Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
Symbol AIRE contributors: mct - updated : 11-07-2017
HGNC name autoimmune regulator
HGNC id 360
TYPE functioning gene
STRUCTURE 12.35 kb     14 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
text structure
  • CpG methylation in the promoter of the AIRE gene has been suggested to control its tissue-specific expression pattern (promoter hypomethylation is necessary but not sufficient for tissue-specific regulation of the AIRE gene)
  • MAPPING cloned Y linked N status confirmed
    Map cen - TMEM1 - D21S1460 - C21orf33 - D21S1912 - D21S25 - AIRE - D21S1461 - PFKL PFKL - D21S400 - TRPC7 /D21S154 - D21S171 - qter
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    14 splicing initiation site 2257 58 545 - 2009 19124002
    8 splicing initiation site 1963 - 348 weakly expressed 2009 19124002
    Rna function B cells
    Type restricted
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunethymusmedulla    Homo sapiens
    Reproductivemale systemtestis    Homo sapiens
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier lining    Homo sapiens
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immuneepithelial cell Homo sapiens
    Lymphoid/Immunelymphocyte Homo sapiens
    cell lineage
    cell lines
    at STAGE
    physiological period fetal
    Text liver
  • a N-terminal homogeneously staining region (HSR) of Sp100 and Sp140 proteins and functioning as a dimerization domain, this HSR/CARD domain together with a nuclear localization signal is sufficient to induce apoptosis
  • a DEAF-1 domain
  • two nuclear localization signals (NLS)
  • two putative DNA binding sequences referred as the SAND domain
  • a proline-rich region between
  • two PHD-type (C4-H-C3) zinc finger domains (the two PHD domains can bind to specific DNA sequence motifs), and PHD2 was required for AIRE to interact with sets of protein partners involved in chromatin structure/binding or transcription but not with those implicated in pre-mRNA processing
  • a leucine zipper motif within the first PHD domain
  • four dispersed nuclear receptor-binding LXXLL motifs
  • mono polymer homomer , heteromer , dimer , tetramer
    interspecies homolog to murine Aire
    CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    text separated from the PML bodies and colocalizing with cytoskeletal filaments
    basic FUNCTION
  • may be involved in the regulation of gene expression
  • autoimmune regulator gene, transactivating transcription through heteromeric molecular interactions regulated by homomultimerization
  • AIRE regulates gene expression by recruiting components of the transcription complex to specific regions of the genome via interactions with nuclear matrix
  • promotes the establishment of self-tolerance by regulating gene expression in the thymus
  • with PIAS1 interact functionally to regulate the activities of the target genes of AIRE
  • functions as a transcriptional regulator, and has a central role in the development of immunological tolerance
  • has a critical role in dendritic cells responses to microbial stimuli
  • able to promote ectopic gene expression from chromatin associated with histone modifications characteristic to inactive genes, and of tissue-specific genes from chromatin lacking transcriptionally active histone H3 modifications
  • may be involved in structural changes of larger chromatin regions
  • regulates the expression of differentiation-associated genes and self-renewal of embryonic stem cells
  • transcription factor involved in the presentation of tissue-restricted antigens during T-cell development in the thymus
  • transcription factor that induces the expression of a large subset of otherwise strictly tissue restricted antigens in medullary thymic epithelial cells, thereby enabling their presentation to developing T cells for negative selection
  • AIRE requires CDK9 to activate transcription elongation and co-transcriptional processing of target genes
  • has a central role in the transcriptional regulation of self-antigens in medullary thymic epithelial cells, which is necessary for negative selection of autoreactive T cells
  • the pathways behind AIRE-induced apoptosis may be directly linked to the induction of central tolerance in thymus
  • AIRE-induced cellular stress and apoptosis are associated with GAPDH translocation into the nuclei
  • impacts immunological tolerance by regulating the expression of a large set of genes in thymic medullary epithelial cells
  • multidomain protein that performs a fundamental function in the thymus and possibly in the secondary lymphoid organs: the regulation, especially in the sense of activation, of the process of gene transcription in cell lines deputed to the presentation of self-antigens to the maturing T lymphocytes
  • plays a remarkable role as a regulator of central tolerance by controlling the promiscuous expression of tissue-specific antigens in thymic medullary epithelial cells
  • fundamental role of AIRE and promiscuous gene expression (pGE), namely, central tolerance, in the predisposition to autoimmunity of Down syndrome individuals
  • key factor in thymic negative selection of autoreactive T cells by promoting the ectopic expression of tissue-specific genes in the thymic medullary epithelium
  • presence of AIRE can trigger molecular events leading to an altered chromatin landscape and the enhanced transcription of low-expressed genes
  • CELLULAR PROCESS nucleotide, transcription
    a component
    DNA DNA binding, through HSR/CARD domain and AAs R113 and K114 that are key elements involved in AIRE binding to DNA
    small molecule metal binding,
  • Zn2+
  • protein
  • AIRE gene is a downstream target for the Ets family of transcription factors
  • AIRE interacts with multiple components of the transcription complex including a novel interaction with the UBA domain protein, UBAC1
  • interaction with TP63 through a SAND domain and a transactivation domain, respectively (involvement of AIRE and TP63 in the regulation of HLA class II)
  • increases the expression of its target genes, S100A8, involucrin and insulin
  • interacting with DAXX
  • AIRE-dependent production of XCL1 mediates medullary accumulation of thymic dendritic cells and contributes to regulatory T cell development
  • interacts with proteins involved in nuclear transport, DNA-damage response, chromatin remodeling, transcription and pre-mRNA-splicing
  • correlation between the presence of AIRE and proteasomal breakdown of CCNB2, which leads us to speculate that CCNB2 could be a target of AIRE E3-ubiquitin ligase activity
  • AIRE-induced apoptosis pathway is associated with GAPDH nuclear translocation and induction of NO-induced cellular stress in AIRE-expressing cells
  • AIRE interacts with the transcriptional coactivator and acetyltransferase CREBBP and synergistically cooperates with it in transcriptional activation
  • interaction of AIRE with deacetylases complexes inhibits its transcriptional activity and is probably responsible for the instability of AIRE, which becomes more susceptible to degradation in the proteasome
  • CDK9 is required for the transition from initiation to elongation of transcription, and its AIRE interaction ensures proper expression of AIRE-responsive tissue-specific antigens in the thymus
  • promote DNA breaks via its interaction with topoisomerase 2 (TOP2A)
  • cell & other
    Other is modified post-translationally by phosphorylation and ubiquitylation
    corresponding disease(s) PGA1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    decreased AIRE expression and global thymic hypofunction in Down syndrome (Trisomy 21)
    constitutional germinal mutation      
    could specifically affect human insulin gene expression in thymic epithelial cells through INS-VNTR and subsequently induce either insulin tolerance or autoimmunity
    constitutional     --low  
    significantly reduced by 2-fold in Down syndrome thymuses compared with controls
  • to vitiligo
  • to rheumatoid arthritis
  • to melanoma
  • Variant & Polymorphism SNP
  • Ser278Arg polymorphism not associated with increased risk for alopecia areata, in German population
  • strong association between AIRE 7215C and vitiligo
  • SNPs rs1055311, rs1800520 and rs1800522 were significantly more frequent in healthy subjects than in melanoma patients
  • Candidate gene
    Therapy target