arg41

UniProt ID: P50514
Organism: Schizosaccharomyces pombe 972h-
Review Status: COMPLETE
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Gene Description

arg41 (SPBC1539.03c; UniProt gene name argx) encodes an argininosuccinate lyase (EC 4.3.2.1) of the lyase 1 family, orthologous to S. cerevisiae ARG4. It cleaves 2-(N-omega-L-arginino)succinate into L-arginine and fumarate, the final step of arginine biosynthesis, and acts in the cytosol. S. pombe has a second argininosuccinate lyase paralog, arg7 (SPBC1773.14); deletion of arg41 causes arginine auxotrophy whereas deletion of arg7 does not, showing a requirement for arg41 under the tested conditions, without quantifying the relative catalytic flux through the two paralogs. The catalytic activity is inferred from sequence; it has not been assayed for the purified S. pombe protein.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000050 urea cycle
IC
GO_REF:0000111
KEEP AS NON CORE
Summary: This enzyme performs a shared ornithine-to-arginine reaction within the fungal arginine/urea reaction network.
Reason: Live GO:0000050 defines ornithine-to-arginine synthesis followed by arginine cleavage to urea and regenerated ornithine; it does not require a ureotelic organism or nitrogen excretion. The target has the annotated OTC/ASS/ASL reaction and native fungal arginase supplies the return chemistry. Retain the existing process annotation as a contextual role, without asserting measured net full-cycle flux or a metazoan detoxification function. The primary role remains arginine biosynthesis. PMID:20435771 directly measures S. pombe Car1/Car3 arginase activity and urea production.
Supporting Evidence:
PMID:20435771
arginase catalyzes the degradation of arginine into urea and ornithine.
GO:0000050 urea cycle
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: This enzyme performs a shared ornithine-to-arginine reaction within the fungal arginine/urea reaction network.
Reason: Live GO:0000050 defines ornithine-to-arginine synthesis followed by arginine cleavage to urea and regenerated ornithine; it does not require a ureotelic organism or nitrogen excretion. The target has the annotated OTC/ASS/ASL reaction and native fungal arginase supplies the return chemistry. Retain the existing process annotation as a contextual role, without asserting measured net full-cycle flux or a metazoan detoxification function. The primary role remains arginine biosynthesis. PMID:20435771 directly measures S. pombe Car1/Car3 arginase activity and urea production.
Supporting Evidence:
PMID:20435771
arginase catalyzes the degradation of arginine into urea and ornithine.
GO:0003824 catalytic activity
IEA
GO_REF:0000002
MODIFY
Summary: InterPro2GO (IPR008948 L-aspartase-like, IPR020557 fumarate lyase signature) mapping to catalytic activity.
Reason: Uninformative root-level term; the specific activity is argininosuccinate lyase.
Proposed replacements: argininosuccinate lyase activity
Supporting Evidence:
file:SCHPO/arg41/arg41-uniprot.txt
Reaction=2-(N(omega)-L-arginino)succinate = fumarate + L-arginine;
file:SCHPO/arg41/arg41-uniprot.txt
SIMILARITY: Belongs to the lyase 1 family. Argininosuccinate lyase
GO:0004056 argininosuccinate lyase activity
IBA
GO_REF:0000033
ACCEPT
Summary: PAINT IBA for argininosuccinate lyase (node PTN000154674) with S. cerevisiae ARG4, rat Asl and the S. pombe paralog arg7 among sources.
Reason: arg41 retains the lyase 1 catalytic residues and is genetically required for arginine synthesis.
Supporting Evidence:
file:SCHPO/arg41/arg41-uniprot.txt
Reaction=2-(N(omega)-L-arginino)succinate = fumarate + L-arginine;
PMID:32896087
arg7 is one of two argininosuccinate lyases (with deletion of the other one, arg41, showing arginine auxotrophy)
GO:0004056 argininosuccinate lyase activity
IEA
GO_REF:0000120
ACCEPT
Summary: InterPro (IPR009049) / Rhea 24020 / EC 4.3.2.1 mapping to argininosuccinate lyase activity.
Reason: Correct activity.
Supporting Evidence:
file:SCHPO/arg41/arg41-uniprot.txt
Reaction=2-(N(omega)-L-arginino)succinate = fumarate + L-arginine;
GO:0005829 cytosol
HDA
PMID:16823372
ORFeome cloning and global analysis of protein localization ...
ACCEPT
Summary: Cytosolic signal for arg41 in the ORFeome localisation screen.
Reason: Consistent with the cytosolic final steps of fungal arginine biosynthesis.
Supporting Evidence:
PMID:16823372
we determined the localization of 4,431 proteins
GO:0005829 cytosol
IBA
GO_REF:0000033
ACCEPT
Summary: PAINT IBA for cytosol (S. cerevisiae ARG4 source).
Reason: Correct, corroborated by HDA.
Supporting Evidence:
PMID:16823372
we determined the localization of 4,431 proteins
GO:0006526 L-arginine biosynthetic process
EXP
PMID:32896087
Mitochondrial respiration is required to provide amino acids...
ACCEPT
Summary: Malecki et al. 2020 report that deletion of arg41, but not of its paralog arg7, causes arginine auxotrophy.
Reason: Direct deletion phenotype establishes a requirement for arg41 under the tested growth conditions; it does not quantify its share of total lyase activity or negate independently supported arg7 function.
Supporting Evidence:
PMID:32896087
arg7 is one of two argininosuccinate lyases (with deletion of the other one, arg41, showing arginine auxotrophy)
GO:0006526 L-arginine biosynthetic process
IBA
GO_REF:0000033
ACCEPT
Summary: PAINT IBA for L-arginine biosynthetic process (node PTN000154674); arg41 (SPBC1539.03c) itself is among the sources.
Reason: Correct and experimentally grounded.
Supporting Evidence:
PMID:32896087
arg7 is one of two argininosuccinate lyases (with deletion of the other one, arg41, showing arginine auxotrophy)
GO:0006526 L-arginine biosynthetic process
IEA
GO_REF:0000120
ACCEPT
Summary: ARBA/InterPro/UniPathway mapping to L-arginine biosynthetic process.
Reason: Correct pathway.
Supporting Evidence:
file:SCHPO/arg41/arg41-uniprot.txt
Reaction=2-(N(omega)-L-arginino)succinate = fumarate + L-arginine;

Core Functions

Cytosolic argininosuccinate lyase cleaving argininosuccinate to L-arginine and fumarate, the last step of arginine biosynthesis; the paralog whose deletion causes arginine auxotrophy under the conditions examined in PMID:32896087. Same core function as S. cerevisiae ARG4.

Directly Involved In:
Cellular Locations:
Supporting Evidence:
  • file:SCHPO/arg41/arg41-uniprot.txt
    Reaction=2-(N(omega)-L-arginino)succinate = fumarate + L-arginine;
  • PMID:32896087
    arg7 is one of two argininosuccinate lyases (with deletion of the other one, arg41, showing arginine auxotrophy)
  • PMID:16823372
    we determined the localization of 4,431 proteins

References

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Suggested Questions for Experts

Q: What is the role of the second argininosuccinate lyase paralog arg7, whose deletion does not cause auxotrophy: redundant low-level activity, a different expression condition, or a divergent function?

Q: How much native argininosuccinate lyase flux is carried by Arg41 versus Arg7 under different growth conditions? The deletion phenotype establishes a condition-specific requirement, while the catalytic assignment also relies on conserved lyase architecture and phylogenetic inference.

Suggested Experiments

Experiment: Assay argininosuccinate lyase activity in extracts of arg41 and arg7 single and double deletions, and test complementation of arg41 deletion by arg7 overexpression.

πŸ“š Additional Documentation

Notes

(arg41-notes.md)

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