arg11

UniProt ID: P31318
Organism: Schizosaccharomyces pombe 972h-
Review Status: COMPLETE
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Gene Description

arg11 (SPAC4G9.09c) encodes the S. pombe acetylglutamate kinase / N-acetyl-gamma-glutamyl-phosphate reductase precursor, the ortholog of S. cerevisiae ARG5,6. The 885-residue polyprotein carries an N-terminal mitochondrial transit peptide, an N-terminal acetylglutamate kinase (EC 2.7.2.8) region and a C-terminal NADPH-dependent N-acetylglutamyl-phosphate reductase (EC 1.2.1.38) region, and is thought to be cleaved into the two separate enzymes in the mitochondrial matrix. Together they catalyse steps 2 and 3 of the acetylated ornithine route: phosphorylation of N-acetyl-L-glutamate and reduction of N-acetyl-L-glutamyl 5-phosphate to N-acetyl-L-glutamate 5-semialdehyde. The kinase is the arginine feedback-inhibited step. arg11 mutants are arginine auxotrophs. The name is a nomenclature trap: S. pombe arg11 is not the ortholog of S. cerevisiae ARG11, which encodes the mitochondrial ornithine carrier ORT1.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0003942 N-acetyl-gamma-glutamyl-phosphate reductase (NADP+) activity
IBA
GO_REF:0000033 		ACCEPT
Summary: PAINT IBA for N-acetyl-gamma-glutamyl-phosphate reductase (node PTN001155520) with S. cerevisiae ARG5,6 and arg11 itself among sources; arg11's presence reflects its own experimental annotation.
Reason: The C-terminal region is an NAGSA dehydrogenase (ArgC type 1) domain; activity is experimentally supported for arg11.
Supporting Evidence:
file:SCHPO/arg11/arg11-uniprot.txt
Reaction=N-acetyl-L-glutamate 5-semialdehyde + phosphate + NADP(+) = N-acetyl-L-glutamyl 5-phosphate + NADPH + H(+);
PMID:1313366
The acetylglutamate kinase and acetylglutamate-phosphate reductase domains have been defined by their identity with the S. cerevisiae ARG5,6 protein.
GO:0003942 N-acetyl-gamma-glutamyl-phosphate reductase (NADP+) activity
IEA
GO_REF:0000120 		ACCEPT
Summary: ARBA/InterPro (IPR000706, IPR023013) mapping to N-acetyl-gamma-glutamyl-phosphate reductase.
Reason: Correct activity of the C-terminal domain.
Supporting Evidence:
file:SCHPO/arg11/arg11-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
IMP
PMID:1313366
Cloning and sequencing of arg3 and arg11 genes of Schizosacc... 		ACCEPT
Summary: Van Huffel et al. 1992 cloned arg11 by complementation of an arg11 mutant and defined the kinase and reductase domains; UniProt cites this paper for the EC 1.2.1.38 activity (abstract-only in cache).
Reason: Deferred to the curator, who read the full text; consistent with domain architecture and orthology to ARG5,6.
Supporting Evidence:
PMID:1313366
carbamoyltransferase (arg3) and acetylglutamate kinase/acetylglutamyl-phosphate
PMID:1313366
The acetylglutamate kinase and acetylglutamate-phosphate reductase domains have been defined by their identity with the S. cerevisiae ARG5,6 protein.
GO:0003991 acetylglutamate kinase activity
EXP
PMID:1313366
Cloning and sequencing of arg3 and arg11 genes of Schizosacc... 		ACCEPT
Summary: Experimental acetylglutamate kinase annotation from Van Huffel et al. 1992; UniProt cites the paper for EC 2.7.2.8 with experimental evidence (enzyme data in full text, not in the cached abstract).
Reason: Deferred to the curator; the N-terminal region is an acetylglutamate kinase domain identical in architecture to ARG5,6.
Supporting Evidence:
PMID:1313366
carbamoyltransferase (arg3) and acetylglutamate kinase/acetylglutamyl-phosphate
file:SCHPO/arg11/arg11-uniprot.txt
Reaction=N-acetyl-L-glutamate + ATP = N-acetyl-L-glutamyl 5-phosphate + ADP;
GO:0003991 acetylglutamate kinase activity
IBA
GO_REF:0000033 		ACCEPT
Summary: PAINT IBA for acetylglutamate kinase (node PTN000597373), sources include ARG5,6, Arabidopsis NAGK and arg11 itself.
Reason: Correct, experimentally grounded activity.
Supporting Evidence:
file:SCHPO/arg11/arg11-uniprot.txt
Reaction=N-acetyl-L-glutamate + ATP = N-acetyl-L-glutamyl 5-phosphate + ADP;
GO:0003991 acetylglutamate kinase activity
IEA
GO_REF:0000120 		ACCEPT
Summary: ARBA/InterPro (IPR011241) / Rhea 14629 mapping to acetylglutamate kinase activity.
Reason: Correct activity of the N-terminal domain.
Supporting Evidence:
file:SCHPO/arg11/arg11-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:
file:SCHPO/arg11/arg11-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion {ECO:0000305|PubMed:1313366}.
PMID:1313366
The acetylglutamate kinase and acetylglutamate-phosphate reductase domains have been defined by their identity with the S. cerevisiae ARG5,6 protein.
GO:0005739 mitochondrion
HDA
PMID:16823372
ORFeome cloning and global analysis of protein localization ... 		ACCEPT
Summary: arg11 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
GO:0005739 mitochondrion
IEA
GO_REF:0000120 		ACCEPT
Summary: arg11 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/arg11/arg11-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion {ECO:0000305|PubMed:1313366}.
GO:0005759 mitochondrial matrix
IBA
GO_REF:0000033 		ACCEPT
Summary: PAINT IBA for mitochondrial matrix from the fungal ARG5,6 clade (S. cerevisiae ARG5,6 and ARG2 among sources, plus arg11).
Reason: Matrix localization is supported by the fungal targeting/localization evidence. Internal cleavage is demonstrated for budding-yeast Arg5,6; processing of S. pombe Arg11 remains a curated family inference.
Supporting Evidence:
file:SCHPO/arg11/arg11-uniprot.txt
PTM: The protein precursor is probably cleaved into the two
file:SCHPO/arg11/arg11-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion {ECO:0000305|PubMed:1313366}.
GO:0005759 mitochondrial matrix
IDA
PMID:1313366
Cloning and sequencing of arg3 and arg11 genes of Schizosacc... 		ACCEPT
Summary: Mitochondrial targeting of the arg11 translation product (Van Huffel et al. 1992; title reports mitochondrial targeting of both arg3 and arg11 products).
Reason: Experimental localisation; deferred to the curator for the matrix-level detail in the full text.
Supporting Evidence:
PMID:1313366
Heterologous expression and mitochondrial targeting of their translation products.
GO:0005759 mitochondrial matrix
IEA
GO_REF:0000117 		ACCEPT
Summary: ARBA (ARBA00028628) mapping to mitochondrial matrix.
Reason: Correct location.
Supporting Evidence:
file:SCHPO/arg11/arg11-uniprot.txt
PTM: The protein precursor is probably cleaved into the two
GO:0006526 L-arginine biosynthetic process
EXP
PMID:32896087
Mitochondrial respiration is required to provide amino acids... 		ACCEPT
Summary: Genome-wide arginine-auxotrophy screen of the deletion collection (Malecki et al. 2020); arg11 deletion recorded as arginine-requiring.
Reason: Consistent with the classical arg11 mutant phenotype.
Supporting Evidence:
PMID:32896087
This screen identified 31 mutants that grew substantially better when supplemented with arginine
PMID:32896087
eight were identified in our screen
GO:0006526 L-arginine biosynthetic process
IBA
GO_REF:0000033 		ACCEPT
Summary: PAINT IBA for L-arginine biosynthetic process (node PTN000597373) with arg11 and arg6 among sources.
Reason: Correct and experimentally grounded.
Supporting Evidence:
file:SCHPO/arg11/arg11-uniprot.txt
Reaction=N-acetyl-L-glutamate + ATP = N-acetyl-L-glutamyl 5-phosphate + ADP;
GO:0006526 L-arginine biosynthetic process
IEA
GO_REF:0000120 		ACCEPT
Summary: InterPro/UniPathway (UPA00068) mapping to L-arginine biosynthetic process.
Reason: Correct pathway.
Supporting Evidence:
file:SCHPO/arg11/arg11-uniprot.txt
L-ornithine from L-glutamate: step 2/4. {ECO:0000305|PubMed:1313366}.
GO:0006526 L-arginine biosynthetic process
IMP
PMID:1313366
Cloning and sequencing of arg3 and arg11 genes of Schizosacc... 		ACCEPT
Summary: arg11 mutants are arginine auxotrophs complemented by the cloned gene (Van Huffel et al. 1992).
Reason: Direct genetic evidence.
Supporting Evidence:
PMID:1313366
were cloned by functional complementation of S. pombe arg3 and
GO:0008652 amino acid biosynthetic process
IEA
GO_REF:0000117 		MODIFY
Summary: ARBA (ARBA00027355) generic amino acid biosynthetic process.
Reason: Uninformative parent; the pathway is L-arginine biosynthesis.
Proposed replacements: L-arginine biosynthetic process
Supporting Evidence:
PMID:1313366
carbamoyltransferase (arg3) and acetylglutamate kinase/acetylglutamyl-phosphate
GO:0016620 oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor
IEA
GO_REF:0000002 		MODIFY
Summary: InterPro2GO (IPR000534, semialdehyde dehydrogenase NAD-binding domain) mapping to the generic aldehyde-oxidoreductase (NAD or NADP acceptor) class.
Reason: Correct class but the specific activity of the reductase domain is N-acetyl-gamma-glutamyl-phosphate reductase (NADP+).
Supporting Evidence:
file:SCHPO/arg11/arg11-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: ARBA (ARBA00027883) carboxylic acid biosynthetic process.
Reason: Very general; replace with L-arginine biosynthetic process.
Proposed replacements: L-arginine biosynthetic process
Supporting Evidence:
PMID:1313366
carbamoyltransferase (arg3) and acetylglutamate kinase/acetylglutamyl-phosphate
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:SCHPO/arg11/arg11-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:SCHPO/arg11/arg11-uniprot.txt
Reaction=N-acetyl-L-glutamate 5-semialdehyde + phosphate + NADP(+) = N-acetyl-L-glutamyl 5-phosphate + NADPH + H(+);

