ID RN5A_HUMAN Reviewed; 741 AA. AC Q05823; Q5W0L2; Q6AI46; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1996, sequence version 2. DT 24-JAN-2024, entry version 210. DE RecName: Full=2-5A-dependent ribonuclease; DE Short=2-5A-dependent RNase; DE EC=3.1.26.-; DE AltName: Full=Ribonuclease 4; DE AltName: Full=Ribonuclease L; DE Short=RNase L; GN Name=RNASEL; Synonyms=RNS4; 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], AND MUTAGENESIS OF LYS-240 AND LYS-274. RC TISSUE=Kidney; RX PubMed=7680958; DOI=10.1016/0092-8674(93)90403-d; RA Zhou A., Hassel B.A., Silverman R.H.; RT "Expression cloning of 2-5A-dependent RNAase: a uniquely regulated mediator RT of interferon action."; RL Cell 72:753-765(1993). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Placenta; RX PubMed=11063255; DOI=10.1007/s003350010194; RA Zhou A., Nie H., Silverman R.H.; RT "Analysis and origins of the human and mouse RNase L genes: mediators of RT interferon action."; RL Mamm. Genome 11:989-992(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Colon carcinoma; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Lymph; 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 [7] RP CHARACTERIZATION OF RNASEL ACTIVITY. RX PubMed=7514601; DOI=10.1016/s0021-9258(17)36767-4; RA Dong B., Xu L., Zhou A., Hassel B.A., Lee X., Torrence P.F., RA Silverman R.H.; RT "Intrinsic molecular activities of the interferon-induced 2-5A-dependent RT RNase."; RL J. Biol. Chem. 269:14153-14158(1994). RN [8] RP INTERACTION WITH ABCE1. RX PubMed=7539425; DOI=10.1074/jbc.270.22.13308; RA Bisbal C., Martinand C., Silhol M., Lebleu B., Salehzada T.; RT "Cloning and characterization of a RNase L inhibitor. A new component of RT the interferon-regulated 2-5A pathway."; RL J. Biol. Chem. 270:13308-13317(1995). RN [9] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=11585831; DOI=10.1074/jbc.m107482200; RA Le Roy F., Bisbal C., Silhol M., Martinand C., Lebleu B., Salehzada T.; RT "The 2-5A/RNase L/RNase L inhibitor (RNI) pathway regulates mitochondrial RT mRNAs stability in interferon alpha-treated H9 cells."; RL J. Biol. Chem. 276:48473-48482(2001). RN [10] RP ERRATUM OF PUBMED:11585831. RA Le Roy F., Bisbal C., Silhol M., Martinand C., Lebleu B., Salehzada T.; RL J. Biol. Chem. 277:13354-13354(2002). RN [11] RP REVIEW. RX PubMed=9856285; DOI=10.1016/s0753-3322(99)80006-7; RA Castelli J., Wood K.A., Youle R.J.; RT "The 2-5A system in viral infection and apoptosis."; RL Biomed. Pharmacother. 52:386-390(1998). RN [12] RP MUTAGENESIS OF LYS-392. RX PubMed=9862963; DOI=10.1093/nar/27.2.439; RA Dong B., Silverman R.H.; RT "Alternative function of a protein kinase homology domain in 2', 5'- RT oligoadenylate dependent RNase L."; RL Nucleic Acids Res. 27:439-445(1999). RN [13] RP MUTAGENESIS OF HIS-583; PRO-584; TRP-632; ASP-661; ARG-667 AND HIS-672. RX PubMed=11333017; DOI=10.1017/s1355838201002230; RA Dong B., Niwa M., Walter P., Silverman R.H.; RT "Basis for regulated RNA cleavage by functional analysis of RNase L and RT Ire1p."; RL RNA 7:361-373(2001). RN [14] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-684, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [15] RP FUNCTION. RX PubMed=26263979; DOI=10.3390/ijms160817611; RA Siddiqui M.A., Mukherjee S., Manivannan P., Malathi K.; RT "RNase L cleavage products promote switch from autophagy to apoptosis by RT caspase-mediated cleavage of beclin-1."; RL Int. J. Mol. Sci. 16:17611-17636(2015). RN [16] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 21-305 IN COMPLEX WITH THE RP ACTIVATOR 2-5A. RX PubMed=15385955; DOI=10.1038/sj.emboj.7600420; RA Tanaka N., Nakanishi M., Kusakabe Y., Goto Y., Kitade Y., Nakamura K.T.; RT "Structural basis for recognition of 2',5'-linked oligoadenylates by human RT ribonuclease L."; RL EMBO J. 23:3929-3938(2004). RN [17] RP VARIANTS SER-59; PHE-406; GLN-462 AND GLU-541. RX PubMed=11941539; DOI=10.1086/340450; RA Roekman A., Ikonen T., Seppaelae E.H., Nupponen N., Autio V., Mononen N., RA Bailey-Wilson J., Trent J., Carpten J., Matikainen M.P., Koivisto P.A., RA Tammela T.L.J., Kallioniemi O.-P., Schleutker J.; RT "Germline alterations of the RNASEL gene, a candidate HPC1 gene at 1q25, in RT patients and families with prostate cancer."; RL Am. J. Hum. Genet. 70:1299-1304(2002). RN [18] RP VARIANTS SER-59; GLN-462 AND GLU-541. RX PubMed=11799394; DOI=10.1038/ng823; RA Carpten J., Nupponen N., Isaacs S., Sood R., Robbins C., Xu J., Faruque M., RA Moses T., Ewing C., Gillanders E., Hu P., Bujnovszky P., Makalowska I., RA Baffoe-Bonnie A., Faith D., Smith J., Stephan D., Wiley K., Brownstein M., RA Gildea D., Kelly B., Jenkins R., Hostetter G., Matikainen M., RA Schleutker J., Klinger K., Connors T., Xiang Y., Wang Z., De Marzo A., RA Papadopoulos N., Kallioniemi O.-P., Burk R., Meyers D., Groenberg H., RA Meltzer P., Silverman R., Bailey-Wilson J., Walsh P., Isaacs W., Trent J.; RT "Germline mutations in the ribonuclease L gene in families showing linkage RT with HPC1."; RL Nat. Genet. 30:181-184(2002). RN [19] RP CHARACTERIZATION OF VARIANTS GLN-462 AND GLU-541. RX PubMed=12415269; DOI=10.1038/ng1021; RA Casey G., Neville P.J., Plummer S.J., Xiang Y., Krumroy L.M., Klein E.A., RA Catalona W.J., Nupponen N., Carpten J.D., Trent J.M., Silverman R.H., RA Witte J.S.; RT "RNASEL Arg462Gln variant is implicated in up to 13% of prostate cancer RT cases."; RL Nat. Genet. 32:581-583(2002). RN [20] RP VARIANTS [LARGE SCALE ANALYSIS] LEU-97; THR-289; GLN-462; GLU-541 AND RP HIS-592. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- FUNCTION: Endoribonuclease that functions in the interferon (IFN) CC antiviral response. In INF treated and virus infected cells, RNASEL CC probably mediates its antiviral effects through a combination of direct CC cleavage of single-stranded viral RNAs, inhibition of protein synthesis CC through the degradation of rRNA, induction of apoptosis, and induction CC of other antiviral genes. RNASEL mediated apoptosis is the result of a CC JNK-dependent stress-response pathway leading to cytochrome c release CC from mitochondria and caspase-dependent apoptosis. Therefore, CC activation of RNASEL could lead to elimination of virus infected cells CC under some circumstances. In the crosstalk between autophagy and CC apoptosis proposed to induce autophagy as an early stress response to CC small double-stranded RNA and at later stages of prolonged stress to CC activate caspase-dependent proteolytic cleavage of BECN1 to terminate CC autophagy and promote apoptosis (PubMed:26263979). Might play a central CC role in the regulation of mRNA turnover (PubMed:11585831). Cleaves 3' CC of UpNp dimers, with preference for UU and UA sequences, to sets of CC discrete products ranging from between 4 and 22 nucleotides in length. CC {ECO:0000269|PubMed:11585831, ECO:0000269|PubMed:26263979}. CC -!- COFACTOR: CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Note=Manganese or magnesium. Required for optimal RNA cleavage rates.; CC -!- ACTIVITY REGULATION: After binding to 2-5A (5'-phosphorylated 2',5'- CC linked oligoadenylates) the homodimerization and subsequent activation CC occurs. Inhibited by RNASEL inhibitor ABCE1/RLI, a cytoplasmic member CC of the ATP-binding cassette (ABC) transporter family. CC -!- SUBUNIT: Monomer (inactive form) or homodimer. Interacts with ABCE1; CC this interaction inhibits the RNASEL. {ECO:0000269|PubMed:15385955, CC ECO:0000269|PubMed:7539425}. CC -!- INTERACTION: CC Q05823; P46940: IQGAP1; NbExp=2; IntAct=EBI-8390477, EBI-297509; CC Q05823-1; Q05823-1: RNASEL; NbExp=2; IntAct=EBI-16094551, EBI-16094551; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11585831}. CC Mitochondrion {ECO:0000269|PubMed:11585831}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q05823-1; Sequence=Displayed; CC Name=2; CC IsoId=Q05823-2; Sequence=VSP_056272, VSP_056273; CC -!- TISSUE SPECIFICITY: Highly expressed in spleen and thymus followed by CC prostate, testis, uterus, small intestine, colon and peripheral blood CC leukocytes. CC -!- INDUCTION: By interferons. Virus replication in higher vertebrates is CC restrained by IFNs that cause cells to transcribe genes encoding CC antiviral proteins, such as 2'-5' oligoadenylate synthetases (OASs). CC oligoadenylate synthetase is stimulated by dsRNA to produce 5'- CC phosphorylated, 2'-5'-linked oligoadenylates (2-5A), whose function is CC to activate RNASEL. CC -!- DOMAIN: The nine ankyrin repeats also called 2-5A sensor constitute the CC N-terminus 2-5A binding domain. CC -!- DOMAIN: The protein kinase domain is predicted to be catalytically CC inactive. It allows the homodimerization. CC -!- DOMAIN: The ribonuclease domain is located in the C-terminus. A single CC active nuclease domain in a dimer is sufficient for ribonuclease CC activity (By similarity). {ECO:0000250}. CC -!- DISEASE: Prostate cancer, hereditary, 1 (HPC1) [MIM:601518]: A CC condition associated with familial predisposition to cancer of the CC prostate. Most prostate cancers are adenocarcinomas that develop in the CC acini of the prostatic ducts. Other rare histopathologic types of CC prostate cancer that occur in approximately 5% of patients include CC small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, CC transitional cell carcinoma, squamous cell carcinoma, basal cell CC carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell CC carcinoma and neuroendocrine carcinoma. {ECO:0000305|PubMed:11799394, CC ECO:0000305|PubMed:11941539, ECO:0000305|PubMed:12415269, CC ECO:0000305|PubMed:17344846}. Note=Disease susceptibility is associated CC with variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. {ECO:0000305}. 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; L10381; AAA18032.1; -; Genomic_DNA. DR EMBL; CR627369; CAH10468.1; -; mRNA. DR EMBL; AL138776; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471067; EAW91128.1; -; Genomic_DNA. DR EMBL; BC090934; AAH90934.1; -; mRNA. DR EMBL; BC114433; AAI14434.1; -; mRNA. DR CCDS; CCDS1347.1; -. [Q05823-1] DR PIR; A45771; A45771. DR RefSeq; NP_066956.1; NM_021133.3. [Q05823-1] DR PDB; 1WDY; X-ray; 1.80 A; A=21-305. DR PDB; 4G8K; X-ray; 2.40 A; A/B=1-337. DR PDB; 4G8L; X-ray; 2.80 A; A/B/C/D=1-337. DR PDB; 4OAU; X-ray; 2.60 A; C=21-719. DR PDB; 4OAV; X-ray; 2.10 A; B/D=21-719. DR PDBsum; 1WDY; -. DR PDBsum; 4G8K; -. DR PDBsum; 4G8L; -. DR PDBsum; 4OAU; -. DR PDBsum; 4OAV; -. DR AlphaFoldDB; Q05823; -. DR SMR; Q05823; -. DR BioGRID; 111969; 33. DR DIP; DIP-61367N; -. DR IntAct; Q05823; 22. DR MINT; Q05823; -. DR STRING; 9606.ENSP00000356530; -. DR BindingDB; Q05823; -. DR ChEMBL; CHEMBL3575; -. DR GlyGen; Q05823; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q05823; -. DR PhosphoSitePlus; Q05823; -. DR BioMuta; RNASEL; -. DR DMDM; 1350802; -. DR EPD; Q05823; -. DR jPOST; Q05823; -. DR MassIVE; Q05823; -. DR PaxDb; 9606-ENSP00000356530; -. DR PeptideAtlas; Q05823; -. DR ProteomicsDB; 58353; -. [Q05823-1] DR ProteomicsDB; 66189; -. DR Pumba; Q05823; -. DR Antibodypedia; 1127; 231 antibodies from 28 providers. DR DNASU; 6041; -. DR Ensembl; ENST00000367559.7; ENSP00000356530.3; ENSG00000135828.11. [Q05823-1] DR Ensembl; ENST00000539397.1; ENSP00000440844.1; ENSG00000135828.11. [Q05823-2] DR GeneID; 6041; -. DR KEGG; hsa:6041; -. DR MANE-Select; ENST00000367559.7; ENSP00000356530.3; NM_021133.4; NP_066956.1. DR UCSC; uc001gpk.4; human. [Q05823-1] DR AGR; HGNC:10050; -. DR CTD; 6041; -. DR DisGeNET; 6041; -. DR GeneCards; RNASEL; -. DR HGNC; HGNC:10050; RNASEL. DR HPA; ENSG00000135828; Low tissue specificity. DR MalaCards; RNASEL; -. DR MIM; 176807; phenotype. DR MIM; 180435; gene. DR MIM; 601518; phenotype. DR neXtProt; NX_Q05823; -. DR OpenTargets; ENSG00000135828; -. DR Orphanet; 1331; Familial prostate cancer. DR PharmGKB; PA34418; -. DR VEuPathDB; HostDB:ENSG00000135828; -. DR eggNOG; KOG1027; Eukaryota. DR eggNOG; KOG4177; Eukaryota. DR GeneTree; ENSGT00940000161114; -. DR HOGENOM; CLU_022542_0_0_1; -. DR InParanoid; Q05823; -. DR OMA; YGSESHK; -. DR OrthoDB; 2994922at2759; -. DR PhylomeDB; Q05823; -. DR TreeFam; TF344032; -. DR BioCyc; MetaCyc:HS06069-MONOMER; -. DR BRENDA; 4.6.1.19; 2681. DR PathwayCommons; Q05823; -. DR Reactome; R-HSA-8983711; OAS antiviral response. DR Reactome; R-HSA-909733; Interferon alpha/beta signaling. DR SignaLink; Q05823; -. DR SIGNOR; Q05823; -. DR BioGRID-ORCS; 6041; 9 hits in 1192 CRISPR screens. DR ChiTaRS; RNASEL; human. DR EvolutionaryTrace; Q05823; -. DR GeneWiki; Ribonuclease_L; -. DR GeneWiki; RNASEL; -. DR GenomeRNAi; 6041; -. DR Pharos; Q05823; Tchem. DR PRO; PR:Q05823; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q05823; Protein. DR Bgee; ENSG00000135828; Expressed in amniotic fluid and 174 other cell types or tissues. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0016363; C:nuclear matrix; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004672; F:protein kinase activity; IEA:InterPro. DR GO; GO:0043021; F:ribonucleoprotein complex binding; IEA:Ensembl. DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB. DR GO; GO:0004521; F:RNA endonuclease activity; NAS:UniProtKB. DR GO; GO:0004540; F:RNA nuclease activity; IDA:ARUK-UCL. DR GO; GO:0019843; F:rRNA binding; IEA:Ensembl. DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB. DR GO; GO:0045444; P:fat cell differentiation; IEA:Ensembl. DR GO; GO:0006397; P:mRNA processing; IEA:InterPro. DR GO; GO:0045071; P:negative regulation of viral genome replication; IDA:UniProtKB. DR GO; GO:0046326; P:positive regulation of glucose import; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; NAS:UniProtKB. DR GO; GO:0043488; P:regulation of mRNA stability; IEA:Ensembl. DR GO; GO:0006396; P:RNA processing; IBA:GO_Central. DR GO; GO:0006364; P:rRNA processing; IEA:Ensembl. DR CDD; cd10423; RNase_RNase-L; 1. DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 1. DR Gene3D; 1.20.1440.180; KEN domain; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR002110; Ankyrin_rpt. DR InterPro; IPR036770; Ankyrin_rpt-contain_sf. DR InterPro; IPR010513; KEN_dom. DR InterPro; IPR038357; KEN_sf. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR042745; RNase-L_RNase. DR PANTHER; PTHR24141; 2-5A-DEPENDENT RIBONUCLEASE; 1. DR PANTHER; PTHR24141:SF1; 2-5A-DEPENDENT RIBONUCLEASE; 1. DR Pfam; PF12796; Ank_2; 3. DR Pfam; PF13857; Ank_5; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF06479; Ribonuc_2-5A; 1. DR PRINTS; PR01415; ANKYRIN. DR SMART; SM00248; ANK; 8. DR SMART; SM00580; PUG; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF48403; Ankyrin repeat; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS50297; ANK_REP_REGION; 1. DR PROSITE; PS50088; ANK_REPEAT; 6. DR PROSITE; PS51392; KEN; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR Genevisible; Q05823; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ANK repeat; KW Antiviral defense; ATP-binding; Cytoplasm; Endonuclease; Hydrolase; KW Metal-binding; Mitochondrion; Nuclease; Nucleotide-binding; KW Reference proteome; Repeat; RNA-binding; Zinc; Zinc-finger. FT CHAIN 1..741 FT /note="2-5A-dependent ribonuclease" FT /id="PRO_0000067051" FT REPEAT 24..53 FT /note="ANK 1" FT REPEAT 58..87 FT /note="ANK 2" FT REPEAT 91..120 FT /note="ANK 3" FT REPEAT 124..153 FT /note="ANK 4" FT REPEAT 167..197 FT /note="ANK 5" FT REPEAT 201..234 FT /note="ANK 6" FT REPEAT 238..268 FT /note="ANK 7" FT REPEAT 272..301 FT /note="ANK 8" FT REPEAT 303..329 FT /note="ANK 9" FT DOMAIN 365..586 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 589..723 FT /note="KEN" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00725" FT ZN_FING 395..444 FT /note="C6-type; atypical" FT REGION 1..21 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 229..242 FT /note="2-5A binding (P-loop) 1" FT REGION 253..275 FT /note="2-5A binding (P-loop) 2" FT REGION 715..741 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 684 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT VAR_SEQ 636..652 FT /note="INECVMKKMNKFYEKRG -> MSKLRHRQIIFPTTQNQ (in isoform FT 2)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:17974005" FT /id="VSP_056272" FT VAR_SEQ 653..741 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:17974005" FT /id="VSP_056273" FT VARIANT 59 FT /note="G -> S (in dbSNP:rs151296858)" FT /evidence="ECO:0000269|PubMed:11799394, FT ECO:0000269|PubMed:11941539" FT /id="VAR_013509" FT VARIANT 97 FT /note="I -> L (in