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|Functional site class:||eIF4E binding motif|
|Functional site description:||Variant YxxxxL motifs that mediate binding to the dorsal surface of eIF4E through interactions with the Tryptophan at position 73 (in human and mouse). eIF4E is a key regulator of eukaryotic cap-dependent translation and these motifs play a role in both translation initiation, via interactions with eIF4G, and repression, via binding of eIF4E inhibitory proteins.|
|Description:|| A conserved YxxxxLϕ motif mediates binding of key regulatory proteins to the dorsal surface of eIF4E through interactions with the Tryptophan at position 73 (in human and mouse). This interaction plays a crucial role in eukaryotic cap-dependent translation initiation, recruiting the scaffold eIF4G to the cap-binding eIF4E protein as part of the eIF4F complex. eIF4G, recruits the ribosome to the bound mRNA through additional interactions with the ribosome-associated factor eIF3. The same region is also targeted by a group of "eIF4E inhibitory proteins", which competitively bind and sequester the available eIF4E and preventing eIF4F complex formation. These inhibitory proteins play a key role in important cellular processes, including cell cycle progression and metabolism.
Although the motif is defined by the literature as YxxxxLϕ, it should be noted that there are variants that do not have a Y at position 1 and/or have a positively charged residue in the final position.
|Pattern:||Y....L[VILMF] (Probability: 0.0001891)|
|Present in taxons:||Eukaryota|
The eukaryotic translation initiation factor eIF4E recognises the 5' 7-methylguanosine cap structure of mRNA, m7GpppX, during cap-dependent translation initiation. It has been identified as the rate-limiting component of the eukaryotic translation apparatus. eIF4E directly binds to the cap structure and additional scaffolding proteins of the eIF4F complex, which recruits the 40S subunit of the ribosome. The main scaffold protein, eIF4G, binds the dorsal surface of eIF4E through a conserved motif, recruting the ribosome through additional interactions with the ribosome-associated factor eIF3. The other subunit of the eIF4F complex is eIF4A, an RNA helicase responsible for unwinding mRNA secondary structure.
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