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Protein

Autoimmune regulator

Gene

AIRE

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity2 Publications3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri296 – 343PHD-type 1PROSITE-ProRule annotationAdd BLAST48
Zinc fingeri434 – 475PHD-type 2PROSITE-ProRule annotationAdd BLAST42

GO - Molecular functioni

  • chromatin binding Source: UniProtKB
  • histone binding Source: UniProtKB
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: NTNU_SB
  • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding Source: NTNU_SB
  • transcription cofactor activity Source: GO_Central
  • transcription regulatory region DNA binding Source: UniProtKB
  • translation regulator activity Source: InterPro
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • central tolerance induction to self antigen Source: UniProtKB
  • chemokine production Source: UniProtKB
  • humoral immune response Source: Ensembl
  • immune response Source: ProtInc
  • negative thymic T cell selection Source: Ensembl
  • peripheral T cell tolerance induction Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  • regulation of thymocyte migration Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB
  • thymus epithelium morphogenesis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000160224-MONOMER.
SIGNORiO43918.

Names & Taxonomyi

Protein namesi
Recommended name:
Autoimmune regulator
Alternative name(s):
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy protein
Short name:
APECED protein
Gene namesi
Name:AIRE
Synonyms:APECED
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

HGNCiHGNC:360. AIRE.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB-SubCell
  • nuclear body Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Autoimmune polyendocrine syndrome 1, with or without reversible metaphyseal dysplasia (APS1)13 Publications
The disease is caused by mutations 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). Heterozigous mutations within the PHD1 domain have dominant-negatif 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).3 Publications
Disease descriptionA 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.
See also OMIM:240300
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02648015R → C in APS1. 1 PublicationCorresponds to variant rs179363875dbSNPEnsembl.1
Natural variantiVAR_01371315R → L in APS1; prevents homooligomerization; slightly alters subcellular localization; no effect on the transcriptional transactivation activity. 3 PublicationsCorresponds to variant rs179363876dbSNPEnsembl.1
Natural variantiVAR_01371416T → M in APS1; prevents homooligomerization; slightly alters subcellular localization; no effect on the transcriptional transactivation activity. 4 PublicationsCorresponds to variant rs179363877dbSNPEnsembl.1
Natural variantiVAR_02648121A → V in APS1; no effect on homooligomerization; no effect on subcellular localization; no effect on the transcriptional transactivation activity. 2 PublicationsCorresponds to variant rs179363886dbSNPEnsembl.1
Natural variantiVAR_02648222 – 23Missing in APS1; prevents homodimerization. 1 Publication2
Natural variantiVAR_00500428L → P in APS1; abolishes association with cytoplasmic tubular structures and homodimerization; loss of doted nuclear localization; nuclear smear. 5 PublicationsCorresponds to variant rs179363878dbSNPEnsembl.1
Natural variantiVAR_01371529L → P in APS1. 2 PublicationsCorresponds to variant rs179363879dbSNPEnsembl.1
Natural variantiVAR_02648377F → S in APS1; loss of homooligomerization. 1 PublicationCorresponds to variant rs179363887dbSNPEnsembl.1
Natural variantiVAR_01371678W → R in APS1; loss of homooligomerization. 5 PublicationsCorresponds to variant rs179363880dbSNPEnsembl.1
Natural variantiVAR_01371780V → L in APS1. 3 PublicationsCorresponds to variant rs179363881dbSNPEnsembl.1
Natural variantiVAR_00500583K → E in APS1. 3 PublicationsCorresponds to variant rs121434255dbSNPEnsembl.1
Natural variantiVAR_01371885Y → C in APS1. 3 PublicationsCorresponds to variant rs179363882dbSNPEnsembl.1
Natural variantiVAR_01371990Y → C in APS1; decreases doted nuclear localization. 3 PublicationsCorresponds to variant rs179363883dbSNPEnsembl.1
Natural variantiVAR_01372093L → R in APS1. 2 PublicationsCorresponds to variant rs179363884dbSNPEnsembl.1
Natural variantiVAR_014422228G → W in APS1; changes the subcellular localization and in addition disrupts the transactivating capacity of the wild-type AIRE; acts with a dominant negative effect by binding to the wild-type AIRE thus preventing the protein from forming the complexes needed for transactivation. 3 PublicationsCorresponds to variant rs121434257dbSNPEnsembl.1
Natural variantiVAR_026484252P → L in APS1. 1 PublicationCorresponds to variant rs34397615dbSNPEnsembl.1
Natural variantiVAR_013721301V → M in APS1; no effect on protein structure or on interaction with histone H3; no effect on doted nuclear localization; dominant-negatif effect on regulation of target gene transcription. 5 PublicationsCorresponds to variant rs150634562dbSNPEnsembl.1
Natural variantiVAR_013723311C → Y in APS1; impairs zinc binding and folding of the PHD-type 1 zinc finger; dominant-negatif effect on the regulation of target gene transcription; no effect on doted nuclear localization; dominant-negatif effect on regulation of target gene transcription. 7 PublicationsCorresponds to variant rs386833674dbSNPEnsembl.1
Natural variantiVAR_026485326P → L in APS1; no significant effect on structure, but may alter protein interactions; no effect on doted nuclear localization; dominant-negatif effect on regulation of target gene transcription. 3 PublicationsCorresponds to variant rs179363888dbSNPEnsembl.1
Natural variantiVAR_013724326P → Q in APS1; alters folding of the PHD-type 1 zinc finger. 5 PublicationsCorresponds to variant rs179363885dbSNPEnsembl.1
Natural variantiVAR_026486539P → L in APS1. 1 PublicationCorresponds to variant rs179363889dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi28 – 29LL → PP: Loss of doted nuclear location, forms nuclear smears. Loss of transactivation activity on target genes transcription. 1 Publication2
Mutagenesisi97L → P: Loss of transactivation activity on target gene transcritpion; no dominant-negatif effect on target gene transcription. Loss of doted nuclear localization. 1 Publication1
Mutagenesisi295N → A: Abolishes interaction with histone H3. 1 Publication1
Mutagenesisi297D → 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-negatif effect on target gene transcription. 2 Publications1
Mutagenesisi298E → A: Reduces interaction with histone H3. 1 Publication1
Mutagenesisi302C → P: Reduces transcriptional activation. 1 Publication1
Mutagenesisi303R → P: Alters protein folding and abolishes interaction with histone H3. No effect on doted nuclear localization. Dominant-negatif effect on target gene transcription. 2 Publications1
Mutagenesisi304D → A: Strongly reduces interaction with histone H3. 1 Publication1
Mutagenesisi307E → A: Reduces interaction with histone H3. 1 Publication1
Mutagenesisi312D → A: Abolishes interaction with histone H3. 1 Publication1
Mutagenesisi312D → N: No effect on doted nuclear localization. Dominant-negatif effect on target gene transcription. 1 Publication1
Mutagenesisi437C → P: Reduces transcription activation. 1 Publication1
Mutagenesisi446C → G: Dominant-negatif effect on regulation of target gene transcription. 1 Publication1
Mutagenesisi471R → C: No effect on regulation of target gene transcription. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi326.
MalaCardsiAIRE.
MIMi109100. phenotype.
240300. phenotype.
OpenTargetsiENSG00000160224.
Orphaneti3453. Autoimmune polyendocrinopathy type 1.
PharmGKBiPA24654.

Polymorphism and mutation databases

BioMutaiAIRE.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000645131 – 545Autoimmune regulatorAdd BLAST545

Post-translational modificationi

Phosphorylated. Phosphorylation could trigger oligomerization.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO43918.
PaxDbiO43918.
PeptideAtlasiO43918.
PRIDEiO43918.

PTM databases

iPTMnetiO43918.
PhosphoSitePlusiO43918.

Expressioni

Tissue specificityi

Widely expressed. Expressed at higher level in thymus (medullary epithelial cells and monocyte-dendritic cells), pancreas, adrenal cortex and testis. Expressed at lower level in the spleen, fetal liver and lymph nodes. In secondary lymphoid organs, expressed in a discrete population of bone marrow-derived toleregenic antigen presenting cells (APCs) called extrathymic AIRE expressing cells (eTAC)(at protein level) (PubMed:23993652). Isoform 2 and isoform 3 seem to be less frequently expressed than isoform 1, if at all.1 Publication

Gene expression databases

BgeeiENSG00000160224.
CleanExiHS_AIRE.
GenevisibleiO43918. HS.

Organism-specific databases

HPAiHPA038267.

Interactioni

Subunit structurei

Homodimer and homotetramer. Interacts with CREBBP. Interacts preferentially with histone H3 that is not methylated at 'Lys-4'. Binds with lower affinity to histone H3 that is monomethylated at 'Lys-4'. Trimethylation of histone H3 at 'Lys-4' or phosphorylation at 'Thr-3' abolish the interaction. Binds with lower affinity to histone H3 that is acetylated at 'Lys-4', or that is acetylated at 'Lys-9' or trimethylated at 'Lys-9'. Binds histone H3 that is dimethylated at 'Arg-2' with very low affinity.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
DAXXQ9UER75EBI-1753081,EBI-77321
HIST1H3DP6843120EBI-1753081,EBI-79722
NCK1P163332EBI-1753081,EBI-389883
PRKDCP785272EBI-1753081,EBI-352053

GO - Molecular functioni

  • histone binding Source: UniProtKB

Protein-protein interaction databases

BioGridi106823. 80 interactors.
DIPiDIP-47504N.
IntActiO43918. 24 interactors.
MINTiMINT-6542056.
STRINGi9606.ENSP00000291582.

Structurei

Secondary structure

1545
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi298 – 303Combined sources6
Beta strandi306 – 310Combined sources5
Beta strandi312 – 314Combined sources3
Beta strandi317 – 319Combined sources3
Turni320 – 322Combined sources3
Beta strandi323 – 325Combined sources3
Helixi338 – 342Combined sources5
Turni423 – 426Combined sources4
Turni435 – 437Combined sources3
Beta strandi447 – 449Combined sources3
Helixi455 – 458Combined sources4
Turni460 – 462Combined sources3
Beta strandi467 – 469Combined sources3
Turni473 – 476Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1XWHNMR-A293-354[»]
2KE1NMR-A293-354[»]
2KFTNMR-A294-347[»]
2LRINMR-C423-485[»]
ProteinModelPortaliO43918.
SMRiO43918.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43918.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 105HSRPROSITE-ProRule annotationAdd BLAST105
Domaini181 – 280SANDPROSITE-ProRule annotationAdd BLAST100

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni295 – 298Interaction with histone H3 not methylated at 'Lys-4'4
Regioni304 – 312Interaction with histone H3 not methylated at 'Lys-4'9
Regioni331 – 335Interaction with histone H3 not methylated at 'Lys-4'5

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi7 – 11LXXLL motif 15
Motifi63 – 67LXXLL motif 25
Motifi414 – 418LXXLL motif 35
Motifi516 – 520LXXLL motif 45

Domaini

The L-X-X-L-L repeats may be implicated in binding to nuclear receptors.
The HSR domain is required for localization on tubular structures (N-terminal part) and for homodimerization.
Interacts via the first PHD domain with the N-terminus of histone H3 that is not methylated at 'Lys-4'. Disruption of the first PHD domain has been shown to lead to reduced transcriptional activity and to localization of the protein mainly in the cytoplasm in small granules. While the PHD zinc fingers are necessary for the transactivation capacity of the protein, other regions also modulate this function.

Sequence similaritiesi

Contains 1 HSR domain.PROSITE-ProRule annotation
Contains 2 PHD-type zinc fingers.PROSITE-ProRule annotation
Contains 1 SAND domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri296 – 343PHD-type 1PROSITE-ProRule annotationAdd BLAST48
Zinc fingeri434 – 475PHD-type 2PROSITE-ProRule annotationAdd BLAST42

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IRE7. Eukaryota.
ENOG410XQQA. LUCA.
GeneTreeiENSGT00530000062982.
HOGENOMiHOG000033872.
HOVERGENiHBG014961.
InParanoidiO43918.
KOiK10603.
OMAiLLSEHTF.
OrthoDBiEOG091G055U.
PhylomeDBiO43918.
TreeFamiTF336193.

Family and domain databases

Gene3Di3.10.390.10. 1 hit.
3.30.40.10. 2 hits.
InterProiIPR008087. AIRE.
IPR004865. HSR_dom.
IPR000770. SAND_dom.
IPR010919. SAND_dom-like.
IPR019786. Zinc_finger_PHD-type_CS.
IPR011011. Znf_FYVE_PHD.
IPR001965. Znf_PHD.
IPR019787. Znf_PHD-finger.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF03172. HSR. 1 hit.
PF00628. PHD. 1 hit.
PF01342. SAND. 1 hit.
[Graphical view]
PRINTSiPR01711. AIREGULATOR.
SMARTiSM00249. PHD. 2 hits.
SM00258. SAND. 1 hit.
[Graphical view]
SUPFAMiSSF57903. SSF57903. 2 hits.
SSF63763. SSF63763. 1 hit.
PROSITEiPS51414. HSR. 1 hit.
PS50864. SAND. 1 hit.
PS01359. ZF_PHD_1. 2 hits.
PS50016. ZF_PHD_2. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist. Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: O43918-1) [UniParc]FASTAAdd to basket
Also known as: AIRE-1

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MATDAALRRL LRLHRTEIAV AVDSAFPLLH ALADHDVVPE DKFQETLHLK
60 70 80 90 100
EKEGCPQAFH ALLSWLLTQD STAILDFWRV LFKDYNLERY GRLQPILDSF
110 120 130 140 150
PKDVDLSQPR KGRKPPAVPK ALVPPPRLPT KRKASEEARA AAPAALTPRG
160 170 180 190 200
TASPGSQLKA KPPKKPESSA EQQRLPLGNG IQTMSASVQR AVAMSSGDVP
210 220 230 240 250
GARGAVEGIL IQQVFESGGS KKCIQVGGEF YTPSKFEDSG SGKNKARSSS
260 270 280 290 300
GPKPLVRAKG AQGAAPGGGE ARLGQQGSVP APLALPSDPQ LHQKNEDECA
310 320 330 340 350
VCRDGGELIC CDGCPRAFHL ACLSPPLREI PSGTWRCSSC LQATVQEVQP
360 370 380 390 400
RAEEPRPQEP PVETPLPPGL RSAGEEVRGP PGEPLAGMDT TLVYKHLPAP
410 420 430 440 450
PSAAPLPGLD SSALHPLLCV GPEGQQNLAP GARCGVCGDG TDVLRCTHCA
460 470 480 490 500
AAFHWRCHFP AGTSRPGTGL RCRSCSGDVT PAPVEGVLAP SPARLAPGPA
510 520 530 540
KDDTASHEPA LHRDDLESLL SEHTFDGILQ WAIQSMARPA APFPS
Length:545
Mass (Da):57,727
Last modified:June 1, 1998 - v1
Checksum:i8CF703F8C9411BC5
GO
Isoform 2 (identifier: O43918-2) [UniParc]FASTAAdd to basket
Also known as: AIRE-2

The sequence of this isoform differs from the canonical sequence as follows:
     1-292: MATDAALRRL...LALPSDPQLH → MWLVYSSGAP...VALRRVLHPS

Show »
Length:338
Mass (Da):35,507
Checksum:i7C99ABAD92DDC565
GO
Isoform 3 (identifier: O43918-3) [UniParc]FASTAAdd to basket
Also known as: AIRE-3

The sequence of this isoform differs from the canonical sequence as follows:
     1-292: MATDAALRRL...LALPSDPQLH → MWLVYSSGAP...VALRRVLHPS
     377-545: VRGPPGEPLA...MARPAAPFPS → PRCQGWTPRP...ACAADPAQET

Show »
Length:244
Mass (Da):25,927
Checksum:iBD26FC231E0E5611
GO
Isoform 4 (identifier: O43918-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-292: MATDAALRRL...LALPSDPQLH → MWLVYSSGAP...VALRRVLHPS
     293-293: Q → PVCMGVSCLCQ

Note: No experimental confirmation available.
Show »
Length:348
Mass (Da):36,501
Checksum:i37045012FF585F6E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti437 – 467CGDGT…TSRPG → W in CAA08759 (Ref. 3) CuratedAdd BLAST31

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02648015R → C in APS1. 1 PublicationCorresponds to variant rs179363875dbSNPEnsembl.1
Natural variantiVAR_01371315R → L in APS1; prevents homooligomerization; slightly alters subcellular localization; no effect on the transcriptional transactivation activity. 3 PublicationsCorresponds to variant rs179363876dbSNPEnsembl.1
Natural variantiVAR_01371416T → M in APS1; prevents homooligomerization; slightly alters subcellular localization; no effect on the transcriptional transactivation activity. 4 PublicationsCorresponds to variant rs179363877dbSNPEnsembl.1
Natural variantiVAR_02648121A → V in APS1; no effect on homooligomerization; no effect on subcellular localization; no effect on the transcriptional transactivation activity. 2 PublicationsCorresponds to variant rs179363886dbSNPEnsembl.1
Natural variantiVAR_02648222 – 23Missing in APS1; prevents homodimerization. 1 Publication2
Natural variantiVAR_00500428L → P in APS1; abolishes association with cytoplasmic tubular structures and homodimerization; loss of doted nuclear localization; nuclear smear. 5 PublicationsCorresponds to variant rs179363878dbSNPEnsembl.1
Natural variantiVAR_01371529L → P in APS1. 2 PublicationsCorresponds to variant rs179363879dbSNPEnsembl.1
Natural variantiVAR_02648377F → S in APS1; loss of homooligomerization. 1 PublicationCorresponds to variant rs179363887dbSNPEnsembl.1
Natural variantiVAR_01371678W → R in APS1; loss of homooligomerization. 5 PublicationsCorresponds to variant rs179363880dbSNPEnsembl.1
Natural variantiVAR_01371780V → L in APS1. 3 PublicationsCorresponds to variant rs179363881dbSNPEnsembl.1
Natural variantiVAR_00500583K → E in APS1. 3 PublicationsCorresponds to variant rs121434255dbSNPEnsembl.1
Natural variantiVAR_01371885Y → C in APS1. 3 PublicationsCorresponds to variant rs179363882dbSNPEnsembl.1
Natural variantiVAR_01371990Y → C in APS1; decreases doted nuclear localization. 3 PublicationsCorresponds to variant rs179363883dbSNPEnsembl.1
Natural variantiVAR_01372093L → R in APS1. 2 PublicationsCorresponds to variant rs179363884dbSNPEnsembl.1
Natural variantiVAR_014422228G → W in APS1; changes the subcellular localization and in addition disrupts the transactivating capacity of the wild-type AIRE; acts with a dominant negative effect by binding to the wild-type AIRE thus preventing the protein from forming the complexes needed for transactivation. 3 PublicationsCorresponds to variant rs121434257dbSNPEnsembl.1
Natural variantiVAR_026484252P → L in APS1. 1 PublicationCorresponds to variant rs34397615dbSNPEnsembl.1
Natural variantiVAR_005006278S → R.3 PublicationsCorresponds to variant rs1800520dbSNPEnsembl.1
Natural variantiVAR_076940298E → K Unknown pathological significance. 1 Publication1
Natural variantiVAR_076941299C → W Unknown pathological significance. 1 Publication1
Natural variantiVAR_013721301V → M in APS1; no effect on protein structure or on interaction with histone H3; no effect on doted nuclear localization; dominant-negatif effect on regulation of target gene transcription. 5 PublicationsCorresponds to variant rs150634562dbSNPEnsembl.1
