AIRE

Protein identityUniProt · HPA

UniProt accession

O43918

Gene

AIRE

Ensembl

ENSG00000160224

Chromosome

21

Canonical length

545 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors

Quaternary structure

Homotetramer

OverviewNCBI Gene

This gene encodes a transcriptional regulator that forms nuclear bodies and interacts with the transcriptional coactivator CREB binding protein. The encoded protein plays an important role in immunity by regulating the expression of autoantigens and negative selection of autoreactive T-cells in the thymus. Mutations in this gene cause the rare autosomal-recessive systemic autoimmune disease termed autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED). [provided by RefSeq, Jun 2012]

Canonical amino-acid sequenceUniProt

545 residues, UniProt reviewed canonical sequence.

>O43918|AIRE
     1  MATDAALRRL LRLHRTEIAV AVDSAFPLLH ALADHDVVPE DKFQETLHLK EKEGCPQAFH
    61  ALLSWLLTQD STAILDFWRV LFKDYNLERY GRLQPILDSF PKDVDLSQPR KGRKPPAVPK
   121  ALVPPPRLPT KRKASEEARA AAPAALTPRG TASPGSQLKA KPPKKPESSA EQQRLPLGNG
   181  IQTMSASVQR AVAMSSGDVP GARGAVEGIL IQQVFESGGS KKCIQVGGEF YTPSKFEDSG
   241  SGKNKARSSS GPKPLVRAKG AQGAAPGGGE ARLGQQGSVP APLALPSDPQ LHQKNEDECA
   301  VCRDGGELIC CDGCPRAFHL ACLSPPLREI PSGTWRCSSC LQATVQEVQP RAEEPRPQEP
   361  PVETPLPPGL RSAGEEVRGP PGEPLAGMDT TLVYKHLPAP PSAAPLPGLD SSALHPLLCV
   421  GPEGQQNLAP GARCGVCGDG TDVLRCTHCA AAFHWRCHFP AGTSRPGTGL RCRSCSGDVT
   481  PAPVEGVLAP SPARLAPGPA KDDTASHEPA LHRDDLESLL SEHTFDGILQ WAIQSMARPA
   541  APFPS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against AIRE can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.56

Highest tissue expression

2 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about AIRE.

Disease | AllUniProt

Conditions AIRE is implicated in, by any mechanism.

• Autoimmune polyendocrine syndrome 1, with or without reversible metaphyseal dysplasia (APS1) MIM:240300

Disease | GeneticClinVar

230 pathogenic / likely-pathogenic of 1,358 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Polyglandular autoimmune syndrome, type 1
• AIRE-related disorder
• Inborn genetic diseases
• Retinal disorder
• Autoimmune polyglandular syndrome type 1, with reversible metaphyseal dysplasia

ReferencesPubMed · IEDB

Publications for AIRE from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.12

gnomAD pLI

0

gnomAD missense Z

0

DepMap mean gene effect

0.12

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• humoral immune response
• immune response
• negative thymic T cell selection
• positive regulation of chemokine production
• positive regulation of DNA-templated transcription
• positive regulation of transcription by RNA polymerase II
• regulation of DNA-templated transcription
• thymus epithelium morphogenesis
• transcription by RNA polymerase II
• central tolerance induction to self antigen
• peripheral T cell tolerance induction
• regulation of thymocyte migration

Molecular functions

• chromatin binding
• histone binding
• identical protein binding
• RNA polymerase II transcription regulatory region sequence-specific DNA binding
• translation regulator activity
• zinc ion binding

Cellular components

• cytoplasm
• female germ cell nucleus
• male germ cell nucleus
• nuclear body
• nucleus

Protein domainsUniProt · Pfam · InterPro

• SAND domain
• Zinc finger, PHD-type
• HSR domain
• SAND-like domain superfamily
• Zinc finger, FYVE/PHD-type
• Zinc finger, RING/FYVE/PHD-type
• Zinc finger, PHD-type, conserved site
• Zinc finger, PHD-finger
• Nuclear body protein Sp110/Sp140/Sp140L-like
• PHD-finger
• SAND domain
• HSR domain
• Autoimmune regulator, AIRE
• AIRE, PHD finger 2

KeywordsUniProt

• Activator
• Cytoplasm
• DNA-binding
• Metal-binding
• Nucleus
• Phosphoprotein
• Repeat
• Transcription
• Transcription regulation
• Zinc
• Zinc-finger

InteractionsUniProt · HPA

Protein binding partners of AIRE in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CREBBP
• DAXX
• PRKDC