GATC encodes the C subunit of the mitochondrial glutamyl-tRNA(Gln) amidotransferase GatCAB, a heterotrimer with the catalytic subunits QRSL1 (GatA, glutaminase) and GATB (GatB, kinase/transamidase). Because mammalian mitochondria lack a glutaminyl-tRNA synthetase, mitochondrial tRNA(Gln) is first misacylated with glutamate by the mitochondrial glutamyl-tRNA synthetase (EARS2), and GatCAB then converts Glu-tRNA(Gln) to Gln-tRNA(Gln) using glutamine and ATP, via a phosphorylated glutamyl-tRNA intermediate. GATC is a small non-catalytic structural subunit that, by analogy with bacterial GatC, wraps around the interface of the A and B subunits to stabilise the complex. GatCAB activity is required for correct charging of mitochondrial tRNA(Gln), for exclusion of misacylated Glu-tRNA(Gln) from translation (it binds mitochondrial EF-Tu weakly), and therefore for accurate mitochondrial protein synthesis and respiration. Biallelic GATC variants, like those in QRSL1 and GATB, cause combined oxidative phosphorylation deficiency 42, a lethal infantile metabolic cardiomyopathy with lactic acidosis; in patient fibroblasts tRNA(Gln) aminoacylation and mitochondrial translation are deficient in low glutamine and restored by high glutamine.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:19805282 Biogenesis of glutaminyl-mt tRNAGln in human mitochondria. | REMOVE | Summary: IPI with QRSL1 (GatA) from the study that identified human GatCAB. The interaction reflects assembly of the heterotrimeric amidotransferase. Reason: protein binding (GO:0005515) is uninformative; the interaction is captured by membership of the glutamyl-tRNA(Gln) amidotransferase complex. Supporting Evidence: PMID:19805282 we have identified a human homolog of the Glu-tRNA(Gln) amidotransferase, the hGatCAB heterotrimer |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: High-throughput Y2H interaction with SRSF11. Generic protein binding. Reason: protein binding (GO:0005515) is uninformative and the nuclear splicing factor partner is not linked to GATC function. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: BioPlex affinity-purification interaction with CYP4V2. Generic protein binding. Reason: protein binding (GO:0005515) is uninformative and not linked to GATC function. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: BioPlex interaction with QRSL1 (GatA), reflecting GatCAB assembly. Reason: protein binding (GO:0005515) is uninformative; captured by GatCAB complex membership. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI binary Y2H interactions (ALOX5, CTAG1B, HGS, SRSF11 isoform, TOMM20L). Generic protein binding. Reason: protein binding (GO:0005515) is uninformative; none of these partners is linked to GATC function. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI binary Y2H interactions (ALOX5, CTAG1B, HGS, SRSF11 isoform, TOMM20L). Generic protein binding. Reason: protein binding (GO:0005515) is uninformative; none of these partners is linked to GATC function. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI binary Y2H interactions (ALOX5, CTAG1B, HGS, SRSF11 isoform, TOMM20L). Generic protein binding. Reason: protein binding (GO:0005515) is uninformative; none of these partners is linked to GATC function. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI binary Y2H interactions (ALOX5, CTAG1B, HGS, SRSF11 isoform, TOMM20L). Generic protein binding. Reason: protein binding (GO:0005515) is uninformative; none of these partners is linked to GATC function. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI binary Y2H interactions (ALOX5, CTAG1B, HGS, SRSF11 isoform, TOMM20L). Generic protein binding. Reason: protein binding (GO:0005515) is uninformative; none of these partners is linked to GATC function. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: BioPlex dual-network interaction with CYP4V2. Generic protein binding. Reason: protein binding (GO:0005515) is uninformative. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: BioPlex dual-network interaction with QRSL1, reflecting GatCAB assembly. Reason: protein binding (GO:0005515) is uninformative; captured by GatCAB complex membership. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Multimodal cell-map interaction with QRSL1, reflecting GatCAB assembly. Reason: protein binding (GO:0005515) is uninformative; captured by GatCAB complex membership. Supporting Evidence: PMID:40205054 Multimodal cell maps as a foundation for structural and functional genomics. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: High-confidence human mitochondrial proteome. Reason: GatCAB acts in mitochondria. Supporting Evidence: PMID:34800366 Quantitative high-confidence human mitochondrial proteome |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA is_active_in mitochondrion for the eukaryotic GatC clade. Reason: Correct; eukaryotic GatCAB functions in mitochondria. Supporting Evidence: PMID:19805282 implying that Gln-tRNA(Gln) is synthesized via an indirect pathway in the mammalian mitochondria |
