Tbio AIRE Autoimmune regulator

Protein Summary

Description

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). This gene encodes a transcriptional regulator that forms nuclear bodies and interacts with the transcriptional coactivator CREB binding protein. The encoded protein plays an important role in immunity by regulating the expression of autoantigens and negative selection of autoreactive T-cells in the thymus. Mutations in this gene cause the rare autosomal-recessive systemic autoimmune disease termed autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED). [provided by RefSeq, Jun 2012]

Uniprot Accession IDs

• O43918
• B2RP50
• O43922
• O43932
• O75745

Gene Name

• AIRE

Ensembl ID

• ENST00000291582
• ENSP00000291582
• ENSG00000160224

Symbol

• APECED
• APS1
• APSI
• PGA1
• AIRE1
• APECED

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	0.99
hub protein	0.95
molecular function	0.9
tissue	0.67
gene perturbation	0.66

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 723.18   (req: < 5)

Gene RIFs: 141   (req: <= 3)

Antibodies: 590   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 723.18   (req: >= 5)

Gene RIFs: 141   (req: > 3)

Antibodies: 590   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 20

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

Related Tools

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (123)

Explore Interacting Targets

1 – 10 of 123

• See Interactions on String-DB

NAA30

Tbio

Family:  Enzyme

Novelty:  0.04701961

p_int:  0.999926607

p_ni:  0.000060896

p_wrong:  0.000012497

Data Source:  BioPlex

MAD2L1BP

Tbio

Novelty:  0.48374717

p_int:  0.99865544

p_ni:  0.001314273

p_wrong:  0.000030286

Data Source:  BioPlex

GDPD3

Tbio

Family:  Enzyme

Novelty:  0.18121762

p_int:  0.998240073

p_ni:  0.001046736

p_wrong:  0.00071319

Score:  0.194

Data Source:  BioPlex,STRINGDB

CTSH

Tchem

Family:  Enzyme

Novelty:  0.00336694

p_int:  0.997741797

p_ni:  0.002255984

p_wrong:  0.000002219

Score:  0.214

Data Source:  BioPlex,STRINGDB

FBXW5

Tbio

Novelty:  0.13100873

p_int:  0.993976332

p_ni:  0.005669299

p_wrong:  0.000354369

Data Source:  BioPlex

SDR9C7

Tbio

Family:  Enzyme

Novelty:  0.01618496

p_int:  0.991349017

p_ni:  0.008650732

p_wrong:  2.52e-7

Score:  0.173

Data Source:  BioPlex,STRINGDB

CPA4

Tchem

Family:  Enzyme

Novelty:  0.01439845

p_int:  0.989757993

p_ni:  0.010242007

Data Source:  BioPlex

ACPP

Tchem

Family:  Enzyme

Novelty:  0.00364265

p_int:  0.986807517

p_ni:  0.013192482

p_wrong:  1e-9

Data Source:  BioPlex

PTPRD

Tbio

Family:  Enzyme

Novelty:  0.01059407

p_int:  0.938336342

p_ni:  0.051413777

p_wrong:  0.010249882

Data Source:  BioPlex

ALOX12B

Tbio

Family:  Enzyme

Novelty:  0.02778552

p_int:  0.918632508

p_ni:  0.081367491

Score:  0.183

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (2)

KEGG (2)

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1 – 2 of 2

Data Source	Name	Explore in Pharos	Explore in Source
KEGG	Ubiquitin mediated proteolysis	136 targets	path:hsa04120
KEGG	Primary immunodeficiency	36 targets	path:hsa05340

Name	Explore in Pharos	Explore in Source
Ubiquitin mediated proteolysis	136 targets	path:hsa04120
Primary immunodeficiency	36 targets	path:hsa05340

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (23)

Functions (9)

Components (3)

Processes (11)

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1 – 9 of 9

GO Term	Evidence	Assigned by
chromatin binding	Inferred from Direct Assay (IDA)	UniProtKB
histone binding	Inferred from Direct Assay (IDA)	UniProtKB
RNA polymerase II regulatory region sequence-specific DNA binding	Inferred from Direct Assay (IDA)	NTNU_SB
transcription regulatory region DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
zinc ion binding	Inferred from Direct Assay (IDA)	UniProtKB
DNA-binding transcription factor activity, RNA polymerase II-specific	Inferred from Sequence Model (ISM)	NTNU_SB
DNA-binding transcription activator activity, RNA polymerase II-specific	Inferred by Curator (IC)	NTNU_SB
identical protein binding	Inferred from Electronic Annotation (IEA)	Ensembl
translation regulator activity	Inferred from Electronic Annotation (IEA)	InterPro

Disease Associations ()

No disease associations found

GWAS Traits (14)

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5

1 – 5 of 14

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
Crohn's disease	EFO_0000384	3	3	0	1.1	90.1
Addison disease	MONDO_0009410	1	2	0	2.8	88.2
eosinophil count	EFO_0004842	3	2	3		85.1
eosinophil percentage of leukocytes	EFO_0007991	2	2	2		82.2
inflammatory bowel disease	EFO_0003767	1	1	0	1.1	77.7

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5

1 – 5 of 14

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
Crohn's disease	EFO_0000384	0	1.1	90.1
Addison disease	MONDO_0009410	0	2.8	88.2
eosinophil count	EFO_0004842	3		85.1
eosinophil percentage of leukocytes	EFO_0007991	2		82.2
inflammatory bowel disease	EFO_0003767	0	1.1	77.7

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Activator
Alternative splicing
Complete proteome
Cytoplasm
Direct protein sequencing
Disease mutation
DNA-binding
Metal-binding
Nucleus

GWAS Trait Find Similar Targets

No Header	No Header
Addison disease
amyotrophic lateral sclerosis
ankylosing spondylitis
celiac disease
Crohn's disease
eosinophil count
eosinophil percentage of granulocytes
eosinophil percentage of leukocytes
HbA1c measurement
hematocrit

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
cellular phenotype
digestive/alimentary phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
liver/biliary system phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (9)

1 – 5 of 9

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	autoimmune regulator	VGNC:1159	474134
Macaque	autoimmune regulator		712858
Mouse	autoimmune regulator (autoimmune polyendocrinopathy candidiasis ectodermal dystrophy)	MGI:1338803	11634
Rat	autoimmune regulator	RGD:1311139	294328
Dog	autoimmune regulator	VGNC:37743	487796

Species	Name	OMA	EggNOG	Inparanoid
Chimp	autoimmune regulator
Macaque	autoimmune regulator
Mouse	autoimmune regulator (autoimmune polyendocrinopathy candidiasis ectodermal dystrophy)
Rat	autoimmune regulator
Dog	autoimmune regulator

Publication Statistics

PubMed Score 723.18

PubMed score by year

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PubTator Score 725.47

PubTator score by year

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Related Publications

Text Mined References (172)

GeneRif Annotations (141)

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PMID	Year	Title