LIG_eIF4E_1
| 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)
|
 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. |
11 selected references:
-
A novel inhibitor of cap-dependent translation initiation in yeast: p20
competes with eIF4G for binding to eIF4E.
Altmann M, Schmitz N, Berset C, Trachsel H
EMBO J 1997 Mar 3; 16 (5), 1114-21
PMID: 9118949
-
eIF4G: translation's mystery factor begins to yield its secrets.
Morley SJ, Curtis PS, Pain VM
RNA 1997 Oct; 3 (10), 1085-104
PMID: 9326485
-
The mRNA 5' cap-binding protein eIF4E and control of cell growth.
Sonenberg N, Gingras AC
Curr Opin Cell Biol 1998 Apr; 10 (2), 268-75
PMID: 9561852
-
Cap-dependent translation initiation in eukaryotes is regulated by a
molecular mimic of eIF4G.
Marcotrigiano J, Gingras AC, Sonenberg N, Burley SK
Mol Cell 1999 Jun; 3 (6), 707-16
PMID: 10394359
-
eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and
regulators of translation.
Gingras AC, Raught B, Sonenberg N
Annu Rev Biochem 1999; 68, 913-63
PMID: 10872469
-
A conserved ER targeting motif in three families of lipid binding proteins
and in Opi1p binds VAP.
Loewen CJ, Roy A, Levine TP
EMBO J 2003 May 1; 22 (9), 2025-35
PMID: 12727870
-
Ribosome loading onto the mRNA cap is driven by conformational coupling
between eIF4G and eIF4E.
Gross JD, Moerke NJ, von der Haar T, Lugovskoy AA, Sachs AB, McCarthy JE, Wagner G
Cell 2003 Dec 12; 115 (6), 739-50
PMID: 14675538
-
The mRNA cap-binding protein eIF4E in post-transcriptional gene
expression.
von der Haar T, Gross JD, Wagner G, McCarthy JE
Nat Struct Mol Biol 2004 Jun; 11 (6), 503-11
PMID: 15164008
-
Molecular mechanisms of translational control.
Gebauer F, Hentze MW
Nat Rev Mol Cell Biol 2004 Oct; 5 (10), 827-35
PMID: 15459663
-
Regulation of cap-dependent translation by eIF4E inhibitory proteins.
Richter JD, Sonenberg N
Nature 2005 Feb 3; 433 (7025), 477-80
PMID: 15690031
-
Quantitative proteomics identifies Gemin5, a scaffolding protein involved
in ribonucleoprotein assembly, as a novel partner for eukaryotic
initiation factor 4E.
Fierro-Monti I, Mohammed S, Matthiesen R, Santoro R, Burns JS, Williams DJ, Proud CG, Kassem M, Jensen ON, Roepstorff P
J Proteome Res 2006 Jun; 5 (6), 1367-78
PMID: 16739988
4 GO-Terms:
13 Instances for LIG_eIF4E_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Please cite:
ELM-the Eukaryotic Linear Motif resource-2024 update.
(PMID:37962385)
ELM data can be downloaded & distributed for non-commercial use according to the ELM Software License Agreement
ELM data can be downloaded & distributed for non-commercial use according to the ELM Software License Agreement