Core Functions

Acetylglutamate kinase (N-terminal region of the arg11 precursor): ATP-dependent phosphorylation of N-acetyl-L-glutamate in the mitochondrial matrix, the arginine-feedback-regulated step 2 of ornithine synthesis. Same core function as the kinase half of S. cerevisiae ARG5,6.

Molecular Function:
acetylglutamate kinase activity
Directly Involved In:
L-arginine biosynthetic process
Cellular Locations:
mitochondrial matrix
Supporting Evidence:
  • file:SCHPO/arg11/arg11-uniprot.txt
    Reaction=N-acetyl-L-glutamate + ATP = N-acetyl-L-glutamyl 5-phosphate + ADP;
  • PMID:1313366
    The acetylglutamate kinase and acetylglutamate-phosphate reductase domains have been defined by their identity with the S. cerevisiae ARG5,6 protein.
  • file:SCHPO/arg11/arg11-uniprot.txt
    ACTIVITY REGULATION: The kinase activity is inhibited by arginine.

N-acetyl-gamma-glutamyl-phosphate reductase (C-terminal region of the arg11 precursor): NADPH-dependent reduction of N-acetyl-L-glutamyl 5-phosphate to N-acetyl-L-glutamate 5-semialdehyde, step 3 of ornithine synthesis in the mitochondrial matrix.

Molecular Function:
N-acetyl-gamma-glutamyl-phosphate reductase (NADP+) activity
Directly Involved In:
L-arginine biosynthetic process
Cellular Locations:
mitochondrial matrix
Supporting Evidence:
  • file:SCHPO/arg11/arg11-uniprot.txt
    Reaction=N-acetyl-L-glutamate 5-semialdehyde + phosphate + NADP(+) = N-acetyl-L-glutamyl 5-phosphate + NADPH + H(+);
  • PMID:1313366
    The acetylglutamate kinase and acetylglutamate-phosphate reductase domains have been defined by their identity with the S. cerevisiae ARG5,6 protein.
  • PMID:1313366
    were cloned by functional complementation of S. pombe arg3 and

References

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Suggested Questions for Experts

Q: Does S. pombe arg11-derived acetylglutamate kinase form a NAGS/NAGK metabolon with arg6, as ARG5,6 does with ARG2 in S. cerevisiae?

Q: Why does arg11 fail to complement S. cerevisiae arg5,6 (and vice versa): processing, import, or partner specificity?

Suggested Experiments

Experiment: Co-immunoprecipitate arg11 kinase chain with arg6 from mitochondrial extracts, and test whether arg6 N-acetylglutamate synthase activity depends on arg11.

📚 Additional Documentation

Notes

(arg11-notes.md)

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