RED1_RAT
ID RED1_RAT Reviewed; 711 AA.
AC P51400;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Double-stranded RNA-specific editase 1;
DE EC=3.5.4.37;
DE AltName: Full=RNA-editing deaminase 1;
DE AltName: Full=RNA-editing enzyme 1;
DE AltName: Full=dsRNA adenosine deaminase;
GN Name=Adarb1; Synonyms=Red1;
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].
RX PubMed=8559253; DOI=10.1038/379460a0;
RA Melcher T., Maas S., Herb A., Sprengel R., Seeburg P.H., Higuchi M.;
RT "A mammalian RNA editing enzyme.";
RL Nature 379:460-464(1996).
RN [2]
RP FUNCTION.
RX PubMed=20501795; DOI=10.1096/fj.09-152363;
RA Yang L., Zhao L., Gan Z., He Z., Xu J., Gao X., Wang X., Han W., Chen L.,
RA Xu T., Li W., Liu Y.;
RT "Deficiency in RNA editing enzyme ADAR2 impairs regulated exocytosis.";
RL FASEB J. 24:3720-3732(2010).
RN [3]
RP STRUCTURE BY NMR OF 74-301, FUNCTION, MUTAGENESIS OF LYS-128 AND LYS-281,
RP AND RNA-BINDING.
RX PubMed=16472753; DOI=10.1016/j.str.2005.11.013;
RA Stefl R., Xu M., Skrisovska L., Emeson R.B., Allain F.H.;
RT "Structure and specific RNA binding of ADAR2 double-stranded RNA binding
RT motifs.";
RL Structure 14:345-355(2006).
RN [4]
RP STRUCTURE BY NMR OF 74-301 IN COMPLEX WITH RNA, FUNCTION, AND MUTAGENESIS
RP OF MET-84; 104-VAL-HIS-105; MET-238 AND 258-SER-HIS-259.
RX PubMed=20946981; DOI=10.1016/j.cell.2010.09.026;
RA Stefl R., Oberstrass F.C., Hood J.L., Jourdan M., Zimmermann M.,
RA Skrisovska L., Maris C., Peng L., Hofr C., Emeson R.B., Allain F.H.;
RT "The solution structure of the ADAR2 dsRBM-RNA complex reveals a sequence-
RT specific readout of the minor groove.";
RL Cell 143:225-237(2010).
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 GRIK2) and serotonin (HTR2C), GABA receptor
CC (GABRA3) and potassium voltage-gated channel (KCNA1). Site-specific RNA
CC editing of transcripts encoding these proteins results in amino acid
CC substitutions which consequently alter their functional activities.
CC Edits GRIA2 at both the Q/R and R/G sites efficiently but converts the
CC adenosine in hotspot1 much less efficiently (By similarity). Can
CC inhibit cell proliferation and migration and can stimulate exocytosis.
CC {ECO:0000250, ECO:0000269|PubMed:16472753, ECO:0000269|PubMed:20501795,
CC ECO:0000269|PubMed:20946981}.
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 -!- COFACTOR:
CC Name=1D-myo-inositol hexakisphosphate; Xref=ChEBI:CHEBI:58130;
CC Evidence={ECO:0000250};
CC Note=Binds 1 myo-inositol hexakisphosphate (IP6) per subunit.
CC {ECO:0000250};
CC -!- SUBUNIT: Homodimer. Homodimerization is essential for its catalytic
CC activity (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Nucleus, nucleolus
CC {ECO:0000250}. Note=Shuttles between nucleoli and the nucleoplasm.
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Brain and peripheral tissues.
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DR EMBL; U43534; AAA96755.1; -; mRNA.
DR PIR; S68443; S68443.
DR RefSeq; NP_001104525.1; NM_001111055.1.
DR RefSeq; NP_001104526.1; NM_001111056.1.
DR RefSeq; NP_001104527.1; NM_001111057.1.
DR RefSeq; NP_037026.2; NM_012894.2.
DR PDB; 2B7T; NMR; -; A=74-146.
DR PDB; 2B7V; NMR; -; A=231-301.
DR PDB; 2L3C; NMR; -; A=74-147.
DR PDB; 2L3J; NMR; -; A=74-301.
DR PDBsum; 2B7T; -.
DR PDBsum; 2B7V; -.
DR PDBsum; 2L3C; -.
DR PDBsum; 2L3J; -.
DR AlphaFoldDB; P51400; -.
DR BMRB; P51400; -.
DR SMR; P51400; -.
DR STRING; 10116.ENSRNOP00000001642; -.
DR PhosphoSitePlus; P51400; -.
DR PaxDb; P51400; -.
DR GeneID; 25367; -.
DR KEGG; rno:25367; -.
DR UCSC; RGD:2033; rat.
DR CTD; 104; -.
DR RGD; 2033; Adarb1.
DR eggNOG; KOG2777; Eukaryota.
DR InParanoid; P51400; -.
DR OrthoDB; 947117at2759; -.
DR PhylomeDB; P51400; -.
DR Reactome; R-RNO-75102; C6 deamination of adenosine.
DR Reactome; R-RNO-77042; Formation of editosomes by ADAR proteins.
DR EvolutionaryTrace; P51400; -.
DR PRO; PR:P51400; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005730; C:nucleolus; IDA:RGD.
DR GO; GO:0005654; C:nucleoplasm; IDA:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0003726; F:double-stranded RNA adenosine deaminase activity; IDA:RGD.
DR GO; GO:0003725; F:double-stranded RNA binding; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IDA:RGD.
DR GO; GO:0008251; F:tRNA-specific adenosine deaminase activity; IBA:GO_Central.
DR GO; GO:0006382; P:adenosine to inosine editing; IDA:RGD.
DR GO; GO:0016553; P:base conversion or substitution editing; IDA:RGD.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0021610; P:facial nerve morphogenesis; ISO:RGD.
DR GO; GO:0021618; P:hypoglossal nerve morphogenesis; ISO:RGD.
DR GO; GO:0060384; P:innervation; ISO:RGD.
DR GO; GO:0061744; P:motor behavior; ISO:RGD.
DR GO; GO:0097049; P:motor neuron apoptotic process; ISO:RGD.
DR GO; GO:0016556; P:mRNA modification; IDA:RGD.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0035264; P:multicellular organism growth; ISO:RGD.
DR GO; GO:0060415; P:muscle tissue morphogenesis; ISO:RGD.
DR GO; GO:0030336; P:negative regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0044387; P:negative regulation of protein kinase activity by regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0050884; P:neuromuscular process controlling posture; ISO:RGD.
DR GO; GO:0007274; P:neuromuscular synaptic transmission; ISO:RGD.
DR GO; GO:0050685; P:positive regulation of mRNA processing; IDA:RGD.
DR GO; GO:0045070; P:positive regulation of viral genome replication; ISS:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0006396; P:RNA processing; ISS:HGNC-UCL.
DR GO; GO:0021965; P:spinal cord ventral commissure morphogenesis; ISO:RGD.
DR CDD; cd19895; DSRM_RED1_rpt1; 1.
DR CDD; cd19898; DSRM_RED1_rpt2; 1.
DR DisProt; DP03065; -.
DR InterPro; IPR002466; A_deamin.
DR InterPro; IPR044458; ADAR2_DSRM_1.
DR InterPro; IPR044459; ADAR2_DSRM_2.
DR InterPro; IPR014720; dsRBD_dom.
DR Pfam; PF02137; A_deamin; 1.
DR Pfam; PF00035; dsrm; 2.
DR SMART; SM00552; ADEAMc; 1.
DR SMART; SM00358; DSRM; 2.
DR PROSITE; PS50141; A_DEAMIN_EDITASE; 1.
DR PROSITE; PS50137; DS_RBD; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Metal-binding; mRNA processing; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; RNA-binding; Zinc.
FT CHAIN 1..711
FT /note="Double-stranded RNA-specific editase 1"
FT /id="PRO_0000171781"
FT DOMAIN 78..144
FT /note="DRBM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00266"
FT DOMAIN 231..298
FT /note="DRBM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00266"
FT DOMAIN 370..707
FT /note="A to I editase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00240"
FT REGION 1..79
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 83..88
FT /note="Interaction with substrate RNA"
FT REGION 104..105
FT /note="Interaction with substrate RNA"
FT REGION 176..220
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 237..242
FT /note="Interaction with substrate RNA"
FT REGION 259
FT /note="Interaction with substrate RNA"
FT COMPBIAS 195..215
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 396
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00240"
FT BINDING 394
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00240"
FT BINDING 400
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250"
FT BINDING 401
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250"
FT BINDING 451
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00240"
FT BINDING 526
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00240"
FT BINDING 529
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250"
FT BINDING 532
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250"
FT BINDING 639
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250"
FT BINDING 672
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250"
FT BINDING 682
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250"
FT BINDING 700
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250"
FT MOD_RES 149
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P78563"
FT MUTAGEN 84
FT /note="M->A: Strongly reduced RNA editing activity."
FT /evidence="ECO:0000269|PubMed:20946981"
FT MUTAGEN 104..105
FT /note="VH->AA: Strongly reduced RNA editing activity."
FT /evidence="ECO:0000269|PubMed:20946981"
FT MUTAGEN 128
FT /note="K->A: Reduced RNA editing activity; when associated
FT with A-281."
FT /evidence="ECO:0000269|PubMed:16472753"
FT MUTAGEN 238
FT /note="M->A: Strongly reduced RNA editing activity."
FT /evidence="ECO:0000269|PubMed:20946981"
FT MUTAGEN 258..259
FT /note="SH->AA: Abolishes RNA editing activity."
FT /evidence="ECO:0000269|PubMed:20946981"
FT MUTAGEN 281
FT /note="K->A: Reduced RNA editing activity; when associated
FT with A-128."
FT /evidence="ECO:0000269|PubMed:16472753"
FT STRAND 76..79
FT /evidence="ECO:0007829|PDB:2B7T"
FT HELIX 80..89
FT /evidence="ECO:0007829|PDB:2B7T"
FT STRAND 94..101
FT /evidence="ECO:0007829|PDB:2B7T"
FT STRAND 103..106
FT /evidence="ECO:0007829|PDB:2B7T"
FT STRAND 108..126
FT /evidence="ECO:0007829|PDB:2B7T"
FT HELIX 127..143
FT /evidence="ECO:0007829|PDB:2B7T"
FT STRAND 183..186
FT /evidence="ECO:0007829|PDB:2L3J"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:2L3J"
FT STRAND 197..201
FT /evidence="ECO:0007829|PDB:2L3J"
FT STRAND 217..219
FT /evidence="ECO:0007829|PDB:2L3J"
FT STRAND 221..224
FT /evidence="ECO:0007829|PDB:2L3J"
FT HELIX 236..243
FT /evidence="ECO:0007829|PDB:2B7V"
FT STRAND 248..253
FT /evidence="ECO:0007829|PDB:2B7V"
FT TURN 258..260
FT /evidence="ECO:0007829|PDB:2B7V"
FT STRAND 263..268
FT /evidence="ECO:0007829|PDB:2B7V"
FT STRAND 273..280
FT /evidence="ECO:0007829|PDB:2B7V"
FT HELIX 281..299
FT /evidence="ECO:0007829|PDB:2B7V"
SQ SEQUENCE 711 AA; 77925 MW; 5A25C4B202530C54 CRC64;
MDIEDEENMS SSSIDVKENR NLDNMPPKDS STPGPGEGIP LSNGGGGSTS RKRPLEEGSN
GHSKYRLKKR RKTPGPVLPK NALMQLNEIK PGLQYMLLSQ TGPVHAPLFV MSVEVNGQVF
EGSGPTKKKA KLHAAEKALR SFVQFPNASE AHLAMGRTLS VNTDFTSDQA DFPDTLFNGF
ETPDKSEPPF YVGSNGDDSF SSSGDVSLSA SPVPASLTQP PLPIPPPFPP PSGKNPVMIL
NELRPGLKYD FLSESGESHA KSFVMSVVVD GQFFEGSGRN KKLAKARAAQ SALATVFNLH
LDQTPSRQPV LSEGLQLHLP QVLADAVSRL VLGKFSDLTD NFSSPHARRK VLSGVVMTTG
TDVKDAKVIS VSTGTKCING EYMSDRGLAL NDCHAEIISR RSLLRFLYAQ LELYLNNKED
QKKSIFQKSE RGGFRLKDTV QFHLYISTSP CGDARIFSPH EPVLEGMAPD SHQLTEPADR
HPNRKARGQL RTKIESGEGT IPVRSNASIQ TWDGVLQGER LLTMSCSDKI ARWNVVGIQG
ALLSIFVEPI YFSSIILGSL YHGDHLSRAM YQRISNIEDL PPLYTLNKPL LSGISNAEAR
QPGKAPNFSV NWTVGDTAIE VINATTGKDE LGRPSRLCKH ALYCRWMRVH GKVPPHLLRT
KITKPTTYHE SKLAAKEYQA AKARLFTAFI KAGLGAWVEK PTEQDQFSFT P
