TyrRS is the cytoplasmic tyrosyl-tRNA synthetase of Drosophila melanogaster. It charges tRNA(Tyr) through an ATP-dependent aminoacyl-adenylate intermediate, supplying tyrosine for protein synthesis. During cell competition, loser cells secrete TyrRS through a JNK- and Kish-dependent mechanism. Extracellular proteolysis produces an EMAP fragment that attracts haemocytes for removal of dying cells. Fly S2 cells also secrete TyrRS after serum deprivation. The gene encodes a 525-residue polypeptide distinct from mitochondrial TyrRS-m.
Summary: The fly aaRS catalogue identifies CG4561/TyrRS as the cytoplasmic tyrosyl-tRNA synthetase, and functional/complementation experiments support its conserved aminoacylation activity.
Reason: The fly aaRS catalogue identifies CG4561/TyrRS as the cytoplasmic tyrosyl-tRNA synthetase, and functional/complementation experiments support its conserved aminoacylation activity. The single native 525-residue polypeptide has the corresponding tRNA-binding architecture. The annotation is grounded in characterized gene identity and conserved mechanism rather than its electronic provenance.
Summary: ATP is the nucleotide substrate consumed to activate tyrosine before transfer to tRNA.
Reason: ATP is the nucleotide substrate consumed to activate tyrosine before transfer to tRNA. ATP binding is therefore the informative supported specificity; generic nucleotide binding is unnecessarily broad.
Summary: The enzyme recognizes cognate tRNA during aminoacylation.
Reason: The enzyme recognizes cognate tRNA during aminoacylation. The specific tRNA-binding annotation is supported by the known reaction and encoded tRNA-binding domain, so replace broad RNA binding.
Summary: Tyrosine is the supported substrate of this cytoplasmic TyrRS family member; the more precise tyrosine-tRNA ligase activity is established independently of the InterPro parent-term mapping..
Reason: Tyrosine is the supported substrate of this cytoplasmic TyrRS family member; the more precise tyrosine-tRNA ligase activity is established independently of the InterPro parent-term mapping.
Summary: The fly aaRS catalogue identifies CG4561/TyrRS as the cytoplasmic tyrosyl-tRNA synthetase, and functional/complementation experiments support its conserved aminoacylation activity.
Reason: The fly aaRS catalogue identifies CG4561/TyrRS as the cytoplasmic tyrosyl-tRNA synthetase, and functional/complementation experiments support its conserved aminoacylation activity. The single native 525-residue polypeptide has the corresponding tRNA-binding architecture. The annotation is grounded in characterized gene identity and conserved mechanism rather than its electronic provenance.
IDA PMID:19561293 Dominant mutations in the tyrosyl-tRNA synthetase gene recap...
ACCEPT
Summary: The fly aaRS catalogue identifies CG4561/TyrRS as the cytoplasmic tyrosyl-tRNA synthetase, and functional/complementation experiments support its conserved aminoacylation activity.
Reason: The fly aaRS catalogue identifies CG4561/TyrRS as the cytoplasmic tyrosyl-tRNA synthetase, and functional/complementation experiments support its conserved aminoacylation activity. The single native 525-residue polypeptide has the corresponding tRNA-binding architecture. The annotation is grounded in characterized gene identity and conserved mechanism rather than its electronic provenance.
Summary: The fly aaRS catalogue identifies CG4561/TyrRS as the cytoplasmic tyrosyl-tRNA synthetase, and functional/complementation experiments support its conserved aminoacylation activity.
Reason: The fly aaRS catalogue identifies CG4561/TyrRS as the cytoplasmic tyrosyl-tRNA synthetase, and functional/complementation experiments support its conserved aminoacylation activity. The single native 525-residue polypeptide has the corresponding tRNA-binding architecture. The annotation is grounded in characterized gene identity and conserved mechanism rather than its electronic provenance.
TAS PMID:26761199 The aminoacyl-tRNA synthetases of Drosophila melanogaster.
ACCEPT
Summary: The fly aaRS catalogue identifies CG4561/TyrRS as the cytoplasmic tyrosyl-tRNA synthetase, and functional/complementation experiments support its conserved aminoacylation activity.
Reason: The fly aaRS catalogue identifies CG4561/TyrRS as the cytoplasmic tyrosyl-tRNA synthetase, and functional/complementation experiments support its conserved aminoacylation activity. The single native 525-residue polypeptide has the corresponding tRNA-binding architecture. The annotation is grounded in characterized gene identity and conserved mechanism rather than its electronic provenance.
Summary: The fly aaRS catalogue identifies CG4561/TyrRS as the cytoplasmic tyrosyl-tRNA synthetase, and functional/complementation experiments support its conserved aminoacylation activity.
Reason: The fly aaRS catalogue identifies CG4561/TyrRS as the cytoplasmic tyrosyl-tRNA synthetase, and functional/complementation experiments support its conserved aminoacylation activity. The single native 525-residue polypeptide has the corresponding tRNA-binding architecture. The annotation is grounded in characterized gene identity and conserved mechanism rather than its electronic provenance.
Summary: The native fly protein is established as a cytoplasmic aaRS.
Reason: The native fly protein is established as a cytoplasmic aaRS. Mammalian TyrRS can enter nuclei during stress, but ARBA-derived compartment text is not independent evidence of nuclear localization by native Drosophila TyrRS. Native-protein localization or a justified conserved regulatory mechanism is missing; nuclear residence is neither accepted from ARBA nor refuted by cytoplasmic function.
Summary: The fly aaRS catalogue identifies CG4561/TyrRS as the cytoplasmic tyrosyl-tRNA synthetase, and functional/complementation experiments support its conserved aminoacylation activity.
Reason: The fly aaRS catalogue identifies CG4561/TyrRS as the cytoplasmic tyrosyl-tRNA synthetase, and functional/complementation experiments support its conserved aminoacylation activity. The single native 525-residue polypeptide has the corresponding tRNA-binding architecture. The annotation is grounded in characterized gene identity and conserved mechanism rather than its electronic provenance.
TAS PMID:26761199 The aminoacyl-tRNA synthetases of Drosophila melanogaster.
ACCEPT
Summary: The fly aaRS catalogue identifies CG4561/TyrRS as the cytoplasmic tyrosyl-tRNA synthetase, and functional/complementation experiments support its conserved aminoacylation activity.
Reason: The fly aaRS catalogue identifies CG4561/TyrRS as the cytoplasmic tyrosyl-tRNA synthetase, and functional/complementation experiments support its conserved aminoacylation activity. The single native 525-residue polypeptide has the corresponding tRNA-binding architecture. The annotation is grounded in characterized gene identity and conserved mechanism rather than its electronic provenance.
GO:0006418 tRNA aminoacylation for protein translation
IEA GO_REF:0000002
ACCEPT
Summary: The fly aaRS catalogue identifies CG4561/TyrRS as the cytoplasmic tyrosyl-tRNA synthetase, and functional/complementation experiments support its conserved aminoacylation activity.
Reason: The fly aaRS catalogue identifies CG4561/TyrRS as the cytoplasmic tyrosyl-tRNA synthetase, and functional/complementation experiments support its conserved aminoacylation activity. The single native 525-residue polypeptide has the corresponding tRNA-binding architecture. The annotation is grounded in characterized gene identity and conserved mechanism rather than its electronic provenance.
Summary: QuickGO verifies that GO:0006437 is obsolete because it restates the tyrosine-tRNA ligase molecular function.
Reason: QuickGO verifies that GO:0006437 is obsolete because it restates the tyrosine-tRNA ligase molecular function. Preserve the source identifier in this row but propose GO:0006418 for the biological process; GO:0004831 separately captures tyrosine specificity.
The reason for obsoletion is that this term restates an existing molecular function, GO:0004831 tyrosine-tRNA ligase activity, and adds nothing beyond it.
TAS PMID:26761199 The aminoacyl-tRNA synthetases of Drosophila melanogaster.
MODIFY
Summary: QuickGO verifies that GO:0006437 is obsolete because it restates the tyrosine-tRNA ligase molecular function.
Reason: QuickGO verifies that GO:0006437 is obsolete because it restates the tyrosine-tRNA ligase molecular function. Preserve the source identifier in this row but propose GO:0006418 for the biological process; GO:0004831 separately captures tyrosine specificity.
The reason for obsoletion is that this term restates an existing molecular function, GO:0004831 tyrosine-tRNA ligase activity, and adds nothing beyond it.
Summary: Fly TyrRS undergoes regulated secretion after serum deprivation and during cell competition; starvation response is a more informative term for the directly tested cellular condition.
Reason: PMID:26658841 Figure 3 detects TyrRS-HA secretion from serum-deprived S2 cells and controls for cellular contamination and membrane damage. This supports a cellular response to nourishment deprivation, without establishing whole-animal starvation survival or a mammalian PARP1 mechanism.
IDA PMID:26658841 Active JNK-dependent secretion of Drosophila Tyrosyl-tRNA sy...
NEW
Summary: Endogenous TyrRS is detected outside loser cells and in larval haemolymph during cell competition. This is a regulated extracellular pool in addition to the cytoplasmic enzyme.
Reason: Endogenous TyrRS is detected outside loser cells and in larval haemolymph during cell competition. This is a regulated extracellular pool in addition to the cytoplasmic enzyme.
IDA PMID:26658841 Active JNK-dependent secretion of Drosophila Tyrosyl-tRNA sy...
NEW
Summary: Secreted TyrRS and its cleaved EMAP fragment recruit haemocytes; the activity belongs to the extracellular processed product, distinct from aminoacylation.
Reason: Secreted TyrRS and its cleaved EMAP fragment recruit haemocytes; the activity belongs to the extracellular processed product, distinct from aminoacylation.
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
Fly TyrRS has established aminoacylation and regulated extracellular functions. Its secretion upon serum deprivation supports the broad starvation-response prediction, while the specific resveratrol-binding GO term is obsolete and direct fly binding is unmeasured.
Review rationale: The primary fly study detects TyrRS-HA secretion from S2 cells after serum deprivation, with membrane-integrity and tubulin controls excluding release by cell lysis. GO:0042594 includes secretion changes in response to nourishment deprivation, so this cellular experiment supports the broad claim. Existing target GOA contains only a broader stress annotation. This does not establish organismal starvation tolerance or the rat donor’s detailed nuclear mechanism; original training-set novelty is not known. The function was described in fly literature before this prediction release, so it is correct but not biologically novel (CNN); actual inclusion in the model training set is not established.
Review rationale: The exact predicted term, GO:1905594 resveratrol binding, is obsolete, replacement-less and explicitly out of scope for evolved molecular functions. OpenScientist found the fly tyrosine active-site pocket conserved with the human YARS1 pocket that binds resveratrol, so in-vitro binding by fly Q9VV60 remains plausible by homology but unmeasured. The biological prediction therefore cannot be validated or refuted with available evidence, and the obsolete xenobiotic-specific GO term should not be curated even if an in-vitro fly-binding assay is eventually positive.
Supporting Evidence:
file:DROME/TyrRS/TyrRS-hypotheses/fly41-resveratrol-recognition/openscientist.md: "Fly TyrRS almost certainly *can* accommodate resveratrol in its conserved tyrosine pocket (68.4% identity to human, all nine contact residues identical), but this has never been measured in *Drosophila*, represents a xenobiotic pharmacological interaction rather than an evolved function"