EIF4E Recombinant Protein

The protein encoded by this gene is a component of the eukaryotic translation initiation factor 4F complex, which recognizes the 7-methylguanosine cap structure at the 5' end of cellular mRNAs. The encoded protein aids in translation initiation by recruiting ribosomes to the mRNA. Association of this protein with the 4F complex is the rate-limiting step in translation initiation. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

Function: 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. Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit mediates the binding to the mRNA cap. Ref.25 Ref.28

Subunit structure: eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions. It is composed of at least EIF4A, EIF4E and EIF4G1/EIF4G3. EIF4E is also known to interact with other partners. The interaction with EIF4ENIF1 mediates the import into the nucleus. Hypophosphorylated EIF4EBP1, EIF4EBP2 and EIF4EBP3 compete with EIF4G1/EIF4G3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation. Rapamycin can attenuate insulin stimulation, mediated by FKBPs. Interacts mutually exclusive with EIF4A1 or EIF4A2. Interacts with NGDN and PIWIL2. Component of the CYFIP1-EIF4E-FMR1 complex composed of CYFIP, EIF4E and FMR1. Interacts directly with CYFIP1

By similarity. Interacts with Lassa virus Z protein. Binds to MKNK2 in nucleus. Interacts with LIMD1, WTIP and AJUBA. Interacts with APOBEC3G in an RNA-dependent manner. Ref.14 Ref.15 Ref.17 Ref.19 Ref.20 Ref.23 Ref.28

Subcellular location: Cytoplasm › P-body Ref.23.

Post-translational modification: Phosphorylation increases the ability of the protein to bind to mRNA caps and to form the eIF4F complex.

Involvement in disease: Autism 19 (AUTS19) [MIM:615091]: A complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate mental retardation.Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. A heterozygous single-nucleotide insertion has been found in families affected by autism. The variant results in increased promoter activity and is involved in disease pathogenesis through EIF4E deregulation (Ref.22). Ref.22A chromosomal aberration involving EIF4E has been found in a patient with classic autism. Translocation t45(q23q31.3). The breakpoint on chromosome 4 is located 56 kb downstream of EIF4E (Ref.22).

Sequence similarities: Belongs to the eukaryotic initiation factor 4E family.

Caution: Was originally thought to be phosphorylated on Ser-53 (Ref.9); this was later shown to be wrong (Ref.13).

Mass spectrometry: Molecular mass is 24964.3 Da from positions 2 - 217. Determined by ESI. Ref.29Molecular mass is 24960 Da from positions 2 - 217. Determined by ESI. Ref.30