The Eukaryote Linear Motif resource for Functional Sites in Proteins
LIG_eIF4E_1 317
 
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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.
ELMs: LIG_eIF4E_1 LIG_eIF4E_2
Description: A conserved YxxxxL&#981; 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 YxxxxL&#981;, 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
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)
SequenceStartEndSubsequence
Instance LogicPDB Organism
IF4F1_YEAST 452 458 EHVKYTYGPTFLLQFKDKLN true positive --- Saccharomyces cerevisiae S288c
IF4F2_YEAST 423 429 PSVKYTYGPTFLLQFKDKLK true positive --- Saccharomyces cerevisiae S288c
O61380_DROME 621 627 PSGKKQYDREQLLQLREVKA true positive --- Drosophila melanogaster (Fruit fly)
CAF20_YEAST 4 10 MIKYTIDELFQLKPSLTLEV true positive --- Saccharomyces cerevisiae S288c
4EBP3_HUMAN 40 46 GGTRIIYDRKFLLECKNSPI true positive --- Homo sapiens (Human)
4EBP2_HUMAN 54 60 GGTRIIYDRKFLLDRRNSPM true positive --- Homo sapiens (Human)
IF41_WHEAT 66 72 SRERVRYSRDQLLDLRKITD true positive --- Triticum aestivum (Bread wheat)
4EBP1_HUMAN 54 60 GGTRIIYDRKFLMECRNSPV true positive --- Homo sapiens (Human)
GEMI5_HUMAN 992 998 LSIHKVYEAVELLKSNHFYR true positive --- Homo sapiens (Human)
CUP_DROME 327 333 SKPVKSYTRSRLMDIRNGMF true positive --- Drosophila melanogaster (Fruit fly)
IF4G_SCHPO 830 836 KAGKYEYDVPFLLQFQSVYT true positive --- Schizosaccharomyces pombe 972h-
IF4G1_HUMAN 612 618 LEEKKRYDREFLLGFQFIFA true positive --- Homo sapiens (Human)
IF4G3_HUMAN 624 630 TEGKKQYDREFLLDFQFMPA true positive --- Homo sapiens (Human)

Please cite: ELM - the database of eukaryotic linear motifs (PMID:22110040)

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