DSRAD_CAEEL
ID DSRAD_CAEEL Reviewed; 495 AA.
AC Q22618; O76295;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-2002, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Double-stranded RNA-specific adenosine deaminase adr-2 {ECO:0000305};
DE Short=DRADA;
DE EC=3.5.4.37 {ECO:0000269|PubMed:12426375};
GN Name=adr-2; ORFNames=T20H4.4;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Bristol N2;
RX PubMed=10446229; DOI=10.1093/nar/27.17.3424;
RA Hough R.F., Lingam A.T., Bass B.L.;
RT "Caenorhabditis elegans mRNAs that encode a protein similar to ADARs derive
RT from an operon containing six genes.";
RL Nucleic Acids Res. 27:3424-3432(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=12426375; DOI=10.1093/emboj/cdf607;
RA Tonkin L.A., Saccomanno L., Morse D.P., Brodigan T., Krause M., Bass B.L.;
RT "RNA editing by ADARs is important for normal behavior in Caenorhabditis
RT elegans.";
RL EMBO J. 21:6025-6035(2002).
RN [4]
RP FUNCTION, AND ROLE IN TRANSGENE SILENCING.
RX PubMed=12419225; DOI=10.1016/s1097-2765(02)00649-4;
RA Knight S.W., Bass B.L.;
RT "The role of RNA editing by ADARs in RNAi.";
RL Mol. Cell 10:809-817(2002).
RN [5]
RP FUNCTION.
RX PubMed=14657490; DOI=10.1126/science.1091340;
RA Tonkin L.A., Bass B.L.;
RT "Mutations in RNAi rescue aberrant chemotaxis of ADAR mutants.";
RL Science 302:1725-1725(2003).
RN [6]
RP INTERACTION WITH ADBP-1, SUBCELLULAR LOCATION, AND ROLE IN TRANSGENE
RP SILENCING.
RX PubMed=18780728; DOI=10.1534/genetics.108.093310;
RA Ohta H., Fujiwara M., Ohshima Y., Ishihara T.;
RT "ADBP-1 regulates an ADAR RNA-editing enzyme to antagonize RNA-
RT interference-mediated gene silencing in Caenorhabditis elegans.";
RL Genetics 180:785-796(2008).
RN [7]
RP DEVELOPMENTAL STAGE.
RX PubMed=18719245; DOI=10.1261/rna.1165008;
RA Hundley H.A., Krauchuk A.A., Bass B.L.;
RT "C. elegans and H. sapiens mRNAs with edited 3' UTRs are present on
RT polysomes.";
RL RNA 14:2050-2060(2008).
RN [8]
RP FUNCTION.
RX PubMed=20011587; DOI=10.1371/journal.pone.0008210;
RA Sebastiani P., Montano M., Puca A., Solovieff N., Kojima T., Wang M.C.,
RA Melista E., Meltzer M., Fischer S.E., Andersen S., Hartley S.H.,
RA Sedgewick A., Arai Y., Bergman A., Barzilai N., Terry D.F., Riva A.,
RA Anselmi C.V., Malovini A., Kitamoto A., Sawabe M., Arai T., Gondo Y.,
RA Steinberg M.H., Hirose N., Atzmon G., Ruvkun G., Baldwin C.T., Perls T.T.;
RT "RNA editing genes associated with extreme old age in humans and with
RT lifespan in C. elegans.";
RL PLoS ONE 4:E8210-E8210(2009).
RN [9]
RP INTERACTION WITH ADR-1.
RX PubMed=24508457; DOI=10.1016/j.celrep.2014.01.011;
RA Washburn M.C., Kakaradov B., Sundararaman B., Wheeler E., Hoon S.,
RA Yeo G.W., Hundley H.A.;
RT "The dsRBP and inactive editor ADR-1 utilizes dsRNA binding to regulate A-
RT to-I RNA editing across the C. elegans transcriptome.";
RL Cell Rep. 6:599-607(2014).
RN [10]
RP FUNCTION.
RX PubMed=25373143; DOI=10.1101/gr.176107.114;
RA Zhao H.Q., Zhang P., Gao H., He X., Dou Y., Huang A.Y., Liu X.M., Ye A.Y.,
RA Dong M.Q., Wei L.;
RT "Profiling the RNA editomes of wild-type C. elegans and ADAR mutants.";
RL Genome Res. 25:66-75(2015).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF GLY-184.
RX PubMed=28925356; DOI=10.7554/elife.28625;
RA Deffit S.N., Yee B.A., Manning A.C., Rajendren S., Vadlamani P.,
RA Wheeler E.C., Domissy A., Washburn M.C., Yeo G.W., Hundley H.A.;
RT "The C. elegans neural editome reveals an ADAR target mRNA required for
RT proper chemotaxis.";
RL Elife 6:0-0(2017).
CC -!- FUNCTION: Catalyzes the hydrolytic deamination of adenosine to inosine
CC in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing
CC (PubMed:12426375). Acts primarily on non-coding regions of protein-
CC coding genes including introns and untranslated regions (UTR)
CC (PubMed:28925356, PubMed:25373143). Required for normal chemotaxis
CC (PubMed:12426375, PubMed:14657490). Edits the 3' UTR of clec-41 which
CC is required for normal clec-41 expression and for chemotaxis
CC (PubMed:28925356). Plays a role in determining lifespan
CC (PubMed:20011587, PubMed:25373143). Not required for RNA interference
CC (PubMed:12419225). Likely to play a role in determining whether a dsRNA
CC enters the RNAi pathway (PubMed:14657490).
CC {ECO:0000269|PubMed:12419225, ECO:0000269|PubMed:12426375,
CC ECO:0000269|PubMed:14657490, ECO:0000269|PubMed:20011587,
CC ECO:0000269|PubMed:25373143, ECO:0000269|PubMed:28925356}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine in double-stranded RNA + H(+) + H2O = inosine in
CC double-stranded RNA + NH4(+); Xref=Rhea:RHEA:10120, Rhea:RHEA-
CC COMP:13885, Rhea:RHEA-COMP:13886, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:74411,
CC ChEBI:CHEBI:82852; EC=3.5.4.37;
CC Evidence={ECO:0000269|PubMed:12426375};
CC -!- SUBUNIT: Interacts with A-to-I RNA editing regulator adr-1
CC (PubMed:24508457). Interacts with adbp-1; the interaction facilitates
CC adr-2 nuclear localization (PubMed:18780728).
CC {ECO:0000269|PubMed:18780728, ECO:0000269|PubMed:24508457}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18780728}. Cytoplasm
CC {ECO:0000269|PubMed:18780728}.
CC -!- DEVELOPMENTAL STAGE: Highest expression observed in the embryo. Levels
CC decrease dramatically after embryogenesis, remain relatively constant
CC during larval stages and increase again at the onset of adulthood.
CC {ECO:0000269|PubMed:18719245}.
CC -!- MISCELLANEOUS: Can prevent somatic transgenes from inducing gene
CC silencing via the RNA interference (RNAi) pathway. This may occur due
CC to A-to-I editing of transgene-derived dsRNA, preventing transgene
CC RNAi. {ECO:0000269|PubMed:12419225, ECO:0000269|PubMed:18780728}.
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DR EMBL; AF051275; AAC25097.1; -; mRNA.
DR EMBL; FO081693; CCD73351.1; -; Genomic_DNA.
DR PIR; T16913; T16913.
DR PIR; T42758; T42758.
DR RefSeq; NP_498594.1; NM_066193.4.
DR AlphaFoldDB; Q22618; -.
DR SMR; Q22618; -.
DR BioGRID; 41234; 8.
DR DIP; DIP-26710N; -.
DR IntAct; Q22618; 1.
DR STRING; 6239.T20H4.4; -.
DR iPTMnet; Q22618; -.
DR EPD; Q22618; -.
DR PaxDb; Q22618; -.
DR PeptideAtlas; Q22618; -.
DR EnsemblMetazoa; T20H4.4.1; T20H4.4.1; WBGene00000080.
DR GeneID; 176022; -.
DR KEGG; cel:CELE_T20H4.4; -.
DR UCSC; T20H4.4.1; c. elegans.
DR CTD; 176022; -.
DR WormBase; T20H4.4; CE25120; WBGene00000080; adr-2.
DR eggNOG; KOG2777; Eukaryota.
DR GeneTree; ENSGT00940000157243; -.
DR HOGENOM; CLU_005382_3_1_1; -.
DR InParanoid; Q22618; -.
DR OMA; HAFSARW; -.
DR OrthoDB; 947117at2759; -.
DR PhylomeDB; Q22618; -.
DR Reactome; R-CEL-75102; C6 deamination of adenosine.
DR Reactome; R-CEL-77042; Formation of editosomes by ADAR proteins.
DR PRO; PR:Q22618; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00000080; Expressed in embryo and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005730; C:nucleolus; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0003726; F:double-stranded RNA adenosine deaminase activity; IMP:UniProtKB.
DR GO; GO:0003725; F:double-stranded RNA binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008251; F:tRNA-specific adenosine deaminase activity; IBA:GO_Central.
DR GO; GO:0006382; P:adenosine to inosine editing; IMP:UniProtKB.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0050921; P:positive regulation of chemotaxis; IMP:UniProtKB.
DR GO; GO:0006396; P:RNA processing; IBA:GO_Central.
DR InterPro; IPR002466; A_deamin.
DR InterPro; IPR014720; dsRBD_dom.
DR Pfam; PF02137; A_deamin; 1.
DR Pfam; PF00035; dsrm; 1.
DR SMART; SM00552; ADEAMc; 1.
DR PROSITE; PS50141; A_DEAMIN_EDITASE; 1.
DR PROSITE; PS50137; DS_RBD; 1.
PE 1: Evidence at protein level;
KW Chemotaxis; Cytoplasm; Hydrolase; Metal-binding; mRNA processing; Nucleus;
KW Reference proteome; RNA-binding; Zinc.
FT CHAIN 1..495
FT /note="Double-stranded RNA-specific adenosine deaminase
FT adr-2"
FT /id="PRO_0000171778"
FT DOMAIN 36..105
FT /note="DRBM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00266"
FT DOMAIN 167..492
FT /note="A to I editase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00240"
FT ACT_SITE 193
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00240"
FT BINDING 191
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00240"
FT BINDING 244
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00240"
FT BINDING 305
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00240"
FT MUTAGEN 184
FT /note="G->R: Abolishes editing of clec-41 RNA, leads to a
FT threefold reduction in expression of clec-41 mRNA in neural
FT cells and impairs chemotaxis."
FT /evidence="ECO:0000269|PubMed:28925356"
SQ SEQUENCE 495 AA; 55320 MW; EDE9D9E06A5A8A89 CRC64;
MSVEEGMEVE LKSEKMDLDD NIPDFVKETV ERSGKNPMSL FSELYVHMTG NTPVFDFYNR
NQPNGSMKFI CVVILNGERI EGNVKSKKKE AKVSCSLKGL EVVLKHVSEY VVPAVKFEEK
TTFFEMLREH TYAKFYELCK NNALIYGFEK VIASVFLKIN GNLQIIALST GNKGLRGDKI
VNDGTALIDC HAEILARRGL LRFLYSEVLK FSTEPPNSIF TKGKNALVLK PGISFHLFIN
TAPCGVARID KKLKPGTSDD LQNSSRLRFK IDKGMGTVLG GASEFEAPQT FDGIMMGERM
RTMSCSDKLL RANVLGVQGA ILSHFIDPIY YSSIAVAELN NADRLRKAVY SRAATFKPPA
PFHVQDVEIG ECQVEDTEQS TSAAARSTIS SMNWNLADGN TEVVRTSDGM VHDKDMSGAD
ITTPSRLCKK NMAELMITIC TLTKTSVDYP ISYEELKAGS QEYAAAKKSF ITWLRQKDLG
IWQRKPREFQ MFTIN
