FARS2 encodes a monomeric mitochondrial phenylalanyl-tRNA synthetase. It activates L-phenylalanine with ATP and transfers the amino acid to mitochondrial tRNA(Phe), providing charged tRNA for mitochondrial protein synthesis. Its catalytic and anticodon-binding regions are contained within one polypeptide. Unlike the cytosolic phenylalanyl-tRNA synthetase, it lacks an editing domain and can also charge meta-tyrosine, an oxidized phenylalanine derivative, in vitro. Biallelic pathogenic FARS2 variants cause neurological disease, including early-onset mitochondrial encephalopathy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000049 tRNA binding | IDA PMID:10329163 Expression and characterization of a human mitochondrial phe... | ACCEPT | Summary: Human mitochondrial phenylalanyl-tRNA synthetase recognizes tRNA as its aminoacylation substrate. Reason: The purified human enzyme charged tRNA(Phe), and substrate-dependent steady-state kinetics were measured in PMID:10329163 (Results, enzymatic properties; Table 1; Methods, aminoacylation assays). These are functional tRNA-recognition assays, not a measured equilibrium binding constant. They support the existing substrate-binding annotation together with its cognate ligase activity. Supporting Evidence: |
| GO:0000049 tRNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: FARS2 binds the tRNA substrate during phenylalanyl-tRNA synthesis. Reason: The actual O95363 InterPro matches include IPR002319 at residues 76–198 and 242–343. Its tRNA-binding mapping agrees with purified human mitochondrial PheRS aminoacylation assays in PMID:10329163 and PMID:19549855. This is substrate recognition by the enzyme, not an unrelated RNA-binding function. |
| GO:0000166 nucleotide binding | IEA GO_REF:0000002 | TOO GENERAL | Summary: Nucleotide binding is true but subsumed by the accepted ATP-binding activity. Reason: O95363 matches mitochondrial PheRS family IPR004530 at residues 225–446. ATP-dependent amino acid activation and tRNA charging by recombinant human mitochondrial PheRS support this nucleotide-binding mapping (PMID:10329163; PMID:19549855). The accepted GO:0005524 ATP binding is a strict descendant of GO:0000166 and supplies the relevant nucleotide specificity. TOO_GENERAL records that the broad claim is true but subsumed; it does not reject the electronic source. |
| GO:0004812 aminoacyl-tRNA ligase activity | IEA GO_REF:0000120 | TOO GENERAL | Summary: Aminoacyl-tRNA ligase activity is true but subsumed by accepted phenylalanine-tRNA ligase activity. Reason: IPR002319 is an actual O95363 domain match and maps to this activity; direct human enzyme assays establish GO:0004826 phenylalanine-tRNA ligase activity (PMID:10329163; PMID:19549855), an accepted strict descendant of GO:0004812. The broad activity is therefore TOO_GENERAL. ARBA00026908 also has GO:0004812 as a consequent, but the retrieved current rule does not establish which complete condition set matched O95363: the superficially related two-FunFam clause contains FF000053 whereas the target record has FF000041. This term-level subsumption judgment preserves that unresolved source limit and does not claim independent reproduction of the ARBA clause. GO_REF:0000120 combines methods and is not a new experiment. |
| GO:0004826 phenylalanine-tRNA ligase activity | EXP PMID:19549855 Eukaryotic cytosolic and mitochondrial phenylalanyl-tRNA syn... | ACCEPT | Summary: Human mitochondrial PheRS retains its cognate phenylalanine-tRNA ligase activity while also accepting meta-tyrosine in vitro. Reason: PMID:19549855 distinguishes the human mitochondrial and cytosolic enzymes and directly compares phenylalanine and meta-tyrosine aminoacylation. Its Results and Methods support cognate phenylalanine charging by FARS2. The alternative-substrate results do not replace that core activity or transfer cytosolic editing activity to FARS2. Supporting Evidence: |
| GO:0004826 phenylalanine-tRNA ligase activity | EXP PMID:22833457 Mitochondrial phenylalanyl-tRNA synthetase mutations underli... | ACCEPT | Summary: Wild-type human FARS2 catalyzes phenylalanyl-tRNA formation in biochemical comparisons with disease variants. Reason: PMID:22833457, Results on recombinant mutant mtPheRS and Tables 1–3, compares wild-type and variant amino acid activation and tRNA charging. Methods describe purified human recombinant proteins, ATP:pyrophosphate exchange and aminoacylation assays. This directly supports the enzyme activity without assigning downstream neurological or respiratory phenotypes as separate molecular functions. Supporting Evidence: |
| GO:0004826 phenylalanine-tRNA ligase activity | IBA GO_REF:0000033 | ACCEPT | Summary: FARS2 retains ancestral phenylalanine-tRNA ligase activity. Reason: The actual PTHR11538 tree places O95363 at PTN002480027, descending from the GO:0004826 IBD at PTN000165932 (2023-01-10); its aligned sequence reconstructs the complete 451-residue UniProt sequence. The loss annotations at PTN000711660 lie outside this path. Recombinant human mitochondrial PheRS is catalytically active in PMID:10329163 and PMID:19549855. Human O95363 in WITH/FROM is legitimate descendant experimental grounding for the ancestral assertion, not circular propagation. |
| GO:0004826 phenylalanine-tRNA ligase activity | IDA PMID:10329163 Expression and characterization of a human mitochondrial phe... | ACCEPT | Summary: FARS2 catalyzes ATP-dependent phenylalanyl-tRNA formation. Reason: PMID:10329163 directly assayed purified recombinant human mitochondrial PheRS by ATP:pyrophosphate exchange and radiolabeled phenylalanine incorporation into tRNA. Results and Table 1 establish amino acid activation and tRNA charging by a monomeric enzyme. The expressed construct used a predicted mitochondrial processing boundary; no natural isoform or experimentally mapped cleavage site is inferred. Supporting Evidence: |
| GO:0004826 phenylalanine-tRNA ligase activity | IEA GO_REF:0000120 | ACCEPT | Summary: The merged electronic sources identify the experimentally established phenylalanine-tRNA ligase reaction. Reason: The actual IPR004530 target match, RHEA:19413 and EC:6.1.1.20 agree on ATP-dependent esterification of phenylalanine to tRNA(Phe), producing AMP and diphosphate. Direct human mitochondrial enzyme assays in PMID:10329163 and PMID:19549855 support this reaction. The combined mapping is retained as one source context; it does not establish editing or deacylation activity. |
| GO:0004826 phenylalanine-tRNA ligase activity | TAS Reactome:R-HSA-380203 | ACCEPT | Summary: Reactome assigns the phenylalanyl-tRNA synthesis reaction to FARS2. Reason: The inspected target route R-HSA-380203 → catalystActivity 379675 → physicalEntity 379565 explicitly resolves to human O95363 and GO:0004826. The reaction consumes phenylalanine, tRNA(Phe) and ATP and produces charged tRNA, AMP and diphosphate. Its cited PMID:10329163 reports active recombinant human mitochondrial PheRS, with corroborating direct assays in PMID:19549855. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: HI-II-14 reports an interaction between FARS2 and UniProtKB:A1A4E9. Reason: The exact PMID-specific IntAct record EBI-10191452 joins O95363 to A1A4E9. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: HI-II-14 reports an interaction between FARS2 and UniProtKB:O75478. Reason: The exact PMID-specific IntAct record EBI-10191472 joins O95363 to O75478. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: HI-II-14 reports an interaction between FARS2 and UniProtKB:O75558. Reason: The exact PMID-specific IntAct record EBI-10191482 joins O95363 to O75558. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: HI-II-14 reports an interaction between FARS2 and UniProtKB:O95199. Reason: The exact PMID-specific IntAct record EBI-10191492 joins O95363 to O95199. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: HI-II-14 reports an interaction between FARS2 and UniProtKB:P14373. Reason: The exact PMID-specific IntAct record EBI-10191502 joins O95363 to P14373. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: HI-II-14 reports an interaction between FARS2 and UniProtKB:P60370. Reason: The exact PMID-specific IntAct record EBI-10191514 joins O95363 to P60370. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: HI-II-14 reports an interaction between FARS2 and UniProtKB:P60409. Reason: The exact PMID-specific IntAct record EBI-10191524 joins O95363 to P60409. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: HI-II-14 reports an interaction between FARS2 and UniProtKB:P60411. Reason: The exact PMID-specific IntAct record EBI-10191534 joins O95363 to P60411. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: HI-II-14 reports an interaction between FARS2 and UniProtKB:Q12800. Reason: The exact PMID-specific IntAct record EBI-10191544 joins O95363 to Q12800. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: HI-II-14 reports an interaction between FARS2 and UniProtKB:Q13064. Reason: The exact PMID-specific IntAct record EBI-10546338 joins O95363 to Q13064. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: HI-II-14 reports an interaction between FARS2 and UniProtKB:Q13137. Reason: The exact PMID-specific IntAct record EBI-10191564 joins O95363 to Q13137. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: HI-II-14 reports an interaction between FARS2 and UniProtKB:Q15323. Reason: The exact PMID-specific IntAct record EBI-10191576 joins O95363 to Q15323. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: HI-II-14 reports an interaction between FARS2 and UniProtKB:Q6A162. Reason: The exact PMID-specific IntAct record EBI-10191586 joins O95363 to Q6A162. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: HI-II-14 reports an interaction between FARS2 and UniProtKB:Q6NT76. Reason: The exact PMID-specific IntAct record EBI-10569818 joins O95363 to Q6NT76. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: HI-II-14 reports an interaction between FARS2 and UniProtKB:Q6RW13. Reason: The exact PMID-specific IntAct record EBI-10191606 joins O95363 to Q6RW13. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: HI-II-14 reports an interaction between FARS2 and UniProtKB:Q6UY14-3. Reason: The exact PMID-specific IntAct record EBI-10191616 joins O95363 to Q6UY14-3. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: HI-II-14 reports an interaction between FARS2 and UniProtKB:Q7Z3S9. Reason: The exact PMID-specific IntAct record EBI-10191628 joins O95363 to Q7Z3S9. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: HI-II-14 reports an interaction between FARS2 and UniProtKB:Q96DZ9. Reason: The exact PMID-specific IntAct record EBI-10191638 joins O95363 to Q96DZ9. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: HI-II-14 reports an interaction between FARS2 and UniProtKB:Q9BYV2. Reason: The exact PMID-specific IntAct record EBI-10191648 joins O95363 to Q9BYV2. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: HI-II-14 reports an interaction between FARS2 and UniProtKB:Q9UJV3-2. Reason: The exact PMID-specific IntAct record EBI-10191658 joins O95363 to Q9UJV3-2. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: HI-II-14 reports an interaction between FARS2 and UniProtKB:Q9UKG1. Reason: The exact PMID-specific IntAct record EBI-10191670 joins O95363 to Q9UKG1. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: HI-II-14 reports an interaction between FARS2 and UniProtKB:Q9UKT9. Reason: The exact PMID-specific IntAct record EBI-10191680 joins O95363 to Q9UKT9. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: BioPlex reports a FARS2 association with UniProtKB:Q14353 (GAMT). Reason: The exact PMID-specific anti-tag co-immunoprecipitation record EBI-21814498 joins O95363 and Q14353. The original AP-MS workflow supports co-purification, which can be indirect. Retain the existing association as non-core; it does not establish direct binary contact or a role for FARS2 in the partner enzyme’s reaction. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: FARS2 interacts with UniProtKB:Q13137 in the variant-interaction study. Reason: Supplementary Data 2 row 3201 (CALCOCO2 E222K) identify FARS2 by interactor Entrez ID 10667 and score disruption as 0. The Methods compare mutant pairs with positive wild-type interactions, and exact IntAct record EBI-22141157 confirms the human pair. Retain as non-core; these are partner variants, not FARS2 mutations, and no partner-derived function is inferred. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: FARS2 interacts with UniProtKB:Q9UKG1 in the variant-interaction study. Reason: Supplementary Data 2 row 797 (APPL1 E67G) and Data 3 row 67 (APPL1 E643Q) identify FARS2 by interactor Entrez ID 10667 and score disruption as 0. The Methods compare mutant pairs with positive wild-type interactions, and exact IntAct record EBI-22142192 confirms the human pair. Retain as non-core; these are partner variants, not FARS2 mutations, and no partner-derived function is inferred. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:A1L4K1. Reason: The exact PMID-specific IntAct record EBI-24427910 joins O95363 to A1L4K1. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:A8MQ03. Reason: The exact PMID-specific IntAct record EBI-24491435 joins O95363 to A8MQ03. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:A8MV81. Reason: The exact PMID-specific IntAct record EBI-24582464 joins O95363 to A8MV81. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:O43609. Reason: The exact PMID-specific IntAct record EBI-24613160 joins O95363 to O43609. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:O60304. Reason: The exact PMID-specific IntAct record EBI-24654249 joins O95363 to O60304. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:O76011. Reason: The exact PMID-specific IntAct record EBI-23106019 joins O95363 to O76011. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:O95070. Reason: The exact PMID-specific IntAct record EBI-24579745 joins O95363 to O95070. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:O95199. Reason: The exact PMID-specific IntAct record EBI-22782751 joins O95363 to O95199. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:O95429. Reason: The exact PMID-specific IntAct record EBI-23155286 joins O95363 to O95429. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:P07951-2. Reason: The exact PMID-specific IntAct record EBI-24630857 joins O95363 to P07951-2. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:P08247. Reason: The exact PMID-specific IntAct record EBI-24683522 joins O95363 to P08247. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:P60409. Reason: The exact PMID-specific IntAct record EBI-24352404 joins O95363 to P60409. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:P60410. Reason: The exact PMID-specific IntAct record EBI-24297595 joins O95363 to P60410. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:P60411. Reason: The exact PMID-specific IntAct record EBI-24382896 joins O95363 to P60411. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q07627. Reason: The exact PMID-specific IntAct record EBI-24322535 joins O95363 to Q07627. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q10567-3. Reason: The exact PMID-specific IntAct record EBI-24416767 joins O95363 to Q10567-3. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q12933. Reason: The exact PMID-specific IntAct record EBI-22966136 joins O95363 to Q12933. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q13137. Reason: The exact PMID-specific IntAct record EBI-23121037 joins O95363 to Q13137. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q13322-4. Reason: The exact PMID-specific IntAct record EBI-24601678 joins O95363 to Q13322-4. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q14696. Reason: The exact PMID-specific IntAct record EBI-24772425 joins O95363 to Q14696. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q15654. Reason: The exact PMID-specific IntAct record EBI-25247540 joins O95363 to Q15654. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q4G0S7. Reason: The exact PMID-specific IntAct record EBI-25281534 joins O95363 to Q4G0S7. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q5H9J7. Reason: The exact PMID-specific IntAct record EBI-24638359 joins O95363 to Q5H9J7. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q5TD97. Reason: The exact PMID-specific IntAct record EBI-24433767 joins O95363 to Q5TD97. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q6A162. Reason: The exact PMID-specific IntAct record EBI-24312219 joins O95363 to Q6A162. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q6PF18. Reason: The exact PMID-specific IntAct record EBI-23523862 joins O95363 to Q6PF18. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q6RW13-2. Reason: The exact PMID-specific IntAct record EBI-23107315 joins O95363 to Q6RW13-2. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q6ZPD8. Reason: The exact PMID-specific IntAct record EBI-23432472 joins O95363 to Q6ZPD8. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q7Z4V0. Reason: The exact PMID-specific IntAct record EBI-24757369 joins O95363 to Q7Z4V0. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q8N5Z5. Reason: The exact PMID-specific IntAct record EBI-24803867 joins O95363 to Q8N5Z5. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q8N720. Reason: The exact PMID-specific IntAct record EBI-24537077 joins O95363 to Q8N720. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q8N9N5-2. Reason: The exact PMID-specific IntAct record EBI-25291916 joins O95363 to Q8N9N5-2. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q8NA61-2. Reason: The exact PMID-specific IntAct record EBI-24300591 joins O95363 to Q8NA61-2. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q8NI38. Reason: The exact PMID-specific IntAct record EBI-24696372 joins O95363 to Q8NI38. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q8TF50. Reason: The exact PMID-specific IntAct record EBI-24312599 joins O95363 to Q8TF50. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q92824-2. Reason: The exact PMID-specific IntAct record EBI-24594872 joins O95363 to Q92824-2. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q92997. Reason: The exact PMID-specific IntAct record EBI-24422694 joins O95363 to Q92997. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q96DZ9-2. Reason: The exact PMID-specific IntAct record EBI-24332433 joins O95363 to Q96DZ9-2. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q96IF1. Reason: The exact PMID-specific IntAct record EBI-24590708 joins O95363 to Q96IF1. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q96N21. Reason: The exact PMID-specific IntAct record EBI-24745864 joins O95363 to Q96N21. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q96T49. Reason: The exact PMID-specific IntAct record EBI-23983060 joins O95363 to Q96T49. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q99750. Reason: The exact PMID-specific IntAct record EBI-23178015 joins O95363 to Q99750. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q9BQC3. Reason: The exact PMID-specific IntAct record EBI-22802027 joins O95363 to Q9BQC3. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q9BXL8. Reason: The exact PMID-specific IntAct record EBI-24570117 joins O95363 to Q9BXL8. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q9BYR6. Reason: The exact PMID-specific IntAct record EBI-24566777 joins O95363 to Q9BYR6. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q9BYV9. Reason: The exact PMID-specific IntAct record EBI-23167405 joins O95363 to Q9BYV9. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q9H3M0. Reason: The exact PMID-specific IntAct record EBI-23543777 joins O95363 to Q9H3M0. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q9NR34. Reason: The exact PMID-specific IntAct record EBI-24568292 joins O95363 to Q9NR34. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q9UFD9. Reason: The exact PMID-specific IntAct record EBI-24432024 joins O95363 to Q9UFD9. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q9UGI0. Reason: The exact PMID-specific IntAct record EBI-24355874 joins O95363 to Q9UGI0. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q9UJV3-2. Reason: The exact PMID-specific IntAct record EBI-24352285 joins O95363 to Q9UJV3-2. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q9UKG1. Reason: The exact PMID-specific IntAct record EBI-24311685 joins O95363 to Q9UKG1. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q9UKT9. Reason: The exact PMID-specific IntAct record EBI-22801917 joins O95363 to Q9UKT9. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q9ULR0-1. Reason: The exact PMID-specific IntAct record EBI-23720074 joins O95363 to Q9ULR0-1. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports an interaction between FARS2 and UniProtKB:Q9Y680. Reason: The exact PMID-specific IntAct record EBI-25170973 joins O95363 to Q9Y680. Original screening and retesting procedures support a physical interaction; no partner-specific biochemical role for FARS2 is established. Retain as non-core under the project binding convention; source-guide records the assay and historical-accession limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BioPlex reports a FARS2 association with UniProtKB:Q14353 (GAMT). Reason: The exact PMID-specific anti-tag co-immunoprecipitation record EBI-54727449 joins O95363 and Q14353. The original AP-MS workflow supports co-purification, which can be indirect. Retain the existing association as non-core; it does not establish direct binary contact or a role for FARS2 in the partner enzyme’s reaction. Supporting Evidence: |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding is integral to phenylalanine activation by FARS2. Reason: Both actual O95363 matches IPR002319 and IPR004530 map to ATP binding. PMID:10329163 measures ATP:pyrophosphate exchange and ATP-dependent radiolabeled phenylalanine incorporation into tRNA; PMID:19549855 also assays ATP-dependent charging by human mitochondrial PheRS. These data support a catalytic substrate interaction, not ATPase or helicase activity. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | TOO GENERAL | Summary: Cytoplasm is true but subsumed by the positively supported mitochondrial location. Reason: O95363 descends from the GO:0005737 IBD at PTN000165932 (2026-05-28), with no intervening NOT on its actual target path. Cytoplasm includes organelles; the accepted GO:0005739 mitochondrion is a strict is_a/part_of descendant and is positively supported by human MitoCoP measurements (PMID:34800366), the mitochondrial specialization at PTN000165999, and rat Fars2/COXIV colocalization (PMID:26553276). TOO_GENERAL records subsumption of this true ancestral location by the retained organelle assertion. It does not deny the PAINT placement or reinterpret it as cytosol. The cytosolic PheRS complex is assigned at the separate, off-path node PTN000165935. |
| GO:0005737 cytoplasm | IEA GO_REF:0000002 | TOO GENERAL | Summary: The InterPro cytoplasm mapping is true but subsumed by the retained mitochondrial location. Reason: The actual IPR004530 mitochondrial PheRS family match maps to GO:0005737. Cytoplasm includes organelles and differs from GO:0005829 cytosol, which excludes them. Accepted GO:0005739 mitochondrion is a strict is_a/part_of descendant, positively supported by human MitoCoP measurements (PMID:34800366) and rat Fars2/COXIV colocalization (PMID:26553276). TOO_GENERAL marks the broad term as subsumed by that supported location without claiming the InterPro mapping itself resolved a narrower compartment. No separate cytosolic FARS2 activity, localization or natural product is inferred. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: FARS2 is supported as a mitochondrial protein by multiple quantitative proteomics measurements. Reason: PMID:34800366 contains FARS2/O95363 in Table S1B row 334. Its own measurements place it in subtractive Class 1 (Table S2B row 1554), spatial Cluster 1 (S2E row 1760), and TOMM40-importomics Class 1 (S3A row 1233). The mitochondrial cluster assignment also recurs across four cell lines in S2G row 2482. These positive data support mitochondrion; the protein-group measurement and peripheral association in S3C do not resolve a particular natural isoform or submitochondrial compartment. Supporting Evidence: |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: FARS2 belongs to the mitochondrial PheRS clade carrying the mitochondrial-location IBD. Reason: The actual target path passes through PTN000165999, where the GO:0005739 IBD was placed on 2026-05-28, and reaches O95363/PTN002480027 with an exact 451-residue MSA sequence match. No on-path NOT or target-specific loss was found. Rat ortholog Fars2 has direct mitochondrial colocalization evidence in PMID:26553276. This supports the inherited organellar location; it does not convert that experiment into a human matrix-localization assay. |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: The merged electronic localization sources support mitochondrial residence. Reason: The human UniProt record links its mitochondrial location to rat Q6AYQ3, and the merged context also records the rat Ensembl protein and SL-0173. Rat Q6AYQ3 has a mitochondrial IDA annotation and UniProt experimental localization evidence from PMID:26553276, whose rat brain immunostaining shows Fars2/COXIV colocalization. These are related transfer/mapping routes, not independent human localization experiments. The molecular and phylogenetic evidence is consistent with mitochondrial specialization. |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | ACCEPT | Summary: The rat-to-human ortholog transfer of mitochondrial location has positive donor evidence. Reason: Q6AYQ3 is rat Fars2. Its official mitochondrial annotation traces to PMID:26553276, and the recovered original Results and Figure 2 legend report Fars2 colocalization with COXIV in rat cerebellum. This is relevant ortholog evidence for the mitochondrial human PheRS. The accepted manuscript and figure caption were read; figure pixels and supplementary methods were not. The experiment supports mitochondrion, not a measured submitochondrial matrix assignment. |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000044 | ACCEPT | Summary: Mitochondrial matrix is a supported curated localization inference for FARS2. Reason: This electronic row maps the human UniProt SL-0170 location to GO:0005759. The human statement is transferred from rat Q6AYQ3, whose matrix statement is curator inference (ECO:0000305), while its PMID:26553276 experiment demonstrates mitochondria rather than matrix specifically. Retain the matrix placement as an inference consistent with mitochondrial tRNA aminoacylation and the explicit O95363 matrix catalyst in Reactome R-HSA-380203. Do not describe it as an experimentally measured matrix localization or derive an exact transit-peptide cleavage site from it. |
| GO:0005759 mitochondrial matrix | ISS GO_REF:0000024 | ACCEPT | Summary: The ortholog-based matrix assignment is retained with its inferential source boundary. Reason: The source Q6AYQ3 matrix annotation is a UniProt curator inference, not the experimentally supported portion of its mitochondrial-location statement. PMID:26553276 provides positive Fars2/COXIV colocalization in rat, but no inspected matrix-specific assay. The specific matrix inference remains biologically coherent for mitochondrial tRNA aminoacylation and agrees with Reactome physicalEntity 379565 for O95363. Accept the inferred placement without claiming an experimental rat-to-human matrix transfer was verified under the general GO_REF:0000024 method title. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-380203 | ACCEPT | Summary: Reactome places the FARS2 catalyst in the mitochondrial matrix. Reason: The inspected reaction R-HSA-380203 links through catalystActivity 379675 to physicalEntity 379565, which resolves to O95363 and carries GO:0005759. This placement is coherent with the mitochondrial tRNA aminoacylation pathway and UniProt localization inference. PMID:10329163 establishes human enzyme catalysis; its predicted mature construct and heterologous expression do not directly measure cellular matrix residence. Reactome FARS2(1-?) also leaves the processing boundary unknown and does not establish a separate natural isoform. |
| GO:0006418 tRNA aminoacylation for protein translation | TAS Reactome:R-HSA-379726 | ACCEPT | Summary: FARS2 directly catalyzes mitochondrial tRNA aminoacylation for translation. Reason: The actual R-HSA-379726 pathway contains R-HSA-380203, whose O95363 catalyst performs the phenylalanine-tRNA ligation step. Human mitochondrial PheRS directly charges tRNA in PMID:10329163 and PMID:19549855. FARS2 therefore performs the process rather than merely being required for it. This pathway annotation does not claim every pathway reaction or a separate cytosolic translation role. |
| GO:0006432 obsolete phenylalanyl-tRNA aminoacylation | IBA GO_REF:0000033 | MODIFY | Summary: The conserved aminoacylation assertion is correct, but its process term is obsolete. Reason: O95363 descends from the GO:0006432 IBD at PTN000165932 (2025-09-02); the IRD/NOT at PTN000711660 is off-path. Direct human enzyme assays support the inherited aminoacylation function (PMID:10329163; PMID:19549855). The retrieved official QuickGO record explicitly marks GO:0006432 obsolete because it duplicates the molecular function GO:0004826 and states that the biological process is covered by GO:0006418. This is the recorded obsoletion comment, not an invented formal replaced_by relation. Keep the original machine term unchanged and propose the current biological-process term; the phenylalanine specificity remains in the existing catalytic annotations. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000165932 SUPPORTS TRANSFER The actual GO:0006432 IBD (2025-09-02) lies on the O95363 ancestry path, with no on-path NOT. Human biochemical evidence supports the conserved aminoacylation function. MODIFY addresses the officially obsolete vocabulary, not a biological propagation failure; the source machine term is preserved. Proposed replacements: tRNA aminoacylation for protein translation |
| GO:0006432 obsolete phenylalanyl-tRNA aminoacylation | IDA PMID:10329163 Expression and characterization of a human mitochondrial phe... | MODIFY | Summary: The supported process is phenylalanine charging of tRNA for translation. Reason: PMID:10329163 directly establishes aminoacylation. The official QuickGO record marks the imported GO:0006432 obsolete and explains that it duplicated molecular function GO:0004826; the biological process is covered by GO:0006418. Refine the review to that process while preserving the original machine-sourced ID and label. Proposed replacements: tRNA aminoacylation for protein translation Supporting Evidence: |
| GO:0006432 obsolete phenylalanyl-tRNA aminoacylation | IEA GO_REF:0000002 | MODIFY | Summary: The InterPro aminoacylation assertion needs the current translation-associated process term. Reason: The retrieved IPR004530 target family match still maps to GO:0006432, and human enzyme assays establish tRNA aminoacylation (PMID:10329163; PMID:19549855). The retrieved official QuickGO record explicitly marks GO:0006432 obsolete because it duplicates the molecular function GO:0004826 and states that the biological process is covered by GO:0006418. This is the recorded obsoletion comment, not an invented formal replaced_by relation. Keep the original machine term unchanged and propose the current biological-process term; the phenylalanine specificity remains in the existing catalytic annotations. Proposed replacements: tRNA aminoacylation for protein translation |
| GO:0008033 tRNA processing | IDA PMID:10329163 Expression and characterization of a human mitochondrial phe... | MODIFY | Summary: The original experiments establish aminoacylation rather than pre-tRNA maturation. Reason: GO:0008033 defines processing of pre-tRNA into mature tRNA ready for aminoacylation. PMID:10329163 measured amino acid activation and charging of tRNA substrates; its Methods even remove contaminating nuclease before aminoacylation assays. The supported biological process is GO:0006418. This retains the original functional observation without assigning pre-tRNA cleavage or maturation activity. Proposed replacements: tRNA aminoacylation for protein translation Supporting Evidence: |
| GO:0043039 tRNA charging | IEA GO_REF:0000002 | TOO GENERAL | Summary: tRNA charging is true but subsumed by accepted tRNA aminoacylation for protein translation. Reason: IPR002319 is an actual O95363 domain match and maps to GO:0043039, whose current name is tRNA charging. ATP-dependent radiolabeled phenylalanine incorporation into tRNA by recombinant human mitochondrial PheRS establishes charging (PMID:10329163; PMID:19549855). Accepted GO:0006418 tRNA aminoacylation for protein translation is a strict descendant and supplies the relevant biological specificity. TOO_GENERAL marks the broad electronic assertion as true but subsumed by that retained process. |
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Download this section (compressed HTML)Experiment: In human cells, measure amino acids recovered from purified mitochondrial tRNA(Phe) and use targeted mass spectrometry on newly synthesized mitochondrially encoded proteins under basal and defined oxidative-stress conditions. Compare controlled FARS2 depletion and wild-type rescue, with mitochondrial translation output, free amino-acid pools, direct protein oxidation and cytosolic contamination measured as controls. Isotopic substrate tracing should distinguish incorporation during translation from oxidation of phenylalanine residues after synthesis.
Hypothesis: FARS2 can contribute to meta-tyrosine incorporation into mitochondrial translation products when the available meta-tyrosine pool increases.
Type: Cellular aminoacyl-tRNA analysis and isotope-resolved mitochondrial proteomics
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The extent to which FARS2-dependent meta-tyrosyl-tRNA formation contributes to incorporation of meta-tyrosine into mitochondrially encoded proteins in living human cells is not established by the available enzyme experiments.
OPEN BIOLOGY
What is known: PMID:19549855 directly demonstrates meta-tyrosine activation, tRNA charging and substrate binding by human mitochondrial PheRS in vitro. Its charging assays use bacterial or yeast tRNA substrates; the proposed contribution to mitochondrial protein misincorporation is an inference rather than a measurement of FARS2-dependent incorporation in human cells.
Significance: This distinguishes an alternative-substrate property of the enzyme from a physiological route of mitochondrial protein damage.
What would resolve it: Measure meta-tyrosylated mitochondrial tRNA(Phe) and newly synthesized mitochondrial proteins in human cells while resolving FARS2 dependence and controlling amino-acid pools and mitochondrial translation.
Provenance (the field's own admissions):
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