophic lateral RT sclerosis."; RL Ann. Neurol. 70:964-973(2011). RN [64] RP VARIANTS ALS9 HIS-38; ILE-41 AND GLY-46. RX PubMed=22292843; DOI=10.3109/17482968.2011.643899; RA Brown J.A., Min J., Staropoli J.F., Collin E., Bi S., Feng X., Barone R., RA Cao Y., O'Malley L., Xin W., Mullen T.E., Sims K.B.; RT "SOD1, ANG, TARDBP and FUS mutations in amyotrophic lateral sclerosis: a RT United States clinical testing lab experience."; RL Amyotroph. Lateral Scler. 13:217-222(2012). RN [65] RP VARIANT ALS9 ILE-127. RX PubMed=22292798; DOI=10.3109/17482968.2011.643900; RA Zou Z.Y., Wang X.N., Liu M.S., Sun Q., Li X.G., Cui L.Y., Kong J.; RT "Identification of a novel missense mutation in angiogenin in a Chinese RT amyotrophic lateral sclerosis cohort."; RL Amyotroph. Lateral Scler. 13:270-275(2012). RN [66] RP VARIANT ALS9 GLY-46, CHARACTERIZATION OF VARIANT ALS9 GLY-46, MUTAGENESIS RP OF LEU-59, SUBUNIT, AND SUBCELLULAR LOCATION. RX PubMed=25372031; DOI=10.1371/journal.pone.0111963; RA Padhi A.K., Banerjee K., Gomes J., Banerjee M.; RT "Computational and functional characterization of Angiogenin mutations, and RT correlation with amyotrophic lateral sclerosis."; RL PLoS ONE 9:E111963-E111963(2014). CC -!- FUNCTION: Secreted ribonuclease that can either promote or restrict CC cell proliferation of target cells, depending on the context CC (PubMed:12051708, PubMed:1400510, PubMed:19332886, PubMed:20129916, CC PubMed:21855800, PubMed:23047679, PubMed:23843625, PubMed:2424496, CC PubMed:2459697, PubMed:2730651, PubMed:27518564, PubMed:28176817, CC PubMed:29100074, PubMed:29748193, PubMed:3122207, PubMed:32510170, CC PubMed:38718836, PubMed:8159680, PubMed:8570639, PubMed:8622921, CC PubMed:9578571). Endocytosed in target cells via its receptor PLXNB2 CC and translocates to the cytoplasm or nucleus (PubMed:29100074, CC PubMed:32510170). Under stress conditions, localizes to the cytoplasm CC and promotes the assembly of stress granules (SGs): specifically CC cleaves a subset of tRNAs within anticodon loops to produce tRNA- CC derived stress-induced fragments (tiRNAs), resulting in translation CC repression and inhibition of cell proliferation (PubMed:1400510, CC PubMed:19332886, PubMed:20129916, PubMed:21855800, PubMed:23047679, CC PubMed:27518564, PubMed:29100074, PubMed:29748193, PubMed:32510170, CC PubMed:38718836). tiRNas also prevent formation of apoptosome, thereby CC promoting cell survival (By similarity). Preferentially cleaves RNAs CC between a pyrimidine and an adenosine residue, suggesting that it CC cleaves the anticodon loop of tRNA(Ala) (32-UUAGCAU-38) after positions CC 33 and 36 (PubMed:3289612, PubMed:38718836). Cleaves a subset of tRNAs, CC including tRNA(Ala), tRNA(Glu), tRNA(Gly), tRNA(Lys), tRNA(Val), CC tRNA(His), tRNA(Asp) and tRNA(Sec) (PubMed:31582561). Under growth CC conditions and in differentiated cells, translocates to the nucleus and CC stimulates ribosomal RNA (rRNA) transcription, including that CC containing the initiation site sequences of 45S rRNA, thereby promoting CC cell growth and proliferation (PubMed:12051708, PubMed:15735021, CC PubMed:27518564, PubMed:29100074, PubMed:8127865). Angiogenin induces CC vascularization of normal and malignant tissues via its ability to CC promote rRNA transcription (PubMed:19354288, PubMed:4074709, CC PubMed:8448182). Involved in hematopoietic stem and progenitor cell CC (HSPC) growth and survival by promoting rRNA transcription in growth CC conditions and inhibiting translation in response to stress, CC respectively (PubMed:27518564). Mediates the crosstalk between myeloid CC and intestinal epithelial cells to protect the intestinal epithelial CC barrier integrity: secreted by myeloid cells and promotes intestinal CC epithelial cells proliferation and survival (PubMed:32510170). Also CC mediates osteoclast-endothelial cell crosstalk in growing bone: CC produced by osteoclasts and protects the neighboring vascular cells CC against senescence by promoting rRNA transcription (By similarity). CC {ECO:0000250|UniProtKB:P21570, ECO:0000269|PubMed:12051708, CC ECO:0000269|PubMed:1400510, ECO:0000269|PubMed:15735021, CC ECO:0000269|PubMed:19332886, ECO:0000269|PubMed:19354288, CC ECO:0000269|PubMed:20129916, ECO:0000269|PubMed:21855800, CC ECO:0000269|PubMed:23047679, ECO:0000269|PubMed:23843625, CC ECO:0000269|PubMed:2424496, ECO:0000269|PubMed:2459697, CC ECO:0000269|PubMed:2730651, ECO:0000269|PubMed:27518564, CC ECO:0000269|PubMed:28176817, ECO:0000269|PubMed:29100074, CC ECO:0000269|PubMed:29748193, ECO:0000269|PubMed:3122207, CC ECO:0000269|PubMed:31582561, ECO:0000269|PubMed:32510170, CC ECO:0000269|PubMed:3289612, ECO:0000269|PubMed:38718836, CC ECO:0000269|PubMed:4074709, ECO:0000269|PubMed:8127865, CC ECO:0000269|PubMed:8159680, ECO:0000269|PubMed:8448182, CC ECO:0000269|PubMed:8570639, ECO:0000269|PubMed:8622921, CC ECO:0000269|PubMed:9578571}. CC -!- ACTIVITY REGULATION: Has weak tRNA ribonuclease activity by itself due CC to partial autoinhibition by its C-terminus (residues 140-147), which CC folds into a short alpha-helix that partially occludes the substrate- CC binding site (PubMed:38718836, PubMed:8159680, PubMed:8622921, CC PubMed:9578571). In absence of stress, the ribonuclease activity is CC inhibited by RNH1 in the cytoplasm (PubMed:19332886, PubMed:19354288, CC PubMed:23843625, PubMed:3243277, PubMed:32510170, PubMed:38718836). In CC response to stress, dissociates from RNH1 in the cytoplasm and CC associates with cytoplasmic ribosomes with vacant A-sites: ribosomes CC directly activate the tRNA ribonuclease activity of ANG by refolding CC the C-terminal alpha-helix (PubMed:38718836). In response to stress, CC the angiogenic activity of ANG is inhibited by RNH1 in the nucleus CC (PubMed:23843625). {ECO:0000269|PubMed:19332886, CC ECO:0000269|PubMed:19354288, ECO:0000269|PubMed:23843625, CC ECO:0000269|PubMed:3243277, ECO:0000269|PubMed:32510170, CC ECO:0000269|PubMed:38718836, ECO:0000269|PubMed:8159680, CC ECO:0000269|PubMed:8622921, ECO:0000269|PubMed:9578571}. CC -!- SUBUNIT: Homodimer (PubMed:25372031). Interacts with RNH1; inhibiting CC ANG ribonuclease activity (PubMed:10413501, PubMed:19332886, CC PubMed:19354288, PubMed:23843625, PubMed:27518564, PubMed:3243277, CC PubMed:32510170, PubMed:9311977). Interacts with PCNA CC (PubMed:37218877). {ECO:0000269|PubMed:10413501, CC ECO:0000269|PubMed:19332886, ECO:0000269|PubMed:19354288, CC ECO:0000269|PubMed:23843625, ECO:0000269|PubMed:25372031, CC ECO:0000269|PubMed:27518564, ECO:0000269|PubMed:3243277, CC ECO:0000269|PubMed:32510170, ECO:0000269|PubMed:37218877, CC ECO:0000269|PubMed:9311977}. CC -!- INTERACTION: CC P03950; P35609: ACTN2; NbExp=4; IntAct=EBI-525291, EBI-77797; CC P03950; P19883: FST; NbExp=3; IntAct=EBI-525291, EBI-1571188; CC P03950; P12004: PCNA; NbExp=4; IntAct=EBI-525291, EBI-358311; CC P03950; Q03405: PLAUR; NbExp=5; IntAct=EBI-525291, EBI-716505; CC P03950; P13489: RNH1; NbExp=6; IntAct=EBI-525291, EBI-1237106; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:23047679, CC ECO:0000269|PubMed:29748193, ECO:0000269|PubMed:3663649}. Nucleus CC {ECO:0000269|PubMed:12051708, ECO:0000269|PubMed:15735021, CC ECO:0000269|PubMed:23047679, ECO:0000269|PubMed:23843625, CC ECO:0000269|PubMed:25372031, ECO:0000269|PubMed:29100074, CC ECO:0000269|PubMed:8127865}. Nucleus, nucleolus CC {ECO:0000269|PubMed:12051708, ECO:0000269|PubMed:7945327}. Cytoplasm, CC Stress granule {ECO:0000269|PubMed:23843625, CC ECO:0000269|PubMed:27518564, ECO:0000269|PubMed:29100074}. Note=The CC secreted protein is rapidly endocytosed by target cells following CC interaction with PLXNB2 receptor and translocated to the cytoplasm and CC nucleus (PubMed:29100074). In the nucleus, accumulates in the nucleolus CC and binds to DNA (PubMed:12051708). {ECO:0000269|PubMed:12051708, CC ECO:0000269|PubMed:29100074}. CC -!- TISSUE SPECIFICITY: Expressed predominantly in the liver CC (PubMed:2440105). Also detected in endothelial cells and spinal cord CC neurons (PubMed:17886298, PubMed:2440105). CC {ECO:0000269|PubMed:17886298, ECO:0000269|PubMed:2440105}. CC -!- DEVELOPMENTAL STAGE: Low level expression in the developing fetus, CC increased in the neonate, and maximal in the adult. CC {ECO:0000269|PubMed:2440105}. CC -!- DISEASE: Amyotrophic lateral sclerosis 9 (ALS9) [MIM:611895]: A CC neurodegenerative disorder affecting upper motor neurons in the brain CC and lower motor neurons in the brain stem and spinal cord, resulting in CC fatal paralysis. Sensory abnormalities are absent. The pathologic CC hallmarks of the disease include pallor of the corticospinal tract due CC to loss of motor neurons, presence of ubiquitin-positive inclusions CC within surviving motor neurons, and deposition of pathologic CC aggregates. The etiology of amyotrophic lateral sclerosis is likely to CC be multifactorial, involving both genetic and environmental factors. CC The disease is inherited in 5-10% of the cases. CC {ECO:0000269|PubMed:15557516, ECO:0000269|PubMed:16501576, CC ECO:0000269|PubMed:17703939, ECO:0000269|PubMed:17886298, CC ECO:0000269|PubMed:17900154, ECO:0000269|PubMed:18087731, CC ECO:0000269|PubMed:18852347, ECO:0000269|PubMed:19153377, CC ECO:0000269|PubMed:19332886, ECO:0000269|PubMed:19363631, CC ECO:0000269|PubMed:22190368, ECO:0000269|PubMed:22292798, CC ECO:0000269|PubMed:22292843, ECO:0000269|PubMed:25372031, CC ECO:0000269|PubMed:29748193, ECO:0000269|PubMed:38718836}. Note=Disease CC susceptibility is associated with variants affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the pancreatic ribonuclease family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH20704.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding; CC Note=Angiogenin; CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_other_803"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/635/ANG"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M11567; AAA51678.1; -; Genomic_DNA. DR EMBL; AF449647; AAL67710.1; -; Genomic_DNA. DR EMBL; AF449648; AAL67711.1; -; Genomic_DNA. DR EMBL; AF449649; AAL67712.1; -; Genomic_DNA. DR EMBL; AF449650; AAL67713.1; -; Genomic_DNA. DR EMBL; AF449651; AAL67714.1; -; Genomic_DNA. DR EMBL; FJ236304; ACI45236.1; -; mRNA. DR EMBL; CR407633; CAG28561.1; -; mRNA. DR EMBL; AK313989; BAG36701.1; -; mRNA. DR EMBL; CH471078; EAW66450.1; -; Genomic_DNA. DR EMBL; CH471078; EAW66451.1; -; Genomic_DNA. DR EMBL; BC020704; AAH20704.1; ALT_INIT; mRNA. DR EMBL; BC054880; AAH54880.1; -; mRNA. DR EMBL; BC062698; AAH62698.1; -; mRNA. DR CCDS; CCDS9554.1; -. DR PIR; A90498; NRHUAG. DR RefSeq; NP_001091046.1; NM_001097577.3. DR RefSeq; NP_001136.1; NM_001145.4. DR RefSeq; NP_001372200.1; NM_001385271.1. DR RefSeq; NP_001372201.1; NM_001385272.1. DR RefSeq; NP_001372202.1; NM_001385273.1. DR RefSeq; NP_001372203.1; NM_001385274.1. DR PDB; 1A4Y; X-ray; 2.00 A; B/E=25-147. DR PDB; 1ANG; X-ray; 2.40 A; A=25-147. DR PDB; 1AWZ; NMR; -; A=25-147. DR PDB; 1B1E; X-ray; 2.00 A; A=25-147. DR PDB; 1B1I; X-ray; 1.80 A; A=26-147. DR PDB; 1B1J; X-ray; 2.00 A; A=25-147. DR PDB; 1GV7; X-ray; 2.10 A; A=26-145. DR PDB; 1H0D; X-ray; 2.00 A; C=26-147. DR PDB; 1H52; X-ray; 2.00 A; A=25-147. DR PDB; 1H53; X-ray; 2.00 A; A=26-147. DR PDB; 1HBY; X-ray; 2.00 A; A=25-147. DR PDB; 1K58; X-ray; 2.70 A; A=25-147. DR PDB; 1K59; X-ray; 1.80 A; A=25-147. DR PDB; 1K5A; X-ray; 2.33 A; A=25-147. DR PDB; 1K5B; X-ray; 1.80 A; A=25-144. DR PDB; 1UN3; X-ray; 1.70 A; A=26-147. DR PDB; 1UN4; X-ray; 2.10 A; A=26-147. DR PDB; 1UN5; X-ray; 2.60 A; A=25-147. DR PDB; 2ANG; X-ray; 2.00 A; A=25-147. DR PDB; 4AHD; X-ray; 2.47 A; A/B=25-147. DR PDB; 4AHE; X-ray; 2.08 A; A=25-147. DR PDB; 4AHF; X-ray; 2.12 A; A=25-147. DR PDB; 4AHG; X-ray; 2.45 A; A=25-147. DR PDB; 4AHH; X-ray; 2.50 A; A=25-147. DR PDB; 4AHI; X-ray; 2.80 A; A=25-147. DR PDB; 4AHJ; X-ray; 2.03 A; A=25-147. DR PDB; 4AHK; X-ray; 1.97 A; A/B=25-147. DR PDB; 4AHL; X-ray; 2.05 A; A=25-147. DR PDB; 4AHM; X-ray; 1.96 A; A=25-147. DR PDB; 4AHN; X-ray; 2.98 A; A=25-147. DR PDB; 4AOH; X-ray; 1.04 A; A=24-147. DR PDB; 4B36; X-ray; 1.76 A; A/B=25-147. DR PDB; 5EOP; X-ray; 1.35 A; A=26-146. DR PDB; 5EPZ; X-ray; 1.85 A; A=26-145. DR PDB; 5EQO; X-ray; 2.40 A; A=25-145. DR PDB; 5M9A; X-ray; 1.95 A; A=25-147. DR PDB; 5M9C; X-ray; 2.05 A; A=25-147. DR PDB; 5M9G; X-ray; 2.28 A; A=25-147. DR PDB; 5M9J; X-ray; 1.90 A; A=25-147. DR PDB; 5M9M; X-ray; 1.65 A; A/B/C/D=25-147. DR PDB; 5M9P; X-ray; 1.80 A; A=25-147. DR PDB; 5M9Q; X-ray; 1.35 A; A=25-147. DR PDB; 5M9R; X-ray; 1.44 A; A/B=25-147. DR PDB; 5M9S; X-ray; 1.85 A; A=25-147. DR PDB; 5M9T; X-ray; 2.20 A; A/B=25-147. DR PDB; 5M9V; X-ray; 1.70 A; A=25-147. DR PDB; 7NPM; X-ray; 1.86 A; AAA=26-146. DR PDB; 7PNJ; X-ray; 3.10 A; A=25-145. DR PDB; 7PNP; X-ray; 1.80 A; A=25-147. DR PDB; 7PNR; X-ray; 1.60 A; A=25-145. DR PDB; 8AF0; X-ray; 2.43 A; A/B=25-147. DR PDB; 9BDL; EM; 2.80 A; ANG=1-147. DR PDB; 9BDN; EM; 3.10 A; ANG=1-147. DR PDB; 9BDP; EM; 3.70 A; ANG=1-147. DR PDBsum; 1A4Y; -. DR PDBsum; 1ANG; -. DR PDBsum; 1AWZ; -. DR PDBsum; 1B1E; -. DR PDBsum; 1B1I; -. DR PDBsum; 1B1J; -. DR PDBsum; 1GV7; -. DR PDBsum; 1H0D; -. DR PDBsum; 1H52; -. DR PDBsum; 1H53; -. DR PDBsum; 1HBY; -. DR PDBsum; 1K58; -. DR PDBsum; 1K59; -. DR PDBsum; 1K5A; -. DR PDBsum; 1K5B; -. DR PDBsum; 1UN3; -. DR PDBsum; 1UN4; -. DR PDBsum; 1UN5; -. DR PDBsum; 2ANG; -. DR PDBsum; 4AHD; -. DR PDBsum; 4AHE; -. DR PDBsum; 4AHF; -. DR PDBsum; 4AHG; -. DR PDBsum; 4AHH; -. DR PDBsum; 4AHI; -. DR PDBsum; 4AHJ; -. DR