Q9Z0E3 · AIRE_MOUSE
- ProteinAutoimmune regulator
- GeneAire
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids552 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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) (Probable). 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 (By similarity).
Also induces self-tolerance through other mechanisms such as the regulation of the mTEC differentiation program (PubMed:19015306).
Controls the medullary accumulation of thymic dendritic cells and the development of regulatory T-cell through the regulation of XCL1 expression (PubMed:21300913).
Regulates the production of CCR4 and CCR7 ligands in medullary thymic epithelial cells and alters the coordinated maturation and migration of thymocytes (PubMed:19923453).
In thimic B-cells, allows the presentation of licensing-dependent endogenous self-anitgen for negative selection (PubMed:26070482).
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 (PubMed:23993652).
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 (By similarity).
Also induces self-tolerance through other mechanisms such as the regulation of the mTEC differentiation program (PubMed:19015306).
Controls the medullary accumulation of thymic dendritic cells and the development of regulatory T-cell through the regulation of XCL1 expression (PubMed:21300913).
Regulates the production of CCR4 and CCR7 ligands in medullary thymic epithelial cells and alters the coordinated maturation and migration of thymocytes (PubMed:19923453).
In thimic B-cells, allows the presentation of licensing-dependent endogenous self-anitgen for negative selection (PubMed:26070482).
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 (PubMed:23993652).
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameAutoimmune regulator
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9Z0E3
- Secondary accessions
Proteomes
Organism-specific databases
Phenotypes & Variants
Disruption phenotype
Deficient mice show an altered thymic organization with altered morphology and location of mTECs (PubMed:19015306).
They exhibit defective accumulation of thymic dendritic cells in the medullary region and generation of naturally ocurring T cells in the thymus (PubMed:21300913).
They exhibit defective accumulation of thymic dendritic cells in the medullary region and generation of naturally ocurring T cells in the thymus (PubMed:21300913).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 299 | Abolishes interaction with histone H3. | ||||
Sequence: D → A | ||||||
Mutagenesis | 303 | No effect on interaction with histone H3. | ||||
Sequence: V → M | ||||||
Mutagenesis | 312 | Abolishes interaction with histone H3. | ||||
Sequence: C → W | ||||||
Mutagenesis | 313 | Abolishes interaction with histone H3. | ||||
Sequence: C → Y | ||||||
Mutagenesis | 328 | Reduces interaction with histone H3. | ||||
Sequence: P → L |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 38 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000064514 | 1-552 | Autoimmune regulator | |||
Sequence: MAGGDGMLRRLLRLHRTEIAVAIDSAFPLLHALADHDVVPEDKFQETLRLKEKEGCPQAFHALLSWLLTRDSGAILDFWRILFKDYNLERYSRLHSILDGFPKDVDLNQSRKGRKPLAGPKAAVLPPRPPTKRKALEEPRATPPATLASKSVSSPGSHLKTKPPKKPDGNLESQHLPLGNGIQTMAASVQRAVTVASGDVPGTRGAVEGILIQQVFESGRSKKCIQVGGEFYTPNKFEDPSGNLKNKARSGSSLKPVVRAKGAQVTIPGRDEQKVGQQCGVPPLPSLPSEPQVNQKNEDECAVCHDGGELICCDGCPRAFHLACLSPPLQEIPSGLWRCSCCLQGRVQQNLSQPEVSRPPELPAETPILVGLRSASEKTRGPSRELKASSDAAVTYVNLLAPHPAAPLLEPSALCPLLSAGNEGRPGPAPSARCSVCGDGTEVLRCAHCAAAFHWRCHFPTAAARPGTNLRCKSCSADSTPTPGTPGEAVPTSGPRPAPGLAKVGDDSASHDPVLHRDDLESLLNEHSFDGILQWAIQSMSRPLAETPPFSS |
Post-translational modification
Phosphorylated.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in a few cells in the medulla of the thymus (medullary epithelial cells) (at protein level) (PubMed:23993652).
Expressed in thymic but no peripheral B-cells (PubMed:26070482).
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).
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
Expressed in thymic but no peripheral B-cells (PubMed:26070482).
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).
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
Developmental stage
In the thymus, not expressed at 13.5 dpc but present at 16.5 dpc and postnatal day 1.
