GTPBP1 (GTP-binding protein 1, also called GP-1) is a cytoplasmic translational GTPase of the TRAFAC-class translation-factor superfamily, most closely related to eEF1A, eRF3 and Hbs1. It possesses eEF1A-like elongation activity, forming ternary complexes with GTP and aminoacyl-tRNA and delivering cognate aa-tRNA to the ribosomal A site in a GTP-dependent manner, and can also deliver deacylated tRNA. aa-tRNA binding stabilizes its GTP binding and stimulates GTP hydrolysis. Unlike canonical eEF1A, GTP hydrolysis by GTPBP1 is not promptly followed by peptide-bond formation; it retains aa-tRNA in the A site, which delays accommodation and can stall the ribosome, coupling GTPBP1 to mRNA surveillance and ribosome-associated quality control, notably by promoting exosome-mediated degradation of faulty mRNAs engaged in elongation complexes. GTPBP1 associates with cytoplasmic exosome subunits and has been implicated in the regulation of circadian mRNA stability. Loss-of-function variants cause an autosomal-recessive neurodevelopmental disorder (NEDFET1).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006414 translational elongation | IBA GO_REF:0000033 | ACCEPT | Summary: GTPBP1 has eEF1A-like elongation activity (aa-tRNA delivery), placing it in the translational-elongation process. IBA agrees with direct biochemistry. Reason: Supported by direct demonstration of eEF1A-like aa-tRNA delivery; GTPBP1 acts during elongation, although its non-canonical kinetics link it to surveillance. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt delivering aa-tRNAs to the ribosomal A site in a GTP-dependent manner |
| GO:0003746 translation elongation factor activity | IBA GO_REF:0000033 | ACCEPT | Summary: GTPBP1 enables eEF1A-like translation elongation factor activity, delivering aa-tRNA to the A site. Core molecular function. Reason: Directly demonstrated eEF1A-like elongation factor activity. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt forming ternary complexes with GTP and aminoacyl-transfer |
| GO:0003924 GTPase activity | IEA GO_REF:0000120 | ACCEPT | Summary: GTPBP1 hydrolyzes GTP as a translational GTPase. Core catalytic function. Reason: Directly demonstrated GTP hydrolysis; the UniProt catalytic activity record documents EC 3.6.5.3. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt aa-tRNA binding stabilizes GTP binding and stimulates GTP hydrolysis |
| GO:0005525 GTP binding | IEA GO_REF:0000002 | ACCEPT | Summary: GTPBP1 binds GTP as part of its ternary-complex / GTPase cycle. Reason: Well-supported molecular function underlying GTPase activity. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt forming ternary complexes with GTP and aminoacyl-transfer |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasmic localization, consistent with the documented site of action. Reason: Correct compartment for this cytoplasmic translational GTPase. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:1904678 alpha-aminoacyl-tRNA binding | IEA GO_REF:0000117 | ACCEPT | Summary: GTPBP1 binds aminoacyl-tRNA in forming its ternary complex; this is a directly demonstrated molecular function. Reason: Directly supported by the aa-tRNA delivery activity. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt forming ternary complexes with GTP and aminoacyl-transfer |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Binary interactome capturing a GTPBP1 interaction (C7orf25). Bare protein binding is uninformative. Reason: Records a physical interaction but the generic term adds nothing to GTPBP1's elongation/surveillance function. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt Q9BPX7: C7orf25 |
| GO:0000177 cytoplasmic exosome (RNase complex) | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: GTPBP1 associates with cytoplasmic exosome subunits and promotes exosomal degradation, but it is not a stoichiometric core component of the exosome RNase complex. Reason: GTPBP1 functionally recruits/associates with the exosome rather than being a structural subunit; part_of overstates the relationship. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt promotes exosomal degradation of faulty mRNAs engaged in 80S elongation complexes |
| GO:0005829 cytosol | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cytosolic localization, consistent with the cytoplasmic site of action. Reason: Correct but generic localization. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0046039 GTP metabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Reflects GTP hydrolysis by GTPBP1; a generic process companion to GTPase activity. Reason: Correct but generic; the informative function is the translation/surveillance role enabled by GTP hydrolysis. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt aa-tRNA binding stabilizes GTP binding and stimulates GTP hydrolysis |
| GO:0061014 positive regulation of mRNA catabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: GTPBP1 promotes exosomal degradation of faulty mRNAs from stalled elongation complexes, positively regulating mRNA catabolism. Reason: Supported by direct evidence that GTPBP1 stimulates exosomal mRNA degradation. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt promotes exosomal degradation of faulty mRNAs engaged in 80S elongation complexes |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity transfer of cytoplasmic localization, consistent with direct evidence. Reason: Correct compartment. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0000049 tRNA binding | IDA PMID:30108131 Functions of unconventional mammalian translational GTPases ... | ACCEPT | Summary: GTPBP1 directly binds tRNA (aminoacyl- and deacylated), demonstrated in vitro. Core molecular function. Reason: Directly demonstrated tRNA binding underlying aa-tRNA delivery. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt Is also able to deliver deacylated tRNA to the A site |
| GO:0003924 GTPase activity | IDA PMID:30108131 Functions of unconventional mammalian translational GTPases ... | ACCEPT | Summary: Direct demonstration of GTP hydrolysis by GTPBP1. Reason: Directly demonstrated core catalytic activity. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt aa-tRNA binding stabilizes GTP binding and stimulates GTP hydrolysis |
| GO:0005525 GTP binding | IDA PMID:30108131 Functions of unconventional mammalian translational GTPases ... | ACCEPT | Summary: Direct demonstration of GTP binding by GTPBP1. Reason: Directly demonstrated molecular function. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt forming ternary complexes with GTP and aminoacyl-transfer |
| GO:0071025 RNA surveillance | IDA PMID:30108131 Functions of unconventional mammalian translational GTPases ... | ACCEPT | Summary: GTPBP1's stalling-and-exosome-recruitment behavior implicates it directly in mRNA surveillance / ribosome-associated quality control. Reason: Directly demonstrated role in mRNA surveillance via exosomal degradation of faulty elongation-complex mRNAs. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt it is also involved in RNA quality control |
| GO:0002181 cytoplasmic translation | IDA PMID:30108131 Functions of unconventional mammalian translational GTPases ... | KEEP AS NON CORE | Summary: GTPBP1 participates in cytoplasmic translation as an eEF1A-like elongation factor, though its specific role is non-canonical/surveillance-linked. Reason: Broad cytoplasmic-translation process; the informative core is its elongation-factor activity and surveillance role. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt delivering aa-tRNAs to the ribosomal A site in a GTP-dependent manner |
| GO:0003746 translation elongation factor activity | IDA PMID:30108131 Functions of unconventional mammalian translational GTPases ... | ACCEPT | Summary: Direct demonstration of eEF1A-like elongation factor activity for GTPBP1. Reason: Best-supported core molecular function. Supporting Evidence: PMID:30108131 GTPBP1 possesses eEF1A-like |
| GO:1904678 alpha-aminoacyl-tRNA binding | IDA PMID:30108131 Functions of unconventional mammalian translational GTPases ... | ACCEPT | Summary: Direct demonstration that GTPBP1 binds aminoacyl-tRNA. Reason: Directly demonstrated molecular function. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt forming ternary complexes with GTP and aminoacyl-transfer |
| GO:0046039 GTP metabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Generic GTP-metabolism process companion to GTPase activity. Reason: Correct but generic. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt aa-tRNA binding stabilizes GTP binding and stimulates GTP hydrolysis |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: High-throughput NK-cell membrane proteome detection; not the functional compartment for this cytoplasmic GTPase. Reason: Mass-spectrometry catalog localization conflicting with the documented cytoplasmic site of action. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | KEEP AS NON CORE | Summary: mRNA-interactome capture detects GTPBP1 as an RNA-binding protein, consistent with its tRNA/RNA-binding activity. Reason: General RNA binding; the informative functions are tRNA/aa-tRNA binding, captured by more specific terms. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt Is also able to deliver deacylated tRNA to the A site |
| GO:0000177 cytoplasmic exosome (RNase complex) | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Sequence-similarity transfer placing GTPBP1 in the cytoplasmic exosome; GTPBP1 associates with rather than being a core subunit. Reason: GTPBP1 recruits/associates with the exosome functionally; part_of overstates structural membership. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt promotes exosomal degradation of faulty mRNAs engaged in 80S elongation complexes |
| GO:0003924 GTPase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity transfer of GTPase activity, consistent with direct evidence. Reason: Correct core catalytic function. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt aa-tRNA binding stabilizes GTP binding and stimulates GTP hydrolysis |
| GO:0005829 cytosol | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer of cytosolic localization. Reason: Correct but generic localization. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0061014 positive regulation of mRNA catabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: GTPBP1 positively regulates mRNA catabolism via exosomal degradation. Reason: Supported by direct evidence of stimulated exosomal mRNA degradation. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt promotes exosomal degradation of faulty mRNAs engaged in 80S elongation complexes |
| GO:0005525 GTP binding | TAS PMID:9070279 Identification of human and mouse GP-1, a putative member of... | ACCEPT | Summary: Original GP-1 characterization documenting GTP binding. Reason: Author-curated GTP binding, consistent with the core GTPase function. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt forming ternary complexes with GTP and aminoacyl-transfer |
| GO:0006955 immune response | TAS PMID:9070279 Identification of human and mouse GP-1, a putative member of... | MARK AS OVER ANNOTATED | Summary: GP-1 was originally described as an IFN-gamma-induced gene, prompting this immune-response annotation; no direct mechanistic role in immunity has been established. Reason: Based on expression induction rather than a defined function; GTPBP1's characterized role is in translation/mRNA surveillance. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt GTPase that plays a role in the elongation phase of protein synthesis |
| GO:0007165 signal transduction | TAS PMID:9070279 Identification of human and mouse GP-1, a putative member of... | MARK AS OVER ANNOTATED | Summary: Generic signal-transduction assignment from the original characterization; not supported by GTPBP1's defined translational function. Reason: Overly broad and unsupported; GTPBP1 is a translational GTPase, not a signaling component. Supporting Evidence: file:human/GTPBP1/GTPBP1-uniprot.txt GTPase that plays a role in the elongation phase of protein synthesis |
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Download this section (compressed HTML)Q: What endogenous mRNAs or stress conditions trigger GTPBP1-dependent exosomal degradation, and how is the choice between productive elongation (eEF1A) and GTPBP1-mediated stalling made?
Q: Does the neurodevelopmental disorder NEDFET1 arise from loss of GTPBP1's elongation activity, its surveillance/exosome-recruitment role, or both?
Experiment: Ribosome profiling and exosome-substrate (RNA degradome) sequencing in GTPBP1-knockout versus wild-type cells to identify endogenous mRNAs whose turnover depends on GTPBP1.
Experiment: Reconstituted A-site accommodation and peptidyl-transfer kinetics comparing GTPBP1 with eEF1A on defined ribosomal complexes to quantify the stalling propensity that drives surveillance.
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