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.