PDBsum; 4AHK; -. DR PDBsum; 4AHL; -. DR PDBsum; 4AHM; -. DR PDBsum; 4AHN; -. DR PDBsum; 4AOH; -. DR PDBsum; 4B36; -. DR PDBsum; 5EOP; -. DR PDBsum; 5EPZ; -. DR PDBsum; 5EQO; -. DR PDBsum; 5M9A; -. DR PDBsum; 5M9C; -. DR PDBsum; 5M9G; -. DR PDBsum; 5M9J; -. DR PDBsum; 5M9M; -. DR PDBsum; 5M9P; -. DR PDBsum; 5M9Q; -. DR PDBsum; 5M9R; -. DR PDBsum; 5M9S; -. DR PDBsum; 5M9T; -. DR PDBsum; 5M9V; -. DR PDBsum; 7NPM; -. DR PDBsum; 7PNJ; -. DR PDBsum; 7PNP; -. DR PDBsum; 7PNR; -. DR PDBsum; 8AF0; -. DR PDBsum; 9BDL; -. DR PDBsum; 9BDN; -. DR PDBsum; 9BDP; -. DR AlphaFoldDB; P03950; -. DR EMDB; EMD-44461; -. DR EMDB; EMD-44463; -. DR EMDB; EMD-44464; -. DR SMR; P03950; -. DR BioGRID; 106780; 9. DR CORUM; P03950; -. DR FunCoup; P03950; 165. DR IntAct; P03950; 125. DR MINT; P03950; -. DR STRING; 9606.ENSP00000336762; -. DR BindingDB; P03950; -. DR ChEMBL; CHEMBL5829; -. DR DrugBank; DB09130; Copper. DR GlyGen; P03950; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P03950; -. DR PhosphoSitePlus; P03950; -. DR BioMuta; ANG; -. DR DMDM; 113873; -. DR jPOST; P03950; -. DR MassIVE; P03950; -. DR PaxDb; 9606-ENSP00000336762; -. DR PeptideAtlas; P03950; -. DR ProteomicsDB; 51619; -. DR TopDownProteomics; P03950; -. DR ABCD; P03950; 1 sequenced antibody. DR Antibodypedia; 22061; 470 antibodies from 35 providers. DR DNASU; 283; -. DR Ensembl; ENST00000336811.10; ENSP00000336762.6; ENSG00000214274.11. DR Ensembl; ENST00000397990.5; ENSP00000381077.4; ENSG00000214274.11. DR GeneID; 283; -. DR KEGG; hsa:283; -. DR MANE-Select; ENST00000397990.5; ENSP00000381077.4; NM_001097577.3; NP_001091046.1. DR AGR; HGNC:483; -. DR ClinPGx; PA24790; -. DR CTD; 283; -. DR DisGeNET; 283; -. DR GeneCards; ANG; -. DR HGNC; HGNC:483; ANG. DR HPA; ENSG00000214274; Tissue enriched (liver). DR MalaCards; ANG; -. DR MIM; 105850; gene. DR MIM; 611895; phenotype. DR OpenTargets; ENSG00000214274; -. DR Orphanet; 803; Amyotrophic lateral sclerosis. DR VEuPathDB; HostDB:ENSG00000214274; -. DR eggNOG; ENOG502S9Q1; Eukaryota. DR GeneTree; ENSGT00940000162981; -. DR HOGENOM; CLU_117006_3_1_1; -. DR InParanoid; P03950; -. DR OMA; FIHGNKG; -. DR OrthoDB; 8573660at2759; -. DR PAN-GO; P03950; 7 GO annotations based on evolutionary models. DR PhylomeDB; P03950; -. DR PathwayCommons; P03950; -. DR Reactome; R-HSA-418990; Adherens junctions interactions. DR Reactome; R-HSA-9708296; tRNA-derived small RNA (tsRNA or tRNA-related fragment, tRF) biogenesis. DR SABIO-RK; P03950; -. DR SignaLink; P03950; -. DR SIGNOR; P03950; -. DR Agora; ENSG00000214274; -. DR BioGRID-ORCS; 283; 19 hits in 1148 CRISPR screens. DR CD-CODE; DEE660B4; Stress granule. DR EvolutionaryTrace; P03950; -. DR GeneWiki; Angiogenin; -. DR GenomeRNAi; 283; -. DR Pharos; P03950; Tbio. DR PRO; PR:P03950; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; P03950; protein. DR Bgee; ENSG00000214274; Expressed in right lobe of liver and 158 other cell types or tissues. DR ExpressionAtlas; P03950; baseline and differential. DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA. DR GO; GO:0032311; C:angiogenin-PRI complex; IDA:MGI. DR GO; GO:0005604; C:basement membrane; IDA:UniProtKB. DR GO; GO:0005694; C:chromosome; IDA:HPA. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0030139; C:endocytic vesicle; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0030426; C:growth cone; ISS:UniProtKB. DR GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003779; F:actin binding; IDA:UniProtKB. DR GO; GO:0005507; F:copper ion binding; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IC:UniProtKB. DR GO; GO:0004519; F:endonuclease activity; TAS:UniProtKB. DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB. DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW. DR GO; GO:0042277; F:peptide binding; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0048018; F:receptor ligand activity; IDA:UniProt. DR GO; GO:0043022; F:ribosome binding; IDA:UniProtKB. DR GO; GO:0004521; F:RNA endonuclease activity; TAS:Reactome. DR GO; GO:0004540; F:RNA nuclease activity; IDA:UniProtKB. DR GO; GO:0019843; F:rRNA binding; TAS:UniProtKB. DR GO; GO:0005102; F:signaling receptor binding; IDA:UniProtKB. DR GO; GO:0004549; F:tRNA-specific ribonuclease activity; IDA:UniProtKB. DR GO; GO:0030041; P:actin filament polymerization; ISS:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IDA:UniProtKB. DR GO; GO:0019731; P:antibacterial humoral response; IBA:GO_Central. DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IBA:GO_Central. DR GO; GO:0007154; P:cell communication; NAS:UniProtKB. DR GO; GO:0016477; P:cell migration; IMP:UniProtKB. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IBA:GO_Central. DR GO; GO:0071425; P:hematopoietic stem cell proliferation; IDA:UniProtKB. DR GO; GO:0042592; P:homeostatic process; NAS:UniProtKB. DR GO; GO:0045087; P:innate immune response; IBA:GO_Central. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IDA:UniProtKB. DR GO; GO:0032055; P:negative regulation of translation in response to stress; IDA:UniProtKB. DR GO; GO:0001556; P:oocyte maturation; NAS:UniProtKB. DR GO; GO:0001541; P:ovarian follicle development; NAS:UniProtKB. DR GO; GO:0001890; P:placenta development; NAS:UniProtKB. DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IDA:UniProtKB. DR GO; GO:0042327; P:positive regulation of phosphorylation; IDA:UniProtKB. DR GO; GO:0050714; P:positive regulation of protein secretion; IDA:UniProtKB. DR GO; GO:0009725; P:response to hormone; IDA:UniProtKB. DR GO; GO:0001666; P:response to hypoxia; IDA:UniProtKB. DR GO; GO:0009303; P:rRNA transcription; IDA:UniProtKB. DR GO; GO:0007165; P:signal transduction; IDA:UniProt. DR GO; GO:0023052; P:signaling; IDA:UniProtKB. DR GO; GO:0034063; P:stress granule assembly; IDA:UniProtKB. DR GO; GO:0016078; P:tRNA decay; TAS:Reactome. DR CDD; cd06265; RNase_A_canonical; 1. DR FunFam; 3.10.130.10:FF:000001; Ribonuclease pancreatic; 1. DR Gene3D; 3.10.130.10; Ribonuclease A-like domain; 1. DR InterPro; IPR001427; RNaseA. DR InterPro; IPR036816; RNaseA-like_dom_sf. DR InterPro; IPR023411; RNaseA_AS. DR InterPro; IPR023412; RNaseA_domain. DR PANTHER; PTHR11437:SF60; ANGIOGENIN; 1. DR PANTHER; PTHR11437; RIBONUCLEASE; 1. DR Pfam; PF00074; RnaseA; 1. DR PRINTS; PR00794; RIBONUCLEASE. DR SMART; SM00092; RNAse_Pc; 1. DR SUPFAM; SSF54076; RNase A-like; 1. DR PROSITE; PS00127; RNASE_PANCREATIC; 1. PE 1: Evidence at protein level; KW 3D-structure; Amyotrophic lateral sclerosis; Angiogenesis; Cytoplasm; KW Developmental protein; Differentiation; Direct protein sequencing; KW Disease variant; Disulfide bond; DNA-binding; Endonuclease; Hydrolase; KW Neurodegeneration; Nuclease; Nucleus; Protein synthesis inhibitor; KW Proteomics identification; Pyrrolidone carboxylic acid; Reference proteome; KW Secreted; Signal; Stress response. FT SIGNAL 1..24 FT /evidence="ECO:0000269|PubMed:2866794" FT CHAIN 25..147 FT /note="Angiogenin" FT /evidence="ECO:0000269|PubMed:2866794, FT ECO:0000269|PubMed:2866795" FT /id="PRO_0000030843" FT MOTIF 55..59 FT /note="Nucleolar localization signal" FT /evidence="ECO:0000269|PubMed:7945327" FT ACT_SITE 37 FT /note="Proton acceptor" FT /evidence="ECO:0000269|PubMed:11468363, FT ECO:0000269|PubMed:38718836, ECO:0000269|PubMed:9918722" FT ACT_SITE 138 FT /note="Proton donor" FT /evidence="ECO:0000269|PubMed:11468363, FT ECO:0000269|PubMed:38718836, ECO:0000269|PubMed:9918722" FT BINDING 45 FT /ligand="tRNA" FT /ligand_id="ChEBI:CHEBI:17843" FT /evidence="ECO:0000269|PubMed:38718836" FT BINDING 46 FT /ligand="tRNA" FT /ligand_id="ChEBI:CHEBI:17843" FT /evidence="ECO:0000269|PubMed:38718836" FT BINDING 105 FT /ligand="tRNA" FT /ligand_id="ChEBI:CHEBI:17843" FT /evidence="ECO:0000269|PubMed:38718836" FT BINDING 127 FT /ligand="tRNA" FT /ligand_id="ChEBI:CHEBI:17843" FT /evidence="ECO:0000269|PubMed:38718836" FT MOD_RES 25 FT /note="Pyrrolidone carboxylic acid" FT /evidence="ECO:0000269|PubMed:2866794" FT DISULFID 50..105 FT /evidence="ECO:0000269|PubMed:11468363, FT ECO:0000269|PubMed:11851402, ECO:0000269|PubMed:12842050, FT ECO:0000269|PubMed:14756559, ECO:0000269|PubMed:28176817, FT ECO:0000269|PubMed:2866794, ECO:0000269|PubMed:37218877, FT ECO:0000269|PubMed:38718836, ECO:0000269|PubMed:8159679, FT ECO:0000269|PubMed:9311977, ECO:0000269|PubMed:9461294, FT ECO:0000269|PubMed:9918722, ECO:0007744|PDB:1A4Y, FT ECO:0007744|PDB:1ANG, ECO:0007744|PDB:1AWZ, FT ECO:0007744|PDB:1B1E, ECO:0007744|PDB:1B1I, FT ECO:0007744|PDB:1B1J, ECO:0007744|PDB:1H0D, FT ECO:0007744|PDB:1H52, ECO:0007744|PDB:1H53, FT ECO:0007744|PDB:1HBY, ECO:0007744|PDB:1K58, FT ECO:0007744|PDB:1K59, ECO:0007744|PDB:1K5A, FT ECO:0007744|PDB:1K5B, ECO:0007744|PDB:1UN3, FT ECO:0007744|PDB:1UN4, ECO:0007744|PDB:1UN5, FT ECO:0007744|PDB:2ANG, ECO:0007744|PDB:4AHD, FT ECO:0007744|PDB:4AHE, ECO:0007744|PDB:4AHF, FT ECO:0007744|PDB:4AHG, ECO:0007744|PDB:4AHH, FT ECO:0007744|PDB:4AHI, ECO:0007744|PDB:4AHJ, FT ECO:0007744|PDB:4AHK, ECO:0007744|PDB:4AHL, FT ECO:0007744|PDB:4AHM, ECO:0007744|PDB:4AHN, FT ECO:0007744|PDB:4AOH, ECO:0007744|PDB:4B36, FT ECO:0007744|PDB:5EOP, ECO:0007744|PDB:5EPZ, FT ECO:0007744|PDB:5EQO, ECO:0007744|PDB:5M9A, FT ECO:0007744|PDB:5M9C, ECO:0007744|PDB:5M9G, FT ECO:0007744|PDB:5M9J, ECO:0007744|PDB:5M9M, FT ECO:0007744|PDB:5M9P, ECO:0007744|PDB:5M9Q, FT ECO:0007744|PDB:5M9R, ECO:0007744|PDB:5M9S, FT ECO:0007744|PDB:5M9T, ECO:0007744|PDB:5M9V, FT ECO:0007744|PDB:7NPM, ECO:0007744|PDB:7PNJ, FT ECO:0007744|PDB:7PNP, ECO:0007744|PDB:7PNR, FT ECO:0007744|PDB:8AF0" FT DISULFID 63..116 FT /evidence="ECO:0000269|PubMed:11468363, FT ECO:0000269|PubMed:11851402, ECO:0000269|PubMed:12842050, FT ECO:0000269|PubMed:14756559, ECO:0000269|PubMed:28176817, FT ECO:0000269|PubMed:2866794, ECO:0000269|PubMed:37218877, FT ECO:0000269|PubMed:38718836, ECO:0000269|PubMed:8159679, FT ECO:0000269|PubMed:9311977, ECO:0000269|PubMed:9461294, FT ECO:0000269|PubMed:9918722, ECO:0007744|PDB:1A4Y, FT ECO:0007744|PDB:1ANG, ECO:0007744|PDB:1AWZ, FT ECO:0007744|PDB:1B1E, ECO:0007744|PDB:1B1I, FT ECO:0007744|PDB:1B1J, ECO:0007744|PDB:1H0D, FT ECO:0007744|PDB:1H52, ECO:0007744|PDB:1H53, FT ECO:0007744|PDB:1HBY, ECO:0007744|PDB:1K58, FT ECO:0007744|PDB:1K59, ECO:0007744|PDB:1K5A, FT ECO:0007744|PDB:1K5B, ECO:0007744|PDB:1UN3, FT ECO:0007744|PDB:1UN4, ECO:0007744|PDB:1UN5, FT ECO:0007744|PDB:2ANG, ECO:0007744|PDB:4AHD, FT ECO:0007744|PDB:4AHE, ECO:0007744|PDB:4AHF, FT ECO:0007744|PDB:4AHG, ECO:0007744|PDB:4AHH, FT ECO:0007744|PDB:4AHI, ECO:0007744|PDB:4AHJ, FT ECO:0007744|PDB:4AHK, ECO:0007744|PDB:4AHL, FT ECO:0007744|PDB:4AHM, ECO:0007744|PDB:4AHN, FT ECO:0007744|PDB:4AOH, ECO:0007744|PDB:4B36, FT ECO:0007744|PDB:5EOP, ECO:0007744|PDB:5EPZ, FT ECO:0007744|PDB:5EQO, ECO:0007744|PDB:5M9A, FT ECO:0007744|PDB:5M9C, ECO:0007744|PDB:5M9G, FT ECO:0007744|PDB:5M9J, ECO:0007744|PDB:5M9M, FT ECO:0007744|PDB:5M9P, ECO:0007744|PDB:5M9Q, FT ECO:0007744|PDB:5M9R, ECO:0007744|PDB:5M9S, FT ECO:0007744|PDB:5M9T, ECO:0007744|PDB:5M9V, FT ECO:0007744|PDB:7NPM, ECO:0007744|PDB:7PNJ, FT ECO:0007744|PDB:7PNP, ECO:0007744|PDB:7PNR, FT ECO:0007744|PDB:8AF0" FT DISULFID 81..131 FT /evidence="ECO:0000269|PubMed:11468363, FT ECO:0000269|PubMed:11851402, ECO:0000269|PubMed:12842050, FT ECO:0000269|PubMed:14756559, ECO:0000269|PubMed:28176817, FT ECO:0000269|PubMed:2866794, ECO:0000269|PubMed:37218877, FT ECO:0000269|PubMed:38718836, ECO:0000269|PubMed:8159679, FT ECO:0000269|PubMed:9311977, ECO:0000269|PubMed:9461294, FT ECO:0000269|PubMed:9918722, ECO:0007744|PDB:1A4Y, FT ECO:0007744|PDB:1ANG, ECO:0007744|PDB:1AWZ, FT ECO:0007744|PDB:1B1E, ECO:0007744|PDB:1B1I, FT ECO:0007744|PDB:1B1J, ECO:0007744|PDB:1H0D, FT ECO:0007744|PDB:1H52, ECO:0007744|PDB:1H53, FT ECO:0007744|PDB:1HBY, ECO:0007744|PDB:1K58, FT ECO:0007744|PDB:1K59, ECO:0007744|PDB:1K5A, FT ECO:0007744|PDB:1K5B, ECO:0007744|PDB:1UN3, FT ECO:0007744|PDB:1UN4, ECO:0007744|PDB:1UN5, FT ECO:0007744|PDB:2ANG, ECO:0007744|PDB:4AHD, FT ECO:0007744|PDB:4AHE, ECO:0007744|PDB:4AHF, FT ECO:0007744|PDB:4AHG, ECO:0007744|PDB:4AHH, FT ECO:0007744|PDB:4AHI, ECO:0007744|PDB:4AHJ, FT ECO:0007744|PDB:4AHK, ECO:0007744|PDB:4AHL, FT ECO:0007744|PDB:4AHM, ECO:0007744|PDB:4AHN, FT ECO:0007744|PDB:4AOH, ECO:0007744|PDB:4B36, FT ECO:0007744|PDB:5EOP, ECO:0007744|PDB:5EPZ, FT ECO:0007744|PDB:5EQO, ECO:0007744|PDB:5M9A, FT ECO:0007744|PDB:5M9C, ECO:0007744|PDB:5M9G, FT ECO:0007744|PDB:5M9J, ECO:0007744|PDB:5M9M, FT ECO:0007744|PDB:5M9P, ECO:0007744|PDB:5M9Q, FT ECO:0007744|PDB:5M9R, ECO:0007744|PDB:5M9S, FT ECO:0007744|PDB:5M9T, ECO:0007744|PDB:5M9V, FT ECO:0007744|PDB:7NPM, ECO:0007744|PDB:7PNJ, FT ECO:0007744|PDB:7PNP, ECO:0007744|PDB:7PNR, FT ECO:0007744|PDB:8AF0" FT VARIANT 12 FT /note="F -> L (in ALS9)" FT /evidence="ECO:0000269|PubMed:19363631, FT ECO:0000269|PubMed:22190368" FT /id="VAR_089762" FT VARIANT 12 FT /note="F -> S (in ALS9)" FT /evidence="ECO:0000269|PubMed:18087731, FT ECO:0000269|PubMed:22190368" FT /id="VAR_044145" FT VARIANT 13 FT /note="V -> A (found in a patient with Parkinson disease; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:22190368" FT /id="VAR_089763" FT VARIANT 15 FT /note="G -> D (in ALS9; uncertain significance)" FT /evidence="ECO:0000269|PubMed:22190368" FT /id="VAR_089764" FT VARIANT 17 FT /note="G -> D (found in a patient with Parkinson disease; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:22190368" FT /id="VAR_089765" FT VARIANT 20 FT /note="P -> Q (in ALS9; uncertain significance)" FT /evidence="ECO:0000269|PubMed:22190368" FT /id="VAR_089766" FT VARIANT 20 FT /note="P -> S (in ALS9)" FT /evidence="ECO:0000269|PubMed:17886298, FT ECO:0000269|PubMed:18087731, ECO:0000269|PubMed:22190368" FT /id="VAR_044146" FT VARIANT 36 FT /note="Q -> L (in ALS9; reduced ribonucleolytic activity; FT low angiogenic activity; reduced mitogenic activity; wild FT type far-UV CD spectra; dbSNP:rs121909535)" FT /evidence="ECO:0000269|PubMed:16501576, FT ECO:0000269|PubMed:17900154, ECO:0000269|PubMed:22190368" FT /id="VAR_044147" FT VARIANT 37 FT /note="H -> R (found in a patient with Parkinson disease; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:22190368" FT /id="VAR_089767" FT VARIANT 38 FT /note="Y -> H (in ALS9; dbSNP:rs1032422334)" FT /evidence="ECO:0000269|PubMed:22292843" FT /id="VAR_073021" FT VARIANT 41 FT /note="K -> E (in ALS9; reduced ribonucleolytic activity; FT dbSNP:rs121909537)" FT /evidence="ECO:0000269|PubMed:16501576, FT ECO:0000269|PubMed:17900154, ECO:0000269|PubMed:19153377, FT ECO:0000269|PubMed:22190368" FT /id="VAR_044148" FT VARIANT 41 FT /note="K -> I (in ALS9; loss of angiogenic activity; FT reduced ribonucleolytic activity; retains nuclear FT translocation; dbSNP:rs121909536)" FT /evidence="ECO:0000269|PubMed:16501576, FT ECO:0000269|PubMed:17886298, ECO:0000269|PubMed:17900154, FT ECO:0000269|PubMed:22292843" FT /id="VAR_044149" FT VARIANT 46 FT /note="D -> G (in ALS9; homodimerization is similar to FT wild-type; localization in the nucleus is similar to the FT wild-type; strongly reduces ribonucleolytic activity; FT dbSNP:rs1440927797)" FT /evidence="ECO:0000269|PubMed:22292843, FT ECO:0000269|PubMed:25372031" FT /id="VAR_073022" FT VARIANT 46 FT /note="D -> V (found in a patient with Parkinson disease; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:22190368" FT /id="VAR_089768" FT VARIANT 52 FT /note="S -> N (in ALS9; loss of angiogenic activity; FT reduced ribonucleolytic activity; unable to translocate to FT the nucleus; dbSNP:rs121909542)" FT /evidence="ECO:0000269|PubMed:17886298, FT ECO:0000269|PubMed:22190368" FT /id="VAR_044150" FT VARIANT 55 FT /note="R -> K (in ALS9; marginally reduced ribonucleolytic FT activity; wild type far-UV CD spectra; dbSNP:rs121909538)" FT /evidence="ECO:0000269|PubMed:16501576, FT ECO:0000269|PubMed:17900154, ECO:0000269|PubMed:22190368" FT /id="VAR_044151" FT VARIANT 63 FT /note="C -> W (in ALS9; reduced ribonucleolytic activity; FT low angiogenic activity; reduced mitogenic activity; FT reduced thermal stability; dbSNP:rs121909539)" FT /evidence="ECO:0000269|PubMed:16501576, FT ECO:0000269|PubMed:17900154, ECO:0000269|PubMed:22190368" FT /id="VAR_044152" FT VARIANT 64 FT /note="K -> E (in ALS9; uncertain significance)" FT /evidence="ECO:0000269|PubMed:22190368" FT /id="VAR_089769" FT VARIANT 64 FT /note="K -> I (in ALS9; reduced ribonucleolytic activity; FT low angiogenic activity; reduced mitogenic activity; FT moderate reduction of thermal stability; FT dbSNP:rs121909540)" FT /evidence="ECO:0000269|PubMed:15557516, FT ECO:0000269|PubMed:16501576, ECO:0000269|PubMed:17900154, FT ECO:0000269|PubMed:22190368" FT /id="VAR_044153" FT VARIANT 70 FT /note="I -> V (in ALS9; uncertain significance; reduced FT ribonucleolytic activity; moderate reduction of thermal FT stability; dbSNP:rs121909541)" FT /evidence="ECO:0000269|PubMed:16501576, FT ECO:0000269|PubMed:17900154, ECO:0000269|PubMed:18087731, FT ECO:0000269|PubMed:18852347" FT /id="VAR_044154" FT VARIANT 78 FT /note="K -> E (in ALS9; decreased interaction with the FT ribosome and ability to repress translation)" FT /evidence="ECO:0000269|PubMed:19363631, FT ECO:0000269|PubMed:38718836" FT /id="VAR_089770" FT VARIANT 78 FT /note="K -> R (found in a patient with Parkinson disease; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:22190368" FT /id="VAR_089771" FT VARIANT 84 FT /note="K -> E (in dbSNP:rs17560)" FT /evidence="ECO:0000269|PubMed:11919285" FT /id="VAR_013148" FT VARIANT 104 FT /note="T -> S (in ALS9; uncertain significance)" FT /evidence="ECO:0000269|PubMed:22190368" FT /id="VAR_089772" FT VARIANT 119 FT /note="R -> Q (found in a patient with Parkinson disease; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:22190368" FT /id="VAR_089773" FT VARIANT 124 FT /note="F -> I (in ALS9; uncertain significance)" FT /evidence="ECO:0000269|PubMed:22190368" FT /id="VAR_089774" FT VARIANT 127 FT /note="V -> I (in ALS9; uncertain significance)" FT /evidence="ECO:0000269|PubMed:22292798" FT /id="VAR_089775" FT VARIANT 136 