CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-008974
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
 AAB06697.1; AAB97116.1; AAB97116.1; AAB97116.1; AAB97116.1; AAB97116.1; AAB97116.1; AAB97116.1; AAB97116.1; AAB97116.1; AAB97116.1; AAB97116.1; AAB97116.1; AAB97116.1; AAB97116.1; AAB97116.1; AAB97117.1; AAB97117.1; AAB97117.1; AAB97117.1; AAB97117.1; AAB97117.1; AAB97117.1; AAB97117.1; AAB97117.1; AAB97117.1; AAB97117.1; AAB97117.1; AAB97117.1; AAB97117.1; AAB97117.1; AAB97118.1; AAB97118.1; AAB97118.1; AAB97118.1; AAB97118.1; AAB97118.1; AAB97118.1; AAB97118.1; AAB97118.1; AAB97118.1; AAB97118.1; AAB97118.1; AAB97118.1; AAB97118.1; AAB97118.1; AAC13782.1; CAA55967.1; CAA55968.1; CAA67169.1; CAA67170.1; CAD98075.1; CAE45853.1; CAH71907.1; CAH71907.1; CAH71907.1; CAH71908.1; CAH71908.1; CAH71908.1; CAI16183.1; CAI16183.1; CAI16183.1; CAI16185.1; CAI16185.1; CAI16185.1; CAI17375.1; CAI17375.1; CAI17375.1; CAI17376.1; CAI17376.1; CAI17376.1; EAW53183.1; EAW53187.1; AAH38227.1 
Protein Name
 Double-stranded RNA-specific adenosine deaminase 
Protein Synonyms/Alias
 DRADA; 136 kDa double-stranded RNA-binding protein; p136; Interferon-inducible protein 4; IFI-4; K88DSRBP 
Gene Name
 ADAR 
Gene Synonyms/Alias
 ADAR1; DSRAD; G1P1; IFI4 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
418NGQEPVIKLENRQEAsumoylation[1, 2]
443VHYNGPSKAGYVDFEubiquitination[3]
595STEKESEKTAESQTPubiquitination[4]
665PSVSAPSKKVAKQMAubiquitination[4]
757SGPPHEPKFVYQAKVubiquitination[3]
936KYNSQTAKDSIFEPAubiquitination[4]
944DSIFEPAKGGEKLQIubiquitination[4]
1166KNIFLLFKKLCSFRYubiquitination[4]
Reference
 [1] SUMO-1 modification alters ADAR1 editing activity.
 Desterro JM, Keegan LP, Jaffray E, Hay RT, O'Connell MA, Carmo-Fonseca M.
 Mol Biol Cell. 2005 Nov;16(11):5115-26. [PMID: 16120648]
 [2] Site-specific identification of SUMO-2 targets in cells reveals an inverted SUMOylation motif and a hydrophobic cluster SUMOylation motif.
 Matic I, Schimmel J, Hendriks IA, van Santen MA, van de Rijke F, van Dam H, Gnad F, Mann M, Vertegaal AC.
 Mol Cell. 2010 Aug 27;39(4):641-52. [PMID: 20797634]
 [3] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [4] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983] 
Functional Description
 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. Its viral RNA substrates include: hepatitis C virus (HCV), vesicular stomatitis virus (VSV), measles virus (MV), hepatitis delta virus (HDV), and human immunodeficiency virus type 1 (HIV-1). Exhibits either a proviral (HDV, MV, VSV and HIV-1) or an antiviral effect (HCV) and this can be editing-dependent (HDV and HCV), editing-independent (VSV and MV) or both (HIV-1). Impairs HCV replication via RNA editing at multiple sites. Enhances the replication of MV, VSV and HIV-1 through an editing- independent mechanism via suppression of EIF2AK2/PKR activation and function. Stimulates both the release and infectivity of HIV-1 viral particles by an editing-dependent mechanism where it associates with viral RNAs and edits adenosines in the 5'UTR and the Rev and Tat coding sequence. Can enhance viral replication of HDV via A-to-I editing at a site designated as amber/W, thereby changing an UAG amber stop codon to an UIG tryptophan (W) codon that permits synthesis of the large delta antigen (L-HDAg) which has a key role in the assembly of viral particles. However, high levels of ADAR1 inhibit HDV replication. 
Sequence Annotation
 REPEAT 133 202 DRADA 1.
 REPEAT 293 360 DRADA 2.
 DOMAIN 503 571 DRBM 1.
 DOMAIN 614 682 DRBM 2.
 DOMAIN 726 794 DRBM 3.
 DOMAIN 886 1221 A to I editase.
 DNA_BIND 169 195
 ACT_SITE 912 912 Proton donor (By similarity).
 METAL 910 910 Zinc (By similarity).
 METAL 966 966 Zinc (By similarity).
 METAL 1036 1036 Zinc (By similarity).
 MOD_RES 601 601 Phosphothreonine.
 MOD_RES 614 614 Phosphoserine.
 MOD_RES 808 808 Phosphothreonine.
 MOD_RES 823 823 Phosphoserine.
 MOD_RES 825 825 Phosphoserine.
 CROSSLNK 418 418 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Aicardi-Goutieres syndrome; Alternative promoter usage; Alternative splicing; Antiviral defense; Complete proteome; Cytoplasm; Direct protein sequencing; Disease mutation; DNA-binding; Hydrolase; Immunity; Innate immunity; Isopeptide bond; Metal-binding; mRNA processing; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; RNA-binding; RNA-mediated gene silencing; Ubl conjugation; Zinc. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1226 AA 
Protein Sequence
MNPRQGYSLS GYYTHPFQGY EHRQLRYQQP GPGSSPSSFL LKQIEFLKGQ LPEAPVIGKQ 60
TPSLPPSLPG LRPRFPVLLA SSTRGRQVDI RGVPRGVHLR SQGLQRGFQH PSPRGRSLPQ 120
RGVDCLSSHF QELSIYQDQE QRILKFLEEL GEGKATTAHD LSGKLGTPKK EINRVLYSLA 180
KKGKLQKEAG TPPLWKIAVS TQAWNQHSGV VRPDGHSQGA PNSDPSLEPE DRNSTSVSED 240
LLEPFIAVSA QAWNQHSGVV RPDSHSQGSP NSDPGLEPED SNSTSALEDP LEFLDMAEIK 300
EKICDYLFNV SDSSALNLAK NIGLTKARDI NAVLIDMERQ GDVYRQGTTP PIWHLTDKKR 360
ERMQIKRNTN SVPETAPAAI PETKRNAEFL TCNIPTSNAS NNMVTTEKVE NGQEPVIKLE 420
NRQEARPEPA RLKPPVHYNG PSKAGYVDFE NGQWATDDIP DDLNSIRAAP GEFRAIMEMP 480
SFYSHGLPRC SPYKKLTECQ LKNPISGLLE YAQFASQTCE FNMIEQSGPP HEPRFKFQVV 540
INGREFPPAE AGSKKVAKQD AAMKAMTILL EEAKAKDSGK SEESSHYSTE KESEKTAESQ 600
TPTPSATSFF SGKSPVTTLL ECMHKLGNSC EFRLLSKEGP AHEPKFQYCV AVGAQTFPSV 660
SAPSKKVAKQ MAAEEAMKAL HGEATNSMAS DNQPEGMISE SLDNLESMMP NKVRKIGELV 720
RYLNTNPVGG LLEYARSHGF AAEFKLVDQS GPPHEPKFVY QAKVGGRWFP AVCAHSKKQG 780
KQEAADAALR VLIGENEKAE RMGFTEVTPV TGASLRRTML LLSRSPEAQP KTLPLTGSTF 840
HDQIAMLSHR CFNTLTNSFQ PSLLGRKILA AIIMKKDSED MGVVVSLGTG NRCVKGDSLS 900
LKGETVNDCH AEIISRRGFI RFLYSELMKY NSQTAKDSIF EPAKGGEKLQ IKKTVSFHLY 960
ISTAPCGDGA LFDKSCSDRA MESTESRHYP VFENPKQGKL RTKVENGEGT IPVESSDIVP 1020
TWDGIRLGER LRTMSCSDKI LRWNVLGLQG ALLTHFLQPI YLKSVTLGYL FSQGHLTRAI 1080
CCRVTRDGSA FEDGLRHPFI VNHPKVGRVS IYDSKRQSGK TKETSVNWCL ADGYDLEILD 1140
GTRGTVDGPR NELSRVSKKN IFLLFKKLCS FRYRRDLLRL SYGEAKKAAR DYETAKNYFK 1200
KGLKDMGYGN WISKPQEEKN FYLCPV 1226 
Gene Ontology
 GO:0005737; C:cytoplasm; IDA:UniProtKB.
 GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0044530; C:supraspliceosomal complex; IDA:UniProtKB.
 GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
 GO:0003726; F:double-stranded RNA adenosine deaminase activity; NAS:UniProtKB.
 GO:0003725; F:double-stranded RNA binding; IEA:InterPro.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0006382; P:adenosine to inosine editing; IDA:UniProtKB.
 GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
 GO:0010467; P:gene expression; TAS:Reactome.
 GO:0031047; P:gene silencing by RNA; IEA:UniProtKB-KW.
 GO:0016556; P:mRNA modification; TAS:Reactome.
 GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
 GO:0043066; P:negative regulation of apoptotic process; IEA:Compara.
 GO:0044387; P:negative regulation of protein kinase activity by regulation of protein phosphorylation; IDA:UniProtKB.
 GO:0045070; P:positive regulation of viral genome replication; IDA:UniProtKB.
 GO:0006611; P:protein export from nucleus; IDA:UniProtKB.
 GO:0006606; P:protein import into nucleus; IDA:UniProtKB.
 GO:0035455; P:response to interferon-alpha; IDA:UniProtKB.
 GO:0009615; P:response to virus; IMP:UniProtKB.
 GO:0060337; P:type I interferon-mediated signaling pathway; TAS:Reactome. 
Interpro
 IPR002466; A_deamin.
 IPR001159; Ds-RNA-bd.
 IPR014720; dsRNA-bd-like_dom.
 IPR000607; dsRNA_A_deaminase.
 IPR011991; WHTH_DNA-bd_dom. 
Pfam
 PF02137; A_deamin
 PF00035; dsrm
 PF02295; z-alpha 
SMART
 SM00552; ADEAMc
 SM00358; DSRM
 SM00550; Zalpha 
PROSITE
 PS50141; A_DEAMIN_EDITASE
 PS50139; DRADA_REPEAT
 PS50137; DS_RBD 
PRINTS