Q9Z0E3 (AIRE_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 105.
History...
Clusters with 
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Autoimmune regulator Alternative name(s): Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy protein homolog Short name=APECED protein homolog | ||
| Gene names |
| ||
| Organism | Mus musculus (Mouse) [Reference proteome] | ||
| Taxonomic identifier | 10090 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus |
Protein attributes
| Sequence length | 552 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence 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
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| itself | 4 | EBI-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 key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 552 | 552 | Autoimmune regulator | PRO_0000064514 | |||||
Regions | |||||||||
| Domain | 1 – 106 | 106 | HSR | ||||||
| Domain | 182 – 282 | 101 | SAND | ||||||
| Zinc finger | 298 – 345 | 48 | PHD-type 1 | ||||||
| Zinc finger | 434 – 475 | 42 | PHD-type 2 | ||||||
| Motif | 8 – 12 | 5 | LXXLL motif 1 | ||||||
| Motif | 64 – 68 | 5 | LXXLL motif 2 | ||||||
| Motif | 114 – 134 | 21 | Nuclear localization signal Potential | ||||||
| Motif | 414 – 418 | 5 | LXXLL motif 3 | ||||||
| Motif | 520 – 524 | 5 | LXXLL motif 4 | ||||||
Natural variations | |||||||||
| Alternative sequence | 265 – 268 | 4 | Missing in isoform 1c, isoform 1d, isoform 2c, isoform 2d, isoform 3c and isoform 3d. | VSP_004091 | |||||
| Alternative sequence | 296 | 1 | Missing in isoform 1b, isoform 1d, isoform 2b, isoform 2d, isoform 3b and isoform 3d. | VSP_004092 | |||||
| Alternative sequence | 367 – 425 | 59 | Missing in isoform 2a, isoform 2b, isoform 2c and isoform 2d. | VSP_004093 | |||||
| Alternative sequence | 368 – 409 | 42 | ILVGL…AAPLL → DQSPLQILLCRLDSHARHTG RSCTHLWAPSSTWACQGRGR LC in isoform 3a, isoform 3b, isoform 3c and isoform 3d. | VSP_004094 | |||||
| Alternative sequence | 410 – 552 | 143 | Missing in isoform 3a, isoform 3b, isoform 3c and isoform 3d. | VSP_004095 | |||||
Experimental info | |||||||||
| Mutagenesis | 299 | 1 | D → A: Abolishes interaction with histone H3. Ref.8 | ||||||
| Mutagenesis | 303 | 1 | V → M: No effect on interaction with histone H3. Ref.8 | ||||||
| Mutagenesis | 312 | 1 | C → W: Abolishes interaction with histone H3. Ref.8 | ||||||
| Mutagenesis | 313 | 1 | C → Y: Abolishes interaction with histone H3. Ref.8 | ||||||
| Mutagenesis | 328 | 1 | P → L: Reduces interaction with histone H3. Ref.8 | ||||||
Sequences
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
Entry information
| Entry name | AIRE_MOUSE | ||||||||
| Accession | Primary (citable) accession number: Q9Z0E3 Secondary accession number(s): Q9JLW0  Q9JLX0 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
Relevant documents
| MGD cross-references Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |