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Aliases for AIRE Gene

Aliases for AIRE Gene

  • Autoimmune Regulator 2 3
  • APECED 3 4 6
  • Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy Protein 3 4
  • APS1 3 6
  • Autoimmune Regulator (Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy) 2
  • Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy 2
  • APECED Protein 4
  • AIRE1 3
  • APSI 3
  • PGA1 3

External Ids for AIRE Gene

Previous Symbols for AIRE Gene

  • APECED

Summaries for AIRE Gene

Entrez Gene Summary for AIRE Gene

  • This gene encodes a transcriptional regulator that forms nuclear bodies and interacts with the transcriptional coactivator CREB binding protein. The encoded protein plays an important role in immunity by regulating the expression of autoantigens and negative selection of autoreactive T-cells in the thymus. Mutations in this gene cause the rare autosomal-recessive systemic autoimmune disease termed autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED). [provided by RefSeq, Jun 2012]

GeneCards Summary for AIRE Gene

AIRE (Autoimmune Regulator) is a Protein Coding gene. Diseases associated with AIRE include parathyroid gland disease and autoimmune polyendocrine syndrome. Among its related pathways are Class I MHC mediated antigen processing and presentation and Primary immunodeficiency. GO annotations related to this gene include identical protein binding and transcription regulatory region DNA binding. An important paralog of this gene is TRIM28.

UniProtKB/Swiss-Prot for AIRE Gene

  • Transcriptional regulator that binds to DNA as a dimer or as a tetramer, but not as a monomer. 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. Functions as a transcriptional activator and promotes the expression of otherwise tissue-specific self-antigens in the thymus, which is important for self tolerance and the avoidance of autoimmune reactions.

Gene Wiki entry for AIRE Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for AIRE Gene

Genomics for AIRE Gene

Genomic Location for AIRE Gene

Start:
44,285,838 bp from pter
End:
44,298,648 bp from pter
Size:
12,811 bases
Orientation:
Plus strand

Genomic View for AIRE Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for AIRE Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for AIRE Gene

Regulatory Elements for AIRE Gene

Transcription factor binding sites by QIAGEN in the AIRE gene promoter:

Proteins for AIRE Gene

  • Protein details for AIRE Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O43918-AIRE_HUMAN
    Recommended name:
    Autoimmune regulator
    Protein Accession:
    O43918
    Secondary Accessions:
    • B2RP50
    • O43922
    • O43932
    • O75745

    Protein attributes for AIRE Gene

    Size:
    545 amino acids
    Molecular mass:
    57727 Da
    Quaternary structure:
    • Homodimer and homotetramer. Interacts with CREBBP. Interacts preferentially with histone H3 that is not methylated at Lys-4. Binds with lower affinity to histone H3 that is monomethylated at Lys-4. Trimethylation of histone H3 at Lys-4 or phosphorylation at Thr-3 abolish the interaction. Binds with lower affinity to histone H3 that is acetylated at Lys-4, or that is acetylated at Lys-9 or trimethylated at Lys-9. Binds histone H3 that is dimethylated at Arg-2 with very low affinity.

    Three dimensional structures from OCA and Proteopedia for AIRE Gene

    Alternative splice isoforms for AIRE Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for AIRE Gene

Proteomics data for AIRE Gene at MOPED

Post-translational modifications for AIRE Gene

  • Phosphorylated. Phosphorylation could trigger oligomerization.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for AIRE Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for AIRE Gene

Domains for AIRE Gene

Gene Families for AIRE Gene

HGNC:
  • PHF :Zinc fingers, PHD-type

UniProtKB/Swiss-Prot:

AIRE_HUMAN
Domain:
  • The L-X-X-L-L repeats may be implicated in binding to nuclear receptors:
    • O43918
  • The HSR domain is required for localization on tubular structures (N-terminal part) and for homodimerization:
    • O43918
  • Interacts via the first PHD domain with the N-terminus of histone H3 that is not methylated at Lys-4. Disruption of the first PHD domain has been shown to lead to reduced transcriptional activity and to localization of the protein mainly in the cytoplasm in small granules. While the PHD zinc fingers are necessary for the transactivation capacity of the protein, other regions also modulate this function:
    • O43918
  • Contains 1 HSR domain.:
    • O43918
  • Contains 1 SAND domain.:
    • O43918
Similarity:
  • Contains 2 PHD-type zinc fingers.:
    • O43918
genes like me logo Genes that share domains with AIRE: view

Function for AIRE Gene

Molecular function for AIRE Gene

GENATLAS Biochemistry: autoimmune regulator gene with three alternatively spliced isoforms,expressed in immunological tissues,also expressed in the cytoplasm,located in nuclear bodies separated from the PML bodies and colocalizing with cytoskeletal filaments,may be involved in the regulation of gene expression
UniProtKB/Swiss-Prot Function: Transcriptional regulator that binds to DNA as a dimer or as a tetramer, but not as a monomer. 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. Functions as a transcriptional activator and promotes the expression of otherwise tissue-specific self-antigens in the thymus, which is important for self tolerance and the avoidance of autoimmune reactions.

Gene Ontology (GO) - Molecular Function for AIRE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding IDA 11533054
GO:0001228 RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription IC --
GO:0003677 DNA binding --
GO:0003682 chromatin binding IDA 18292755
GO:0005515 protein binding IPI 17474147
genes like me logo Genes that share ontologies with AIRE: view
genes like me logo Genes that share phenotypes with AIRE: view

Animal Models for AIRE Gene

MGI Knock Outs for AIRE:

No data available for Enzyme Numbers (IUBMB) , miRNA , Transcription Factor Targeting and HOMER Transcription for AIRE Gene

Localization for AIRE Gene

Subcellular locations from UniProtKB/Swiss-Prot for AIRE Gene

Nucleus. Cytoplasm. Note=Associated with tubular structures and in discrete nuclear dots resembling ND10 nuclear bodies. May shuttle between nucleus and cytoplasm.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for AIRE Gene COMPARTMENTS Subcellular localization image for AIRE gene
Compartment Confidence
nucleus 5
cytoskeleton 4
plasma membrane 4
cytosol 3
extracellular 2
chloroplast 1
mitochondrion 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for AIRE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005622 intracellular --
GO:0005634 nucleus NAS 9398840
GO:0005737 cytoplasm IEA --
genes like me logo Genes that share ontologies with AIRE: view

Pathways for AIRE Gene

genes like me logo Genes that share pathways with AIRE: view

Pathways by source for AIRE Gene

Interacting Proteins for AIRE Gene

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)
http://string-db.org/version_10/api/image/networkList?limit=0&targetmode=proteins&caller_identity=gene_cards&network_flavor=evidence&identifiers=9606.ENSP00000291582%0d%0a9606.ENSP00000262367%0d%0a9606.ENSP00000430432%0d%0a9606.ENSP00000362649%0d%0a9606.ENSP00000350580%0d%0a9606.ENSP00000350275%0d%0a
Selected Interacting proteins: O43918-AIRE_HUMAN ENSP00000291582 for AIRE Gene via MINT STRING UniProtKB I2D

Symbol External ID(s) Details
HIST1H3D
HIST1H3H
HIST1H3J
HIST1H3A
HIST1H3B

Gene Ontology (GO) - Biological Process for AIRE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006351 transcription, DNA-templated IEA --
GO:0006355 regulation of transcription, DNA-templated IDA 18292755
GO:0006417 regulation of translation IEA --
GO:0006955 immune response TAS 9398840
GO:0006959 humoral immune response IEA --
genes like me logo Genes that share ontologies with AIRE: view

Compounds for AIRE Gene

(5) Novoseek inferred chemical compound relationships for AIRE Gene

Compound -log(P) Hits PubMed IDs
zinc 34.4 13
sb 203580 12.6 2
cytosine 4.36 2
tyrosine 0 2
serine 0 2
genes like me logo Genes that share compounds with AIRE: view

Transcripts for AIRE Gene

mRNA/cDNA for AIRE Gene

Unigene Clusters for AIRE Gene

Autoimmune regulator:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for AIRE Gene

ExUns: 1 ^ 2a · 2b ^ 3a · 3b · 3c ^ 4 ^ 5a · 5b ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15
SP1: - -
SP2:
SP3:
SP4:
SP5:

Relevant External Links for AIRE Gene

GeneLoc Exon Structure for
AIRE
ECgene alternative splicing isoforms for
AIRE

Expression for AIRE Gene

mRNA expression in normal human tissues for AIRE Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for AIRE Gene

This gene is overexpressed in Brain - Hypothalamus (10.5) and Brain - Anterior cingulate cortex (BA24) (4.2).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for AIRE Gene

SOURCE GeneReport for Unigene cluster for AIRE Gene Hs.129829

mRNA Expression by UniProt/SwissProt for AIRE Gene

O43918-AIRE_HUMAN
Tissue specificity: Widely expressed. Expressed at higher level in thymus (medullary epithelial cells and monocyte-dendritic cells), pancreas, adrenal cortex and testis. Expressed at lower level in the spleen, fetal liver and lymph nodes. Isoform 2 and isoform 3 seem to be less frequently expressed than isoform 1, if at all
genes like me logo Genes that share expressions with AIRE: view

Orthologs for AIRE Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for AIRE Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia AIRE 36
  • 98.23 (n)
  • 98.17 (a)
AIRE 37
  • 98 (a)
OneToOne
cow
(Bos Taurus)
Mammalia AIRE 36
  • 79.57 (n)
  • 76.85 (a)
AIRE 37
  • 74 (a)
OneToOne
dog
(Canis familiaris)
Mammalia AIRE 36
  • 82.98 (n)
  • 79.62 (a)
AIRE 37
  • 78 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Aire 36
  • 76.74 (n)
  • 72.43 (a)
Aire 16
Aire 37
  • 70 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia AIRE 37
  • 51 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia AIRE 37
  • 54 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Aire 36
  • 74.82 (n)
  • 71.7 (a)
chicken
(Gallus gallus)
Aves AIRE 37
  • 43 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia AIRE 37
  • 71 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii aire 36
  • 50.69 (n)
  • 38.96 (a)
aire 37
  • 35 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta bon 37
  • 8 (a)
OneToOne
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes RCO1 39
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 7 (a)
OneToOne
Species with no ortholog for AIRE:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for AIRE Gene

ENSEMBL:
Gene Tree for AIRE (if available)
TreeFam:
Gene Tree for AIRE (if available)

Paralogs for AIRE Gene

Paralogs for AIRE Gene

genes like me logo Genes that share paralogs with AIRE: view

Variants for AIRE Gene

Sequence variations from dbSNP and Humsavar for AIRE Gene

SNP ID Clin Chr 21 pos Sequence Context AA Info Type MAF
rs751032 -- 44,285,777(+) GTCCC(C/T)GCGGG upstream-variant-2KB
rs760426 -- 44,295,931(+) GTTCA(A/G)TGTAA intron-variant
rs760427 -- 44,296,108(+) TTGCT(A/G)GTTCC intron-variant
rs878080 -- 44,288,138(+) CACAC(A/T)TGGGT intron-variant
rs878081 Likely benign 44,288,394(+) TCCTC(C/T)GGGGA reference, synonymous-codon, upstream-variant-2KB

Structural Variations from Database of Genomic Variants (DGV) for AIRE Gene

Variant ID Type Subtype PubMed ID
esv33817 CNV Loss 17666407
nsv913898 CNV Loss 21882294
nsv913902 CNV Loss 21882294
nsv913906 CNV Loss 21882294
nsv913907 CNV Loss 21882294
esv2723638 CNV Deletion 23290073
dgv4768n71 CNV Loss 21882294
dgv4769n71 CNV Loss 21882294
dgv4770n71 CNV Loss 21882294
nsv913912 CNV Loss 21882294
dgv4771n71 CNV Loss 21882294
nsv913915 CNV Loss 21882294
dgv4772n71 CNV Loss 21882294
dgv4773n71 CNV Loss 21882294
nsv913923 CNV Loss 21882294
dgv4774n71 CNV Loss 21882294
nsv509800 CNV Insertion 20534489
nsv526673 CNV Loss 19592680

Relevant External Links for AIRE Gene

HapMap Linkage Disequilibrium report
AIRE
Human Gene Mutation Database (HGMD)
AIRE
Locus Specific Mutation Databases (LSDB)
AIRE

Disorders for AIRE Gene

(1) OMIM Diseases for AIRE Gene (607358)

UniProtKB/Swiss-Prot

AIRE_HUMAN
  • Autoimmune polyendocrine syndrome 1, with or without reversible metaphyseal dysplasia (APS1) [MIM:240300]: A rare disease characterized by the combination of chronic mucocutaneous candidiasis, hypoparathyroidism and Addison disease. Symptoms of mucocutaneous candidiasis manifest first, followed by hypotension or fatigue occurring as a result of Addison disease. APS1 is associated with other autoimmune disorders including diabetes mellitus, vitiligo, alopecia, hepatitis, pernicious anemia and primary hypothyroidism. {ECO:0000269 PubMed:10677297, ECO:0000269 PubMed:11275943, ECO:0000269 PubMed:11524731, ECO:0000269 PubMed:11524733, ECO:0000269 PubMed:11600535, ECO:0000269 PubMed:11836330, ECO:0000269 PubMed:12050215, ECO:0000269 PubMed:12173302, ECO:0000269 PubMed:12625412, ECO:0000269 PubMed:15712268, ECO:0000269 PubMed:9398839, ECO:0000269 PubMed:9888391}. Note=The disease is caused by mutations affecting the gene represented in this entry. Most of the mutations alter the nucleus-cytoplasm distribution of AIRE and disturb its association with nuclear dots and cytoplasmic filaments. Most of the mutations also decrease transactivation of the protein. The HSR domain is responsible for the homomultimerization activity of AIRE. All the missense mutations of the HSR and the SAND domains decrease this activity, but those in other domains do not. The AIRE protein is present in soluble high-molecular-weight complexes. Mutations in the HSR domain and deletion of PHD zinc fingers disturb the formation of these complexes (PubMed:14974083). {ECO:0000269 PubMed:14974083}.

(35) Novoseek inferred disease relationships for AIRE Gene

Disease -log(P) Hits PubMed IDs
apeced 99.1 161
polyendocrinopathies autoimmune 97.8 38
candidiasis chronic mucocutaneous 94.7 4
hypoparathyroidism 89.4 8
addisons disease 88.8 9

Relevant External Links for AIRE

Genetic Association Database (GAD)
AIRE
Human Genome Epidemiology (HuGE) Navigator
AIRE
genes like me logo Genes that share disorders with AIRE: view

Publications for AIRE Gene

  1. Localization of the APECED protein in distinct nuclear structures. (PMID: 9931333) Bjoerses P. … Ulmanen I. (Hum. Mol. Genet. 1999) 3 4 23
  2. Mutations in the AIRE gene: effects on subcellular location and transactivation function of the autoimmune polyendocrinopathy- candidiasis-ectodermal dystrophy protein. (PMID: 10677297) Bjeorses P. … Peltonen L. (Am. J. Hum. Genet. 2000) 3 4 23
  3. Subcellular localization of the autoimmune regulator protein. characterization of nuclear targeting and transcriptional activation domain. (PMID: 11274163) Pitkaenen J. … Peterson P. (J. Biol. Chem. 2001) 3 4 23
  4. Identification of a novel mutation in the autoimmune regulator (AIRE- 1) gene in a French family with autoimmune polyendocrinopathy- candidiasis-ectodermal dystrophy. (PMID: 11275943) Saugier-Veber P. … Lefebvre H. (Eur. J. Endocrinol. 2001) 3 4 23
  5. Screening for an AIRE-1 mutation in patients with Addison's disease, type 1 diabetes, Graves' disease and Hashimoto's thyroiditis as well as in APECED syndrome. (PMID: 11298085) Meyer G. … Badenhoop K. (Clin. Endocrinol. (Oxf) 2001) 3 23 49

Products for AIRE Gene

Sources for AIRE Gene

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