Browse AIRE

Summary
SymbolAIRE
Nameautoimmune regulator
Aliases PGA1; autoimmune polyendocrinopathy candidiasis ectodermal dystrophy; APECED; autoimmune regulator (autoimmu ......
Chromosomal Location21q22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Nucleus Cytoplasm 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).
Domain PF03172 HSR domain
PF00628 PHD-finger
PF01342 SAND domain
Function

Transcription 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).

> Gene Ontology
 
Biological Process GO:0002521 leukocyte differentiation
GO:0006417 regulation of translation
GO:0006959 humoral immune response
GO:0007159 leukocyte cell-cell adhesion
GO:0010608 posttranscriptional regulation of gene expression
GO:0030098 lymphocyte differentiation
GO:0030217 T cell differentiation
GO:0033077 T cell differentiation in thymus
GO:0034248 regulation of cellular amide metabolic process
GO:0042110 T cell activation
GO:0043383 negative T cell selection
GO:0045058 T cell selection
GO:0045060 negative thymic T cell selection
GO:0045061 thymic T cell selection
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0071593 lymphocyte aggregation
GO:0071594 thymocyte aggregation
Molecular Function GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0003682 chromatin binding
GO:0042393 histone binding
GO:0045182 translation regulator activity
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04120 Ubiquitin mediated proteolysis
Reactome -
Summary
SymbolAIRE
Nameautoimmune regulator
Aliases PGA1; autoimmune polyendocrinopathy candidiasis ectodermal dystrophy; APECED; autoimmune regulator (autoimmu ......
Chromosomal Location21q22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between AIRE and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between AIRE and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
23370329MelanomaInhibit immunityIn this study, we show that Aire deficiency decreases thymic expression of TRP-1 (TYRP1), which is a self-antigen in melanocytes and a cancer antigen in melanomas. Aire deficiency resulted in defective negative selection of TRP-1-specific T cells without affecting thymic numbers of regulatory T cells.
Summary
SymbolAIRE
Nameautoimmune regulator
Aliases PGA1; autoimmune polyendocrinopathy candidiasis ectodermal dystrophy; APECED; autoimmune regulator (autoimmu ......
Chromosomal Location21q22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of AIRE in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolAIRE
Nameautoimmune regulator
Aliases PGA1; autoimmune polyendocrinopathy candidiasis ectodermal dystrophy; APECED; autoimmune regulator (autoimmu ......
Chromosomal Location21q22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of AIRE in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.1160.485
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.190.732
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.0580.877
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.0580.924
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.4160.673
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.6630.554
729033130MelanomaallAnti-PD-1 (nivolumab) 262301
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 151101
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 111201
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 4801
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 2801
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.1560.536
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of AIRE in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14177.107.10.452
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 103100101
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277302.7-2.71
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275903.4-3.41
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21179.509.50.492
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)86250250.473
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38275.33.71.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.57.7-3.21
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.206.21
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolAIRE
Nameautoimmune regulator
Aliases PGA1; autoimmune polyendocrinopathy candidiasis ectodermal dystrophy; APECED; autoimmune regulator (autoimmu ......
Chromosomal Location21q22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of AIRE. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolAIRE
Nameautoimmune regulator
Aliases PGA1; autoimmune polyendocrinopathy candidiasis ectodermal dystrophy; APECED; autoimmune regulator (autoimmu ......
Chromosomal Location21q22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of AIRE. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by AIRE.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolAIRE
Nameautoimmune regulator
Aliases PGA1; autoimmune polyendocrinopathy candidiasis ectodermal dystrophy; APECED; autoimmune regulator (autoimmu ......
Chromosomal Location21q22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of AIRE. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolAIRE
Nameautoimmune regulator
Aliases PGA1; autoimmune polyendocrinopathy candidiasis ectodermal dystrophy; APECED; autoimmune regulator (autoimmu ......
Chromosomal Location21q22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of AIRE expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolAIRE
Nameautoimmune regulator
Aliases PGA1; autoimmune polyendocrinopathy candidiasis ectodermal dystrophy; APECED; autoimmune regulator (autoimmu ......
Chromosomal Location21q22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between AIRE and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolAIRE
Nameautoimmune regulator
Aliases PGA1; autoimmune polyendocrinopathy candidiasis ectodermal dystrophy; APECED; autoimmune regulator (autoimmu ......
Chromosomal Location21q22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting AIRE collected from DrugBank database.
> Drugs from DrugBank database
 

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