The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
Accession:
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:
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 in 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]
Pattern Probability: 0.0001891
Present in taxon: Eukaryota
Interaction Domain:
IF4E (PF01652) Eukaryotic initiation factor 4E (Stochiometry: 1 : 1)
o See 13 Instances for LIG_eIF4E_1
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 11 selected references:

o 4 GO-Terms:

o 13 Instances for LIG_eIF4E_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
Q04637 EIF4G1
IF4G1_HUMAN
612 618 LEEKKRYDREFLLGFQFIFA TP 2 Homo sapiens (Human)
1 
Q10475 tif471
IF4G_SCHPO
830 836 KAGKYEYDVPFLLQFQSVYT TP 1 Schizosaccharomyces pombe 972h-
1 
Q9VMA3 cup
CUP_DROME
327 333 SKPVKSYTRSRLMDIRNGMF TP 1 Drosophila melanogaster (Fruit fly)
1 
Q8TEQ6 GEMIN5
GEMI5_HUMAN
992 998 LSIHKVYEAVELLKSNHFYR TP 1 Homo sapiens (Human)
1 
O60516 EIF4EBP3
4EBP3_HUMAN
40 46 GGTRIIYDRKFLLECKNSPI TP 1 Homo sapiens (Human)
1 
Q13541 EIF4EBP1
4EBP1_HUMAN
54 60 GGTRIIYDRKFLMECRNSPV TP 2 Homo sapiens (Human)
1 
1 
Q03387 
IF41_WHEAT
66 72 SRERVRYSRDQLLDLRKITD TP 1 Triticum aestivum (Bread wheat)
1 
Q13542 EIF4EBP2
4EBP2_HUMAN
54 60 GGTRIIYDRKFLLDRRNSPM TP 1 Homo sapiens (Human)
1 
P12962 CAF20
CAF20_YEAST
4 10 MIKYTIDELFQLKPSLTLEV TP 1 Saccharomyces cerevisiae S288c
1 
O61380 eIF4G
O61380_DROME
621 627 PSGKKQYDREQLLQLREVKA TP 1 Drosophila melanogaster (Fruit fly)
1 
P39936 TIF4632
IF4F2_YEAST
423 429 PSVKYTYGPTFLLQFKDKLK TP 1 Saccharomyces cerevisiae S288c
1 
P39935 TIF4631
IF4F1_YEAST
452 458 EHVKYTYGPTFLLQFKDKLN TP 1 Saccharomyces cerevisiae S288c
1 
O43432 EIF4G3
IF4G3_HUMAN
624 630 TEGKKQYDREFLLDFQFMPA TP 1 Homo sapiens (Human)
1 
Please cite: ELM 2016-data update and new functionality of the eukaryotic linear motif resource. (PMID:26615199)

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