Eukaryotic translation initiation factor 4E (EIF4E)

The protein contains 217 amino acids for an estimated molecular weight of 25097 Da.

 

Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures (PubMed:16271312, PubMed:22578813). In addition to its role in translation initiation, also acts as a regulator of translation and stability in the cytoplasm (PubMed:24335285). Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression: in the complex, EIF4E mediates the binding to the mRNA cap (By similarity). Component of a multiprotein complex that sequesters and represses translation of proneurogenic factors during neurogenesis (By similarity). In P-bodies, component of a complex that mediates the storage of translationally inactive mRNAs in the cytoplasm and prevents their degradation (PubMed:24335285). May play an important role in spermatogenesis through translational regulation of stage-specific mRNAs during germ cell development (By similarity). (updated: Oct. 7, 2020)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 100%
Model score: 100
No model available.

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The reference OMIM entry for this protein is 133440

Eukaryotic translation initiation factor 4e; eif4e
Eukaryotic translation initiation factor 4e family, member 1; eif4e1
Eif4e family, member 1
Eif4e-like 1; eif4el1
Messenger rna cap-binding protein eif4e

DESCRIPTION

All eukaryotic cellular mRNAs are blocked at their 5-prime ends with the 7-methylguanosine cap structure, m7GpppX (where X is any nucleotide). This structure is involved in several cellular processes including enhanced translational efficiency, splicing, mRNA stability, and RNA nuclear export. EIF4E is a eukaryotic translation initiation factor involved in directing ribosomes to the cap structure of mRNAs. It is a 24-kD polypeptide that exists as both a free form and as part of a multiprotein complex termed EIF4F. The EIF4E polypeptide is the rate-limiting component of the eukaryotic translation apparatus and is involved in the mRNA-ribosome binding step of eukaryotic protein synthesis. The other subunits of EIF4F are a 50-kD polypeptide, termed EIF4A (see 601102), that possesses ATPase and RNA helicase activities, and a 220-kD polypeptide, EIF4G (600495) (summary by Rychlik et al., 1987).

CLONING

Rychlik et al. (1987) cloned and sequenced EIF4E from human erythrocytes.

GENE FUNCTION

Pause et al. (1994) identified 2 homologous proteins, EIF4EBP1 (602223) and EIF4EBP2 (602224), that bind to EIF4E and may regulate its activity. Jones et al. (1997) stated that EIF4E is the rate-limiting component in protein synthesis and may play a role in growth regulation. The overexpression of EIF4E can cause malignant transformation. Waskiewicz et al. (1997) identified EIF4E as a potential physiologic substrate for Mnk1 (MKNK1; 606724) and Mnk2 (MKNK2; 605069) in mouse. Using coimmunoprecipitation experiments, Pyronnet et al. (1999) demonstrated that MNK1 interacts with the EIF4F complex via its interaction with the C-terminal region of EIF4G, not through a direct interaction with EIF4E. An EIF4E mutant lacking EIF4G-binding capability was poorly phosphorylated in cells. Pyronnet et al. (1999) hypothesized that EIF4G provides a docking site for MNK1 to phosphorylate EIF4E. In mammals, MTOR (601231) cooperates with PI3K (see 171834)-dependent effectors in a biochemical signaling pathway to regulate the size of proliferating cells. Fingar et al. (2002) presented evidence that rat S6k1 alpha-II (608938), Eif4e, and Eif4ebp1 mediate Mtor-dependent cell size control. Using a murine lymphoma model, Wendel et al. (2004) demonstrated that Akt (164730) promotes tumorigenesis and drug resistance by disrupting apoptosis, and that disruption of Akt signaling using the mTOR inhibitor rapamycin reverses chemoresistance in lymphomas expressing Akt, but not in those with other apoptotic defects. The translational regulator Eif4e, which acts downstream of Akt and mTOR, recapitulated the action of Akt in tumorigenesis and drug resistance but was unable to confer sensitivity to rapamycin and chemotherapy. Wendel et al. (2004) concluded that their results established Akt signaling through mTOR and Eif4e as an important mechanism of oncogenesis and drug resistance in vivo and revealed how targeting apoptotic programs can restore drug sensitivity in a genotype-dependent manner. Syntichaki et. al. (2007) showed that loss of a specific eIF4E isoform, Ife2, that functions in somatic tissues reduces global protein synthesis, protects from oxidative stress, and extends life span in Caenorhabditis elegans. Life span extension was independent of the forkhead transcription factor Daf16 (see 136533), which mediates the effects of the insulin-like signaling pathway on aging. Furthermore, Ife2 deficiency further extended the life span of lo ... More on the omim web site

Subscribe to this protein entry history

Oct. 20, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 133440 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed