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O43918 (AIRE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 154. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Autoimmune regulator
Alternative name(s):
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy protein
Short name=APECED protein
Gene names
Name:AIRE
Synonyms:APECED
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length545 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 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. 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. Ref.10 Ref.12

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. Ref.8 Ref.11 Ref.12 Ref.14

Subcellular location

Nucleus. Cytoplasm. Note: Associated with tubular structures and in discrete nuclear dots resembling ND10 nuclear bodies. May shuttle between nucleus and cytoplasm. Ref.7 Ref.9 Ref.10 Ref.11

Tissue specificity

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. Isoform 2 and isoform 3 seem to be less frequently expressed than isoform 1, if at all.

Domain

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.

Post-translational modification

Phosphorylated. Phosphorylation could trigger oligomerization. Ref.8

Involvement in disease

Autoimmune polyendocrine syndrome 1, with or without reversible metaphyseal dysplasia (APS1) [MIM:240300]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.15 Ref.16 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27

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.

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
Polymorphism
   DiseaseDisease mutation
   DomainRepeat
Zinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionActivator
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processhumoral immune response

Inferred from electronic annotation. Source: Ensembl

immune response

Traceable author statement Ref.2. Source: ProtInc

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Inferred from direct assay Ref.12. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from direct assay Ref.12. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Non-traceable author statement Ref.2. Source: UniProtKB

   Molecular_functionchromatin binding

Inferred from direct assay Ref.12. Source: UniProtKB

histone binding

Inferred from direct assay Ref.12Ref.15. Source: UniProtKB

transcription regulatory region DNA binding

Inferred from direct assay Ref.12. Source: UniProtKB

translation regulator activity

Inferred from electronic annotation. Source: InterPro

zinc ion binding

Inferred from direct assay Ref.15. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist. Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: O43918-1)

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.
Isoform 2 (identifier: O43918-2)

Also known as: AIRE-2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-292: MATDAALRRL...LALPSDPQLH → MWLVYSSGAP...VALRRVLHPS
Isoform 3 (identifier: O43918-3)

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
Isoform 4 (identifier: O43918-4)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 545545Autoimmune regulator
PRO_0000064513

Regions

Domain1 – 105105HSR
Domain181 – 280100SAND
Zinc finger296 – 34348PHD-type 1
Zinc finger434 – 47542PHD-type 2
Region295 – 2984Interaction with histone H3 not methylated at 'Lys-4'
Region304 – 3129Interaction with histone H3 not methylated at 'Lys-4'
Region331 – 3355Interaction with histone H3 not methylated at 'Lys-4'
Motif7 – 115LXXLL motif 1
Motif63 – 675LXXLL motif 2
Motif414 – 4185LXXLL motif 3
Motif516 – 5205LXXLL motif 4

Natural variations

Alternative sequence1 – 292292MATDA…DPQLH → MWLVYSSGAPGTQQPARNRV FFPIGMAPGGVCWRPDGWGT GGQGRISGPGSMGAGQRLGS SGTQRCCWGSCFGKEVALRR VLHPS in isoform 2, isoform 3 and isoform 4.
VSP_004089
Alternative sequence2931Q → PVCMGVSCLCQ in isoform 4.
VSP_043529
Alternative sequence377 – 545169VRGPP…APFPS → PRCQGWTPRPCTPYCVWVLR VSRTWLLVRVAGCAEMVRTC CGVLTAPLPSTGAATSQPAP PGPGRACAADPAQET in isoform 3.
VSP_004090
Natural variant151R → C in APS1. Ref.23
Corresponds to variant rs179363875 [ dbSNP | Ensembl ].
VAR_026480
Natural variant151R → L in APS1; prevents homooligomerization; slightly alters subcellular localization; no effect on the transcriptional transactivation activity. Ref.11 Ref.19 Ref.26
Corresponds to variant rs179363876 [ dbSNP | Ensembl ].
VAR_013713
Natural variant161T → M in APS1; prevents homooligomerization; slightly alters subcellular localization; no effect on the transcriptional transactivation activity. Ref.11 Ref.19 Ref.20 Ref.26
Corresponds to variant rs179363877 [ dbSNP | Ensembl ].
VAR_013714
Natural variant211A → V in APS1; no effect on homooligomerization; no effect on subcellular localization; no effect on the transcriptional transactivation activity. Ref.11 Ref.25
Corresponds to variant rs179363886 [ dbSNP | Ensembl ].
VAR_026481
Natural variant22 – 232Missing in APS1; prevents homodimerization.
VAR_026482
Natural variant281L → P in APS1; abolishes association with cytoplasmic tubular structures and homodimerization. Ref.10 Ref.11 Ref.16 Ref.19
Corresponds to variant rs179363878 [ dbSNP | Ensembl ].
VAR_005004
Natural variant291L → P in APS1. Ref.11 Ref.22
Corresponds to variant rs179363879 [ dbSNP | Ensembl ].
VAR_013715
Natural variant771F → S in APS1; loss of homooligomerization. Ref.26
Corresponds to variant rs179363887 [ dbSNP | Ensembl ].
VAR_026483
Natural variant781W → R in APS1; loss of homooligomerization. Ref.11 Ref.19 Ref.20 Ref.24 Ref.26
Corresponds to variant rs179363880 [ dbSNP | Ensembl ].
VAR_013716
Natural variant801V → L in APS1. Ref.9 Ref.11 Ref.19
Corresponds to variant rs179363881 [ dbSNP | Ensembl ].
VAR_013717
Natural variant831K → E in APS1. Ref.1 Ref.11 Ref.19
VAR_005005
Natural variant851Y → C in APS1. Ref.9 Ref.19 Ref.25
Corresponds to variant rs179363882 [ dbSNP | Ensembl ].
VAR_013718
Natural variant901Y → C in APS1. Ref.11 Ref.19
Corresponds to variant rs179363883 [ dbSNP | Ensembl ].
VAR_013719
Natural variant931L → R in APS1. Ref.11 Ref.19
Corresponds to variant rs179363884 [ dbSNP | Ensembl ].
VAR_013720
Natural variant2281G → 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. Ref.11 Ref.21 Ref.27
VAR_014422
Natural variant2521P → L in APS1. Ref.24
Corresponds to variant rs34397615 [ dbSNP | Ensembl ].
VAR_026484
Natural variant2781S → R. Ref.17 Ref.19 Ref.23
Corresponds to variant rs1800520 [ dbSNP | Ensembl ].
VAR_005006
Natural variant3011V → M in APS1; no effect on protein structure or on interaction with histone H3. Ref.12 Ref.13 Ref.15 Ref.19
Corresponds to variant rs150634562 [ dbSNP | Ensembl ].
VAR_013721
Natural variant3051G → S.
VAR_013722
Natural variant3111C → Y in APS1; impairs zinc binding and folding of the PHD-type 1 zinc finger. Ref.9 Ref.12 Ref.13 Ref.15 Ref.19 Ref.25
VAR_013723
Natural variant3261P → L in APS1; no significant effect on structure, but may alter protein interactions. Ref.15 Ref.18
Corresponds to variant rs179363888 [ dbSNP | Ensembl ].
VAR_026485
Natural variant3261P → Q in APS1; alters folding of the PHD-type 1 zinc finger. Ref.9 Ref.11 Ref.13 Ref.15 Ref.19
Corresponds to variant rs179363885 [ dbSNP | Ensembl ].
VAR_013724
Natural variant5391P → L in APS1. Ref.24
Corresponds to variant rs179363889 [ dbSNP | Ensembl ].
VAR_026486

Experimental info

Mutagenesis2951N → A: Abolishes interaction with histone H3. Ref.14
Mutagenesis2971D → A: Strongly reduces interaction with unmethylated histone H3 and abolishes interaction with histone H3 trimethylated at 'Lys-4'. Ref.12
Mutagenesis2981E → A: Reduces interaction with histone H3. Ref.14
Mutagenesis3021C → P: Reduces transcriptional activation. Ref.10
Mutagenesis3031R → P: Alters protein folding and abolishes interaction with histone H3. Ref.14
Mutagenesis3041D → A: Strongly reduces interaction with histone H3. Ref.14
Mutagenesis3071E → A: Reduces interaction with histone H3. Ref.14
Mutagenesis3121D → A: Abolishes interaction with histone H3. Ref.12
Mutagenesis4371C → P: Reduces transcription activation. Ref.10
Sequence conflict437 – 46731CGDGT…TSRPG → W in CAA08759. Ref.3

Secondary structure

........................... 545
Helix Strand Turn

Details...

Sequences

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

Last modified June 1, 1998. Version 1.
Checksum: 8CF703F8C9411BC5

FASTA54557,727
        10         20         30         40         50         60 
MATDAALRRL LRLHRTEIAV AVDSAFPLLH ALADHDVVPE DKFQETLHLK EKEGCPQAFH 

        70         80         90        100        110        120 
ALLSWLLTQD STAILDFWRV LFKDYNLERY GRLQPILDSF PKDVDLSQPR KGRKPPAVPK 

       130        140        150        160        170        180 
ALVPPPRLPT KRKASEEARA AAPAALTPRG TASPGSQLKA KPPKKPESSA EQQRLPLGNG 

       190        200        210        220        230        240 
IQTMSASVQR AVAMSSGDVP GARGAVEGIL IQQVFESGGS KKCIQVGGEF YTPSKFEDSG 

       250        260        270        280        290        300 
SGKNKARSSS GPKPLVRAKG AQGAAPGGGE ARLGQQGSVP APLALPSDPQ LHQKNEDECA 

       310        320        330        340        350        360 
VCRDGGELIC CDGCPRAFHL ACLSPPLREI PSGTWRCSSC LQATVQEVQP RAEEPRPQEP 

       370        380        390        400        410        420 
PVETPLPPGL RSAGEEVRGP PGEPLAGMDT TLVYKHLPAP PSAAPLPGLD SSALHPLLCV 

       430        440        450        460        470        480 
GPEGQQNLAP GARCGVCGDG TDVLRCTHCA AAFHWRCHFP AGTSRPGTGL RCRSCSGDVT 

       490        500        510        520        530        540 
PAPVEGVLAP SPARLAPGPA KDDTASHEPA LHRDDLESLL SEHTFDGILQ WAIQSMARPA 


APFPS 

« Hide

Isoform 2 (AIRE-2) [UniParc].

Checksum: 7C99ABAD92DDC565
Show »

FASTA33835,507
Isoform 3 (AIRE-3) [UniParc].

Checksum: BD26FC231E0E5611
Show »

FASTA24425,927
Isoform 4 [UniParc].

Checksum: 37045012FF585F6E
Show »

FASTA34836,501

References

« Hide 'large scale' references
[1]"Positional cloning of the APECED gene."
Nagamine K., Peterson P., Scott H.S., Kudoh J., Minoshima S., Heino M., Krohn K.J.E., Lalioti M.D., Mullis P.E., Antonarakis S.E., Kawasaki K., Asakawa S., Ito F., Shimizu N.
Nat. Genet. 17:393-398(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2 AND 3), VARIANT APS1 GLU-83.
Tissue: Thymus.
[2]"An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains."
Aaltonen J., Bjoerses P., Perheentupa J., Horelli-Kuitunen N., Palotie A., Peltonen L., Lee Y.S., Francis F., Hennig S., Thiel C., Lehrach H., Yaspo M.-L.
Nat. Genet. 17:399-403(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
Tissue: Thymus.
[3]Lee Y.S., Francis F., Hennig S., Thiel C., Reinhard R., Lehrach H., Yaspo M.-L.
Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"The DNA sequence of human chromosome 21."
Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. expand/collapse author list , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.
Nature 405:311-319(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
[7]"Localization of the APECED protein in distinct nuclear structures."
Bjoerses P., Pelto-Huikko M., Kaukonen J., Aaltonen J., Peltonen L., Ulmanen I.
Hum. Mol. Genet. 8:259-266(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[8]"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: PARTIAL PROTEIN SEQUENCE, SUBUNIT STRUCTURE, DNA-BINDING, PHOSPHORYLATION.
[9]"Mutations in the AIRE gene: effects on subcellular location and transactivation function of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protein."
Bjeorses P., Halonen M., Palvimo J.J., Kolmer M., Aaltonen J., Ellonen P., Perheentupa J., Ulmanen I., Peltonen L.
Am. J. Hum. Genet. 66:378-392(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, VARIANTS APS1 LEU-80; CYS-85; TYR-311 AND GLN-326.
[10]"Subcellular localization of the autoimmune regulator protein. characterization of nuclear targeting and transcriptional activation domain."
Pitkaenen J., Vaehaemurto P., Krohn K.J.E., Peterson P.
J. Biol. Chem. 276:19597-19602(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF CYS-302 AND CYS-437, CHARACTERIZATION OF VARIANT APS1 PRO-28.
[11]"APECED-causing mutations in AIRE reveal the functional domains of the protein."
Halonen M., Kangas H., Rueppell T., Ilmarinen T., Ollila J., Kolmer M., Vihinen M., Palvimo J., Saarela J., Ulmanen I., Eskelin P.
Hum. Mutat. 23:245-257(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, HOMOOLIGOMERIZATION, CHARACTERIZATION OF VARIANTS APS1 LEU-15; MET-16; VAL-21; PRO-28; PRO-29; ARG-78; LEU-80; GLU-83; CYS-90; ARG-93; TRP-228 AND GLN-326.
[12]"The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression."
Org T., Chignola F., Hetenyi C., Gaetani M., Rebane A., Liiv I., Maran U., Mollica L., Bottomley M.J., Musco G., Peterson P.
EMBO Rep. 9:370-376(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HISTONE H3 NON-METHYLATED OR MONO-METHYLATED AT LYS-4, FUNCTION, MUTAGENESIS OF ASP-297 AND ASP-312, CHARACTERIZATION OF VARIANTS APS1 MET-301 AND TYR-311.
[13]"NMR structure of the first PHD finger of autoimmune regulator protein (AIRE1). Insights into autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) disease."
Bottomley M.J., Stier G., Pennacchini D., Legube G., Simon B., Akhtar A., Sattler M., Musco G.
J. Biol. Chem. 280:11505-11512(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 293-354 IN COMPLEX WITH ZINC IONS, CHARACTERIZATION OF VARIANTS APS1 MET-301; TYR-311 AND GLN-326.
[14]"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."
Chignola F., Gaetani M., Rebane A., Org T., Mollica L., Zucchelli C., Spitaleri A., Mannella V., Peterson P., Musco G.
Nucleic Acids Res. 37:2951-2961(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 293-354 IN COMPLEX WITH ZINC IONS AND UNMETHYLATED HISTONE H3 N-TERMINUS, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF ASN-295; GLU-298; ARG-303; ASP-304 AND GLU-307, INTERACTION WITH HISTOME H3.
[15]"Structure and site-specific recognition of histone H3 by the PHD finger of human autoimmune regulator."
Chakravarty S., Zeng L., Zhou M.-M.
Structure 17:670-679(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 294-347 IN COMPLEX WITH ZINC IONS AND UNMETHYLATED HISTONE H3 N-TERMINUS, CHARACTERIZATION OF VARIANTS APS1 MET-301; TYR-311; LEU-326 AND GLN-326.
[16]"Mutation analyses of North American APS-1 patients."
Heino M., Scott H.S., Chen Q., Peterson P., Maeenpaeae U., Papasavvas M.-P., Mittaz L., Barras C., Rossier C., Chrousos G.P., Stratakis C.A., Nagamine K., Kudoh J., Shimizu N., Maclaren N., Antonarakis S.E., Krohn K.J.E.
Hum. Mutat. 13:69-74(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT APS1 PRO-28.
[17]"Common mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients of different origins."
Scott H.S., Heino M., Peterson P., Mittaz L., Lalioti M.D., Betterle C., Cohen A., Seri M., Lerone M., Romeo G., Collin P., Salo M., Metcalfe R., Weetman A., Papasavvas M.-P., Rossier C., Nagamine K., Kudoh J. expand/collapse author list , Shimizu N., Krohn K.J.E., Antonarakis S.E.
Mol. Endocrinol. 12:1112-1119(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ARG-278.
[18]"Identification of a novel mutation in the autoimmune regulator (AIRE-1) gene in a French family with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy."
Saugier-Veber P., Drouot N., Wolf L.M., Kuhn J.M., Frebourg T., Lefebvre H.
Eur. J. Endocrinol. 144:347-351(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT APS1 LEU-326.
[19]"APECED mutations in the autoimmune regulator (AIRE) gene."
Heino M., Peterson P., Kudoh J., Shimizu N., Antonarakis S.E., Scott H.S., Krohn K.J.E.
Hum. Mutat. 18:205-211(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS APS1 LEU-15; MET-16; PRO-28; PR0-29; ARG-78; LEU-80; GLU-83; CYS-85; CYS-90; ARG-93; MET-301; TYR-311 AND GLN-326, VARIANT ARG-278.
[20]"Novel AIRE mutations and P450 cytochrome autoantibodies in Central and Eastern European patients with APECED."
The MEWPE-APECED study group
Cihakova D., Trebusak K., Heino M., Fadeyev V., Tiulpakov A., Battelino T., Tar A., Halasz Z., Bluemel P., Tawfik S., Krohn K., Lebl J., Peterson P.
Hum. Mutat. 18:225-232(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS APS1 MET-16 AND ARG-78.
[21]"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."
Cetani F., Barbesino G., Borsari S., Pardi E., Cianferotti L., Pinchera A., Marcocci C.
J. Clin. Endocrinol. Metab. 86:4747-4752(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT APS1 TRP-228.
[22]"Distinct clinical phenotype and immunoreactivity in Japanese siblings with autoimmune polyglandular syndrome type 1 (APS-1) associated with compound heterozygous novel AIRE gene mutations."
Kogawa K., Kudoh J., Nagafuchi S., Ohga S., Katsuta H., Ishibashi H., Harada M., Hara T., Shimizu N.
Clin. Immunol. 103:277-283(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT APS1 PRO-29.
[23]"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."
Sato K., Nakajima K., Imamura H., Deguchi T., Horinouchi S., Yamazaki K., Yamada E., Kanaji Y., Takano K.
Endocr. J. 49:625-633(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT APS1 CYS-15, VARIANT ARG-278.
[24]"Delineation of the molecular defects in the AIRE gene in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients from Southern Italy."
Meloni A., Perniola R., Faa V., Corvaglia E., Cao A., Rosatelli M.C.
J. Clin. Endocrinol. Metab. 87:841-846(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS APS1 ARG-78; LEU-252 AND LEU-539.
[25]"AIRE mutations and human leukocyte antigen genotypes as determinants of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy phenotype."
Halonen M., Eskelin P., Myhre A.-G., Perheentupa J., Husebye E.S., Kaempe O., Rorsman F., Peltonen L., Ulmanen I., Partanen J.
J. Clin. Endocrinol. Metab. 87:2568-2574(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS APS1 VAL-21; CYS-85 AND TYR-311.
[26]"Two novel mutations of the AIRE protein affecting its homodimerization properties."
Meloni A., Fiorillo E., Corda D., Perniola R., Cao A., Rosatelli M.C.
Hum. Mutat. 25:319-319(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS APS1 22-VAL-ASP-23 DEL; SER-77 AND ARG-78, CHARACTERIZATION OF VARIANTS APS1 LEU-15; MET-16; 22-VAL-ASP-23 DEL; SER-77 AND ARG-78.
[27]"Functional analysis of SAND mutations in AIRE supports dominant inheritance of the G228W mutation."
Ilmarinen T., Eskelin P., Halonen M., Rueppell T., Kilpikari R., Torres G.D., Kangas H., Ulmanen I.
Hum. Mutat. 26:322-331(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT APS1 TRP-228.
+Additional computationally mapped references.

Web resources

AIREbase

AIRE mutation db

GeneReviews
Mendelian genes autoimmune regulator (AIRE)

Leiden Open Variation Database (LOVD)

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_000374.1. NM_000383.3.
XP_005261167.1. XM_005261110.1.
UniGeneHs.129829.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1XWHNMR-A293-354[»]
2KE1NMR-A293-354[»]
2KFTNMR-A294-347[»]
2LRINMR-C423-485[»]
ProteinModelPortalO43918.
SMRO43918. Positions 190-250, 294-347, 423-485.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106823. 53 interactions.
DIPDIP-47504N.
IntActO43918. 23 interactions.
MINTMINT-6542056.
STRING9606.ENSP00000291582.

PTM databases

PhosphoSiteO43918.

Proteomic databases

PaxDbO43918.
PRIDEO43918.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000291582; ENSP00000291582; ENSG00000160224. [O43918-1]
GeneID326.
KEGGhsa:326.
UCSCuc002zei.3. human. [O43918-1]
uc002zej.3. human. [O43918-4]

Organism-specific databases

CTD326.
GeneCardsGC21P045705.
HGNCHGNC:360. AIRE.
HPAHPA038267.
MIM109100. phenotype.
240300. phenotype.
607358. gene.
neXtProtNX_O43918.
Orphanet3453. Autoimmune polyendocrinopathy type 1.
PharmGKBPA24654.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG317492.
HOGENOMHOG000060093.
HOVERGENHBG014961.
InParanoidO43918.
KOK10603.
OMAAAILDFW.
OrthoDBEOG7ZSHT7.
PhylomeDBO43918.
TreeFamTF336193.

Gene expression databases

ArrayExpressO43918.
BgeeO43918.
CleanExHS_AIRE.
GenevestigatorO43918.

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.
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.
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

EvolutionaryTraceO43918.
GeneWikiAutoimmune_regulator.
GenomeRNAi326.
NextBio1337.
PROO43918.
SOURCESearch...

Entry information

Entry nameAIRE_HUMAN
AccessionPrimary (citable) accession number: O43918
Secondary accession number(s): B2RP50 expand/collapse secondary AC list , O43922, O43932, O75745
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: June 1, 1998
Last modified: April 16, 2014
This is version 154 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 21

Human chromosome 21: entries, gene names and cross-references to MIM