Autoimmune regulator

From Wikipedia, the free encyclopedia

Autoimmune regulator (autoimmune polyendocrinopathy candidiasis ectodermal dystrophy)

PDB rendering based on 1xwh.

Available structures: 1xwh

Identifiers

Symbol(s)

AIRE; AIRE1; APECED; APS1; APSI; PGA1

External IDs

OMIM: 607358 MGI: 1338803 HomoloGene: 327

Gene ontology
Molecular Function:	• transcription factor activity • protein binding • zinc ion binding • translation regulator activity • metal ion binding
Cellular Component:	• nucleus • cytoplasm
Biological Process:	• transcription • regulation of transcription, DNA-dependent • humoral immune response

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

Refseq

NM_000383 (mRNA)
NP_000374 (protein)

NM_009646 (mRNA)
NP_033776 (protein)

Location

Chr 21: 44.53 - 44.54 Mb

Chr 10: 77.43 - 77.45 Mb

Pubmed search

[2]

[3]

The Autoimmune Regulator, abbreviated AIRE, is a human gene which is expressed in the thymus. It causes transcription of a wide selection of organ-specific genes. This reduces the threat of autoimmunity occurring by allowing the elimination of autoreactive T cells by the process of negative selection if they are too reactive to self.

It is mutated in the rare autoimmune syndrome Autoimmune Polyendocrinopathy Syndrome type 1 (APS-1), also known as Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED). Disruption of AIRE results in the development of a range of autoimmune diseases, the most common clinical conditions in the syndrome are hypoparathyroidism, primary adrenocortical failure and chronic mucocutaneous candidiasis.^[1] AIRE is expressed primarily in the thymus.

A gene knockout of the murine homolog Aire has created a transgenic mouse model to study the mechanism of disease in human patients.^[2]

Research on the knockout mouse has demonstrated that Aire functions through initiating the transcription of a diverse set of self-antigens, such as insulin, in the thymus.^[3] This expression then allows maturing thymocytes to become tolerant towards peripheral organs, thereby suppressing autoimmune disease.^[4]

1 See also
2 References
3 Further reading
4 External links

[edit] See also

List of human clusters of differentiation for a list of CD molecules
Immune system
Immune tolerance

[edit] References

^ OMIM. [1]
^ Ramsey C, Winqvist O, Puhakka L, Halonen M, Moro A, Kämpe O, Eskelin P, Pelto-Huikko M, Peltonen L (2002). "Aire deficient mice develop multiple features of APECED phenotype and show altered immune response". Hum. Mol. Genet. 11 (4): 397–409. doi:10.1093/hmg/11.4.397. PMID 11854172.
^ Anderson MS, Venanzi ES, Klein L, Chen Z, Berzins SP, Turley SJ, von Boehmer H, Bronson R, Dierich A, Benoist C, Mathis D (2002). "Projection of an immunological self shadow within the thymus by the aire protein". Science 298 (5597): 1395–401. doi:10.1126/science.1075958. PMID 12376594.
^ Liston A, Lesage S, Wilson J, Peltonen L, Goodnow CC (2003). "Aire regulates negative selection of organ-specific T cells". Nat. Immunol. 4 (4): 350–4. doi:10.1038/ni906. PMID 12612579.

