CG4610

UniProt ID: Q9W245
Organism: Drosophila melanogaster
Review Status: COMPLETE
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Gene Description

CG4610 encodes the Drosophila ortholog of MTO1 (bacterial MnmG/GidA), an FAD-dependent MnmG-family enzyme. By homology it acts with the GTPBP3 ortholog CG18528 in the mitochondrial GTPBP3-MTO1 complex, which modifies the wobble uridine (U34) of a subset of mitochondrial tRNAs at C5 (taurinomethylation in mammals), a modification that supports accurate codon reading during mitochondrial translation. No Drosophila-specific experimental studies have been reported; function and mitochondrial location are inferred from orthologs.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0002098 tRNA wobble uridine modification
IEA
GO_REF:0000002
MODIFY
Summary: tRNA wobble uridine modification (InterPro).
Reason: Correct but less specific than the evidence supports for this mitochondrial MTO1 ortholog; MODIFY to mitochondrial tRNA wobble uridine modification, which CG4610 already carries (IBA, IEA, ISS).
Supporting Evidence:
file:DROME/CG4610/CG4610-uniprot.txt
Belongs to the MnmG family
GO:0005737 cytoplasm
IEA
GO_REF:0000117
MODIFY
Summary: Cytoplasm (InterPro mapping from the bacterial MnmG family).
Reason: Not wrong under the GO definition of cytoplasm, but the eukaryotic MTO1 ortholog is mitochondrial; MODIFY to mitochondrion, which CG4610 already carries (IBA, ISS).
Proposed replacements: mitochondrion
GO:0005739 mitochondrion
IBA
GO_REF:0000033
ACCEPT
Summary: Mitochondrion.
Reason: MTO1 orthologs are mitochondrial; the fly protein belongs to the mitochondrial MTO1 subfamily. No fly localization data exist.
Supporting Evidence:
file:DROME/CG4610/CG4610-deep-research-falcon.md
A mitochondrial tRNA-modification role is plausible because the characterized yeast and human eukaryotic MnmG-family systems act in mitochondria
file:DROME/CG4610/CG4610-uniprot.txt
PROTEIN MTO1 HOMOLOG, MITOCHONDRIAL
GO:0005739 mitochondrion
ISS
GO_REF:0000024
ACCEPT
Summary: Mitochondrion.
Reason: MTO1 orthologs are mitochondrial; the fly protein belongs to the mitochondrial MTO1 subfamily. No fly localization data exist.
Supporting Evidence:
file:DROME/CG4610/CG4610-deep-research-falcon.md
A mitochondrial tRNA-modification role is plausible because the characterized yeast and human eukaryotic MnmG-family systems act in mitochondria
file:DROME/CG4610/CG4610-uniprot.txt
PROTEIN MTO1 HOMOLOG, MITOCHONDRIAL
GO:0008033 tRNA processing
IEA
GO_REF:0000002
MODIFY
Summary: Generic tRNA processing.
Reason: Correct but an uninformative parent of the wobble uridine modification terms; MODIFY to mitochondrial tRNA wobble uridine modification, which CG4610 already carries (IBA, IEA, ISS).
GO:0050660 flavin adenine dinucleotide binding
IEA
GO_REF:0000002
ACCEPT
Summary: FAD binding.
Reason: MnmG/MTO1 proteins carry an FAD-binding Rossmann domain (Pfam GIDA, IPR036188) and FAD is required for the modification reaction. Support is domain classification of CG4610 (the GIDA Pfam domain and the FAD/NAD(P)-binding superfamily signatures); the UniProt FAD cofactor line itself is an ARBA prediction and is not cited.
Supporting Evidence:
file:DROME/CG4610/CG4610-uniprot.txt
InterPro; IPR036188; FAD/NAD-bd_sf.
file:DROME/CG4610/CG4610-uniprot.txt
Pfam; PF01134; GIDA; 1.
GO:0070899 mitochondrial tRNA wobble uridine modification
IBA
GO_REF:0000033
ACCEPT
Summary: Mitochondrial tRNA wobble uridine modification.
Reason: Core process of the eukaryotic MTO1 subfamily, consistent with IBA, ISS and InterPro evidence. Support is family classification of CG4610 (HAMAP MnmG_GidA, NCBIfam mnmG_gidA and the PANTHER mitochondrial MTO1 subfamily); the process itself is experimentally established for the mammalian orthologs, not for the fly protein.
Supporting Evidence:
file:DROME/CG4610/CG4610-uniprot.txt
PANTHER; PTHR11806:SF0; PROTEIN MTO1 HOMOLOG, MITOCHONDRIAL; 1.
file:DROME/CG4610/CG4610-uniprot.txt
HAMAP; MF_00129; MnmG_GidA; 1.
GO:0070899 mitochondrial tRNA wobble uridine modification
IEA
GO_REF:0000117
ACCEPT
Summary: Mitochondrial tRNA wobble uridine modification.
Reason: Core process of the eukaryotic MTO1 subfamily, consistent with IBA, ISS and InterPro evidence. Support is family classification of CG4610 (HAMAP MnmG_GidA, NCBIfam mnmG_gidA and the PANTHER mitochondrial MTO1 subfamily); the process itself is experimentally established for the mammalian orthologs, not for the fly protein.
Supporting Evidence:
file:DROME/CG4610/CG4610-uniprot.txt
PANTHER; PTHR11806:SF0; PROTEIN MTO1 HOMOLOG, MITOCHONDRIAL; 1.
file:DROME/CG4610/CG4610-uniprot.txt
HAMAP; MF_00129; MnmG_GidA; 1.
GO:0070899 mitochondrial tRNA wobble uridine modification
ISS
GO_REF:0000024
ACCEPT
Summary: Mitochondrial tRNA wobble uridine modification.
Reason: Core process of the eukaryotic MTO1 subfamily, consistent with IBA, ISS and InterPro evidence. Support is family classification of CG4610 (HAMAP MnmG_GidA, NCBIfam mnmG_gidA and the PANTHER mitochondrial MTO1 subfamily); the process itself is experimentally established for the mammalian orthologs, not for the fly protein.
Supporting Evidence:
file:DROME/CG4610/CG4610-uniprot.txt
PANTHER; PTHR11806:SF0; PROTEIN MTO1 HOMOLOG, MITOCHONDRIAL; 1.
file:DROME/CG4610/CG4610-uniprot.txt
HAMAP; MF_00129; MnmG_GidA; 1.
GO:0160236 tRNA 5-taurinomethyluridine synthase activity
IBA
GO_REF:0000033
ACCEPT
Summary: Contributes to tRNA 5-taurinomethyluridine synthase activity as the FAD-dependent MTO1 subunit.
Reason: CG4610 is the single fly MnmG/MTO1 family member (PTHR11806:SF0, mitochondrial MTO1 subfamily). Human MTO1 with GTPBP3 forms taum5U34; the contributes_to qualifier correctly reflects that catalysis requires both subunits. Whether fly mt-tRNAs use taurine specifically has not been tested, but this is the current GO term for the eukaryotic GTPBP3-MTO1 activity.
Supporting Evidence:
file:DROME/CG4610/CG4610-uniprot.txt
Belongs to the MnmG family
file:DROME/CG4610/CG4610-deep-research-falcon.md
whereas human mitochondrial GTPBP3–MTO1 uses
GO:0160236 tRNA 5-taurinomethyluridine synthase activity
ISS
GO_REF:0000024
ACCEPT
Summary: Contributes to tRNA 5-taurinomethyluridine synthase activity as the FAD-dependent MTO1 subunit.
Reason: CG4610 is the single fly MnmG/MTO1 family member (PTHR11806:SF0, mitochondrial MTO1 subfamily). Human MTO1 with GTPBP3 forms taum5U34; the contributes_to qualifier correctly reflects that catalysis requires both subunits. Whether fly mt-tRNAs use taurine specifically has not been tested, but this is the current GO term for the eukaryotic GTPBP3-MTO1 activity.
Supporting Evidence:
file:DROME/CG4610/CG4610-uniprot.txt
Belongs to the MnmG family
file:DROME/CG4610/CG4610-deep-research-falcon.md
whereas human mitochondrial GTPBP3–MTO1 uses
GO:7770010 GTPBP3-MTO1 complex
IBA
GO_REF:0000033
ACCEPT
Summary: Member of the GTPBP3-MTO1 complex.
Reason: Fly has single orthologs of both subunits (CG18528 = GTPBP3, CG4610 = MTO1); the complex is conserved from bacterial MnmEG. Support is family classification of CG4610 in the mitochondrial MTO1 subfamily; complex membership is inferred from that family's conserved MnmE/GTPBP3 partnership and has not been tested for the fly proteins.
Supporting Evidence:
file:DROME/CG4610/CG4610-uniprot.txt
PANTHER; PTHR11806:SF0; PROTEIN MTO1 HOMOLOG, MITOCHONDRIAL; 1.
file:DROME/CG4610/CG4610-uniprot.txt
NCBIfam; TIGR00136; mnmG_gidA; 1.
GO:7770010 GTPBP3-MTO1 complex
ISS
GO_REF:0000024
ACCEPT
Summary: Member of the GTPBP3-MTO1 complex.
Reason: Fly has single orthologs of both subunits (CG18528 = GTPBP3, CG4610 = MTO1); the complex is conserved from bacterial MnmEG. Support is family classification of CG4610 in the mitochondrial MTO1 subfamily; complex membership is inferred from that family's conserved MnmE/GTPBP3 partnership and has not been tested for the fly proteins.
Supporting Evidence:
file:DROME/CG4610/CG4610-uniprot.txt
PANTHER; PTHR11806:SF0; PROTEIN MTO1 HOMOLOG, MITOCHONDRIAL; 1.
file:DROME/CG4610/CG4610-uniprot.txt
NCBIfam; TIGR00136; mnmG_gidA; 1.

Core Functions

FAD-dependent MTO1 subunit of the mitochondrial GTPBP3-MTO1 complex that, with the GTPase CG18528, installs the C5 substituent on wobble uridine 34 of mitochondrial tRNAs.

Supporting Evidence:
  • file:DROME/CG4610/CG4610-uniprot.txt
    PANTHER; PTHR11806:SF0; PROTEIN MTO1 HOMOLOG, MITOCHONDRIAL; 1.
  • file:DROME/CG4610/CG4610-uniprot.txt
    HAMAP; MF_00129; MnmG_GidA; 1.

References

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Suggested Questions for Experts

Q: Do Drosophila mitochondrial tRNAs carry taurinomethyluridine at U34, as in mammals, and is the taurine-specific MF term appropriate for the fly GTPBP3-MTO1 complex?

Suggested Experiments

Experiment: Mass-spectrometric nucleoside analysis of purified mt-tRNAs from CG4610 mutant or knockdown flies, combined with mitochondrial ribosome profiling or respiratory chain assays.

Hypothesis: CG4610 loss abolishes the U34 C5 modification of fly mt-tRNAs and impairs mitochondrial translation.

Deep Research

Falcon

(CG4610-deep-research-falcon.md)

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πŸ“š Additional Documentation

Notes

(CG4610-notes.md)

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