met7 (SPBC1709.17; UniProt O74742; the fission yeast MET7 ortholog) encodes folylpolyglutamate synthase (EC 6.3.2.17), which adds gamma-linked glutamates to tetrahydrofolates. Polyglutamylation keeps folates inside the cell and organelles and makes them better cofactors for one-carbon enzymes. By orthology, met7 mutants need methionine because the methionine synthase step requires polyglutamyl 5-methyl-THF. The protein is cytoplasmic in localisation screens and is expected to have a mitochondrial pool as well.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004326 tetrahydrofolylpolyglutamate synthase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference from characterised FPGS (S. cerevisiae MET7); sound. Reason: No S. pombe biochemistry is cached; the activity rests on family membership (UniProt SIMILARITY and the PROSITE folylpolyglutamate synthase signatures) and on UniProt's curated by-similarity function statement (ECO:0000250), which match the PAINT node seeded by experimentally characterised FPGS enzymes (S. cerevisiae MET7, human and plant FPGS). Supporting Evidence: file:SCHPO/met7/met7-uniprot.txt Catalyzes conversion of folates to polyglutamate derivatives file:SCHPO/met7/met7-uniprot.txt Belongs to the folylpolyglutamate synthase family. file:SCHPO/met7/met7-uniprot.txt PROSITE; PS01011; FOLYLPOLYGLU_SYNT_1; 1. |
| GO:0004326 tetrahydrofolylpolyglutamate synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: EC/InterPro/ARBA mapping; consistent. Reason: The mapping rests in part on InterPro folylpolyglutamate synthase signatures, which the record carries; with the curated by-similarity function statement (ECO:0000250) this supports the FPGS activity, although no S. pombe assay is cached. Supporting Evidence: file:SCHPO/met7/met7-uniprot.txt InterPro; IPR001645; Folylpolyglutamate_synth. file:SCHPO/met7/met7-uniprot.txt Catalyzes conversion of folates to polyglutamate derivatives |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: ATP is a cosubstrate of the folylpolyglutamate synthase reaction; binding is subsidiary to the core ligase activity. Reason: ATP binding is inherent to the ATP-dependent glutamate ligation catalysed by met7. The ATP-binding residues are curated by similarity to E. coli FolC (P08192), and the curated reaction consumes ATP; no S. pombe experiment addresses it directly. Supporting Evidence: file:SCHPO/met7/met7-uniprot.txt FT BINDING 70..73 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P08192" file:SCHPO/met7/met7-uniprot.txt L-glutamate + ATP = (6S)-5,6,7,8-tetrahydrofolyl-(gamma-L-Glu)(n+1) + ADP + phosphate |
| GO:0005634 nucleus | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | KEEP AS NON CORE | Summary: ORFeome YFP screen recorded nuclear signal for met7. Soluble metabolic enzymes often show diffuse nucleocytoplasmic signal in this screen; no nuclear role is known. Reason: Experimental HDA kept, but not part of the core function. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0005737 cytoplasm | HDA PMID:10759889 Large-scale screening of intracellular protein localization ... | ACCEPT | Summary: GFP-fusion library screen: cytoplasm. Supporting Evidence: PMID:10759889 we constructed a green fluorescent protein (GFP)-fusion genomic DNA library of S. pombe |
| GO:0005737 cytoplasm | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: ORFeome screen: cytoplasm. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of location; agrees with the localisation screen. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: ARBA/UniProt mapping; consistent. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of mitochondrial location; FPGS acts in both cytosol and mitochondria (S. cerevisiae Met7 has both pools). Reason: The mitochondrial location is by similarity only. UniProt curates mitochondrial inner membrane and matrix locations by similarity (ECO:0000250), and the protein falls in the PANTHER mitochondrial FPGS subfamily (PTHR11136:SF5). The S. pombe GFP/YFP screens (PMID:10759889, PMID:16823372) report cytoplasm and nucleus, not mitochondria. The organelle claim is kept on the phylogenetic inference, at the root organelle term. Supporting Evidence: file:SCHPO/met7/met7-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000250} file:SCHPO/met7/met7-uniprot.txt PANTHER; PTHR11136:SF5; FOLYLPOLYGLUTAMATE SYNTHASE, MITOCHONDRIAL; 1. |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt location mapping (mitochondrial inner membrane), curated by similarity; the sub-mitochondrial location has not been shown for S. pombe met7. Reason: The inner-membrane location rests only on a by-similarity UniProt curation (ECO:0000250, no named donor); S. pombe localization experiments (PMID:10759889, PMID:16823372) place met7 in the cytoplasm, and no S. pombe assay resolves a sub-mitochondrial location. Retained as a peripheral, inferred location. Supporting Evidence: file:SCHPO/met7/met7-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000250} |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt location mapping (mitochondrial matrix), curated by similarity; the sub-mitochondrial location has not been shown for S. pombe met7. Reason: The matrix location rests only on a by-similarity UniProt curation (ECO:0000250, no named donor); S. pombe localization experiments (PMID:10759889, PMID:16823372) place met7 in the cytoplasm, and no S. pombe assay resolves a sub-mitochondrial location. Retained as a peripheral, inferred location. Supporting Evidence: file:SCHPO/met7/met7-uniprot.txt Mitochondrion matrix {ECO:0000250}. |
| GO:0005829 cytosol | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: ORFeome YFP screen placed met7 in the cytosol, consistent with a soluble metabolic enzyme. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of location; agrees with the localisation screen. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0006730 one-carbon metabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: Curator transfer of one-carbon metabolism from S. cerevisiae MET7: polyglutamylation retains folates and makes them better cofactors. Reason: UniProt's curated by-similarity function statement (ECO:0000250) places FPGS products as the cofactors of folate-dependent one-carbon transfer enzymes; S. pombe evidence is by similarity to S. cerevisiae MET7 only. Supporting Evidence: file:SCHPO/met7/met7-uniprot.txt substrates for most of the folate-dependent enzymes that are involved in one-carbon transfer reactions |
| GO:0009396 folic acid-containing compound biosynthetic process | IEA GO_REF:0000002 | TOO GENERAL | Summary: Broad parent of tetrahydrofolylpolyglutamate biosynthetic process, which is asserted in this review. Reason: True but uninformative. By similarity to characterized folylpolyglutamate synthases (curated ECO:0000250 function) and by membership of the folylpolyglutamate synthase family (InterPro IPR001645), met7 polyglutamylates folates; the specific process GO:0046901 tetrahydrofolylpolyglutamate biosynthetic process is asserted in this review. Supporting Evidence: file:SCHPO/met7/met7-uniprot.txt Catalyzes conversion of folates to polyglutamate derivatives allowing concentration of folate compounds in the cell file:SCHPO/met7/met7-uniprot.txt PATHWAY: Cofactor biosynthesis; tetrahydrofolylpolyglutamate biosynthesis. |
| GO:0016881 acid-amino acid ligase activity | IEA GO_REF:0000002 | MODIFY | Summary: Generic InterPro-derived parent of the specific tetrahydrofolylpolyglutamate synthase activity, which is already annotated. Reason: Correct but too general. met7 belongs to the folylpolyglutamate synthase family (InterPro IPR001645, NCBIfam TIGR01499 folC), and its curated reaction is ATP-dependent addition of L-glutamate to tetrahydrofolyl-polyglutamate, i.e. GO:0004326, which the gene already carries (IBA, IEA). The evidence is family membership and similarity, not an S. pombe enzyme assay. Proposed replacements: tetrahydrofolylpolyglutamate synthase activity Supporting Evidence: file:SCHPO/met7/met7-uniprot.txt Reaction=(6S)-5,6,7,8-tetrahydrofolyl-(gamma-L-Glu)(n) + L-glutamate + ATP = (6S)-5,6,7,8-tetrahydrofolyl-(gamma-L-Glu)(n+1) + ADP + phosphate + H(+) file:SCHPO/met7/met7-uniprot.txt IPR001645; Folylpolyglutamate_synth. file:SCHPO/met7/met7-uniprot.txt TIGR01499; folC |
| GO:0046901 tetrahydrofolylpolyglutamate biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference; consistent. Reason: Follows from the FPGS activity, which rests on family membership and UniProt's curated by-similarity function statement (ECO:0000250); no S. pombe pathway data are cached. Supporting Evidence: file:SCHPO/met7/met7-uniprot.txt Catalyzes conversion of folates to polyglutamate derivatives file:SCHPO/met7/met7-uniprot.txt Belongs to the folylpolyglutamate synthase family. |
| GO:0046901 tetrahydrofolylpolyglutamate biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway mapping; consistent. Reason: The UniPathway assignment follows from the FPGS activity, which rests on family membership and UniProt's curated by-similarity function statement (ECO:0000250). Supporting Evidence: file:SCHPO/met7/met7-uniprot.txt Catalyzes conversion of folates to polyglutamate derivatives file:SCHPO/met7/met7-uniprot.txt Belongs to the folylpolyglutamate synthase family. |
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