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Reviewed, UniProtKB/Swiss-Prot P55265 (DSRAD_HUMAN)

Last modified November 25, 2008. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Double-stranded RNA-specific adenosine deaminase
      Short name=DRADA
    EC=3.5.4.-
Alternative name(s):
    136 kDa double-stranded RNA-binding protein
    P136
    K88DSRBP
    Interferon-inducible protein 4
      Short name=IFI-4
Gene names
Name: ADAR
Synonyms: ADAR1, DSRAD, G1P1, IFI4
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1226 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Converts multiple adenosines to inosines and creates I/U mismatched base pairs in double-helical RNA substrates without apparent sequence specificity. Has been found to modify more frequently adenosines in AU-rich regions, probably due to the relative ease of melting A/U base pairs as compared to G/C pairs. Functions to modify viral RNA genomes and may be responsible for hypermutation of certain negative-stranded viruses. Edits the messenger RNAs for glutamate receptor (GLUR) subunits by site-selective adenosine deamination. Produces low-level editing at the GLUR-B Q/R site, but edits efficiently at the R/G site and HOTSPOT1. Binds to short interfering RNAs (siRNA) without editing them and suppresses siRNA-mediated RNA interference. Binds to ILF3/NF90 and up-regulates ILF3-mediated gene expression.

Subunit structure

Homodimer. Isoform 1 interacts with ILF2/NF45 and ILF3/NF90.

Subcellular location

Cytoplasm. Nucleusnucleolus. Note= Isoform 1 is found predominantly in cytoplasm but appears to shuttle between the cytoplasm and nucleus. Isoform 5 is found exclusively in the nucleolus.

Tissue specificity

Ubiquitously expressed, highest levels were found in brain and lung.

Induction

Isoform 1 is induced by interferon alpha. Isoform 5 is constitutively expressed.

Post-translational modification

Sumoylation reduces RNA-editing activity.

Involvement in disease

Defects in ADAR are a cause of dyschromatosis symmetrical hereditaria (DSH) [MIM:127400]; also known as reticulate acropigmentation of Dohi. DSH is a pigmentary genodermatosis of autosomal dominant inheritance characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the dorsal parts of the hands and feet.

Sequence similarities

Contains 1 A to I editase domain.

Contains 2 DRADA repeats.

Contains 3 DRBM (double-stranded RNA-binding) domains.

Caution

The N-terminus of isoform 4 has been derived from EST and genomic sequences.

Alternative products

This entry describes 5 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select]
Isoform 1 (identifier: P55265-1)

Also known as: ADAR-a; 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.
Notes: Produced by alternative promoter usage.
Isoform 2 (identifier: P55265-2)

Also known as: ADAR-b;

The sequence of this isoform differs from the canonical sequence as follows:
     807-832: Missing.
Notes: Produced by alternative splicing of isoform 1.
Isoform 3 (identifier: P55265-3)

Also known as: ADAR-c;

The sequence of this isoform differs from the canonical sequence as follows:
     694-712: Missing.
     807-832: Missing.
Notes: Produced by alternative splicing of isoform 1.
Isoform 4 (identifier: P55265-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-5: MNPRQ → MMSPICDQTIDSRLKVEKATWWGRVGGGSRPHWQPPGVRPCPEEVQDP
Notes: Produced by alternative splicing of isoform 1. No experimental confirmation available. The N-terminus has been derived from EST and genomic sequences.
Isoform 5 (identifier: P55265-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-295: Missing.
Notes: Produced by alternative promoter usage.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12261226Double-stranded RNA-specific adenosine deaminase
PRO_0000171774

Regions

Repeat133 – 20270DRADA 1
Repeat293 – 36068DRADA 2
Domain503 – 57169DRBM 1
Domain614 – 68269DRBM 2
Domain726 – 79469DRBM 3
Domain886 – 1221336A to I editase
DNA binding169 – 19527

Sites

Active site9121Proton donor By similarity
Metal binding9101Zinc By similarity
Metal binding9661Zinc By similarity
Metal binding10361Zinc By similarity

Amino acid modifications

Modified residue6011Phosphothreonine
Modified residue6141Phosphoserine
Modified residue8081Phosphothreonine
Modified residue8181Phosphothreonine
Modified residue8231Phosphoserine
Modified residue8251Phosphoserine
Cross-link418Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)

Natural variations

Alternative sequence1 – 295295Missing in isoform 5.
VSP_019235
Alternative sequence1 – 55MNPRQ → MMSPICDQTIDSRLKVEKAT WWGRVGGGSRPHWQPPGVRP CPEEVQDP in isoform 4.
VSP_008872
Alternative sequence694 – 71219Missing in isoform 3.
VSP_008873
Alternative sequence807 – 83226Missing in isoform 2 and isoform 3.
VSP_008874
Natural variant3841R → K: dbSNP rs2229857.
VAR_017240
Natural variant5871Y → C: dbSNP rs17843865.
VAR_024407
Natural variant8061E → V in a breast cancer sample; somatic mutation.
VAR_035805
Natural variant9231L → P in DSH.
VAR_017604
Natural variant9661C → F in DSH.
VAR_021729
Natural variant11551R → W in DSH.
VAR_026669
Natural variant11651F → S in DSH.
VAR_017605

Experimental info

Mutagenesis4181K → R: Abolishes sumoylation
Sequence conflict531E → G in CAA55967 and CAA55968. Ref.4
Sequence conflict11841E → K in CAA55967 and CAA55968. Ref.4

Secondary structure

............................. 1226
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (ADAR-a) (p150) [UniParc].

Last modified November 14, 2003. Version 2.
Checksum: 849D6234379277B4

FASTA1,226135,995
        10         20         30         40         50         60 
MNPRQGYSLS GYYTHPFQGY EHRQLRYQQP GPGSSPSSFL LKQIEFLKGQ LPEAPVIGKQ 

        70         80         90        100        110        120 
TPSLPPSLPG LRPRFPVLLA SSTRGRQVDI RGVPRGVHLG SQGLQRGFQH PSPRGRSLPQ 

       130        140        150        160        170        180 
RGVDCLSSHF QELSIYQDQE QRILKFLEEL GEGKATTAHD LSGKLGTPKK EINRVLYSLA 

       190        200        210        220        230        240 
KKGKLQKEAG TPPLWKIAVS TQAWNQHSGV VRPDGHSQGA PNSDPSLEPE DRNSTSVSED 

       250        260        270        280        290        300 
LLEPFIAVSA QAWNQHSGVV RPDSHSQGSP NSDPGLEPED SNSTSALEDP LEFLDMAEIK 

       310        320        330        340        350        360 
EKICDYLFNV SDSSALNLAK NIGLTKARDI NAVLIDMERQ GDVYRQGTTP PIWHLTDKKR 

       370        380        390        400        410        420 
ERMQIKRNTN SVPETAPAAI PETRRNAEFL TCNIPTSNAS NNMVTTEKVE NGQEPVIKLE 

       430        440        450        460        470        480 
NRQEARPEPA RLKPPVHYNG PSKAGYVDFE NGQWATDDIP DDLNSIRAAP GEFRAIMEMP 

       490        500        510        520        530        540 
SFYSHGLPRC SPYKKLTECQ LKNPISGLLE YAQFASQTCE FNMIEQSGPP HEPRFKFQVV 

       550        560        570        580        590        600 
INGREFPPAE AGSKKVAKQD AAMKAMTILL EEAKAKDSGK SEESSHYSTE KESEKTAESQ 

       610        620        630        640        650        660 
TPTPSATSFF SGKSPVTTLL ECMHKLGNSC EFRLLSKEGP AHEPKFQYCV AVGAQTFPSV 

       670        680        690        700        710        720 
SAPSKKVAKQ MAAEEAMKAL HGEATNSMAS DNQPEGMISE SLDNLESMMP NKVRKIGELV 

       730        740        750        760        770        780 
RYLNTNPVGG LLEYARSHGF AAEFKLVDQS GPPHEPKFVY QAKVGGRWFP AVCAHSKKQG 

       790        800        810        820        830        840 
KQEAADAALR VLIGENEKAE RMGFTEVTPV TGASLRRTML LLSRSPEAQP KTLPLTGSTF 

       850        860        870        880        890        900 
HDQIAMLSHR CFNTLTNSFQ PSLLGRKILA AIIMKKDSED MGVVVSLGTG NRCVKGDSLS 

       910        920        930        940        950        960 
LKGETVNDCH AEIISRRGFI RFLYSELMKY NSQTAKDSIF EPAKGGEKLQ IKKTVSFHLY 

       970        980        990       1000       1010       1020 
ISTAPCGDGA LFDKSCSDRA MESTESRHYP VFENPKQGKL RTKVENGEGT IPVESSDIVP 

      1030       1040       1050       1060       1070       1080 
TWDGIRLGER LRTMSCSDKI LRWNVLGLQG ALLTHFLQPI YLKSVTLGYL FSQGHLTRAI 

      1090       1100       1110       1120       1130       1140 
CCRVTRDGSA FEDGLRHPFI VNHPKVGRVS IYDSKRQSGK TKETSVNWCL ADGYDLEILD 

      1150       1160       1170       1180       1190       1200 
GTRGTVDGPR NELSRVSKKN IFLLFKKLCS FRYRRDLLRL SYGEAKKAAR DYETAKNYFK 

      1210       1220 
KGLKDMGYGN WISKPQEEKN FYLCPV 

« Hide

Isoform 2 (ADAR-b) [UniParc].

Checksum: 76EAF4C0E9B9AADD
Show »

1,200133,203
Isoform 3 (ADAR-c) [UniParc].

Checksum: 329A03A0DC702D56
Show »

1,181131,099
Isoform 4 [UniParc].

Checksum: A3E6EA1355DEF005
Show »

1,269140,767
Isoform 5 [UniParc].

Checksum: 976C613CD94308C7
Show »

931103,670

References

« Hide 'large scale' references
[1]"Molecular cloning of cDNA for double-stranded RNA adenosine deaminase, a candidate enzyme for nuclear RNA editing."
Kim U., Wang Y., Sanford T., Zeng Y., Nishikura K.
Proc. Natl. Acad. Sci. U.S.A. 91:11457-11461(1994) [PubMed: 7972084] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
[2]"Expression and regulation by interferon of a double-stranded-RNA-specific adenosine deaminase from human cells: evidence for two forms of the deaminase."
Patterson J.B., Samuel C.E.
Mol. Cell. Biol. 15:5376-5388(1995) [PubMed: 7565688] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Kidney.
[3]"Functionally distinct double-stranded RNA-binding domains associated with alternative splice site variants of the interferon-inducible double-stranded RNA-specific adenosine deaminase."
Liu Y., George C.X., Patterson J.B., Samuel C.E.
J. Biol. Chem. 272:4419-4428(1997) [PubMed: 9020165] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2 AND 3).
Tissue: Placenta.
[4]"The gene coding for the interferon-inducible human dsRNA adenosine deaminase is transcribed into several messengers specifying different proteins."
Deblandre G., Marinx O., Nols C., Defrance P., Berr P., Huez G., Caput D.
Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Cervix carcinoma.
[5]The German cDNA consortium
Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
Tissue: