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Protein

Autoimmune regulator

Gene

AIRE

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcriptional regulator that binds to DNA as a dimer or as a tetramer, but not as a monomer. Binds to G-doublets in an A/T-rich environment; the preferred motif is a tandem repeat of 5'-. ATTGGTTA-3' combined with a 5'-TTATTA-3' box. Binds to nucleosomes (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. Functions as a transcriptional activator and promotes the expression of otherwise tissue-specific self-antigens in the thymus, which is important for self tolerance and the avoidance of autoimmune reactions.By similarity2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri296 – 34348PHD-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri434 – 47542PHD-type 2PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • chromatin binding Source: UniProtKB
  • histone binding Source: UniProtKB
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: NTNU_SB
  • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding Source: NTNU_SB
  • transcription cofactor activity Source: GO_Central
  • transcription regulatory region DNA binding Source: UniProtKB
  • translation regulator activity Source: InterPro
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • humoral immune response Source: Ensembl
  • immune response Source: ProtInc
  • negative thymic T cell selection Source: Ensembl
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  • regulation of transcription, DNA-templated Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

SIGNORiO43918.

Names & Taxonomyi

Protein namesi
Recommended name:
Autoimmune regulator
Alternative name(s):
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy protein
Short name:
APECED protein
Gene namesi
Name:AIRE
Synonyms:APECED
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

HGNCiHGNC:360. AIRE.

Subcellular locationi

  • Nucleus
  • Cytoplasm

  • Note: Associated with tubular structures and in discrete nuclear dots resembling ND10 nuclear bodies. May shuttle between nucleus and cytoplasm.

GO - Cellular componenti

  • cytoplasm Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Autoimmune polyendocrine syndrome 1, with or without reversible metaphyseal dysplasia (APS1)12 Publications
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).1 Publication
Disease descriptionA 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.
See also OMIM:240300
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti15 – 151R → C in APS1. 1 Publication
Corresponds to variant rs179363875 [ dbSNP | Ensembl ].
VAR_026480
Natural varianti15 – 151R → L in APS1; prevents homooligomerization; slightly alters subcellular localization; no effect on the transcriptional transactivation activity. 3 Publications
Corresponds to variant rs179363876 [ dbSNP | Ensembl ].
VAR_013713
Natural varianti16 – 161T → M in APS1; prevents homooligomerization; slightly alters subcellular localization; no effect on the transcriptional transactivation activity. 4 Publications
Corresponds to variant rs179363877 [ dbSNP | Ensembl ].
VAR_013714
Natural varianti21 – 211A → V in APS1; no effect on homooligomerization; no effect on subcellular localization; no effect on the transcriptional transactivation activity. 2 Publications
Corresponds to variant rs179363886 [ dbSNP | Ensembl ].
VAR_026481
Natural varianti22 – 232Missing in APS1; prevents homodimerization. 1 Publication
VAR_026482
Natural varianti28 – 281L → P in APS1; abolishes association with cytoplasmic tubular structures and homodimerization. 4 Publications
Corresponds to variant rs179363878 [ dbSNP | Ensembl ].
VAR_005004
Natural varianti29 – 291L → P in APS1. 2 Publications
Corresponds to variant rs179363879 [ dbSNP | Ensembl ].
VAR_013715
Natural varianti77 – 771F → S in APS1; loss of homooligomerization. 1 Publication
Corresponds to variant rs179363887 [ dbSNP | Ensembl ].
VAR_026483
Natural varianti78 – 781W → R in APS1; loss of homooligomerization. 5 Publications
Corresponds to variant rs179363880 [ dbSNP | Ensembl ].
VAR_013716
Natural varianti80 – 801V → L in APS1. 3 Publications
Corresponds to variant rs179363881 [ dbSNP | Ensembl ].
VAR_013717
Natural varianti83 – 831K → E in APS1. 3 Publications
Corresponds to variant rs121434255 [ dbSNP | Ensembl ].
VAR_005005
Natural varianti85 – 851Y → C in APS1. 3 Publications
Corresponds to variant rs179363882 [ dbSNP | Ensembl ].
VAR_013718
Natural varianti90 – 901Y → C in APS1. 2 Publications
Corresponds to variant rs179363883 [ dbSNP | Ensembl ].
VAR_013719
Natural varianti93 – 931L → R in APS1. 2 Publications
Corresponds to variant rs179363884 [ dbSNP | Ensembl ].
VAR_013720
Natural varianti228 – 2281G → 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. 3 Publications
Corresponds to variant rs121434257 [ dbSNP | Ensembl ].
VAR_014422
Natural varianti252 – 2521P → L in APS1. 1 Publication
Corresponds to variant rs34397615 [ dbSNP | Ensembl ].
VAR_026484
Natural varianti301 – 3011V → M in APS1; no effect on protein structure or on interaction with histone H3. 4 Publications
Corresponds to variant rs150634562 [ dbSNP | Ensembl ].
VAR_013721
Natural varianti311 – 3111C → Y in APS1; impairs zinc binding and folding of the PHD-type 1 zinc finger. 6 Publications
Corresponds to variant rs386833674 [ dbSNP | Ensembl ].
VAR_013723
Natural varianti326 – 3261P → L in APS1; no significant effect on structure, but may alter protein interactions. 2 Publications
Corresponds to variant rs179363888 [ dbSNP | Ensembl ].
VAR_026485
Natural varianti326 – 3261P → Q in APS1; alters folding of the PHD-type 1 zinc finger. 5 Publications
Corresponds to variant rs179363885 [ dbSNP | Ensembl ].
VAR_013724
Natural varianti539 – 5391P → L in APS1. 1 Publication
Corresponds to variant rs179363889 [ dbSNP | Ensembl ].
VAR_026486

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi295 – 2951N → A: Abolishes interaction with histone H3. 1 Publication
Mutagenesisi297 – 2971D → A: Strongly reduces interaction with unmethylated histone H3 and abolishes interaction with histone H3 trimethylated at 'Lys-4'. 1 Publication
Mutagenesisi298 – 2981E → A: Reduces interaction with histone H3. 1 Publication
Mutagenesisi302 – 3021C → P: Reduces transcriptional activation. 1 Publication
Mutagenesisi303 – 3031R → P: Alters protein folding and abolishes interaction with histone H3. 1 Publication
Mutagenesisi304 – 3041D → A: Strongly reduces interaction with histone H3. 1 Publication
Mutagenesisi307 – 3071E → A: Reduces interaction with histone H3. 1 Publication
Mutagenesisi312 – 3121D → A: Abolishes interaction with histone H3. 1 Publication
Mutagenesisi437 – 4371C → P: Reduces transcription activation. 1 Publication

Keywords - Diseasei

Disease mutation

Organism-specific databases

MalaCardsiAIRE.
MIMi109100. phenotype.
240300. phenotype.
Orphaneti3453. Autoimmune polyendocrinopathy type 1.
PharmGKBiPA24654.

Polymorphism and mutation databases

BioMutaiAIRE.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 545545Autoimmune regulatorPRO_0000064513Add
BLAST

Post-translational modificationi

Phosphorylated. Phosphorylation could trigger oligomerization.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO43918.
PaxDbiO43918.
PeptideAtlasiO43918.
PRIDEiO43918.

PTM databases

iPTMnetiO43918.
PhosphoSiteiO43918.

Expressioni

Tissue specificityi

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. Isoform 2 and isoform 3 seem to be less frequently expressed than isoform 1, if at all.

Gene expression databases

BgeeiENSG00000160224.
CleanExiHS_AIRE.
GenevisibleiO43918. HS.

Organism-specific databases

HPAiHPA038267.

Interactioni

Subunit structurei

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.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
DAXXQ9UER75EBI-1753081,EBI-77321
HIST1H3DP6843120EBI-1753081,EBI-79722
NCK1P163332EBI-1753081,EBI-389883
PRKDCP785272EBI-1753081,EBI-352053

GO - Molecular functioni

  • histone binding Source: UniProtKB

Protein-protein interaction databases

BioGridi106823. 80 interactions.
DIPiDIP-47504N.
IntActiO43918. 23 interactions.
MINTiMINT-6542056.
STRINGi9606.ENSP00000291582.

Structurei

Secondary structure

1
545
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi298 – 3036Combined sources
Beta strandi306 – 3105Combined sources
Beta strandi312 – 3143Combined sources
Beta strandi317 – 3193Combined sources
Turni320 – 3223Combined sources
Beta strandi323 – 3253Combined sources
Helixi338 – 3425Combined sources
Turni423 – 4264Combined sources
Turni435 – 4373Combined sources
Beta strandi447 – 4493Combined sources
Helixi455 – 4584Combined sources
Turni460 – 4623Combined sources
Beta strandi467 – 4693Combined sources
Turni473 – 4764Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1XWHNMR-A293-354[»]
2KE1NMR-A293-354[»]
2KFTNMR-A294-347[»]
2LRINMR-C423-485[»]
ProteinModelPortaliO43918.
SMRiO43918. Positions 294-347, 423-485.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43918.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 105105HSRPROSITE-ProRule annotationAdd
BLAST
Domaini181 – 280100SANDPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni295 – 2984Interaction with histone H3 not methylated at 'Lys-4'
Regioni304 – 3129Interaction with histone H3 not methylated at 'Lys-4'
Regioni331 – 3355Interaction with histone H3 not methylated at 'Lys-4'

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi7 – 115LXXLL motif 1
Motifi63 – 675LXXLL motif 2
Motifi414 – 4185LXXLL motif 3
Motifi516 – 5205LXXLL motif 4

Domaini

The L-X-X-L-L repeats may be implicated in binding to nuclear receptors.
The HSR domain is required for localization on tubular structures (N-terminal part) and for homodimerization.
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.

Sequence similaritiesi

Contains 1 HSR domain.PROSITE-ProRule annotation
Contains 2 PHD-type zinc fingers.PROSITE-ProRule annotation
Contains 1 SAND domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri296 – 34348PHD-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri434 – 47542PHD-type 2PROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IRE7. Eukaryota.
ENOG410XQQA. LUCA.
GeneTreeiENSGT00530000062982.
HOGENOMiHOG000033872.
HOVERGENiHBG014961.
InParanoidiO43918.
KOiK10603.
OMAiLLSEHTF.
OrthoDBiEOG091G055U.
PhylomeDBiO43918.
TreeFamiTF336193.

Family and domain databases

Gene3Di3.10.390.10. 1 hit.
3.30.40.10. 2 hits.
InterProiIPR008087. AIRE.
IPR004865. HSR_dom.
IPR000770. SAND_dom.
IPR010919. SAND_dom-like.
IPR019786. Zinc_finger_PHD-type_CS.
IPR011011. Znf_FYVE_PHD.
IPR001965. Znf_PHD.
IPR019787. Znf_PHD-finger.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF00628. PHD. 1 hit.
PF01342. SAND. 1 hit.
PF03172. Sp100. 1 hit.
[Graphical view]
PRINTSiPR01711. AIREGULATOR.
SMARTiSM00249. PHD. 2 hits.
SM00258. SAND. 1 hit.
[Graphical view]
SUPFAMiSSF57903. SSF57903. 2 hits.
SSF63763. SSF63763. 1 hit.
PROSITEiPS51414. HSR. 1 hit.
PS50864. SAND. 1 hit.
PS01359. ZF_PHD_1. 2 hits.
PS50016. ZF_PHD_2. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist. Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: O43918-1) [UniParc]FASTAAdd to basket
Also known as: AIRE-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.

« Hide

        10         20         30         40         50
MATDAALRRL LRLHRTEIAV AVDSAFPLLH ALADHDVVPE DKFQETLHLK
60 70 80 90 100
EKEGCPQAFH ALLSWLLTQD STAILDFWRV LFKDYNLERY GRLQPILDSF
110 120 130 140 150
PKDVDLSQPR KGRKPPAVPK ALVPPPRLPT KRKASEEARA AAPAALTPRG
160 170 180 190 200
TASPGSQLKA KPPKKPESSA EQQRLPLGNG IQTMSASVQR AVAMSSGDVP
210 220 230 240 250
GARGAVEGIL IQQVFESGGS KKCIQVGGEF YTPSKFEDSG SGKNKARSSS
260 270 280 290 300
GPKPLVRAKG AQGAAPGGGE ARLGQQGSVP APLALPSDPQ LHQKNEDECA
310 320 330 340 350
VCRDGGELIC CDGCPRAFHL ACLSPPLREI PSGTWRCSSC LQATVQEVQP
360 370 380 390 400
RAEEPRPQEP PVETPLPPGL RSAGEEVRGP PGEPLAGMDT TLVYKHLPAP
410 420 430 440 450
PSAAPLPGLD SSALHPLLCV GPEGQQNLAP GARCGVCGDG TDVLRCTHCA
460 470 480 490 500
AAFHWRCHFP AGTSRPGTGL RCRSCSGDVT PAPVEGVLAP SPARLAPGPA
510 520 530 540
KDDTASHEPA LHRDDLESLL SEHTFDGILQ WAIQSMARPA APFPS
Length:545
Mass (Da):57,727
Last modified:June 1, 1998 - v1
Checksum:i8CF703F8C9411BC5
GO
Isoform 2 (identifier: O43918-2) [UniParc]FASTAAdd to basket
Also known as: AIRE-2

The sequence of this isoform differs from the canonical sequence as follows:
     1-292: MATDAALRRL...LALPSDPQLH → MWLVYSSGAP...VALRRVLHPS

Show »
Length:338
Mass (Da):35,507
Checksum:i7C99ABAD92DDC565
GO
Isoform 3 (identifier: O43918-3) [UniParc]FASTAAdd to basket
Also known as: AIRE-3

The sequence of this isoform differs from the canonical sequence as follows:
     1-292: MATDAALRRL...LALPSDPQLH → MWLVYSSGAP...VALRRVLHPS
     377-545: VRGPPGEPLA...MARPAAPFPS → PRCQGWTPRP...ACAADPAQET

Show »
Length:244
Mass (Da):25,927
Checksum:iBD26FC231E0E5611
GO
Isoform 4 (identifier: O43918-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-292: MATDAALRRL...LALPSDPQLH → MWLVYSSGAP...VALRRVLHPS
     293-293: Q → PVCMGVSCLCQ

Note: No experimental confirmation available.
Show »
Length:348
Mass (Da):36,501
Checksum:i37045012FF585F6E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti437 – 46731CGDGT…TSRPG → W in CAA08759 (Ref. 3) CuratedAdd
BLAST

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti15 – 151R → C in APS1. 1 Publication
Corresponds to variant rs179363875 [ dbSNP | Ensembl ].
VAR_026480
Natural varianti15 – 151R → L in APS1; prevents homooligomerization; slightly alters subcellular localization; no effect on the transcriptional transactivation activity. 3 Publications
Corresponds to variant rs179363876 [ dbSNP | Ensembl ].
VAR_013713
Natural varianti16 – 161T → M in APS1; prevents homooligomerization; slightly alters subcellular localization; no effect on the transcriptional transactivation activity. 4 Publications
Corresponds to variant rs179363877 [ dbSNP | Ensembl ].
VAR_013714
Natural varianti21 – 211A → V in APS1; no effect on homooligomerization; no effect on subcellular localization; no effect on the transcriptional transactivation activity. 2 Publications
Corresponds to variant rs179363886 [ dbSNP | Ensembl ].
VAR_026481
Natural varianti22 – 232Missing in APS1; prevents homodimerization. 1 Publication
VAR_026482
Natural varianti28 – 281L → P in APS1; abolishes association with cytoplasmic tubular structures and homodimerization. 4 Publications
Corresponds to variant rs179363878 [ dbSNP | Ensembl ].
VAR_005004
Natural varianti29 – 291L → P in APS1. 2 Publications
Corresponds to variant rs179363879 [ dbSNP | Ensembl ].
VAR_013715
Natural varianti77 – 771F → S in APS1; loss of homooligomerization. 1 Publication
Corresponds to variant rs179363887 [ dbSNP | Ensembl ].
VAR_026483
Natural varianti78 – 781W → R in APS1; loss of homooligomerization. 5 Publications
Corresponds to variant rs179363880 [ dbSNP | Ensembl ].
VAR_013716
Natural varianti80 – 801V → L in APS1. 3 Publications
Corresponds to variant rs179363881 [ dbSNP | Ensembl ].
VAR_013717
Natural varianti83 – 831K → E in APS1. 3 Publications
Corresponds to variant rs121434255 [ dbSNP | Ensembl ].
VAR_005005
Natural varianti85 – 851Y → C in APS1. 3 Publications
Corresponds to variant rs179363882 [ dbSNP | Ensembl ].
VAR_013718
Natural varianti90 – 901Y → C in APS1. 2 Publications
Corresponds to variant rs179363883 [ dbSNP | Ensembl ].
VAR_013719
Natural varianti93 – 931L → R in APS1. 2 Publications
Corresponds to variant rs179363884 [ dbSNP | Ensembl ].
VAR_013720
Natural varianti228 – 2281G → 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. 3 Publications
Corresponds to variant rs121434257 [ dbSNP | Ensembl ].
VAR_014422
Natural varianti252 – 2521P → L in APS1. 1 Publication
Corresponds to variant rs34397615 [ dbSNP | Ensembl ].
VAR_026484
Natural varianti278 – 2781S → R.3 Publications
Corresponds to variant rs1800520 [ dbSNP | Ensembl ].
VAR_005006
Natural varianti301 – 3011V → M in APS1; no effect on protein structure or on interaction with histone H3. 4 Publications
Corresponds to variant rs150634562 [ dbSNP | Ensembl ].
VAR_013721
Natural varianti305 – 3051G → S.
VAR_013722
Natural varianti311 – 3111C → Y in APS1; impairs zinc binding and folding of the PHD-type 1 zinc finger. 6 Publications
Corresponds to variant rs386833674 [ dbSNP | Ensembl ].
VAR_013723
Natural varianti326 – 3261P → L in APS1; no significant effect on structure, but may alter protein interactions. 2 Publications
Corresponds to variant rs179363888 [ dbSNP | Ensembl ].
VAR_026485
Natural varianti326 – 3261P → Q in APS1; alters folding of the PHD-type 1 zinc finger. 5 Publications
Corresponds to variant rs179363885 [ dbSNP | Ensembl ].
VAR_013724
Natural varianti539 – 5391P → L in APS1. 1 Publication
Corresponds to variant rs179363889 [ dbSNP | Ensembl ].
VAR_026486

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 292292MATDA…DPQLH → MWLVYSSGAPGTQQPARNRV FFPIGMAPGGVCWRPDGWGT GGQGRISGPGSMGAGQRLGS SGTQRCCWGSCFGKEVALRR VLHPS in isoform 2, isoform 3 and isoform 4. 2 PublicationsVSP_004089Add
BLAST
Alternative sequencei293 – 2931Q → PVCMGVSCLCQ in isoform 4. 1 PublicationVSP_043529
Alternative sequencei377 – 545169VRGPP…APFPS → PRCQGWTPRPCTPYCVWVLR VSRTWLLVRVAGCAEMVRTC CGVLTAPLPSTGAATSQPAP PGPGRACAADPAQET in isoform 3. 1 PublicationVSP_004090Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB006682 mRNA. Translation: BAA23988.1.
AB006683 mRNA. Translation: BAA23989.1.
AB006684 Genomic DNA. Translation: BAA23990.1.
AB006684 Genomic DNA. Translation: BAA23991.1.
AB006684 Genomic DNA. Translation: BAA23992.1.
AB006685 mRNA. Translation: BAA23993.1.
Z97990 mRNA. Translation: CAB10790.1.
AJ009610 Genomic DNA. Translation: CAA08759.1.
AP001754 Genomic DNA. Translation: BAA95560.1.
AP001060 Genomic DNA. No translation available.
CH471079 Genomic DNA. Translation: EAX09443.1.
BC137268 mRNA. Translation: AAI37269.1.
BC137270 mRNA. Translation: AAI37271.1.
CCDSiCCDS13706.1. [O43918-1]
RefSeqiNP_000374.1. NM_000383.3. [O43918-1]
UniGeneiHs.129829.

Genome annotation databases

EnsembliENST00000291582; ENSP00000291582; ENSG00000160224. [O43918-1]
GeneIDi326.
KEGGihsa:326.
UCSCiuc002zei.4. human. [O43918-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

AIREbase

AIRE mutation db

Mendelian genes autoimmune regulator (AIRE)

Leiden Open Variation Database (LOVD)

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB006682 mRNA. Translation: BAA23988.1.
AB006683 mRNA. Translation: BAA23989.1.
AB006684 Genomic DNA. Translation: BAA23990.1.
AB006684 Genomic DNA. Translation: BAA23991.1.
AB006684 Genomic DNA. Translation: BAA23992.1.
AB006685 mRNA. Translation: BAA23993.1.
Z97990 mRNA. Translation: CAB10790.1.
AJ009610 Genomic DNA. Translation: CAA08759.1.
AP001754 Genomic DNA. Translation: BAA95560.1.
AP001060 Genomic DNA. No translation available.
CH471079 Genomic DNA. Translation: EAX09443.1.
BC137268 mRNA. Translation: AAI37269.1.
BC137270 mRNA. Translation: AAI37271.1.
CCDSiCCDS13706.1. [O43918-1]
RefSeqiNP_000374.1. NM_000383.3. [O43918-1]
UniGeneiHs.129829.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1XWHNMR-A293-354[»]
2KE1NMR-A293-354[»]
2KFTNMR-A294-347[»]
2LRINMR-C423-485[»]
ProteinModelPortaliO43918.
SMRiO43918. Positions 294-347, 423-485.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106823. 80 interactions.
DIPiDIP-47504N.
IntActiO43918. 23 interactions.
MINTiMINT-6542056.
STRINGi9606.ENSP00000291582.

PTM databases

iPTMnetiO43918.
PhosphoSiteiO43918.

Polymorphism and mutation databases

BioMutaiAIRE.

Proteomic databases

EPDiO43918.
PaxDbiO43918.
PeptideAtlasiO43918.
PRIDEiO43918.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000291582; ENSP00000291582; ENSG00000160224. [O43918-1]
GeneIDi326.
KEGGihsa:326.
UCSCiuc002zei.4. human. [O43918-1]

Organism-specific databases

CTDi326.
GeneCardsiAIRE.
HGNCiHGNC:360. AIRE.
HPAiHPA038267.
MalaCardsiAIRE.
MIMi109100. phenotype.
240300. phenotype.
607358. gene.
neXtProtiNX_O43918.
Orphaneti3453. Autoimmune polyendocrinopathy type 1.
PharmGKBiPA24654.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IRE7. Eukaryota.
ENOG410XQQA. LUCA.
GeneTreeiENSGT00530000062982.
HOGENOMiHOG000033872.
HOVERGENiHBG014961.
InParanoidiO43918.
KOiK10603.
OMAiLLSEHTF.
OrthoDBiEOG091G055U.
PhylomeDBiO43918.
TreeFamiTF336193.

Enzyme and pathway databases

SIGNORiO43918.

Miscellaneous databases

EvolutionaryTraceiO43918.
GeneWikiiAutoimmune_regulator.
GenomeRNAii326.
PROiO43918.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000160224.
CleanExiHS_AIRE.
GenevisibleiO43918. HS.

Family and domain databases

Gene3Di3.10.390.10. 1 hit.
3.30.40.10. 2 hits.
InterProiIPR008087. AIRE.
IPR004865. HSR_dom.
IPR000770. SAND_dom.
IPR010919. SAND_dom-like.
IPR019786. Zinc_finger_PHD-type_CS.
IPR011011. Znf_FYVE_PHD.
IPR001965. Znf_PHD.
IPR019787. Znf_PHD-finger.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF00628. PHD. 1 hit.
PF01342. SAND. 1 hit.
PF03172. Sp100. 1 hit.
[Graphical view]
PRINTSiPR01711. AIREGULATOR.
SMARTiSM00249. PHD. 2 hits.
SM00258. SAND. 1 hit.
[Graphical view]
SUPFAMiSSF57903. SSF57903. 2 hits.
SSF63763. SSF63763. 1 hit.
PROSITEiPS51414. HSR. 1 hit.
PS50864. SAND. 1 hit.
PS01359. ZF_PHD_1. 2 hits.
PS50016. ZF_PHD_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAIRE_HUMAN
AccessioniPrimary (citable) accession number: O43918
Secondary accession number(s): B2RP50
, O43922, O43932, O75745
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: June 1, 1998
Last modified: September 7, 2016
This is version 177 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 21
    Human chromosome 21: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.