| GO:0005739 mitochondrion | IDA PMID:19805282 Biogenesis of glutaminyl-mt tRNAGln in human mitochondria. | ACCEPT | Summary: IDA mitochondrial localisation of human GatCAB subunits. Reason: Core location. Supporting Evidence: PMID:19805282 we have identified a human homolog of the Glu-tRNA(Gln) amidotransferase, the hGatCAB heterotrimer |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: Automated mitochondrion annotation (mouse ortholog + UniProt SubCell). Reason: Consistent with experimental evidence. Supporting Evidence: file:human/GATC/GATC-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0006450 regulation of translational fidelity | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro (GatC domain) mapping to regulation of translational fidelity. GatCAB converts misacylated Glu-tRNA(Gln) to Gln-tRNA(Gln), and the misacylated form is excluded from translation, so the complex contributes to accurate decoding of Gln codons. Reason: Defensible in that GatCAB prevents glutamate misincorporation, but the direct role is tRNA(Gln) charging rather than regulation of the fidelity of the translational machinery; non-core. Supporting Evidence: PMID:19805282 the misaminoacylated form of tRNA(Gln) is rejected from the translational apparatus to maintain the accuracy of mitochondrial protein synthesis |
| GO:0030956 glutamyl-tRNA(Gln) amidotransferase complex | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA glutamyl-tRNA(Gln) amidotransferase complex. Reason: Core complex membership, confirmed experimentally for human GATC. Supporting Evidence: PMID:19805282 we have identified a human homolog of the Glu-tRNA(Gln) amidotransferase, the hGatCAB heterotrimer |
| GO:0030956 glutamyl-tRNA(Gln) amidotransferase complex | IDA PMID:19805282 Biogenesis of glutaminyl-mt tRNAGln in human mitochondria. | ACCEPT | Summary: IDA: recombinant hGatCAB (QRSL1, GATB, GATC) reconstituted with mtGluRS forms Gln-tRNA(Gln) in vitro. Reason: Core complex membership. Supporting Evidence: PMID:19805282 We successfully reconstituted in vitro Gln-tRNA(Gln) formation catalyzed by the recombinant mtGluRS and hGatCAB. |
| GO:0030956 glutamyl-tRNA(Gln) amidotransferase complex | IEA GO_REF:0000104 | ACCEPT | Summary: UniRule transfer of GatCAB complex membership. Reason: Consistent with experimental evidence. Supporting Evidence: file:human/GATC/GATC-uniprot.txt Subunit of the heterotrimeric GatCAB amidotransferase (AdT) |
| GO:0030956 glutamyl-tRNA(Gln) amidotransferase complex | IPI PMID:19805282 Biogenesis of glutaminyl-mt tRNAGln in human mitochondria. | ACCEPT | Summary: IPI GatCAB complex membership via interaction with the other subunits. Reason: Core complex membership. Supporting Evidence: PMID:19805282 we have identified a human homolog of the Glu-tRNA(Gln) amidotransferase, the hGatCAB heterotrimer |
| GO:0032543 mitochondrial translation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT IBA mitochondrial translation. Reason: Kept as non-core context, not core. GatCAB transamidates Glu-tRNA(Gln) to Gln-tRNA(Gln), preparing the charged tRNA that mitochondrial translation consumes; it does not itself perform a step of translation on the mitoribosome. The knockdown and patient data show that GatCAB is necessary for mitochondrial protein synthesis, which is necessity evidence, not participation. The MTO1 review takes the same line for a tRNA-preparing enzyme. The core process for this subunit is GO:0019988 charged-tRNA amino acid modification. Supporting Evidence: PMID:30283131 Aminoacylation of mt-tRNAGln and mitochondrial protein translation are deficient in patients' fibroblasts cultured in the absence of glutamine but restore in high glutamine. |
| GO:0032543 mitochondrial translation | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: UniRule transfer of mitochondrial translation. Reason: Kept as non-core context, not core. GatCAB transamidates Glu-tRNA(Gln) to Gln-tRNA(Gln), preparing the charged tRNA that mitochondrial translation consumes; it does not itself perform a step of translation on the mitoribosome. The knockdown and patient data show that GatCAB is necessary for mitochondrial protein synthesis, which is necessity evidence, not participation. The MTO1 review takes the same line for a tRNA-preparing enzyme. The core process for this subunit is GO:0019988 charged-tRNA amino acid modification. Supporting Evidence: PMID:30283131 mt-tRNAGln is indirectly charged by a transamidation reaction involving the GatCAB aminoacyl-tRNA amidotransferase complex. |
| GO:0032543 mitochondrial translation | IMP PMID:19805282 Biogenesis of glutaminyl-mt tRNAGln in human mitochondria. | KEEP AS NON CORE | Summary: IMP: siRNA knockdown of any GatCAB subunit caused accumulation of Glu-tRNA(Gln) and respiratory defects. Reason: Kept as non-core context, not core. GatCAB transamidates Glu-tRNA(Gln) to Gln-tRNA(Gln), preparing the charged tRNA that mitochondrial translation consumes; it does not itself perform a step of translation on the mitoribosome. The knockdown and patient data show that GatCAB is necessary for mitochondrial protein synthesis, which is necessity evidence, not participation. The MTO1 review takes the same line for a tRNA-preparing enzyme. The core process for this subunit is GO:0019988 charged-tRNA amino acid modification. Supporting Evidence: PMID:19805282 When any of the hGatCAB subunits were inactivated by siRNA-mediated knock down in human cells, the Glu-charged form of tRNA(Gln) accumulated and defects in respiration could be observed. |
| GO:0070681 obsolete glutaminyl-tRNAGln biosynthesis via transamidation | IBA GO_REF:0000033 | MODIFY | Summary: PAINT IBA to glutaminyl-tRNAGln biosynthesis via transamidation, a term now obsolete (QuickGO: pathway variant out of scope; replacements to consider are GO:0050567 for the amidotransferase step and charged-tRNA amino acid modification for the process acting on already-charged tRNA). The biology is correct and central for GATC. Reason: The underlying assertion (GatCAB converts Glu-tRNA(Gln) to Gln-tRNA(Gln)) is correct, but the term is obsolete. GatCAB acts on an already-charged tRNA, so the process is best captured by charged-tRNA amino acid modification; the activity is captured by the NEW contributes_to glutaminyl-tRNA synthase (glutamine-hydrolyzing) activity annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN000385050 SUPPORTS TRANSFER The GatC node correctly transfers participation in tRNA(Gln) transamidation; the defect is only that the target term has since been obsoleted as a pathway variant. Proposed replacements: charged-tRNA amino acid modification Supporting Evidence: PMID:19805282 We successfully reconstituted in vitro Gln-tRNA(Gln) formation catalyzed by the recombinant mtGluRS and hGatCAB. |
| GO:0070681 obsolete glutaminyl-tRNAGln biosynthesis via transamidation | IDA PMID:19805282 Biogenesis of glutaminyl-mt tRNAGln in human mitochondria. | MODIFY | Summary: IDA to the now-obsolete glutaminyl-tRNAGln biosynthesis via transamidation, from the in vitro reconstitution of Gln-tRNA(Gln) formation by mtGluRS and hGatCAB. Reason: Correct biology on an obsolete term; replace with charged-tRNA amino acid modification (process) alongside the contributes_to amidotransferase activity. Proposed replacements: charged-tRNA amino acid modification Supporting Evidence: PMID:19805282 We successfully reconstituted in vitro Gln-tRNA(Gln) formation catalyzed by the recombinant mtGluRS and hGatCAB. |
| GO:0070681 obsolete glutaminyl-tRNAGln biosynthesis via transamidation | IEA GO_REF:0000104 | MODIFY | Summary: UniRule transfer of the now-obsolete transamidation pathway term. Reason: Correct biology on an obsolete term; replace as for the IDA annotation. Proposed replacements: charged-tRNA amino acid modification Supporting Evidence: PMID:30283131 mt-tRNAGln is indirectly charged by a transamidation reaction involving the GatCAB aminoacyl-tRNA amidotransferase complex. |
| GO:0050567 glutaminyl-tRNA synthase (glutamine-hydrolyzing) activity | IDA PMID:19805282 Biogenesis of glutaminyl-mt tRNAGln in human mitochondria. | NEW | Summary: GATC is a non-catalytic subunit required for the Glu-tRNA(Gln) amidotransferase activity of the GatCAB heterotrimer, which was reconstituted in vitro from recombinant subunits. Knockdown of any subunit, including GATC, blocks conversion of Glu-tRNA(Gln). The contributes_to qualifier reflects that the catalytic sites lie in QRSL1 and GATB. Reason: GOA carries no molecular function for GATC. The reconstitution and knockdown data establish that GATC is an essential component of the complex that carries this activity, the standard case for a contributes_to annotation. Supporting Evidence: PMID:19805282 When any of the hGatCAB subunits were inactivated by siRNA-mediated knock down in human cells, the Glu-charged form of tRNA(Gln) accumulated PMID:19805282 We successfully reconstituted in vitro Gln-tRNA(Gln) formation catalyzed by the recombinant mtGluRS and hGatCAB. |
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Download this section (compressed HTML)Q: Does human GATC simply stabilise the QRSL1-GATB interface, as inferred from bacterial GatCAB structures, or does it also influence tRNA(Gln) recognition or glutamine channelling?
Q: Why does high extracellular glutamine rescue tRNA(Gln) aminoacylation in GatCAB-deficient fibroblasts, and could this be exploited therapeutically in COXPD42?
Experiment: Determine the structure of human mitochondrial GatCAB bound to tRNA(Gln) to define the contacts made by GATC, and test patient GATC variants for effects on complex stability and amidotransferase kinetics in vitro.
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