Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Double-stranded RNA-specific adenosine deaminase

Gene

Adar

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.3 Publications

Catalytic activityi

Adenine in double-stranded RNA + H2O = hypoxanthine in double-stranded RNA + NH3.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi859Zinc1
Active sitei861Proton donor1
Metal bindingi915Zinc1
Metal bindingi985Zinc1

GO - Molecular functioni

  • double-stranded RNA adenosine deaminase activity Source: MGI
  • left-handed Z-DNA binding Source: MGI
  • metal ion binding Source: UniProtKB-KW
  • RNA binding Source: MGI

GO - Biological processi

  • adenosine to inosine editing Source: UniProtKB
  • base conversion or substitution editing Source: MGI
  • cellular response to virus Source: UniProtKB
  • defense response to virus Source: MGI
  • definitive hemopoiesis Source: MGI
  • erythrocyte differentiation Source: MGI
  • hematopoietic progenitor cell differentiation Source: MGI
  • hematopoietic stem cell homeostasis Source: MGI
  • innate immune response Source: UniProtKB-KW
  • in utero embryonic development Source: MGI
  • miRNA loading onto RISC involved in gene silencing by miRNA Source: MGI
  • mRNA processing Source: UniProtKB-KW
  • negative regulation of apoptotic process Source: MGI
  • negative regulation of protein kinase activity by regulation of protein phosphorylation Source: UniProtKB
  • negative regulation of RNA interference Source: MGI
  • negative regulation of type I interferon-mediated signaling pathway Source: MGI
  • negative regulation of viral genome replication Source: MGI
  • osteoblast differentiation Source: MGI
  • positive regulation of viral genome replication Source: UniProtKB
  • pre-miRNA processing Source: MGI
  • production of miRNAs involved in gene silencing by miRNA Source: MGI
  • protein export from nucleus Source: MGI
  • protein import into nucleus Source: MGI
  • regulation of transcription, DNA-templated Source: UniProtKB-KW
  • response to interferon-alpha Source: UniProtKB
  • response to virus Source: UniProtKB
  • somatic diversification of immune receptors via somatic mutation Source: MGI
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionDNA-binding, Hydrolase, RNA-binding
Biological processAntiviral defense, Immunity, Innate immunity, mRNA processing, RNA-mediated gene silencing, Transcription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.5.4.37. 3474.
ReactomeiR-MMU-75102. C6 deamination of adenosine.
R-MMU-77042. Formation of editosomes by ADAR proteins.

Names & Taxonomyi

Protein namesi
Recommended name:
Double-stranded RNA-specific adenosine deaminase (EC:3.5.4.37)
Short name:
DRADA
Alternative name(s):
RNA adenosine deaminase 1
Gene namesi
Name:Adar
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1889575. Adar.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice do not survive past E11.0-E12.5 and embryos display widespread apoptosis, a rapidly disintegrating liver structure and severe defects in hematopoiesis.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001717751 – 1178Double-stranded RNA-specific adenosine deaminaseAdd BLAST1178

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei30Asymmetric dimethylarginineCombined sources1
Modified residuei42Asymmetric dimethylarginineCombined sources1
Modified residuei231PhosphoserineBy similarity1
Modified residuei238PhosphoserineBy similarity1
Cross-linki371Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Cross-linki371Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateBy similarity
Cross-linki371Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei434PhosphoserineBy similarity1
Modified residuei567PhosphoserineBy similarity1
Modified residuei582PhosphoserineCombined sources1
Modified residuei589PhosphoserineBy similarity1
Modified residuei757PhosphothreonineBy similarity1
Modified residuei763PhosphoserineBy similarity1
Modified residuei772PhosphoserineBy similarity1
Modified residuei774PhosphoserineBy similarity1
Cross-linki824Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity

Post-translational modificationi

Sumoylation reduces RNA-editing activity.By similarity

Keywords - PTMi

Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ99MU3.
PeptideAtlasiQ99MU3.
PRIDEiQ99MU3.

PTM databases

iPTMnetiQ99MU3.
PhosphoSitePlusiQ99MU3.

