DSRAD_RAT
ID DSRAD_RAT Reviewed; 1175 AA.
AC P55266;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Double-stranded RNA-specific adenosine deaminase;
DE Short=DRADA;
DE EC=3.5.4.37;
GN Name=Adar; Synonyms=Dsrad;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Wistar; TISSUE=Brain;
RX PubMed=7862132; DOI=10.1128/mcb.15.3.1389;
RA O'Connell M.A., Krause S., Higuchi M., Hsuan J.J., Totty N.F., Jenny A.,
RA Keller W.;
RT "Cloning of cDNAs encoding mammalian double-stranded RNA-specific adenosine
RT deaminase.";
RL Mol. Cell. Biol. 15:1389-1397(1995).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-228 AND SER-235, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Catalyzes the hydrolytic deamination of adenosine to inosine
CC in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing. This
CC may affect gene expression and function in a number of ways that
CC include mRNA translation by changing codons and hence the amino acid
CC sequence of proteins; pre-mRNA splicing by altering splice site
CC recognition sequences; RNA stability by changing sequences involved in
CC nuclease recognition; genetic stability in the case of RNA virus
CC genomes by changing sequences during viral RNA replication; and RNA
CC structure-dependent activities such as microRNA production or targeting
CC or protein-RNA interactions. Can edit both viral and cellular RNAs and
CC can edit RNAs at multiple sites (hyper-editing) or at specific sites
CC (site-specific editing). Its cellular RNA substrates include: bladder
CC cancer-associated protein (BLCAP), neurotransmitter receptors for
CC glutamate (GRIA2) and serotonin (HTR2C) and GABA receptor (GABRA3).
CC Site-specific RNA editing of transcripts encoding these proteins
CC results in amino acid substitutions which consequently alters their
CC functional activities. Exhibits low-level editing at the GRIA2 Q/R
CC site, but edits efficiently at the R/G site and HOTSPOT1. Does not
CC affect polyomavirus replication but provides protection against virus-
CC induced cytopathic effects. Essential for embryonic development and
CC cell survival and plays a critical role in the maintenance of
CC hematopoietic stem cells (By similarity).
CC {ECO:0000250|UniProtKB:P55265, ECO:0000250|UniProtKB:Q99MU3}.
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:0000250|UniProtKB:P55265};
CC -!- SUBUNIT: Homodimer. Homodimerization is essential for its catalytic
CC activity. Isoform 5 can form heterodimers with ADARB1/ADAR2. Isoform 1
CC interacts with ILF2/NF45 and ILF3/NF90. Binding to ILF3/NF90 up-
CC regulates ILF3-mediated gene expression. Isoform 1 and isoform 5 (via
CC DRBM 3 domain) interact with TNPO1. Isoform 5 (via DRBM domains)
CC interacts with XPO5. Isoform 1 and isoform 5 can interact with
CC EIF2AK2/PKR and UPF1. {ECO:0000250|UniProtKB:P55265}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P55265}. Nucleus
CC {ECO:0000250|UniProtKB:P55265}. Note=Shuttles between the cytoplasm and
CC nucleus. {ECO:0000250|UniProtKB:P55265}.
CC -!- TISSUE SPECIFICITY: Detected in brain. {ECO:0000269|PubMed:7862132}.
CC -!- DOMAIN: The first DRADA repeat binds Z-DNA.
CC {ECO:0000250|UniProtKB:P55265}.
CC -!- DOMAIN: The third dsRNA-binding domain (DRBM 3) contains an additional
CC N-terminal alpha-helix that is part of a bi-partite nuclear
CC localization signal, together with the sequence immediately C-terminal
CC to DRBM 3. The presence of DRBM 3 is important to bring together the N-
CC terminal and the C-terminal part of the bi-partite nuclear localization
CC signal for import mediated by TNPO1. RNA binding interferes with
CC nuclear import. {ECO:0000250|UniProtKB:P55265}.
CC -!- PTM: Sumoylation reduces RNA-editing activity.
CC {ECO:0000250|UniProtKB:P55265}.
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DR EMBL; U18942; AAA65039.1; -; mRNA.
DR PIR; I57549; I57549.
DR RefSeq; NP_112268.1; NM_031006.1.
DR AlphaFoldDB; P55266; -.
DR SMR; P55266; -.
DR BioGRID; 249535; 1.
DR STRING; 10116.ENSRNOP00000028181; -.
DR iPTMnet; P55266; -.
DR PhosphoSitePlus; P55266; -.
DR PaxDb; P55266; -.
DR PRIDE; P55266; -.
DR GeneID; 81635; -.
DR KEGG; rno:81635; -.
DR UCSC; RGD:71099; rat.
DR CTD; 103; -.
DR RGD; 71099; Adar.
DR eggNOG; KOG2777; Eukaryota.
DR InParanoid; P55266; -.
DR OrthoDB; 947117at2759; -.
DR PhylomeDB; P55266; -.
DR Reactome; R-RNO-75102; C6 deamination of adenosine.
DR Reactome; R-RNO-77042; Formation of editosomes by ADAR proteins.
DR PRO; PR:P55266; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0016607; C:nuclear speck; IDA:RGD.
DR GO; GO:0005730; C:nucleolus; IDA:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0044530; C:supraspliceosomal complex; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003726; F:double-stranded RNA adenosine deaminase activity; ISO:RGD.
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; ISS:UniProtKB.
DR GO; GO:0016553; P:base conversion or substitution editing; ISO:RGD.
DR GO; GO:0098586; P:cellular response to virus; ISO:RGD.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0060216; P:definitive hemopoiesis; ISO:RGD.
DR GO; GO:0030218; P:erythrocyte differentiation; ISO:RGD.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; ISO:RGD.
DR GO; GO:0061484; P:hematopoietic stem cell homeostasis; ISO:RGD.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0035196; P:miRNA processing; ISO:RGD.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:1900369; P:negative regulation of post-transcriptional gene silencing by RNA; ISO:RGD.
DR GO; GO:0044387; P:negative regulation of protein kinase activity by regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; ISO:RGD.
DR GO; GO:0001649; P:osteoblast differentiation; ISO:RGD.
DR GO; GO:0045070; P:positive regulation of viral genome replication; ISS:UniProtKB.
DR GO; GO:0031054; P:pre-miRNA processing; ISO:RGD.
DR GO; GO:0035455; P:response to interferon-alpha; ISS:UniProtKB.
DR GO; GO:0009615; P:response to virus; ISS:UniProtKB.
DR GO; GO:0070922; P:RISC complex assembly; ISO:RGD.
DR GO; GO:0006396; P:RNA processing; IBA:GO_Central.
DR GO; GO:0002566; P:somatic diversification of immune receptors via somatic mutation; ISO:RGD.
DR CDD; cd19913; DSRM_DRADA_rpt1; 1.
DR CDD; cd19915; DSRM_DRADA_rpt3; 1.
DR Gene3D; 1.10.10.10; -; 2.
DR InterPro; IPR002466; A_deamin.
DR InterPro; IPR044456; ADAR1_DSRM_1.
DR InterPro; IPR044457; ADAR1_DSRM_3.
DR InterPro; IPR014720; dsRBD_dom.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR InterPro; IPR042371; Z_dom.
DR Pfam; PF02137; A_deamin; 1.
DR Pfam; PF00035; dsrm; 3.
DR Pfam; PF02295; z-alpha; 2.
DR SMART; SM00552; ADEAMc; 1.
DR SMART; SM00358; DSRM; 3.
DR SMART; SM00550; Zalpha; 2.
DR SUPFAM; SSF46785; SSF46785; 2.
DR PROSITE; PS50141; A_DEAMIN_EDITASE; 1.
DR PROSITE; PS50137; DS_RBD; 3.
DR PROSITE; PS50139; Z_BINDING; 2.
PE 1: Evidence at protein level;
KW Antiviral defense; Cytoplasm; DNA-binding; Hydrolase; Immunity;
KW Innate immunity; Isopeptide bond; Metal-binding; Methylation;
KW mRNA processing; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW RNA-binding; RNA-mediated gene silencing; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc.
FT CHAIN 1..1175
FT /note="Double-stranded RNA-specific adenosine deaminase"
FT /id="PRO_0000171776"
FT DOMAIN 135..201
FT /note="Z-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00073"
FT DOMAIN 243..307
FT /note="Z-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00073"
FT DOMAIN 453..521
FT /note="DRBM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00266"
FT DOMAIN 564..632
FT /note="DRBM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00266"
FT DOMAIN 672..740
FT /note="DRBM 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00266"
FT DOMAIN 832..1167
FT /note="A to I editase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00240"
FT REGION 135..204
FT /note="Interaction with Z-DNA"
FT /evidence="ECO:0000250|UniProtKB:P55265"
FT REGION 207..239
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 315..384
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 524..561
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 632..652
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 662..671
FT /note="N-terminal extension of DRBM 3 and constituent of a
FT bi-partite nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P55265"
FT REGION 741..747
FT /note="C-terminal extension of DRBM 3 and constituent of a
FT bi-partite nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P55265"
FT COMPBIAS 319..362
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 363..381
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 635..652
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 858
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00240"
FT BINDING 856
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00240"
FT BINDING 912
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00240"
FT BINDING 982
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00240"
FT MOD_RES 30
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P55265"
FT MOD_RES 42
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q99MU3"
FT MOD_RES 228
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 235
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 431
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55265"
FT MOD_RES 564
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55265"
FT MOD_RES 579
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55265"
FT MOD_RES 586
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55265"
FT MOD_RES 754
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P55265"
FT MOD_RES 760
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55265"
FT MOD_RES 769
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55265"
FT MOD_RES 771
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55265"
FT CROSSLNK 368
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 368
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0000250|UniProtKB:P55265"
FT CROSSLNK 368
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P55265"
FT CROSSLNK 821
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P55265"
SQ SEQUENCE 1175 AA; 129911 MW; F5C7B5FFB771168C CRC64;
MSQGFRGPTG VFPHQTQPCL DPSYEHSKWR YLQPRGSESY LRSFQLQQIE FLKGRLPEAP
LIGAQTQSLP PFLPGHWPRF PGPPAQGKQP EIWGFPRSVT LRNQGFHIGP PLPPPHSRGP
PWRGAEGLCS HFQELSISQN PEQKVLNRLE ELGEGKATTA YALARELRTP KKDINRILYS
LERKGKLHRG VGKPPLWSLV PLSQACTQPP RAVNSDKEVP RGEPDLDSED GDPASDLEGP
SELLDMAEIK EKICDYLFNV SKSSALNLAK NIGLAKARDV NAVLIDLERQ GDVYREGATP
PIWYLTDKKR ERLQMKRSTH SGPAATPAAV SEATQSTSFP TCHPPQSGGS SSMATSKRVE
NGQEPVTKYE SRHEARPGPV RLRPHAYHNG PSRAGYVASE NGPWATDDIP DNLNSIHTAP
GEFRAIMEMP SFYSPTLPRC SPYKKLTECQ LKNPVSGLLE YAQFTSQTCD FNLIEQSGPS
HEPRFKFQVV INGREFPPAE AGSKKVAKQD AAVKAMAILL REAKAKDSGQ PEELSNCPME
EDPEKPAESQ PPSSSATSLF SGKSPVTTLL ECMHKLGNSC EFRLLSKEGP AHDPKFQYCV
AVGAQTFPSV SAPSKKVAKQ MAAEEAMKAL QEEAANSADD QSGGANTDSL DESVAPNKIR
RIGELVRYLN TNPVGGLLEY ARSHGFAAEF KLIDQSGPPH EPKFVYQAKV GGRWFPAVCA
HSKKQGKQDA ADAALRVLIG ESEKAEQLGF AEVTPVTGAS LRRTMLLLSR SPDAHPKTLP
LTGSTFHDQI AMLSHRCFNA LTNSFQPSLL GRKILAAIIM KRDPEDMGVV VSLGTGNRCV
KGDSLSLKGE TVNDCHAEII SRRGFIRFLY SELMKYNHHT AKNSIFELAR GGEKLQIKKT
VSFHLYISTA PCGDGAHFDK SCSDRAVEST ESRHYPVFEN PKQGKLRTKV ENGEGTIPVE
SSDIVPTWDG IRLGERLRTM SCSDKILRWN VLGLQGALLT HFLQPVYLKS VTLGYLFSQG
HLTRAICCRV TRDGNAFEDG LRYPFIVNHP KVGRVSVYDS KRQSGKTKET SVNWCLADGY
DLEILDGTRG TVDGPGKELS RVSKKNIFLQ FKKLCSFRAR RDLLQLSYGE AKKAARDYDL
AKNYFKKSLR DMGYGNWISK PQEEKNFYLC PVPND
