AIRE_MOUSE
ID AIRE_MOUSE Reviewed; 552 AA.
AC Q9Z0E3; Q9JLW0; Q9JLW1; Q9JLW2; Q9JLW3; Q9JLW4; Q9JLW5; Q9JLW6; Q9JLW7;
AC Q9JLW8; Q9JLW9; Q9JLX0;
DT 13-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Autoimmune regulator;
DE AltName: Full=Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy protein homolog;
DE Short=APECED protein homolog;
GN Name=Aire;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1A).
RX PubMed=10593569; DOI=10.3109/08916939908993859;
RA Shi J.-D., Wang C.-Y., Marron M.P., Ruan Q.-G., Huang Y.Q., Detter J.C.,
RA She J.-X.;
RT "Chromosomal localization and complete genomic sequence of the murine
RT autoimmune regulator gene (Aire).";
RL Autoimmunity 31:47-53(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1A).
RC STRAIN=129/Sv;
RX PubMed=10049735; DOI=10.1006/bbrc.1999.0223;
RA Mittaz L., Rossier C., Heino M., Petersen P., Krohn K.J.E., Gos A.,
RA Morris M.A., Kudoh J., Shimizu N., Antonarakis S.E., Scott H.S.;
RT "Isolation and characterization of the mouse Aire gene.";
RL Biochem. Biophys. Res. Commun. 255:483-490(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1A).
RC STRAIN=C57BL/6J; TISSUE=Thymus;
RX PubMed=10049587; DOI=10.1006/geno.1998.5656;
RA Wang C.-Y., Shi J.-D., Davoodi-Semiromi A., She J.-X.;
RT "Cloning of Aire, the mouse homologue of the autoimmune regulator (AIRE)
RT gene responsible for autoimmune polyglandular syndrome type 1 (ASP1).";
RL Genomics 55:322-326(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING.
RC STRAIN=129;
RX PubMed=10022980;
RA Blechschmidt K., Schweiger M., Wertz K., Poulson R., Christensen H.-M.,
RA Rosenthal A., Lehrach H., Yaspo M.-L.;
RT "The mouse Aire gene: comparative genomic sequencing, gene organization,
RT and expression.";
RL Genome Res. 9:158-166(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1A; 1B; 1C; 1D; 2A; 2B; 2C; 2D; 3A;
RP 3B; 3C AND 3D).
RC STRAIN=C57BL/6J, NOD, and SJL/J;
RX PubMed=10550218; DOI=10.1006/jaut.1999.0326;
RA Ruan Q.-G., Wang C.-Y., Shi J.-D., She J.-X.;
RT "Expression and alternative splicing of the mouse autoimmune regulator gene
RT (Aire).";
RL J. Autoimmun. 13:307-313(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1A), AND SUBCELLULAR LOCATION.
RC TISSUE=Kidney, and Thymus;
RX PubMed=11156688; DOI=10.1177/002215540104900207;
RA Halonen M., Pelto-Huikko M., Eskelin P., Peltonen L., Ulmanen I.,
RA Kolmer M.;
RT "Subcellular location and expression pattern of autoimmune regulator
RT (Aire), the mouse orthologue for human gene defective in autoimmune
RT polyendocrinopathy candidiasis ectodermal dystrophy (APECED).";
RL J. Histochem. Cytochem. 49:197-208(2001).
RN [7]
RP SUBUNIT STRUCTURE, AND PHOSPHORYLATION.
RX PubMed=11533054; DOI=10.1074/jbc.m104898200;
RA Kumar P.G., Laloraya M., Wang C.-Y., Ruan Q.-G., Davoodi-Semiromi A.,
RA Kao K.-J., She J.-X.;
RT "The autoimmune regulator (AIRE) is a DNA-binding protein.";
RL J. Biol. Chem. 276:41357-41364(2001).
RN [8]
RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=19015306; DOI=10.1084/jem.20080046;
RA Yano M., Kuroda N., Han H., Meguro-Horike M., Nishikawa Y., Kiyonari H.,
RA Maemura K., Yanagawa Y., Obata K., Takahashi S., Ikawa T., Satoh R.,
RA Kawamoto H., Mouri Y., Matsumoto M.;
RT "Aire controls the differentiation program of thymic epithelial cells in
RT the medulla for the establishment of self-tolerance.";
RL J. Exp. Med. 205:2827-2838(2008).
RN [9]
RP FUNCTION, INTERACTION WITH THE N-TERMINUS OF UNMODIFIED HISTONE H3,
RP INTERACTION WITH NUCLEOSOMES, DNA-BINDING, AND MUTAGENESIS OF ASP-299;
RP VAL-303; CYS-312; CYS-313 AND PRO-328.
RX PubMed=18840680; DOI=10.1073/pnas.0808470105;
RA Koh A.S., Kuo A.J., Park S.Y., Cheung P., Abramson J., Bua D., Carney D.,
RA Shoelson S.E., Gozani O., Kingston R.E., Benoist C., Mathis D.;
RT "Aire employs a histone-binding module to mediate immunological tolerance,
RT linking chromatin regulation with organ-specific autoimmunity.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:15878-15883(2008).
RN [10]
RP REVIEW OF FUNCTION IN SELF-TOLERANCE.
RX PubMed=19302042; DOI=10.1146/annurev.immunol.25.022106.141532;
RA Mathis D., Benoist C.;
RT "Aire.";
RL Annu. Rev. Immunol. 27:287-312(2009).
RN [11]
RP FUNCTION.
RX PubMed=19923453; DOI=10.4049/jimmunol.0804133;
RA Laan M., Kisand K., Kont V., Moell K., Tserel L., Scott H.S., Peterson P.;
RT "Autoimmune regulator deficiency results in decreased expression of CCR4
RT and CCR7 ligands and in delayed migration of CD4+ thymocytes.";
RL J. Immunol. 183:7682-7691(2009).
RN [12]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=21300913; DOI=10.1084/jem.20102327;
RA Lei Y., Ripen A.M., Ishimaru N., Ohigashi I., Nagasawa T., Jeker L.T.,
RA Boesl M.R., Hollaender G.A., Hayashi Y., Malefyt R.W., Nitta T.,
RA Takahama Y.;
RT "Aire-dependent production of XCL1 mediates medullary accumulation of
RT thymic dendritic cells and contributes to regulatory T cell development.";
RL J. Exp. Med. 208:383-394(2011).
RN [13]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=23993652; DOI=10.1016/j.immuni.2013.08.005;
RA Gardner J.M., Metzger T.C., McMahon E.J., Au-Yeung B.B., Krawisz A.K.,
RA Lu W., Price J.D., Johannes K.P., Satpathy A.T., Murphy K.M., Tarbell K.V.,
RA Weiss A., Anderson M.S.;
RT "Extrathymic Aire-expressing cells are a distinct bone marrow-derived
RT population that induce functional inactivation of CD4[?] T cells.";
RL Immunity 39:560-572(2013).
RN [14]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=26070482; DOI=10.1016/j.immuni.2015.05.013;
RA Yamano T., Nedjic J., Hinterberger M., Steinert M., Koser S., Pinto S.,
RA Gerdes N., Lutgens E., Ishimaru N., Busslinger M., Brors B., Kyewski B.,
RA Klein L.;
RT "Thymic B Cells Are Licensed to Present Self Antigens for Central T Cell
RT Tolerance Induction.";
RL Immunity 42:1048-1061(2015).
CC -!- FUNCTION: Transcription factor playing an essential role to promote
CC self-tolerance in the thymus by regulating the expression of a wide
CC array of self-antigens that have the commonality of being tissue-
CC restricted in their expression pattern in the periphery, called tissue
CC restricted antigens (TRA) (Probable). Binds to G-doublets in an A/T-
CC rich environment; the preferred motif is a tandem repeat of 5'-.
CC ATTGGTTA-3' combined with a 5'-TTATTA-3' box. Binds to nucleosomes (By
CC similarity). Binds to chromatin and interacts selectively with histone
CC H3 that is not methylated at 'Lys-4', not phosphorylated at 'Thr-3' and
CC not methylated at 'Arg-2'. Functions as a sensor of histone H3
CC modifications that are important for the epigenetic regulation of gene
CC expression. Mainly expressed by medullary thymic epithelial cells
CC (mTECs), induces the expression of thousands of tissue-restricted
CC proteins, which are presented on major histocompatibility complex class
CC I (MHC-I) and MHC-II molecules to developing T-cells percolating
CC through the thymic medulla (By similarity). Also induces self-tolerance
CC through other mechanisms such as the regulation of the mTEC
CC differentiation program (PubMed:19015306). Controls the medullary
CC accumulation of thymic dendritic cells and the development of
CC regulatory T-cell through the regulation of XCL1 expression
CC (PubMed:21300913). Regulates the production of CCR4 and CCR7 ligands in
CC medullary thymic epithelial cells and alters the coordinated maturation
CC and migration of thymocytes (PubMed:19923453). In thimic B-cells,
CC allows the presentation of licensing-dependent endogenous self-anitgen
CC for negative selection (PubMed:26070482). In secondary lymphoid organs,
CC induces functional inactivation of CD4(+) T-cells. Expressed by a
CC distinct bone marrow-derived population, induces self-tolerance through
CC a mechanism that does not require regulatory T-cells and is resitant to
CC innate inflammatory stimuli (PubMed:23993652).
CC {ECO:0000250|UniProtKB:O43918, ECO:0000269|PubMed:19015306,
CC ECO:0000269|PubMed:19923453, ECO:0000269|PubMed:21300913,
CC ECO:0000269|PubMed:23993652, ECO:0000269|PubMed:26070482,
CC ECO:0000305|PubMed:19302042}.
CC -!- SUBUNIT: Homodimer and homotetramer. Interacts with CREBBP. Interacts
CC preferentially with histone H3 that is not methylated at 'Lys-4'. Binds
CC with lower affinity to histone H3 that is monomethylated at 'Lys-4'.
CC Trimethylation of histone H3 at 'Lys-4' or phosphorylation at 'Thr-3'
CC abolish the interaction. Binds with lower affinity to histone H3 that
CC is acetylated at 'Lys-4', or that is acetylated at 'Lys-9' or
CC trimethylated at 'Lys-9'. Binds histone H3 that is dimethylated at
CC 'Arg-2' with very low affinity (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q9Z0E3; Q9Z0E3: Aire; NbExp=4; IntAct=EBI-80858, EBI-80858;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00185,
CC ECO:0000255|PROSITE-ProRule:PRU00747, ECO:0000269|PubMed:11156688,
CC ECO:0000269|PubMed:19015306, ECO:0000269|PubMed:26070482}. Cytoplasm
CC {ECO:0000269|PubMed:11156688}. Note=Predominantly nuclear but also
CC cytoplasmic. Found in nuclear body-like structures (dots) and in a
CC filamentous vimentin-like pattern. {ECO:0000250|UniProtKB:O43918,
CC ECO:0000269|PubMed:19015306}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=12;
CC Comment=Additional isoforms seem to exist.;
CC Name=1a;
CC IsoId=Q9Z0E3-1; Sequence=Displayed;
CC Name=1b;
CC IsoId=Q9Z0E3-2; Sequence=VSP_004092;
CC Name=1c;
CC IsoId=Q9Z0E3-3; Sequence=VSP_004091;
CC Name=1d;
CC IsoId=Q9Z0E3-4; Sequence=VSP_004091, VSP_004092;
CC Name=2a;
CC IsoId=Q9Z0E3-5; Sequence=VSP_004093;
CC Name=2b;
CC IsoId=Q9Z0E3-6; Sequence=VSP_004092, VSP_004093;
CC Name=2c;
CC IsoId=Q9Z0E3-7; Sequence=VSP_004091, VSP_004093;
CC Name=2d;
CC IsoId=Q9Z0E3-8; Sequence=VSP_004091, VSP_004092, VSP_004093;
CC Name=3a;
CC IsoId=Q9Z0E3-9; Sequence=VSP_004094, VSP_004095;
CC Name=3b;
CC IsoId=Q9Z0E3-10; Sequence=VSP_004092, VSP_004094, VSP_004095;
CC Name=3c;
CC IsoId=Q9Z0E3-11; Sequence=VSP_004091, VSP_004094, VSP_004095;
CC Name=3d;
CC IsoId=Q9Z0E3-12; Sequence=VSP_004091, VSP_004092, VSP_004094,
CC VSP_004095;
CC -!- TISSUE SPECIFICITY: Highly expressed in a few cells in the medulla of
CC the thymus (medullary epithelial cells) (at protein level)
CC (PubMed:23993652). Expressed in thymic but no peripheral B-cells
CC (PubMed:26070482). In secondary lymphoid organs, expressed in a
CC discrete population of bone marrow-derived toleregenic antigen
CC presenting cells (APCs) called extrathymic AIRE expressing cells
CC (eTAC)(at protein level) (PubMed:23993652). Detected at very low levels
CC in thymus, lymph node, liver, brain, ovary, lung, testis, kidney,
CC heart, spleen, bone marrow, skeletal muscle and adrenal gland. Isoforms
CC 1a to 1d predominate, isoforms 2a to 2d are intermediate and isoforms
CC 3a to 3d are expressed at extremely low levels.
CC {ECO:0000269|PubMed:23993652, ECO:0000269|PubMed:26070482}.
CC -!- DEVELOPMENTAL STAGE: In the thymus, not expressed at 13.5 dpc but
CC present at 16.5 dpc and postnatal day 1. {ECO:0000269|PubMed:19015306}.
CC -!- DOMAIN: Interacts via the first PHD domain with the N-terminus of
CC histone H3 that is not methylated at 'Lys-4'. Disruption of the first
CC PHD domain has been shown to lead to reduced transcriptional activity
CC and to localization of the protein mainly in the cytoplasm in small
CC granules. While the PHD zinc fingers are necessary for the
CC transactivation capacity of the protein, other regions also modulate
CC this function (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The L-X-X-L-L repeats may be implicated in binding to nuclear
CC receptors.
CC -!- DOMAIN: The N-terminal HSR domain is required for localization on
CC tubular structures. {ECO:0000250}.
CC -!- PTM: Phosphorylated. {ECO:0000269|PubMed:11533054}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice show an altered thymic
CC organization with altered morphology and location of mTECs
CC (PubMed:19015306). They exhibit defective accumulation of thymic
CC dendritic cells in the medullary region and generation of naturally
CC ocurring T cells in the thymus (PubMed:21300913).
CC {ECO:0000269|PubMed:19015306, ECO:0000269|PubMed:21300913}.
CC -!- MISCELLANEOUS: [Isoform 3a]: Probably inactive. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3b]: Probably inactive. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3c]: Probably inactive. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3d]: Probably inactive. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF105002; AAD46421.1; -; Genomic_DNA.
DR EMBL; AF128772; AAF36481.1; -; mRNA.
DR EMBL; AF128773; AAF36482.1; -; mRNA.
DR EMBL; AJ007715; CAA07620.1; -; Genomic_DNA.
DR EMBL; AF079536; AAD20444.1; -; mRNA.
DR EMBL; AJ132243; CAB36909.1; -; mRNA.
DR EMBL; AF128115; AAF36460.1; -; mRNA.
DR EMBL; AF128116; AAF36461.1; -; mRNA.
DR EMBL; AF128117; AAF36462.1; -; mRNA.
DR EMBL; AF128118; AAF36463.1; -; mRNA.
DR EMBL; AF128119; AAF36464.1; -; mRNA.
DR EMBL; AF128120; AAF36465.1; -; mRNA.
DR EMBL; AF128121; AAF36466.1; -; mRNA.
DR EMBL; AF128122; AAF36467.1; -; mRNA.
DR EMBL; AF128123; AAF36468.1; -; mRNA.
DR EMBL; AF128124; AAF36469.1; -; mRNA.
DR EMBL; AF128125; AAF36470.1; -; mRNA.
DR EMBL; AJ243821; CAB66141.1; -; mRNA.
DR CCDS; CCDS23961.1; -. [Q9Z0E3-1]
DR CCDS; CCDS70051.1; -. [Q9Z0E3-10]
DR CCDS; CCDS70052.1; -. [Q9Z0E3-6]
DR CCDS; CCDS70053.1; -. [Q9Z0E3-2]
DR CCDS; CCDS70054.1; -. [Q9Z0E3-9]
DR CCDS; CCDS70055.1; -. [Q9Z0E3-5]
DR CCDS; CCDS70056.1; -. [Q9Z0E3-12]
DR CCDS; CCDS70057.1; -. [Q9Z0E3-8]
DR CCDS; CCDS70058.1; -. [Q9Z0E3-4]
DR CCDS; CCDS70059.1; -. [Q9Z0E3-11]
DR CCDS; CCDS70060.1; -. [Q9Z0E3-3]
DR RefSeq; NP_001258478.1; NM_001271549.1. [Q9Z0E3-2]
DR RefSeq; NP_001258479.1; NM_001271550.1. [Q9Z0E3-3]
DR RefSeq; NP_001258480.1; NM_001271551.1. [Q9Z0E3-4]
DR RefSeq; NP_001258481.1; NM_001271552.1. [Q9Z0E3-5]
DR RefSeq; NP_001258482.1; NM_001271553.1. [Q9Z0E3-6]
DR RefSeq; NP_001258483.1; NM_001271554.1. [Q9Z0E3-7]
DR RefSeq; NP_001258484.1; NM_001271555.1. [Q9Z0E3-8]
DR RefSeq; NP_001258485.1; NM_001271556.1. [Q9Z0E3-9]
DR RefSeq; NP_001258486.1; NM_001271557.1. [Q9Z0E3-10]
DR RefSeq; NP_001258487.1; NM_001271558.1. [Q9Z0E3-11]
DR RefSeq; NP_001258488.1; NM_001271559.1. [Q9Z0E3-12]
DR RefSeq; NP_033776.1; NM_009646.2. [Q9Z0E3-1]
DR AlphaFoldDB; Q9Z0E3; -.
DR SMR; Q9Z0E3; -.
DR BioGRID; 198044; 3.
DR DIP; DIP-31030N; -.
DR IntAct; Q9Z0E3; 90.
DR STRING; 10090.ENSMUSP00000114904; -.
DR iPTMnet; Q9Z0E3; -.
DR PhosphoSitePlus; Q9Z0E3; -.
DR jPOST; Q9Z0E3; -.
DR PaxDb; Q9Z0E3; -.
DR PRIDE; Q9Z0E3; -.
DR ProteomicsDB; 282046; -. [Q9Z0E3-1]
DR ProteomicsDB; 282047; -. [Q9Z0E3-2]
DR ProteomicsDB; 282048; -. [Q9Z0E3-3]
DR ProteomicsDB; 282049; -. [Q9Z0E3-4]
DR ProteomicsDB; 282050; -. [Q9Z0E3-5]
DR ProteomicsDB; 282051; -. [Q9Z0E3-6]
DR ProteomicsDB; 282052; -. [Q9Z0E3-7]
DR ProteomicsDB; 282053; -. [Q9Z0E3-8]
DR ProteomicsDB; 282054; -. [Q9Z0E3-9]
DR ProteomicsDB; 282055; -. [Q9Z0E3-10]
DR ProteomicsDB; 282056; -. [Q9Z0E3-11]
DR ProteomicsDB; 282057; -. [Q9Z0E3-12]
DR Antibodypedia; 10157; 649 antibodies from 43 providers.
DR DNASU; 11634; -.
DR Ensembl; ENSMUST00000019257; ENSMUSP00000019257; ENSMUSG00000000731. [Q9Z0E3-2]
DR Ensembl; ENSMUST00000105395; ENSMUSP00000101034; ENSMUSG00000000731. [Q9Z0E3-9]
DR Ensembl; ENSMUST00000105396; ENSMUSP00000101035; ENSMUSG00000000731. [Q9Z0E3-6]
DR Ensembl; ENSMUST00000128241; ENSMUSP00000114904; ENSMUSG00000000731. [Q9Z0E3-1]
DR Ensembl; ENSMUST00000130972; ENSMUSP00000122659; ENSMUSG00000000731. [Q9Z0E3-4]
DR Ensembl; ENSMUST00000140636; ENSMUSP00000121477; ENSMUSG00000000731. [Q9Z0E3-12]
DR Ensembl; ENSMUST00000145975; ENSMUSP00000120150; ENSMUSG00000000731. [Q9Z0E3-3]
DR Ensembl; ENSMUST00000148469; ENSMUSP00000118317; ENSMUSG00000000731. [Q9Z0E3-11]
DR Ensembl; ENSMUST00000154374; ENSMUSP00000117094; ENSMUSG00000000731. [Q9Z0E3-5]
DR Ensembl; ENSMUST00000155021; ENSMUSP00000122190; ENSMUSG00000000731. [Q9Z0E3-8]
DR Ensembl; ENSMUST00000156417; ENSMUSP00000115162; ENSMUSG00000000731. [Q9Z0E3-10]
DR GeneID; 11634; -.
DR KEGG; mmu:11634; -.
DR UCSC; uc007fwr.2; mouse. [Q9Z0E3-1]
DR UCSC; uc007fws.2; mouse. [Q9Z0E3-4]
DR UCSC; uc007fwt.2; mouse. [Q9Z0E3-10]
DR UCSC; uc007fwu.2; mouse. [Q9Z0E3-6]
DR UCSC; uc007fwv.2; mouse. [Q9Z0E3-12]
DR UCSC; uc007fww.2; mouse. [Q9Z0E3-8]
DR UCSC; uc007fwx.2; mouse. [Q9Z0E3-3]
DR UCSC; uc007fwz.2; mouse. [Q9Z0E3-9]
DR UCSC; uc007fxa.2; mouse. [Q9Z0E3-11]
DR UCSC; uc007fxb.2; mouse. [Q9Z0E3-7]
DR CTD; 326; -.
DR MGI; MGI:1338803; Aire.
DR VEuPathDB; HostDB:ENSMUSG00000000731; -.
DR eggNOG; KOG0383; Eukaryota.
DR GeneTree; ENSGT00940000161104; -.
DR HOGENOM; CLU_042233_1_0_1; -.
DR InParanoid; Q9Z0E3; -.
DR OMA; GIHKAMY; -.
DR PhylomeDB; Q9Z0E3; -.
DR TreeFam; TF336193; -.
DR BioGRID-ORCS; 11634; 3 hits in 76 CRISPR screens.
DR ChiTaRS; Aire; mouse.
DR PRO; PR:Q9Z0E3; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q9Z0E3; protein.
DR Bgee; ENSMUSG00000000731; Expressed in primary oocyte and 69 other tissues.
DR ExpressionAtlas; Q9Z0E3; baseline and differential.
DR Genevisible; Q9Z0E3; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0001674; C:female germ cell nucleus; IDA:MGI.
DR GO; GO:0001673; C:male germ cell nucleus; IDA:MGI.
DR GO; GO:0016604; C:nuclear body; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0042393; F:histone binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0045182; F:translation regulator activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0002509; P:central tolerance induction to self antigen; ISS:UniProtKB.
DR GO; GO:0006959; P:humoral immune response; IMP:MGI.
DR GO; GO:0045060; P:negative thymic T cell selection; IGI:MGI.
DR GO; GO:0002458; P:peripheral T cell tolerance induction; IDA:UniProtKB.
DR GO; GO:0032722; P:positive regulation of chemokine production; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:2000410; P:regulation of thymocyte migration; IMP:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0097536; P:thymus epithelium morphogenesis; IMP:UniProtKB.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IMP:MGI.
DR CDD; cd15540; PHD2_AIRE; 1.
DR Gene3D; 3.10.390.10; -; 1.
DR Gene3D; 3.30.40.10; -; 2.
DR InterPro; IPR008087; AIRE.
DR InterPro; IPR042580; AIRE_PHD2.
DR InterPro; IPR004865; HSR_dom.
DR InterPro; IPR010919; SAND-like_dom_sf.
DR InterPro; IPR000770; SAND_dom.
DR InterPro; IPR019786; Zinc_finger_PHD-type_CS.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR001965; Znf_PHD.
DR InterPro; IPR019787; Znf_PHD-finger.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF03172; HSR; 1.
DR Pfam; PF00628; PHD; 1.
DR Pfam; PF01342; SAND; 1.
DR PRINTS; PR01711; AIREGULATOR.
DR SMART; SM00249; PHD; 2.
DR SMART; SM00258; SAND; 1.
DR SUPFAM; SSF57903; SSF57903; 2.
DR SUPFAM; SSF63763; SSF63763; 1.
DR PROSITE; PS51414; HSR; 1.
DR PROSITE; PS50864; SAND; 1.
DR PROSITE; PS01359; ZF_PHD_1; 2.
