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Autoimmune regulator (Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy protein) (APECED protein)

 AIRE_HUMAN              Reviewed;         545 AA.
O43918; B2RP50; O43922; O43932; O75745;
15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
01-JUN-1998, sequence version 1.
05-DEC-2018, entry version 198.
RecName: Full=Autoimmune regulator;
AltName: Full=Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy protein;
Short=APECED protein;
Name=AIRE; Synonyms=APECED;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2 AND 3), AND
VARIANT APS1 GLU-83.
TISSUE=Thymus;
PubMed=9398839; DOI=10.1038/ng1297-393;
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.;
"Positional cloning of the APECED gene.";
Nat. Genet. 17:393-398(1997).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
TISSUE=Thymus;
PubMed=9398840; DOI=10.1038/ng1297-399;
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.;
"An autoimmune disease, APECED, caused by mutations in a novel gene
featuring two PHD-type zinc-finger domains.";
Nat. Genet. 17:399-403(1997).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=10830953; DOI=10.1038/35012518;
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., 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.;
"The DNA sequence of human chromosome 21.";
Nature 405:311-319(2000).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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., 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.
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
SUBCELLULAR LOCATION.
PubMed=9931333; DOI=10.1093/hmg/8.2.259;
Bjoerses P., Pelto-Huikko M., Kaukonen J., Aaltonen J., Peltonen L.,
Ulmanen I.;
"Localization of the APECED protein in distinct nuclear structures.";
Hum. Mol. Genet. 8:259-266(1999).
[8]
PARTIAL PROTEIN SEQUENCE, SUBUNIT STRUCTURE, DNA-BINDING, AND
PHOSPHORYLATION.
PubMed=11533054; DOI=10.1074/jbc.M104898200;
Kumar P.G., Laloraya M., Wang C.-Y., Ruan Q.-G., Davoodi-Semiromi A.,
Kao K.-J., She J.-X.;
"The autoimmune regulator (AIRE) is a DNA-binding protein.";
J. Biol. Chem. 276:41357-41364(2001).
[9]
SUBCELLULAR LOCATION, AND VARIANTS APS1 LEU-80; CYS-85; TYR-311 AND
GLN-326.
PubMed=10677297; DOI=10.1086/302765;
Bjeorses P., Halonen M., Palvimo J.J., Kolmer M., Aaltonen J.,
Ellonen P., Perheentupa J., Ulmanen I., Peltonen L.;
"Mutations in the AIRE gene: effects on subcellular location and
transactivation function of the autoimmune polyendocrinopathy-
candidiasis-ectodermal dystrophy protein.";
Am. J. Hum. Genet. 66:378-392(2000).
[10]
SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF CYS-302 AND CYS-437,
AND CHARACTERIZATION OF VARIANT APS1 PRO-28.
PubMed=11274163; DOI=10.1074/jbc.M008322200;
Pitkaenen J., Vaehaemurto P., Krohn K.J.E., Peterson P.;
"Subcellular localization of the autoimmune regulator protein.
characterization of nuclear targeting and transcriptional activation
domain.";
J. Biol. Chem. 276:19597-19602(2001).
[11]
SUBCELLULAR LOCATION, HOMOOLIGOMERIZATION, AND 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.
PubMed=14974083; DOI=10.1002/humu.20003;
Halonen M., Kangas H., Rueppell T., Ilmarinen T., Ollila J.,
Kolmer M., Vihinen M., Palvimo J., Saarela J., Ulmanen I., Eskelin P.;
"APECED-causing mutations in AIRE reveal the functional domains of the
protein.";
Hum. Mutat. 23:245-257(2004).
[12]
INTERACTION WITH HISTONE H3 NON-METHYLATED OR MONO-METHYLATED AT
LYS-4, FUNCTION, MUTAGENESIS OF ASP-297 AND ASP-312, AND
CHARACTERIZATION OF VARIANTS APS1 MET-301 AND TYR-311.
PubMed=18292755; DOI=10.1038/sj.embor.2008.11;
Org T., Chignola F., Hetenyi C., Gaetani M., Rebane A., Liiv I.,
Maran U., Mollica L., Bottomley M.J., Musco G., Peterson P.;
"The autoimmune regulator PHD finger binds to non-methylated histone
H3K4 to activate gene expression.";
EMBO Rep. 9:370-376(2008).
[13]
REVIEW OF FUNCTION IN SELF-TOLERANCE.
PubMed=19302042; DOI=10.1146/annurev.immunol.25.022106.141532;
Mathis D., Benoist C.;
"Aire.";
Annu. Rev. Immunol. 27:287-312(2009).
[14]
TISSUE SPECIFICITY.
PubMed=23993652; DOI=10.1016/j.immuni.2013.08.005;
Gardner J.M., Metzger T.C., McMahon E.J., Au-Yeung B.B., Krawisz A.K.,
Lu W., Price J.D., Johannes K.P., Satpathy A.T., Murphy K.M.,
Tarbell K.V., Weiss A., Anderson M.S.;
"Extrathymic Aire-expressing cells are a distinct bone marrow-derived
population that induce functional inactivation of CD4[?] T cells.";
Immunity 39:560-572(2013).
[15]
REVIEW OF FUNCTION IN SELF-TOLERANCE.
PubMed=26972725; DOI=10.1038/nri.2016.9;
Anderson M.S., Su M.A.;
"AIRE expands: new roles in immune tolerance and beyond.";
Nat. Rev. Immunol. 16:247-258(2016).
[16]
STRUCTURE BY NMR OF 293-354 IN COMPLEX WITH ZINC IONS, AND
CHARACTERIZATION OF VARIANTS APS1 MET-301; TYR-311 AND GLN-326.
PubMed=15649886; DOI=10.1074/jbc.M413959200;
Bottomley M.J., Stier G., Pennacchini D., Legube G., Simon B.,
Akhtar A., Sattler M., Musco G.;
"NMR structure of the first PHD finger of autoimmune regulator protein
(AIRE1). Insights into autoimmune polyendocrinopathy-candidiasis-
ectodermal dystrophy (APECED) disease.";
J. Biol. Chem. 280:11505-11512(2005).
[17]
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, AND
INTERACTION WITH HISTOME H3.
PubMed=19293276; DOI=10.1093/nar/gkp166;
Chignola F., Gaetani M., Rebane A., Org T., Mollica L., Zucchelli C.,
Spitaleri A., Mannella V., Peterson P., Musco G.;
"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.";
Nucleic Acids Res. 37:2951-2961(2009).
[18]
STRUCTURE BY NMR OF 294-347 IN COMPLEX WITH ZINC IONS AND UNMETHYLATED
HISTONE H3 N-TERMINUS, AND CHARACTERIZATION OF VARIANTS APS1 MET-301;
TYR-311; LEU-326 AND GLN-326.
PubMed=19446523; DOI=10.1016/j.str.2009.02.017;
Chakravarty S., Zeng L., Zhou M.-M.;
"Structure and site-specific recognition of histone H3 by the PHD
finger of human autoimmune regulator.";
Structure 17:670-679(2009).
[19]
VARIANT APS1 PRO-28.
PubMed=9888391;
DOI=10.1002/(SICI)1098-1004(1999)13:1<69::AID-HUMU8>3.0.CO;2-6;
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.;
"Mutation analyses of North American APS-1 patients.";
Hum. Mutat. 13:69-74(1999).
[20]
VARIANT ARG-278.
PubMed=9717837; DOI=10.1210/mend.12.8.0143;
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., Shimizu N., Krohn K.J.E., Antonarakis S.E.;
"Common mutations in autoimmune polyendocrinopathy-candidiasis-
ectodermal dystrophy patients of different origins.";
Mol. Endocrinol. 12:1112-1119(1998).
[21]
VARIANT APS1 LEU-326.
PubMed=11275943; DOI=10.1530/eje.0.1440347;
Saugier-Veber P., Drouot N., Wolf L.M., Kuhn J.M., Frebourg T.,
Lefebvre H.;
"Identification of a novel mutation in the autoimmune regulator (AIRE-
1) gene in a French family with autoimmune polyendocrinopathy-
candidiasis-ectodermal dystrophy.";
Eur. J. Endocrinol. 144:347-351(2001).
[22]
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, AND VARIANT
ARG-278.
PubMed=11524731; DOI=10.1002/humu.1176;
Heino M., Peterson P., Kudoh J., Shimizu N., Antonarakis S.E.,
Scott H.S., Krohn K.J.E.;
"APECED mutations in the autoimmune regulator (AIRE) gene.";
Hum. Mutat. 18:205-211(2001).
[23]
VARIANTS APS1 MET-16 AND ARG-78.
PubMed=11524733; DOI=10.1002/humu.1178;
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.;
"Novel AIRE mutations and P450 cytochrome autoantibodies in Central
and Eastern European patients with APECED.";
Hum. Mutat. 18:225-232(2001).
[24]
VARIANT APS1 TRP-228.
PubMed=11600535; DOI=10.1210/jcem.86.10.7884;
Cetani F., Barbesino G., Borsari S., Pardi E., Cianferotti L.,
Pinchera A., Marcocci C.;
"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.";
J. Clin. Endocrinol. Metab. 86:4747-4752(2001).
[25]
VARIANT APS1 PRO-29.
PubMed=12173302; DOI=10.1006/clim.2002.5208;
Kogawa K., Kudoh J., Nagafuchi S., Ohga S., Katsuta H., Ishibashi H.,
Harada M., Hara T., Shimizu N.;
"Distinct clinical phenotype and immunoreactivity in Japanese siblings
with autoimmune polyglandular syndrome type 1 (APS-1) associated with
compound heterozygous novel AIRE gene mutations.";
Clin. Immunol. 103:277-283(2002).
[26]
VARIANT APS1 CYS-15, AND VARIANT ARG-278.
PubMed=12625412; DOI=10.1507/endocrj.49.625;
Sato K., Nakajima K., Imamura H., Deguchi T., Horinouchi S.,
Yamazaki K., Yamada E., Kanaji Y., Takano K.;
"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.";
Endocr. J. 49:625-633(2002).
[27]
VARIANTS APS1 ARG-78; LEU-252 AND LEU-539.
PubMed=11836330; DOI=10.1210/jcem.87.2.8209;
Meloni A., Perniola R., Faa V., Corvaglia E., Cao A., Rosatelli M.C.;
"Delineation of the molecular defects in the AIRE gene in autoimmune
polyendocrinopathy-candidiasis-ectodermal dystrophy patients from
Southern Italy.";
J. Clin. Endocrinol. Metab. 87:841-846(2002).
[28]
VARIANTS APS1 VAL-21; CYS-85 AND TYR-311.
PubMed=12050215; DOI=10.1210/jcem.87.6.8564;
Halonen M., Eskelin P., Myhre A.-G., Perheentupa J., Husebye E.S.,
Kaempe O., Rorsman F., Peltonen L., Ulmanen I., Partanen J.;
"AIRE mutations and human leukocyte antigen genotypes as determinants
of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy
phenotype.";
J. Clin. Endocrinol. Metab. 87:2568-2574(2002).
[29]
VARIANTS APS1 22-VAL-ASP-23 DEL; SER-77 AND ARG-78, AND
CHARACTERIZATION OF VARIANTS APS1 LEU-15; MET-16; 22-VAL-ASP-23 DEL;
SER-77 AND ARG-78.
PubMed=15712268; DOI=10.1002/humu.9309;
Meloni A., Fiorillo E., Corda D., Perniola R., Cao A., Rosatelli M.C.;
"Two novel mutations of the AIRE protein affecting its
homodimerization properties.";
Hum. Mutat. 25:319-319(2005).
[30]
CHARACTERIZATION OF VARIANT APS1 TRP-228.
PubMed=16114041; DOI=10.1002/humu.20224;
Ilmarinen T., Eskelin P., Halonen M., Rueppell T., Kilpikari R.,
Torres G.D., Kangas H., Ulmanen I.;
"Functional analysis of SAND mutations in AIRE supports dominant
inheritance of the G228W mutation.";
Hum. Mutat. 26:322-331(2005).
[31]
INVOLVEMENT IN APS1, FUNCTION, SUBCELLULAR LOCATION, VARIANTS APS1
PRO-28; CYS-90; MET-301; TYR-311 AND LEU-326, CHARACTERIZATION OF
VARIANTS PRO-28; CYS-90; MET-301; TYR-311 AND LEU-326, MUTAGENESIS OF
28-LEU-LEU-29; LEU-97; ASP-297; ARG-303; ASP-312; CYS-446 AND ARG-471,
VARIANTS LYS-298; TRP-299; TYR-302; GLN-303; TRP-303; SER-305;
ARG-306; MET-309; GLN-316; TRP-316; PRO-319; GLN-328; TRP-328; ARG-332
AND ALA-484, AND CHARACTERIZATION OF VARIANTS LYS-298; TYR-302;
SER-305 AND GLN-328.
PubMed=26084028; DOI=10.1016/j.immuni.2015.04.021;
Oftedal B.E., Hellesen A., Erichsen M.M., Bratland E., Vardi A.,
Perheentupa J., Kemp E.H., Fiskerstrand T., Viken M.K., Weetman A.P.,
Fleishman S.J., Banka S., Newman W.G., Sewell W.A., Sozaeva L.S.,
Zayats T., Haugarvoll K., Orlova E.M., Haavik J., Johansson S.,
Knappskog P.M., Loevaas K., Wolff A.S., Abramson J., Husebye E.S.;
"Dominant mutations in the autoimmune regulator AIRE are associated
with common organ-specific autoimmune diseases.";
Immunity 42:1185-1196(2015).
[32]
INVOLVEMENT IN APS1, AND FUNCTION.
PubMed=27426947; DOI=10.1016/j.cell.2016.06.024;
APECED patient collaborative;
Meyer S., Woodward M., Hertel C., Vlaicu P., Haque Y., Kaerner J.,
Macagno A., Onuoha S.C., Fishman D., Peterson H., Metskuela K.,
Uibo R., Jaentti K., Hokynar K., Wolff A.S., Krohn K., Ranki A.,
Peterson P., Kisand K., Hayday A.;
"AIRE-deficient patients harbor unique high-affinity disease-
ameliorating autoantibodies.";
Cell 166:582-595(2016).
-!- 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)
(PubMed:26084028). 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
(PubMed:26084028). Also induces self-tolerance through other
mechanisms such as the regulation of the mTEC differentiation
program. Controls the medullary accumulation of thymic dendritic
cells and the development of regulatory T-cell through the
regulation of XCL1 expression. Regulates the production of CCR4
and CCR7 ligands in medullary thymic epithelial cells and alters
the coordinated maturation and migration of thymocytes. In thimic
B-cells, allows the presentation of licensing-dependent endogenous
self-anitgen for negative selection. 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 (By similarity).
{ECO:0000250|UniProtKB:Q9Z0E3, ECO:0000269|PubMed:11274163,
ECO:0000269|PubMed:18292755, ECO:0000269|PubMed:26084028,
ECO:0000305|PubMed:19302042, ECO:0000305|PubMed:26972725}.
-!- 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.
{ECO:0000269|PubMed:11533054, ECO:0000269|PubMed:15649886,
ECO:0000269|PubMed:18292755, ECO:0000269|PubMed:19293276,
ECO:0000269|PubMed:19446523}.
-!- INTERACTION:
Q9UER7:DAXX; NbExp=5; IntAct=EBI-1753081, EBI-77321;
P68431:HIST1H3D; NbExp=20; IntAct=EBI-1753081, EBI-79722;
P16333:NCK1; NbExp=2; IntAct=EBI-1753081, EBI-389883;
P78527:PRKDC; NbExp=2; IntAct=EBI-1753081, EBI-352053;
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14974083,
ECO:0000269|PubMed:26084028}. Cytoplasm
{ECO:0000269|PubMed:11274163, ECO:0000269|PubMed:14974083}.
Note=Predominantly nuclear but also cytoplasmic (PubMed:11274163,
PubMed:14974083). Found in nuclear body-like structures (dots) and
in a filamentous vimentin-like pattern (PubMed:11274163,
PubMed:14974083, PubMed:26084028). Associated with tubular
structures (PubMed:11274163, PubMed:14974083).
{ECO:0000269|PubMed:11274163, ECO:0000269|PubMed:14974083,
ECO:0000269|PubMed:26084028}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=4;
Comment=Additional isoforms seem to exist. Experimental
confirmation may be lacking for some isoforms.;
Name=1; Synonyms=AIRE-1;
IsoId=O43918-1; Sequence=Displayed;
Name=2; Synonyms=AIRE-2;
IsoId=O43918-2; Sequence=VSP_004089;
Name=3; Synonyms=AIRE-3;
IsoId=O43918-3; Sequence=VSP_004089, VSP_004090;
Name=4;
IsoId=O43918-4; Sequence=VSP_004089, VSP_043529;
Note=No experimental confirmation available.;
-!- 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. 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).
Isoform 2 and isoform 3 seem to be less frequently expressed than
isoform 1, if at all. {ECO:0000269|PubMed:23993652}.
-!- DOMAIN: The L-X-X-L-L repeats may be implicated in binding to
nuclear receptors.
-!- DOMAIN: The HSR domain is required for localization on tubular
structures (N-terminal part) and for homodimerization.
-!- 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.
-!- PTM: Phosphorylated. Phosphorylation could trigger
oligomerization. {ECO:0000269|PubMed:11533054}.
-!- 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. {ECO:0000269|PubMed:10677297,
ECO:0000269|PubMed:11274163, ECO:0000269|PubMed:11275943,
ECO:0000269|PubMed:11524731, ECO:0000269|PubMed:11524733,
ECO:0000269|PubMed:11600535, ECO:0000269|PubMed:11836330,
ECO:0000269|PubMed:12050215, ECO:0000269|PubMed:12173302,
ECO:0000269|PubMed:12625412, ECO:0000269|PubMed:14974083,
ECO:0000269|PubMed:15649886, ECO:0000269|PubMed:15712268,
ECO:0000269|PubMed:16114041, ECO:0000269|PubMed:18292755,
ECO:0000269|PubMed:19446523, ECO:0000269|PubMed:26084028,
ECO:0000269|PubMed:27426947, ECO:0000269|PubMed:9398839,
ECO:0000269|PubMed:9888391}. Note=The disease is caused by
mutations affecting the gene represented in this entry. 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 (PubMed:14974083). Heterozygous mutations within the
PHD1 domain have dominant-negatif effects and cause organ-specific
autoimmune diseases (PubMed:26084028). Patients harbor extremely
high-affinity, neutralizing autoantibodies, particularly against
specific cytokines such as type I interferons which could protect
them from some types of autoimmune diseases, like type I diabetes
(PubMed:27426947). {ECO:0000269|PubMed:14974083,
ECO:0000269|PubMed:26084028, ECO:0000269|PubMed:27426947}.
-!- WEB RESOURCE: Name=AIREbase; Note=AIRE mutation db;
URL="http://structure.bmc.lu.se/idbase/AIREbase/";
-!- WEB RESOURCE: Name=Mendelian genes autoimmune regulator (AIRE);
Note=Leiden Open Variation Database (LOVD);
URL="http://www.lovd.nl/AIRE";
-----------------------------------------------------------------------
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EMBL; AB006682; BAA23988.1; -; mRNA.
EMBL; AB006683; BAA23989.1; -; mRNA.
EMBL; AB006684; BAA23990.1; -; Genomic_DNA.
EMBL; AB006684; BAA23991.1; -; Genomic_DNA.
EMBL; AB006684; BAA23992.1; -; Genomic_DNA.
EMBL; AB006685; BAA23993.1; -; mRNA.
EMBL; Z97990; CAB10790.1; -; mRNA.
EMBL; AJ009610; CAA08759.1; -; Genomic_DNA.
EMBL; AP001754; BAA95560.1; -; Genomic_DNA.
EMBL; AP001060; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH471079; EAX09443.1; -; Genomic_DNA.
EMBL; BC137268; AAI37269.1; -; mRNA.
EMBL; BC137270; AAI37271.1; -; mRNA.
CCDS; CCDS13706.1; -. [O43918-1]
RefSeq; NP_000374.1; NM_000383.3. [O43918-1]
UniGene; Hs.129829; -.
PDB; 1XWH; NMR; -; A=293-354.
PDB; 2KE1; NMR; -; A=293-354.
PDB; 2KFT; NMR; -; A=294-347.
PDB; 2LRI; NMR; -; C=423-485.
PDBsum; 1XWH; -.
PDBsum; 2KE1; -.
PDBsum; 2KFT; -.
PDBsum; 2LRI; -.
ProteinModelPortal; O43918; -.
SMR; O43918; -.
BioGrid; 106823; 93.
CORUM; O43918; -.
DIP; DIP-47504N; -.
IntAct; O43918; 32.
MINT; O43918; -.
STRING; 9606.ENSP00000291582; -.
iPTMnet; O43918; -.
PhosphoSitePlus; O43918; -.
BioMuta; AIRE; -.
EPD; O43918; -.
PaxDb; O43918; -.
PeptideAtlas; O43918; -.
PRIDE; O43918; -.
ProteomicsDB; 49233; -.
ProteomicsDB; 49234; -. [O43918-2]
ProteomicsDB; 49235; -. [O43918-3]
ProteomicsDB; 49236; -. [O43918-4]
Ensembl; ENST00000291582; ENSP00000291582; ENSG00000160224. [O43918-1]
GeneID; 326; -.
KEGG; hsa:326; -.
UCSC; uc002zei.4; human. [O43918-1]
CTD; 326; -.
DisGeNET; 326; -.
EuPathDB; HostDB:ENSG00000160224.16; -.
GeneCards; AIRE; -.
HGNC; HGNC:360; AIRE.
HPA; HPA038267; -.
MalaCards; AIRE; -.
MIM; 109100; phenotype.
MIM; 240300; phenotype.
MIM; 607358; gene.
neXtProt; NX_O43918; -.
OpenTargets; ENSG00000160224; -.
Orphanet; 3453; Autoimmune polyendocrinopathy type 1.
Orphanet; 189466; Familial isolated hypoparathyroidism due to impaired PTH secretion.
PharmGKB; PA24654; -.
eggNOG; ENOG410IRE7; Eukaryota.
eggNOG; ENOG410XQQA; LUCA.
GeneTree; ENSGT00940000161104; -.
HOGENOM; HOG000033872; -.
HOVERGEN; HBG014961; -.
InParanoid; O43918; -.
KO; K10603; -.
OMA; LLSEHTF; -.
OrthoDB; EOG091G055U; -.
PhylomeDB; O43918; -.
TreeFam; TF336193; -.
SIGNOR; O43918; -.
EvolutionaryTrace; O43918; -.
GeneWiki; Autoimmune_regulator; -.
GenomeRNAi; 326; -.
PRO; PR:O43918; -.
Proteomes; UP000005640; Chromosome 21.
Bgee; ENSG00000160224; Expressed in 88 organ(s), highest expression level in amniotic fluid.
CleanEx; HS_AIRE; -.
Genevisible; O43918; HS.
GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
GO; GO:0016604; C:nuclear body; ISS:UniProtKB.
GO; GO:0005634; C:nucleus; IBA:GO_Central.
GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IC:NTNU_SB.
GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISM:NTNU_SB.
GO; GO:0042393; F:histone binding; IDA:UniProtKB.
GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
GO; GO:0000977; F:RNA polymerase II regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
GO; GO:0044212; F:transcription regulatory region DNA binding; IDA:UniProtKB.
GO; GO:0045182; F:translation regulator activity; IEA:InterPro.
GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
GO; GO:0002509; P:central tolerance induction to self antigen; IMP:UniProtKB.
GO; GO:0032602; P:chemokine production; ISS:UniProtKB.
GO; GO:0006959; P:humoral immune response; IBA:GO_Central.
GO; GO:0006955; P:immune response; TAS:ProtInc.
GO; GO:0045060; P:negative thymic T cell selection; IBA:GO_Central.
GO; GO:0002458; P:peripheral T cell tolerance induction; ISS:UniProtKB.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:NTNU_SB.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
GO; GO:2000410; P:regulation of thymocyte migration; ISS:UniProtKB.
GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
GO; GO:0097536; P:thymus epithelium morphogenesis; ISS:UniProtKB.
Gene3D; 3.10.390.10; -; 1.
Gene3D; 3.30.40.10; -; 2.
InterPro; IPR008087; AIRE.
InterPro; IPR004865; HSR_dom.
InterPro; IPR010919; SAND-like_dom_sf.
InterPro; IPR000770; SAND_dom.
InterPro; IPR019786; Zinc_finger_PHD-type_CS.
InterPro; IPR011011; Znf_FYVE_PHD.
InterPro; IPR001965; Znf_PHD.
InterPro; IPR019787; Znf_PHD-finger.
InterPro; IPR013083; Znf_RING/FYVE/PHD.
Pfam; PF03172; HSR; 1.
Pfam; PF00628; PHD; 1.
Pfam; PF01342; SAND; 1.
PRINTS; PR01711; AIREGULATOR.
SMART; SM00249; PHD; 2.
SMART; SM00258; SAND; 1.
SUPFAM; SSF57903; SSF57903; 2.
SUPFAM; SSF63763; SSF63763; 1.
PROSITE; PS51414; HSR; 1.
PROSITE; PS50864; SAND; 1.
PROSITE; PS01359; ZF_PHD_1; 2.
PROSITE; PS50016; ZF_PHD_2; 1.
1: Evidence at protein level;
3D-structure; Activator; Alternative splicing; Complete proteome;
Cytoplasm; Direct protein sequencing; Disease mutation; DNA-binding;
Metal-binding; Nucleus; Phosphoprotein; Polymorphism;
Reference proteome; Repeat; Transcription; Transcription regulation;
Zinc; Zinc-finger.
CHAIN 1 545 Autoimmune regulator.
/FTId=PRO_0000064513.
DOMAIN 1 105 HSR. {ECO:0000255|PROSITE-
ProRule:PRU00747}.
DOMAIN 181 280 SAND. {ECO:0000255|PROSITE-
ProRule:PRU00185}.
ZN_FING 296 343 PHD-type 1. {ECO:0000255|PROSITE-
ProRule:PRU00146}.
ZN_FING 434 475 PHD-type 2. {ECO:0000255|PROSITE-
ProRule:PRU00146}.
REGION 295 298 Interaction with histone H3 not
methylated at 'Lys-4'.
REGION 304 312 Interaction with histone H3 not
methylated at 'Lys-4'.
REGION 331 335 Interaction with histone H3 not
methylated at 'Lys-4'.
MOTIF 7 11 LXXLL motif 1.
MOTIF 63 67 LXXLL motif 2.
MOTIF 414 418 LXXLL motif 3.
MOTIF 516 520 LXXLL motif 4.
VAR_SEQ 1 292 MATDAALRRLLRLHRTEIAVAVDSAFPLLHALADHDVVPED
KFQETLHLKEKEGCPQAFHALLSWLLTQDSTAILDFWRVLF
KDYNLERYGRLQPILDSFPKDVDLSQPRKGRKPPAVPKALV
PPPRLPTKRKASEEARAAAPAALTPRGTASPGSQLKAKPPK
KPESSAEQQRLPLGNGIQTMSASVQRAVAMSSGDVPGARGA
VEGILIQQVFESGGSKKCIQVGGEFYTPSKFEDSGSGKNKA
RSSSGPKPLVRAKGAQGAAPGGGEARLGQQGSVPAPLALPS
DPQLH -> MWLVYSSGAPGTQQPARNRVFFPIGMAPGGVC
WRPDGWGTGGQGRISGPGSMGAGQRLGSSGTQRCCWGSCFG
KEVALRRVLHPS (in isoform 2, isoform 3 and
isoform 4). {ECO:0000303|PubMed:15489334,
ECO:0000303|PubMed:9398839}.
/FTId=VSP_004089.
VAR_SEQ 293 293 Q -> PVCMGVSCLCQ (in isoform 4).
{ECO:0000303|PubMed:15489334}.
/FTId=VSP_043529.
VAR_SEQ 377 545 VRGPPGEPLAGMDTTLVYKHLPAPPSAAPLPGLDSSALHPL
LCVGPEGQQNLAPGARCGVCGDGTDVLRCTHCAAAFHWRCH
FPAGTSRPGTGLRCRSCSGDVTPAPVEGVLAPSPARLAPGP
AKDDTASHEPALHRDDLESLLSEHTFDGILQWAIQSMARPA
APFPS -> PRCQGWTPRPCTPYCVWVLRVSRTWLLVRVAG
CAEMVRTCCGVLTAPLPSTGAATSQPAPPGPGRACAADPAQ
ET (in isoform 3).
{ECO:0000303|PubMed:9398839}.
/FTId=VSP_004090.
VARIANT 15 15 R -> C (in APS1; dbSNP:rs179363875).
{ECO:0000269|PubMed:12625412}.
/FTId=VAR_026480.
VARIANT 15 15 R -> L (in APS1; prevents
homooligomerization; slightly alters
subcellular localization; no effect on
the transcriptional transactivation
activity; dbSNP:rs179363876).
{ECO:0000269|PubMed:11524731,
ECO:0000269|PubMed:14974083,
ECO:0000269|PubMed:15712268}.
/FTId=VAR_013713.
VARIANT 16 16 T -> M (in APS1; prevents
homooligomerization; slightly alters
subcellular localization; no effect on
the transcriptional transactivation
activity; dbSNP:rs179363877).
{ECO:0000269|PubMed:11524731,
ECO:0000269|PubMed:11524733,
ECO:0000269|PubMed:14974083,
ECO:0000269|PubMed:15712268}.
/FTId=VAR_013714.
VARIANT 21 21 A -> V (in APS1; no effect on
homooligomerization; no effect on
subcellular localization; no effect on
the transcriptional transactivation
activity; dbSNP:rs179363886).
{ECO:0000269|PubMed:12050215,
ECO:0000269|PubMed:14974083}.
/FTId=VAR_026481.
VARIANT 22 23 Missing (in APS1; prevents
homodimerization).
{ECO:0000269|PubMed:15712268}.
/FTId=VAR_026482.
VARIANT 28 28 L -> P (in APS1; abolishes association
with cytoplasmic tubular structures and
homodimerization; loss of doted nuclear
localization; nuclear smear;
dbSNP:rs179363878).
{ECO:0000269|PubMed:11274163,
ECO:0000269|PubMed:11524731,
ECO:0000269|PubMed:14974083,
ECO:0000269|PubMed:26084028,
ECO:0000269|PubMed:9888391}.
/FTId=VAR_005004.
VARIANT 29 29 L -> P (in APS1; dbSNP:rs179363879).
{ECO:0000269|PubMed:12173302,
ECO:0000269|PubMed:14974083}.
/FTId=VAR_013715.
VARIANT 77 77 F -> S (in APS1; loss of
homooligomerization; dbSNP:rs179363887).
{ECO:0000269|PubMed:15712268}.
/FTId=VAR_026483.
VARIANT 78 78 W -> R (in APS1; loss of
homooligomerization; dbSNP:rs179363880).
{ECO:0000269|PubMed:11524731,
ECO:0000269|PubMed:11524733,
ECO:0000269|PubMed:11836330,
ECO:0000269|PubMed:14974083,
ECO:0000269|PubMed:15712268}.
/FTId=VAR_013716.
VARIANT 80 80 V -> L (in APS1; dbSNP:rs179363881).
{ECO:0000269|PubMed:10677297,
ECO:0000269|PubMed:11524731,
ECO:0000269|PubMed:14974083}.
/FTId=VAR_013717.
VARIANT 83 83 K -> E (in APS1; dbSNP:rs121434255).
{ECO:0000269|PubMed:11524731,
ECO:0000269|PubMed:14974083,
ECO:0000269|PubMed:9398839}.
/FTId=VAR_005005.
VARIANT 85 85 Y -> C (in APS1; dbSNP:rs179363882).
{ECO:0000269|PubMed:10677297,
ECO:0000269|PubMed:11524731,
ECO:0000269|PubMed:12050215}.
/FTId=VAR_013718.
VARIANT 90 90 Y -> C (in APS1; decreases doted nuclear
localization; dbSNP:rs179363883).
{ECO:0000269|PubMed:11524731,
ECO:0000269|PubMed:14974083,
ECO:0000269|PubMed:26084028}.
/FTId=VAR_013719.
VARIANT 93 93 L -> R (in APS1; dbSNP:rs179363884).
{ECO:0000269|PubMed:11524731,
ECO:0000269|PubMed:14974083}.
/FTId=VAR_013720.
VARIANT 228 228 G -> 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;
dbSNP:rs121434257).
{ECO:0000269|PubMed:11600535,
ECO:0000269|PubMed:14974083,
ECO:0000269|PubMed:16114041}.
/FTId=VAR_014422.
VARIANT 252 252 P -> L (in APS1; dbSNP:rs34397615).
{ECO:0000269|PubMed:11836330}.
/FTId=VAR_026484.
VARIANT 278 278 S -> R (in dbSNP:rs1800520).
{ECO:0000269|PubMed:11524731,
ECO:0000269|PubMed:12625412,
ECO:0000269|PubMed:9717837}.
/FTId=VAR_005006.
VARIANT 298 298 E -> K (unknown pathological
significance; dbSNP:rs763636007).
{ECO:0000269|PubMed:26084028}.
/FTId=VAR_076940.
VARIANT 299 299 C -> W (unknown pathological
significance; dbSNP:rs751066946).
{ECO:0000269|PubMed:26084028}.
/FTId=VAR_076941.
VARIANT 301 301 V -> M (in APS1; no effect on protein
structure or on interaction with histone
H3; no effect on doted nuclear
localization; dominant-negatif effect on
regulation of target gene transcription;
dbSNP:rs150634562).
{ECO:0000269|PubMed:11524731,
ECO:0000269|PubMed:15649886,
ECO:0000269|PubMed:18292755,
ECO:0000269|PubMed:19446523,
ECO:0000269|PubMed:26084028}.
/FTId=VAR_013721.
VARIANT 302 302 C -> Y (found in patients with
hypothyroidism and organ- and cytokine-
specific autoantibodies; no effect on
doted nuclear localization; dominant-
negatif effect on regulation of target
gene transcription).
{ECO:0000269|PubMed:26084028}.
/FTId=VAR_076942.
VARIANT 303 303 R -> Q (unknown pathological
significance; dbSNP:rs139808903).
{ECO:0000269|PubMed:26084028}.
/FTId=VAR_076943.
VARIANT 303 303 R -> W (unknown pathological
significance; dbSNP:rs778929451).
{ECO:0000269|PubMed:26084028}.
/FTId=VAR_076944.
VARIANT 305 305 G -> S (found in a patient with
pernicious anemia and neuropathy; unknown
pathological significance; no effect on
doted nuclear localization; dominant-
negatif effect on regulation of target
gene transcription).
{ECO:0000269|PubMed:26084028}.
/FTId=VAR_013722.
VARIANT 306 306 G -> R (unknown pathological
significance; dbSNP:rs754932526).
{ECO:0000269|PubMed:26084028}.
/FTId=VAR_076945.
VARIANT 309 309 I -> M (unknown pathological
significance; dbSNP:rs74162062).
{ECO:0000269|PubMed:26084028}.
/FTId=VAR_076946.
VARIANT 311 311 C -> Y (in APS1; impairs zinc binding and
folding of the PHD-type 1 zinc finger;
dominant-negatif effect on the regulation
of target gene transcription; no effect
on doted nuclear localization; dominant-
negatif effect on regulation of target
gene transcription; dbSNP:rs386833674).
{ECO:0000269|PubMed:10677297,
ECO:0000269|PubMed:11524731,
ECO:0000269|PubMed:12050215,
ECO:0000269|PubMed:15649886,
ECO:0000269|PubMed:18292755,
ECO:0000269|PubMed:19446523,
ECO:0000269|PubMed:26084028}.
/FTId=VAR_013723.
VARIANT 316 316 R -> Q (unknown pathological
significance; dbSNP:rs202027254).
{ECO:0000269|PubMed:26084028}.
/FTId=VAR_076947.
VARIANT 316 316 R -> W (unknown pathological
significance; found in a patient with
pernicious anemia; dbSNP:rs139874934).
{ECO:0000269|PubMed:26084028}.
/FTId=VAR_076948.
VARIANT 319 319 H -> P (unknown pathological
significance; dbSNP:rs776951380).
{ECO:0000269|PubMed:26084028}.
/FTId=VAR_076949.
VARIANT 326 326 P -> L (in APS1; no significant effect on
structure, but may alter protein
interactions; no effect on doted nuclear
localization; dominant-negatif effect on
regulation of target gene transcription;
dbSNP:rs179363885).
{ECO:0000269|PubMed:11275943,
ECO:0000269|PubMed:19446523,
ECO:0000269|PubMed:26084028}.
/FTId=VAR_026485.
VARIANT 326 326 P -> Q (in APS1; alters folding of the
PHD-type 1 zinc finger;
dbSNP:rs179363885).
{ECO:0000269|PubMed:10677297,
ECO:0000269|PubMed:11524731,
ECO:0000269|PubMed:14974083,
ECO:0000269|PubMed:15649886,
ECO:0000269|PubMed:19446523}.
/FTId=VAR_013724.
VARIANT 328 328 R -> Q (found in a patient with
acrofacial vitiligo and gastric parietal
cell autoantibodies; no effect on doted
nuclear localization; dominant-negatif
effect on regulation of target gene
transcription; dbSNP:rs775921321).
{ECO:0000269|PubMed:26084028}.
/FTId=VAR_076950.
VARIANT 328 328 R -> W (unknown pathological
significance; dbSNP:rs74162063).
{ECO:0000269|PubMed:26084028}.
/FTId=VAR_076951.
VARIANT 332 332 S -> R (unknown pathological
significance; dbSNP:rs766901260).
{ECO:0000269|PubMed:26084028}.
/FTId=VAR_076952.
VARIANT 484 484 V -> A (found in a patient with
acrofacial vitiligo and gastric parietal
cell autoantibodies; unknown pathological
significance; dbSNP:rs769470638).
{ECO:0000269|PubMed:26084028}.
/FTId=VAR_076953.
VARIANT 539 539 P -> L (in APS1; dbSNP:rs179363889).
{ECO:0000269|PubMed:11836330}.
/FTId=VAR_026486.
MUTAGEN 28 29 LL->PP: Loss of doted nuclear location,
forms nuclear smears. Loss of
transactivation activity on target genes
transcription.
{ECO:0000269|PubMed:26084028}.
MUTAGEN 97 97 L->P: Loss of transactivation activity on
target gene transcription; no dominant-
negatif effect on target gene
transcription. Loss of doted nuclear
localization.
{ECO:0000269|PubMed:26084028}.
MUTAGEN 295 295 N->A: Abolishes interaction with histone
H3. {ECO:0000269|PubMed:19293276}.
MUTAGEN 297 297 D->A: Strongly reduces interaction with
unmethylated histone H3 and abolishes
interaction with histone H3 trimethylated
at 'Lys-4'. No effect on doted nuclear
localization. Dominant-negatif effect on
target gene transcription.
{ECO:0000269|PubMed:18292755,
ECO:0000269|PubMed:26084028}.
MUTAGEN 298 298 E->A: Reduces interaction with histone
H3. {ECO:0000269|PubMed:19293276}.
MUTAGEN 302 302 C->P: Reduces transcriptional activation.
{ECO:0000269|PubMed:11274163}.
MUTAGEN 303 303 R->P: Alters protein folding and
abolishes interaction with histone H3. No
effect on doted nuclear localization.
Dominant-negatif effect on target gene
transcription.
{ECO:0000269|PubMed:19293276,
ECO:0000269|PubMed:26084028}.
MUTAGEN 304 304 D->A: Strongly reduces interaction with
histone H3.
{ECO:0000269|PubMed:19293276}.
MUTAGEN 307 307 E->A: Reduces interaction with histone
H3. {ECO:0000269|PubMed:19293276}.
MUTAGEN 312 312 D->A: Abolishes interaction with histone
H3. {ECO:0000269|PubMed:18292755}.
MUTAGEN 312 312 D->N: No effect on doted nuclear
localization. Dominant-negatif effect on
target gene transcription.
{ECO:0000269|PubMed:26084028}.
MUTAGEN 437 437 C->P: Reduces transcription activation.
{ECO:0000269|PubMed:11274163}.
MUTAGEN 446 446 C->G: Dominant-negatif effect on
regulation of target gene transcription.
{ECO:0000269|PubMed:26084028}.
MUTAGEN 471 471 R->C: No effect on regulation of target
gene transcription.
{ECO:0000269|PubMed:26084028}.
CONFLICT 437 467 CGDGTDVLRCTHCAAAFHWRCHFPAGTSRPG -> W (in
Ref. 3; CAA08759). {ECO:0000305}.
STRAND 298 303 {ECO:0000244|PDB:1XWH}.
STRAND 306 310 {ECO:0000244|PDB:2KE1}.
STRAND 312 314 {ECO:0000244|PDB:2KE1}.
STRAND 317 319 {ECO:0000244|PDB:2KE1}.
TURN 320 322 {ECO:0000244|PDB:1XWH}.
STRAND 323 325 {ECO:0000244|PDB:1XWH}.
HELIX 338 342 {ECO:0000244|PDB:1XWH}.
TURN 423 426 {ECO:0000244|PDB:2LRI}.
TURN 435 437 {ECO:0000244|PDB:2LRI}.
STRAND 447 449 {ECO:0000244|PDB:2LRI}.
HELIX 455 458 {ECO:0000244|PDB:2LRI}.
TURN 460 462 {ECO:0000244|PDB:2LRI}.
STRAND 467 469 {ECO:0000244|PDB:2LRI}.
TURN 473 476 {ECO:0000244|PDB:2LRI}.
SEQUENCE 545 AA; 57727 MW; 8CF703F8C9411BC5 CRC64;
MATDAALRRL LRLHRTEIAV AVDSAFPLLH ALADHDVVPE DKFQETLHLK EKEGCPQAFH
ALLSWLLTQD STAILDFWRV LFKDYNLERY GRLQPILDSF PKDVDLSQPR KGRKPPAVPK
ALVPPPRLPT KRKASEEARA AAPAALTPRG TASPGSQLKA KPPKKPESSA EQQRLPLGNG
IQTMSASVQR AVAMSSGDVP GARGAVEGIL IQQVFESGGS KKCIQVGGEF YTPSKFEDSG
SGKNKARSSS GPKPLVRAKG AQGAAPGGGE ARLGQQGSVP APLALPSDPQ LHQKNEDECA
VCRDGGELIC CDGCPRAFHL ACLSPPLREI PSGTWRCSSC LQATVQEVQP RAEEPRPQEP
PVETPLPPGL RSAGEEVRGP PGEPLAGMDT TLVYKHLPAP PSAAPLPGLD SSALHPLLCV
GPEGQQNLAP GARCGVCGDG TDVLRCTHCA AAFHWRCHFP AGTSRPGTGL RCRSCSGDVT
PAPVEGVLAP SPARLAPGPA KDDTASHEPA LHRDDLESLL SEHTFDGILQ WAIQSMARPA
APFPS


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