GATB is the catalytic subunit of the heterotrimeric mitochondrial GatCAB complex. The other subunits are QRSL1 (GatA, the glutaminase subunit) and GATC (GatC).
Why the complex is needed. Human mitochondria have no mitochondrial glutaminyl-tRNA synthetase. Mitochondrial glutamyl-tRNA synthetase (EARS2) mischarges mt-tRNA(Gln) with glutamate, giving Glu-tRNA(Gln). GatCAB then converts this to Gln-tRNA(Gln).
Experimental evidence. Nagao et al. (PNAS 2009, PMID:19805282(https://pmc.ncbi.nlm.nih.gov/articles/PMC2752530)) showed the following:
- They identified the human GatCAB heterotrimer.
- Knocking down any subunit caused Glu-tRNA(Gln) to accumulate in cells and produced respiratory defects.
- They reconstituted Gln-tRNA(Gln) formation in vitro from recombinant enzymes.
- Misacylated Glu-tRNA(Gln) binds mitochondrial EF-Tu only weakly, which the authors interpret as a quality-control step for translation.
Reaction. Based on the UniProt record and the HAMAP rule MF_03147 (the first two steps are inferred by similarity to bacterial GatCAB, not shown directly for the human enzyme):
- Overall: L-Glu-tRNA(Gln) + L-glutamine + ATP + H2O → L-Gln-tRNA(Gln) + L-glutamate + ADP + Pi + H+ (Rhea:17521).
- Step 1: GatB phosphorylates the Glu side chain, giving 5-phospho-Glu-tRNA(Gln) + ADP (Rhea:57908).
- Step 2: ammonia from the GatA glutaminase domain attacks the activated intermediate, giving Gln-tRNA(Gln) + Pi (Rhea:57912).
- The enzyme uses Mg2+ as a cofactor.
Substrate specificity. The mitochondrial substrate is Glu-mt-tRNA(Gln). Unlike bacterial GatCAB, which also makes Asn-tRNA(Asn), the human complex works on tRNA(Gln) only.
Friederich et al. (Nat Commun 2018, doi:10.1038/s41467-018-06250-w) reported nine patients from five families with defects in QRSL1, GATB or GATC. All had a lethal metabolic cardiomyopathy syndrome. The cited summary (a search-result abstract, not full text) says patient cells had combined respiratory chain deficiencies. The tRNA charging and translation defects were reversed by high glutamine in patient fibroblasts. Lentiviral rescue and S. cerevisiae modeling supported pathogenicity. I did not read the full text, so I can't give variant-level or clinical details, and I found no follow-up studies.
These come from the function and localization evidence above.
- Core molecular function: glutaminyl-tRNA synthase (glutamine-hydrolyzing) activity, GO:0050567, which corresponds to EC 6.3.5.7. ATP binding is supported by the catalytic mechanism but is not a core function.
- Core process: glutamyl-tRNA(Gln) to glutaminyl-tRNA(Gln) conversion, supporting mitochondrial translation. The matching GO terms are mitochondrial translation and mitochondrial tRNA aminoacylation (I did not look up identifiers).
- Core location and complex: mitochondrial matrix, as part of the GatCAB complex.
- Avoid: "protein binding". The reaction-based terms above are more informative.
GATB-uniprot.txt