QRSL1 notes

Deep research

QRSL1-deep-research-claude-code.md came from just deep-research-claude-code human QRSL1 --timeout 1700.
It ran for 32 s with 2 web searches (web_search_requests: 2) and 5 citations, and states that it did not
read any full text and could not confirm the Friederich 2018 PMID. It was used only for leads; the PMID
for Friederich et al. 2018 (PMID:30283131) was obtained from the GATC review and fetched with just fetch-pmid.

Function

• QRSL1 = human GatA, the amidase-signature subunit of mitochondrial GatCAB (QRSL1-GATB-GATC).
  UniProt active sites: Lys76 and Ser171 (charge relay), Ser195 (acyl-ester intermediate).
• GatCAB converts Glu-tRNA(Gln) (made by EARS2) to Gln-tRNA(Gln) with glutamine and ATP; GatA hydrolyses
  glutamine and channels NH3 to GatB [UniProt FUNCTION; PMID:30283131 "In the bacterial GatCAB complex, GatA and GatB possess the catalytic amidase and kinase functions, respectively, while GatC serves as a stabilizing linker between them"].
• Human GatCAB identified, siRNA of any subunit accumulates Glu-tRNA(Gln), reconstituted in vitro [PMID:19805282, abstract only].
• Kohda 2016: QRSL1 patient variants "were associated with severe transamidation activity defects" PMID:26741492.
• Friederich 2018: QRSL1 patients (family 2, 3) with lethal cardiomyopathy; mt-tRNA(Gln) charging and
  mitochondrial translation defective under glutamine restriction PMID:30283131.
• Mouse/human cell work (Echevarria 2014, PMID:24579914, cached without abstract text) is cited by UniProt for GatA being required for GATB stability; not quoted.

Curation decisions

• GO:0070681 is obsolete (QuickGO: "Annotations require review rather than migration"; consider GO:0043039,
  GO:0050567). Replaced with GO:0019988 charged-tRNA amino acid modification, matching the GATC review, since
  GatCAB modifies an amino acid already attached to tRNA(Gln).
• GO:0004359 glutaminase activity (IEA from HAMAP/EC 3.5.1.2): kept as non-core. QRSL1 does catalyse the
  glutamine-hydrolysis half-reaction, but the ammonia is channelled rather than released, so the meaningful
  activity is the complex-level GO:0050567.
• Protein binding IPI rows (partners GATB, GATC) removed; captured by GO:0030956 membership.

Mitochondrial translation (GO:0032543) and GO:0070127 (2026-10-30, PR #5739 review round)

• GO:0032543 mitochondrial translation is kept as non-core context, not core, and is no
  longer listed in core_functions. GatCAB transamidates Glu-tRNA(Gln) to Gln-tRNA(Gln); it
  prepares a charged tRNA that translation consumes and performs no step of translation on
  the mitoribosome. The knockdown and patient data (PMID:19805282, PMID:30283131) show that
  GatCAB is necessary for mitochondrial protein synthesis, which is necessity evidence, not
  participation. The earlier justification "in the same sense used for mitochondrial
  aminoacyl-tRNA synthetases" was wrong: none of the human mt-aaRS GOA files checked
  (DARS2, AARS2, EARS2, FARS2, TARS2) carries GO:0032543, and the DARS2 and TARS2 reviews use
  GO:0070127 instead. The MTO1 review likewise does not claim GO:0032543.
• GO:0070127 tRNA aminoacylation for mitochondrial protein translation was considered and
  not added. Its definition is "the synthesis of aminoacyl tRNA by the formation of an ester
  bond between the 3'-hydroxyl group of the most 3' adenosine of the tRNA" (go.db). GatCAB
  forms no ester bond: it amidates the side chain of glutamate already esterified to
  tRNA(Gln) by EARS2, so the reaction is a modification of a charged tRNA (GO:0019988), not
  aminoacylation.