RN5A_HUMAN
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 03-AUG-2022, entry version 202.
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}.
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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; 23.
DR DIP; DIP-61367N; -.
DR IntAct; Q05823; 22.
DR MINT; Q05823; -.
DR STRING; 9606.ENSP00000356530; -.
DR BindingDB; Q05823; -.
DR ChEMBL; CHEMBL3575; -.
DR iPTMnet; Q05823; -.
DR PhosphoSitePlus; Q05823; -.
DR BioMuta; RNASEL; -.
DR DMDM; 1350802; -.
DR EPD; Q05823; -.
DR jPOST; Q05823; -.
DR MassIVE; Q05823; -.
DR PaxDb; Q05823; -.
DR PeptideAtlas; Q05823; -.
DR PRIDE; Q05823; -.
DR ProteomicsDB; 58353; -. [Q05823-1]
DR ProteomicsDB; 66189; -.
DR Antibodypedia; 1127; 217 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 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; VLYVVRK; -.
DR OrthoDB; 222916at2759; -.
DR PhylomeDB; Q05823; -.
DR TreeFam; TF344032; -.
DR BioCyc; MetaCyc:HS06069-MON; -.
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; 8 hits in 1112 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 172 other tissues.
DR Genevisible; Q05823; HS.
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:0004521; F:endoribonuclease activity; NAS:UniProtKB.
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:0004540; F:ribonuclease activity; IBA:GO_Central.
DR GO; GO:0043021; F:ribonucleoprotein complex binding; IEA:Ensembl.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
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; 1.20.1440.180; -; 1.
DR Gene3D; 1.25.40.20; -; 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 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; SM00220; S_TKc; 1.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF56112; SSF56112; 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.
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
