ANGI_HUMAN
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 03-AUG-2022, entry version 237.
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 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 [13]
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 26-147.
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 [20]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 26-147 OF MUTANT GLY-141 IN
RP COMPLEX WITH PHOSPHATE AND PYROPHOSPHATE.
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 [21]
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 [22]
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 [23]
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 [24]
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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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 [30]
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 [31]
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 [32]
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 [33]
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: Binds to actin on the surface of endothelial cells; once
CC bound, angiogenin is endocytosed and translocated to the nucleus.
CC Stimulates ribosomal RNA synthesis including that containing the
CC initiation site sequences of 45S rRNA. Cleaves tRNA within anticodon
CC loops to produce tRNA-derived stress-induced fragments (tiRNAs) which
CC inhibit protein synthesis and triggers the assembly of stress granules
CC (SGs). Angiogenin induces vascularization of normal and malignant
CC tissues. Angiogenic activity is regulated by interaction with RNH1 in
CC vivo. {ECO:0000269|PubMed:12051708, ECO:0000269|PubMed:1400510,
CC ECO:0000269|PubMed:19354288, ECO:0000269|PubMed:21855800}.
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}. Nucleus, nucleolus
CC {ECO:0000269|PubMed:7945327}. Note=Rapidly endocytosed by target cells
CC and translocated to the nucleus where it accumulates in the nucleolus
CC and binds to DNA (PubMed:12051708). {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="http://atlasgeneticsoncology.org/Genes/ANGID635ch14q11.html";
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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; 7PNR; X-ray; 1.60 A; A=25-145.
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; 7PNR; -.
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 iPTMnet; P03950; -.
DR PhosphoSitePlus; P03950; -.
DR BioMuta; ANG; -.
DR DMDM; 113873; -.
DR EPD; P03950; -.
DR jPOST; P03950; -.
DR MassIVE; P03950; -.
DR PaxDb; P03950; -.
DR PeptideAtlas; P03950; -.
DR PRIDE; P03950; -.
DR ProteomicsDB; 51619; -.
DR TopDownProteomics; P03950; -.
DR ABCD; P03950; 1 sequenced antibody.
DR Antibodypedia; 22061; 456 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 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; FIHGNKG; -.
DR OrthoDB; 1549558at2759; -.
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 1069 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 156 other tissues.
DR ExpressionAtlas; P03950; baseline and differential.
DR Genevisible; P03950; HS.
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:0004521; F:endoribonuclease activity; TAS:Reactome.
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:0004540; F:ribonuclease 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; IDA:UniProtKB.
DR GO; GO:0019732; P:antifungal humoral response; IDA:UniProtKB.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
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; IDA:UniProtKB.
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; IDA:UniProtKB.
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:0001878; P:response to yeast; IDA:UniProtKB.
DR GO; GO:0009303; P:rRNA transcription; IMP:UniProtKB.
DR GO; GO:0016078; P:tRNA catabolic process; TAS:Reactome.
DR Gene3D; 3.10.130.10; -; 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; PTHR11437; 1.
DR Pfam; PF00074; RnaseA; 1.
DR PRINTS; PR00794; RIBONUCLEASE.
DR SMART; SM00092; RNAse_Pc; 1.
DR SUPFAM; SSF54076; SSF54076; 1.
DR PROSITE; PS00127; RNASE_PANCREATIC; 1.
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 ACT_SITE 37
FT /note="Proton acceptor"
FT ACT_SITE 138
FT /note="Proton donor"
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-UV CD 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; reduces strongly 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-UV CD 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; pathogenicity
FT uncertain; 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; reduces strongly
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
