UniProt:P55265 ADAR

chain
  • chain:1-1226
checksum 9CE095D6F9C1BC79
comment
  • FUNCTION Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing (PubMed:12618436, PubMed:7565688, PubMed:7972084). 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 since the translational machinery read the inosine as a guanosine; 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.CATALYTIC ACTIVITY adenosine in double-stranded RNA + H2O + H(+) = inosine in double-stranded RNA + NH4(+)SUBUNIT Homodimer. Homodimerization is essential for its catalytic activity (PubMed:12618436). Isoform 5 can form heterodimers with ADARB1/ADAR2. 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 (via DRBM 3 domain) interact with TNPO1 (PubMed:19124606, PubMed:24753571). Isoform 5 (via DRBM domains) interacts with XPO5 (PubMed:19124606). Isoform 1 and isoform 5 can interact with EIF2AK2/PKR and UPF1 (PubMed:17079286, PubMed:18362360).INTERACTION Shuttles between the cytoplasm and nucleus (PubMed:24753571, PubMed:7565688). Nuclear import is mediated by TNPO1 (PubMed:24753571).SUBCELLULAR LOCATION Predominantly nuclear but can shuttle between nucleus and cytoplasm. TNPO1 can mediate its nuclear import whereas XPO5 can mediate its nuclear export.ALTERNATIVE PRODUCTS Ubiquitously expressed, highest levels were found in brain and lung (PubMed:7972084). Isoform 5 is expressed at higher levels in astrocytomas as compared to normal brain tissue and expression increases strikingly with the severity of the tumor, being higher in the most aggressive tumors.INDUCTION Isoform 1 is induced by interferon alpha. Isoform 5 is constitutively expressed.DOMAIN 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 (PubMed:24753571). RNA binding interferes with nuclear import (PubMed:19124606, PubMed:24753571).DOMAIN The first Z-binding domain binds Z-DNA.PTM Sumoylation reduces RNA-editing activity.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS Produced by alternative promoter usage.MISCELLANEOUS Produced by alternative splicing of isoform 1.MISCELLANEOUS Produced by alternative splicing of isoform 1.MISCELLANEOUS Produced by alternative splicing of isoform 1.MISCELLANEOUS Produced by alternative promoter usage.CAUTION The N-terminus of isoform 4 has been derived from EST and genomic sequences.SEQUENCE CAUTION Extended C-terminus.
crossReference
databaseName UniProt
dbId 72209
description
  • recommendedName: Double-stranded RNA-specific adenosine deaminase shortName evidence="40"DRADA ecNumber evidence="35 36"3.5.4.37 alternativeName: 136 kDa double-stranded RNA-binding protein shortName: p136 alternativeName: Interferon-inducible protein 4 shortName: IFI-4 alternativeName: K88DSRBP
displayName UniProt:P55265 ADAR
geneName
  • ADAR
  • ADAR1
  • DSRAD
  • G1P1
  • IFI4
identifier P55265
isSequenceChanged false
keyword
  • 3D-structure
  • Aicardi-Goutieres syndrome
  • Alternative promoter usage
  • Alternative splicing
  • Antiviral defense
  • Cytoplasm
  • Direct protein sequencing
  • Disease variant
  • DNA-binding
  • Hydrolase
  • Immunity
  • Innate immunity
  • Isopeptide bond
  • Metal-binding
  • Methylation
  • mRNA processing
  • Nucleus
  • Phosphoprotein
  • Proteomics identification
  • Reference proteome
  • Repeat
  • RNA-binding
  • RNA-mediated gene silencing
  • Ubl conjugation
  • Zinc
modified [InstanceEdit:9939033] Weiser, Joel, 2025-02-21
moleculeType Protein
name
  • ADAR
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • DSRAD_HUMAN
  • B1AQQ9
  • B1AQR0
  • D3DV76
  • O15223
  • O43859
  • O43860
  • Q9BYM3
  • Q9BYM4
sequenceLength 1226
species [Species:48887] Homo sapiens
stId uniprot:P55265
url http://purl.uniprot.org/uniprot/P55265
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