Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0008483
UniProt IDO43918
Primary gene name(s)AIRE
Synonym gene name(s)APECED
Protein nameAutoimmune regulator
Protein functionTranscription factor playing an essential role to promote self-tolerance in the thymus by regulating the expression of a wide array of self-antigens that have the commonality of being tissue-restricted in their expression pattern in the periphery, called tissue restricted antigens, TRA, PubMed:26084028. Binds to G-doublets in an A/T-rich environment; the preferred motif is a tandem repeat of 5'-ATTGGTTA-3' combined with a 5'-TTATTA-3' box. Binds to nucleosomes, By similarity. Binds to chromatin and interacts selectively with histone H3 that is not methylated at 'Lys-4', not phosphorylated at 'Thr-3' and not methylated at 'Arg-2'. Functions as a sensor of histone H3 modifications that are important for the epigenetic regulation of gene expression. Mainly expressed by medullary thymic epithelial cells, mTECs, induces the expression of thousands of tissue-restricted proteins, which are presented on major histocompatibility complex class I, MHC-I and MHC-II molecules to developing T-cells percolating through the thymic medulla, PubMed:26084028. Also induces self-tolerance through other mechanisms such as the regulation of the mTEC differentiation program. Controls the medullary accumulation of thymic dendritic cells and the development of regulatory T-cell through the regulation of XCL1 expression. Regulates the production of CCR4 and CCR7 ligands in medullary thymic epithelial cells and alters the coordinated maturation and migration of thymocytes. In thimic B-cells, allows the presentation of licensing-dependent endogenous self-anitgen for negative selection. In secondary lymphoid organs, induces functional inactivation of CD4(+ T-cells. Expressed by a distinct bone marrow-derived population, induces self-tolerance through a mechanism that does not require regulatory T-cells and is resitant to innate inflammatory stimuli, By similarity. {ECO:0000250|UniProtKB:Q9Z0E3, ECO:0000269|PubMed:11274163, ECO:0000269|PubMed:18292755, ECO:0000269|PubMed:26084028, ECO:0000305|PubMed:19302042, ECO:0000305|PubMed:26972725}.
Subcellular locationNucleus {ECO:0000269|PubMed:14974083, ECO:0000269|PubMed:26084028}. Cytoplasm {ECO:0000269|PubMed:11274163, ECO:0000269|PubMed:14974083}. Note=Predominantly nuclear but also cytoplasmic, PubMed:11274163, PubMed:14974083. Found in nuclear body-like structures, dots and in a filamentous vimentin-like pattern, PubMed:11274163, PubMed:14974083, PubMed:26084028. Associated with tubular structures, PubMed:11274163, PubMed:14974083. {ECO:0000269|PubMed:11274163, ECO:0000269|PubMed:14974083, ECO:0000269|PubMed:26084028}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O43918
Gene Ontology
(Biological Process)
Complete annatation
central tolerance induction to self antigen [GO:0002509];
chemokine production [GO:0032602];
humoral immune response [GO:0006959];
immune response [GO:0006955];
negative thymic T cell selection [GO:0045060];
peripheral T cell tolerance induction [GO:0002458];
positive regulation of transcription, DNA-templated [GO:0045893];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
regulation of thymocyte migration [GO:2000410];
regulation of transcription, DNA-templated [GO:0006355];
thymus epithelium morphogenesis [GO:0097536]
Gene Ontology
(Molecular Function)
Complete annatation
chromatin binding [GO:0003682];
histone binding [GO:0042393];
RNA polymerase II regulatory region sequence-specific DNA binding [GO:0000977];
transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding [GO:0001228];
transcription cofactor activity [GO:0003712];
transcription regulatory region DNA binding [GO:0044212];
translation regulator activity [GO:0045182];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
nucleus [GO:0005634]
Protein-protein interaction106823
Phylogenetic treeO43918
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: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
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. CD3-8.5572518718848200
AZA vs. DISU-0.4482388780120590.5109322230582170.938109377229618
AZA vs. IL7-0.02572890305258550.9429199029695870.999311006273513
AZA vs. SAHA-2.986080402308890.0005542077705864570.0137856896597694
DISU vs. CD38.247433917703591.59205981731247e-136.39965591631153e-12
DISU vs. IL70.4114306822684550.5486323374719530.852740924511229
DISU vs. SAHA-2.533169669639570.02333098725699070.17839741702187
DMSO vs. AZA0.2174921251274010.5187575529051981
DMSO vs. CD38.7201095466454800
DMSO vs. DISU0.6650700079874540.3138373201663580.817839427928817
DMSO vs. IL7-0.2365189051858750.4310718713432780.858231939149073
DMSO vs. SAHA-3.206873149383940.0001367502503586420.00448035439816323
HIV vs. Mock in Activationunknownunknownunknown
HIV vs. Mock in Latency0.8672963557721390.004568642935716790.192906788831919
IL7 vs. CD38.4502173710438400
SAHA vs. CD35.568505573525052.17443227390479e-061.63125045081973e-05
SAHA vs. IL7-2.959378787220990.000326242539215760.00495244716630248
(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
-0.4793 0.01647

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) unknown
(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
NOTEST -0.423083 1
(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
unknown unknown unknown unknown unknown
(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
1XWH NMR - A=293-354.
2KE1 NMR - A=293-354.
2KFT NMR - A=294-347.
2LRI NMR - C=423-485.

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

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
hsa05340 Primary immunodeficiency - Homo sapiens (human)
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