ARG5,6

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003942 N-acetyl-gamma-glutamyl-phosphate reductase (NADP+) activity	IBA GO_REF:0000033	ACCEPT	Summary: N-acetyl-gamma-glutamyl-phosphate reductase activity of the C-terminal (ARG5) moiety. Core function. Supporting Evidence: file:yeast/ARG5,6/ARG5,6-uniprot.txt Reaction=N-acetyl-L-glutamate 5-semialdehyde + phosphate + NADP(+) = N-acetyl-L-glutamyl 5-phosphate + NADPH + H(+);
GO:0003942 N-acetyl-gamma-glutamyl-phosphate reductase (NADP+) activity	IDA PMID:1851947 Characterization of the yeast ARG5,6 gene: determination of ...	ACCEPT	Summary: ARG5,6 shown to encode acetylglutamyl-P reductase. Core function. Supporting Evidence: PMID:1851947 the ARG5,6 gene encodes acetylglutamyl-P reductase and acetylglutamate kinase, two arginine anabolic enzymes which are localized in the mitochondria
GO:0003942 N-acetyl-gamma-glutamyl-phosphate reductase (NADP+) activity	IEA GO_REF:0000120	ACCEPT	Summary: Automated EC/RHEA assignment; correct. Core function. Supporting Evidence: file:yeast/ARG5,6/ARG5,6-uniprot.txt Reaction=N-acetyl-L-glutamate 5-semialdehyde + phosphate + NADP(+) = N-acetyl-L-glutamyl 5-phosphate + NADPH + H(+);
GO:0003942 N-acetyl-gamma-glutamyl-phosphate reductase (NADP+) activity	RCA GO_REF:0000123	ACCEPT	Summary: YeastPathways assignment; correct. Supporting Evidence: file:yeast/ARG5,6/ARG5,6-uniprot.txt Reaction=N-acetyl-L-glutamate 5-semialdehyde + phosphate + NADP(+) = N-acetyl-L-glutamyl 5-phosphate + NADPH + H(+);
GO:0003991 acetylglutamate kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: Acetylglutamate kinase activity of the N-terminal (ARG6) moiety. Core function. Supporting Evidence: file:yeast/ARG5,6/ARG5,6-uniprot.txt Reaction=N-acetyl-L-glutamate + ATP = N-acetyl-L-glutamyl 5-phosphate + ADP;
GO:0003991 acetylglutamate kinase activity	IDA PMID:1851947 Characterization of the yeast ARG5,6 gene: determination of ...	ACCEPT	Summary: ARG5,6 shown to encode acetylglutamate kinase. Core function. Supporting Evidence: PMID:1851947 the ARG5,6 gene encodes acetylglutamyl-P reductase and acetylglutamate kinase, two arginine anabolic enzymes which are localized in the mitochondria
GO:0003991 acetylglutamate kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Automated EC/RHEA assignment; correct. Core function. Supporting Evidence: file:yeast/ARG5,6/ARG5,6-uniprot.txt Reaction=N-acetyl-L-glutamate + ATP = N-acetyl-L-glutamyl 5-phosphate + ADP;
GO:0003991 acetylglutamate kinase activity	RCA GO_REF:0000123	ACCEPT	Summary: YeastPathways assignment; correct. Supporting Evidence: file:yeast/ARG5,6/ARG5,6-uniprot.txt Reaction=N-acetyl-L-glutamate + ATP = N-acetyl-L-glutamyl 5-phosphate + ADP;
GO:0005737 cytoplasm	IEA GO_REF:0000002	MODIFY	Summary: The cytoplasm annotation is compatible with the more specific supported cellular compartment. Reason: Cytoplasm includes the relevant organelle/cytosolic compartment in GO. Refine this broad true term to mitochondrial matrix, supported by the combined localization evidence; do not call the broad term a contradictory location or infer tag interference without examining the original images. Proposed replacements: mitochondrial matrix Supporting Evidence: PMID:1851947 the ARG5,6 gene encodes acetylglutamyl-P reductase and acetylglutamate kinase, two arginine anabolic enzymes which are localized in the mitochondria
GO:0005739 mitochondrion	HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen...	ACCEPT	Summary: ARG5,6 has supported mitochondrial localization; the matrix assertion is retained separately. Reason: The curated HDA row derives from the PROMITO mitochondrial proteome. It establishes an organelle-level location; the general dataset quotation is not by itself a target-specific matrix assay. 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:16823961 A total of 851 different proteins (PROMITO dataset) were identified
GO:0005739 mitochondrion	HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph...	ACCEPT	Summary: ARG5,6 has supported mitochondrial localization; the matrix assertion is retained separately. Reason: The curated HDA row derives from quantitative proteomics of isolated yeast mitochondria. Retain the organelle observation without treating the study-wide quotation as direct matrix resolution. 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:24769239 we performed an overall quantitative proteomic and phosphoproteomic study of isolated mitochondria
GO:0005739 mitochondrion	IEA GO_REF:0000120	ACCEPT	Summary: ARG5,6 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: PMID:16823961 A total of 851 different proteins (PROMITO dataset) were identified
GO:0005759 mitochondrial matrix	IBA GO_REF:0000033	ACCEPT	Summary: Mitochondrial matrix location; consistent with experimental data. Supporting Evidence: PMID:1851947 the ARG5,6 gene encodes acetylglutamyl-P reductase and acetylglutamate kinase, two arginine anabolic enzymes which are localized in the mitochondria
GO:0005759 mitochondrial matrix	IDA PMID:1851947 Characterization of the yeast ARG5,6 gene: determination of ...	ACCEPT	Summary: Both enzymes localised to mitochondria; curator assigned matrix from the full text. Supporting Evidence: PMID:1851947 the ARG5,6 gene encodes acetylglutamyl-P reductase and acetylglutamate kinase, two arginine anabolic enzymes which are localized in the mitochondria
GO:0005759 mitochondrial matrix	IEA GO_REF:0000117	ACCEPT	Summary: Mitochondrial matrix; correct. Supporting Evidence: PMID:1851947 the ARG5,6 gene encodes acetylglutamyl-P reductase and acetylglutamate kinase, two arginine anabolic enzymes which are localized in the mitochondria
GO:0005829 cytosol	RCA GO_REF:0000123	REMOVE	Summary: YeastPathways-derived (GO_REF:0000123) location assigning activity to the cytosol. This enzyme of the acetylated (ornithine-producing) part of the yeast arginine pathway is a mitochondrial matrix protein, shown by subcellular fractionation and by the cleaved mitochondrial presequence; the cytosol term contradicts the experimental location data. Reason: PMID:205532 explicitly included acetylglutamate kinase and acetylglutamyl-phosphate reductase among the measured activities restricted to particulate fractions, distinguished from the soluble downstream arginine-pathway enzymes. This is direct biochemical compartment discrimination for the target activity, not rejection from a targeting peptide or absence of a cytosolic database entry. It supports rejecting the pathway-derived cytosolic assignment under the measured native conditions; it does not prove that no precursor molecule or minor conditional pool can ever occur outside mitochondria. Unlike ARG7, no target-specific pre-import autocatalysis is established in the inspected evidence. PMID:1649049 additionally links processing into its two mature enzymes to mitochondrial import; this differs from Arg7 self-cleavage before targeting. Supporting Evidence: PMID:205532 These enzymes were exclusively particulate. PMID:205532 suggested that these enzymes were associated with the mitochondria PMID:1649049 import of the ARG5/ARG6 precursor into the mitochondria is required for its processing into two mature enzymes.
GO:0006355 regulation of DNA-templated transcription	IMP PMID:15486299 Regulation of gene expression by a metabolic enzyme.	KEEP AS NON CORE	Summary: Moonlighting role: Arg5,6 was identified in a proteome-array DNA-binding screen, associates with specific nuclear and mitochondrial loci by ChIP, and its deletion alters transcript levels of target genes. The experimental annotation is retained, but this is not the core metabolic function, the mechanism is not established, and the deletion phenotype could partly be indirect (arginine auxotrophy). Deferring to the curator on the full text. Supporting Evidence: PMID:15486299 Chromatin immunoprecipitation experiments revealed that Arg5,6 is associated with specific nuclear and mitochondrial loci in vivo PMID:15486299 Deletion of Arg5,6 causes altered transcript levels of both nuclear and mitochondrial target genes.
GO:0006526 L-arginine biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Steps 2 and 3 of arginine biosynthesis. Core process. Supporting Evidence: PMID:1851947 the ARG5,6 gene encodes acetylglutamyl-P reductase and acetylglutamate kinase, two arginine anabolic enzymes which are localized in the mitochondria
GO:0006526 L-arginine biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Automated pathway assignment; correct. Supporting Evidence: PMID:1851947 the ARG5,6 gene encodes acetylglutamyl-P reductase and acetylglutamate kinase, two arginine anabolic enzymes which are localized in the mitochondria
GO:0006526 L-arginine biosynthetic process	RCA GO_REF:0000123	ACCEPT	Summary: YeastPathways assignment; correct. Supporting Evidence: PMID:1851947 the ARG5,6 gene encodes acetylglutamyl-P reductase and acetylglutamate kinase, two arginine anabolic enzymes which are localized in the mitochondria
GO:0006526 L-arginine biosynthetic process	TAS PMID:12603335 The N-acetylglutamate synthase/N-acetylglutamate kinase meta...	ACCEPT	Summary: Arg5,6 kinase in the NAGS/NAGK metabolon controlling flux of the first steps of arginine biosynthesis. Supporting Evidence: PMID:12603335 the NAGS/NAGK metabolon promotes the co-ordination of the catalytic activities and feedback regulation of the first two, flux controlling, enzymes of the arginine pathway
GO:0006592 L-ornithine biosynthetic process	TAS PMID:1851947 Characterization of the yeast ARG5,6 gene: determination of ...	ACCEPT	Summary: The kinase and reductase steps are part of the acetylated route producing ornithine. Supporting Evidence: PMID:1851947 the ARG5,6 gene encodes acetylglutamyl-P reductase and acetylglutamate kinase, two arginine anabolic enzymes which are localized in the mitochondria
GO:0008652 amino acid biosynthetic process	IEA GO_REF:0000117	MODIFY	Summary: Very general ARBA-derived process term (amino acid / carboxylic acid biosynthesis). Correct but uninformative; the specific process is L-arginine biosynthesis, which is already annotated. Reason: Replace the grouping term with the specific pathway term. Proposed replacements: L-arginine biosynthetic process Supporting Evidence: PMID:1851947 the ARG5,6 gene encodes acetylglutamyl-P reductase and acetylglutamate kinase, two arginine anabolic enzymes which are localized in the mitochondria
GO:0016620 oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor	IEA GO_REF:0000002	MODIFY	Summary: Parent oxidoreductase term derived from the semialdehyde dehydrogenase NAD(P)-binding domain; the specific activity is the NADP-dependent N-acetyl-gamma-glutamyl-phosphate reductase. Reason: Replace with the specific activity term. Proposed replacements: N-acetyl-gamma-glutamyl-phosphate reductase (NADP+) activity Supporting Evidence: file:yeast/ARG5,6/ARG5,6-uniprot.txt Reaction=N-acetyl-L-glutamate 5-semialdehyde + phosphate + NADP(+) = N-acetyl-L-glutamyl 5-phosphate + NADPH + H(+);
GO:0046394 carboxylic acid biosynthetic process	IEA GO_REF:0000117	MODIFY	Summary: Very general ARBA-derived process term (amino acid / carboxylic acid biosynthesis). Correct but uninformative; the specific process is L-arginine biosynthesis, which is already annotated. Reason: Replace the grouping term with the specific pathway term. Proposed replacements: L-arginine biosynthetic process Supporting Evidence: PMID:1851947 the ARG5,6 gene encodes acetylglutamyl-P reductase and acetylglutamate kinase, two arginine anabolic enzymes which are localized in the mitochondria
GO:0051287 NAD binding	IEA GO_REF:0000002	MODIFY	Summary: The supported reductase cofactor is NADP(H); refine the generic-domain-derived NAD assignment. Reason: The proximate source InterPro:IPR000534 is a broad semialdehyde-dehydrogenase nucleotide-binding domain. Target-specific catalytic annotation specifies NADP(H). Replace NAD binding with the independently supported NADP+ binding term already present here; this does not claim that an unreported NAD-binding experiment proved absolute exclusion. Proposed replacements: NADP+ binding Supporting Evidence: file:yeast/ARG5,6/ARG5,6-uniprot.txt Reaction=N-acetyl-L-glutamate 5-semialdehyde + phosphate + NADP(+) = N-acetyl-L-glutamyl 5-phosphate + NADPH + H(+);
GO:0070401 NADP+ binding	IEA GO_REF:0000002	ACCEPT	Summary: NADP(H) cofactor binding is intrinsic to the core catalytic reaction. Reason: This experimentally established or conserved substrate/cofactor interaction is part of the core enzyme mechanism. Being required for catalysis or already implied by a catalytic activity does not make it a peripheral function. Supporting Evidence: file:yeast/ARG5,6/ARG5,6-uniprot.txt Reaction=N-acetyl-L-glutamate 5-semialdehyde + phosphate + NADP(+) = N-acetyl-L-glutamyl 5-phosphate + NADPH + H(+);
GO:0106098 NAGS/NAGK complex	IPI PMID:11553611 A new yeast metabolon involving at least the two first enzym...	NEW	Summary: Proposed reciprocal complex annotation. The acetylglutamate kinase chain derived from Arg5,6 was identified by microsequencing as the protein co-immunoprecipitating with HA-tagged Arg2, and the ascomycete-specific C-terminal domain of the kinase is required for synthase activity. GOA has the NAGS/NAGK complex on ARG2 (IPI, same paper) but not on Arg5,6; the kinase is a structural and catalytic member of the complex, so the membership applies to it as well. Reason: Retain the existing NEW complex-membership annotation because the kinase chain was directly identified by microsequencing in the Arg2 co-immunoprecipitate. This is positive physical membership evidence, not merely an inference from the partner having the annotation. PMID:12603335 establishes that the kinase-associated domain, but not the reductase, is required for NAGS support. Supporting Evidence: PMID:11553611 hemagglutinin-tagged synthase coprecipitated with a protein proven by microsequencing to be the kinase PMID:12603335 we demonstrate that the ascomycete-specific domain is required to maintain synthase activity and protein level

Gene Description

Existing Annotations Review

Core Functions

N-acetylglutamate kinase (EC 2.7.2.8; ARG6 moiety): ATP-dependent phosphorylation of N-acetyl-L-glutamate, step 2 of arginine biosynthesis, feedback-inhibited by arginine and acting in the mitochondrial matrix in complex with Arg2 (NAGS).

N-acetyl-gamma-glutamyl-phosphate reductase (EC 1.2.1.38; ARG5 moiety): NADPH-dependent reduction of N-acetylglutamyl phosphate to N-acetylglutamate semialdehyde, step 3 of arginine biosynthesis, in the mitochondrial matrix.

References

Deep Research

SGD

SGD gene description for ARG5,6 (yeast)

📚 Additional Documentation

Notes

📄 View Raw YAML