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Q9Z0E3 (AIRE_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Autoimmune regulator
Alternative name(s):
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy protein homolog
Short name=APECED protein homolog
Gene names
Name:Aire
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length552 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 By similarity. Ref.8

Subunit structure

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 By similarity. Ref.7 Ref.8

Subcellular location

Nucleus. Cytoplasm. Note: Predominantly nuclear but also cytoplasmic. Found in nuclear body-like structures and in a filamentous vimentin-like pattern. Ref.6

Tissue specificity

Expression may be restricted to a small number of scattered cells in most tissues. Highly expressed in a few cells in the medulla of the thymus. Detected at very low levels in thymus, lymph node, liver, brain, ovary, lung, testis, kidney, heart, spleen, bone marrow, skeletal muscle and adrenal gland. Isoforms 1a to 1d predominate, isoforms 2a to 2d are intermediate and isoforms 3a to 3d are expressed at extremely low levels.

Domain

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 By similarity.

The L-X-X-L-L repeats may be implicated in binding to nuclear receptors.

The N-terminal HSR domain is required for localization on tubular structures By similarity.

Post-translational modification

Phosphorylated. Ref.7

Sequence similarities

Contains 1 HSR domain.

Contains 2 PHD-type zinc fingers.

Contains 1 SAND domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   DomainRepeat
Zinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionActivator
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processhumoral immune response

Inferred from mutant phenotype PubMed 11854172. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 17599412. Source: MGI

positive regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentactin cytoskeleton

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay Ref.6. Source: MGI

intracellular

Inferred from direct assay PubMed 17599412. Source: MGI

nucleus

Inferred from direct assay Ref.6PubMed 11854172. Source: MGI

plasma membrane

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionchromatin binding

Inferred from sequence or structural similarity. Source: UniProtKB

histone binding

Inferred from sequence or structural similarity. Source: UniProtKB

identical protein binding

Inferred from physical interaction Ref.7. Source: IntAct

transcription regulatory region DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

translation regulator activity

Inferred from electronic annotation. Source: InterPro

zinc ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself4EBI-80858,EBI-80858

Alternative products

This entry describes 12 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1a (identifier: Q9Z0E3-1)

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.
Isoform 1b (identifier: Q9Z0E3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     296-296: Missing.
Isoform 1c (identifier: Q9Z0E3-3)

The sequence of this isoform differs from the canonical sequence as follows:
     265-268: Missing.
Isoform 1d (identifier: Q9Z0E3-4)

The sequence of this isoform differs from the canonical sequence as follows:
     265-268: Missing.
     296-296: Missing.
Isoform 2a (identifier: Q9Z0E3-5)

The sequence of this isoform differs from the canonical sequence as follows:
     367-425: Missing.
Isoform 2b (identifier: Q9Z0E3-6)

The sequence of this isoform differs from the canonical sequence as follows:
     296-296: Missing.
     367-425: Missing.
Isoform 2c (identifier: Q9Z0E3-7)

The sequence of this isoform differs from the canonical sequence as follows:
     265-268: Missing.
     367-425: Missing.
Isoform 2d (identifier: Q9Z0E3-8)

The sequence of this isoform differs from the canonical sequence as follows:
     265-268: Missing.
     296-296: Missing.
     367-425: Missing.
Isoform 3a (identifier: Q9Z0E3-9)

The sequence of this isoform differs from the canonical sequence as follows:
     368-409: ILVGLRSASE...LAPHPAAPLL → DQSPLQILLC...WACQGRGRLC
     410-552: Missing.
Note: Probably inactive.
Isoform 3b (identifier: Q9Z0E3-10)

The sequence of this isoform differs from the canonical sequence as follows:
     296-296: Missing.
     368-409: ILVGLRSASE...LAPHPAAPLL → DQSPLQILLC...WACQGRGRLC
     410-552: Missing.
Note: Probably inactive.
Isoform 3c (identifier: Q9Z0E3-11)

The sequence of this isoform differs from the canonical sequence as follows:
     265-268: Missing.
     368-409: ILVGLRSASE...LAPHPAAPLL → DQSPLQILLC...WACQGRGRLC
     410-552: Missing.
Note: Probably inactive.
Isoform 3d (identifier: Q9Z0E3-12)

The sequence of this isoform differs from the canonical sequence as follows:
     265-268: Missing.
     296-296: Missing.
     368-409: ILVGLRSASE...LAPHPAAPLL → DQSPLQILLC...WACQGRGRLC
     410-552: Missing.
Note: Probably inactive.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 552552Autoimmune regulator
PRO_0000064514

Regions

Domain1 – 106106HSR
Domain182 – 282101SAND
Zinc finger298 – 34548PHD-type 1
Zinc finger434 – 47542PHD-type 2
Motif8 – 125LXXLL motif 1
Motif64 – 685LXXLL motif 2
Motif114 – 13421Nuclear localization signal Potential
Motif414 – 4185LXXLL motif 3
Motif520 – 5245LXXLL motif 4

Natural variations

Alternative sequence265 – 2684Missing in isoform 1c, isoform 1d, isoform 2c, isoform 2d, isoform 3c and isoform 3d.
VSP_004091
Alternative sequence2961Missing in isoform 1b, isoform 1d, isoform 2b, isoform 2d, isoform 3b and isoform 3d.
VSP_004092
Alternative sequence367 – 42559Missing in isoform 2a, isoform 2b, isoform 2c and isoform 2d.
VSP_004093
Alternative sequence368 – 40942ILVGL…AAPLL → DQSPLQILLCRLDSHARHTG RSCTHLWAPSSTWACQGRGR LC in isoform 3a, isoform 3b, isoform 3c and isoform 3d.
VSP_004094
Alternative sequence410 – 552143Missing in isoform 3a, isoform 3b, isoform 3c and isoform 3d.
VSP_004095

Experimental info

Mutagenesis2991D → A: Abolishes interaction with histone H3. Ref.8
Mutagenesis3031V → M: No effect on interaction with histone H3. Ref.8
Mutagenesis3121C → W: Abolishes interaction with histone H3. Ref.8
Mutagenesis3131C → Y: Abolishes interaction with histone H3. Ref.8
Mutagenesis3281P → L: Reduces interaction with histone H3. Ref.8

Sequences

Sequence LengthMass (Da)Tools
Isoform 1a [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: BF30F8F66B71239A

FASTA55259,042
        10         20         30         40         50         60 
MAGGDGMLRR LLRLHRTEIA VAIDSAFPLL HALADHDVVP EDKFQETLRL KEKEGCPQAF 

        70         80         90        100        110        120 
HALLSWLLTR DSGAILDFWR ILFKDYNLER YSRLHSILDG FPKDVDLNQS RKGRKPLAGP 

       130        140        150        160        170        180 
KAAVLPPRPP TKRKALEEPR ATPPATLASK SVSSPGSHLK TKPPKKPDGN LESQHLPLGN 

       190        200        210        220        230        240 
GIQTMAASVQ RAVTVASGDV PGTRGAVEGI LIQQVFESGR SKKCIQVGGE FYTPNKFEDP 

       250        260        270        280        290        300 
SGNLKNKARS GSSLKPVVRA KGAQVTIPGR DEQKVGQQCG VPPLPSLPSE PQVNQKNEDE 

       310        320        330        340        350        360 
CAVCHDGGEL ICCDGCPRAF HLACLSPPLQ EIPSGLWRCS CCLQGRVQQN LSQPEVSRPP 

       370        380        390        400        410        420 
ELPAETPILV GLRSASEKTR GPSRELKASS DAAVTYVNLL APHPAAPLLE PSALCPLLSA 

       430        440        450        460        470        480 
GNEGRPGPAP SARCSVCGDG TEVLRCAHCA AAFHWRCHFP TAAARPGTNL RCKSCSADST 

       490        500        510        520        530        540 
PTPGTPGEAV PTSGPRPAPG LAKVGDDSAS HDPVLHRDDL ESLLNEHSFD GILQWAIQSM 

       550 
SRPLAETPPF SS 

« Hide

Isoform 1b [UniParc].

Checksum: 77C75E773B48B72C
Show »

FASTA55158,914
Isoform 1c [UniParc].

Checksum: 0B0524A3C5EDCBE6
Show »

FASTA54858,632
Isoform 1d [UniParc].

Checksum: 421B0BD9A7A0CBEC
Show »

FASTA54758,504
Isoform 2a [UniParc].

Checksum: 13307FC59268E06E
Show »

FASTA49352,996
Isoform 2b [UniParc].

Checksum: 9BE6428E275E5781
Show »

FASTA49252,868
Isoform 2c [UniParc].

Checksum: BA09175B96C9824A
Show »

FASTA48952,586
Isoform 2d [UniParc].

Checksum: 628EDC8A863C7355
Show »

FASTA48852,458
Isoform 3a [UniParc].

Checksum: 4F95F6914E91E109
Show »

FASTA40944,571
Isoform 3b [UniParc].

Checksum: 36857622FFED94C8
Show »

FASTA40844,443
Isoform 3c [UniParc].

Checksum: 4D820E9642824F3A
Show »

FASTA40544,161
Isoform 3d [UniParc].

Checksum: F17D712EEC43A7CB
Show »

FASTA40444,032

References

[1]"Chromosomal localization and complete genomic sequence of the murine autoimmune regulator gene (Aire)."
Shi J.-D., Wang C.-Y., Marron M.P., Ruan Q.-G., Huang Y.Q., Detter J.C., She J.-X.
Autoimmunity 31:47-53(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1A).
[2]"Isolation and characterization of the mouse Aire gene."
Mittaz L., Rossier C., Heino M., Petersen P., Krohn K.J.E., Gos A., Morris M.A., Kudoh J., Shimizu N., Antonarakis S.E., Scott H.S.
Biochem. Biophys. Res. Commun. 255:483-490(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1A).
Strain: 129/Sv.
[3]"Cloning of Aire, the mouse homologue of the autoimmune regulator (AIRE) gene responsible for autoimmune polyglandular syndrome type 1 (ASP1)."
Wang C.-Y., Shi J.-D., Davoodi-Semiromi A., She J.-X.
Genomics 55:322-326(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1A).
Strain: C57BL/6.
Tissue: Thymus.
[4]"The mouse Aire gene: comparative genomic sequencing, gene organization, and expression."
Blechschmidt K., Schweiger M., Wertz K., Poulson R., Christensen H.-M., Rosenthal A., Lehrach H., Yaspo M.-L.
Genome Res. 9:158-166(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING.
Strain: 129.
[5]"Expression and alternative splicing of the mouse autoimmune regulator gene (Aire)."
Ruan Q.-G., Wang C.-Y., Shi J.-D., She J.-X.
J. Autoimmun. 13:307-313(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1A; 1B; 1C; 1D; 2A; 2B; 2C; 2D; 3A; 3B; 3C AND 3D).
Strain: C57BL/6, NOD and SJL.
[6]"Subcellular location and expression pattern of autoimmune regulator (Aire), the mouse orthologue for human gene defective in autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED)."
Halonen M., Pelto-Huikko M., Eskelin P., Peltonen L., Ulmanen I., Kolmer M.
J. Histochem. Cytochem. 49:197-208(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1A), SUBCELLULAR LOCATION.
Tissue: Kidney and Thymus.
[7]"The autoimmune regulator (AIRE) is a DNA-binding protein."
Kumar P.G., Laloraya M., Wang C.-Y., Ruan Q.-G., Davoodi-Semiromi A., Kao K.-J., She J.-X.
J. Biol. Chem. 276:41357-41364(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT STRUCTURE, PHOSPHORYLATION.
[8]"Aire employs a histone-binding module to mediate immunological tolerance, linking chromatin regulation with organ-specific autoimmunity."
Koh A.S., Kuo A.J., Park S.Y., Cheung P., Abramson J., Bua D., Carney D., Shoelson S.E., Gozani O., Kingston R.E., Benoist C., Mathis D.
Proc. Natl. Acad. Sci. U.S.A. 105:15878-15883(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH THE N-TERMINUS OF UNMODIFIED HISTONE H3, INTERACTION WITH NUCLEOSOMES, DNA-BINDING, MUTAGENESIS OF ASP-299; VAL-303; CYS-312; CYS-313 AND PRO-328.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF105002 Genomic DNA. Translation: AAD46421.1.
AF128772 mRNA. Translation: AAF36481.1.
AF128773 mRNA. Translation: AAF36482.1.
AJ007715 Genomic DNA. Translation: CAA07620.1.
AF079536 mRNA. Translation: AAD20444.1.
AJ132243 mRNA. Translation: CAB36909.1.
AF128115 mRNA. Translation: AAF36460.1.
AF128116 mRNA. Translation: AAF36461.1.
AF128117 mRNA. Translation: AAF36462.1.
AF128118 mRNA. Translation: AAF36463.1.
AF128119 mRNA. Translation: AAF36464.1.
AF128120 mRNA. Translation: AAF36465.1.
AF128121 mRNA. Translation: AAF36466.1.
AF128122 mRNA. Translation: AAF36467.1.
AF128123 mRNA. Translation: AAF36468.1.
AF128124 mRNA. Translation: AAF36469.1.
AF128125 mRNA. Translation: AAF36470.1.
AJ243821 mRNA. Translation: CAB66141.1.
RefSeqNP_001258478.1. NM_001271549.1.
NP_001258479.1. NM_001271550.1.
NP_001258480.1. NM_001271551.1.
NP_001258481.1. NM_001271552.1.
NP_001258482.1. NM_001271553.1.
NP_001258483.1. NM_001271554.1.
NP_001258484.1. NM_001271555.1.
NP_001258485.1. NM_001271556.1.
NP_001258486.1. NM_001271557.1.
NP_001258487.1. NM_001271558.1.
NP_001258488.1. NM_001271559.1.
NP_033776.1. NM_009646.2.
XP_006513166.1. XM_006513103.1.
UniGeneMm.35300.

3D structure databases

ProteinModelPortalQ9Z0E3.
SMRQ9Z0E3. Positions 191-269, 295-381, 423-483.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-31030N.
IntActQ9Z0E3. 90 interactions.

PTM databases

PhosphoSiteQ9Z0E3.

Proteomic databases

PRIDEQ9Z0E3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000019257; ENSMUSP00000019257; ENSMUSG00000000731. [Q9Z0E3-2]
ENSMUST00000105395; ENSMUSP00000101034; ENSMUSG00000000731. [Q9Z0E3-9]
ENSMUST00000105396; ENSMUSP00000101035; ENSMUSG00000000731. [Q9Z0E3-6]
ENSMUST00000128241; ENSMUSP00000114904; ENSMUSG00000000731. [Q9Z0E3-1]
ENSMUST00000130972; ENSMUSP00000122659; ENSMUSG00000000731. [Q9Z0E3-4]
ENSMUST00000140636; ENSMUSP00000121477; ENSMUSG00000000731. [Q9Z0E3-12]
ENSMUST00000145975; ENSMUSP00000120150; ENSMUSG00000000731. [Q9Z0E3-3]
ENSMUST00000148469; ENSMUSP00000118317; ENSMUSG00000000731. [Q9Z0E3-11]
ENSMUST00000154374; ENSMUSP00000117094; ENSMUSG00000000731. [Q9Z0E3-5]
ENSMUST00000155021; ENSMUSP00000122190; ENSMUSG00000000731. [Q9Z0E3-8]
ENSMUST00000156417; ENSMUSP00000115162; ENSMUSG00000000731. [Q9Z0E3-10]
GeneID11634.
KEGGmmu:11634.
UCSCuc007fwr.1. mouse. [Q9Z0E3-1]
uc007fws.1. mouse. [Q9Z0E3-4]
uc007fwt.1. mouse. [Q9Z0E3-10]
uc007fwu.1. mouse. [Q9Z0E3-6]
uc007fwv.1. mouse. [Q9Z0E3-12]
uc007fww.1. mouse. [Q9Z0E3-8]
uc007fwx.1. mouse. [Q9Z0E3-3]
uc007fwz.1. mouse. [Q9Z0E3-9]
uc007fxa.1. mouse. [Q9Z0E3-11]
uc007fxb.1. mouse. [Q9Z0E3-7]

Organism-specific databases

CTD326.
MGIMGI:1338803. Aire.

Phylogenomic databases

eggNOGNOG317492.
GeneTreeENSGT00530000062982.
HOVERGENHBG014961.
InParanoidQ9Z0E3.
KOK10603.
OMAAAILDFW.
OrthoDBEOG7ZSHT7.
PhylomeDBQ9Z0E3.
TreeFamTF336193.

Gene expression databases

BgeeQ9Z0E3.
GenevestigatorQ9Z0E3.

Family and domain databases

Gene3D3.10.390.10. 1 hit.
3.30.40.10. 2 hits.
InterProIPR008087. AIRE.
IPR000770. SAND_dom.
IPR010919. SAND_dom-like.
IPR004865. Sp100.
IPR019786. Zinc_finger_PHD-type_CS.
IPR011011. Znf_FYVE_PHD.
IPR001965. Znf_PHD.
IPR019787. Znf_PHD-finger.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PANTHERPTHR24102:SF3. PTHR24102:SF3. 1 hit.
PfamPF00628. PHD. 1 hit.
PF01342. SAND. 1 hit.
PF03172. Sp100. 1 hit.
[Graphical view]
PRINTSPR01711. AIREGULATOR.
SMARTSM00249. PHD. 2 hits.
SM00184. RING. 2 hits.
SM00258. SAND. 1 hit.
[Graphical view]
SUPFAMSSF57903. SSF57903. 2 hits.
SSF63763. SSF63763. 1 hit.
PROSITEPS51414. HSR. 1 hit.
PS50864. SAND. 1 hit.
PS01359. ZF_PHD_1. 2 hits.
PS50016. ZF_PHD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSAIRE. mouse.
NextBio279201.
PROQ9Z0E3.
SOURCESearch...

Entry information

Entry nameAIRE_MOUSE
AccessionPrimary (citable) accession number: Q9Z0E3
Secondary accession number(s): Q9JLW0 expand/collapse secondary AC list , Q9JLW1, Q9JLW2, Q9JLW3, Q9JLW4, Q9JLW5, Q9JLW6, Q9JLW7, Q9JLW8, Q9JLW9, Q9JLX0
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 2002
Last sequence update: May 1, 1999
Last modified: April 16, 2014
This is version 114 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot