EIF5A (eukaryotic translation initiation factor 5A-1, historically eIF-4D and "Rev-binding factor") is a small, highly conserved translation factor that, despite its legacy "initiation factor" name, acts mainly in translation elongation and termination. It is the only cellular protein to carry hypusine, a unique post-translational modification formed at Lys-50 by deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH) using spermidine; this modification is essential for its activity. eIF5A binds the 80S ribosome between the exit (E) and peptidyl (P) tRNA sites and stimulates peptide-bond formation at sequences that are intrinsically difficult to translate, most notably consecutive prolines (polyproline tracts) and other stalling motifs, thereby promoting efficient elongation through these contexts and resolving ribosome stalling. eIF5A and eEF2 bind translating ribosomes in a mutually exclusive manner. Through this elongation-promoting activity it supports specific cellular programs, including autophagy (by enabling translation of ATG3) and broad proteome synthesis. eIF5A is predominantly cytoplasmic and ribosome-associated, with a hypusine- and XPO4/RanGTP-dependent nucleocytoplasmic shuttling pool that can localize to the nucleus, nuclear pore and annulate lamellae. Hypusine-dependent localization and abundance changes underlie additional context-dependent roles in apoptosis and stress responses, and eIF5A serves as a cellular cofactor for retroviral (HIV-1 Rev / HTLV-1 Rex) mRNA export. Loss-of-function variants cause the autosomal dominant Faundes-Banka syndrome.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006414 translational elongation | IBA GO_REF:0000033 | ACCEPT | Summary: eIF5A promotes translation elongation, particularly through ribosome-stalling motifs such as polyproline tracts. This phylogenetically inferred BP annotation captures the gene's core biological role. Reason: Strongly supported by UniProt function and experimental work across eukaryotes; this is the central biological process of eIF5A. Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt Translation factor that promotes translation elongation and termination, particularly upon ribosome stalling at specific amino acid |
| GO:0003746 translation elongation factor activity | IBA GO_REF:0000033 | ACCEPT | Summary: eIF5A acts as a translation elongation factor, binding between the E and P sites of the ribosome to stimulate peptide-bond formation at difficult motifs. This is the core molecular function. Reason: Well established across eukaryotes and supported by UniProt; this is eIF5A's defining molecular activity (hypusine-dependent). Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt Binds between the exit (E) and |
| GO:0003723 RNA binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: eIF5A contains an OB-fold and binds RNA (mRNA, and in vitro U6 snRNA / RRE). RNA binding is real but is a supporting activity subordinate to its ribosome-associated elongation function. Reason: RNA binding is documented but generic; the informative function is ribosome binding / elongation factor activity. Retained as a real but non-core capability. Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt MRNA-BINDING |
| GO:0003746 translation elongation factor activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based electronic transfer of the elongation factor activity, redundant with and consistent with the IBA/ISS annotations for the same function. Reason: Correct molecular function, corroborated by stronger IBA and experimental evidence for eIF5A as an elongation factor. Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt Binds between the exit (E) and |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic (SubCell) nuclear localization, consistent with the experimentally documented hypusine/XPO4-dependent nuclear pool of eIF5A. Reason: A genuine but minor shuttling pool; the predominant site of action is the cytoplasmic ribosome. Retained as non-core nuclear localization. Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt Nuclear export of hypusinated protein is mediated by |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic (SubCell) cytoplasmic localization, the predominant compartment where eIF5A acts on translating ribosomes. Reason: Cytoplasm is eIF5A's primary site of action; corroborated by multiple experimental (EXP/IDA) annotations. Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: eIF5A was detected as a peripheral protein on the cytoplasmic face of the ER membrane in early fractionation work. This is a peripheral/contextual localization, not its core compartment. Reason: Supported by a single early study (peripheral, cytoplasmic side); consistent with ribosome association at the ER but peripheral to the core cytosolic function. Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt Endoplasmic reticulum membrane |
| GO:0006414 translational elongation | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based electronic transfer of the elongation BP, redundant with the IBA/IMP annotations for the same process. Reason: Correct biological process; corroborated by stronger evidence. Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt promotes translation elongation and |
| GO:0043022 ribosome binding | IEA GO_REF:0000002 | ACCEPT | Summary: eIF5A binds the 80S ribosome (experimentally demonstrated), inserting between the E and P sites. Ribosome binding is the structural basis for its elongation factor activity. Reason: Experimentally validated 80S ribosome binding; central to and supporting the elongation factor mechanism. Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt Binds to 80S ribosomes PMID:27115996 Negative Cooperativity between eIF5A and eEF2 on Binding to the Ribosome. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: High-throughput Y2H interactome screen capturing eIF5A interactions, mostly with homeodomain/bZIP transcription factors (CRX, MEOX2, REL) plus DHPS. The bare protein binding term is uninformative. Reason: Records real binary interactions but the term is uninformative and the partners (largely homeodomain TFs) are likely OB-fold/Y2H artifacts; not part of the core elongation function. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:25416956 UniProtKB:O43186 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI binary interactome screen capturing eIF5A interactions (including SDCBP/syntenin and DHPS among many homeodomain TFs). Bare protein binding is uninformative. Reason: Real binary interactions but uninformative term; the biologically meaningful partners (DHPS, SDCBP) are captured elsewhere. Not core. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32296183 UniProtKB:O00560 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: BioPlex affinity-purification capturing the eIF5A-DOHH (Q9BU89) interaction. DOHH is the deoxyhypusine hydroxylase that completes hypusine synthesis, so this interaction is biologically meaningful, though the term itself is uninformative. Reason: Bare protein binding is uninformative. The WITH partner is DOHH (Q9BU89), an enzyme of the hypusination pathway acting on eIF5A; the specific enzyme-binding relationship is better captured by enzyme binding. Proposed replacements: enzyme binding Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:33961781 UniProtKB:Q9BU89 |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: HPA immunofluorescence places a pool of eIF5A in the nucleoplasm, consistent with the documented hypusine/XPO4-dependent shuttling pool. Reason: Genuine nuclear pool but peripheral to the cytoplasmic ribosome-associated core function. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0005654 nucleoplasm cellular_component ECO:0000314 IDA |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence cytosolic localization, agreeing with eIF5A's predominant cytosolic ribosome-associated site of action. Reason: Direct evidence for cytosolic localization, consistent with the core function. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0005829 cytosol cellular_component ECO:0000314 IDA |
| GO:0005634 nucleus | EXP PMID:10944119 Exportin 4: a mediator of a novel nuclear export pathway in ... | KEEP AS NON CORE | Summary: Experimental nuclear localization linked to XPO4/Ran-mediated nuclear export of hypusinated eIF5A. Reason: Genuine shuttling pool; non-core relative to cytoplasmic ribosome function. Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt Nuclear export of hypusinated protein is mediated by |
| GO:0005634 nucleus | EXP PMID:19379712 The effect of hypusine modification on the intracellular loc... | KEEP AS NON CORE | Summary: Experimental nuclear localization shown to depend on hypusine/acetylation status of eIF5A. Reason: Real but PTM-dependent shuttling pool; non-core. Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt Hypusine modification promotes the |
| GO:0005634 nucleus | EXP PMID:27306458 Structure of the exportin Xpo4 in complex with RanGTP and th... | KEEP AS NON CORE | Summary: Structural/biochemical study of XPO4-RanGTP-eIF5A export complex; nuclear annotation reflects the shuttling pool. Reason: Nuclear localization is part of XPO4-mediated shuttling; non-core relative to cytoplasmic translation. Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt Nuclear export of hypusinated protein is mediated by |
| GO:0005634 nucleus | EXP PMID:8253832 Eukaryotic initiation factor 5A is a cellular target of the ... | KEEP AS NON CORE | Summary: Nuclear localization in the context of eIF5A serving as an HIV-1 Rev cofactor for retroviral mRNA export. Reason: Nuclear pool tied to the Rev/Rex viral-cofactor context; non-core relative to translation elongation. Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt essential for mRNA export of retroviral transcripts |
| GO:0005737 cytoplasm | EXP PMID:10944119 Exportin 4: a mediator of a novel nuclear export pathway in ... | ACCEPT | Summary: Experimental cytoplasmic localization, the predominant compartment for eIF5A. Reason: Cytoplasm is the core site of action; experimentally supported. Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005737 cytoplasm | EXP PMID:19379712 The effect of hypusine modification on the intracellular loc... | ACCEPT | Summary: Experimental cytoplasmic localization; hypusination promotes the cytoplasmic pool. Reason: Consistent with the predominant cytoplasmic site of action. Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt Hypusine modification promotes the |
| GO:0005737 cytoplasm | EXP PMID:27306458 Structure of the exportin Xpo4 in complex with RanGTP and th... | ACCEPT | Summary: Cytoplasmic localization consistent with eIF5A's ribosome-associated function. Reason: Core compartment, experimentally supported. Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005737 cytoplasm | EXP PMID:8660923 The subcellular distribution of eukaryotic translation initi... | ACCEPT | Summary: Early cell-fractionation study documenting cytoplasmic distribution of eIF5A. Reason: Core compartment, experimentally supported. Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:8660923 The subcellular distribution of eukaryotic translation initi... | KEEP AS NON CORE | Summary: Same fractionation study detecting eIF5A as a peripheral protein on the cytoplasmic face of the ER membrane. Reason: Peripheral membrane association (cytoplasmic side), consistent with ER-associated ribosomes; peripheral to the core function. Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt Endoplasmic reticulum membrane |
| GO:0006414 translational elongation | IMP PMID:29712776 eIF5A is required for autophagy by mediating ATG3 translatio... | ACCEPT | Summary: eIF5A is required for translation of ATG3 (at a difficult motif), thereby enabling autophagy. This is a specific, experimentally demonstrated example of eIF5A's elongation function. Reason: IMP evidence that eIF5A mediates ATG3 translation directly supports its role in translational elongation. Supporting Evidence: PMID:29712776 eIF5A is required for autophagy by mediating ATG3 translation. file:human/EIF5A/EIF5A-uniprot.txt is required for autophagy by assisting the ribosome in translating the ATG3 protein |
| GO:0033209 tumor necrosis factor-mediated signaling pathway | IDA PMID:17187778 Eukaryotic translation initiation factor 5A induces apoptosi... | KEEP AS NON CORE | Summary: eIF5A nuclear accumulation and apoptotic effects in response to TNF-alpha signaling. This is a context-dependent downstream role, not the core translation function. Reason: A genuine but pleiotropic stress/apoptosis-context role distinct from the core elongation function. Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt Also regulates TNF-mediated apoptosis |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:15371445 A novel eIF5A complex functions as a regulator of p53 and p5... | MARK AS OVER ANNOTATED | Summary: Derived from a study where eIF5A (with SDCBP) regulates p53 and p53-dependent apoptosis. The transcriptional effect is an indirect downstream consequence, not a direct eIF5A transcription function. Reason: eIF5A is a translation factor, not a transcriptional regulator; the transcription effect here is indirect (via p53). Over-annotation of an indirect outcome. Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt functions as a regulator of p53 and p53-dependent apoptosis |
| GO:0098586 cellular response to virus | IMP PMID:8596953 Inhibition of HIV-1 replication in lymphocytes by mutants of... | KEEP AS NON CORE | Summary: eIF5A serves as a cellular cofactor for HIV-1 Rev-mediated retroviral mRNA export. The "cellular response to virus" framing reflects this viral-cofactor role. Reason: A genuine microbial-infection cofactor role (Rev/Rex), but distinct from and non-core relative to translation elongation. Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt Cellular cofactor of human T-cell |
| GO:0098586 cellular response to virus | IMP PMID:9465063 Interaction of the HIV-1 rev cofactor eukaryotic initiation ... | KEEP AS NON CORE | Summary: eIF5A interaction with ribosomal protein L5 in the HIV-1 Rev cofactor context; same viral-cofactor role. Reason: Genuine Rev-cofactor / viral mRNA export role; non-core relative to translation. Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt essential for mRNA export of retroviral transcripts |
| GO:1902255 positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator | IDA PMID:15371445 A novel eIF5A complex functions as a regulator of p53 and p5... | KEEP AS NON CORE | Summary: eIF5A, with SDCBP/syntenin, positively regulates p53-dependent apoptosis. A genuine context-dependent role, downstream of its translation function. Reason: Real but pleiotropic apoptosis-regulatory role; non-core relative to the elongation function. Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt functions as a regulator of p53 and p53-dependent apoptosis |
| GO:0005829 cytosol | TAS Reactome:R-HSA-204617 | ACCEPT | Summary: Reactome curated cytosolic localization (hypusine synthesis pathway), consistent with the core compartment. Reason: Correct cytosolic localization, agrees with experimental evidence. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-204617 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-204647 | ACCEPT | Summary: Reactome curated cytosolic localization, redundant with the other cytosol annotations. Reason: Correct cytosolic localization. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-204647 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-204662 | ACCEPT | Summary: Reactome curated cytosolic localization, redundant with the other cytosol annotations. Reason: Correct cytosolic localization. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-204662 |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: eIF5A appeared in a high-throughput membrane-proteome dataset of NK cells. This is a generic, non-specific localization likely reflecting ribosome/peripheral membrane association. Reason: Generic "membrane" from a high-throughput proteomics survey; uninformative and not a meaningful compartment assignment for a cytosolic translation factor. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0016020 membrane cellular_component ECO:0007005 HDA PMID:19946888 |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | KEEP AS NON CORE | Summary: eIF5A captured in an mRNA-interactome (RNA interactome capture) dataset, consistent with its RNA/mRNA-binding OB-fold and ribosome association. Reason: Real RNA-binding capability but generic; the informative function is ribosome binding / elongation factor activity. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0003723 RNA binding molecular_function ECO:0007005 HDA PMID:22681889 |
| GO:0003746 translation elongation factor activity | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity transfer of elongation factor activity from yeast eIF5A, consistent with the IBA/IEA annotations for the same core function. Reason: Correct core molecular function, supported by orthology and experimental data. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0003746 translation elongation factor activity molecular_function ECO:0000250 ISS |
| GO:0045901 positive regulation of translational elongation | ISS GO_REF:0000024 | ACCEPT | Summary: eIF5A positively regulates elongation, especially through stalling motifs. Captures the directionality of its core role. Reason: Consistent with eIF5A's documented elongation-promoting activity at polyproline and other difficult motifs. Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt specifically required for efficient translation of |
| GO:0017070 U6 snRNA binding | IDA PMID:9285100 Interaction of eukaryotic initiation factor 5A with the huma... | KEEP AS NON CORE | Summary: eIF5A binds U6 snRNA (and the HIV-1 RRE) in vitro in a hypusine-dependent manner. An isolated in vitro RNA-binding observation, peripheral to its core function. Reason: Single in vitro RNA-binding observation; a real but peripheral activity, not part of the core elongation role. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0017070 U6 snRNA binding molecular_function ECO:0000314 IDA PMID:9285100 |
| GO:0005515 protein binding | IPI PMID:10381392 Nuclear pore localization and nucleocytoplasmic transport of... | KEEP AS NON CORE | Summary: Interaction with the export receptor CRM1 in the context of nucleocytoplasmic shuttling of eIF5A. Bare protein binding is uninformative. Reason: Records a real interaction tied to nuclear export, but the term is uninformative; not part of the core elongation function. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:10381392 UniProtKB:Q9PW90 |
| GO:0005515 protein binding | IPI PMID:10944119 Exportin 4: a mediator of a novel nuclear export pathway in ... | KEEP AS NON CORE | Summary: Interaction with the XPO4/RanGTP export machinery. The biologically meaningful relationship is eIF5A's export by XPO4; the bare term is uninformative. Reason: Real interaction underlying nuclear export, but uninformative term; non-core. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:10944119 UniProtKB:Q9C0E2 |
| GO:0005515 protein binding | IPI PMID:15371445 A novel eIF5A complex functions as a regulator of p53 and p5... | KEEP AS NON CORE | Summary: Interaction with SDCBP/syntenin in the p53 apoptosis-regulation study. Bare protein binding is uninformative. Reason: Records a real interaction (SDCBP) but uninformative term; the functional context (p53/apoptosis) is captured in the BP annotations. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:15371445 UniProtKB:O00560 |
| GO:0005515 protein binding | IPI PMID:17213197 Specificity of the deoxyhypusine hydroxylase-eukaryotic tran... | MODIFY | Summary: Interaction with DOHH (deoxyhypusine hydroxylase), the enzyme that completes hypusine synthesis on eIF5A. Biologically meaningful enzyme-substrate binding. Reason: Bare protein binding is uninformative. The partner is the hypusination enzyme DOHH acting on eIF5A; enzyme binding is the appropriate specific term. Proposed replacements: enzyme binding Supporting Evidence: file:human/EIF5A/EIF5A-uniprot.txt Interacts with DOHH |
| GO:0005515 protein binding | IPI PMID:9442029 Identification of the eukaryotic initiation factor 5A as a r... | KEEP AS NON CORE | Summary: Interaction with tissue transglutaminase II reported as a retinoic-acid-stimulated binding partner. Isolated interaction; bare term is uninformative. Reason: Records a real but isolated interaction unrelated to the core function; uninformative term. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:9442029 UniProtKB:P21980 |
| GO:0005515 protein binding | IPI PMID:9465063 Interaction of the HIV-1 rev cofactor eukaryotic initiation ... | KEEP AS NON CORE | Summary: Interaction with ribosomal protein L5 in the HIV-1 Rev cofactor context. Bare protein binding is uninformative. Reason: Real interaction tied to the viral-cofactor/ribosome context, but uninformative term; non-core. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:9465063 UniProtKB:P46777 |
| GO:0005634 nucleus | IDA PMID:12210765 Subcellular localization of the hypusine-containing eukaryot... | KEEP AS NON CORE | Summary: Immunofluorescence/GFP localization showing a nuclear pool of hypusine-containing eIF5A. Reason: Genuine nuclear pool; non-core relative to the cytoplasmic ribosome function. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0005634 nucleus cellular_component ECO:0000314 IDA PMID:12210765 |
| GO:0005642 annulate lamellae | IDA PMID:12210765 Subcellular localization of the hypusine-containing eukaryot... | KEEP AS NON CORE | Summary: eIF5A detected at annulate lamellae (stacked nuclear-pore-containing ER membranes), consistent with its nuclear-pore/shuttling association. Reason: A specialized localization tied to nuclear pore/shuttling; peripheral to the core function. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0005642 annulate lamellae cellular_component ECO:0000314 IDA |
| GO:0005643 nuclear pore | IDA PMID:10381392 Nuclear pore localization and nucleocytoplasmic transport of... | KEEP AS NON CORE | Summary: eIF5A localized to the nuclear pore, consistent with its CRM1/XPO4-mediated nucleocytoplasmic transport. Reason: Reflects transport through the nuclear pore; peripheral to the core cytoplasmic function. The part_of qualifier is questionable but the localization is real. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0005643 nuclear pore cellular_component ECO:0000314 IDA PMID:10381392 |
| GO:0005737 cytoplasm | IDA PMID:12210765 Subcellular localization of the hypusine-containing eukaryot... | ACCEPT | Summary: Direct immunofluorescence/GFP evidence for cytoplasmic localization, the predominant compartment. Reason: Core compartment, directly supported. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0005737 cytoplasm cellular_component ECO:0000314 IDA PMID:12210765 |
| GO:0003723 RNA binding | IDA PMID:15303967 Identification of mRNA that binds to eukaryotic initiation f... | KEEP AS NON CORE | Summary: Direct evidence that eIF5A binds specific mRNAs (affinity co-purification). A real RNA-binding activity supporting its ribosome-associated function. Reason: Genuine mRNA binding but generic; the informative function is ribosome binding / elongation factor activity. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0003723 RNA binding molecular_function ECO:0000314 IDA PMID:15303967 |
| GO:0005515 protein binding | IPI PMID:14622290 Identification and characterization of eukaryotic initiation... | KEEP AS NON CORE | Summary: Interaction reported during characterization of the paralog eIF5A-2. Bare protein binding is uninformative. Reason: Records an interaction but uninformative term; not part of the core function. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:14622290 UniProtKB:P49366 |
| GO:0005634 nucleus | IDA PMID:17187778 Eukaryotic translation initiation factor 5A induces apoptosi... | KEEP AS NON CORE | Summary: eIF5A nuclear accumulation in response to TNF-alpha (apoptosis context). Reason: Stimulus-dependent nuclear pool; non-core relative to cytoplasmic translation. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0005634 nucleus cellular_component ECO:0000314 IDA PMID:17187778 |
| GO:0005737 cytoplasm | IDA PMID:17187778 Eukaryotic translation initiation factor 5A induces apoptosi... | ACCEPT | Summary: Cytoplasmic localization of eIF5A (baseline) in the same TNF-alpha study. Reason: Core compartment, directly supported. Supporting Evidence: file:human/EIF5A/EIF5A-goa.tsv GO:0005737 cytoplasm cellular_component ECO:0000314 IDA PMID:17187778 |
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Download this section (compressed HTML)Q: Beyond polyproline tracts, what is the full sequence/structural repertoire of stalling motifs whose translation depends on hypusinated eIF5A in human cells?
Q: To what extent are eIF5A's apoptosis, p53, and viral-cofactor roles direct versus indirect consequences of its elongation activity on specific mRNAs?
Q: How does the hypusine- and acetylation-dependent nucleocytoplasmic shuttling of eIF5A contribute (if at all) to function beyond regulating its cytoplasmic availability?
Experiment: Ribosome profiling in eIF5A-depleted or hypusination-deficient (DHPS/DOHH-inhibited) human cells to map genome-wide stalling sites and the dependency of specific transcripts (e.g., ATG3) on eIF5A.
Experiment: Cryo-EM of human hypusinated eIF5A on stalled 80S ribosomes at defined motifs to resolve the mechanism of peptidyl-transfer stimulation.
Experiment: Structure-function analysis of FABAS disease variants (e.g., T48N, G106R, E122K) measuring ribosome binding, hypusination efficiency, and polyproline translation, with spermidine rescue.
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