DR PROSITE; PS50016; ZF_PHD_2; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Cytoplasm; DNA-binding; Metal-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..552
FT /note="Autoimmune regulator"
FT /id="PRO_0000064514"
FT DOMAIN 1..106
FT /note="HSR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00747"
FT DOMAIN 182..282
FT /note="SAND"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00185"
FT ZN_FING 298..345
FT /note="PHD-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 434..475
FT /note="PHD-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT REGION 109..177
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 472..514
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 8..12
FT /note="LXXLL motif 1"
FT MOTIF 64..68
FT /note="LXXLL motif 2"
FT MOTIF 114..134
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 414..418
FT /note="LXXLL motif 3"
FT MOTIF 520..524
FT /note="LXXLL motif 4"
FT COMPBIAS 472..487
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 265..268
FT /note="Missing (in isoform 1c, isoform 1d, isoform 2c,
FT isoform 2d, isoform 3c and isoform 3d)"
FT /evidence="ECO:0000303|PubMed:10550218"
FT /id="VSP_004091"
FT VAR_SEQ 296
FT /note="Missing (in isoform 1b, isoform 1d, isoform 2b,
FT isoform 2d, isoform 3b and isoform 3d)"
FT /evidence="ECO:0000303|PubMed:10550218"
FT /id="VSP_004092"
FT VAR_SEQ 367..425
FT /note="Missing (in isoform 2a, isoform 2b, isoform 2c and
FT isoform 2d)"
FT /evidence="ECO:0000303|PubMed:10550218"
FT /id="VSP_004093"
FT VAR_SEQ 368..409
FT /note="ILVGLRSASEKTRGPSRELKASSDAAVTYVNLLAPHPAAPLL -> DQSPLQ
FT ILLCRLDSHARHTGRSCTHLWAPSSTWACQGRGRLC (in isoform 3a,
FT isoform 3b, isoform 3c and isoform 3d)"
FT /evidence="ECO:0000303|PubMed:10550218"
FT /id="VSP_004094"
FT VAR_SEQ 410..552
FT /note="Missing (in isoform 3a, isoform 3b, isoform 3c and
FT isoform 3d)"
FT /evidence="ECO:0000303|PubMed:10550218"
FT /id="VSP_004095"
FT MUTAGEN 299
FT /note="D->A: Abolishes interaction with histone H3."
FT /evidence="ECO:0000269|PubMed:18840680"
FT MUTAGEN 303
FT /note="V->M: No effect on interaction with histone H3."
FT /evidence="ECO:0000269|PubMed:18840680"
FT MUTAGEN 312
FT /note="C->W: Abolishes interaction with histone H3."
FT /evidence="ECO:0000269|PubMed:18840680"
FT MUTAGEN 313
FT /note="C->Y: Abolishes interaction with histone H3."
FT /evidence="ECO:0000269|PubMed:18840680"
FT MUTAGEN 328
FT /note="P->L: Reduces interaction with histone H3."
FT /evidence="ECO:0000269|PubMed:18840680"
SQ SEQUENCE 552 AA; 59042 MW; BF30F8F66B71239A CRC64;
MAGGDGMLRR LLRLHRTEIA VAIDSAFPLL HALADHDVVP EDKFQETLRL KEKEGCPQAF
HALLSWLLTR DSGAILDFWR ILFKDYNLER YSRLHSILDG FPKDVDLNQS RKGRKPLAGP
KAAVLPPRPP TKRKALEEPR ATPPATLASK SVSSPGSHLK TKPPKKPDGN LESQHLPLGN
GIQTMAASVQ RAVTVASGDV PGTRGAVEGI LIQQVFESGR SKKCIQVGGE FYTPNKFEDP
SGNLKNKARS GSSLKPVVRA KGAQVTIPGR DEQKVGQQCG VPPLPSLPSE PQVNQKNEDE
CAVCHDGGEL ICCDGCPRAF HLACLSPPLQ EIPSGLWRCS CCLQGRVQQN LSQPEVSRPP
ELPAETPILV GLRSASEKTR GPSRELKASS DAAVTYVNLL APHPAAPLLE PSALCPLLSA
GNEGRPGPAP SARCSVCGDG TEVLRCAHCA AAFHWRCHFP TAAARPGTNL RCKSCSADST
PTPGTPGEAV PTSGPRPAPG LAKVGDDSAS HDPVLHRDDL ESLLNEHSFD GILQWAIQSM
SRPLAETPPF SS
