P55266 (DSRAD_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Double-stranded RNA-specific adenosine deaminase
Short name=DRADA
EC=3.5.4.-

Gene names

Name:	Adar
Synonyms:	Dsrad

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1175 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing. This may affect gene expression and function in a number of ways that include mRNA translation by changing codons and hence the amino acid sequence of proteins; pre-mRNA splicing by altering splice site recognition sequences; RNA stability by changing sequences involved in nuclease recognition; genetic stability in the case of RNA virus genomes by changing sequences during viral RNA replication; and RNA structure-dependent activities such as microRNA production or targeting or protein-RNA interactions. Can edit both viral and cellular RNAs and can edit RNAs at multiple sites (hyper-editing) or at specific sites (site-specific editing). Its cellular RNA substrates include: bladder cancer-associated protein (BLCAP), neurotransmitter receptors for glutamate (GRIA2) and serotonin (HTR2C) and GABA receptor (GABRA3). Site-specific RNA editing of transcripts encoding these proteins results in amino acid substitutions which consequently alters their functional activities. Exhibits low-level editing at the GRIA2 Q/R site, but edits efficiently at the R/G site and HOTSPOT1. Does not affect polyomavirus replication but provides protection against virus-induced cytopathic effects. Essential for embryonic development and cell survival and plays a critical role in the maintenance of hematopoietic stem cells By similarity.
Subunit structure	Homodimer. Homodimerization is essential for its catalytic activity. Interacts with ILF2/NF45 and ILF3/NF90. Binding to ILF3/NF90 up-regulates ILF3-mediated gene expression. Interacts with UPF1 and EIF2AK2/PKR By similarity.
Subcellular location	Cytoplasm By similarity. Nucleus › nucleolus By similarity. Note: Shuttles between the cytoplasm and nucleus By similarity.
Post-translational modification	Sumoylation reduces RNA-editing activity By similarity.
Sequence similarities	Contains 1 A to I editase domain. Contains 2 DRADA repeats. Contains 3 DRBM (double-stranded RNA-binding) domains.

Ontologies

Keywords
Biological process	Antiviral defense Immunity Innate immunity RNA-mediated gene silencing Transcription Transcription regulation mRNA processing
Cellular component	Cytoplasm Nucleus
Domain	Repeat
Ligand	DNA-binding Metal-binding RNA-binding Zinc
Molecular function	Hydrolase
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adenosine to inosine editing Inferred from sequence or structural similarity. Source: UniProtKB defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW gene silencing by RNA Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Inferred from electronic annotation. Source: UniProtKB-KW mRNA processing Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of protein kinase activity by regulation of protein phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of viral genome replication Inferred from sequence or structural similarity. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW response to interferon-alpha Inferred from sequence or structural similarity. Source: UniProtKB response to virus Inferred from sequence or structural similarity. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell supraspliceosomal complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW double-stranded RNA adenosine deaminase activity Inferred from direct assay Ref.1. Source: RGD double-stranded RNA binding Inferred from mutant phenotype Ref.1. Source: RGD metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1175	1175	Double-stranded RNA-specific adenosine deaminase		PRO_0000171776
Regions
	Repeat	135 – 204	70	DRADA 1
	Repeat	243 – 310	68	DRADA 2
	Domain	453 – 521	69	DRBM 1
	Domain	564 – 632	69	DRBM 2
	Domain	672 – 740	69	DRBM 3
	Domain	832 – 1167	336	A to I editase
	DNA binding	171 – 197	27	By similarity
	Compositional bias	70 – 121	52	Pro-rich
Sites
	Active site	858	1	Proton donor By similarity
	Metal binding	856	1	Zinc By similarity
	Metal binding	912	1	Zinc By similarity
	Metal binding	982	1	Zinc By similarity
Amino acid modifications
	Modified residue	564	1	Phosphoserine By similarity
	Modified residue	754	1	Phosphothreonine By similarity
	Modified residue	769	1	Phosphoserine By similarity
	Modified residue	771	1	Phosphoserine By similarity
	Cross-link	368		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Sequences

	Sequence		Length	Mass (Da)
	P55266 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: F5C7B5FFB771168C	FASTA	1,175	129,911
	10 20 30 40 50 60 MSQGFRGPTG VFPHQTQPCL DPSYEHSKWR YLQPRGSESY LRSFQLQQIE FLKGRLPEAP 70 80 90 100 110 120 LIGAQTQSLP PFLPGHWPRF PGPPAQGKQP EIWGFPRSVT LRNQGFHIGP PLPPPHSRGP 130 140 150 160 170 180 PWRGAEGLCS HFQELSISQN PEQKVLNRLE ELGEGKATTA YALARELRTP KKDINRILYS 190 200 210 220 230 240 LERKGKLHRG VGKPPLWSLV PLSQACTQPP RAVNSDKEVP RGEPDLDSED GDPASDLEGP 250 260 270 280 290 300 SELLDMAEIK EKICDYLFNV SKSSALNLAK NIGLAKARDV NAVLIDLERQ GDVYREGATP 310 320 330 340 350 360 PIWYLTDKKR ERLQMKRSTH SGPAATPAAV SEATQSTSFP TCHPPQSGGS SSMATSKRVE 370 380 390 400 410 420 NGQEPVTKYE SRHEARPGPV RLRPHAYHNG PSRAGYVASE NGPWATDDIP DNLNSIHTAP 430 440 450 460 470 480 GEFRAIMEMP SFYSPTLPRC SPYKKLTECQ LKNPVSGLLE YAQFTSQTCD FNLIEQSGPS 490 500 510 520 530 540 HEPRFKFQVV INGREFPPAE AGSKKVAKQD AAVKAMAILL REAKAKDSGQ PEELSNCPME 550 560 570 580 590 600 EDPEKPAESQ PPSSSATSLF SGKSPVTTLL ECMHKLGNSC EFRLLSKEGP AHDPKFQYCV 610 620 630 640 650 660 AVGAQTFPSV SAPSKKVAKQ MAAEEAMKAL QEEAANSADD QSGGANTDSL DESVAPNKIR 670 680 690 700 710 720 RIGELVRYLN TNPVGGLLEY ARSHGFAAEF KLIDQSGPPH EPKFVYQAKV GGRWFPAVCA 730 740 750 760 770 780 HSKKQGKQDA ADAALRVLIG ESEKAEQLGF AEVTPVTGAS LRRTMLLLSR SPDAHPKTLP 790 800 810 820 830 840 LTGSTFHDQI AMLSHRCFNA LTNSFQPSLL GRKILAAIIM KRDPEDMGVV VSLGTGNRCV 850 860 870 880 890 900 KGDSLSLKGE TVNDCHAEII SRRGFIRFLY SELMKYNHHT AKNSIFELAR GGEKLQIKKT 910 920 930 940 950 960 VSFHLYISTA PCGDGAHFDK SCSDRAVEST ESRHYPVFEN PKQGKLRTKV ENGEGTIPVE 970 980 990 1000 1010 1020 SSDIVPTWDG IRLGERLRTM SCSDKILRWN VLGLQGALLT HFLQPVYLKS VTLGYLFSQG 1030 1040 1050 1060 1070 1080 HLTRAICCRV TRDGNAFEDG LRYPFIVNHP KVGRVSVYDS KRQSGKTKET SVNWCLADGY 1090 1100 1110 1120 1130 1140 DLEILDGTRG TVDGPGKELS RVSKKNIFLQ FKKLCSFRAR RDLLQLSYGE AKKAARDYDL 1150 1160 1170 AKNYFKKSLR DMGYGNWISK PQEEKNFYLC PVPND

References

[1]	"Cloning of cDNAs encoding mammalian double-stranded RNA-specific adenosine deaminase." O'Connell M.A., Krause S., Higuchi M., Hsuan J.J., Totty N.F., Jenny A., Keller W. Mol. Cell. Biol. 15:1389-1397(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Wistar. Tissue: Brain.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U18942 mRNA. Translation: AAA65039.1.
IPI	IPI00215318.
PIR	I57549.
RefSeq	NP_112268.1. NM_031006.1.
UniGene	Rn.10056.
3D structure databases
ProteinModelPortal	P55266.
SMR	P55266. Positions 128-199, 244-316.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000028181.
PTM databases
PhosphoSite	P55266.
Proteomic databases
PaxDb	P55266.
PRIDE	P55266.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	81635.
KEGG	rno:81635.
UCSC	RGD:71099. rat.
Organism-specific databases
CTD	103.
RGD	71099. Adar.
Phylogenomic databases
eggNOG	NOG292433.
HOGENOM	HOG000049121.
HOVERGEN	HBG067087.
InParanoid	P55266.
KO	K12968.
OrthoDB	EOG4HDSSW.
Gene expression databases
Genevestigator	P55266.
GermOnline	ENSRNOG00000020744. Rattus norvegicus.
Family and domain databases
Gene3D	1.10.10.10. 2 hits. 3.30.160.20. 3 hits.
InterPro	IPR002466. A_deamin. IPR001159. Ds-RNA-bd. IPR014720. dsRNA-bd-like_dom. IPR000607. dsRNA_A_deaminase. IPR011991. WHTH_DNA-bd_dom. [Graphical view]
Pfam	PF02137. A_deamin. 1 hit. PF00035. dsrm. 3 hits. PF02295. z-alpha. 2 hits. [Graphical view]
SMART	SM00552. ADEAMc. 1 hit. SM00358. DSRM. 3 hits. SM00550. Zalpha. 2 hits. [Graphical view]
PROSITE	PS50141. A_DEAMIN_EDITASE. 1 hit. PS50139. DRADA_REPEAT. 2 hits. PS50137. DS_RBD. 3 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	615120.

Entry information

Entry name

DSRAD_RAT

Accession

Primary (citable) accession number: P55266

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program