Expressioni

Tissue specificityi

Highest levels in brain and spleen. Lowest levels in liver.1 Publication

Inductioni

By inflammation. Under normal conditions, long forms starting at Met-1 are dominant. Inflammation causes selective induction of short forms starting at Met-519.2 Publications

Gene expression databases

BgeeiENSMUSG00000027951.
CleanExiMM_ADAR.
GenevisibleiQ99MU3. MM.

Interactioni

Subunit structurei

Homodimer. Homodimerization is essential for its catalytic activity (PubMed:12618436). Isoform 5 can form heterodimers with ADARB1/ADAR2. Isoform 1 and isoform 5 (via DRBM 3 domain) interact with TNPO1. Isoform 5 (via DRBM domains) interacts with XPO5. Isoform 1 and isoform 5 can interact with UPF1 (By similarity). Isoform 1 interacts with ILF2/NF45 and ILF3/NF90 (PubMed:16055709). Binding to ILF3/NF90 up-regulates ILF3-mediated gene expression. Isoform 1 and isoform 5 interact with EIF2AK2/PKR (PubMed:17079286).By similarity3 Publications

Protein-protein interaction databases

BioGridi207963. 1 interactor.
IntActiQ99MU3. 1 interactor.
MINTiMINT-4093631.
STRINGi10090.ENSMUSP00000103028.

Structurei

3D structure databases

ProteinModelPortaliQ99MU3.
SMRiQ99MU3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati135 – 204DRADA 1Add BLAST70
Repeati246 – 313DRADA 2Add BLAST68
Domaini456 – 524DRBM 1Add BLAST69
Domaini567 – 635DRBM 2Add BLAST69
Domaini675 – 743DRBM 3Add BLAST69
Domaini835 – 1170A to I editaseAdd BLAST336

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni135 – 204Interaction with Z-DNABy similarityAdd BLAST70
Regioni665 – 674N-terminal extension of DRBM 3 and constituent of a bi-partite nuclear localization signalBy similarity10
Regioni744 – 750C-terminal extension of DRBM 3 and constituent of a bi-partite nuclear localization signalBy similarity7

Domaini

The first DRADA repeat binds Z-DNA.By similarity
The third dsRNA-binding domain (DRBM 3) contains an additional N-terminal alpha-helix that is part of a bi-partite nuclear localization signal, together with the sequence immediately C-terminal to DRBM 3. The presence of DRBM 3 is important to bring together the N-terminal and the C-terminal part of the bi-partite nuclear localization signal for import mediated by TNPO1. RNA binding interferes with nuclear import.By similarity

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG2777. Eukaryota.
ENOG410XT0Z. LUCA.
GeneTreeiENSGT00550000074412.
HOVERGENiHBG067087.
InParanoidiQ99MU3.
KOiK12968.
OMAiDPKFQYC.
OrthoDBiEOG091G0MZP.
PhylomeDBiQ99MU3.
TreeFamiTF315806.

Family and domain databases

Gene3Di1.10.10.10. 2 hits.
InterProiView protein in InterPro
IPR002466. A_deamin.
IPR014720. dsRBD_dom.
IPR000607. dsRNA_A_deaminase.
IPR036388. WH-like_DNA-bd_sf.
IPR036390. WH_DNA-bd_sf.
PfamiView protein in Pfam
PF02137. A_deamin. 1 hit.
PF00035. dsrm. 3 hits.
PF02295. z-alpha. 2 hits.
SMARTiView protein in SMART
SM00552. ADEAMc. 1 hit.
SM00358. DSRM. 3 hits.
SM00550. Zalpha. 2 hits.
SUPFAMiSSF46785. SSF46785. 2 hits.
PROSITEiView protein in PROSITE
PS50141. A_DEAMIN_EDITASE. 1 hit.
PS50139. DRADA_REPEAT. 2 hits.
PS50137. DS_RBD. 3 hits.

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q99MU3-1) [UniParc]FASTAAdd to basket
Also known as: ADAR1Lb, p150

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSQGFRGPTG VFPHQTQSYL DPSHEHSKWR YPQPQGPESY PRSFQLQQIE
60 70 80 90 100
FLKGRLPEAP LIGIQTQSLP PFLPGHWPRF PGPPAQDRQL EIWEFPRSVT
110 120 130 140 150
LRNQGFHIGP PLPPPHSRGT PWRGADGLCS HFRELSISQS PEQKVLNRLE
160 170 180 190 200
ELGEGKATTA HVLARELRIP KRDINRILYS LEKKGKLHRG RGKPPLWSLV
210 220 230 240 250
PLSQAWTQPP GVVNPDSCIQ EFPRGEPGLD SEDGDPASDL EGPSEPLDMA
260 270 280 290 300
EIKEKICDYL FNVSNSSALN LAKNIGLTKA RDVTSVLIDL ERQGDVYRQG
310 320 330 340 350
ATPPIWYLTD KKRERLQMKR STHSAPAPTP TAVPEATRSP SFPACHPPPA
360 370 380 390 400
GASSSVAASK RVENGQEPAI KHESRHEARP GPMRLRPHAY HNGPSRAGYV
410 420 430 440 450
ASENGQWATD DIPDNLNSIH TAPGEFRAIM EMPSFYSPTL PRCSPYKKLT
460 470 480 490 500
ECQLKNPVSG LLEYAQFTSQ TCDFNLIEQS GPSHEPRFKF QVVINGREFP
510 520 530 540 550
PAEAGSKKVA KQDAAVKAMA ILLREAKAKD SGQPEDLSHC PMEEDSEKPA
560 570 580 590 600
EAQAPSSSAT SLFSGKSPVT TLLECMHKLG NSCEFRLLSK EGPAHDPKFQ
610 620 630 640 650
YCVAVGAQTF PPVSAPSKKV AKQMAAEEAM KALQEEAASS ADDQSGGANT
660 670 680 690 700
DSLDESMAPN KIRRIGELVR YLNTNPVGGL LEYARSHGFA AEFKLIDQSG
710 720 730 740 750
PPHEPKFVYQ AKVGGRWFPA VCAHSKKQGK QDAADAALRV LIGESEKAEQ
760 770 780 790 800
LGFAEVTPVT GASLRRTMLL LSRSPDAHPK TLPLSGSTFH DQIAMLSHRC
810 820 830 840 850
FNALTNSFQP SLLGRKILAA IIMKRDPEDM GVVVSLGTGN RCVKGDSLSL
860 870 880 890 900
KGETVNDCHA EIISRRGFIR FLYSELMKYN HHTAKNSIFE LARGGEKLQI
910 920 930 940 950
KKTVSFHLYI STAPCGDGAL FDKSCSDRAV ESTESRHYPV FENPKQGKLR
960 970 980 990 1000
TKVENGEGTI PVESSDIVPT WDGIRLGERL RTMSCSDKIL RWNVLGLQGA
1010 1020 1030 1040 1050
LLTHFLQPVY LKSVTLGYLF SQGHLTRAIC CRVTRDGKAF EDGLRYPFIV
1060 1070 1080 1090 1100
NHPKVGRVSV YDSKRQSGKT KETSVNWCMA DGYDLEILDG TRGTVDGPGK
1110 1120 1130 1140 1150
ELSRVSKKNI FLQFKKLCSF RARRDLLQLS YGEAKKAARD YDLAKNYFKK
1160 1170
SLRDMGYGNW ISKPQEEKNF YLCPVPND
Length:1,178
Mass (Da):130,447
Last modified:November 14, 2003 - v2
Checksum:i8C28B71F00744724
GO
Isoform 2 (identifier: Q99MU3-2) [UniParc]FASTAAdd to basket
Also known as: ADAR1La

The sequence of this isoform differs from the canonical sequence as follows:
     756-781: Missing.

Show »
Length:1,152
Mass (Da):127,660
Checksum:i084406057050D3EB
GO
Isoform 3 (identifier: Q99MU3-3) [UniParc]FASTAAdd to basket
Also known as: ADAR1Sa

The sequence of this isoform differs from the canonical sequence as follows:
     1-518: Missing.
     756-781: Missing.

Show »
Length:634
Mass (Da):70,102
Checksum:iFF1AE77D36F08920
GO
Isoform 4 (identifier: Q99MU3-4) [UniParc]FASTAAdd to basket
Also known as: ADAR1Sb, p80

The sequence of this isoform differs from the canonical sequence as follows:
     1-518: Missing.

Show »
Length:660
Mass (Da):72,889
Checksum:i4FEA49B89A5B9B75
GO
Isoform 5 (identifier: Q99MU3-5) [UniParc]FASTAAdd to basket
Also known as: p110

The sequence of this isoform differs from the canonical sequence as follows:
     1-248: Missing.

Note: No experimental confirmation available.
Show »
Length:930
Mass (Da):102,580
Checksum:i94CDFC1E3EFBA538
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti415N → D in AAK16102 (PubMed:12954622).Curated1
Sequence conflicti644Q → K in AAC06233 (Ref. 3) Curated1
Sequence conflicti730K → R in AAC06233 (Ref. 3) Curated1
Sequence conflicti920L → H in AAC06233 (Ref. 3) Curated1
Sequence conflicti1003T → A in BAC40888 (PubMed:16141072).Curated1
Sequence conflicti1098P → S in AAK16102 (PubMed:12954622).Curated1
Sequence conflicti1149K → R in AAK16102 (PubMed:12954622).Curated1
Sequence conflicti1173C → R in BAC40888 (PubMed:16141072).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti20L → S in strain: Czech II. 1 Publication1
Natural varianti32P → L in strain: Czech II. 1 Publication1
Natural varianti120T → P in strain: Czech II. 1
Natural varianti330P → L in strain: Czech II. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0192361 – 518Missing in isoform 3 and isoform 4. 1 PublicationAdd BLAST518
Alternative sequenceiVSP_0192371 – 248Missing in isoform 5. 1 PublicationAdd BLAST248
Alternative sequenceiVSP_008875756 – 781Missing in isoform 2 and isoform 3. 4 PublicationsAdd BLAST26

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF291875 mRNA. Translation: AAK16101.1.
AF291876 mRNA. Translation: AAK16102.1.
AF291877 mRNA. Translation: AAK16103.1.
AF291050 mRNA. Translation: AAK17103.1.
AF052506 mRNA. Translation: AAC06233.1.
BC042505 mRNA. Translation: AAH42505.1.
AK089451 mRNA. Translation: BAC40888.2.
CCDSiCCDS17513.1. [Q99MU3-2]
CCDS17514.1. [Q99MU3-5]
CCDS50963.1. [Q99MU3-1]
RefSeqiNP_001139768.1. NM_001146296.1. [Q99MU3-1]
NP_062629.3. NM_019655.3. [Q99MU3-2]
XP_006501817.1. XM_006501754.2. [Q99MU3-5]
UniGeneiMm.316628.

Genome annotation databases

EnsembliENSMUST00000029563; ENSMUSP00000029563; ENSMUSG00000027951. [Q99MU3-2]
ENSMUST00000098924; ENSMUSP00000096525; ENSMUSG00000027951. [Q99MU3-5]
ENSMUST00000107405; ENSMUSP00000103028; ENSMUSG00000027951. [Q99MU3-1]
ENSMUST00000118341; ENSMUSP00000113453; ENSMUSG00000027951. [Q99MU3-4]
ENSMUST00000121094; ENSMUSP00000112969; ENSMUSG00000027951. [Q99MU3-3]
GeneIDi56417.
KEGGimmu:56417.
UCSCiuc008pzv.2. mouse. [Q99MU3-1]
uc008pzw.2. mouse. [Q99MU3-2]
uc008pzy.2. mouse. [Q99MU3-3]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiDSRAD_MOUSE
AccessioniPrimary (citable) accession number: Q99MU3
Secondary accession number(s): O70375
, Q80UZ6, Q8C222, Q99MU2, Q99MU4, Q99MU7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 14, 2003
Last sequence update: November 14, 2003
Last modified: October 25, 2017
This is version 145 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot