ADAR - Double-stranded RNA-specific adenosine deaminase - human protein (Function)
 
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ADAR »  Double-stranded RNA-specific adenosine deaminase   [ EC 3.5.4.37 ]  (DRADA)
 
Protein also known as:  136 kDa double-stranded RNA-binding protein (p136).
Gene name:  ADAR
Entry whose protein(s) existence is based on evidence at protein level
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1 157 5
GENE REF ISO

Function

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Overview 
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.  
10
  • CuratedUniProtKB
GO molecular function 
DNA bindingdefinition[GO:0003677]  
  • IEAUniProtKB KW
Double-stranded RNA adenosine deaminase activitydefinition[GO:0003726]  
2
  • IDAMGI
  • NASUniProtKB
Metal ion bindingdefinition[GO:0046872]  
  • IEAUniProtKB KW
Poly(A) RNA bindingdefinition[GO:0044822]  
2
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
4
  • IPIIntAct
  • IPIUniProtKB
GO biological process 
Adenosine to inosine editingdefinition[GO:0006382]  
4
  • IDAUniProtKB
Base conversion or substitution editingdefinition[GO:0016553]  
1
  • IDAMGI
Defense response to virusdefinition[GO:0051607]  
  • IEAUniProtKB KW
Gene silencing by RNAdefinition[GO:0031047]  
  • IEAUniProtKB KW
Innate immune responsedefinition[GO:0045087]  
1
  • TASUniProtKB
mRNA processingdefinition[GO:0006397]  
  • IEAUniProtKB KW
Negative regulation of apoptotic processdefinition[GO:0043066] silver  
  • IEAOrtholog Compara
Negative regulation of protein kinase activity by regulation of protein phosphorylationdefinition[GO:0044387]  
2
  • IDAUniProtKB
Positive regulation of viral genome replicationdefinition[GO:0045070]  
2
  • IDAUniProtKB
Isoform  Iso 5   Protein export from nucleusdefinition[GO:0006611]  
1
  • IDAUniProtKB
Isoform  Iso 5   Protein import into nucleusdefinition[GO:0006606]  
1
  • IDAUniProtKB
Response to interferon-alphadefinition[GO:0035455]  
1
  • IDAUniProtKB
Response to virusdefinition[GO:0009615]  
1
  • IMPUniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 3.5.4.37: Adenine in double-stranded RNA + H(2)O hypoxanthine in double-stranded RNA + NH(3).  
  • CuratedUniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathways:
Cytosolic DNA-sensing pathway  hsa04623+103  
Influenza A  hsa05164+103  
Measles  hsa05162+103  
According to Reactome, this protein belongs to the following pathways:
C6 deamination of adenosine  REACT_1231  
Formation of editosomes by ADAR proteins  REACT_1966  
Interferon alpha/beta signaling  REACT_25162  
Caution 
The N-terminus of isoform 4 has been derived from EST and genomic sequences.  
  • CuratedUniProtKB
 

Keywords

Biological process 
Antiviral defense  definition   [KW-0051]
Immunity  definition   [KW-0391]
Innate immunity  definition   [KW-0399]
RNA-mediated gene silencing  definition   [KW-0943]
mRNA processing  definition   [KW-0507]
Molecular function 
Hydrolase  definition   [KW-0378]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: ADAR
GenomeRNAi: 103
PRO: PR:P55265