Gene expression databases
Interaction
Subunit
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).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9Z0E3 | Aire Q9Z0E3 | 4 | EBI-80858, EBI-80858 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, motif, region, zinc finger, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 1-106 | HSR | ||||
Sequence: MAGGDGMLRRLLRLHRTEIAVAIDSAFPLLHALADHDVVPEDKFQETLRLKEKEGCPQAFHALLSWLLTRDSGAILDFWRILFKDYNLERYSRLHSILDGFPKDVD | ||||||
Motif | 8-12 | LXXLL motif 1 | ||||
Sequence: LRRLL | ||||||
Motif | 64-68 | LXXLL motif 2 | ||||
Sequence: LSWLL | ||||||
Region | 109-177 | Disordered | ||||
Sequence: QSRKGRKPLAGPKAAVLPPRPPTKRKALEEPRATPPATLASKSVSSPGSHLKTKPPKKPDGNLESQHLP | ||||||
Motif | 114-134 | Nuclear localization signal | ||||
Sequence: RKPLAGPKAAVLPPRPPTKRK | ||||||
Domain | 182-282 | SAND | ||||
Sequence: IQTMAASVQRAVTVASGDVPGTRGAVEGILIQQVFESGRSKKCIQVGGEFYTPNKFEDPSGNLKNKARSGSSLKPVVRAKGAQVTIPGRDEQKVGQQCGVP | ||||||
Zinc finger | 298-345 | PHD-type 1 | ||||
Sequence: EDECAVCHDGGELICCDGCPRAFHLACLSPPLQEIPSGLWRCSCCLQG | ||||||
Motif | 414-418 | LXXLL motif 3 | ||||
Sequence: LCPLL | ||||||
Zinc finger | 434-475 | PHD-type 2 | ||||
Sequence: CSVCGDGTEVLRCAHCAAAFHWRCHFPTAAARPGTNLRCKSC | ||||||
Compositional bias | 472-487 | Polar residues | ||||
Sequence: CKSCSADSTPTPGTPG | ||||||
Region | 472-514 | Disordered | ||||
Sequence: CKSCSADSTPTPGTPGEAVPTSGPRPAPGLAKVGDDSASHDPV | ||||||
Motif | 520-524 | LXXLL motif 4 | ||||
Sequence: LESLL |
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.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 12 isoforms produced by Alternative splicing. Additional isoforms seem to exist.
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.
- Name1a
- Length552
- Mass (Da)59,042
- Last updated1999-05-01 v1
- ChecksumBF30F8F66B71239A
Q9Z0E3-2
- Name1b
- Differences from canonical
- 296-296: Missing
Q9Z0E3-3
- Name1c
- Differences from canonical
- 265-268: Missing
Q9Z0E3-4
- Name1d
Q9Z0E3-5
- Name2a
- Differences from canonical
- 367-425: Missing
Q9Z0E3-6
- Name2b
Q9Z0E3-7
- Name2c
Q9Z0E3-8
- Name2d
Q9Z0E3-9
- Name3a
- NoteProbably inactive.
Q9Z0E3-10
- Name3b
- NoteProbably inactive.
Q9Z0E3-11
- Name3c
- NoteProbably inactive.
Q9Z0E3-12
- Name3d
- NoteProbably inactive.
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Features
Showing features for alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_004091 | 265-268 | in isoform 1c, isoform 1d, isoform 2c, isoform 2d, isoform 3c and isoform 3d | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_004092 | 296 | in isoform 1b, isoform 1d, isoform 2b, isoform 2d, isoform 3b and isoform 3d | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_004093 | 367-425 | in isoform 2a, isoform 2b, isoform 2c and isoform 2d | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_004094 | 368-409 | in isoform 3a, isoform 3b, isoform 3c and isoform 3d | |||
Sequence: ILVGLRSASEKTRGPSRELKASSDAAVTYVNLLAPHPAAPLL → DQSPLQILLCRLDSHARHTGRSCTHLWAPSSTWACQGRGRLC | ||||||
Alternative sequence | VSP_004095 | 410-552 | in isoform 3a, isoform 3b, isoform 3c and isoform 3d | |||
Sequence: Missing | ||||||
Compositional bias | 472-487 | Polar residues | ||||
Sequence: CKSCSADSTPTPGTPG |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF105002 EMBL· GenBank· DDBJ | AAD46421.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF128772 EMBL· GenBank· DDBJ | AAF36481.1 EMBL· GenBank· DDBJ | mRNA | ||
AF128773 EMBL· GenBank· DDBJ | AAF36482.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ007715 EMBL· GenBank· DDBJ | CAA07620.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF079536 EMBL· GenBank· DDBJ | AAD20444.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ132243 EMBL· GenBank· DDBJ | CAB36909.1 EMBL· GenBank· DDBJ | mRNA | ||
AF128115 EMBL· GenBank· DDBJ | AAF36460.1 EMBL· GenBank· DDBJ | mRNA | ||
AF128116 EMBL· GenBank· DDBJ | AAF36461.1 EMBL· GenBank· DDBJ | mRNA | ||
AF128117 EMBL· GenBank· DDBJ | AAF36462.1 EMBL· GenBank· DDBJ | mRNA | ||
AF128118 EMBL· GenBank· DDBJ | AAF36463.1 EMBL· GenBank· DDBJ | mRNA | ||
AF128119 EMBL· GenBank· DDBJ | AAF36464.1 EMBL· GenBank· DDBJ | mRNA | ||
AF128120 EMBL· GenBank· DDBJ | AAF36465.1 EMBL· GenBank· DDBJ | mRNA | ||
AF128121 EMBL· GenBank· DDBJ | AAF36466.1 EMBL· GenBank· DDBJ | mRNA | ||
AF128122 EMBL· GenBank· DDBJ | AAF36467.1 EMBL· GenBank· DDBJ | mRNA | ||
AF128123 EMBL· GenBank· DDBJ | AAF36468.1 EMBL· GenBank· DDBJ | mRNA | ||
AF128124 EMBL· GenBank· DDBJ | AAF36469.1 EMBL· GenBank· DDBJ | mRNA | ||
AF128125 EMBL· GenBank· DDBJ | AAF36470.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ243821 EMBL· GenBank· DDBJ | CAB66141.1 EMBL· GenBank· DDBJ | mRNA |