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 24-JAN-2024, entry version 245. DE RecName: Full=Angiogenin; DE EC=3.1.27.-; DE AltName: Full=Ribonuclease 5; DE Short=RNase 5; DE Flags: Precursor; GN Name=ANG; 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 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 [10] 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 [11] 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 [12] 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 [13] 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 [14] 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 [15] 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 [16] RP FUNCTION, INTERACTION WITH RNH1, AND MUTAGENESIS OF 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 [17] 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 [18] RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 25-147. 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 [19] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 25-147 IN COMPLEX WITH RNH1 AND RP 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 [20] RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 26-147, AND ACTIVE SITES. 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 [21] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 26-147 OF MUTANT GLY-141 IN RP COMPLEX WITH PHOSPHATE AND PYROPHOSPHATE, AND ACTIVE SITES. 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 [22] RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 26-147, AND MUTAGENESIS OF RP 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 [23] RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 26-147. 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 [24] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF MUTANTS ASP-68 AND ALA-104. 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 [25] RP STRUCTURE BY NMR. 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 [26] 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 [27] 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 [28] RP VARIANTS ALS9 LEU-36; ILE-41; GLU-41; LYS-55; TRP-63 AND ILE-64, AND RP VARIANT 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 [29] 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 [30] RP CHARACTERIZATION OF VARIANTS ALS9 LEU-36; ILE-41; GLU-41; LYS-55; TRP-63 RP AND ILE-64, AND CHARACTERIZATION OF VARIANT 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 [31] RP VARIANTS ALS9 SER-12; SER-20; ILE-137 AND ARG-138, AND VARIANT VAL-70. 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 [32] 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 [33] 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 [34] 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: Ribonuclease that cleaves tRNA within anticodon loops to CC produce tRNA-derived stress-induced fragments (tiRNAs) which inhibit CC protein synthesis and triggers the assembly of stress granules (SGs) CC (PubMed:1400510, PubMed:21855800). Binds to actin on the surface of CC endothelial cells; once bound, angiogenin is endocytosed and CC translocated to the nucleus (PubMed:8127865). Stimulates ribosomal RNA CC synthesis including that containing the initiation site sequences of CC 45S rRNA (PubMed:12051708). Angiogenin induces vascularization of CC normal and malignant tissues (PubMed:19354288). Angiogenic activity is CC regulated by interaction with RNH1 in vivo (PubMed:19354288). CC {ECO:0000269|PubMed:12051708, ECO:0000269|PubMed:1400510, CC ECO:0000269|PubMed:19354288, ECO:0000269|PubMed:21855800, CC ECO:0000269|PubMed:8127865}. CC -!- SUBUNIT: Homodimer (PubMed:25372031). Interacts with and forms a tight CC 1:1 complex with RNH1. Dimerization of two such complexes may occur. CC {ECO:0000269|PubMed:10413501, ECO:0000269|PubMed:11468363, CC ECO:0000269|PubMed:19354288, ECO:0000269|PubMed:25372031, 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=3; IntAct=EBI-525291, EBI-1237106; CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle lumen CC {ECO:0000250|UniProtKB:Q3TMQ6}. Secreted CC {ECO:0000250|UniProtKB:P10152}. Nucleus {ECO:0000269|PubMed:12051708, CC ECO:0000269|PubMed:25372031, ECO:0000269|PubMed:8127865}. Nucleus, CC nucleolus {ECO:0000269|PubMed:7945327}. Note=Rapidly endocytosed by CC target cells and translocated to the nucleus where it accumulates in CC the nucleolus and binds to DNA (PubMed:12051708). CC {ECO:0000269|PubMed:12051708}. CC -!- TISSUE SPECIFICITY: Expressed predominantly in the liver. Also detected CC in endothelial cells and spinal cord neurons. 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 -!- 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:22292843, ECO:0000269|PubMed:25372031}. 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 -!- CAUTION: It is uncertain whether Met-1 or Met-3 is the initiator. 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_001097577.2. DR RefSeq; NP_001136.1; NM_001145.4. 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 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 AlphaFoldDB; P03950; -. DR SMR; P03950; -. DR BioGRID; 106780; 9. DR CORUM; P03950; -. DR IntAct; P03950; 124. 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 EPD; P03950; -. 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; 495 antibodies from 34 providers. DR DNASU; 283; -. DR Ensembl; ENST00000336811.10; ENSP00000336762.6; ENSG00000214274.10. DR Ensembl; ENST00000397990.5; ENSP00000381077.4; ENSG00000214274.10. 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 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 neXtProt; NX_P03950; -. DR OpenTargets; ENSG00000214274; -. DR Orphanet; 803; Amyotrophic lateral sclerosis. DR PharmGKB; PA24790; -. DR VEuPathDB; HostDB:ENSG00000214274; -. DR eggNOG; ENOG502S9Q1; Eukaryota. DR GeneTree; ENSGT00940000162981; -. DR HOGENOM; CLU_117006_3_1_1; -. DR InParanoid; P03950; -. DR OMA; INTFVHG; -. DR OrthoDB; 4612546at2759; -. DR PhylomeDB; P03950; -. DR TreeFam; TF333393; -. 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 BioGRID-ORCS; 283; 19 hits in 1148 CRISPR screens. 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:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW. DR GO; GO:0005829; C:cytosol; TAS:Reactome. 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:0042277; F:peptide binding; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; 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:0030041; P:actin filament polymerization; ISS:UniProtKB. DR GO; GO:0032431; P:activation of phospholipase A2 activity; IMP:UniProtKB. DR GO; GO:0007202; P:activation of phospholipase C activity; IMP:UniProtKB. DR GO; GO:0032148; P:activation of protein kinase B activity; IMP:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IDA:MGI. 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:0006651; P:diacylglycerol biosynthetic process; 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:0048662; P:negative regulation of smooth muscle cell proliferation; IDA:UniProtKB. DR GO; GO:0017148; P:negative regulation of translation; IEA:UniProtKB-KW. 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; IMP:UniProtKB. DR GO; GO:0016078; P:tRNA catabolic process; TAS:Reactome. DR CDD; cd06265; RNase_A_canonical; 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. DR Genevisible; P03950; HS. PE 1: Evidence at protein level; KW 3D-structure; Amyotrophic lateral sclerosis; Angiogenesis; KW Cytoplasmic vesicle; Developmental protein; Differentiation; KW Direct protein sequencing; Disease variant; Disulfide bond; DNA-binding; KW Endonuclease; Hydrolase; Neurodegeneration; Nuclease; Nucleus; KW Protein synthesis inhibitor; Pyrrolidone carboxylic acid; KW Reference proteome; 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:9918722" FT ACT_SITE 138 FT /note="Proton donor" FT /evidence="ECO:0000269|PubMed:11468363, FT ECO:0000269|PubMed:9918722" FT BINDING 64..68 FT /ligand="substrate" FT MOD_RES 25 FT /note="Pyrrolidone carboxylic acid" FT /evidence="ECO:0000269|PubMed:2866794" FT DISULFID 50..105 FT /evidence="ECO:0000269|PubMed:2866794" FT DISULFID 63..116 FT /evidence="ECO:0000269|PubMed:2866794" FT DISULFID 81..131 FT /evidence="ECO:0000269|PubMed:2866794" FT VARIANT 12 FT /note="F -> S (in ALS9)" FT /evidence="ECO:0000269|PubMed:18087731" FT /id="VAR_044145" FT VARIANT 20 FT /note="P -> S (in ALS9)" FT /evidence="ECO:0000269|PubMed:17886298, FT ECO:0000269|PubMed:18087731" 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-UVCD spectra; dbSNP:rs121909535)" FT /evidence="ECO:0000269|PubMed:16501576, FT ECO:0000269|PubMed:17900154" FT /id="VAR_044147" 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" 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 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 /id="VAR_044150" FT VARIANT 55 FT /note="R -> K (in ALS9; marginally reduced ribonucleolytic FT activity; wild type far-UVCD spectra; dbSNP:rs121909538)" FT /evidence="ECO:0000269|PubMed:16501576, FT ECO:0000269|PubMed:17900154" 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" FT /id="VAR_044152" 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 /id="VAR_044153" FT VARIANT 70 FT /note="I -> V (in some ALS9 patients; uncertain FT significance; reduced ribonucleolytic activity; moderate FT reduction of thermal stability; dbSNP:rs121909541)" FT /evidence="ECO:0000269|PubMed:16501576, FT ECO:0000269|PubMed:17900154, ECO:0000269|PubMed:18087731" FT /id="VAR_044154" FT VARIANT 84 FT /note="K -> E (in dbSNP:rs17560)" FT /evidence="ECO:0000269|PubMed:11919285" FT /id="VAR_013148" FT VARIANT 136 FT /note="P -> L (in ALS9; loss of angiogenic activity; FT reduced ribonucleolytic activity; unable to translocate to FT the nucleus; dbSNP:rs121909543)" FT /evidence="ECO:0000269|PubMed:17886298" FT /id="VAR_044155" FT VARIANT 137 FT /note="V -> I (in ALS9; dbSNP:rs121909544)" FT /evidence="ECO:0000269|PubMed:18087731" FT /id="VAR_044156" FT VARIANT 138 FT /note="H -> R (in ALS9)" FT /evidence="ECO:0000269|PubMed:18087731" FT /id="VAR_044157" FT MUTAGEN 29 FT /note="R->A: Significantly decreases binding affinity for FT RNH1." FT /evidence="ECO:0000269|PubMed:10413501" 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 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 92 FT /note="N->A: Slightly decreases binding affinity for RNH1." FT /evidence="ECO:0000269|PubMed:9050852" 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 FT /note="D->H,S,A: 15- to 18-fold increase in RNase FT activity." FT /evidence="ECO:0000269|PubMed:11851402" FT MUTAGEN 141 FT /note="Q->G: Over 18-fold increase in RNase activity." FT /evidence="ECO:0000269|PubMed:11851402" FT MUTAGEN 143..144 FT /note="IF->AA: 3- to 5-fold increase in RNase activity." FT /evidence="ECO:0000269|PubMed:11851402" FT CONFLICT 59 FT /note="L -> P (in Ref. 7; AAH62698)" FT /evidence="ECO:0000305" 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 //