The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
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.
ELMs with same func. site: LIG_eIF4E_1  LIG_eIF4E_2 
ELM Description:
This is a variant of the standard LIG_eIF4E_1 binding motif. Most of the instances of this motif are predictions based on a SLiMSearch of Y.PP.[ILMV]R against the human proteome. Given deviations from the consensus motif in other LIG_eIF4E_1 instances, the LIG_eIF4E_2 instance with experimental support (DDX3) could be considered an atypical LIG_eIF4E_1 instance.
Pattern: Y.PP.[ILMV]R
Pattern Probability: 0.0000013
Present in taxon: Eukaryota
Interaction Domain:
IF4E (PF01652) Eukaryotic initiation factor 4E (Stochiometry: 1 : 1)
o See 5 Instances for LIG_eIF4E_2
o Abstract
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.
Due to its critical role in translation initation, eIF4E is the target of a group of "eIF4E inhibitory proteins", which competitively bind to the same region as eIF4G, sequestering 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. Downstream activity of the Akt and mTOR signalling pathways has implicated eIF4E and its regulation in tumorigenesis and drug resistance in murine lymphoma models. Signaling via eIF4e has also been associated with altered aging phenotypes in the nematode C. elegans.
o 1 selected reference:

o 4 GO-Terms:

o 5 Instances for LIG_eIF4E_2
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
O75821 EIF3G
213 219 QNKTGKYVPPSLRDGASRRG TP 13 Homo sapiens (Human)
338 344 CGSGEKYIPPHVRQAEETVD TP 13 Homo sapiens (Human)
O15523 DDX3Y
38 44 TASKGRYIPPHLRNREASKG TP 13 Homo sapiens (Human)
446 452 PKVATAYRPPALRNKPITNS TP 13 Homo sapiens (Human)
O00571 DDX3X
38 44 TASKGRYIPPHLRNREATKG TP 1 Homo sapiens (Human)
Please cite: The Eukaryotic Linear Motif resource: 2022 release. (PMID:34718738)

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