FT /note="P -> L (in ALS9; loss of angiogenic activity; FT reduced tRNA ribonucleolytic activity; unable to FT translocate to the nucleus; dbSNP:rs121909543)" FT /evidence="ECO:0000269|PubMed:17886298, FT ECO:0000269|PubMed:19332886, ECO:0000269|PubMed:22190368, FT ECO:0000269|PubMed:29748193" FT /id="VAR_044155" FT VARIANT 137 FT /note="V -> I (in ALS9; dbSNP:rs121909544)" FT /evidence="ECO:0000269|PubMed:18087731, FT ECO:0000269|PubMed:22190368" FT /id="VAR_044156" FT VARIANT 138 FT /note="H -> R (in ALS9; uncertain significance)" FT /evidence="ECO:0000269|PubMed:18087731, FT ECO:0000269|PubMed:22190368" FT /id="VAR_044157" FT VARIANT 145 FT /note="R -> C (found in a patient with Parkinson disease)" FT /evidence="ECO:0000269|PubMed:22190368" FT /id="VAR_089776" FT VARIANT 145 FT /note="R -> H (in ALS9; uncertain significance)" FT /evidence="ECO:0000269|PubMed:18852347, FT ECO:0000269|PubMed:22190368" FT /id="VAR_089777" FT MUTAGEN 29 FT /note="R->A: Affects substrate preference. Significantly FT decreases binding affinity for RNH1." FT /evidence="ECO:0000269|PubMed:10413501, FT ECO:0000269|PubMed:8570639" FT MUTAGEN 32 FT /note="H->A: Significantly decreases binding affinity for FT RNH1." FT /evidence="ECO:0000269|PubMed:9050852" FT MUTAGEN 36 FT /note="Q->A: Slightly decreases binding affinity for RNH1." FT /evidence="ECO:0000269|PubMed:9050852" FT MUTAGEN 37 FT /note="H->A: Abolished ribonuclease activity. does not FT affect binding to PLXNB2 receptor." FT /evidence="ECO:0000269|PubMed:29100074, FT ECO:0000269|PubMed:38718836" FT MUTAGEN 59 FT /note="L->P: Homodimerization is similar to wild-type; FT causes mislocalization in the cytoplasm; strongly reduces FT ribonucleolytic activity." FT /evidence="ECO:0000269|PubMed:25372031" FT MUTAGEN 64 FT /note="K->Q: Significantly decreases binding affinity for FT RNH1." FT /evidence="ECO:0000269|PubMed:10413501, FT ECO:0000269|PubMed:9050852" FT MUTAGEN 68 FT /note="T->A: Decreased ribonuclease activity." FT /evidence="ECO:0000269|PubMed:9578571" FT MUTAGEN 90 FT /note="R->A: Abolished binding to PLXNB2 receptor." FT /evidence="ECO:0000269|PubMed:29100074" FT MUTAGEN 92 FT /note="N->A: Slightly decreases binding affinity for RNH1." FT /evidence="ECO:0000269|PubMed:9050852" FT MUTAGEN 92 FT /note="N->D: Abolished binding to PLXNB2 receptor." FT /evidence="ECO:0000269|PubMed:29100074" FT MUTAGEN 104 FT /note="T->A: Increased ribonuclease activity." FT /evidence="ECO:0000269|PubMed:9578571" FT MUTAGEN 104 FT /note="T->D: Slightly increased ribonuclease activity." FT /evidence="ECO:0000269|PubMed:9578571" FT MUTAGEN 109..110 FT /note="GG->RR: Significantly decreases binding affinity for FT RNH1." FT /evidence="ECO:0000269|PubMed:19354288" FT MUTAGEN 132 FT /note="E->A: Slightly decreases binding affinity for RNH1." FT /evidence="ECO:0000269|PubMed:9050852" FT MUTAGEN 140..141 FT /note="DQ->AA: Slightly increased ribonuclease activity." FT /evidence="ECO:0000269|PubMed:8159680" FT MUTAGEN 140 FT /note="D->N,H,S,A: Strongly increased ribonuclease FT activity." FT /evidence="ECO:0000269|PubMed:11851402, FT ECO:0000269|PubMed:2459697" FT MUTAGEN 141 FT /note="Q->A,G: Strongly increased ribonuclease activity." FT /evidence="ECO:0000269|PubMed:11851402, FT ECO:0000269|PubMed:8159680" FT MUTAGEN 143..144 FT /note="IF->AA: Increased ribonuclease activity." FT /evidence="ECO:0000269|PubMed:11851402, FT ECO:0000269|PubMed:8622921" FT HELIX 28..37 FT /evidence="ECO:0007829|PDB:4AOH" FT HELIX 47..56 FT /evidence="ECO:0007829|PDB:4AOH" FT TURN 60..63 FT /evidence="ECO:0007829|PDB:4AOH" FT STRAND 65..70 FT /evidence="ECO:0007829|PDB:4AOH" FT HELIX 74..78 FT /evidence="ECO:0007829|PDB:4AOH" FT HELIX 79..81 FT /evidence="ECO:0007829|PDB:4AOH" FT TURN 83..85 FT /evidence="ECO:0007829|PDB:4AOH" FT STRAND 86..89 FT /evidence="ECO:0007829|PDB:4AOH" FT TURN 90..92 FT /evidence="ECO:0007829|PDB:4AOH" FT STRAND 93..98 FT /evidence="ECO:0007829|PDB:4AOH" FT STRAND 100..110 FT /evidence="ECO:0007829|PDB:4AOH" FT STRAND 112..115 FT /evidence="ECO:0007829|PDB:4AOH" FT STRAND 117..125 FT /evidence="ECO:0007829|PDB:4AOH" FT STRAND 128..132 FT /evidence="ECO:0007829|PDB:4AOH" FT STRAND 135..139 FT /evidence="ECO:0007829|PDB:4AOH" FT HELIX 141..144 FT /evidence="ECO:0007829|PDB:4AOH" SQ SEQUENCE 147 AA; 16550 MW; 9C462DA3C8D39ACC CRC64; MVMGLGVLLL VFVLGLGLTP PTLAQDNSRY THFLTQHYDA KPQGRDDRYC ESIMRRRGLT SPCKDINTFI HGNKRSIKAI CENKNGNPHR ENLRISKSSF QVTTCKLHGG SPWPPCQYRA TAGFRNVVVA CENGLPVHLD QSIFRRP //