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Protein Page:
AIRE (human)

AIRE 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. 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. Defects in AIRE are a cause of autoimmune poly- endocrinopathy candidiasis ectodermal dystrophy (APS1). An autosomal recessive 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. 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. 4 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Transcription factor
Chromosomal Location of Human Ortholog: 21q22.3
Molecular Function: chromatin binding; histone binding; protein binding; transcription cofactor activity; zinc ion binding
Biological Process: central tolerance induction to self antigen; immune response; peripheral T cell tolerance induction; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-dependent; regulation of transcription, DNA-dependent
Disease: Autoimmune Polyendocrine Syndrome, Type I, With Or Without Reversible Metaphyseal Dysplasia
Reference #:  O43918 (UniProtKB)
Alt. Names/Synonyms: AIRE; AIRE1; APECED; APECED protein; APS1; APSI; Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy protein; Autoimmune regulator; PGA1
Gene Symbols: AIRE
Molecular weight: 57,727 Da
Basal Isoelectric point: 7.53  Predict pI for various phosphorylation states
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Protein Structure Not Found.
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