Affinage

EIF5

Eukaryotic translation initiation factor 5 · UniProt P55010

Length
431 aa
Mass
49.2 kDa
Annotated
2026-06-09
58 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

eIF5 is a bifunctional regulator of eukaryotic translation initiation that couples GTP hydrolysis on eIF2 to AUG start-codon recognition and the assembly of the multifactor preinitiation complex (PMID:8161539, PMID:11166181). It functions as a GTPase-activating protein (GAP) for eIF2: forming a 1:1 complex with eIF2, its N-terminal domain supplies an 'arginine finger' (Arg15, with a contribution from Arg48) that stimulates hydrolysis of eIF2-bound GTP in the 40S initiation complex, an activity required for 80S complex formation and translation (PMID:8161539, PMID:11166181). Through a glutamic acid-rich bipartite motif in its α-helical, HEAT/W2-type C-terminal domain (CTD), eIF5 bridges eIF2 (via eIF2β) and eIF3 (via the NIP1/eIF3c N-terminus) and simultaneously contacts eIF1, eIF4G, and eIF5B, nucleating the multifactor complex (MFC) that also contains initiator tRNA(Met); disruption of this motif (tif5-7A) collapses MFC assembly and impairs initiation (PMID:11018020, PMID:10805737, PMID:16781736). eIF5 enforces start-codon fidelity by controlling Pi release and the open-to-closed conformational transition of the scanning PIC: its CTD antagonizes eIF1 binding, eIF1 dissociation coupled to eIF1A-CTT movement toward the eIF5-NTD triggers Pi release, and the eIF5-NTD engages Met-tRNAi at the position vacated by eIF1 to stabilize the accommodated state (PMID:23293029, PMID:25114053, PMID:30475211). Beyond the GAP cycle, eIF5 acts as a GDP dissociation inhibitor (GDI) that stabilizes eIF2•GDP between initiation rounds — a distinct activity that requires eIF2β and is displaced by eIF2B acting as a GDP dissociation factor (GDF) prior to nucleotide exchange (PMID:20485439, PMID:24352424, PMID:27458202). eIF5 is phosphorylated by casein kinase II within a C-terminal acidic cluster (Ser-387/Ser-388), which increases its affinity for eIF2β, eIF1A, and other CTD partners (PMID:11861906, PMID:34923394, PMID:40670154). eIF5 GAP activity preferentially stimulates poly-GA RAN translation from a CUG near-cognate codon in C9orf72 FTLD/ALS, linking the factor to repeat-associated non-AUG translation (PMID:38301895).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1994 High

    Established that eIF5 directly partners eIF2 and that this complex is the unit responsible for hydrolyzing GTP at the 40S initiation complex, defining eIF5's core catalytic role.

    Evidence Glycerol gradient sedimentation and in vitro GTPase/80S assembly assays with purified recombinant eIF5

    PMID:8161539

    Open questions at the time
    • Did not identify the catalytic residue or mechanism of GAP action
    • Stoichiometry within the larger 40S complex not resolved
  2. 2000 High

    Defined eIF5 as the physical scaffold of the multifactor complex, showing its glutamic acid-rich bipartite CTD motif bridges eIF2β and eIF3c to assemble eIF1 and initiator tRNA into one entity.

    Evidence In vitro binding, co-IP from yeast extracts, and the tif5-7A bipartite-motif mutant; alanine substitution of conserved glutamates

    PMID:10805737 PMID:11018020 PMID:9671501

    Open questions at the time
    • Atomic basis of the bipartite interactions not yet resolved
    • How MFC assembly couples to ribosome loading unclear
  3. 2001 High

    Identified eIF5 as a classical arginine-finger GAP for eIF2 and showed it bridges the cap-binding eIF4G to the PIC, placing 48S-to-80S conversion as the rate-limiting initiation step.

    Evidence AlF4- transition-state mimic binding, R15M/R48M mutagenesis with GTPase and in vitro translation readouts; GST pulldowns and polysome analysis

    PMID:11166181 PMID:11331597

    Open questions at the time
    • Structure of the catalytic NTD on the ribosome not yet available
    • How GAP triggering is timed to AUG recognition not yet defined
  4. 2004 High

    Showed that the eIF3c/NIP1 N-terminal domain coordinates eIF1–eIF5 contacts to suppress GTP hydrolysis at non-AUG codons, linking MFC architecture to start-codon fidelity.

    Evidence NIP1-NTD mutagenesis, yeast Sui- genetics, in vitro binding, and eIF1/eIF5 overexpression suppression

    PMID:15485912

    Open questions at the time
    • Molecular switch converting fidelity-checkpoint to GAP-active state not defined
    • Quantitative contribution of each contact to AUG selection unclear
  5. 2006 High

    Provided atomic structures of the eIF5-CTD (human and yeast), revealing an α-helical HEAT/W2 domain homologous to eIF2Bε-CTD and mapping non-overlapping electrostatic patches for eIF2β and eIF3c.

    Evidence X-ray crystallography of human (high-resolution) and S. cerevisiae (1.5 Å) eIF5-CTD with electrostatic surface analysis

    PMID:16616930 PMID:16781736

    Open questions at the time
    • Did not capture partner-bound complexes
    • Conformation of the catalytic NTD unresolved
  6. 2010 High

    Revealed a second, GAP-independent function for eIF5 as a GDP dissociation inhibitor that retains eIF2•GDP between rounds and as a component of the eIF2(αP) complex inhibiting eIF2B, mechanistically separating fidelity from recycling control.

    Evidence Fluorescence nucleotide-binding assays, GDI-specific residue mutagenesis, GCN4 genetic assays, in vitro GEF inhibition

    PMID:20485439

    Open questions at the time
    • Structural basis of GDI clamping on eIF2•GDP not resolved
    • How the GAP-to-GDI handoff is regulated unclear
  7. 2013 High

    Defined how eIF5-bound eIF2•GDP is recycled, identifying eIF2B as a GDF that displaces eIF5 GDI before exchanging nucleotide, with GDF and GEF being independent and differently regulated by eIF2α phosphorylation.

    Evidence Protein-interaction and fluorescent nucleotide-exchange kinetic assays with eIF2B subunit mutagenesis

    PMID:24352424

    Open questions at the time
    • Structural mechanism of GDI displacement not resolved
    • In vivo flux through the GDF step not quantified
  8. 2013 High

    Resolved the conformational trigger for hydrolysis completion, showing eIF1A-CTT movement toward the eIF5-NTD coupled to eIF1 dissociation drives Pi release, with the eIF5-CTD antagonizing eIF1.

    Evidence FRET distance measurements in reconstituted yeast PICs, mutagenesis, and phosphate release assays

    PMID:23293029

    Open questions at the time
    • Order of eIF1 release versus eIF1A movement not fully resolved
    • Structural snapshot of the transition state lacking
  9. 2014 High

    Demonstrated that eIF5 controls both Pi release and the open-to-closed PIC transition, with the Sui- G31R mutation stabilizing the closed state at UUG, mechanistically linking eIF5 to start-codon accuracy.

    Evidence In vitro GTP hydrolysis, Pi release, and FRET PIC-conformation assays with systematic eIF5 mutagenesis; reconstituted 48S assembly with eIF5B

    PMID:25114053 PMID:25260592

    Open questions at the time
    • How eIF5 distinguishes cognate from near-cognate codons mechanistically incomplete
    • Handoff from eIF5 to eIF5B in subunit joining not structurally defined
  10. 2018 High

    Captured the eIF5-NTD on the 40S subunit at the site vacated by eIF1, showing it engages Met-tRNAi to favor the accommodated PIN state, providing a structural basis for fidelity control.

    Evidence 3.0 Å cryo-EM of a yeast 48S PIC with in vivo UUG assays and in vitro conformation assays

    PMID:30475211

    Open questions at the time
    • Pre-hydrolysis catalytic geometry of the arginine finger not captured
    • Dynamics of NTD docking after eIF1 release not time-resolved
  11. 2018 Medium

    Showed human eIF5 binds eIF5B via a C-terminal motif with much higher affinity than eIF1A, suggesting eIF5 coordinates start-codon selection with subunit joining and is displaced by eIF1A to leave the ribosome.

    Evidence ITC/fluorescence binding affinity and competition assays with eIF5B-binding motif identification

    PMID:30211544

    Open questions at the time
    • Single lab; reciprocal in vivo validation lacking
    • Structural detail of the eIF5–eIF5B interface not resolved
  12. 2021 Medium

    Defined eIF5's intrinsically disordered DWEAR and CTT regions as competing intramolecular elements that toggle CTD preference between eIF2β and eIF1A, and showed CK2 phosphorylation increases eIF2 affinity.

