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PR00375

Identifier
HUNTINGTIN  [View Relations]  [View Alignment]  
Accession
PR00375
No. of Motifs
6
Creation Date
12-JUN-1995  (UPDATE 07-JUN-1999)
Title
Huntingtin signature
Database References

INTERPRO; IPR000091
Literature References
1. BAXENDALE, S., ABDULLA, S., ELGAR, G., BUCK, D., BERKS, M., MICKLEM, G.,
DURBIN, R., BATES, G., BRENNER, S., BECK, S. AND LEHRACH, H.
Comparative sequence analysis of the human and pufferfish Huntington's
disease genes.
NAT.GENET. 10 67-75 (1995).
 
2. TROTTIER, Y., DEVYS, D., IMBERT, G., SAUDOU, F., AN, I., LUTZ, Y.,
WEBER, C., AGID, Y., HIRSCH, E.C. AND MANDEL, J-L.
Cellular localisation of the Huntington's disease protein and
discrimination of the normal and mutated form.
NAT.GENET. 104-110 (1995).
 
3. PERUTZ, M.F., JOHNSTON, T., SUZUKI, M. AND FINCH, J.T.
Glutamine repeats as polar zippers: their possible role in inherited
neurodegenerative diseases. 
PROC.NATL.ACAD.SCI.U.S.A. 91 5355-5358 (1994).

Documentation
Huntington's disease (HD) is a mid-life onset, inherited, neurodegenerative
disorder characterised by motor impairment, involuntary movements (chorea),
psychiatric disorders and dementia [1,2]. The disease results from the
expansion of a polyglutamine-encoding CAG repeat in a gene of unknown
function. Moderate expansion of glutamine-coding CAG repeats has been
found in other neurological diseases (e.g. spinobulbar muscular atrophy
and Machado-Joseph disease), in all of which the pathological mechanism
linked to the expansion of the polyglutamine tract in the protein remains
a mystery.
 
The HD transcript is highly conserved, significant differences, as already
noted, occurring in the N-terminal Gln-repeat region. Huntingtin normally
contains 10-35 repeats, but shows 36-120 repeats in the disease form.
Migration differences between normal and mutated huntingtin in a denaturing
polyacrylamide gel suggest that the poly-Gln stretch disrupts the protein
conformation [2]. This finding is consistent with the observation that
Gln repeats may form tightly-linked beta-sheets that could act as polar
zippers [3]. 
 
HUNTINGTIN is a 6-element fingerprint that provides a signature for the
Huntington's disease protein. The fingerprint was derived from an initial
alignment of 3 sequences: the motifs were drawn from conserved regions
spanning virtually the full alignment length, but not including the 
N-terminal poly-glutamine region. A single iteration on OWL26.0 was
required to reach convergence, no further sequences being identified
beyond the starting set.
 
An update on SPTR37_9f identified a true set of 5 sequences.
Summary Information
5 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
6555555
5000000
4000000
3000000
2000000
123456
True Positives
HD_FUGRU      HD_HUMAN      HD_MOUSE      HD_RAT        
O42269
Sequence Titles
HD_FUGRU    HUNTINGTIN (HUNTINGTON'S DISEASE PROTEIN HOMOLOG) (HD PROTEIN) - FUGU RUBRIPES (JAPANESE PUFFERFISH) (TAKIFUGU RUBRIPES). 
HD_HUMAN HUNTINGTIN (HUNTINGTON'S DISEASE PROTEIN) (HD PROTEIN) - HOMO SAPIENS (HUMAN).
HD_MOUSE HUNTINGTIN (HUNTINGTON'S DISEASE PROTEIN HOMOLOG) (HD PROTEIN) - MUS MUSCULUS (MOUSE).
HD_RAT HUNTINGTIN (HUNTINGTON'S DISEASE PROTEIN HOMOLOG) (HD PROTEIN) - RATTUS NORVEGICUS (RAT).
O42269 HUNTINGTIN - BRACHYDANIO RERIO (ZEBRAFISH) (ZEBRA DANIO).
Scan History
OWL26_0    1  50   NSINGLE    
SPTR37_9f 2 6 NSINGLE
Initial Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
SPEFQKLLGIAMELFLLCSDD A46068 120 120 -
SPEFQKLLGIAMELFLLCSDD HUMHDA 120 120 -
SPEFQKLLGIAMELFLLCSDD MUSHDH 97 97 -

Motif 2 width=21
Element Seqn Id St Int Rpt
ESDVRMVADECLNKVIKALMD A46068 142 1 -
ESDVRMVADECLNKVIKALMD HUMHDA 142 1 -
ESDVRMVADECLNKVIKALMD MUSHDH 119 1 -

Motif 3 width=20
Element Seqn Id St Int Rpt
LQKQVLDLLAQLVQLRVNYC A46068 1446 1283 -
LQKQVLDLLAQLVQLRVNYC HUMHDA 1446 1283 -
LQKQVLDLLAQLVQLRVNYC MUSHDH 1424 1284 -

Motif 4 width=20
Element Seqn Id St Int Rpt
VFIGFVLKQFEYIEVGQFRE A46068 1472 6 -
VFIGFVLKQFEYIEVGQFRE HUMHDA 1472 6 -
VFIGFVLKQFEYIEVGQFRE MUSHDH 1450 6 -

Motif 5 width=20
Element Seqn Id St Int Rpt
PDSESVIVAMERVSVLFDRI A46068 2948 1456 -
PDSESVIVAMERVSVLFDRI HUMHDA 2948 1456 -
PDSESVIVAMERVSVLFDRI MUSHDH 2923 1453 -

Motif 6 width=22
Element Seqn Id St Int Rpt
GFPCEARVVARILPQFLDDFFP A46068 2970 2 -
GFPCEARVVARILPQFLDDFFP HUMHDA 2970 2 -
GFPCEARVVARILPQFLDDFFP MUSHDH 2945 2 -
Final Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
SPEFQKLLGIAMELFLLCSDD HD_HUMAN 120 120 -
SPEFQKLLGIAMELFLLCSND HD_MOUSE 97 97 -
SPEFQKLLGIAMEMFLLCSDD O42269 63 63 -
SPEFQKLLGIAMELFLLCSDD HD_RAT 89 89 -
SPEFQKLLGIAMEMFLLCSDD HD_FUGRU 63 63 -

Motif 2 width=21
Element Seqn Id St Int Rpt
ESDVRMVADECLNKVIKALMD HD_HUMAN 142 1 -
ESDVRMVADECLNKVIKALMD HD_MOUSE 119 1 -
ESDVRMVADECLNKIIKALMD O42269 85 1 -
ASRRRMVADECLNKVIKALMD HD_RAT 110 0 -
ESDVRMVADECLNRIIKALMD HD_FUGRU 85 1 -

Motif 3 width=20
Element Seqn Id St Int Rpt
LQKQVLDLLAQLVQLRVNYC HD_HUMAN 1446 1283 -
LQKQVLDLLAQLVQLRVNYC HD_MOUSE 1424 1284 -
LQRQVLDLLAQLVQLRVNYC O42269 1418 1312 -
LQKQVLDLLAQLVQLRVNYC HD_RAT 1415 1284 -
LQRQVLDLLAQLVQLRVNYC HD_FUGRU 1439 1333 -

Motif 4 width=20
Element Seqn Id St Int Rpt
VFIGFVLKQFEYIEVGQFRE HD_HUMAN 1472 6 -
VFIGFVLKQFEYIEVGQFRE HD_MOUSE 1450 6 -
VFIGFVLKQFEYIEVGQFRD O42269 1444 6 -
VFIGFVLKQFEYIEVGQFRE HD_RAT 1441 6 -
VFIGFVLKQFEYIEVGQFRD HD_FUGRU 1465 6 -

Motif 5 width=20
Element Seqn Id St Int Rpt
PDSESVIVAMERVSVLFDRI HD_HUMAN 2948 1456 -
PDSESVIVAMERVSVLFDRI HD_MOUSE 2923 1453 -
PDSESVIVAMERVSVLFDRI O42269 2925 1461 -
PDSESVIVAMERVSVLFDRI HD_RAT 2914 1453 -
PDSESIIVAMERVSVLFDRI HD_FUGRU 2952 1467 -

Motif 6 width=22
Element Seqn Id St Int Rpt
GFPCEARVVARILPQFLDDFFP HD_HUMAN 2970 2 -
GFPCEARVVARILPQFLDDFFP HD_MOUSE 2945 2 -
GFPSEARVVARILPQFLDDLFP O42269 2947 2 -
GFPCEARVVARILPQFLDDFFP HD_RAT 2936 2 -
GLPSEARVVARILPQFLDDFFP HD_FUGRU 2974 2 -