Natural variantiVAR_076942302C → Y Found in patients with hypothyroidism and organ- and cytokine-specific autoantibodies; no effect on doted nuclear localization; dominant-negatif effect on regulation of target gene transcription. 1 Publication1
Natural variantiVAR_076943303R → Q Unknown pathological significance. 1 Publication1
Natural variantiVAR_076944303R → W Unknown pathological significance. 1 Publication1
Natural variantiVAR_013722305G → S Found in a patient with pernicious anemia and neuropathy; no effect on doted nuclear localization; dominant-negatif effect on regulation of target gene transcription. 1 Publication1
Natural variantiVAR_076945306G → R Unknown pathological significance. 1 Publication1
Natural variantiVAR_076946309I → M Unknown pathological significance. 1 Publication1
Natural variantiVAR_013723311C → Y in APS1; impairs zinc binding and folding of the PHD-type 1 zinc finger; dominant-negatif effect on the regulation of target gene transcription; no effect on doted nuclear localization; dominant-negatif effect on regulation of target gene transcription. 7 PublicationsCorresponds to variant rs386833674dbSNPEnsembl.1
Natural variantiVAR_076947316R → Q Unknown pathological significance. 1 Publication1
Natural variantiVAR_076948316R → W Unknown pathological significance; found in a patient with pernicious anemia. 1 Publication1
Natural variantiVAR_076949319H → P Unknown pathological significance. 1 Publication1
Natural variantiVAR_026485326P → L in APS1; no significant effect on structure, but may alter protein interactions; no effect on doted nuclear localization; dominant-negatif effect on regulation of target gene transcription. 3 PublicationsCorresponds to variant rs179363888dbSNPEnsembl.1
Natural variantiVAR_013724326P → Q in APS1; alters folding of the PHD-type 1 zinc finger. 5 PublicationsCorresponds to variant rs179363885dbSNPEnsembl.1
Natural variantiVAR_076950328R → Q Found in a patient with acrofacial vitiligo and gastric parietal cell autoantibodies; no effect on doted nuclear localization; dominant-negatif effect on regulation of target gene transcription. 1 Publication1
Natural variantiVAR_076951328R → W Unknown pathological significance. 1 Publication1
Natural variantiVAR_076952332S → R Unknown pathological significance. 1 Publication1
Natural variantiVAR_076953484V → A Found in a patient with acrofacial vitiligo and gastric parietal cell autoantibodies; unknown pathological significance. 1 Publication1
Natural variantiVAR_026486539P → L in APS1. 1 PublicationCorresponds to variant rs179363889dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0040891 – 292MATDA…DPQLH → MWLVYSSGAPGTQQPARNRV FFPIGMAPGGVCWRPDGWGT GGQGRISGPGSMGAGQRLGS SGTQRCCWGSCFGKEVALRR VLHPS in isoform 2, isoform 3 and isoform 4. 2 PublicationsAdd BLAST292
Alternative sequenceiVSP_043529293Q → PVCMGVSCLCQ in isoform 4. 1 Publication1
Alternative sequenceiVSP_004090377 – 545VRGPP…APFPS → PRCQGWTPRPCTPYCVWVLR VSRTWLLVRVAGCAEMVRTC CGVLTAPLPSTGAATSQPAP PGPGRACAADPAQET in isoform 3. 1 PublicationAdd BLAST169

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB006682 mRNA. Translation: BAA23988.1.
AB006683 mRNA. Translation: BAA23989.1.
AB006684 Genomic DNA. Translation: BAA23990.1.
AB006684 Genomic DNA. Translation: BAA23991.1.
AB006684 Genomic DNA. Translation: BAA23992.1.
AB006685 mRNA. Translation: BAA23993.1.
Z97990 mRNA. Translation: CAB10790.1.
AJ009610 Genomic DNA. Translation: CAA08759.1.
AP001754 Genomic DNA. Translation: BAA95560.1.
AP001060 Genomic DNA. No translation available.
CH471079 Genomic DNA. Translation: EAX09443.1.
BC137268 mRNA. Translation: AAI37269.1.
BC137270 mRNA. Translation: AAI37271.1.
CCDSiCCDS13706.1. [O43918-1]
RefSeqiNP_000374.1. NM_000383.3. [O43918-1]
UniGeneiHs.129829.

Genome annotation databases

EnsembliENST00000291582; ENSP00000291582; ENSG00000160224. [O43918-1]
GeneIDi326.
KEGGihsa:326.
UCSCiuc002zei.4. human. [O43918-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

AIREbase

AIRE mutation db

Mendelian genes autoimmune regulator (AIRE)

Leiden Open Variation Database (LOVD)

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB006682 mRNA. Translation: BAA23988.1.
AB006683 mRNA. Translation: BAA23989.1.
AB006684 Genomic DNA. Translation: BAA23990.1.
AB006684 Genomic DNA. Translation: BAA23991.1.
AB006684 Genomic DNA. Translation: BAA23992.1.
AB006685 mRNA. Translation: BAA23993.1.
Z97990 mRNA. Translation: CAB10790.1.
AJ009610 Genomic DNA. Translation: CAA08759.1.
AP001754 Genomic DNA. Translation: BAA95560.1.
AP001060 Genomic DNA. No translation available.
CH471079 Genomic DNA. Translation: EAX09443.1.
BC137268 mRNA. Translation: AAI37269.1.
BC137270 mRNA. Translation: AAI37271.1.
CCDSiCCDS13706.1. [O43918-1]
RefSeqiNP_000374.1. NM_000383.3. [O43918-1]
UniGeneiHs.129829.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1XWHNMR-A293-354[»]
2KE1NMR-A293-354[»]
2KFTNMR-A294-347[»]
2LRINMR-C423-485[»]
ProteinModelPortaliO43918.
SMRiO43918.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106823. 80 interactors.
DIPiDIP-47504N.
IntActiO43918. 24 interactors.
MINTiMINT-6542056.
STRINGi9606.ENSP00000291582.

PTM databases

iPTMnetiO43918.
PhosphoSitePlusiO43918.

Polymorphism and mutation databases

BioMutaiAIRE.

Proteomic databases

EPDiO43918.
PaxDbiO43918.
PeptideAtlasiO43918.
PRIDEiO43918.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000291582; ENSP00000291582; ENSG00000160224. [O43918-1]
GeneIDi326.
KEGGihsa:326.
UCSCiuc002zei.4. human. [O43918-1]

Organism-specific databases

CTDi326.
DisGeNETi326.
GeneCardsiAIRE.
HGNCiHGNC:360. AIRE.
HPAiHPA038267.
MalaCardsiAIRE.
MIMi109100. phenotype.
240300. phenotype.
607358. gene.
neXtProtiNX_O43918.
OpenTargetsiENSG00000160224.
Orphaneti3453. Autoimmune polyendocrinopathy type 1.
PharmGKBiPA24654.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IRE7. Eukaryota.
ENOG410XQQA. LUCA.
GeneTreeiENSGT00530000062982.
HOGENOMiHOG000033872.
HOVERGENiHBG014961.
InParanoidiO43918.
KOiK10603.
OMAiLLSEHTF.
OrthoDBiEOG091G055U.
PhylomeDBiO43918.
TreeFamiTF336193.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000160224-MONOMER.
SIGNORiO43918.

Miscellaneous databases

EvolutionaryTraceiO43918.
GeneWikiiAutoimmune_regulator.
GenomeRNAii326.
PROiO43918.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000160224.
CleanExiHS_AIRE.
GenevisibleiO43918. HS.

Family and domain databases

Gene3Di3.10.390.10. 1 hit.
3.30.40.10. 2 hits.
InterProiIPR008087. AIRE.
IPR004865. HSR_dom.
IPR000770. SAND_dom.
IPR010919. SAND_dom-like.
IPR019786. Zinc_finger_PHD-type_CS.
IPR011011. Znf_FYVE_PHD.
IPR001965. Znf_PHD.
IPR019787. Znf_PHD-finger.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF03172. HSR. 1 hit.
PF00628. PHD. 1 hit.
PF01342. SAND. 1 hit.
[Graphical view]
PRINTSiPR01711. AIREGULATOR.
SMARTiSM00249. PHD. 2 hits.
SM00258. SAND. 1 hit.
[Graphical view]
SUPFAMiSSF57903. SSF57903. 2 hits.
SSF63763. SSF63763. 1 hit.
PROSITEiPS51414. HSR. 1 hit.
PS50864. SAND. 1 hit.
PS01359. ZF_PHD_1. 2 hits.
PS50016. ZF_PHD_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAIRE_HUMAN
AccessioniPrimary (citable) accession number: O43918
Secondary accession number(s): B2RP50
, O43922, O43932, O75745
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: June 1, 1998
Last modified: November 30, 2016
This is version 180 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 21
    Human chromosome 21: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.