EIF4B

Eukaryotic translation initiation factor 4B is a protein that in humans is encoded by the EIF4B gene.^[5]

EIF4B
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1WI8, 2J76
Identifiers
Aliases	EIF4B, EIF-4B, PRO1843, eukaryotic translation initiation factor 4B
External IDs	OMIM: 603928; MGI: 95304; HomoloGene: 83162; GeneCards: EIF4B; OMA:EIF4B - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q13.13 Start 53,006,282 bp[1] End 53,042,215 bp[1]
Gene location (Mouse) Chr. Chromosome 15 (mouse)[2] Band 15|15 F2 Start 101,982,208 bp[2] End 102,005,608 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Achilles tendon ganglionic eminence left ovary epithelium of colon islet of Langerhans stromal cell of endometrium body of pancreas right ovary ventricular zone monocyte Top expressed in tail of embryo lacrimal gland genital tubercle epiblast ankle ventricular zone somite mandibular prominence left lung lobe vas deferens More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding nucleic acid binding ribosomal small subunit binding helicase activity RNA strand-exchange activity RNA strand annealing activity RNA binding translation initiation factor activity Cellular component cytosol eukaryotic translation initiation factor 4F complex polysome Biological process nuclear-transcribed mRNA poly(A) tail shortening regulation of translational initiation formation of translation preinitiation complex eukaryotic translation initiation factor 4F complex assembly protein biosynthesis translational initiation cytoplasmic translation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1975 75705 Ensembl ENSG00000063046 ENSMUSG00000058655 UniProt P23588 Q8BGD9 RefSeq (mRNA) NM_001300821 NM_001417 NM_018507 NM_001330654 NM_145625 RefSeq (protein) NP_001287750 NP_001317583 NP_001408 NP_663600 Location (UCSC) Chr 12: 53.01 – 53.04 Mb Chr 15: 101.98 – 102.01 Mb PubMed search [3] [4]
Wikidata
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Structure

EIF4B is characterized by a single folded RNA recognition motif (RRM) near its N-terminus, which adopts a classical beta alpha beta beta alpha beta topology. This RRM is responsible for RNA binding but interacts with RNA relatively weakly on its own; high-affinity binding is facilitated by adjacent N- and C-terminal extensions. The majority of the EIF4B protein, encompassing roughly 400 amino acids downstream of the RRM, is intrinsically disordered and forms what is known as the intrinsically disordered region (IDR). This IDR does not adopt a stable three-dimensional structure but instead enables dynamic interactions, self-association, and the formation of large oligomers and biomolecular condensates under certain cellular conditions. A short helical segment within the IDR, coinciding with an arginine-rich motif (ARM), further contributes to RNA binding.^[6][7]

Mammalian eIF4B acts as a dimer, and other studies had shown that it could form higher-order oligomers as well, through intrinsically disordered regions (IDR).^[7]

Function

Eukaryotic translation initiation factor 4B (EIF4B) is a multidomain protein essential for efficient cap-dependent translation in eukaryotic cells. Structurally, EIF4B contains a single folded RNA recognition motif (RRM) near its N-terminus.^[6][8][9] This RRM is responsible for RNA binding but interacts with RNA relatively weakly on its own; high-affinity binding is facilitated by adjacent N- and C-terminal extensions.^[6][10] The majority of the EIF4B protein, encompassing roughly 400 amino acids downstream of the RRM, is intrinsically disordered and forms what is known as the intrinsically disordered region (IDR).^[7] This IDR does not adopt a stable three-dimensional structure but instead enables dynamic interactions, self-association, and the formation of large oligomers and biomolecular condensates under certain cellular conditions.^[7] A short helical segment within the IDR, coinciding with an arginine-rich motif (ARM), further contributes to RNA binding.^[7] The flexible and highly dynamic nature of the IDR allows EIF4B to orchestrate diverse molecular interactions critical for translation initiation, including stimulation of the helicase activity of eIF4A and supporting the assembly of other components of the translation initiation machinery.^[11]

EIF4B is a critical protein in the process of cap-dependent translation initiation in eukaryotic cells. Its primary function is to enhance the helicase activity of eIF4A, a DEAD-box RNA helicase, by stimulating its ability to unwind secondary structures in the 5′ untranslated regions (UTRs) of mRNAs[9].^[11][12] This unwinding activity is vital for the ribosome to scan along the mRNA and locate the start codon efficiently. eIF4B also acts as a scaffold by interacting with other translation initiation factors, such as eIF3 and eIF4F, facilitating the assembly of the translation initiation complex.^[13] Furthermore, eIF4B’s RNA binding capacity—mediated both by its RNA recognition motif (RRM) and its arginine-rich motif (ARM)—directly supports the recruitment and stabilization of mRNA on the ribosome, ensuring efficient and accurate initiation of protein synthesis.^[6][10] The multifaceted functions of eIF4B are essential for regulating translational output and adapting protein synthesis to cellular conditions.^[14]

eIF4B has been shown to interact with and stimulate the enzymatic/RNA helicase activity of eIF4A, also increasing its RNA and ATP binding activity, and bind to the eIF3 complex through the eIF3A subunit.^[15] This interaction results in the recruitment of the eukaryotic small ribosomal subunit (40S) to the mRNA which will in turn set the stage for the later steps leading to elongation.

Clinical significance

eIF4B is overexpressed in cancer cells and certain studies had named eIF4B as a potential therapeutic target for treatment of certain types of cancer.^[16]

See also

• Eukaryotic translation
• eIF4F