GTPBP1

UniProt ID: O00178
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

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).

Existing Annotations Review

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

Core Functions

eEF1A-like translational GTPase that forms a GTP/aminoacyl-tRNA ternary complex and delivers aa-tRNA to the ribosomal A site; its non-canonical kinetics (delayed peptide-bond formation) couple it to ribosome stalling and quality control.

Molecular Function:
translation elongation factor activity
Cellular Locations:
cytoplasm
Supporting Evidence:
  • PMID:30108131
    GTPBP1 possesses eEF1A-like
  • file:human/GTPBP1/GTPBP1-uniprot.txt
    delivering aa-tRNAs to the ribosomal A site in a GTP-dependent manner

Promotes mRNA surveillance / ribosome-associated quality control by stalling on faulty elongation complexes and stimulating exosome-mediated degradation of the engaged mRNA.

Molecular Function:
GTPase activity
Cellular Locations:
cytoplasm
Supporting Evidence:
  • file:human/GTPBP1/GTPBP1-uniprot.txt
    promotes exosomal degradation of faulty mRNAs engaged in 80S elongation complexes

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000024
Manual transfer of annotations from one model organism to another based on sequence orthology
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
GO_REF:0000107
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
GO_REF:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:19946888
Defining the membrane proteome of NK cells.
PMID:22658674
Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
PMID:30108131
Functions of unconventional mammalian translational GTPases GTPBP1 and GTPBP2.
  • GTPBP1 possesses eEF1A-like elongation activity, delivering cognate aa-tRNA to the A site; after GTP hydrolysis it retains aa-tRNA, delaying accommodation and promoting exosomal degradation of faulty mRNAs.
PMID:32296183
A reference map of the human binary protein interactome.
PMID:9070279
Identification of human and mouse GP-1, a putative member of a novel G-protein family.

Suggested Questions for Experts

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?

Suggested Experiments

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.

📚 Additional Documentation

Notes

(GTPBP1-notes.md)

GTPBP1 (GP-1) — research notes

UniProt: O00178. TRAFAC-class translation-factor GTPase, GTPBP1 subfamily; closely related to eEF1A, eRF3, Hbs1.

Core function (PMID:30108131, Zinoviev et al. 2018)

  • GTPBP1 has eEF1A-like elongation activity: forms ternary complexes with GTP + aa-tRNA and delivers cognate aa-tRNA to the ribosomal A site in a GTP-dependent manner.
    PMID:30108131
  • After GTP hydrolysis, peptide bond formation is NOT rapid; GTPBP1 retains aa-tRNA, delaying A-site accommodation → ribosome stalling → triggers quality-control programs, e.g. recruiting the exosome to degrade faulty mRNAs in elongation complexes.
    [file:human/GTPBP1/GTPBP1-uniprot.txt "after GTP hydrolysis, which is not immediately followed by rapid peptide bond formation, GTPBP1 likely retains aa-tRNA in the A site and promotes exosomal degradation of faulty mRNAs engaged in 80S elongation complexes"]
  • Can also deliver deacylated tRNA to the A site (relevant under stress).
  • aa-tRNA binding stabilizes GTP binding and stimulates GTP hydrolysis.
  • Interacts with exosome subunits (EXOSC2/3/5) and HNRNPD/R, SYNCRIP; involved in circadian mRNA stability (by similarity).
  • Disease: NEDFET1 (autosomal recessive neurodevelopmental disorder) PMID:38118446.

Annotations

  • IDA-supported (PMID:30108131): GTPase activity, GTP binding, tRNA binding (GO:0000049), alpha-aminoacyl-tRNA binding (GO:1904678), translation elongation factor activity (GO:0003746), cytoplasmic translation (GO:0002181), RNA surveillance (GO:0071025).
  • Exosome (cytoplasmic exosome RNase complex GO:0000177) part_of (IEA/ISS) — GTPBP1 associates with but is not a stoichiometric core exosome subunit; better as a functional association. Mark over-annotated/keep non-core.
  • PMID:9070279 (original GP-1 cloning, IFN-gamma induced): immune response, signal transduction, GTP binding — TAS. Immune response/signal transduction are dated, indirect; keep non-core / over-annotated.
  • HDA RNA binding (PMID:22658674 mRNA interactome) — consistent with tRNA/RNA binding; keep non-core.

Action plan

  • Core MF: GO:0003746 translation elongation factor activity (eEF1A-like aa-tRNA delivery); GO:0003924 GTPase activity. Core BP: GO:0071025 RNA surveillance / GO:0061014 positive regulation of mRNA catabolic process.
  • translational elongation GO:0006414 / cytoplasmic translation: keep as the elongation-factor context (accept/non-core).

Pn Notes

(GTPBP1-pn-notes.md)

GTPBP1 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: O00178
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-batch-2026-06-07c
  • Batch change status: added

Source Files Checked

Deep Research Files

  • No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

  • Description: 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).
  • Existing/core annotation action counts: ACCEPT: 17; KEEP_AS_NON_CORE: 7; MARK_AS_OVER_ANNOTATED: 5

PN Consistency Summary

  • Consistency: Largely consistent on biology, with one term-level mismatch. Deep research, notes, and review agree GTPBP1 is an eEF1A-like translational GTPase that delivers aa-tRNA to the A site but, with non-canonical kinetics (delayed peptide-bond formation), retains aa-tRNA, stalls the ribosome, and promotes exosome-mediated degradation of faulty mRNAs — i.e., couples elongation to mRNA surveillance/RQC (PMID:30108131). Review ACCEPTs GO:0003746 (elongation factor activity), GO:0003924 (GTPase), GO:0071025 (RNA surveillance, IDA), GO:0061014 (positive regulation of mRNA catabolic process). The review does NOT carry GO:0072344 — it frames GTPBP1's QC role as mRNA surveillance/decay (GO:0071025/GO:0061014), not ribosome rescue.
  • PN story / NEW pressure: PN's "Ribosomal rescue" type→GO:0072344 (verified real; goa_status=more_specific_than_existing_goa) asserts GTPBP1 rescues stalled cytosolic ribosomes. This is the divergence: GTPBP1's documented role is to CAUSE stalling and recruit the exosome to degrade the mRNA (a surveillance/decay outcome), not to split/rescue the stalled ribosome (the PELO/HBS1L/ABCE1 sense of GO:0072344). GTPBP1 GOA contains GO:0071025 but NOT GO:0072344. So GO:0072344 is a candidate NEW term that over-reaches: the evidence supports mRNA surveillance (GO:0071025, already present) rather than ribosome rescue. The PN "more_specific_than_existing_goa" framing is questionable — GO:0072344 is not strictly more specific than GO:0071025; they are different processes.
  • Evidence alignment: PN dossier lists no reference titles for GTPBP1; the single mechanistic anchor (PMID:30108131) is shared with the review (cited HIGH/VERIFIED). The review reads that paper as surveillance/exosomal decay (GO:0071025/GO:0061014); PN reads it as ribosome rescue (GO:0072344) — same paper, divergent term interpretation.
  • Verdict: Biology consistent; PN's GO:0072344 "Ribosomal rescue" mapping over-reaches vs the review's surveillance/decay framing (GO:0071025 present in GOA; GO:0072344 absent). Recommended edits: [MAP] do not project GO:0072344 (rescue of stalled cytosolic ribosome) onto GTPBP1 — its evidenced role is mRNA surveillance/exosomal decay (GO:0071025/GO:0061014), not ribosome rescue; reclassify the PN row from "Ribosomal rescue" to "other RQC processes" (RQC-group→GO:0006515 still applies). [REF] PMID:30108131 supports surveillance, not rescue — note the interpretive divergence.

Full Consistency Review

  • UniProt: O00178 · batch: proteostasis-batch-2026-06-07c · review status: COMPLETE
  • PN placement: Translation|Cytosolic translation|Ribosome-associated QC|Ribosomal rescue ; PN-node mapping: rescue type=mapped→GO:0072344 (rescue of stalled cytosolic ribosome); RQC group=mapped→GO:0006515; class/branch context_only (GO:0002181/GO:0006412 too_broad).
  • Consistency: Largely consistent on biology, with one term-level mismatch. Deep research, notes, and review agree GTPBP1 is an eEF1A-like translational GTPase that delivers aa-tRNA to the A site but, with non-canonical kinetics (delayed peptide-bond formation), retains aa-tRNA, stalls the ribosome, and promotes exosome-mediated degradation of faulty mRNAs — i.e., couples elongation to mRNA surveillance/RQC (PMID:30108131). Review ACCEPTs GO:0003746 (elongation factor activity), GO:0003924 (GTPase), GO:0071025 (RNA surveillance, IDA), GO:0061014 (positive regulation of mRNA catabolic process). The review does NOT carry GO:0072344 — it frames GTPBP1's QC role as mRNA surveillance/decay (GO:0071025/GO:0061014), not ribosome rescue.
  • PN story / NEW pressure: PN's "Ribosomal rescue" type→GO:0072344 (verified real; goa_status=more_specific_than_existing_goa) asserts GTPBP1 rescues stalled cytosolic ribosomes. This is the divergence: GTPBP1's documented role is to CAUSE stalling and recruit the exosome to degrade the mRNA (a surveillance/decay outcome), not to split/rescue the stalled ribosome (the PELO/HBS1L/ABCE1 sense of GO:0072344). GTPBP1 GOA contains GO:0071025 but NOT GO:0072344. So GO:0072344 is a candidate NEW term that over-reaches: the evidence supports mRNA surveillance (GO:0071025, already present) rather than ribosome rescue. The PN "more_specific_than_existing_goa" framing is questionable — GO:0072344 is not strictly more specific than GO:0071025; they are different processes.
  • Mapping strategy: This gene's placement under "Ribosomal rescue" is the issue. GTPBP1 fits "other RQC processes" / mRNA surveillance better than "Ribosomal rescue." The rescue type→GO:0072344 projection should not be applied to O00178. RQC group→GO:0006515 (umbrella) is acceptable. Recommend reclassifying or, at minimum, not projecting GO:0072344.
  • Evidence alignment: PN dossier lists no reference titles for GTPBP1; the single mechanistic anchor (PMID:30108131) is shared with the review (cited HIGH/VERIFIED). The review reads that paper as surveillance/exosomal decay (GO:0071025/GO:0061014); PN reads it as ribosome rescue (GO:0072344) — same paper, divergent term interpretation.
  • Verdict: Biology consistent; PN's GO:0072344 "Ribosomal rescue" mapping over-reaches vs the review's surveillance/decay framing (GO:0071025 present in GOA; GO:0072344 absent). Recommended edits: [MAP] do not project GO:0072344 (rescue of stalled cytosolic ribosome) onto GTPBP1 — its evidenced role is mRNA surveillance/exosomal decay (GO:0071025/GO:0061014), not ribosome rescue; reclassify the PN row from "Ribosomal rescue" to "other RQC processes" (RQC-group→GO:0006515 still applies). [REF] PMID:30108131 supports surveillance, not rescue — note the interpretive divergence.

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07c
  • review_yaml: genes/human/GTPBP1/GTPBP1-ai-review.yaml
  • PN workbook rows: 1

PN row 1: Translation | Cytosolic translation | Ribosome-associated QC | Ribosomal rescue

  • UniProt: O00178
  • In branches: TR
  • PN-node mapping records (path + ancestors):
    • [type] Translation|Cytosolic translation|Ribosome-associated QC|Ribosomal rescue
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0072344 rescue of stalled cytosolic ribosome]
      rationale: This PN RQC type denotes rescue of stalled cytosolic ribosomes. The matching GO process term is the direct target.
    • [group] Translation|Cytosolic translation|Ribosome-associated QC
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0006515 protein quality control for misfolded or incompletely synthesized proteins]
      rationale: The PN ribosome-associated quality-control group covers surveillance and disposal of stalled or defective nascent-chain translation products. GO lacks a dedicated ribosome-associated QC term in the local cache, so the broader protein-quality-control process is the best supported target.
    • [class] Translation|Cytosolic translation
      status=context_only scope=too_broad_to_propagate GO=[GO:0002181 cytoplasmic translation]
      rationale: The PN class Cytosolic translation is centered on the cytoplasmic translation apparatus and process, but it also houses supporting machinery such as ribosome biogenesis factors. The GO process term is a useful high-level label for the class, but propagating it to all members would over-annotate genes whose PN placement is through assembly or maturation context rather than core cytoplasmic translation.
    • [branch] Translation
      status=context_only scope=too_broad_to_propagate GO=[GO:0006412 translation]
      rationale: The PN Translation branch is organized around the translation apparatus and immediately associated cotranslational quality-control systems. GO translation is the closest high-level process label, but the PN branch also contains adjacent machinery such as ribosome biogenesis and nascent-chain handling. Keeping this relationship is useful for interpretation, but it is too broad to project safely onto every member.

Projected GO annotations (2)

  • GO:0006515 protein quality control for misfolded or incompletely synthesized proteins | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Translation|Cytosolic translation|Ribosome-associated QC
  • GO:0072344 rescue of stalled cytosolic ribosome | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Translation|Cytosolic translation|Ribosome-associated QC|Ribosomal rescue

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

 
id: O00178
gene_symbol: GTPBP1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 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).
existing_annotations:
- term:
    id: GO:0006414
    label: translational elongation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: GTPBP1 has eEF1A-like elongation activity (aa-tRNA delivery), placing
      it in the translational-elongation process. IBA agrees with direct biochemistry.
    action: ACCEPT
    reason: Supported by direct demonstration of eEF1A-like aa-tRNA delivery; GTPBP1
      acts during elongation, although its non-canonical kinetics link it to surveillance.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: delivering aa-tRNAs to the ribosomal A site in a GTP-dependent
        manner
- term:
    id: GO:0003746
    label: translation elongation factor activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: GTPBP1 enables eEF1A-like translation elongation factor activity, delivering
      aa-tRNA to the A site. Core molecular function.
    action: ACCEPT
    reason: Directly demonstrated eEF1A-like elongation factor activity.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: forming ternary complexes with GTP and aminoacyl-transfer
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: GTPBP1 hydrolyzes GTP as a translational GTPase. Core catalytic function.
    action: ACCEPT
    reason: Directly demonstrated GTP hydrolysis; the UniProt catalytic activity record
      documents EC 3.6.5.3.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: aa-tRNA binding stabilizes GTP binding and stimulates GTP hydrolysis
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: GTPBP1 binds GTP as part of its ternary-complex / GTPase cycle.
    action: ACCEPT
    reason: Well-supported molecular function underlying GTPase activity.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: forming ternary complexes with GTP and aminoacyl-transfer
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Cytoplasmic localization, consistent with the documented site of action.
    action: ACCEPT
    reason: Correct compartment for this cytoplasmic translational GTPase.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:1904678
    label: alpha-aminoacyl-tRNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: enables
  review:
    summary: GTPBP1 binds aminoacyl-tRNA in forming its ternary complex; this is a
      directly demonstrated molecular function.
    action: ACCEPT
    reason: Directly supported by the aa-tRNA delivery activity.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: forming ternary complexes with GTP and aminoacyl-transfer
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Binary interactome capturing a GTPBP1 interaction (C7orf25). Bare protein
      binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a physical interaction but the generic term adds nothing to GTPBP1's
      elongation/surveillance function.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: 'Q9BPX7: C7orf25'
- term:
    id: GO:0000177
    label: cytoplasmic exosome (RNase complex)
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: part_of
  review:
    summary: GTPBP1 associates with cytoplasmic exosome subunits and promotes exosomal
      degradation, but it is not a stoichiometric core component of the exosome RNase
      complex.
    action: MARK_AS_OVER_ANNOTATED
    reason: GTPBP1 functionally recruits/associates with the exosome rather than being
      a structural subunit; part_of overstates the relationship.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: promotes exosomal degradation of faulty mRNAs engaged in 80S
        elongation complexes
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Cytosolic localization, consistent with the cytoplasmic site of action.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic localization.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0046039
    label: GTP metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Reflects GTP hydrolysis by GTPBP1; a generic process companion to GTPase
      activity.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; the informative function is the translation/surveillance
      role enabled by GTP hydrolysis.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: aa-tRNA binding stabilizes GTP binding and stimulates GTP hydrolysis
- term:
    id: GO:0061014
    label: positive regulation of mRNA catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: GTPBP1 promotes exosomal degradation of faulty mRNAs from stalled elongation
      complexes, positively regulating mRNA catabolism.
    action: ACCEPT
    reason: Supported by direct evidence that GTPBP1 stimulates exosomal mRNA degradation.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: promotes exosomal degradation of faulty mRNAs engaged in 80S
        elongation complexes
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Sequence-similarity transfer of cytoplasmic localization, consistent with
      direct evidence.
    action: ACCEPT
    reason: Correct compartment.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0000049
    label: tRNA binding
  evidence_type: IDA
  original_reference_id: PMID:30108131
  qualifier: enables
  review:
    summary: GTPBP1 directly binds tRNA (aminoacyl- and deacylated), demonstrated in
      vitro. Core molecular function.
    action: ACCEPT
    reason: Directly demonstrated tRNA binding underlying aa-tRNA delivery.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: Is also able to deliver deacylated tRNA to the A site
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: IDA
  original_reference_id: PMID:30108131
  qualifier: enables
  review:
    summary: Direct demonstration of GTP hydrolysis by GTPBP1.
    action: ACCEPT
    reason: Directly demonstrated core catalytic activity.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: aa-tRNA binding stabilizes GTP binding and stimulates GTP hydrolysis
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IDA
  original_reference_id: PMID:30108131
  qualifier: enables
  review:
    summary: Direct demonstration of GTP binding by GTPBP1.
    action: ACCEPT
    reason: Directly demonstrated molecular function.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: forming ternary complexes with GTP and aminoacyl-transfer
- term:
    id: GO:0071025
    label: RNA surveillance
  evidence_type: IDA
  original_reference_id: PMID:30108131
  qualifier: involved_in
  review:
    summary: GTPBP1's stalling-and-exosome-recruitment behavior implicates it directly
      in mRNA surveillance / ribosome-associated quality control.
    action: ACCEPT
    reason: Directly demonstrated role in mRNA surveillance via exosomal degradation
      of faulty elongation-complex mRNAs.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: it is also involved in RNA quality control
- term:
    id: GO:0002181
    label: cytoplasmic translation
  evidence_type: IDA
  original_reference_id: PMID:30108131
  qualifier: involved_in
  review:
    summary: GTPBP1 participates in cytoplasmic translation as an eEF1A-like elongation
      factor, though its specific role is non-canonical/surveillance-linked.
    action: KEEP_AS_NON_CORE
    reason: Broad cytoplasmic-translation process; the informative core is its elongation-factor
      activity and surveillance role.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: delivering aa-tRNAs to the ribosomal A site in a GTP-dependent
        manner
- term:
    id: GO:0003746
    label: translation elongation factor activity
  evidence_type: IDA
  original_reference_id: PMID:30108131
  qualifier: enables
  review:
    summary: Direct demonstration of eEF1A-like elongation factor activity for GTPBP1.
    action: ACCEPT
    reason: Best-supported core molecular function.
    supported_by:
    - reference_id: PMID:30108131
      supporting_text: GTPBP1 possesses eEF1A-like
- term:
    id: GO:1904678
    label: alpha-aminoacyl-tRNA binding
  evidence_type: IDA
  original_reference_id: PMID:30108131
  qualifier: enables
  review:
    summary: Direct demonstration that GTPBP1 binds aminoacyl-tRNA.
    action: ACCEPT
    reason: Directly demonstrated molecular function.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: forming ternary complexes with GTP and aminoacyl-transfer
- term:
    id: GO:0046039
    label: GTP metabolic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Generic GTP-metabolism process companion to GTPase activity.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: aa-tRNA binding stabilizes GTP binding and stimulates GTP hydrolysis
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: High-throughput NK-cell membrane proteome detection; not the functional
      compartment for this cytoplasmic GTPase.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mass-spectrometry catalog localization conflicting with the documented
      cytoplasmic site of action.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22658674
  qualifier: enables
  review:
    summary: mRNA-interactome capture detects GTPBP1 as an RNA-binding protein, consistent
      with its tRNA/RNA-binding activity.
    action: KEEP_AS_NON_CORE
    reason: General RNA binding; the informative functions are tRNA/aa-tRNA binding,
      captured by more specific terms.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: Is also able to deliver deacylated tRNA to the A site
- term:
    id: GO:0000177
    label: cytoplasmic exosome (RNase complex)
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: part_of
  review:
    summary: Sequence-similarity transfer placing GTPBP1 in the cytoplasmic exosome;
      GTPBP1 associates with rather than being a core subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: GTPBP1 recruits/associates with the exosome functionally; part_of overstates
      structural membership.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: promotes exosomal degradation of faulty mRNAs engaged in 80S
        elongation complexes
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: Sequence-similarity transfer of GTPase activity, consistent with direct
      evidence.
    action: ACCEPT
    reason: Correct core catalytic function.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: aa-tRNA binding stabilizes GTP binding and stimulates GTP hydrolysis
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Sequence-similarity transfer of cytosolic localization.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic localization.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0061014
    label: positive regulation of mRNA catabolic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: GTPBP1 positively regulates mRNA catabolism via exosomal degradation.
    action: ACCEPT
    reason: Supported by direct evidence of stimulated exosomal mRNA degradation.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: promotes exosomal degradation of faulty mRNAs engaged in 80S
        elongation complexes
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: TAS
  original_reference_id: PMID:9070279
  qualifier: enables
  review:
    summary: Original GP-1 characterization documenting GTP binding.
    action: ACCEPT
    reason: Author-curated GTP binding, consistent with the core GTPase function.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: forming ternary complexes with GTP and aminoacyl-transfer
- term:
    id: GO:0006955
    label: immune response
  evidence_type: TAS
  original_reference_id: PMID:9070279
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Based on expression induction rather than a defined function; GTPBP1's
      characterized role is in translation/mRNA surveillance.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: GTPase that plays a role in the elongation phase of protein
        synthesis
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: TAS
  original_reference_id: PMID:9070279
  qualifier: involved_in
  review:
    summary: Generic signal-transduction assignment from the original characterization;
      not supported by GTPBP1's defined translational function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Overly broad and unsupported; GTPBP1 is a translational GTPase, not a signaling
      component.
    supported_by:
    - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
      supporting_text: GTPase that plays a role in the elongation phase of protein
        synthesis
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of annotations from one model organism to another based on
    sequence orthology
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
- id: PMID:22658674
  title: Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
  findings: []
- id: PMID:30108131
  title: Functions of unconventional mammalian translational GTPases GTPBP1 and GTPBP2.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Cached publications/PMID_30108131.md frontmatter title matches the
      YAML title; review establishes the eEF1A-like translational-GTPase / ribosome
      surveillance function. Cited in core_functions supported_by for GO:0003746."
  findings:
  - statement: GTPBP1 possesses eEF1A-like elongation activity, delivering cognate
      aa-tRNA to the A site; after GTP hydrolysis it retains aa-tRNA, delaying accommodation
      and promoting exosomal degradation of faulty mRNAs.
    reference_section_type: RESULTS
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:9070279
  title: 'Identification of human and mouse GP-1, a putative member of a novel G-protein family.'
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: "Not cached, but anchored to GOA: this PMID supports GO:0005525
      (GTP binding), GO:0006955 (immune response) and GO:0007165 (signal transduction)
      by TAS in GTPBP1-goa.tsv, consistent with the title (original GP-1/GTPBP1
      cloning and IFN-gamma inducibility). Background characterization rather than
      the core translation-elongation function."
core_functions:
- description: eEF1A-like translational GTPase that forms a GTP/aminoacyl-tRNA ternary
    complex and delivers aa-tRNA to the ribosomal A site; its non-canonical kinetics
    (delayed peptide-bond formation) couple it to ribosome stalling and quality control.
  molecular_function:
    id: GO:0003746
    label: translation elongation factor activity
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: PMID:30108131
    supporting_text: GTPBP1 possesses eEF1A-like
  - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
    supporting_text: delivering aa-tRNAs to the ribosomal A site in a GTP-dependent
      manner
- description: Promotes mRNA surveillance / ribosome-associated quality control by
    stalling on faulty elongation complexes and stimulating exosome-mediated degradation
    of the engaged mRNA.
  molecular_function:
    id: GO:0003924
    label: GTPase activity
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: file:human/GTPBP1/GTPBP1-uniprot.txt
    supporting_text: promotes exosomal degradation of faulty mRNAs engaged in 80S elongation
      complexes
proposed_new_terms: []
suggested_questions:
- question: 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?
- question: Does the neurodevelopmental disorder NEDFET1 arise from loss of GTPBP1's
    elongation activity, its surveillance/exosome-recruitment role, or both?
suggested_experiments:
- description: Ribosome profiling and exosome-substrate (RNA degradome) sequencing
    in GTPBP1-knockout versus wild-type cells to identify endogenous mRNAs whose turnover
    depends on GTPBP1.
- description: Reconstituted A-site accommodation and peptidyl-transfer kinetics comparing
    GTPBP1 with eEF1A on defined ribosomal complexes to quantify the stalling propensity
    that drives surveillance.