CG18528 encodes the Drosophila ortholog of GTPBP3 (bacterial MnmE/TrmE), a mitochondrial TrmE-family GTPase. By homology it partners with the MTO1 ortholog CG4610 to form the GTPBP3-MTO1 enzyme that installs a C5-substituted methyl group (taurinomethyl in mammals, carboxymethylaminomethyl in bacteria) on the wobble uridine (U34) of a subset of mitochondrial tRNAs, a modification needed for accurate decoding during mitochondrial translation. The protein has an N-terminal folate-binding TrmE domain, a central helical domain and a G domain whose GTP hydrolysis drives the reaction cycle. No Drosophila-specific experimental studies have been reported; function is inferred from orthologs.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002098 tRNA wobble uridine modification | IBA GO_REF:0000033 | MODIFY | Summary: Wobble uridine modification is the conserved process of the MnmE/GTPBP3 family. Reason: The IBA places CG18528 in the PANTHER GTPBP3/MnmE clade (PTHR42714) whose characterized members (E. coli MnmE, yeast MSS1, human GTPBP3) modify U34, so the term is correct, but for this mitochondrial eukaryotic ortholog the more specific mitochondrial term is warranted; MODIFY to mitochondrial tRNA wobble uridine modification, which CG18528 already carries (ISS). Proposed replacements: mitochondrial tRNA wobble uridine modification Supporting Evidence: file:DROME/CG18528/CG18528-uniprot.txt tRNA modification GTPase GTPBP3, mitochondrial |
| GO:0003924 GTPase activity | IEA GO_REF:0000002 | ACCEPT | Summary: GTPase activity of the TrmE G domain. Reason: CG18528 has the full MnmE GTPase domain (IPR004520, IPR031168); GTP hydrolysis is the defining activity of the family. Supporting Evidence: file:DROME/CG18528/CG18528-uniprot.txt TrmE GTPase family |
| GO:0003924 GTPase activity | ISS GO_REF:0000024 | ACCEPT | Summary: GTPase activity transferred from human GTPBP3. Reason: Consistent with the conserved G domain; this is the core molecular function. Supporting Evidence: file:DROME/CG18528/CG18528-uniprot.txt TrmE GTPase family |
| GO:0005525 GTP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: GTP binding by the G domain. Reason: Correct but implied by GTPase activity, which is the informative core function. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | MODIFY | Summary: Cytoplasm, inherited from a node that includes cytoplasmic bacterial MnmE. Reason: Not wrong under the GO definition of cytoplasm (which includes mitochondria), but the eukaryotic GTPBP3 orthologs, including CG18528, are mitochondrial; MODIFY to mitochondrion, which CG18528 already carries (IBA, IEA, ISS). Proposed replacements: mitochondrion Supporting Evidence: file:DROME/CG18528/CG18528-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrial localization. Reason: GTPBP3 orthologs are mitochondrial-matrix enzymes acting on mt-tRNAs; CG18528 is the single fly member of the mitochondrial GTPBP3 subfamily (PTHR42714:SF2). Support is family classification only (the UniProt SUBCELLULAR LOCATION line is ARBA-predicted and no TRANSIT feature is annotated); there is no fly experimental localization, so the claim rests on membership in the mitochondrial PANTHER subfamily, which is why the row stays at the organelle root. Supporting Evidence: file:DROME/CG18528/CG18528-uniprot.txt PANTHER; PTHR42714:SF2; TRNA MODIFICATION GTPASE GTPBP3, MITOCHONDRIAL |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: Mitochondrial localization. Reason: GTPBP3 orthologs are mitochondrial-matrix enzymes acting on mt-tRNAs; CG18528 is the single fly member of the mitochondrial GTPBP3 subfamily (PTHR42714:SF2). Support is family classification only (the UniProt SUBCELLULAR LOCATION line is ARBA-predicted and no TRANSIT feature is annotated); there is no fly experimental localization, so the claim rests on membership in the mitochondrial PANTHER subfamily, which is why the row stays at the organelle root. Supporting Evidence: file:DROME/CG18528/CG18528-uniprot.txt PANTHER; PTHR42714:SF2; TRNA MODIFICATION GTPASE GTPBP3, MITOCHONDRIAL |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | ACCEPT | Summary: Mitochondrial localization. Reason: GTPBP3 orthologs are mitochondrial-matrix enzymes acting on mt-tRNAs; CG18528 is the single fly member of the mitochondrial GTPBP3 subfamily (PTHR42714:SF2). Support is family classification only (the UniProt SUBCELLULAR LOCATION line is ARBA-predicted and no TRANSIT feature is annotated); there is no fly experimental localization, so the claim rests on membership in the mitochondrial PANTHER subfamily, which is why the row stays at the organelle root. Supporting Evidence: file:DROME/CG18528/CG18528-uniprot.txt PANTHER; PTHR42714:SF2; TRNA MODIFICATION GTPASE GTPBP3, MITOCHONDRIAL |
| GO:0006400 tRNA modification | IEA GO_REF:0000002 | MODIFY | Summary: Generic tRNA modification from InterPro. Reason: Correct but an uninformative parent. The evidence supports the specific mitochondrial wobble uridine (U34) modification, so MODIFY to mitochondrial tRNA wobble uridine modification, which CG18528 already carries (ISS). Proposed replacements: mitochondrial tRNA wobble uridine modification |
| GO:0030488 tRNA methylation | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: tRNA methylation, propagated from E. coli MnmE. Reason: The MnmE/GTPBP3-MnmG/MTO1 reaction transfers a methylene from methylene-THF and links an amine (glycine, ammonia or taurine) to C5 of U34, i.e. an aminomethylation, not addition of a methyl group in the sense of GO tRNA methylation. The wobble uridine modification terms describe the process accurately. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P25522 UNRESOLVED E. coli MnmE does participate in U34 modification, but labelling the C5-aminomethylation as tRNA methylation stretches the term; the clade-level wobble uridine modification term transfers safely. Supporting Evidence: file:DROME/CG18528/CG18528-uniprot.txt tRNA modification GTPase GTPBP3, mitochondrial |
| GO:0070899 mitochondrial tRNA wobble uridine modification | ISS GO_REF:0000024 | ACCEPT | Summary: Mitochondrial tRNA wobble uridine modification, by similarity to yeast MSS1. Reason: This is the core process of the GTPBP3/MTO1 enzyme in eukaryotes and is the best descriptor for CG18528. Supporting Evidence: file:DROME/CG18528/CG18528-uniprot.txt tRNA modification GTPase GTPBP3, mitochondrial file:DROME/CG18528/CG18528-deep-research-falcon.md is that CG18528 is the fly counterpart of GTPBP3: a GTP-dependent factor in the pathway that modifies the anticodon |
| GO:7770010 GTPBP3-MTO1 complex | ISS GO_REF:0000024 | ACCEPT | Summary: Member of the GTPBP3-MTO1 complex, by similarity to human GTPBP3. Reason: The fly genome encodes single orthologs of both partners (CG18528 for GTPBP3 and CG4610 for MTO1), so the complex is expected to be conserved. Supporting Evidence: file:DROME/CG18528/CG18528-uniprot.txt tRNA modification GTPase GTPBP3, mitochondrial |
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Download this section (compressed HTML)Q: Which C5 substituent (taurinomethyl, carboxymethylaminomethyl or other) is present on the wobble uridine of Drosophila mitochondrial tRNAs, and does it depend on CG18528?
Experiment: Profile mt-tRNA modifications by LC-MS/MS or nanopore/primer-extension in CG18528 mutant or RNAi tissue, and assay mitochondrial translation and respiration.
Hypothesis: CG18528 is required for the C5 modification of U34 in Drosophila mt-tRNAs.
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