    Evidence NMR spectroscopy, binding assays, and phosphomimetic mutagenesis of human eIF5

    PMID:34923394

    Open questions at the time
    • Single lab; functional consequence of IDR toggling in vivo not tested
    • Number of eIF2β binding sites not definitively established
  13. 2024 Medium

    Linked eIF5 GAP activity to disease by showing it preferentially stimulates poly-GA RAN translation from a CUG near-cognate codon in C9orf72 FTLD/ALS, with catalytic activity required.

    Evidence WT versus inactive eIF5 mutant transfection, RAN reporters, codon mutagenesis, and Drosophila RNAi knockdown

    PMID:38301895

    Open questions at the time
    • Single lab; mechanism of CUG preference at the molecular level unclear
    • Therapeutic relevance of eIF5 targeting untested
  14. 2025 High

    Provided a co-crystal structure of yeast eIF5-CTD bound to eIF2β K-box 3 and showed three competing K-box sites shared by eIF5, eIF2Bε and 5MP1, with CK2 phosphomimetics raising all partner affinities and eIF2B accelerating eIF5 release for exchange.

    Evidence X-ray crystallography, NMR, and quantitative binding assays with phosphomimetic mutants

    PMID:40670154

    Open questions at the time
    • In vivo competition among eIF5/eIF2Bε/5MP1 not quantified
    • How phosphorylation-tuned affinities are coordinated through the cycle unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How eIF5's transient, late association with the initiation complex and its dual GAP/GDI roles are dynamically choreographed and regulated in human cells remains incompletely defined.
  • Time-resolved structural states of the catalytic NTD across the hydrolysis cycle lacking
  • Physiological regulation of CK2-dependent affinity tuning not established
  • Integration of GAP, GDI and eIF5B-handoff roles in vivo not unified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0140313 molecular sequestering activity 3
Localization
GO:0005829 cytosol 2 GO:0005840 ribosome 2
Pathway
R-HSA-392499 Metabolism of proteins 3
Partners
EIF1EIF1AXEIF2B5EIF2S2EIF3CEIF4GEIF5B
Complex memberships
eIF2(αP) regulatory complexeIF2-eIF5 complexeIF3 core complexmultifactor complex (MFC)

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 eIF5 forms a specific complex with eIF2 in a 1:1 stoichiometry (apparent Mr ~160 kDa), and this interaction is required for eIF5 to catalyze hydrolysis of GTP bound to the 40S initiation complex and promote 80S initiation complex formation. Glycerol gradient sedimentation, in vitro GTPase assay with purified recombinant eIF5 Biochemistry High 8161539
1998 eIF5 stably associates with the yeast eIF3 core complex (composed of Tif32p/eIF3a, Nip1p/eIF3c, Prt1p/eIF3b, Tif34p/eIF3i, Tif35p/eIF3g); Nip1p/eIF3c directly binds eIF5 in two-hybrid and in vitro binding assays. Ni2+ affinity purification of His-Prt1p complex, mass spectrometry, yeast two-hybrid, in vitro protein binding Molecular and cellular biology High 9671501
2000 eIF5 bridges interaction between eIF3 (via NIP1/eIF3c N-terminus) and eIF2 (via eIF2β N-terminal half) through a conserved bipartite motif in the eIF5 C-terminal domain (CTD), forming a multifactor complex (MFC) that also contains eIF1 and initiator tRNA(Met) in vivo. The tif5-7A mutation in the bipartite motif disrupts MFC assembly and causes temperature-sensitive growth and reduction in translation initiation. In vitro protein binding, co-immunoprecipitation from yeast cell extracts, genetic analysis (tif5-7A mutant) Genes & development High 11018020
2000 The C-terminus of eIF5 (glutamic acid-rich bipartite motif) is required for interaction with the β subunit of eIF2; alanine substitution of conserved glutamic acid residues (E346A/E347A and E384A/E385A) abolishes eIF5–eIF2β binding, GTP hydrolysis, 80S initiation complex formation, and in vivo cell viability. Deletion and alanine substitution mutagenesis, in vitro binding assays, GTPase assay, yeast complementation Molecular and cellular biology High 10805737
2001 eIF5 acts as a classical GTPase-activating protein (GAP) for eIF2: its interaction with eIF2 is enhanced by AlF4- (mimicking the transition state), and it contains an 'arginine finger' (Arg15) flanked by hydrophobic residues; mutation R15M abolishes both GTP hydrolysis stimulation and in vitro mRNA translation. Arg48 also contributes to the GTPase active site. AlF4- binding assay, site-directed mutagenesis (R15M, R48M), in vitro GTPase assay, in vitro translation assay Current biology High 11166181
2001 The eIF5-CTD simultaneously binds eIF4G (cap-binding complex subunit) and eIF3/NIP1, suggesting it bridges the cap-binding complex to the PIC. In vivo, the tif5-7A mutation (disrupting MFC) eliminates eIF5 from the pre-initiation complex and causes accumulation of 48S complexes, indicating GTP hydrolysis/conversion of 48S to 80S is the rate-limiting step. In vitro protein binding, GST pulldown, polysome/ribosome sedimentation analysis, in vivo crosslinking The EMBO journal High 11331597
2003 eIF5 makes critical contacts with the 40S ribosomal subunit in vivo, performing redundant functions with the TIF32-CTD of eIF3a for 40S binding. The TIF32-CTD binds helices 16–18 of 18S rRNA in vitro, and NIP1/eIF5 interact with 40S protein RPS0A. In vivo co-immunoprecipitation from yeast, in vitro RNA binding assay, deletion analysis Genes & development Medium 12651896
2003 The eIF4G HEAT domain interacts with eIF5 (and eIF1); eIF1 binds simultaneously to eIF4G and eIF3c in vitro; mutations disrupting eIF4G–eIF5 interaction lead to elevated non-AUG initiation in vivo, indicating the eIF4G HEAT domain–eIF5/eIF1 interaction is important for scanning preinitiation complex integrity and AUG stringency. In vitro protein binding, two-hybrid, in vivo genetic suppression, reporter assay for non-AUG initiation Molecular and cellular biology Medium 12861028
2004 The N-terminal domain (NTD) of NIP1/eIF3c directly binds eIF1 and eIF5 to form the MFC; specific NIP1-NTD mutations reduce eIF1 or eIF5 binding, alter UUG start codon utilization (Sui- phenotype), and impair TC recruitment to 40S ribosomes. eIF1 overexpression suppresses the Sui- phenotype of both NIP1 and eIF5-G31R mutants, indicating that NIP1-NTD coordinates eIF1–eIF5 interaction to inhibit GTP hydrolysis at non-AUG codons. Site-directed mutagenesis of NIP1-NTD, yeast genetics (Sui- phenotype assay), in vitro binding, eIF1/eIF5 overexpression suppression Molecular and cellular biology High 15485912
2006 Crystal structure of the human eIF5-CTD at high resolution shows it is exclusively α-helical and homologous to the eIF2Bε-CTD (W2/HEAT domain). The binding sites for eIF2β, eIF3c, and eIF1 were mapped onto the structure: eIF2β and eIF3c bind non-overlapping patches of negative and positive electrostatic potential, respectively. X-ray crystallography (crystal structure), electrostatic surface analysis Journal of molecular biology High 16781736
2006 Crystal structure of the S. cerevisiae eIF5-CTD at 1.5 Å confirms it contains an atypical HEAT motif; surface analysis identifies conserved potential interaction regions for partner eIFs. X-ray crystallography Journal of molecular biology High 16616930
2007 eIF1 has two distinct eIF5-binding faces: its N-terminal tail and a basic/hydrophobic surface (KH region). Mutation of the KH region is lethal and causes dominant relaxation of start codon selection. The eIF1 N-terminal tail plays a stimulatory role in cooperative MFC assembly. NMR solution structure of yeast eIF1 used for interface mapping, yeast two-hybrid, in vitro binding, genetic analysis The Journal of biological chemistry High 17974565
2010 eIF5 has a GDP dissociation inhibitor (GDI) activity distinct from its GAP function: it stabilizes GDP binding to eIF2 between rounds of initiation. Conserved residues in eIF5 are required specifically for GDI (not GAP) activity. eIF5 is also a critical component of the eIF2(αP) regulatory complex that inhibits eIF2B GEF activity. Fluorescence nucleotide binding assays, mutagenesis of eIF5 GDI-specific residues, genetic assays (GCN4 translational control), in vitro GEF inhibition assay Nature High 20485439
2013 eIF2B acts as a GDI displacement factor (GDF) that recruits eIF2 from the eIF2•GDP/eIF5 GDI complex prior to GEF action; GDF activity depends on eIF2Bε and eIF2Bγ subunits and is insensitive to eIF2α phosphorylation (unlike GEF). eIF2B GDF and GEF activities are independent. Protein-protein interaction assays, fluorescent nucleotide exchange kinetic assays, mutagenesis of eIF2B subunits Genes & development High 24352424
2013 Upon AUG codon recognition, the C-terminal tail (CTT) of eIF1A moves closer to the eIF5 NTD; this movement is coupled to eIF1 dissociation from the PIC. eIF1 dissociation plus eIF1A-CTT movement toward eIF5 is required to trigger Pi release from eIF2•GDP•Pi. The eIF5-CTD antagonizes eIF1 binding to the PIC. FRET-based distance measurements in reconstituted yeast PICs, mutagenesis, phosphate release assays The Journal of biological chemistry High 23293029
2014 eIF5-G31R (Sui- mutation) alters Pi release: it accelerates Pi release at UUG codons and decreases it at AUG codons, stabilizing the closed PIC conformation at UUG. Suppressor G62S mitigates both defects; suppressor M18V primarily impairs GTP hydrolysis with little effect on PIC conformation, indicating eIF5 controls both Pi release and open-to-closed PIC conformational transitions for accurate AUG selection. In vitro GTP hydrolysis assays, Pi release assays, FRET-based PIC conformation assays, mutagenesis Nucleic acids research High 25114053
2014 eIF5 and eIF5B together stimulate 48S initiation complex formation during ribosomal scanning; eIF5-induced hydrolysis of eIF2-bound GTP is essential for this stimulation, increasing the probability that scanning complexes arrest at non-optimal start codons. eIF5B then stabilizes the initiator tRNA in the P site after eIF2•GDP dissociation. In vitro 48S IC assembly assays, GTPase assays, mutagenesis of eIF1A and eIF5B Nucleic acids research High 25260592
2002 Casein kinase II (CK II) phosphorylates mammalian eIF5 in vitro and in vivo at Ser-387 and Ser-388 near the C-terminus (within an acidic cluster), accounting for ~90% of total phosphorylation; a minor site is Ser-174. Alanine substitution at S387/S388 abolishes both in vitro and in vivo phosphorylation. Kinase isolation and biochemical characterization, mass spectrometry of phosphorylation sites, alanine substitution mutagenesis, in vivo 32P labeling Nucleic acids research High 11861906
2003 In S. cerevisiae, eIF5 is phosphorylated in vivo on multiple serine residues by casein kinase II; phosphopeptide mapping reveals four major sites identical to in vitro CK II sites. However, Ser-to-Ala mutations at all five CK II consensus sites in eIF5 had no obvious effect on cell growth under normal conditions. In vivo 32P labeling and phosphopeptide mapping, conditional CK II mutant yeast strain, site-directed mutagenesis Yeast Medium 12518314
2017 The eIF3c N-terminal domain (NTD) is divided into 3c0, 3c1, and 3c2 sub-regions; 3c0 binds eIF5 strongly but only weakly to eIF1's ribosome-binding surface, while 3c1/3c2 form a stoichiometric complex with eIF1. The 3c0:eIF5 interaction stabilizes the scanning PIC by preventing the inhibitory 3c0:eIF1 interaction; upon start codon recognition, interactions involving eIF5 and ultimately 3c0:eIF1 facilitate eIF1 release. NMR, in vitro binding assays, mutagenesis of NIP1-NTD subregions Cell reports High 28297669
2018 Cryo-EM structure (3.0 Å) of a yeast 48S PIC shows the eIF5-NTD bound to the 40S subunit at the location vacated by eIF1; eIF5-NTD interacts with Met-tRNAi to allow a more accommodated (PIN) orientation. Substitutions of eIF5 residues at the eIF5-NTD/tRNAi interface influence initiation at near-cognate UUG codons in vivo and closed/open PIC conformation in vitro. Cryo-EM reconstruction, in vivo UUG initiation assays, in vitro PIC conformation assays, mutagenesis eLife High 30475211
2018 Human eIF5 interacts with eIF5B via a C-terminal eIF5B-binding motif, competing with eIF1A for eIF5B binding with ~100-fold higher affinity than eIF1A; this interaction may coordinate start codon selection (eIF5 as GAP of eIF2) with ribosomal subunit joining (eIF5B), with eIF1A displacing eIF5 from eIF5B to allow the eIF5:eIF2-GDP complex to leave the ribosome. Binding affinity measurements (ITC/fluorescence), competition assays, identification of eIF5B-binding motif in eIF5 Biochemistry Medium 30211544
2016 eIF2β acts in concert with eIF5 to prevent premature GDP release from eIF2γ: a growth suppressor mutation in eIF2β specifically prevents eIF5 GDI from stabilizing GDP binding to eIF2 (increases GDP off-rate from eIF2•GDP/eIF5 complexes) without affecting intrinsic eIF2 affinities for GDP or initiator tRNA, impairing GCN4 translational control. Fluorescent nucleotide binding kinetics assays, genetic analysis (GCN4 derepression), mutagenesis of eIF2β Nucleic acids research High 27458202
2021 Human eIF5 contains two intrinsically disordered regions (IDRs): the DWEAR motif and the C-terminal tail (CTT), which dynamically contact the folded CTD and compete with each other. CTD•CTT interaction favors eIF2β binding to eIF5-CTD, whereas CTD•DWEAR interaction favors eIF1A binding. CK2 phosphorylation significantly increases eIF5 affinity for eIF2; eIF2β has at least two (likely three) eIF5-binding sites. NMR spectroscopy, binding assays, phosphomimetic mutagenesis Biophysical chemistry Medium 34923394
2022 CK2 phosphorylation of eIF5 increases its affinity for eIF1A; a new contact interface was identified between eIF5-CTD and the OB domain of eIF1A. Dynamic intramolecular interactions within both eIF5 and eIF1A modulate this interaction. Binding assays, phosphomimetic mutagenesis of eIF5, NMR/structural analysis Current research in structural biology Medium 36164648
2024 eIF5 (via its GAP activity) preferentially stimulates poly-GA RAN translation from a CUG near-cognate start codon in C9orf72 FTLD/ALS; inactive eIF5 mutants do not stimulate. Mutation of the CUG to CCG or AUG abolishes the stimulatory effect. In a Drosophila C9orf72 model, knockdown of eIF5 reduces poly-GA expression in vivo. Transfection of WT and inactive eIF5 mutants, RAN translation reporters, codon mutation analysis, Drosophila RNAi knockdown The Journal of biological chemistry Medium 38301895
2024 Single-molecule fluorescence analysis of human translation initiation showed that eIF5 only transiently binds initiation complexes late in initiation immediately prior to eIF5B association; eIF5 association requires a translation start site and is inhibited by alternative start sites. eIF1 and eIF5 have opposing roles during initiation (knockdown/overexpression experiments in human cells confirmed this). Single-molecule fluorescence (smFRET/TIRF) on reconstituted human PICs, knockdown and overexpression in human cells bioRxivpreprint Medium 39026837
2025 Crystal structure of yeast eIF5-CTD in complex with eIF2β K-box 3 reveals an extended binding site on eIF2β beyond the K-box. eIF2β has three distinct binding sites (one per K-box), and human eIF5, eIF2Bε, and 5MP1 can all bind to all three sites while reducing each other's affinities. CK2 phosphomimetic mutations in eIF5 increase affinities for all these partners, and eIF2B speeds dissociation of eIF5 from eIF2-GDP to promote nucleotide exchange. X-ray crystallography, NMR, binding assays with phosphomimetic mutants RNA High 40670154
2012 Sequential binding of eIF5-CTD to the eIF4G RS1 domain and eIF2β K-boxes stabilizes the 48S PIC and promotes its shift to initiation mode: eIF4G-RS1/eIF5-CTD interaction directly links eIF4G to the PIC to enhance mRNA binding; eIF2β-K-boxes increase mRNA binding in a manner reversed by eIF5-CTD; mutations in these interactions restore AUG selection accuracy impaired by an eIF2β mutation. In vitro 48S complex assembly, mRNA binding assays, in vivo start codon selection assays, mutagenesis Molecular and cellular biology Medium 22851688

Source papers

Stage 0 corpus · 58 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 A multifactor complex of eukaryotic initiation factors, eIF1, eIF2, eIF3, eIF5, and initiator tRNA(Met) is an important translation initiation intermediate in vivo. Genes & development 241 11018020
1998 Identification of a translation initiation factor 3 (eIF3) core complex, conserved in yeast and mammals, that interacts with eIF5. Molecular and cellular biology 160 9671501
2004 Interactions of eukaryotic translation initiation factor 3 (eIF3) subunit NIP1/c with eIF1 and eIF5 promote preinitiation complex assembly and regulate start codon selection. Molecular and cellular biology 140 15485912
2003 The yeast eIF3 subunits TIF32/a, NIP1/c, and eIF5 make critical connections with the 40S ribosome in vivo. Genes & development 128 12651896
2001 Multiple roles for the C-terminal domain of eIF5 in translation initiation complex assembly and GTPase activation. The EMBO journal 99 11331597
2018 Translational initiation factor eIF5 replaces eIF1 on the 40S ribosomal subunit to promote start-codon recognition. eLife 90 30475211
2003 The yeast eukaryotic initiation factor 4G (eIF4G) HEAT domain interacts with eIF1 and eIF5 and is involved in stringent AUG selection. Molecular and cellular biology 86 12861028
2001 Eukaryotic translation initiation factor 5 (eIF5) acts as a classical GTPase-activator protein. Current biology : CB 86 11166181
2010 eIF5 has GDI activity necessary for translational control by eIF2 phosphorylation. Nature 85 20485439
2013 Coordinated movements of eukaryotic translation initiation factors eIF1, eIF1A, and eIF5 trigger phosphate release from eIF2 in response to start codon recognition by the ribosomal preinitiation complex. The Journal of biological chemistry 71 23293029
2017 Competition between translation initiation factor eIF5 and its mimic protein 5MP determines non-AUG initiation rate genome-wide. Nucleic acids research 67 28981728
2013 eIF2B promotes eIF5 dissociation from eIF2*GDP to facilitate guanine nucleotide exchange for translation initiation. Genes & development 64 24352424
2017 Molecular Landscape of the Ribosome Pre-initiation Complex during mRNA Scanning: Structural Role for eIF3c and Its Control by eIF5. Cell reports 58 28297669
2007 Eukaryotic initiation factor (eIF) 1 carries two distinct eIF5-binding faces important for multifactor assembly and AUG selection. The Journal of biological chemistry 54 17974565
2000 Mutational analysis of mammalian translation initiation factor 5 (eIF5): role of interaction between the beta subunit of eIF2 and eIF5 in eIF5 function in vitro and in vivo. Molecular and cellular biology 54 10805737
2011 Mechanisms of translational regulation by a human eIF5-mimic protein. Nucleic acids research 51 21745818
2016 Overexpression of eIF5 or its protein mimic 5MP perturbs eIF2 function and induces ATF4 translation through delayed re-initiation. Nucleic acids research 47 27325740
1996 Characterization of multiple mRNAs that encode mammalian translation initiation factor 5 (eIF-5). The Journal of biological chemistry 42 8663286
2014 eIF5 and eIF5B together stimulate 48S initiation complex formation during ribosomal scanning. Nucleic acids research 39 25260592
2006 The crystal structure of the carboxy-terminal domain of human translation initiation factor eIF5. Journal of molecular biology 38 16781736
2001 Functional significance and mechanism of eIF5-promoted GTP hydrolysis in eukaryotic translation initiation. Progress in nucleic acid research and molecular biology 36 11642363
1994 Purification and characterization of bacterially expressed mammalian translation initiation factor 5 (eIF-5): demonstration that eIF-5 forms a specific complex with eIF-2. Biochemistry 36 8161539
2014 Topological models of heteromeric protein assemblies from mass spectrometry: application to the yeast eIF3:eIF5 complex. Chemistry & biology 35 25544043
2006 Crystal structure of the C-terminal domain of S.cerevisiae eIF5. Journal of molecular biology 33 16616930
2000 Conserved sequences in the beta subunit of archaeal and eukaryal translation initiation factor 2 (eIF2), absent from eIF5, mediate interaction with eIF2gamma. The Biochemical journal 33 10769173
2014 Essential role of eIF5-mimic protein in animal development is linked to control of ATF4 expression. Nucleic acids research 32 25147208
2014 Eukaryotic translation initiation factor eIF5 promotes the accuracy of start codon recognition by regulating Pi release and conformational transitions of the preinitiation complex. Nucleic acids research 31 25114053
2012 Sequential eukaryotic translation initiation factor 5 (eIF5) binding to the charged disordered segments of eIF4G and eIF2β stabilizes the 48S preinitiation complex and promotes its shift to the initiation mode. Molecular and cellular biology 31 22851688
1997 Characterization of translation initiation factor 5 (eIF5) from Saccharomyces cerevisiae. Functional homology with mammalian eIF5 and the effect of depletion of eIF5 on protein synthesis in vivo and in vitro. The Journal of biological chemistry 31 9218474
2007 Expression and purification of recombinant wheat translation initiation factors eIF1, eIF1A, eIF4A, eIF4B, eIF4F, eIF(iso)4F, and eIF5. Methods in enzymology 30 17913646
1999 Cloning and characterization of the p42 subunit of mammalian translation initiation factor 3 (eIF3): demonstration that eIF3 interacts with eIF5 in mammalian cells. Nucleic acids research 29 9973622
2010 eIF5 is a dual function GAP and GDI for eukaryotic translational control. Small GTPases 28 21686265
2016 eIF2β is critical for eIF5-mediated GDP-dissociation inhibitor activity and translational control. Nucleic acids research 21 27458202
2002 Phosphorylation of mammalian translation initiation factor 5 (eIF5) in vitro and in vivo. Nucleic acids research 21 11861906
2003 Casein kinase II phosphorylates translation initiation factor 5 (eIF5) in Saccharomyces cerevisiae. Yeast (Chichester, England) 20 12518314
1993 Characterization of mammalian translation initiation factor 5 (eIF-5). Demonstration that eIF-5 is a phosphoprotein and is present in cells as a single molecular form of apparent M(r) 58,000. The Journal of biological chemistry 19 8376415
2018 Human eIF5 and eIF1A Compete for Binding to eIF5B. Biochemistry 18 30211544
2002 Structure of the beta subunit of translation initiation factor 2 from the archaeon Methanococcus jannaschii: a representative of the eIF2beta/eIF5 family of proteins. Biochemistry 18 11980477
2018 Eukaryotic Initiation Factor 5B (eIF5B) Cooperates with eIF1A and eIF5 to Facilitate uORF2-Mediated Repression of ATF4 Translation. International journal of molecular sciences 16 30551605
2011 The hsa-miR-5787 represses cellular growth by targeting eukaryotic translation initiation factor 5 (eIF5) in fibroblasts. Biochemical and biophysical research communications 16 22062548
2021 Roles of HDAC2, eIF5, and eIF6 in Lung Cancer Tumorigenesis. Current medical science 14 34403101
2000 Isolation and functional characterization of a temperature-sensitive mutant of the yeast Saccharomyces cerevisiae in translation initiation factor eIF5: an eIF5-dependent cell-free translation system. Gene 14 10689193
2024 eIF1 and eIF5 dynamically control translation start site fidelity. bioRxiv : the preprint server for biology 11 39026837
2022 Cyst stem cell lineage eIF5 non-autonomously prevents testicular germ cell tumor formation via eIF1A/eIF2γ-mediated pre-initiation complex. Stem cell research & therapy 11 35883200
2024 eIF5 stimulates the CUG initiation of RAN translation of poly-GA dipeptide repeat protein (DPR) in C9orf72 FTLD/ALS. The Journal of biological chemistry 8 38301895
2017 Defect in the GTPase activating protein (GAP) function of eIF5 causes repression of GCN4 translation. Biochemical and biophysical research communications 8 28385532
2021 Dynamic interaction network involving the conserved intrinsically disordered regions in human eIF5. Biophysical chemistry 7 34923394
2022 Altered proteome in translation initiation fidelity defective eIF5G31R mutant causes oxidative stress and DNA damage. Scientific reports 6 35322093
2024 LINC00894 Regulates Cerebral Ischemia/Reperfusion Injury by Stabilizing EIF5 and Facilitating ATF4-Mediated Induction of FGF21 and ACOD1 Expression. Neurochemical research 3 39060766
2022 Label-free protocol to quantify protein affinity using isothermal titration calorimetry and bio-layer interferometry of a human eIF5-mimic protein. STAR protocols 3 36035794
2022 Regulation of the interactions between human eIF5 and eIF1A by the CK2 kinase. Current research in structural biology 3 36164648
2018 Fidelity of HIS4 start codon selection influences 3-amino-1,2,4-triazole sensitivity in GTPase activating protein function defective eIF5. Journal of genetics 3 30262708
2025 Molecular basis for the interactions of eIF2β with eIF5, eIF2B, and 5MP1 and their regulation by CK2. RNA (New York, N.Y.) 2 40670154
2024 Molecular basis for the interactions of eIF2β with eIF5, eIF2B, and 5MP1 and their regulation by CK2. bioRxiv : the preprint server for biology 1 38712236
2026 The eIF5-mimic protein 5MP1: a regulator of translation stringency and a multifaceted oncogene. Journal of biochemistry 0 41631342
2026 Male germ cell-specific deletion of Eif5 causes the apoptosis of mouse progenitor spermatogonia by excessive endoplasmic reticulum stress and defective DNA repair. Zoological research 0 41983446
2026 Complete genome sequence of Janthinobacterium lividum EIF5 isolated from soil of a temperate broadleaf and mixed forest. Microbiology resource announcements 0 42214355
2025 Translation Initiation Fidelity Defective Mutations in eIF5 and eIF2β Show Distinct Sensitivity to the Sequence Context for Recognition of the UUG Start Codon. Biochemical genetics 0 41460464

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