| Accession: | |
|---|---|
| Functional site class: | Ligand motif binding the CSL BTD |
| Functional site description: | The DNA binding β-trefoil domain is built out of a capped β-barrel, which has an internal pseudo threefold symmetry. In CSL proteins this domain functions as an interaction site for NotchIC (the intracellular post-proteolytic part of the Notch receptor), co-repressors and some viral regulatory proteins such as EBNA2 and EBNA3. CSL (CBF1/RBP-jκ, Su(H), Lag-1) proteins serve as co-repressors or as co-activators of Notch pathway target gene expression. CSL’s regulatory character changes from a repressing to an activating component when the RAM domain of NotchIC binds to it. This interaction with NotchIC is necessary for the expression of genes that are important in embryonic developmental processes and tissue maintenance. |
| ELM Description: | The ɸWɸP motif represents the main interaction site between Notch-like proteins and CSL transcription factors. This interaction plays an important role in the Notch pathway. The very conserved W and P in the CSL binding-motif enter into a hydrophobic pocket provided by CSL(Wilson,2006).The other two positions are less conserved but both also have hydrophobic preferences. Since CSL may function as either a gene expression repressor or activator, depending on it’s conformation, it represents a key step in gene expression where several co-regulatory proteins operate. RITA and KyoT2 are such co-regulators and interact with CSL via the same binding motif as Notch, ɸWɸP (Wacker,2011; Collins,2014). Some viruses have developed mechanisms to manipulate Notch-signalling by expressing proteins that carry this binding motif and thus permanently stimulate Notch-like expression regulation (Calderwood,2011; Heinzelmann,2010). In all non-viral proteins, which carry the motif, a conserved occurrence of a G or an A at least 3 positions in front of the SLiM can be noticed. In Notch proteins, a basic region of circa five amino acids length precedes the hydrophobic motif, separated by a gap of about five residues. The basic residues also bind to CSL. The viral proteins, which tend to manipulate Notch-controlled gene-expression, do not show these extra residues, having just the core WxP-based motif. Often the viral proteins have multiple WxP motifs, some of which do not match the ELM pattern, having a non-hydrophobic residue in the less conserved positions. It is likely that the viral motifs can bind multiple CSL molecules. |
| Pattern: | [AFILMPTVW]W[FHILMPSTVW]P |
| Pattern Probability: | 0.0001278 |
| Present in taxons: | Metazoa Viruses |
| Interaction Domain: |
BTD (PF09270)
Beta-trefoil DNA-binding domain
(Stochiometry: 1 : 1)
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