InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: AIRE

Summary

InnateDB Protein

IDBP-5154.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

AIRE

Protein Name

autoimmune regulator

Synonyms

AIRE1; APECED; APS1; APSI; PGA1;

Species

Homo sapiens

Ensembl Protein

ENSP00000291582

InnateDB Gene

IDBG-5152 (AIRE)

Protein Structure

UniProt Annotation

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. {ECO:0000250, ECO:0000269PubMed:11274163, ECO:0000269PubMed:18292755}.

Subcellular Localization

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

Disease Associations

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:0000269PubMed:10677297, ECO:0000269PubMed:11275943, ECO:0000269PubMed:11524731, ECO:0000269PubMed:11524733, ECO:0000269PubMed:11600535, ECO:0000269PubMed:11836330, ECO:0000269PubMed:12050215, ECO:0000269PubMed:12173302, ECO:0000269PubMed:12625412, ECO:0000269PubMed:15712268, ECO:0000269PubMed:9398839, ECO:0000269PubMed: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:0000269PubMed:14974083}.

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.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 80 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	80 [view]
Protein-Protein	80 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0003682	chromatin binding
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0042393	histone binding
GO:0042802	identical protein binding
GO:0044212	transcription regulatory region DNA binding
GO:0045182	translation regulator activity

Biological Process

GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0006417	regulation of translation
GO:0006955	immune response
GO:0006959	humoral immune response
GO:0045087	innate immune response (InnateDB)
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter

Cellular Component

GO:0005622	intracellular
GO:0005634	nucleus
GO:0005737	cytoplasm

Protein Structure and Domains

PDB ID

InterPro

IPR000770 SAND domain
IPR001965 Zinc finger, PHD-type
IPR004865 Sp100
IPR008087 Autoimmune regulator, AIRE
IPR010919 SAND domain-like
IPR011011 Zinc finger, FYVE/PHD-type
IPR019787 Zinc finger, PHD-finger

PFAM

PF01342
PF03172
PF00628

PRINTS

PR01711

PIRSF

SMART

SM00258
SM00249

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt