ArgA (PA5204) is the classical bacterial N-acetylglutamate synthase (NAGS, EC 2.3.1.1). It catalyses the first step of L-arginine biosynthesis, the transfer of an acetyl group from acetyl-CoA to L-glutamate to form N-acetyl-L-glutamate. The protein has an N-terminal amino acid kinase (AAK) domain, which binds the feedback inhibitor arginine but is catalytically inactive, and a C-terminal GNAT acetyltransferase domain that carries the active site. Three AAK dimers form a hexameric ring, and this architecture is needed for arginine inhibition; the short interdomain linker tunes arginine sensitivity. The AAK domain is related to N-acetylglutamate kinase (ArgB), the next enzyme of the pathway.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004042 L-glutamate N-acetyltransferase activity, acting on acetyl-CoA as donor | IEA GO_REF:0000120 | ACCEPT | Summary: UniRule/InterPro/RHEA-based NAGS activity. Matches the activity measured in PMID:22447897. Reason: Core catalytic activity, supported by the purified-enzyme assays. Supporting Evidence: PMID:22447897 producing N -acetyl- l -glutamate (NAG) from glutamate and acetyl coenzyme A (acetyl-CoA) and being feedback inhibited by arginine PMID:22447897 30 mM l -glutamate (sodium salt), 4 mM acetyl-CoA, and, when used, the indicated concentrations of arginine hydrochloride file:PSEAE/argA/argA-uniprot.txt Reaction=L-glutamate + acetyl-CoA = N-acetyl-L-glutamate + CoA + H(+) |
| GO:0004358 L-glutamate N-acetyltransferase activity, acting on acetyl-L-ornithine as donor | IBA GO_REF:0000033 | MODIFY | Summary: IBA from the PTN004744913 IBD, seeded only by P. aeruginosa ArgA (PseudoCAP IMP) and E. coli ArgA P0A6C5 (EcoCyc IDA, PMID:16890 and PMID:17651682). GO:0004358 is the ornithine acetyltransferase (ArgJ) reaction, which uses N2-acetyl-L-ornithine as the acetyl donor. Both seed proteins are acetyl-CoA-dependent NAGS enzymes, so both seeds carry the wrong term and the node term is wrong for the clade. Reason: The enzyme class is right but the donor is wrong. The clade (HAMAP MF_01105 ArgA-type NAGS) and this protein use acetyl-CoA, so the correct term is GO:0004042, which the gene already carries by IEA. Propagation Review Root cause: SOURCE BAD Failure modes: SOURCE MISCITATION Sources checked: PANTHER:PTN004744913 · PTN004744913 SOURCE BAD Node term should be GO:0004042; GO:0004358 belongs to the ArgJ family, not ArgA. UniProtKB:P22567 · argA (self; PseudoCAP IMP PMID:22447897) SOURCE BAD Paper assays acetyl-CoA plus glutamate; term choice wrong. UniProtKB:P0A6C5 · E. coli argA (EcoCyc IDA PMID:16890, PMID:17651682) SOURCE BAD E. coli ArgA is acetyl-CoA:glutamate NAGS (UniProt P0A6C5 catalytic activity); same term error. Proposed replacements: L-glutamate N-acetyltransferase activity, acting on acetyl-CoA as donor Supporting Evidence: PMID:22447897 producing N -acetyl- l -glutamate (NAG) from glutamate and acetyl coenzyme A (acetyl-CoA) and being feedback inhibited by arginine PMID:22447897 30 mM l -glutamate (sodium salt), 4 mM acetyl-CoA, and, when used, the indicated concentrations of arginine hydrochloride file:PSEAE/argA/argA-uniprot.txt MF_01105; N_acetyl_glu_synth |
| GO:0004358 L-glutamate N-acetyltransferase activity, acting on acetyl-L-ornithine as donor | IEA GO_REF:0000117 | MODIFY | Summary: ARBA machine-learning row for the ArgJ reaction. Wrong donor for an ArgA-type NAGS, as for the IBA row. Reason: Correct term is GO:0004042 (acetyl-CoA donor), already present from the UniRule/InterPro IEA. Proposed replacements: L-glutamate N-acetyltransferase activity, acting on acetyl-CoA as donor Supporting Evidence: PMID:22447897 producing N -acetyl- l -glutamate (NAG) from glutamate and acetyl coenzyme A (acetyl-CoA) and being feedback inhibited by arginine file:PSEAE/argA/argA-uniprot.txt Reaction=L-glutamate + acetyl-CoA = N-acetyl-L-glutamate + CoA + H(+) |
| GO:0004358 L-glutamate N-acetyltransferase activity, acting on acetyl-L-ornithine as donor | IMP PMID:22447897 Functional dissection of N-acetylglutamate synthase (ArgA) o... | MODIFY | Summary: PseudoCAP IMP and one of the two seeds of the PTN004744913 IBD for GO:0004358. The full text measures NAGS activity of purified wild-type and variant enzymes with L-glutamate and acetyl-CoA; acetyl-L-ornithine is never used. Reason: The paper supports GO:0004042 (acetyl-CoA donor), not the ArgJ reaction GO:0004358. Proposed replacements: L-glutamate N-acetyltransferase activity, acting on acetyl-CoA as donor Supporting Evidence: PMID:22447897 producing N -acetyl- l -glutamate (NAG) from glutamate and acetyl coenzyme A (acetyl-CoA) and being feedback inhibited by arginine PMID:22447897 30 mM l -glutamate (sodium salt), 4 mM acetyl-CoA, and, when used, the indicated concentrations of arginine hydrochloride PMID:22447897 The AAK domain was hexameric and inactive, whereas the GNAT domain was monomeric/dimeric and catalytically active |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Cytoplasm from UniRule/InterPro. ArgA is a soluble biosynthetic enzyme with no signal peptide or membrane segment. Reason: Standard location for a soluble amino acid biosynthetic enzyme in bacteria. Supporting Evidence: file:PSEAE/argA/argA-uniprot.txt MF_01105; N_acetyl_glu_synth |
| GO:0006526 L-arginine biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN004744913 (L-arginine biosynthetic process), seeded by P. aeruginosa ArgA (PseudoCAP) and E. coli ArgA (EcoCyc IMP PMID:1102931, IDA PMID:17651682). The process term is right for the clade. Reason: ArgA catalyses the first committed step of arginine biosynthesis. Supporting Evidence: PMID:22447897 N -acetyl- l -glutamate synthase (NAGS), the enzyme encoded by argA , catalyzes the first step of arginine biosynthesis |
| GO:0006526 L-arginine biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Combined UniRule/InterPro/UniPathway assignment to arginine biosynthesis. Reason: Consistent with the enzyme's established pathway step. Supporting Evidence: PMID:22447897 N -acetyl- l -glutamate synthase (NAGS), the enzyme encoded by argA , catalyzes the first step of arginine biosynthesis file:PSEAE/argA/argA-uniprot.txt MF_01105; N_acetyl_glu_synth |
| GO:0006526 L-arginine biosynthetic process | IMP PMID:22447897 Functional dissection of N-acetylglutamate synthase (ArgA) o... | ACCEPT | Summary: PseudoCAP IMP and seed of the PTN004744913 IBD for the process. The paper characterises the enzyme that catalyses the first step of arginine biosynthesis, including its feedback inhibition by arginine. The evidence is biochemical rather than a mutant phenotype, but the participation claim is correct. Reason: Sound seed for the claim: ArgA performs the first step of the pathway. IDA would describe the evidence better than IMP; that does not affect the IBD. Supporting Evidence: PMID:22447897 N -acetyl- l -glutamate synthase (NAGS), the enzyme encoded by argA , catalyzes the first step of arginine biosynthesis PMID:22447897 producing N -acetyl- l -glutamate (NAG) from glutamate and acetyl coenzyme A (acetyl-CoA) and being feedback inhibited by arginine |
| GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO from the GNAT domain. Correct in kind but generic, and GO:0004042 is not under it in the current ontology. Reason: Refine to the specific activity GO:0004042 that the evidence supports. Proposed replacements: L-glutamate N-acetyltransferase activity, acting on acetyl-CoA as donor Supporting Evidence: PMID:22447897 producing N -acetyl- l -glutamate (NAG) from glutamate and acetyl coenzyme A (acetyl-CoA) and being feedback inhibited by arginine PMID:22447897 The AAK domain was hexameric and inactive, whereas the GNAT domain was monomeric/dimeric and catalytically active |
| GO:0042802 identical protein binding | IPI PMID:22447897 Functional dissection of N-acetylglutamate synthase (ArgA) o... | KEEP AS NON CORE | Summary: IntAct self-interaction. ArgA forms a hexameric ring of AAK-domain dimers, which is needed for arginine inhibition. Reason: Real homo-oligomerisation that serves allosteric regulation rather than being a function in itself. Supporting Evidence: PMID:22447897 the hexameric architecture appears to be essential for arginine inhibition |
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