Ass (CG1315) encodes the Drosophila argininosuccinate synthase (citrulline--aspartate ligase), a type 1 argininosuccinate synthase that condenses L-citrulline with L-aspartate in an ATP-dependent reaction to form 2-(N-omega-L-arginino)succinate, AMP and diphosphate. With argininosuccinate lyase (Argl) it converts citrulline back to L-arginine in the cytosol, where the enzyme is expected to act as a homotetramer. Flies are not known to possess a complete ornithine-urea cycle, so this pathway is thought to serve arginine recycling, for instance from the citrulline co-product of nitric oxide synthase, rather than urea production.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000050 urea cycle | IEA GO_REF:0000041 | REMOVE | Summary: UniPathway-based mapping of argininosuccinate synthase to the urea cycle. Reason: The mapping assumes a vertebrate-type hepatic urea cycle. Insects make only one arginase whose role is not ammonia detoxification, and Drosophila is not known to have the carbamoyl-phosphate/ornithine transcarbamylase arm needed to run the cycle. In flies Ass acts in the citrulline-to-arginine segment (L-arginine biosynthetic process), which is already annotated. Treated consistently with the urea-cycle IEA on Arg. A comparative analysis of 150 insect genomes found ornithine carbamoyltransferase absent from all of them, so no insect can run the urea cycle. Supporting Evidence: PMID:10878001 Most organisms, including insects, produce only one type of arginase, whose function is not centered on ammonia detoxification. PMID:40081835 no insect can synthesize arginine via the urea cycle, as ornithine carbamoyltransferase is absent from all genomes analysed |
| GO:0004055 argininosuccinate synthase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Argininosuccinate synthase activity inferred from the PANTHER family node. Reason: Ass is the single fly member of the argininosuccinate synthase family (PTHR11587), type 1 subfamily, with both ARGININOSUCCIN_SYN PROSITE signatures and conserved ATP-binding motif; the IBA placement is sound. Supporting Evidence: file:DROME/Ass/Ass-uniprot.txt DR PROSITE; PS00564; ARGININOSUCCIN_SYN_1; 1. file:DROME/Ass/Ass-uniprot.txt DR PANTHER; PTHR11587; ARGININOSUCCINATE SYNTHASE; 1. |
| GO:0004055 argininosuccinate synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Argininosuccinate synthase activity from combined IEA methods (EC 6.3.4.5). Reason: Consistent with the IBA and the family assignment. Supporting Evidence: file:DROME/Ass/Ass-uniprot.txt EC=6.3.4.5; |
| GO:0004055 argininosuccinate synthase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Argininosuccinate synthase activity transferred by FlyBase from human ASS1. Reason: Core activity; well-founded ortholog transfer. Supporting Evidence: file:DROME/Ass/Ass-uniprot.txt Reaction=L-citrulline + L-aspartate + ATP = 2-(N(omega)-L- |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding from InterPro mapping. Reason: ATP is a substrate of the ligase reaction and the N-terminal ATP-binding loop (residues 9-17) is conserved. Accurate but subsumed by the catalytic activity. Supporting Evidence: file:DROME/Ass/Ass-uniprot.txt Reaction=L-citrulline + L-aspartate + ATP = 2-(N(omega)-L- |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Cytosol, phylogenetic inference. Reason: Argininosuccinate synthase is a cytosolic enzyme throughout the family and the fly protein lacks targeting signals. Supporting Evidence: file:DROME/Ass/Ass-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: Cytosol, from UniProt subcellular-location mapping. Reason: Consistent with the IBA. Supporting Evidence: file:DROME/Ass/Ass-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol |
| GO:0005829 cytosol | ISS GO_REF:0000024 | ACCEPT | Summary: Cytosol, transferred from human ASS1 by FlyBase. Reason: Consistent with the IBA. Supporting Evidence: file:DROME/Ass/Ass-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol |
| GO:0006526 L-arginine biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: L-arginine biosynthetic process, phylogenetic inference. Reason: Ass catalyses the first of the two steps converting citrulline to arginine; in flies this serves arginine regeneration from citrulline but remains an arginine-forming route. Supporting Evidence: file:DROME/Ass/Ass-uniprot.txt PATHWAY: Amino-acid biosynthesis; L-arginine biosynthesis; L-arginine PMID:40081835 the citrulline produced by NOS cannot be converted back to arginine in several insects due to the loss of argininosuccinate synthase and argininosuccinate lyase genes |
| GO:0006526 L-arginine biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: L-arginine biosynthetic process from combined IEA methods. Reason: Consistent with the IBA. Supporting Evidence: file:DROME/Ass/Ass-uniprot.txt PATHWAY: Amino-acid biosynthesis; L-arginine biosynthesis; L-arginine |
| GO:0006526 L-arginine biosynthetic process | ISS GO_REF:0000024 | ACCEPT | Summary: L-arginine biosynthetic process transferred from human ASS1 by FlyBase. Reason: Consistent with the IBA. Supporting Evidence: file:DROME/Ass/Ass-uniprot.txt PATHWAY: Amino-acid biosynthesis; L-arginine biosynthesis; L-arginine |
| GO:0008652 amino acid biosynthetic process | IEA GO_REF:0000117 | MODIFY | Summary: Amino acid biosynthetic process from ARBA rule. Reason: Correct but a general parent; MODIFY to L-arginine biosynthetic process, which Ass already carries (IBA, IEA, ISS). Proposed replacements: L-arginine biosynthetic process Supporting Evidence: file:DROME/Ass/Ass-uniprot.txt PATHWAY: Amino-acid biosynthesis; L-arginine biosynthesis; L-arginine |
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Download this section (compressed HTML)Q: Does Drosophila Ass recycle the citrulline produced by nitric oxide synthase, and is its expression co-regulated with Nos in neurons or immune tissues?
Experiment: Trace 13C/15N-citrulline into arginine in control versus Ass-knockdown larvae to quantify the contribution of the Ass-Argl route to the arginine pool.
Argininosuccinate synthase (Ass) encodes an enzyme that is predicted to catalyze the condensation of L- citrulline, a by-product of nitric oxide formation, and L-aspartate to form L-argininosuccinate. Ass is probably involved in L-arginine biosynthesis.
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