Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000044
UniProt IDP55265
Primary gene name(s)ADAR
Synonym gene name(s)ADAR1, DSRAD, G1P1, IFI4
Protein nameDouble-stranded RNA-specific adenosine deaminase
Protein functionCatalyzes 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. {ECO:0000269|PubMed:15556947, ECO:0000269|PubMed:15858013, ECO:0000269|PubMed:16475990, ECO:0000269|PubMed:17079286, ECO:0000269|PubMed:19605474, ECO:0000269|PubMed:19651874, ECO:0000269|PubMed:19710021, ECO:0000269|PubMed:19908260, ECO:0000269|PubMed:21289159, ECO:0000269|PubMed:22278222}.
Subcellular locationIsoform 1: Cytoplasm. Nucleus. Note=Shuttles between the cytoplasm and nucleus.;
SUBCELLULAR LOCATION: Isoform 5: Cytoplasm. Nucleus. Nucleus, nucleolus. Note=Predominantly nuclear but can shuttle between nucleus and cytoplasm. TNPO1 can mediate its nuclear import whereas XPO1 can mediate its nuclear export.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P55265
Gene Ontology
(Biological Process)
Complete annatation
adenosine to inosine editing [GO:0006382];
base conversion or substitution editing [GO:0016553];
cellular response to virus [GO:0098586];
defense response to virus [GO:0051607];
definitive hemopoiesis [GO:0060216];
erythrocyte differentiation [GO:0030218];
hematopoietic progenitor cell differentiation [GO:0002244];
hematopoietic stem cell homeostasis [GO:0061484];
innate immune response [GO:0045087];
in utero embryonic development [GO:0001701];
miRNA loading onto RISC involved in gene silencing by miRNA [GO:0035280];
mRNA processing [GO:0006397];
negative regulation of apoptotic process [GO:0043066];
negative regulation of protein kinase activity by regulation of protein phosphorylation [GO:0044387];
negative regulation of RNA interference [GO:1900369];
negative regulation of type I interferon-mediated signaling pathway [GO:0060339];
negative regulation of viral genome replication [GO:0045071];
osteoblast differentiation [GO:0001649];
positive regulation of viral genome replication [GO:0045070];
pre-miRNA processing [GO:0031054];
protein export from nucleus [GO:0006611];
protein import into nucleus [GO:0006606];
response to interferon-alpha [GO:0035455];
response to virus [GO:0009615];
somatic diversification of immune receptors via somatic mutation [GO:0002566];
type I interferon signaling pathway [GO:0060337]
Gene Ontology
(Molecular Function)
Complete annatation
DNA binding [GO:0003677];
double-stranded RNA adenosine deaminase activity [GO:0003726];
metal ion binding [GO:0046872];
poly(A RNA binding [GO:0044822]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
membrane [GO:0016020];
nucleolus [GO:0005730];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
supraspliceosomal complex [GO:0044530]
Protein-protein interaction106617
Phylogenetic treeP55265
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: 3.041398799; Folds changes 16h: 2.31871901; Tested: tested;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: HCV(r; HDV [enhances CHIKV; HIV-1; MV; VEEV; VSV; WNV; YFV]
      Viral life cycle: replication
      Mechanism related to antiviral activity: viral RNA editing; suppress PKR
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model


DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD30.6939947876740.03456667940449650.0732755262988146
AZA vs. DISU0.1433458569805860.570046209710430.954304256505839
AZA vs. IL70.1360272615474410.4777313536713720.999311006273513
AZA vs. SAHA-0.0723438295637280.7662063873919780.937635580739298
DISU vs. CD3-0.5630464301683080.1211480745218830.21670654744783
DISU vs. IL7-0.01656348230639750.9474365591295850.991194708338029
DISU vs. SAHA-0.2137791341508240.4625797624359410.800119649301005
DMSO vs. AZA0.02207480233871310.8947053634633081
DMSO vs. CD3-0.6834989137215220.03317182915365350.0681627053462729
DMSO vs. DISU-0.1231358729675030.6128792021727410.939289650701039
DMSO vs. IL70.1212676865374040.498436291319170.885914818891506
DMSO vs. SAHA-0.1004135021946150.6695108970316440.896428458525578
HIV vs. Mock in Activation0.2907600745401210.6417711214141370.999983755607037
HIV vs. Mock in Latency0.03163695708335490.8472453739169160.999834320637052
IL7 vs. CD3-0.5513445153931350.08672551904957750.169525839532393
SAHA vs. CD3-0.7903524588641110.02586353343099760.0571500658072043
SAHA vs. IL7-0.2112654920061310.3848396017543960.634412965534313
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) FALSE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK -1.33829 0.000305467
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
1.015 0.971 0.896 0.863 0.932
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1QBJ X-ray 2.1Å A/B/C=133-209.
1QGP NMR - A=125-200.
1XMK X-ray 0.9Å A=294-366.
2ACJ X-ray 2.6Å A/B/C/D=140-202.
2GXB X-ray 2.2Å A/B=140-202.
2L54 NMR - A=136-198.
2MDR NMR - A=708-801.
3F21 X-ray 2.2Å A/B/C=133-209.
3F22 X-ray 2.5Å A/B/C=133-209.
3F23 X-ray 2.7Å A/B/C=133-209.
3IRQ X-ray 2.8Å A/B/C/D=140-202.
3IRR X-ray 2.6Å A/B/C/D=140-202.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Gag-Pol complexes with 23125841
reverse transcriptase inhibited by 22104209
HIV-1 virus replication inhibited by expression of human gene 25272020
25272020
25272020
Envelope surface glycoprotein gp120 inhibits 9103436
9330696
10899322
11278278
capsid upregulates 19651874
Nef complexes with 23125841
Rev interacts with 22174317
Envelope surface glycoprotein gp120 complexes with 23125841
Envelope surface glycoprotein gp120 inhibited by 22104209
Rev regulated by 22104209
Pr55(Gag) associates with 26363218
Pr55(Gag) complexes with 23125841
capsid inhibited by 22104209
Envelope surface glycoprotein gp120 upregulates 19651874
Tat downregulates 23166591
Nef upregulates 19651874

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04623 Cytosolic DNA-sensing pathway - Homo sapiens (human)
hsa05162 Measles - Homo sapiens (human)
hsa05164 Influenza A - Homo sapiens (human)
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