Autoimmune Regulator (AIRE)

AIRE1; APECED; APS1; APSI; PGA1; Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy

SPN	U523
HGNC	360
MGI	1338803
PubMed	11524731
RGD	1311139
UniProt	O43918
Wiki	AIRE

The Autoimmune Regulator is expressed in the thymus. It causes transcription of a wide selection of organ-specific genes. This reduces the threat of autoimmunity occurring by allowing the elimination of autoreactive T cells by the process of negative selection if they are too reactive to self. It is mutated in the rare autoimmune syndrome Autoimmune Polyendocrinopathy Syndrome type 1 (APS-1), also known as Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED). Disruption of AIRE results in the development of a range of autoimmune diseases, the most common clinical conditions in the syndrome are hypoparathyroidism, primary adrenocortical failure and chronic mucocutaneous candidiasis. AIRE is expressed primarily in the thymus.

Reference

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Nat. Genet. 17:393-398(1997) [PubMed] [Europe PMC] [Abstract]

"An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains."
Nat. Genet. 17:399-403(1997) [PubMed] [Europe PMC] [Abstract]

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Nature 405:311-319(2000) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Localization of the APECED protein in distinct nuclear structures."
Hum. Mol. Genet. 8:259-266(1999) [PubMed] [Europe PMC] [Abstract]

"The autoimmune regulator (AIRE) is a DNA-binding protein."
J. Biol. Chem. 276:41357-41364(2001) [PubMed] [Europe PMC] [Abstract]

"Mutations in the AIRE gene: effects on subcellular location and transactivation function of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protein."
Am. J. Hum. Genet. 66:378-392(2000) [PubMed] [Europe PMC] [Abstract]

"Subcellular localization of the autoimmune regulator protein. characterization of nuclear targeting and transcriptional activation domain."
J. Biol. Chem. 276:19597-19602(2001) [PubMed] [Europe PMC] [Abstract]

"APECED-causing mutations in AIRE reveal the functional domains of the protein."
Hum. Mutat. 23:245-257(2004) [PubMed] [Europe PMC] [Abstract]

"The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression."
EMBO Rep. 9:370-376(2008) [PubMed] [Europe PMC] [Abstract]

"NMR structure of the first PHD finger of autoimmune regulator protein (AIRE1). Insights into autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) disease."
J. Biol. Chem. 280:11505-11512(2005) [PubMed] [Europe PMC] [Abstract]

"The solution structure of the first PHD finger of autoimmune regulator in complex with non-modified histone H3 tail reveals the antagonistic role of H3R2 methylation."
Nucleic Acids Res. 37:2951-2961(2009) [PubMed] [Europe PMC] [Abstract]

"Structure and site-specific recognition of histone H3 by the PHD finger of human autoimmune regulator."
Structure 17:670-679(2009) [PubMed] [Europe PMC] [Abstract]

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Hum. Mutat. 13:69-74(1999) [PubMed] [Europe PMC] [Abstract]

"Common mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients of different origins."
Mol. Endocrinol. 12:1112-1119(1998) [PubMed] [Europe PMC] [Abstract]

"Identification of a novel mutation in the autoimmune regulator (AIRE-1) gene in a French family with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy."
Eur. J. Endocrinol. 144:347-351(2001) [PubMed] [Europe PMC] [Abstract]

"APECED mutations in the autoimmune regulator (AIRE) gene."
Hum. Mutat. 18:205-211(2001) [PubMed] [Europe PMC] [Abstract]

"Novel AIRE mutations and P450 cytochrome autoantibodies in Central and Eastern European patients with APECED."
Hum. Mutat. 18:225-232(2001) [PubMed] [Europe PMC] [Abstract]

"A novel mutation of the autoimmune regulator gene in an Italian kindred with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, acting in a dominant fashion and strongly cosegregating with hypothyroid autoimmune thyroiditis."
J. Clin. Endocrinol. Metab. 86:4747-4752(2001) [PubMed] [Europe PMC] [Abstract]

"Distinct clinical phenotype and immunoreactivity in Japanese siblings with autoimmune polyglandular syndrome type 1 (APS-1) associated with compound heterozygous novel AIRE gene mutations."
Clin. Immunol. 103:277-283(2002) [PubMed] [Europe PMC] [Abstract]

"A novel missense mutation of AIRE gene in a patient with autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy (APECED), accompanied with progressive muscular atrophy: case report and review of the literature in Japan."
Endocr. J. 49:625-633(2002) [PubMed] [Europe PMC] [Abstract]

"Delineation of the molecular defects in the AIRE gene in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients from Southern Italy."
J. Clin. Endocrinol. Metab. 87:841-846(2002) [PubMed] [Europe PMC] [Abstract]

"AIRE mutations and human leukocyte antigen genotypes as determinants of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy phenotype."
J. Clin. Endocrinol. Metab. 87:2568-2574(2002) [PubMed] [Europe PMC] [Abstract]

"Two novel mutations of the AIRE protein affecting its homodimerization properties."
Hum. Mutat. 25:319-319(2005) [PubMed] [Europe PMC] [Abstract]

"Functional analysis of SAND mutations in AIRE supports dominant inheritance of the G228W mutation."
Hum. Mutat. 26:322-331(2005) [PubMed] [Europe PMC] [Abstract]