Autoimmune regulator, AIRE (IPR008087)

Short name: AIRE

Overlapping homologous superfamilies


Family relationships



AIRE (AutoImmune REgulator) is the predicted protein responsible for a rare autosomal recessively inherited disease termed APECED. APECED, also called Autoimmune Polyglandular Syndrome type I (APS 1), is the only described autoimmune disease with established monogenic background, being localised outside the major histocompatibility complex region. It is characterised by the presence of two of the three major clinical entities, chronic mucocutaneus candidiasis, hypoparathyroidism and Addison's disease. Other immunologically mediated phenotypes, including insulin-dependent diabetes mellitus (IDDM), gonadal failure, chronic gastritis, vitiligo, autoimmune thyroid disease, enamel hypoplasia, and alopecia may also be present. Immunologically, APECED patients have deficient T cell responses towards Candida antigens, and clinical symptoms both within and outside the endocrine system, mainly as a result of autoimmunity against organ-specific autoantigens [PMID: 9398840, PMID: 10049735].

AIRE has motifs suggestive of a transcriptional regulator protein. It harbours two zinc fingers of the plant homodomain (PHD) type. A putative DNA- binding domain, termed SAND, as well as four nuclear receptor binding LXXLL motifs, an inverted LXXLL domain, and a variant of the latter (FXXLL), hint that this protein functions as a transcription coactivator. Furthermore, a highly conserved N-terminal 100-amino acid domain in AIRE shows significant similarity to the homogeneously staining (HSR) domain of Sp100 and Sp140 proteins, which has been shown to function as a dimerisation domain in several Sp-100 related proteins [PMID: 10049735, PMID: 10208866, PMID: 11533054].

AIRE has a dual subcellular location. It is not only expressed in multiple immunologically relevant tissues, such as the thymus, spleen, lymph nodes and bone marrow, but it has also been detected in various other tissues, such as kidney, testis, adrenal glands, liver and ovary, suggesting that APECED proteins might also have a function outside the immune system. However, AIRE is not expressed in the target organs of autoimmune destruction. At the subcellular level, AIRE can be found in the cell nucleus in a speckled pattern in domains resembling promyeolocytic leukaemia nuclear bodies, also known as ND10, nuclear dots or potential oncogenic domains associated with the AIRE homologous nuclear proteins Sp100, Sp140, and Lysp100. The nuclear localisation of AIRE, in keeping with its predicted protein domains, suggest that it may regulate the mechanisms involved in the induction and maintenance of immune tolerance.

GO terms

Biological Process

GO:0006959 humoral immune response

Molecular Function

GO:0003677 DNA binding
GO:0045182 translation regulator activity

Cellular Component

GO:0005737 cytoplasm
GO:0005634 nucleus

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.