[1]	NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANT APECED GLU-83. TISSUE=Thymus; DOI=10.1038/ng1297-393; PubMed=9398839 [NCBI, ExPASy, EBI, Israel, Japan] 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; DOI=10.1038/ng1297-399; PubMed=9398840 [NCBI, ExPASy, EBI, Israel, Japan] 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]. DOI=10.1038/35012518; PubMed=10830953 [NCBI, ExPASy, EBI, Israel, Japan] 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]	SUBCELLULAR LOCATION. DOI=10.1093/hmg/8.2.259; PubMed=9931333 [NCBI, ExPASy, EBI, Israel, Japan] 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).
[6]	PARTIAL PROTEIN SEQUENCE, SUBUNIT STRUCTURE, DNA-BINDING, AND PHOSPHORYLATION. DOI=10.1074/jbc.M104898200; PubMed=11533054 [NCBI, ExPASy, EBI, Israel, Japan] 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).
[7]	SUBCELLULAR LOCATION, AND VARIANTS APECED LEU-80; CYS-85; TYR-311 AND GLN-326. DOI=10.1086/302765; PubMed=10677297 [NCBI, ExPASy, EBI, Israel, Japan] 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).
[8]	SUBCELLULAR LOCATION, TRANSCRIPTION ACTIVATION, MUTAGENESIS OF CYS-302 AND CYS-437, AND CHARACTERIZATION OF VARIANT APECED PRO-28. DOI=10.1074/jbc.M008322200; PubMed=11274163 [NCBI, ExPASy, EBI, Israel, Japan] 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).
[9]	SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANTS APECED 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. DOI=10.1002/humu.20003; PubMed=14974083 [NCBI, ExPASy, EBI, Israel, Japan] 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).
[10]	STRUCTURE BY NMR OF 293-354 IN COMPLEX WITH ZINC IONS, AND CHARACTERIZATION OF APECED VARIANTS MET-301; TYR-311 AND GLN-326. DOI=10.1074/jbc.M413959200; PubMed=15649886 [NCBI, ExPASy, EBI, Israel, Japan] 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).
[11]	VARIANT APECED PRO-28. DOI=10.1002/(SICI)1098-1004(1999)13:1<69::AID-HUMU8>3.0.CO;2-6; PubMed=9888391 [NCBI, ExPASy, EBI, Israel, Japan] 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).
[12]	VARIANT ARG-278. DOI=10.1210/me.12.8.1112; PubMed=9717837 [NCBI, ExPASy, EBI, Israel, Japan] 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).
[13]	VARIANT APECED LEU-326. DOI=10.1530/eje.0.1440347; PubMed=11275943 [NCBI, ExPASy, EBI, Israel, Japan] 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).
[14]	VARIANTS APECED 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. DOI=10.1002/humu.1176; PubMed=11524731 [NCBI, ExPASy, EBI, Israel, Japan] 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).
[15]	VARIANTS APECED MET-16 AND ARG-78. DOI=10.1002/humu.1178; PubMed=11524733 [NCBI, ExPASy, EBI, Israel, Japan] 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).
[16]	VARIANT APECED TRP-228. DOI=10.1210/jc.86.10.4747; PubMed=11600535 [NCBI, ExPASy, EBI, Israel, Japan] 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).
[17]	VARIANT APECED PRO-29. DOI=10.1006/clim.2002.5208; PubMed=12173302 [NCBI, ExPASy, EBI, Israel, Japan] 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).
[18]	VARIANT APECED CYS-15. DOI=10.1507/endocrj.49.625; PubMed=12625412 [NCBI, ExPASy, EBI, Israel, Japan] 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).
[19]	VARIANTS APECED ARG-78; LEU-252 AND LEU-539. DOI=10.1210/jc.87.2.841; PubMed=11836330 [NCBI, ExPASy, EBI, Israel, Japan] 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).
[20]	VARIANTS APECED VAL-21; CYS-85 AND TYR-311. DOI=10.1210/jc.87.6.2568; PubMed=12050215 [NCBI, ExPASy, EBI, Israel, Japan] 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).
[21]	VARIANTS APECED 22-VAL-ASP-23 DEL; SER-77 AND ARG-78, AND CHARACTERIZATION OF VARIANTS APECED LEU-15; MET-16; 22-VAL-ASP-23 DEL; SER-77 AND ARG-78. DOI=10.1002/humu.9309; PubMed=15712268 [NCBI, ExPASy, EBI, Israel, Japan] 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).
[22]	CHARACTERIZATION OF VARIANT APECED TRP-228. DOI=10.1002/humu.20224; PubMed=16114041 [NCBI, ExPASy, EBI, Israel, Japan] 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).

Comments

FUNCTION: Probable transcriptional regulator protein that binds to DNA as dimer and 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. May be involved in immune regulation.
SUBUNIT: Homodimer and homotetramer. Interacts with CREBBP.
INTERACTION:
P00519:ABL1; NbExp=1; IntAct=EBI-1753081, EBI-375543;
P46108:CRK; NbExp=1; IntAct=EBI-1753081, EBI-886;
P06241:FYN; NbExp=1; IntAct=EBI-1753081, EBI-515315;
P62993:GRB2; NbExp=1; IntAct=EBI-1753081, EBI-401755;
P16333:NCK1; NbExp=1; IntAct=EBI-1753081, EBI-389883;
P27986:PIK3R1; NbExp=1; IntAct=EBI-1753081, EBI-79464;
P19174:PLCG1; NbExp=1; IntAct=EBI-1753081, EBI-79387;
P12931:SRC; NbExp=1; IntAct=EBI-1753081, EBI-621482;
SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Associated with tubular structures and in discrete nuclear dots resembling ND10 nuclear bodies. May shuttle between nucleus and cytoplasm.

ALTERNATIVE PRODUCTS: 3 named isoforms [FASTA] produced by alternative splicing. Additional isoforms seem to exist. Experimental confirmation may be lacking for some isoforms.

Name	1
Synonyms	AIRE-1
Isoform ID	O43918-1
This is the isoform sequence displayed in this entry.

Name	2
Synonyms	AIRE-2
Isoform ID	O43918-2
Features which should be applied to build the isoform sequence: VSP_004089.

Name	3
Synonyms	AIRE-3
Isoform ID	O43918-3
Features which should be applied to build the isoform sequence: VSP_004089, VSP_004090.

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. Isoforms 2 and 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.
DOMAIN: The HSR domain is required for localization on tubular structures (N-terminal part) and for homodimerization.
DOMAIN: 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.
DISEASE: Defects in AIRE are a cause of autoimmune poly-endocrinopathy candidiasis ectodermal dystrophy (APECED) [MIM:240300]; also known as autoimmune polyglandular syndrome type I (APS-1). APECED is an autosomal recessive disease characterized by: (1) autoimmune polyendocrinopathies: hypoparathyroidism, adrenocortical failure, IDDM, gonadal failure, hypothyroidism, pernicious anemia, and hepatitis; (2) chronic mucocutaneous candidiasis; (3) ectodermal dystrophies: vitiligo, alopecia, keratopathy, dystrophy of dental enamel, nails and tympanic membranes. In addition, a high proportion of patients develop squamous cell carcinoma of the oral mucosa. The disease is reported worldwide but is exceptionally prevalent among the Finnish population (incidence 1:25000) and the Iranian jews (incidence 1:9000).
DISEASE: 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.
SIMILARITY: Contains 1 HSR domain.
SIMILARITY: Contains 2 PHD-type zinc fingers.
SIMILARITY: Contains 1 SAND domain.
WEB RESOURCE: Name=AIREbase; Note=AIRE mutation db; URL="http://bioinf.uta.fi/AIREbase/";.
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=AIRE";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

AB006682; BAA23988.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AB006683; BAA23989.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AB006684; BAA23990.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AB006684; BAA23991.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AB006684; BAA23992.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AB006685; BAA23993.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
Z97990; CAB10790.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AJ009610; CAA08759.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AP001754; BAA95560.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI

IPI00015149; -.
IPI00031178; -.
IPI00031188; -.

RefSeq

NP_000374.1; -.

UniGene

Hs.129829

3D structure databases

PDB

1XWH; NMR; -; A=293-354.	[ExPASy / RCSB / EBI]
2KFT; NMR; -; A=294-347.	[ExPASy / RCSB / EBI]

Detailed list of linked structures.

PDBsum

1XWH; -.
2KFT; -.

ModBase

O43918.

Protein-protein interaction databases

IntAct

O43918; 8.

PTM databases

PhosphoSite

O43918; -.

Organism-specific databases

GC21P044530; -.

HIX0040838; -.

HGNC:360; AIRE.

109100; phenotype. [NCBI / EBI]
240300; phenotype. [NCBI / EBI]
607358; gene. [NCBI / EBI]

Orphanet

3453; Autoimmune polyendocrinopathy, type 1.

PharmGKB

PA24654; -.

Gene expression databases

O43918; -.

O43918; -.

HS_AIRE; -.

ENSG00000160224; Homo sapiens.

Ontologies

GO:0005737;	Cellular component: cytoplasm (inferred from electronic annotation from UniProtKB-SubCell).
GO:0005634;	Cellular component: nucleus (non-traceable author statement from UniProtKB).
GO:0005515;	Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0003700;	Molecular function: transcription factor activity (traceable author statement from ProtInc).
GO:0045182;	Molecular function: translation regulator activity (inferred from electronic annotation from InterPro).
GO:0008270;	Molecular function: zinc ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0006959;	Biological process: humoral immune response (inferred from electronic annotation from InterPro).
GO:0006355;	Biological process: regulation of transcription, DNA-dependent (non-traceable author statement from UniProtKB).
GO:0006350;	Biological process: transcription (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.

Family and domain databases

InterPro

IPR008087; AIRE.
IPR000770; SAND.
IPR004865; Sp100.
IPR019786; Zinc_finger_PHD-type_CS.
IPR001965; Znf_PHD.
IPR019787; Znf_PHD-finger.
Graphical view of domain structure.

Pfam

PF00628; PHD; 2.
PF01342; SAND; 1.
PF03172; Sp100; 1.
Pfam graphical view of domain structure.

PRINTS

PR01711; AIREGULATOR.

SMART

SM00249; PHD; 2.
SM00258; SAND; 1.
SMART graphical view of domain structure.

PROSITE

PS51414; HSR; 1.
PS50864; SAND; 1.
PS01359; ZF_PHD_1; 2.
PS50016; ZF_PHD_2; 1.
PROSITE graphical view of domain structure (profiles).

Proteomic databases

PRIDE

O43918; -.

Genome annotation databases

Ensembl

ENSG00000160224; Homo sapiens. [Contig view]

GeneID

326; -.

KEGG

hsa:326; -.

NMPDR

fig|9606.3.peg.21064; -.

Phylogenomic databases

HOGENOM

O43918; -.

HOVERGEN

O43918; -.

OMA

O43918; SLLNEHS.

Other

1337; -.

AIRE; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Alternative splicing; Cytoplasm; Direct protein sequencing; Disease mutation; DNA-binding; Metal-binding; Nucleus; Phosphoprotein; Polymorphism; Repeat; Transcription; Transcription regulation; Zinc; Zinc-finger.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 545`	`545`	`Autoimmune regulator.`	`PRO_0000064513`
`DOMAIN`	`1 105`	`105`	`HSR.`
`DOMAIN`	`181 280`	`100`	`SAND.`
`ZN_FING`	`296 343`	`48`	`PHD-type 1.`
`ZN_FING`	`434 475`	`42`	`PHD-type 2.`
`MOTIF`	`7 11`	`5`	`LXXLL motif 1.`
`MOTIF`	`63 67`	`5`	`LXXLL motif 2.`
`MOTIF`	`414 418`	`5`	`LXXLL motif 3.`
`MOTIF`	`516 520`	`5`	`LXXLL motif 4.`
`VAR_SEQ`	`1 292`		`MATDAALRRLLRLHRTEIAVAVDSAFPLLHALADHDVVPE` `DKFQETLHLKEKEGCPQAFHALLSWLLTQDSTAILDFWRV` `LFKDYNLERYGRLQPILDSFPKDVDLSQPRKGRKPPAVPK` `ALVPPPRLPTKRKASEEARAAAPAALTPRGTASPGSQLKA` `KPPKKPESSAEQQRLPLGNGIQTMSASVQRAVAMSSGDVP` `GARGAVEGILIQQVFESGGSKKCIQVGGEFYTPSKFEDSG` `SGKNKARSSSGPKPLVRAKGAQGAAPGGGEARLGQQGSVP` `APLALPSDPQLH -> MWLVYSSGAPGTQQPARNRVFFPIGMAPGGVCWRPDGWGT` `GGQGRISGPGSMGAGQRLGSSGTQRCCWGSCFGKEVALRR` `VLHPS (in isoform 2 and isoform 3).`	`VSP_004089`
`VAR_SEQ`	`377 545`		`VRGPPGEPLAGMDTTLVYKHLPAPPSAAPLPGLDSSALHP` `LLCVGPEGQQNLAPGARCGVCGDGTDVLRCTHCAAAFHWR` `CHFPAGTSRPGTGLRCRSCSGDVTPAPVEGVLAPSPARLA` `PGPAKDDTASHEPALHRDDLESLLSEHTFDGILQWAIQSM` `ARPAAPFPS -> PRCQGWTPRPCTPYCVWVLRVSRTWLLVRVAGCAEMVRTC` `CGVLTAPLPSTGAATSQPAPPGPGRACAADPAQET (in isoform 3).`	`VSP_004090`
`VARIANT`	`15 15`	`1`	`R -> C (in APECED).`	`VAR_026480`
`VARIANT`	`15 15`	`1`	`R -> L (in APECED; enzymatic activity of approximately 30% of that of the wild-type).`	`VAR_013713`
`VARIANT`	`16 16`	`1`	`T -> M (in APECED; enzymatic activity of approximately 10% of that of the wild-type).`	`VAR_013714`
`VARIANT`	`21 21`	`1`	`A -> V (in APECED).`	`VAR_026481`
`VARIANT`	`22 23`	`2`	`Missing (in APECED; lack of alpha-galactosidase enzymatic activity; lack of homodimerization).`	`VAR_026482`
`VARIANT`	`28 28`	`1`	`L -> P (in APECED; abolishes association with cytoplasmic tubular structures and homodimerization).`	`VAR_005004`
`VARIANT`	`29 29`	`1`	`L -> P (in APECED).`	`VAR_013715`
`VARIANT`	`77 77`	`1`	`F -> S (in APECED; lack of alpha-galactosidase enzymatic activity; lack of homodimerization).`	`VAR_026483`
`VARIANT`	`78 78`	`1`	`W -> R (in APECED; lack of alpha-galactosidase enzymatic activity; lack of homodimerization).`	`VAR_013716`
`VARIANT`	`80 80`	`1`	`V -> L (in APECED).`	`VAR_013717`
`VARIANT`	`83 83`	`1`	`K -> E (in APECED).`	`VAR_005005`
`VARIANT`	`85 85`	`1`	`Y -> C (in APECED).`	`VAR_013718`
`VARIANT`	`90 90`	`1`	`Y -> C (in APECED).`	`VAR_013719`
`VARIANT`	`93 93`	`1`	`L -> R (in APECED).`	`VAR_013720`
`VARIANT`	`228 228`	`1`	`G -> W (in APECED; 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).`	`VAR_014422`
`VARIANT`	`252 252`	`1`	`P -> L (in APECED).`	`VAR_026484`
`VARIANT`	`278 278`	`1`	`S -> R (in dbSNP:rs1800520 [NCBI]).`	`VAR_005006`
`VARIANT`	`301 301`	`1`	`V -> M (in APECED; no effect on protein structure).`	`VAR_013721`
`VARIANT`	`305 305`	`1`	`G -> S.`	`VAR_013722`
`VARIANT`	`311 311`	`1`	`C -> Y (in APECED; impairs zinc binding and folding of the PHD-type 1 zinc finger).`	`VAR_013723`
`VARIANT`	`326 326`	`1`	`P -> L (in APECED).`	`VAR_026485`
`VARIANT`	`326 326`	`1`	`P -> Q (in APECED; alters folding of the PHD-type 1 zinc finger).`	`VAR_013724`
`VARIANT`	`539 539`	`1`	`P -> L (in APECED).`	`VAR_026486`
`MUTAGEN`	`302 302`		`C->P: Reduces transcription activation.`
`MUTAGEN`	`437 437`		`C->P: Reduces transcription activation.`
`CONFLICT`	`437 467`		`CGDGTDVLRCTHCAAAFHWRCHFPAGTSRPG -> W (in Ref. 3; CAA08759).`
`STRAND`	`298 303`	`6`
`TURN`	`320 322`	`3`
`STRAND`	`323 325`	`3`
`HELIX`	`338 342`	`5`

Sequence information

Length: 545 AA [This is the length of the unprocessed precursor]

Molecular weight: 57727 Da [This is the MW of the unprocessed precursor]

CRC64: 8CF703F8C9411BC5 [This is a checksum on the sequence]

        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

O43918 in FASTA format

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	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools