FC0025
EWS transcription factor  -  Transcription pre-initiation complex

Biological function
EWS is an RNA-binding protein. Chromosomal translocations involving EWS results in EFP fusion proteins, which are implicated in various human cancers.

Domain organization/sequence features
The sequence of the EWS activation domain (EAD) is highly repetitive. The EAD contains several degenerate hexapeptide repeats (SYGQQS).

Biochemical evidence
Systematic mutagenesis of the sequence shows exquisite requirement for the presence of Tyr. Mutation of Phe by Tyr could confer transcriptional activity even without phosphorylation.

Structure/Mechanism
The interaction between EAD and its target is likely mediated by cation - π interactions. Results indicate that it is the sequence composition rather than a specific order of residues, which is essential for transcriptional activation. Binding of EAD to multiple partners -mediated by multiple weak contacts - is also required for transcriptional activity.

Mechanism category
tethering

Significance
Fuzziness enables sequence independent, multivalent interactions with multiple partners.

Further reading
24086122