arg6 (SPBC725.14) encodes the mitochondrial N-acetylglutamate synthase (NAGS, EC 2.3.1.1) of fission yeast, the ortholog of S. cerevisiae ARG2. It transfers the acetyl group of acetyl-CoA to L-glutamate to form N-acetyl-L-glutamate, the first committed step of the acetylated ornithine route of L-ornithine and L-arginine biosynthesis. The protein has an N-terminal mitochondrial transit peptide, an amino-acid-kinase-like domain and a C-terminal vertebrate-like GNAT acetyltransferase domain, and localises to mitochondria. arg6 mutants require arginine. Note that S. pombe arg6 is not the ortholog of the S. cerevisiae ARG6 part of the ARG5,6 polyprotein (S. pombe arg11).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004042 L-glutamate N-acetyltransferase activity, acting on acetyl-CoA as donor | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for acetyl-CoA-dependent glutamate N-acetyltransferase (NAGS) activity at node PTN000597387, with S. cerevisiae ARG2 (SGD:S000003607), human NAGS (Q8N159), mouse and zebrafish NAGS as sources. Reason: arg6 is in the fungal mitochondrial NAGS subfamily (PTHR23342:SF4) together with ARG2, carries the fungal NAGS (IPR011190) and GNAT domains, and its loss causes arginine auxotrophy; the inherited activity is the core function. No purified S. pombe Arg6 assay was established in the sources consulted here. Supporting Evidence: file:SCHPO/arg6/arg6-uniprot.txt Reaction=L-glutamate + acetyl-CoA = N-acetyl-L-glutamate + CoA + H(+); file:SCHPO/arg6/arg6-uniprot.txt N-acetylglutamate synthase involved in arginine biosynthesis. |
| GO:0004042 L-glutamate N-acetyltransferase activity, acting on acetyl-CoA as donor | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA from InterPro IPR011190 (fungal N-acetylglutamate synthase) and Rhea 24292 (L-glutamate + acetyl-CoA = N-acetyl-L-glutamate + CoA). Reason: The family signature and reaction mapping both give the correct NAGS activity for this protein. Supporting Evidence: file:SCHPO/arg6/arg6-uniprot.txt Reaction=L-glutamate + acetyl-CoA = N-acetyl-L-glutamate + CoA + H(+); |
| GO:0005739 mitochondrion | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: arg6 has supported mitochondrial localization; the matrix assertion is retained separately. Reason: The curated HDA assignment is from the fission-yeast ORFeome localization screen. The linked UniProt location and other target evidence are compatible; the screen-level quotation alone does not distinguish matrix from other mitochondrial subcompartments. The root-organelle policy preserves mitochondrion as an informative claim. Matrix localization was checked and remains a separate annotation, with its own experimental or inference basis. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins file:SCHPO/arg6/arg6-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:16823372}. |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: arg6 has supported mitochondrial localization; the matrix assertion is retained separately. Reason: The electronic compartment assignment agrees with the publication-linked curated target localization and existing experimental mitochondrial annotations. Its source stops at the organelle and is retained at that level. The root-organelle policy preserves mitochondrion as an informative claim. Matrix localization was checked and remains a separate annotation, with its own experimental or inference basis. Supporting Evidence: file:SCHPO/arg6/arg6-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:16823372}. |
| GO:0005759 mitochondrial matrix | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for mitochondrial matrix at node PTN000597386 (sources S. pombe arg11, S. cerevisiae ARG5,6 and ARG2). Reason: Fungal NAGS works in the matrix with acetylglutamate kinase; arg6 has a transit peptide and is mitochondrial, and the PomBase GO-CAM 6690711d00000916 also places arg6 NAGS in the matrix. Supporting Evidence: file:SCHPO/arg6/arg6-uniprot.txt FT TRANSIT 1..19 file:SCHPO/arg6/arg6-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:16823372}. |
| GO:0006526 L-arginine biosynthetic process | EXP PMID:17248775 Genetic Mapping in SCHIZOSACCHAROMYCES POMBE by Mitotic and ... | ACCEPT | Summary: PomBase EXP from the 1977 S. pombe genetic mapping paper (Kohli et al.), which mapped auxotrophic markers; only the abstract is cached and it does not name arg6. Reason: arg6 is a classical arginine-requiring locus; the curator read the full text, the annotation is fully consistent with the NAGS activity, and there is no reason to doubt it. Supporting Evidence: PMID:17248775 118 genetic markers have been assigned to 3 linkage groups |
| GO:0006526 L-arginine biosynthetic process | EXP PMID:32896087 Mitochondrial respiration is required to provide amino acids... | ACCEPT | Summary: PomBase EXP from the genome-wide deletion-library screen for arginine auxotrophs (Malecki et al. 2020); arg6 deletion was among the arginine-biosynthesis mutants recovered. Reason: Loss-of-function evidence that arg6 is required for arginine synthesis, consistent with its position as the first enzyme of the pathway. Supporting Evidence: PMID:32896087 As expected, these arginine‐auxotroph mutants included those with impaired arginine biosynthesis. |
| GO:0006526 L-arginine biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for L-arginine biosynthetic process at node PTN000597373 (sources include E. coli ArgB, S. cerevisiae ARG2 and ARG5,6, S. pombe arg11 and arg6 itself). Reason: arg6 appears among its own sources because it carries experimental annotation; the IBA adds that the role is inherited. Correct core process. Supporting Evidence: file:SCHPO/arg6/arg6-uniprot.txt N-acetylglutamate synthase involved in arginine biosynthesis. |
| GO:0006526 L-arginine biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA from ARBA00026424 and UniPathway UPA00068 (L-arginine biosynthesis). Reason: Correct process for NAGS. Supporting Evidence: file:SCHPO/arg6/arg6-uniprot.txt PATHWAY: Amino-acid biosynthesis; L-arginine biosynthesis; N(2)-acetyl- |
| GO:0006592 L-ornithine biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for L-ornithine biosynthetic process at node PTN001155505 (source S. cerevisiae ARG2). Reason: NAGS catalyses the first step of the acetylated route that produces ornithine, which in S. pombe also supplies ferrichrome synthesis; consistent with the yeast ARG2 review. Supporting Evidence: file:SCHPO/arg6/arg6-uniprot.txt PATHWAY: Amino-acid biosynthesis; L-arginine biosynthesis; N(2)-acetyl- |
| GO:0097054 L-glutamate biosynthetic process | NAS GO_REF:0000051 | REMOVE | Summary: PomBase NAS from S. pombe keyword mapping to L-glutamate biosynthetic process. Reason: Directionally wrong: NAGS consumes L-glutamate (acetylating it to N-acetyl-L-glutamate); it does not synthesise glutamate. The term is not supported by the catalysed reaction or by any cited experiment. Supporting Evidence: file:SCHPO/arg6/arg6-uniprot.txt Reaction=L-glutamate + acetyl-CoA = N-acetyl-L-glutamate + CoA + H(+); |
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Download this section (compressed HTML)Q: Does S. pombe arg6 require the arg11 acetylglutamate kinase domain for activity, i.e. does it form a NAGS/NAGK complex (GO:0106098) as S. cerevisiae Arg2 does with Arg5,6?
Q: Is the GO:0097054 L-glutamate biosynthetic process NAS from keyword mapping intended to capture 'glutamate family amino acid metabolism'? As worded it reverses the direction of the reaction.
Experiment: Assay acetyl-CoA:glutamate N-acetyltransferase activity in mitochondrial extracts of wild-type and arg6 deletion strains, including arginine feedback inhibition, and test co-immunoprecipitation with arg11.
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