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PR01711

Identifier
AIREGULATOR  [View Relations]  [View Alignment]  
Accession
PR01711
No. of Motifs
8
Creation Date
13-MAR-2002
Title
Autoimmune regulator (AIRE) signature
Database References
Literature References
1. The Finnish-German APECED Consortium.
An autoimmune disease, APECED, caused by mutations in a novel gene featuring 
two PHD-type zinc-finger domains. 
NAT.GENET. 17 399-403 (1997).
 
2. MITTAZ, L., ROSSIER, C., HEINO, M., PETERSON, P., KROHN, K.J.E., GOS, A., 
MORRIS, M.A., KUDOH, J., SHIMIZU, N., ANTONARAKIS, S.E. AND SCOT, H.S.
Isolation and chatacterisation of the mouse Aire gene.
BIOCHEM.BIOPHYS.RES.COMMUN. 255 483-490 (1999).
 
3. PETERSON, H.M., KUDOH, J., NAGAMINE, K., LAGERSTEDT, A., OVOD, V., 
RANKI, A., RANTALA, I., NIEMINEN, M., TUUKKANEN, J., SCOTT, H.S., 
ANTONARAKIS, S.E., SHIMIZU, N. AND KROHN, K.
Autoimmune regulator is expressed in the cells regulating immune tolerance 
in thymous medulla.
BIOCHEM.BIOPHYS.RES.COMMUN. 257 821-825 (1999).
 
4. KUMAR, P.G., LALORAYA, M., WANG, C.Y., RUAN, Q.G., SEMIROMI, A.D., 
KAO.K.J. AND SHE, J.X.
The autoimmune regulator (AIRE) is a DNA-binding protein.
J.BIOL.CHEM. 276 41357-41364 (2001).

Documentation
AIRE (AutoImmune REgulator) is the predicted protein responsible for a rare 
autosomal recessively inherited disease termed APECED. APECED, also 
called Autoimmune Polyglandular Syndrome type I (APS 1), is the only 
described autoimmune disease with established monogenic background, being 
localised outside the major histocompatibility complex region. It is 
characterised by the presence of two of the three major clinical entities, 
chronic mucocutaneus candidiasis, hypoparathyroidism and Addison's disease. 
Other immunologically mediated phenotypes, including insulin-dependent 
diabetes mellitus (IDDM), gonadal failure, chronic gastritis, vitiligo, 
autoimmune thyroid disease, enamel hypoplasia, and alopecia may also 
be present. Immunologically, APECED patients have deficient T cell 
responses towards Candida antigens, and clinical symptoms both within and 
outside the endocrine system, mainly as a result of autoimmunity against 
organ-specific autoantigens [1,2].
 
AIRE has motifs suggestive of a transcriptional regulator protein. It 
harbours two zinc fingers of the plant homodomain (PHD) type. A putative DNA-
binding domain, termed SAND, as well as four nuclear receptor binding LXXLL 
motifs, an inverted LXXLL domain, and a variant of the latter (FXXLL), hint 
that this protein functions as a transcription coactivator. Furthermore, a 
highly conserved N-terminal 100-amino acid domain in AIRE shows significant
similarity to the homogeneously staining (HSR) domain of Sp100 and Sp140 
proteins, which has been shown to function as a dimerisation domain in
several Sp-100 related proteins [2-4].
 
AIRE has a dual subcellular location. It is not only expressed in multiple 
immunologically relevant tissues, such as the thymus, spleen, lymph nodes 
and bone marrow, but it has also been detected in various other tissues, 
such as kidney, testis, adrenal glands, liver and ovary, suggesting that  
APECED proteins might also have a function outside the immune system. 
However, AIRE is not expressed in the target organs of autoimmune
destruction. At the subcellular level, AIRE can be found in the cell nucleus 
in a speckled pattern in domains resembling promyeolocytic leukaemia nuclear 
bodies, also known as ND10, nuclear dots or potential oncogenic domains 
associated with the AIRE homologous nuclear proteins Sp100, Sp140, and Lysp100.  
The nuclear localisation of AIRE, in keeping with its predicted protein 
domains, suggest that it may regulate the mechanisms involved in the
induction and maintenance of immune tolerance [3,4].
 
AIREGULATOR is an 8-element fingerprint that provides a signature for the
AIRE autoimmune regulators. The fingerprint was derived from an initial 
alignment of 6 sequences: the motifs were drawn from conserved regions 
largely spanning the N-terminal and central portions of the alignment, 
focusing on those sections that characterise the autoregulators but 
distinguish them from those possessing SAND and PHD domains. Two iterations
on SPTR39_17f were required to reach convergence, at which point a true set
comprising 14 sequences was identified. 
Summary Information
14 codes involving  8 elements
0 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
81414141414141414
700000000
600000000
500000000
400000000
300000000
200000000
12345678
True Positives
AIRE_HUMAN    O75745        Q9JLW0        Q9JLW1        
Q9JLW2 Q9JLW3 Q9JLW4 Q9JLW5
Q9JLW6 Q9JLW7 Q9JLW8 Q9JLW9
Q9JLX0 Q9Z0E3
Sequence Titles
AIRE_HUMAN  AUTOIMMUNE REGULATOR (APECED PROTEIN) - Homo sapiens (Human). 
O75745 AIRE PROTEIN - Homo sapiens (Human).
Q9JLW0 AUTOIMMUNE REGULATOR - Mus musculus (Mouse).
Q9JLW1 AUTOIMMUNE REGULATOR - Mus musculus (Mouse).
Q9JLW2 AUTOIMMUNE REGULATOR - Mus musculus (Mouse).
Q9JLW3 AUTOIMMUNE REGULATOR - Mus musculus (Mouse).
Q9JLW4 AUTOIMMUNE REGULATOR - Mus musculus (Mouse).
Q9JLW5 AUTOIMMUNE REGULATOR - Mus musculus (Mouse).
Q9JLW6 AUTOIMMUNE REGULATOR - Mus musculus (Mouse).
Q9JLW7 AUTOIMMUNE REGULATOR - Mus musculus (Mouse).
Q9JLW8 AUTOIMMUNE REGULATOR - Mus musculus (Mouse).
Q9JLW9 AUTOIMMUNE REGULATOR - Mus musculus (Mouse).
Q9JLX0 AUTOIMMUNE REGULATOR - Mus musculus (Mouse).
Q9Z0E3 AIRE PROTEIN (AUTOIMMUNE REGULATOR) - Mus musculus (Mouse).
Scan History
SPTR39_17f 1  200  NSINGLE    
Initial Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
RRLLRLHRTEIA Q9Z0E3 9 9 -
RRLLRLHRTEIA Q9JLX0 9 9 -
RRLLRLHRTEIA Q9JLW9 9 9 -
RRLLRLHRTEIA Q9JLW8 9 9 -
RRLLRLHRTEIA AIRE_HUMAN 8 8 -
RRLLRLHRTEIA O75745 8 8 -

Motif 2 width=14
Element Seqn Id St Int Rpt
DSAFPLLHALADHD Q9Z0E3 24 3 -
DSAFPLLHALADHD Q9JLX0 24 3 -
DSAFPLLHALADHD Q9JLW9 24 3 -
DSAFPLLHALADHD Q9JLW8 24 3 -
DSAFPLLHALADHD AIRE_HUMAN 23 3 -
DSAFPLLHALADHD O75745 23 3 -

Motif 3 width=19
Element Seqn Id St Int Rpt
PEDKFQETLRLKEKEGCPQ Q9Z0E3 40 2 -
PEDKFQETLRLKEKEGCPQ Q9JLX0 40 2 -
PEDKFQETLRLKEKEGCPQ Q9JLW9 40 2 -
PEDKFQETLRLKEKEGCPQ Q9JLW8 40 2 -
PEDKFQETLHLKEKEGCPQ AIRE_HUMAN 39 2 -
PEDKFQETLHLKEKEGCPQ O75745 39 2 -

Motif 4 width=15
Element Seqn Id St Int Rpt
DFWRILFKDYNLERY Q9Z0E3 77 18 -
DFWRILFKDYNLERY Q9JLX0 77 18 -
DFWRILFKDYNLERY Q9JLW9 77 18 -
DFWRILFKDYNLERY Q9JLW8 77 18 -
DFWRVLFKDYNLERY AIRE_HUMAN 76 18 -
DFWRVLFKDYNLERY O75745 76 18 -

Motif 5 width=15
Element Seqn Id St Int Rpt
NLESQHLPLGNGIQT Q9Z0E3 170 78 -
NLESQHLPLGNGIQT Q9JLX0 170 78 -
NLESQHLPLGNGIQT Q9JLW9 170 78 -
NLESQHLPLGNGIQT Q9JLW8 170 78 -
SAEQQRLPLGNGIQT AIRE_HUMAN 169 78 -
SAEQQRLPLGNGIQT O75745 169 78 -

Motif 6 width=23
Element Seqn Id St Int Rpt
SGDVPGTRGAVEGILIQQVFESG Q9Z0E3 197 12 -
SGDVPGTRGAVEGILIQQVFESG Q9JLX0 197 12 -
SGDVPGTRGAVEGILIQQVFESG Q9JLW9 197 12 -
SGDVPGTRGAVEGILIQQVFESG Q9JLW8 197 12 -
SGDVPGARGAVEGILIQQVFESG AIRE_HUMAN 196 12 -
SGDVPGARGAVEGILIQQVFESG O75745 196 12 -

Motif 7 width=19
Element Seqn Id St Int Rpt
SKKCIQVGGEFYTPNKFED Q9Z0E3 221 1 -
SKKCIQVGGEFYTPNKFED Q9JLX0 221 1 -
SKKCIQVGGEFYTPNKFED Q9JLW9 221 1 -
SKKCIQVGGEFYTPNKFED Q9JLW8 221 1 -
SKKCIQVGGEFYTPSKFED AIRE_HUMAN 220 1 -
SKKCIQVGGEFYTPSKFED O75745 220 1 -

Motif 8 width=10
Element Seqn Id St Int Rpt
EIPSGLWRCS Q9Z0E3 331 91 -
EIPSGLWRCS Q9JLX0 330 90 -
EIPSGLWRCS Q9JLW9 327 87 -
EIPSGLWRCS Q9JLW8 326 86 -
EIPSGTWRCS AIRE_HUMAN 329 90 -
EIPSGTWRCS O75745 329 90 -
Final Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
RRLLRLHRTEIA Q9JLW0 9 9 -
RRLLRLHRTEIA Q9Z0E3 9 9 -
RRLLRLHRTEIA Q9JLX0 9 9 -
RRLLRLHRTEIA Q9JLW9 9 9 -
RRLLRLHRTEIA Q9JLW8 9 9 -
RRLLRLHRTEIA Q9JLW7 9 9 -
RRLLRLHRTEIA Q9JLW6 9 9 -
RRLLRLHRTEIA Q9JLW5 9 9 -
RRLLRLHRTEIA Q9JLW4 9 9 -
RRLLRLHRTEIA Q9JLW3 9 9 -
RRLLRLHRTEIA Q9JLW2 9 9 -
RRLLRLHRTEIA Q9JLW1 9 9 -
RRLLRLHRTEIA AIRE_HUMAN 8 8 -
RRLLRLHRTEIA O75745 8 8 -

Motif 2 width=14
Element Seqn Id St Int Rpt
DSAFPLLHALADHD Q9JLW0 24 3 -
DSAFPLLHALADHD Q9Z0E3 24 3 -
DSAFPLLHALADHD Q9JLX0 24 3 -
DSAFPLLHALADHD Q9JLW9 24 3 -
DSAFPLLHALADHD Q9JLW8 24 3 -
DSAFPLLHALADHD Q9JLW7 24 3 -
DSAFPLLHALADHD Q9JLW6 24 3 -
DSAFPLLHALADHD Q9JLW5 24 3 -
DSAFPLLHALADHD Q9JLW4 24 3 -
DSAFPLLHALADHD Q9JLW3 24 3 -
DSAFPLLHALADHD Q9JLW2 24 3 -
DSAFPLLHALADHD Q9JLW1 24 3 -
DSAFPLLHALADHD AIRE_HUMAN 23 3 -
DSAFPLLHALADHD O75745 23 3 -

Motif 3 width=19
Element Seqn Id St Int Rpt
PEDKFQETLRLKEKEGCPQ Q9JLW0 40 2 -
PEDKFQETLRLKEKEGCPQ Q9Z0E3 40 2 -
PEDKFQETLRLKEKEGCPQ Q9JLX0 40 2 -
PEDKFQETLRLKEKEGCPQ Q9JLW9 40 2 -
PEDKFQETLRLKEKEGCPQ Q9JLW8 40 2 -
PEDKFQETLRLKEKEGCPQ Q9JLW7 40 2 -
PEDKFQETLRLKEKEGCPQ Q9JLW6 40 2 -
PEDKFQETLRLKEKEGCPQ Q9JLW5 40 2 -
PEDKFQETLRLKEKEGCPQ Q9JLW4 40 2 -
PEDKFQETLRLKEKEGCPQ Q9JLW3 40 2 -
PEDKFQETLRLKEKEGCPQ Q9JLW2 40 2 -
PEDKFQETLRLKEKEGCPQ Q9JLW1 40 2 -
PEDKFQETLHLKEKEGCPQ AIRE_HUMAN 39 2 -
PEDKFQETLHLKEKEGCPQ O75745 39 2 -

Motif 4 width=15
Element Seqn Id St Int Rpt
DFWRILFKDYNLERY Q9JLW0 77 18 -
DFWRILFKDYNLERY Q9Z0E3 77 18 -
DFWRILFKDYNLERY Q9JLX0 77 18 -
DFWRILFKDYNLERY Q9JLW9 77 18 -
DFWRILFKDYNLERY Q9JLW8 77 18 -
DFWRILFKDYNLERY Q9JLW7 77 18 -
DFWRILFKDYNLERY Q9JLW6 77 18 -
DFWRILFKDYNLERY Q9JLW5 77 18 -
DFWRILFKDYNLERY Q9JLW4 77 18 -
DFWRILFKDYNLERY Q9JLW3 77 18 -
DFWRILFKDYNLERY Q9JLW2 77 18 -
DFWRILFKDYNLERY Q9JLW1 77 18 -
DFWRVLFKDYNLERY AIRE_HUMAN 76 18 -
DFWRVLFKDYNLERY O75745 76 18 -

Motif 5 width=15
Element Seqn Id St Int Rpt
NLESQHLPLGNGIQT Q9JLW0 170 78 -
NLESQHLPLGNGIQT Q9Z0E3 170 78 -
NLESQHLPLGNGIQT Q9JLX0 170 78 -
NLESQHLPLGNGIQT Q9JLW9 170 78 -
NLESQHLPLGNGIQT Q9JLW8 170 78 -
NLESQHLPLGNGIQT Q9JLW7 170 78 -
NLESQHLPLGNGIQT Q9JLW6 170 78 -
NLESQHLPLGNGIQT Q9JLW5 170 78 -
NLESQHLPLGNGIQT Q9JLW4 170 78 -
NLESQHLPLGNGIQT Q9JLW3 170 78 -
NLESQHLPLGNGIQT Q9JLW2 170 78 -
NLESQHLPLGNGIQT Q9JLW1 170 78 -
SAEQQRLPLGNGIQT AIRE_HUMAN 169 78 -
SAEQQRLPLGNGIQT O75745 169 78 -

Motif 6 width=23
Element Seqn Id St Int Rpt
SGDVPGTRGAVEGILIQQVFESG Q9JLW0 197 12 -
SGDVPGTRGAVEGILIQQVFESG Q9Z0E3 197 12 -
SGDVPGTRGAVEGILIQQVFESG Q9JLX0 197 12 -
SGDVPGTRGAVEGILIQQVFESG Q9JLW9 197 12 -
SGDVPGTRGAVEGILIQQVFESG Q9JLW8 197 12 -
SGDVPGTRGAVEGILIQQVFESG Q9JLW7 197 12 -
SGDVPGTRGAVEGILIQQVFESG Q9JLW6 197 12 -
SGDVPGTRGAVEGILIQQVFESG Q9JLW5 197 12 -
SGDVPGTRGAVEGILIQQVFESG Q9JLW4 197 12 -
SGDVPGTRGAVEGILIQQVFESG Q9JLW3 197 12 -
SGDVPGTRGAVEGILIQQVFESG Q9JLW2 197 12 -
SGDVPGTRGAVEGILIQQVFESG Q9JLW1 197 12 -
SGDVPGARGAVEGILIQQVFESG AIRE_HUMAN 196 12 -
SGDVPGARGAVEGILIQQVFESG O75745 196 12 -

Motif 7 width=19
Element Seqn Id St Int Rpt
SKKCIQVGGEFYTPNKFED Q9JLW0 221 1 -
SKKCIQVGGEFYTPNKFED Q9Z0E3 221 1 -
SKKCIQVGGEFYTPNKFED Q9JLX0 221 1 -
SKKCIQVGGEFYTPNKFED Q9JLW9 221 1 -
SKKCIQVGGEFYTPNKFED Q9JLW8 221 1 -
SKKCIQVGGEFYTPNKFED Q9JLW7 221 1 -
SKKCIQVGGEFYTPNKFED Q9JLW6 221 1 -
SKKCIQVGGEFYTPNKFED Q9JLW5 221 1 -
SKKCIQVGGEFYTPNKFED Q9JLW4 221 1 -
SKKCIQVGGEFYTPNKFED Q9JLW3 221 1 -
SKKCIQVGGEFYTPNKFED Q9JLW2 221 1 -
SKKCIQVGGEFYTPNKFED Q9JLW1 221 1 -
SKKCIQVGGEFYTPSKFED AIRE_HUMAN 220 1 -
SKKCIQVGGEFYTPSKFED O75745 220 1 -

Motif 8 width=10
Element Seqn Id St Int Rpt
EIPSGLWRCS Q9JLW0 326 86 -
EIPSGLWRCS Q9Z0E3 331 91 -
EIPSGLWRCS Q9JLX0 330 90 -
EIPSGLWRCS Q9JLW9 327 87 -
EIPSGLWRCS Q9JLW8 326 86 -
EIPSGLWRCS Q9JLW7 331 91 -
EIPSGLWRCS Q9JLW6 330 90 -
EIPSGLWRCS Q9JLW5 327 87 -
EIPSGLWRCS Q9JLW4 326 86 -
EIPSGLWRCS Q9JLW3 331 91 -
EIPSGLWRCS Q9JLW2 330 90 -
EIPSGLWRCS Q9JLW1 327 87 -
EIPSGTWRCS AIRE_HUMAN 329 90 -
EIPSGTWRCS O75745 329 90 -