RN5A_MOUSE
ID RN5A_MOUSE Reviewed; 735 AA.
AC Q05921; Q9ERU7;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 11-FEB-2002, sequence version 2.
DT 03-AUG-2022, entry version 181.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C3H/An; TISSUE=Adipose tissue;
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 [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-679.
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 [3]
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 [4]
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP INTERACTION WITH TMEV LEADER PROTEIN (MICROBIAL INFECTION).
RX PubMed=23825954; DOI=10.1371/journal.ppat.1003474;
RA Sorgeloos F., Jha B.K., Silverman R.H., Michiels T.;
RT "Evasion of Antiviral Innate Immunity by Theiler's Virus L* Protein through
RT Direct Inhibition of RNase L.";
RL PLoS Pathog. 9:E1003474-E1003474(2013).
RN [7]
RP INTERACTION WITH TMEV LEADER PROTEIN (MICROBIAL INFECTION).
RX PubMed=29652922; DOI=10.1371/journal.ppat.1006989;
RA Drappier M., Jha B.K., Stone S., Elliott R., Zhang R., Vertommen D.,
RA Weiss S.R., Silverman R.H., Michiels T.;
RT "A novel mechanism of RNase L inhibition: Theiler's virus L* protein
RT prevents 2-5A from binding to RNase L.";
RL PLoS Pathog. 14:E1006989-E1006989(2018).
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. Might play a central role in the
CC regulation of mRNA turnover (By similarity). Cleaves 3' of UpNp dimers,
CC with preference for UU and UA sequences, to sets of discrete products
CC ranging from between 4 and 22 nucleotides in length (By similarity).
CC {ECO:0000250|UniProtKB:Q05823, ECO:0000269|PubMed:11585831}.
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 (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via N-terminus) with TMEV
CC leader protein; this interaction prevents RNASEL activation by its
CC substrate 2'-5' oligoadenylates. {ECO:0000269|PubMed:23825954,
CC ECO:0000269|PubMed:29652922}.
CC -!- SUBUNIT: Monomer (inactive form) or homodimer. Interacts with ABCE1;
CC this interaction inhibits the RNASEL (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11585831}.
CC Mitochondrion {ECO:0000269|PubMed:11585831}.
CC -!- TISSUE SPECIFICITY: Expressed in spleen, thymus, lung, testis, kidney,
CC liver and heart.
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.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. {ECO:0000305}.
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DR EMBL; AF281045; AAG33708.1; -; mRNA.
DR EMBL; L10382; AAA37117.1; -; Genomic_DNA.
DR CCDS; CCDS15377.1; -.
DR PIR; B45771; B45771.
DR RefSeq; NP_036012.1; NM_011882.2.
DR RefSeq; XP_006529590.1; XM_006529527.3.
DR RefSeq; XP_006529591.1; XM_006529528.3.
DR RefSeq; XP_006529593.1; XM_006529530.2.
DR RefSeq; XP_011246295.1; XM_011247993.2.
DR AlphaFoldDB; Q05921; -.
DR SMR; Q05921; -.
DR BioGRID; 204854; 8.
DR STRING; 10090.ENSMUSP00000083385; -.
DR BindingDB; Q05921; -.
DR ChEMBL; CHEMBL2687; -.
DR iPTMnet; Q05921; -.
DR PhosphoSitePlus; Q05921; -.
DR EPD; Q05921; -.
DR MaxQB; Q05921; -.
DR PaxDb; Q05921; -.
DR PRIDE; Q05921; -.
DR ProteomicsDB; 300452; -.
DR Antibodypedia; 1127; 217 antibodies from 28 providers.
DR DNASU; 24014; -.
DR Ensembl; ENSMUST00000086209; ENSMUSP00000083385; ENSMUSG00000066800.
DR GeneID; 24014; -.
DR KEGG; mmu:24014; -.
DR UCSC; uc007daf.1; mouse.
DR CTD; 6041; -.
DR MGI; MGI:1098272; Rnasel.
DR VEuPathDB; HostDB:ENSMUSG00000066800; -.
DR eggNOG; KOG1027; Eukaryota.
DR eggNOG; KOG4177; Eukaryota.
DR GeneTree; ENSGT00940000161114; -.
DR InParanoid; Q05921; -.
DR OMA; VLYVVRK; -.
DR OrthoDB; 222916at2759; -.
DR PhylomeDB; Q05921; -.
DR TreeFam; TF344032; -.
DR Reactome; R-MMU-8983711; OAS antiviral response.
DR Reactome; R-MMU-909733; Interferon alpha/beta signaling.
DR BioGRID-ORCS; 24014; 3 hits in 73 CRISPR screens.
DR PRO; PR:Q05921; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q05921; protein.
DR Bgee; ENSMUSG00000066800; Expressed in right colon and 210 other tissues.
DR ExpressionAtlas; Q05921; baseline and differential.
DR Genevisible; Q05921; MM.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0016363; C:nuclear matrix; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0043021; F:ribonucleoprotein complex binding; IDA:MGI.
DR GO; GO:0003723; F:RNA binding; ISO:MGI.
DR GO; GO:0019843; F:rRNA binding; ISO:MGI.
DR GO; GO:0051607; P:defense response to virus; ISO:MGI.
DR GO; GO:0045444; P:fat cell differentiation; IMP:MGI.
DR GO; GO:0006397; P:mRNA processing; IEA:InterPro.
DR GO; GO:0045071; P:negative regulation of viral genome replication; ISO:MGI.
DR GO; GO:0046326; P:positive regulation of glucose import; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0043488; P:regulation of mRNA stability; IMP:MGI.
DR GO; GO:0006396; P:RNA processing; IBA:GO_Central.
DR GO; GO:0006364; P:rRNA processing; ISO:MGI.
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; 2.
DR Pfam; PF13637; Ank_4; 1.
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 SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 7.
DR PROSITE; PS51392; KEN; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW ANK repeat; Antiviral defense; ATP-binding; Cytoplasm; Endonuclease;
KW Hydrolase; Metal-binding; Mitochondrion; Nuclease; Nucleotide-binding;
KW Reference proteome; Repeat; RNA-binding; Zinc; Zinc-finger.
FT CHAIN 1..735
FT /note="2-5A-dependent ribonuclease"
FT /id="PRO_0000067052"
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..328
FT /note="ANK 9"
FT DOMAIN 364..584
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 587..722
FT /note="KEN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00725"
FT ZN_FING 401..436
FT /note="C6-type"
FT /evidence="ECO:0000255"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 26..51
FT /note="Binding to TMEV Leader protein"
FT /evidence="ECO:0000269|PubMed:29652922"
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 714..735
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 735 AA; 83275 MW; B6632F4A5B50F711 CRC64;
METPDYNTPQ GGTPSAGSQR TVVEDDSSLI KAVQKGDVVR VQQLLEKGAD ANACEDTWGW
TPLHNAVQAG RVDIVNLLLS HGADPHRRKK NGATPFIIAG IQGDVKLLEI LLSCGADVNE
CDENGFTAFM EAAERGNAEA LRFLFAKGAN VNLRRQTTKD KRRLKQGGAT ALMSAAEKGH
LEVLRILLND MKAEVDARDN MGRNALIRTL LNWDCENVEE ITSILIQHGA DVNVRGERGK
TPLIAAVERK HTGLVQMLLS REGINIDARD NEGKTALLIA VDKQLKEIVQ LLLEKGADKC
DDLVWIARRN HDYHLVKLLL PYVANPDTDP PAGDWSPHSS RWGTALKSLH SMTRPMIGKL
KIFIHDDYKI AGTSEGAVYL GIYDNREVAV KVFRENSPRG CKEVSCLRDC GDHSNLVAFY
GREDDKGCLY VCVSLCEWTL EEFLRLPREE PVENGEDKFA HSILLSIFEG VQKLHLHGYS
HQDLQPQNIL IDSKKAVRLA DFDQSIRWMG ESQMVRRDLE DLGRLVLYVV MKGEIPFETL
KTQNDEVLLT MSPDEETKDL IHCLFSPGEN VKNCLVDLLG HPFFWTWENR YRTLRNVGNE
SDIKVRKCKS DLLRLLQHQT LEPPRSFDQW TSKIDKNVMD EMNHFYEKRK KNPYQDTVGD
LLKFIRNIGE HINEEKKRGM KEILGDPSRY FQETFPDLVI YIYKKLKETE YRKHFPQPPP
RLSVPEAVGP GGIQS
