AIRE
entrez
326
canonical
uniprot
O43918
canonical
ensembl
ENSG00000160224
resolver
ensp
ENSP00000291582
resolver
genesymbol
AIRE
resolver
genesymbol_syn
APECED
resolver
hgnc
HGNC:360
resolver
uniprot
B2RP50
resolver
uniprot
O43922
resolver
uniprot
O43932
resolver
uniprot
O75745
resolver
uniprot_entry
AIRE_HUMAN
resolver
uniprot_sec
B2RP50
resolver
uniprot_sec
O43922
resolver
uniprot_sec
O43932
resolver
uniprot_sec
O75745
resolver
amino_acid_sequence
MATDAALRRLLRLHRTEIAVAVDSAFPLLHALADHDVVPEDKFQETLHLKEKEGCPQAFHALLSWLLTQDSTAILDFWRVLFKDYNLERYGRLQPILDSFPKDVDLSQPRKGRKPPAVPKALVPPPRLPTKRKASEEARAAAPAALTPRGTASPGSQLKAKPPKKPESSAEQQRLPLGNGIQTMSASVQRAVAMSSGDVPGARGAVEGILIQQVFESGGSKKCIQVGGEFYTPSKFEDSGSGKNKARSSSGPKPLVRAKGAQGAAPGGGEARLGQQGSVPAPLALPSDPQLHQKNEDECAVCRDGGELICCDGCPRAFHLACLSPPLREIPSGTWRCSSCLQATVQEVQPRAEEPRPQEPPVETPLPPGLRSAGEEVRGPPGEPLAGMDTTLVYKHLPAPPSAAPLPGLDSSALHPLLCVGPEGQQNLAPGARCGVCGDGTDVLRCTHCAAAFHWRCHFPAGTSRPGTGLRCRSCSGDVTPAPVEGVLAPSPARLAPGPAKDDTASHEPALHRDDLESLLSEHTFDGILQWAIQSMARPAAPFPS
uniprot
proteins
disease_involvement
DISEASE: 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:11274163, 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:14974083, ECO:0000269|PubMed:15649886, ECO:0000269|PubMed:15712268, ECO:0000269|PubMed:16114041, ECO:0000269|PubMed:18292755, ECO:0000269|PubMed:19446523, ECO:0000269|PubMed:26084028, ECO:0000269|PubMed:27426947, ECO:0000269|PubMed:9398839, ECO:0000269|PubMed:9888391}. Note=The disease is caused by variants 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). Heterozygous mutations within the PHD1 domain have dominant-negative effects and cause organ-specific autoimmune diseases (PubMed:26084028). Patients harbor extremely high-affinity, neutralizing autoantibodies, particularly against specific cytokines such as type I interferons which could protect them from some types of autoimmune diseases, like type I diabetes (PubMed:27426947). {ECO:0000269|PubMed:14974083, ECO:0000269|PubMed:26084028, ECO:0000269|PubMed:27426947}.
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:Q9Z0E3, ECO:0000269|PubMed:11274163, ECO:0000269|PubMed:18292755, ECO:0000269|PubMed:26084028, ECO:0000305|PubMed:19302042, ECO:0000305|PubMed:26972725}.
uniprot
proteins
mass_dalton
57727
uniprot
proteins
mutagenesis
MUTAGEN 28..29; /note="LL->PP: Loss of doted nuclear location, forms nuclear smears. Loss of transactivation activity on target genes transcription."; /evidence="ECO:0000269|PubMed:26084028"; MUTAGEN 97; /note="L->P: Loss of transactivation activity on target gene transcription; no dominant-negative effect on target gene transcription. Loss of doted nuclear localization."; /evidence="ECO:0000269|PubMed:26084028"; MUTAGEN 295; /note="N->A: Abolishes interaction with histone H3."; /evidence="ECO:0000269|PubMed:19293276"; MUTAGEN 297; /note="D->A: Strongly reduces interaction with unmethylated histone H3 and abolishes interaction with histone H3 trimethylated at 'Lys-4'. No effect on doted nuclear localization. Dominant-negative effect on target gene transcription."; /evidence="ECO:0000269|PubMed:18292755, ECO:0000269|PubMed:26084028"; MUTAGEN 298; /note="E->A: Reduces interaction with histone H3."; /evidence="ECO:0000269|PubMed:19293276"; MUTAGEN 302; /note="C->P: Reduces transcriptional activation."; /evidence="ECO:0000269|PubMed:11274163"; MUTAGEN 303; /note="R->P: Alters protein folding and abolishes interaction with histone H3. No effect on doted nuclear localization. Dominant-negative effect on target gene transcription."; /evidence="ECO:0000269|PubMed:19293276, ECO:0000269|PubMed:26084028"; MUTAGEN 304; /note="D->A: Strongly reduces interaction with histone H3."; /evidence="ECO:0000269|PubMed:19293276"; MUTAGEN 307; /note="E->A: Reduces interaction with histone H3."; /evidence="ECO:0000269|PubMed:19293276"; MUTAGEN 312; /note="D->A: Abolishes interaction with histone H3."; /evidence="ECO:0000269|PubMed:18292755"; MUTAGEN 312; /note="D->N: No effect on doted nuclear localization. Dominant-negative effect on target gene transcription."; /evidence="ECO:0000269|PubMed:26084028"; MUTAGEN 437; /note="C->P: Reduces transcription activation."; /evidence="ECO:0000269|PubMed:11274163"; MUTAGEN 446; /note="C->G: Dominant-negative effect on regulation of target gene transcription."; /evidence="ECO:0000269|PubMed:26084028"; MUTAGEN 471; /note="R->C: No effect on regulation of target gene transcription."; /evidence="ECO:0000269|PubMed:26084028
uniprot
proteins
post_translational_modification
PTM: Phosphorylated. Phosphorylation could trigger oligomerization. {ECO:0000269|PubMed:11533054}.
uniprot
proteins
pubmed
10677297
uniprot
proteins
pubmed
10830953
uniprot
proteins
pubmed
11274163
uniprot
proteins
pubmed
11275943
uniprot
proteins
pubmed
11524731
uniprot
proteins
pubmed
11524733
uniprot
proteins
pubmed
11533054
uniprot
proteins
pubmed
11600535
uniprot
proteins
pubmed
11836330
uniprot
proteins
pubmed
12050215
uniprot
proteins
pubmed
12173302
uniprot
proteins
pubmed
12625412
uniprot
proteins
pubmed
14974083
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15649886
uniprot
proteins
pubmed
15712268
uniprot
proteins
pubmed
16114041
uniprot
proteins
pubmed
18292755
uniprot
proteins
pubmed
19293276
uniprot
proteins
pubmed
19302042
uniprot
proteins
pubmed
19446523
uniprot
proteins
pubmed
23993652
uniprot
proteins
pubmed
26084028
uniprot
proteins
pubmed
26972725
uniprot
proteins
pubmed
27426947
uniprot
proteins
pubmed
9398839
uniprot
proteins
pubmed
9398840
uniprot
proteins
pubmed
9717837
uniprot
proteins
pubmed
9888391
uniprot
proteins
pubmed
9931333
uniprot
proteins
sequence_length
545
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14974083, ECO:0000269|PubMed:26084028}. Cytoplasm {ECO:0000269|PubMed:11274163, ECO:0000269|PubMed:14974083}. 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). {ECO:0000269|PubMed:11274163, ECO:0000269|PubMed:14974083, ECO:0000269|PubMed:26084028}.
uniprot
proteins