[edit] Further reading

Björses P, Aaltonen J, Horelli-Kuitunen N, et al. (1998). "Gene defect behind APECED: a new clue to autoimmunity.". Hum. Mol. Genet. 7 (10): 1547–53. PMID 9735375.
Heino M, Peterson P, Kudoh J, et al. (2001). "APECED mutations in the autoimmune regulator (AIRE) gene.". Hum. Mutat. 18 (3): 205–11. doi:10.1002/humu.1176. PMID 11524731.
Sato K, Nakajima K, Imamura H, et al. (2003). "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 (6): 625–33. PMID 12625412.
Ruan QG, She JX (2004). "Autoimmune polyglandular syndrome type 1 and the autoimmune regulator.". Clin. Lab. Med. 24 (1): 305–17. doi:10.1016/j.cll.2004.01.008. PMID 15157567.
Holmdahl R (2007). "Aire-ing self antigen variability and tolerance.". Eur. J. Immunol. 37 (3): 598–601. doi:10.1002/eji.200737152. PMID 17323409.
Aaltonen J, Björses P, Sandkuijl L, et al. (1995). "An autosomal locus causing autoimmune disease: autoimmune polyglandular disease type I assigned to chromosome 21.". Nat. Genet. 8 (1): 83–7. doi:10.1038/ng0994-83. PMID 7987397.
Aaltonen J, Horelli-Kuitunen N, Fan JB, et al. (1997). "High-resolution physical and transcriptional mapping of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy locus on chromosome 21q22.3 by FISH.". Genome Res. 7 (8): 820–9. PMID 9267805.
Nagamine K, Peterson P, Scott HS, et al. (1997). "Positional cloning of the APECED gene.". Nat. Genet. 17 (4): 393–8. doi:10.1038/ng1297-393. PMID 9398839.
"An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains." (1997). Nat. Genet. 17 (4): 399–403. doi:10.1038/ng1297-399. PMID 9398840.
Scott HS, Heino M, Peterson P, et al. (1998). "Common mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients of different origins.". Mol. Endocrinol. 12 (8): 1112–9. PMID 9717837.
Heino M, Scott HS, Chen Q, et al. (1999). "Mutation analyses of North American APS-1 patients.". Hum. Mutat. 13 (1): 69–74. doi:10.1002/(SICI)1098-1004(1999)13:1<69::AID-HUMU8>3.0.CO;2-6. PMID 9888391.
Björses P, Pelto-Huikko M, Kaukonen J, et al. (1999). "Localization of the APECED protein in distinct nuclear structures.". Hum. Mol. Genet. 8 (2): 259–66. PMID 9931333.
Rinderle C, Christensen HM, Schweiger S, et al. (1999). "AIRE encodes a nuclear protein co-localizing with cytoskeletal filaments: altered sub-cellular distribution of mutants lacking the PHD zinc fingers.". Hum. Mol. Genet. 8 (2): 277–90. PMID 9931335.
Björses P, Halonen M, Palvimo JJ, et al. (2000). "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 (2): 378–92. PMID 10677297.
Pitkänen J, Doucas V, Sternsdorf T, et al. (2000). "The autoimmune regulator protein has transcriptional transactivating properties and interacts with the common coactivator CREB-binding protein.". J. Biol. Chem. 275 (22): 16802–9. doi:10.1074/jbc.M908944199. PMID 10748110.
Hattori M, Fujiyama A, Taylor TD, et al. (2000). "The DNA sequence of human chromosome 21.". Nature 405 (6784): 311–9. doi:10.1038/35012518. PMID 10830953.
Pitkänen J, Vähämurto P, Krohn K, Peterson P (2001). "Subcellular localization of the autoimmune regulator protein. characterization of nuclear targeting and transcriptional activation domain.". J. Biol. Chem. 276 (22): 19597–602. doi:10.1074/jbc.M008322200. PMID 11274163.
Saugier-Veber P, Drouot N, Wolf LM, et al. (2001). "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 (4): 347–51. PMID 11275943.

[edit] External links

MeSH AIRE+protein

v • d • e

Transcription factors and intracellular receptors

(1) Basic domains

(1.1) Basic leucine zipper (bZIP)	Activating transcription factor (AATF, 1, 2, 3, 4, 5, 6, 7) • AP-1 (c-Fos, FOSB, FOSL1, FOSL2, c-Jun, JUNB, JUND) • BACH (1, 2) • BATF • BLZF1 • C/EBP (α, β, γ, δ, ε, ζ) • CREB (1, 3, L1) • CREM • DBP • DDIT3 • GABPA • HLF • MAF (B, F, G, K) • NFE (2, L1, L2) • NRL • NRF1 • XBP1

(1.2) Basic helix-loop-helix (bHLH)	ATOH1 • AhR • AHRR • ARNT • ASCL1 • BHLHB2 • BMAL (ARNTL, ARNTL2) • CLOCK • EPAS1 • HAND (1, 2) • HES (5, 6) • HEY (1, 2, L) • HES1 • HIF (1A, 3A) • ID (1, 2, 3, 4) • LYL1 • MXD4 • MYCL1 • MYCN • Myogenic regulatory factors (MyoD, Myogenin, MYF5, MYF6) • Neurogenins • NeuroD (1, 2) • NPAS (1, 2, 3) • OLIG (1, 2) • Scleraxis • TAL1 • Twist • USF1

(1.3) bHLH-ZIP	MAX • MITF • MNT • MLX • MXI1 • Myc • SREBP (1, 2)

(1.6) Basic helix-span-helix (bHSH)	AP-2

(2) Zinc finger
DNA-binding domains

(2.1) Nuclear receptor (Cys₄)	subfamily 1 (Thyroid hormone (α, β), CAR, FXR, LXR (α, β), PPAR (α, β/δ, γ), PXR, RAR (α, β, γ), ROR (α, β, γ), Rev-ErbA (α, β), VDR) • subfamily 2 (COUP-TF (I, II), Ear-2, HNF4 (α, γ), PNR, RXR (α, β, γ), Testicular receptor (2, 4), TLX) • subfamily 3 (Steroid hormone (Estrogen (α, β), Estrogen related (α, β, γ), Androgen, Glucocorticoid, Mineralocorticoid, Progesterone)) • subfamily 4 NUR (NGFIB, NOR1, NURR1) • subfamily 5 (LRH-1, SF1) • subfamily 6 (GCNF) • subfamily 0 (DAX1, SHP)

(2.2) Other Cys₄	GATA (1, 2, 3, 4, 5, 6) • MTA (1, 2, 3)

(2.3) Cys₂His₂	ATBF1 • BCL(6, 11A, 11B) • CTCF • E4F1 • EGR (2, 3) • ERV3 • General transcription factors (TFIIA, TFIIB, TFIID, TFIIE, TFIIF: 1, 2, TFIIH: 1, 2, 4, 2I, 3A, 3C1, 3C2) • GFI1 • GLI-Krüppel family (1, 2, 3, YY1) • HIC (1, 2) • HIVEP (1, 2, 3) • IKZF (1, 2, 3) • ILF (2, 3) • KLF (2, 4, 5, 6, 9, 10, 11, 12, 13) • MTF1 • MYT1 • OSR1 • Sp1 • zinc finger ((3, 7, 9, 10, 19, 22, 24, 33B, 34, 35, 41, 43, 44, 51, 74, 143, 146, 148, 165, 202, 217, 219, 238, 239, 259, 267, 268, 281, 295, 318, 330, 346, 350, 365, 366, 384, 451, 452, 471, 593, 638, 649, 655) • Zbtb7 (7A) • ZBT (16, 17, 33)

(2.4) Cys₆	HIVEP1

(2.5) Alternating composition	AIRE • DIDO1 • GRLF1 • ING (1, 2, 4) • JARID (1A, 1B, 1C, 1D, 2) • JMJD1B

(3) Helix-turn-helix
domains

(3.1) Homeo domain	ARX • CDX (1, 2) • CRX • CUTL1 • DLX (3, 4, 5) • EMX2 • EN (1, 2) • FHL (1, 2, 3) • HESX1 • HHEX • HLX • Homeobox (A1, A3, A4, A5, A7, A9, A10, A11, A13, B1, B2, B3, B4, B5, B6, B7, B8, B9, B13, C4, C5, C6, C8, C9, C10, C11, C13, D1, D3, D4, D8, D9, D10, D11, D12, D13) • HOPX • MEIS (1, 2) • MEOX2 • MNX1 • MSX (1, 2) • NANOG • NKX (2-1, 2-5, 3-1) • PHF (3, 6, 10, 17) • POU domain (PIT-1, BRN-3: 1, 2, Octamer transcription factor: 1, 2, 3/4, 6, 7) • OTX (1, 2) • PDX1

(3.2) Paired box	PAX (1, 2, 3, 4, 5, 6, 7, 8, 9)

(3.3) Fork head / winged helix	E2F (1, 2, 3, 4, 5) • FOX proteins (C1, C2, E1, G1, H1, K2, L2, M1, N3, O1A, , O3A, O4, P1, P2, P3)

(3.4) Heat Shock Factors	HSF (1, 2, 4)

(3.5) Tryptophan clusters	ELF (4, 5) • EGF • ELK (1, 3, 4) • ERF • ERG • ETS (1, 2) • ETV (1, 4, 5, 6) • FLI1 • Interferon regulatory factors (1, 2, 3, 4, 5, 6, 7, 8) • MYB • MYBL2

(3.6) TEA domain	transcriptional enhancer factor 1, 2

(4) β-Scaffold factors with
minor groove contacts

(4.1) Rel homology region	NF-κB (NFKB1, NFKB2, REL, RELA, RELB) • NFAT (C1, C2, C3, C4, 5)

(4.2) STAT	STAT (1, 2, 3, 4, 5, 6)

(4.3) p53	p53

(4.4) MADS box	Mef2 (A, B, C, D) • SRF

(4.7) High mobility group	HNF (1A, 1B) • LEF1 • SOX (2, 3, 4, 5, 6, 8, 9, 10, 11, 13, 15, 18) • SRY • SSRP1

(4.10) Cold-shock domain	CSDA, YBX1

(4.11) Runt	CBF (CBFA2T2, CBFA2T3, RUNX1, RUNX2, RUNX3, RUNX1T1)

(0) Other
transcription factors

(0.2) HMGI(Y)	HMGA (1, 2) • HBP1

(0.3) Pocket domain	Rb • RBL1 • RBL2

(0.5) AP-2/EREBP-related factors	Apetala 2 • EREBP • B3

(0.6) Miscellaneous	ARID (1A, 1B, 2, 3A, 3B, 4A) • CAP • IFI (16, 35) • MLL (2, 3, T1) • MNDA • NFI (A, B, C, X) • NFY (A, B, C) • Rho/Sigma • R-SMAD

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Autoimmune regulator

From Wikipedia, the free encyclopedia

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[edit] See also

[edit] References

[edit] Further reading

[edit] External links

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