Arg (CG18104) encodes the single arginase of Drosophila melanogaster, a binuclear manganese ureohydrolase of the arginase family that hydrolyses L-arginine to L-ornithine and urea. The gene, which harbours the elav locus within its third intron, is expressed mainly from late embryogenesis onward, with embryonic transcripts concentrated in the fat body. Insects such as Drosophila make only one arginase and lack a complete hepatic-type urea cycle, so the enzyme is thought to act mainly in arginine catabolism and in supplying ornithine for proline and polyamine synthesis rather than in ammonia detoxification. Its N-terminus resembles a mitochondrial presequence, consistent with a mitochondrial matrix location, and a truncating loss-of-function allele is viable but causes a developmental delay.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000050 urea cycle | IEA GO_REF:0000041 | REMOVE | Summary: UniPathway-based mapping of arginase to the urea cycle. Reason: Arginase catalyses the final step of the vertebrate hepatic urea cycle, but the mapping assumes the presence of that cycle. Drosophila, like other insects, produces only one arginase whose role is not centred on ammonia detoxification, and flies are not ureotelic in the vertebrate sense (nitrogen is excreted mainly as uric acid). Without the upstream carbamoyl-phosphate/ornithine transcarbamylase arm, annotating the fly enzyme to the urea cycle process is an electronic over-propagation; the arginase activity and L-arginine catabolism terms capture the real function. 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:0004053 arginase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Arginase activity, inferred phylogenetically from the arginase family node. Reason: Arg is the sole Drosophila member of the arginase subfamily (PTHR43782:SF3) and conserves the binuclear manganese-binding residues of the ureohydrolase fold; the IBA node placement is sound and the fly protein was originally identified as a predicted arginase with 40% identity to vertebrate arginases. Supporting Evidence: PMID:10878001 A Drosophila gene encoding a 351-amino acid-long predicted arginase (40% identity with vertebrate arginases) is reported. file:DROME/Arg/Arg-uniprot.txt Catalyzes the hydrolysis of L-arginine into urea and L- |
| GO:0004053 arginase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Arginase activity from combined IEA methods (EC 3.5.3.1, InterPro arginase family). Reason: Consistent with the IBA and ISS annotations and with the conserved arginase domain. Supporting Evidence: file:DROME/Arg/Arg-uniprot.txt DR InterPro; IPR014033; Arginase. |
| GO:0004053 arginase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Arginase activity transferred by FlyBase curators from rat arginase. Reason: Core molecular function of the gene product; the sequence-similarity transfer is well founded. Supporting Evidence: PMID:10878001 A Drosophila cDNA encoding a predicted arginase was isolated. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasm, phylogenetic inference from the arginase family. Reason: Cytoplasm is the most specific compartment the evidence supports. Whether the single fly arginase works in the mitochondrion (its N-terminus resembles a presequence) or in the cytosol (as the fungal seeds of the cytosol IBA) is unresolved, and both lie within the cytoplasm. The support is family membership; the protein belongs to the arginase family, whose characterized members are intracellular (cytosolic in fungi and vertebrate ARG1, mitochondrial in vertebrate ARG2; the manganese study names arginase as a mitochondrial enzyme in general terms, not for the fly protein). The fly record has no SUBCELLULAR LOCATION comment and no SIGNAL or TRANSMEM features, so nothing points to a secretory or membrane location. There is no fly localization assay. Supporting Evidence: file:DROME/Arg/Arg-uniprot.txt SIMILARITY: Belongs to the arginase family. file:DROME/Arg/Arg-uniprot.txt PANTHER; PTHR43782; ARGINASE; 1. PMID:31799578 three mitochondrial enzymes: superoxide dismutase (Sod2), arginase |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | UNDECIDED | Summary: Mitochondrion, transferred from human ARG2. Reason: Insects have a single arginase that, like vertebrate extrahepatic ARG2, is not a urea-cycle enzyme, and the Drosophila protein has an arginine/lysine-rich N-terminal extension lacking acidic residues that resembles a mitochondrial presequence. However, that reading is from inspection of the sequence only (no targeting-prediction run), the manganese study mentions arginase among mitochondrial enzymes without testing the fly protein, and the deep research finds no fly evidence separating a mitochondrial from a cytosolic location. As with the competing cytosol IBA, this is left undecided pending localisation data. Supporting Evidence: PMID:31799578 three mitochondrial enzymes: superoxide dismutase (Sod2), arginase file:DROME/Arg/Arg-uniprot.txt MWWSRKFASR SLRLHRLKST |
| GO:0005829 cytosol | IBA GO_REF:0000033 | UNDECIDED | Summary: Cytosol, phylogenetic inference seeded mainly by fungal arginases. Reason: The cytosol IBA node (PTN000144387) is supported largely by yeast Car1 and fission-yeast arginases, which are cytosolic. The Drosophila protein has a presequence-like N-terminus suggesting mitochondrial import, and no fly localisation data exist to decide whether a cytosolic pool also exists (for example via an alternative start). Left undecided pending localisation data. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000144387 SOURCE WEAK OR INFERRED Cytosol node seeded mainly by fungal arginases (S. cerevisiae CAR1, S. pombe), which are cytosolic; whether the fly arginase, which has a presequence-like N-terminus, retains a cytosolic pool is untested. Supporting Evidence: file:DROME/Arg/Arg-uniprot.txt MWWSRKFASR SLRLHRLKST |
| GO:0006525 arginine metabolic process | IBA GO_REF:0000033 | MODIFY | Summary: Arginine metabolic process, phylogenetic inference. Reason: Correct but general; arginase hydrolyses arginine, so MODIFY to L-arginine catabolic process, which Arg already carries (ISS). Proposed replacements: L-arginine catabolic process Supporting Evidence: file:DROME/Arg/Arg-uniprot.txt Catalyzes the hydrolysis of L-arginine into urea and L- |
| GO:0006525 arginine metabolic process | IEA GO_REF:0000002 | MODIFY | Summary: Arginine metabolic process from InterPro arginase family mapping. Reason: Correct but general for an arginase-family enzyme; MODIFY to L-arginine catabolic process, which Arg already carries (ISS). Proposed replacements: L-arginine catabolic process Supporting Evidence: file:DROME/Arg/Arg-uniprot.txt DR InterPro; IPR014033; Arginase. |
| GO:0006527 L-arginine catabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: L-arginine catabolic process, transferred from human ARG1. Reason: Hydrolysis of L-arginine to ornithine and urea is the first step of arginine catabolism, and this is the main role ascribed to the single insect arginase. Supporting Evidence: PMID:10878001 Most organisms, including insects, produce only one type of arginase, whose function is not centered on ammonia detoxification. PMID:40081835 all insects (except some Hemiptera) can degrade it to ornithine and urea, as the arginase (ARG) gene is conserved across the orders analysed |
| GO:0030145 manganese ion binding | IBA GO_REF:0000033 | ACCEPT | Summary: Manganese ion binding, phylogenetic inference. Reason: Arginases are binuclear Mn(2+) metalloenzymes; the Mn-ligating residues are conserved in the fly protein. Supporting Evidence: file:DROME/Arg/Arg-uniprot.txt Note=Binds 2 manganese ions per subunit. |
| GO:0046872 metal ion binding | IEA GO_REF:0000002 | MODIFY | Summary: Metal ion binding from InterPro ureohydrolase mapping. Reason: Correct but less specific; arginase has a binuclear manganese centre, so MODIFY to manganese ion binding, which Arg already carries (IBA). Proposed replacements: manganese ion binding Supporting Evidence: file:DROME/Arg/Arg-uniprot.txt Note=Binds 2 manganese ions per subunit. |
| GO:0140734 ammonium excretion | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Ammonium excretion, transferred from Aedes aegypti arginase. Reason: The mosquito source annotation reflects a blood-feeding-specific nitrogen disposal physiology. There is no evidence that Drosophila arginase contributes to ammonium excretion; arginase itself releases urea rather than ammonium, and the single insect arginase is not considered a nitrogen-detoxification enzyme. Arg mutant flies are viable with only a developmental delay. Supporting Evidence: PMID:10878001 Most organisms, including insects, produce only one type of arginase, whose function is not centered on ammonia detoxification. |
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Download this section (compressed HTML)Q: Is Drosophila arginase exclusively mitochondrial, or does an alternative translation start or isoform produce a cytosolic pool, as the cytosol IBA would imply?
Q: Does Arg compete with nitric oxide synthase for arginine in fly tissues, and does its ornithine output feed proline or polyamine synthesis in the fat body?
Experiment: Tag endogenous Arg (C-terminal knock-in) and co-stain with a mitochondrial matrix marker in fat body and gut to determine its subcellular localisation.
Experiment: Measure arginine, ornithine and urea in Arg loss-of-function larvae by metabolomics to define the in vivo flux through arginase.
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Download this section (compressed HTML)Arginase (Arg) encodes an enzyme that converts arginine into ornithine. Lack of Arg produces a developmental embryonic delay.
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