dbSNP:rs56250729)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042358" FT VARIANT 289 FT /note="A -> T (in dbSNP:rs35553278)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042359" FT VARIANT 406 FT /note="S -> F (in dbSNP:rs145787003)" FT /evidence="ECO:0000269|PubMed:11941539" FT /id="VAR_013510" FT VARIANT 462 FT /note="R -> Q (risk factor for prostate cancer; reduced FT enzymatic activity; dbSNP:rs486907)" FT /evidence="ECO:0000269|PubMed:11799394, FT ECO:0000269|PubMed:11941539, ECO:0000269|PubMed:12415269, FT ECO:0000269|PubMed:17344846" FT /id="VAR_012056" FT VARIANT 541 FT /note="D -> E (no change in enzymatic activity; FT dbSNP:rs627928)" FT /evidence="ECO:0000269|PubMed:11799394, FT ECO:0000269|PubMed:11941539, ECO:0000269|PubMed:12415269, FT ECO:0000269|PubMed:17344846" FT /id="VAR_012057" FT VARIANT 592 FT /note="R -> H (in dbSNP:rs35896902)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042360" FT MUTAGEN 240 FT /note="K->N: Reduced 2-5A binding activity; almost complete FT loss of 2-5A binding activity; when associated with N-274." FT /evidence="ECO:0000269|PubMed:7680958" FT MUTAGEN 274 FT /note="K->N: Reduced 2-5A binding activity; almost complete FT loss of 2-5A binding activity; when associated with N-240." FT /evidence="ECO:0000269|PubMed:7680958" FT MUTAGEN 392 FT /note="K->R: Complete loss of enzymatic activity and enzyme FT dimerization. No change in binding to 2-5A and RNA." FT /evidence="ECO:0000269|PubMed:9862963" FT MUTAGEN 583 FT /note="H->A: No change in enzymatic activity." FT /evidence="ECO:0000269|PubMed:11333017" FT MUTAGEN 584 FT /note="P->A: No change in enzymatic activity." FT /evidence="ECO:0000269|PubMed:11333017" FT MUTAGEN 632 FT /note="W->A: No change in enzymatic activity." FT /evidence="ECO:0000269|PubMed:11333017" FT MUTAGEN 661 FT /note="D->A: Complete loss of enzymatic activity." FT /evidence="ECO:0000269|PubMed:11333017" FT MUTAGEN 667 FT /note="R->A: Complete loss of enzymatic activity. No change FT in 2-5A binding and enzyme dimerization." FT /evidence="ECO:0000269|PubMed:11333017" FT MUTAGEN 672 FT /note="H->A: Complete loss of enzymatic activity. No change FT in 2-5A binding activity and enzyme dimerization." FT /evidence="ECO:0000269|PubMed:11333017" FT HELIX 22..34 FT /evidence="ECO:0007829|PDB:1WDY" FT HELIX 38..46 FT /evidence="ECO:0007829|PDB:1WDY" FT TURN 56..58 FT /evidence="ECO:0007829|PDB:1WDY" FT HELIX 62..68 FT /evidence="ECO:0007829|PDB:1WDY" FT HELIX 72..80 FT /evidence="ECO:0007829|PDB:1WDY" FT HELIX 95..102 FT /evidence="ECO:0007829|PDB:1WDY" FT HELIX 105..113 FT /evidence="ECO:0007829|PDB:1WDY" FT HELIX 128..134 FT /evidence="ECO:0007829|PDB:1WDY" FT HELIX 138..146 FT /evidence="ECO:0007829|PDB:1WDY" FT HELIX 159..163 FT /evidence="ECO:0007829|PDB:1WDY" FT HELIX 171..178 FT /evidence="ECO:0007829|PDB:1WDY" FT HELIX 181..189 FT /evidence="ECO:0007829|PDB:1WDY" FT HELIX 205..211 FT /evidence="ECO:0007829|PDB:1WDY" FT TURN 215..217 FT /evidence="ECO:0007829|PDB:1WDY" FT HELIX 218..227 FT /evidence="ECO:0007829|PDB:1WDY" FT HELIX 237..239 FT /evidence="ECO:0007829|PDB:4G8K" FT HELIX 242..248 FT /evidence="ECO:0007829|PDB:1WDY" FT HELIX 252..260 FT /evidence="ECO:0007829|PDB:1WDY" FT STRAND 261..263 FT /evidence="ECO:0007829|PDB:1WDY" FT HELIX 276..282 FT /evidence="ECO:0007829|PDB:1WDY" FT HELIX 286..295 FT /evidence="ECO:0007829|PDB:1WDY" FT STRAND 301..303 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 304..310 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 314..322 FT /evidence="ECO:0007829|PDB:4OAV" FT STRAND 341..344 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 345..352 FT /evidence="ECO:0007829|PDB:4OAV" FT STRAND 361..363 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 367..369 FT /evidence="ECO:0007829|PDB:4OAV" FT STRAND 370..374 FT /evidence="ECO:0007829|PDB:4OAV" FT STRAND 377..395 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 399..409 FT /evidence="ECO:0007829|PDB:4OAV" FT STRAND 420..425 FT /evidence="ECO:0007829|PDB:4OAV" FT STRAND 427..435 FT /evidence="ECO:0007829|PDB:4OAV" FT STRAND 438..440 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 441..445 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 459..477 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 488..490 FT /evidence="ECO:0007829|PDB:4OAV" FT STRAND 491..493 FT /evidence="ECO:0007829|PDB:4OAV" FT STRAND 495..497 FT /evidence="ECO:0007829|PDB:4OAV" FT STRAND 499..501 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 514..532 FT /evidence="ECO:0007829|PDB:4OAV" FT TURN 533..535 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 539..544 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 547..551 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 557..567 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 576..580 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 584..586 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 589..600 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 603..606 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 613..618 FT /evidence="ECO:0007829|PDB:4OAV" FT TURN 628..631 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 632..634 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 638..645 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 646..648 FT /evidence="ECO:0007829|PDB:4OAV" FT TURN 649..652 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 659..672 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 681..685 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 688..695 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 699..707 FT /evidence="ECO:0007829|PDB:4OAV" FT HELIX 711..715 FT /evidence="ECO:0007829|PDB:4OAV" SQ SEQUENCE 741 AA; 83533 MW; 91385EA307E3CE1D CRC64; MESRDHNNPQ EGPTSSSGRR AAVEDNHLLI KAVQNEDVDL VQQLLEGGAN VNFQEEEGGW TPLHNAVQMS REDIVELLLR HGADPVLRKK NGATPFILAA IAGSVKLLKL FLSKGADVNE CDFYGFTAFM EAAVYGKVKA LKFLYKRGAN VNLRRKTKED QERLRKGGAT ALMDAAEKGH VEVLKILLDE MGADVNACDN MGRNALIHAL LSSDDSDVEA ITHLLLDHGA DVNVRGERGK TPLILAVEKK HLGLVQRLLE QEHIEINDTD SDGKTALLLA VELKLKKIAE LLCKRGASTD CGDLVMTARR NYDHSLVKVL LSHGAKEDFH PPAEDWKPQS SHWGAALKDL HRIYRPMIGK LKFFIDEKYK IADTSEGGIY LGFYEKQEVA VKTFCEGSPR AQREVSCLQS SRENSHLVTF YGSESHRGHL FVCVTLCEQT LEACLDVHRG EDVENEEDEF ARNVLSSIFK AVQELHLSCG YTHQDLQPQN ILIDSKKAAH LADFDKSIKW AGDPQEVKRD LEDLGRLVLY VVKKGSISFE DLKAQSNEEV VQLSPDEETK DLIHRLFHPG EHVRDCLSDL LGHPFFWTWE SRYRTLRNVG NESDIKTRKS ESEILRLLQP GPSEHSKSFD KWTTKINECV MKKMNKFYEK RGNFYQNTVG DLLKFIRNLG EHIDEEKHKK MKLKIGDPSL YFQKTFPDLV IYVYTKLQNT EYRKHFPQTH SPNKPQCDGA GGASGLASPG C //