FlyBase identifies one 525 aa TyrRS-PA/Q9VV60 protein. The catalogue PMID:26761199(https://pubmed.ncbi.nlm.nih.gov/26761199/) distinguishes cytoplasmic TyrRS/CG4561 from mitochondrial TyrRS-m. PMID:19561293(https://pubmed.ncbi.nlm.nih.gov/19561293/) provides functional and genetic complementation support, though this cache is abstract-only and no new construct-specific assay claim is made.
The charging narrative is supported. The resveratrol claim remains UNC. The starvation prediction is CNN on direct fly secretion evidence, scoped to a cellular response to serum deprivation. Direct binding is not refuted by the obsoletion of a nonevolved ligand-binding GO term. QuickGO snapshots verify both resveratrol-term obsoletion and replacement guidance for the obsolete tyrosyl-tRNA aminoacylation BP term. Original IDs/labels remain untouched.
Falcon completed after its wrapper timed out. A separate manual research synthesis documents directly inspected evidence. The completed Falcon report was read and its endogenous secretion finding is evaluated against the primary paper. The human resveratrol/serum-starvation study PMID:25533949 was fetched with full text and read; its direct evidence is acknowledged while transfer to native fly TyrRS remains unresolved.
The full PMID:26658841 article was downloaded and its Results, figures and controls read. The immutable HTML and extracted text are retained locally. Endogenous extracellular staining and haemolymph blots support secretion during competition; TyrRS depletion reduces haemocyte recruitment, while secreted TyrRS/EMAP constructs support chemoattractant activity. Figure 3 reports TyrRS-HA secretion after 24 h serum deprivation in S2 cells with anti-tubulin and membrane-integrity controls. This supports the broad starvation-response prediction under the QuickGO definition, which explicitly includes secretion changes upon nourishment deprivation. It does not establish whole-animal starvation fitness or the rat donor’s nuclear PARP1 mechanism. The cached PMID record is abstract-only, but the separately retained publisher full text supplies the Figure 3 evidence.
Identity: Q9VV60 is the single, full-length FlyBase product TyrRS-PA (525 aa) of CG4561, the cytoplasmic tyrosyl-tRNA synthetase; it is not an isoform, fragment or alternative gene model. The mitochondrial enzyme is the separate gene TyrRS-m PMID:26761199.
Evolutionary grounding: UniProt places Q9VV60 in PTHR11586:SF43 (TYROSINE--TRNA LIGASE, CYTOPLASMIC), the same subfamily as human YARS1 P54577 and the other vertebrate cytoplasmic TyrRS entries in interpro/panther/PTHR11586/PTHR11586-entries.csv. A new global alignment (TyrRS-bioinformatics/compare_motifs.py, RESULTS.md) gives 68% identity over 522 aligned positions, with the HIGH-region (PHVAYF), KMSSS, ELR and the lysine-rich KKKLKKA segment all conserved. The IBA for GO:0004831 comes from PTN000236303 with fly TyrRS and human YARS1 as donors. Per QuickGO (2026-10-20), human YARS1 also carries nucleus IDA, GO:0042594 response to starvation IDA, GO:0036094 and interleukin-8 receptor binding TAS, but PAINT propagated none of these from the node; I treat that as deliberate.
Changes relative to the previous version:
- Rewrote the boilerplate summaries/reasons that had been pasted across rows, so each row now has its own reasoning and support.
- GO:0006950 response to stress (ARBA): changed from MODIFY→response to starvation to MARK_AS_OVER_ANNOTATED. In fly, TyrRS is released by serum-deprived S2 cells and apoptotic loser cells (PMID:26658841), so it is the secreted cargo. Under the participation rule, release under a condition is not doing work in the response, and the human nuclear stress mechanism (PMID:25533949) was not propagated by PAINT and is untested in fly.
- GO:0005634 nucleus: still UNDECIDED. The reason now gives the subfamily comparator, the conserved lysine-rich segment and the fact that fly CMT-model nuclear data use transgenic human YARS1.
- Cytoplasm IEA: ACCEPT, now supported by the catalogue rather than ARBA text.
- NEW extracellular region and chemoattractant activity are retained with fly-specific support (abstract plus publisher full text). Chemoattractant activity is a conditional, non-core function of the processed extracellular protein; human YARS1 cytokine data were not transferred.
- Added PMID:25533949 (comparator only), the falcon report and the new bioinformatics RESULTS.md as references. Added reference_review entries. Kept TyrRS-flybase.txt as a reference even though it is no longer quoted.
- Not added: F-actin binding/bundling (Ermanoska 2023, human YARS1 protein; not tested for the native fly protein), and cell competition / haemocyte migration BP terms (TyrRS is the cue; the chemoattractant MF covers its contribution).
Relative for the next review: human YARS1 (P54577), the SF43 ortholog and PAINT co-donor; no review exists in genes/human/. The PANTHER family review interpro/panther/PTHR11586/PTHR11586-review.yaml lists Q9VV60 under SF43, which agrees with the placement here. The only aaRS module, modules/bacterial_aminoacyl_trna_charging.yaml, is bacterial in scope and does not include this eukaryotic cytoplasmic enzyme.