Homo sapiens Protein: AIRE | |||||||||||||||||||||||
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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.
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Gene Ontology | |||||||||||||||||||||||
Molecular Function |
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Biological Process |
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Cellular Component |
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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 |
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PFAM |
PF01342
PF03172 PF00628 |
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PRINTS |
PR01711
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PIRSF | |||||||||||||||||||||||
SMART |
SM00258
SM00249 |
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TIGRFAMs | |||||||||||||||||||||||
Post-translational Modifications | |||||||||||||||||||||||
Modification | |||||||||||||||||||||||
Cross-References | |||||||||||||||||||||||
SwissProt | O43918 | ||||||||||||||||||||||
PhosphoSite | PhosphoSite-O43918 | ||||||||||||||||||||||
TrEMBL | |||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||
Entrez Gene | 326 | ||||||||||||||||||||||
UniGene | Hs.129829 | ||||||||||||||||||||||
RefSeq | NP_000374 | ||||||||||||||||||||||
HUGO | HGNC:360 | ||||||||||||||||||||||
OMIM | 607358 | ||||||||||||||||||||||
CCDS | CCDS13706 | ||||||||||||||||||||||
HPRD | 06301 | ||||||||||||||||||||||
IMGT | |||||||||||||||||||||||
EMBL | AB006682 AB006683 AB006684 AB006685 AJ009610 AP001060 AP001754 BC137268 BC137270 CH471079 Z97990 | ||||||||||||||||||||||
GenPept | AAI37269 AAI37271 BAA23988 BAA23989 BAA23990 BAA23991 BAA23992 BAA23993 BAA95560 CAA08759 CAB10790 EAX09443 | ||||||||||||||||||||||