The Eukaryote Linear Motif resource for Functional Sites in Proteins
Accession:
Functional site class:
eh1 motif
Functional site description:
The eh1 motif binds to the WD40 domain of the Groucho/TLE corepressor.
ELM Description:
The original eh1 motif identified in homeodomains has been augmented by Eberhard,2000, Barolo,2002, Copley,2005 and Goldstein,2005 who found other TF families with the motif. Any eh1 motif linked to a paired box (including some with homeodomains) shows a variant motif with Y or H at the first position where the classical motif is always F. The motif in ELM is a composite of these two variants which have both been reported to bind Groucho/TLE. There should be some other functional explanation for this consistent variation but at the time of pattern creation this was not resolved. This motif is found in natively disordered polypeptide but the conserved hydrophobic amino acids will cause buried false positives in globular domains.
Pattern: .[FYH].[IVM][^WFYP][^WFYP][ILM][ILMV].
Pattern Probability: 0.0000786
Present in taxon: Metazoa
Interaction Domain:
WD40 (PF00400) WD domain, G-beta repeat (Stochiometry: 1 : 1)
PDB Structure: 2CE8
<a href="http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=2CE8" title="" target="_blank"><img src="/media/pdb.ico.png"/>2CE8</a>
o See 11 Instances for LIG_EH1_1
o Abstract
The eh1 motif was detected by its presence in several homeodomain transcription repressors, such as Engrailed and Goosecoid (Logan,1992, Smith,1996, Jimenez,1999). The motif has the consensus sequence FxIxxIL, where only F is completely conserved, and it allows for the recruitment of the corepressor Groucho/TLE (Jimenez,1997). The structure of the C-terminal WD40 repeat domain of the human Groucho/TLE1 protein, together with analysis of the effect of mutants in C. elegans Groucho/TLE homologue UNC-37 suggests an induced fit mechanism for the binding of the eh1 motif to the WD40 domain of Groucho/TLE (Pickles,2002). The Groucho/TLE corepressor proteins repress transcription by recruiting histione deacetylases, and possibly by additional mechanisms (Chen,2000).
Subsequently paired box protein Pax5 (Eberhard,2000) and hairless (Barolo,2002, Nagel,2005) have been shown to bind Groucho/TLE through eh1 motifs (note that eh1 was termed octapeptide motif in Pax).
More recently Copley,2005 undertook a bioinformatics survey and identified significantly conserved eh1 motifs in other transcription factor families including forkhead, T-box, zinc finger and doublesex. However, it should be noted that all paired box (plus hairless and one T-box protein, brachyury) motifs consistently substitute the conserved Phe with Tyr or His: the meaning of the implied change of function remains to be elucidated since both variants bind Groucho/TLE.
The transcription factor Dorsal is reported to contain an eh1-like motif reported to be responsible for the recruitment of Groucho but it does not match the other motifs (Flores-Saaib,2001).
Other interaction partners of Groucho depend on a LIG_WRPW_1 or LIG_WRPW_2 motif for binding. Remarkably, both eh1 and WRPW bind to the same site on Groucho, across the central hole of the WD40 propeller (Jennings,2006) despite their different sequences and bound conformations. The binding will be mutually exclusive, but it is not known if this is meaningful in practice.
o 13 selected references:

o 3 GO-Terms:

o 11 Instances for LIG_EH1_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
P55317 FOXA1
FOXA1_HUMAN
399 407 YSFNHPFSINNLMSSSEQQH TP 2 Homo sapiens (Human)
Q02308 H
HLES_DROME
662 670 TRLNSSYSIHSLLGGSSGSG TP 4 Drosophila melanogaster (Fruit fly)
P56915 GSC
GSC_HUMAN
5 13 MPASMFSIDNILAARPRCKD TP 1 Homo sapiens (Human)
1 
Q02548 PAX5
PAX5_HUMAN
178 186 DSAGSSYSISGILGITSPSA TP 2 Homo sapiens (Human)
Q9Y5R5 DMRT2
DMRT2_HUMAN
542 550 VNEPLSFSVESILKRPSSAI TP 1 Homo sapiens (Human)
O15178 T
BRAC_HUMAN
14 22 AGKSLQYRVDHLLSAVENEL TP 1 Homo sapiens (Human)
Q9Y458 TBX22
TBX22_HUMAN
9 17 SSRARAFSVEALVGRPSKRK TP 1 Homo sapiens (Human)
Q9VQU9 bowl
BOWEL_DROME
735 743 APPPAPPRRTGFSIEDIMRR TP 2 Drosophila melanogaster (Fruit fly)
P23803 odd
ODD_DROME
383 391 SSSEKPKRMLGFTIDEIMSR TP 3 Drosophila melanogaster (Fruit fly)
P54366 Gsc
GSC_DROME
109 117 AAAASLFTIDSILGSRQQGG TP 2 Drosophila melanogaster (Fruit fly)
P02836 en
HMEN_DROME
174 182 AKPSLAFSISNILSDRFGDV TP 3 Drosophila melanogaster (Fruit fly)
Please cite: The Eukaryotic Linear Motif Resource ELM: 10 Years and Counting (PMID:24214962)

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