ura1 (SPAC22G7.06c) encodes the fission yeast pyrimidine-specific multifunctional GLNase/CPSase-ATCase protein (2244 aa), the ortholog of S. cerevisiae URA2 and of the CPSase/ATCase portions of animal CAD. A glutamine amidotransferase domain hydrolyses glutamine to ammonia, which the carbamoyl-phosphate synthetase domain combines with bicarbonate and ATP to form carbamoyl phosphate (glutamine-dependent CPSase P, EC 6.3.5.5); the C-terminal aspartate transcarbamoylase domain then condenses carbamoyl phosphate with L-aspartate to N-carbamoyl-L-aspartate (EC 2.1.3.2). These are the first two steps of de novo UMP synthesis, and both activities are feedback-inhibited by UTP. As in budding yeast, the protein retains a dihydroorotase-like domain that is catalytically defective; dihydroorotase is provided by the separate ura2 gene. ura1 is cytoplasmic, and its carbamoyl phosphate is channelled to pyrimidine synthesis, separately from the mitochondrial arginine-specific CPSase A (arg5/arg4). Note that S. pombe ura1 is not the ortholog of S. cerevisiae URA1 (dihydroorotate dehydrogenase).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003922 GMP synthase (glutamine-hydrolyzing) activity | IGI PMID:8590465 As in Saccharomyces cerevisiae, aspartate transcarbamoylase ... | MODIFY | Summary: GMP synthase (glutamine-hydrolyzing) activity attached to Lollier et al. 1995, with S. cerevisiae URA2 (SGD:S000003666) in WITH. The paper characterises ura1 as the GLNase/CPSase-ATCase of pyrimidine synthesis by complementation of S. cerevisiae ura2 mutants; it says nothing about GMP synthesis, and S. pombe GMP synthase is a different, unrelated protein. This is almost certainly a term-selection slip for the glutamine-hydrolyzing carbamoyl-phosphate synthase activity, which is also annotated from the same paper with the same WITH entity. Reason: Wrong glutamine-hydrolyzing synthase chosen; the evidence supports carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity (GO:0004088), not GMP synthase. Proposed replacements: carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity Supporting Evidence: PMID:8590465 The URA1 gene encodes the bifunctional protein GLNase/CPSase-ATCase which catalyses the first two steps of the pyrimidine biosynthesis pathway. PMID:8590465 Genetic investigations confirmed that both GLNase/CPSase and ATCase activities are carried out by the same polypeptide. |
| GO:0004070 aspartate carbamoyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from PTN000150227 (CAD/URA2-type ATCase; donors include fly rudimentary, human CAD, S. cerevisiae URA2 and ura1 itself). ura1 is in the clade; core MF. Supporting Evidence: file:SCHPO/ura1/ura1-uniprot.txt Multifunctional protein that encodes the first 2 enzymatic file:SCHPO/ura1/ura1-uniprot.txt Reaction=carbamoyl phosphate + L-aspartate = N-carbamoyl-L-aspartate + |
| GO:0004070 aspartate carbamoyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (ARBA, InterPro IPR002082 ATCase, RHEA:20013, EC 2.1.3.2). Correct. Supporting Evidence: file:SCHPO/ura1/ura1-uniprot.txt Reaction=carbamoyl phosphate + L-aspartate = N-carbamoyl-L-aspartate + |
| GO:0004070 aspartate carbamoyltransferase activity | IGI PMID:8590465 As in Saccharomyces cerevisiae, aspartate transcarbamoylase ... | ACCEPT | Summary: Lollier et al. 1995 cloned ura1 cDNA by complementing an ATCase-deficient S. cerevisiae (ura2) strain and showed genetically that ATCase is on the same polypeptide as GLNase/CPSase. Core MF. Supporting Evidence: PMID:8590465 The URA1 gene encodes the bifunctional protein GLNase/CPSase-ATCase which catalyses the first two steps of the pyrimidine biosynthesis pathway. PMID:8590465 Genetic investigations confirmed that both GLNase/CPSase and ATCase activities are carried out by the same polypeptide. |
| GO:0004070 aspartate carbamoyltransferase activity | IMP PMID:6961452 Cloned ural locus of Schizosaccharomyces pombe propagates au... | ACCEPT | Summary: Sakaguchi & Yamamoto 1982: S. pombe DNA complementing E. coli pyrB (ATCase) also complements ura1, showing ura1 is the ATCase structural gene. Supporting Evidence: PMID:6961452 thereby demonstrating that ural is the structural gene for aspartate transcarbamylase of S. pombe |
| GO:0004087 carbamoyl-phosphate synthase (ammonia) activity | IEA GO_REF:0000120 | ACCEPT | Summary: RHEA:18029/EC 6.3.4.16 mapping for the ammonia-dependent CPSase partial reaction carried out by the synthetase domains once the GATase domain supplies NH3. Correct as a partial activity, as accepted for S. cerevisiae URA2; the physiological activity is the glutamine-dependent one. Supporting Evidence: file:SCHPO/ura1/ura1-uniprot.txt Reaction=hydrogencarbonate + NH4(+) + 2 ATP = carbamoyl phosphate + 2 |
| GO:0004088 carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (ARBA, IPR006274 CarB, RHEA:18633, EC 6.3.5.5). Correct; core MF. Supporting Evidence: file:SCHPO/ura1/ura1-uniprot.txt Reaction=hydrogencarbonate + L-glutamine + 2 ATP + H2O = carbamoyl |
| GO:0004088 carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity | IGI PMID:8590465 As in Saccharomyces cerevisiae, aspartate transcarbamoylase ... | ACCEPT | Summary: Lollier et al. 1995: ura1 complements S. cerevisiae ura2 and GLNase/CPSase is carried by the ura1 polypeptide. Core MF. Supporting Evidence: PMID:8590465 The URA1 gene encodes the bifunctional protein GLNase/CPSase-ATCase which catalyses the first two steps of the pyrimidine biosynthesis pathway. PMID:8590465 Genetic investigations confirmed that both GLNase/CPSase and ATCase activities are carried out by the same polypeptide. |
| GO:0004151 dihydroorotase activity | EXP NOT PMID:8590465 As in Saccharomyces cerevisiae, aspartate transcarbamoylase ... | ACCEPT | Summary: NOT dihydroorotase activity (Lollier et al. 1995). The DHOase-like domain of ura1 is cryptic/defective, as in S. cerevisiae URA2; dihydroorotase is provided by the separate ura2 gene. The negative annotation is correct and informative because sequence-based methods would otherwise predict DHOase for this CAD-like protein. Supporting Evidence: PMID:8590465 one cryptic DHOase (dihydroorotase) domain file:SCHPO/ura1/ura1-uniprot.txt The DHOase domain is defective. The third step of the de novo |
| GO:0004359 glutaminase activity | IEA GO_REF:0000120 | ACCEPT | Summary: RHEA:15889/EC 3.5.1.2 mapping for the glutamine amidotransferase (GLNase) partial reaction; the GATase domain hydrolyses glutamine to supply ammonia to the CPSase domain. Accepted as a genuine sub-activity, as for S. cerevisiae URA2. Supporting Evidence: file:SCHPO/ura1/ura1-uniprot.txt Reaction=L-glutamine + H2O = L-glutamate + NH4(+); PMID:8590465 The URA1 gene encodes the bifunctional protein GLNase/CPSase-ATCase which catalyses the first two steps of the pyrimidine biosynthesis pathway. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO ATP binding from the ATP-grasp domains of the CPSase. True (CPSase consumes 2 ATP) but a ligand-binding term subsumed by the CPSase activity. Reason: Correct but subsumed by carbamoyl-phosphate synthase activity. Supporting Evidence: file:SCHPO/ura1/ura1-uniprot.txt Reaction=hydrogencarbonate + L-glutamine + 2 ATP + H2O = carbamoyl |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: IBA cytoplasm from a broad CPSase node (PTN000150222). ura1 CPSase P is cytoplasmic, in contrast to mitochondrial CPSase A (arg5/arg4). Supporting Evidence: file:SCHPO/ura1/ura1-uniprot.txt it is localized to the cytoplasm and feedback inhibited and |
| GO:0005829 cytosol | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: ORFeome YFP localisation places ura1 in the cytosol; matches the PomBase GO-CAM. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: IBA cytosol from PTN000150227 (human CAD donor). Consistent with HDA. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein |
| GO:0006177 GMP biosynthetic process | IEA GO_REF:0000108 | REMOVE | Summary: GMP biosynthetic process inferred automatically (GO_REF:0000108 MF-to-BP inference) from the erroneous GMP synthase (GO:0003922) IGI annotation. ura1 has no role in GMP synthesis; this annotation inherits the term-selection error of its source. Reason: Derived solely from the mis-selected GO:0003922 annotation; ura1 functions in pyrimidine, not GMP, synthesis. Supporting Evidence: PMID:8590465 The URA1 gene encodes the bifunctional protein GLNase/CPSase-ATCase which catalyses the first two steps of the pyrimidine biosynthesis pathway. |
| GO:0006207 'de novo' pyrimidine nucleobase biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000150227. Steps 1-2 lead to orotate and UMP; accepted as for the S. cerevisiae orthologs (the GO-CAM also uses this process). Supporting Evidence: PMID:8590465 The URA1 gene encodes the bifunctional protein GLNase/CPSase-ATCase which catalyses the first two steps of the pyrimidine biosynthesis pathway. |
| GO:0006207 'de novo' pyrimidine nucleobase biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: ARBA/InterPro (IPR002082, IPR006274) mapping; correct. Supporting Evidence: file:SCHPO/ura1/ura1-uniprot.txt Multifunctional protein that encodes the first 2 enzymatic |
| GO:0006207 'de novo' pyrimidine nucleobase biosynthetic process | IGI PMID:8590465 As in Saccharomyces cerevisiae, aspartate transcarbamoylase ... | ACCEPT | Summary: Lollier et al. 1995 complementation of S. cerevisiae ura2 establishes ura1 in de novo pyrimidine synthesis. Supporting Evidence: PMID:8590465 The URA1 gene encodes the bifunctional protein GLNase/CPSase-ATCase which catalyses the first two steps of the pyrimidine biosynthesis pathway. |
| GO:0006520 amino acid metabolic process | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro2GO 'amino acid metabolic process' from the ATCase/OTCase superfamily signatures (IPR006130-2, IPR036901), whose mapping is driven by ornithine carbamoyltransferase in arginine synthesis. ura1 uses aspartate as a substrate for pyrimidine synthesis; this is not an amino acid metabolic role in a meaningful sense. Reason: Superfamily-level mapping driven by OTCase; ura1 is a pyrimidine-specific enzyme. Supporting Evidence: file:SCHPO/ura1/ura1-uniprot.txt Multifunctional protein that encodes the first 2 enzymatic |
| GO:0006541 L-glutamine metabolic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA L-glutamine metabolic process from a GATase node (PTN000150223). The GATase domain does hydrolyse glutamine, but only as the nitrogen donor for carbamoyl phosphate; kept as non-core, consistent with S. cerevisiae URA2. Reason: Glutamine use is part of the CPSase reaction, not a separate role. Supporting Evidence: file:SCHPO/ura1/ura1-uniprot.txt Reaction=L-glutamine + H2O = L-glutamate + NH4(+); |
| GO:0006541 L-glutamine metabolic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO (IPR006274) glutamine metabolic process; same reasoning as the IBA row. Reason: Glutamine use is part of the CPSase reaction, not a separate role. Supporting Evidence: file:SCHPO/ura1/ura1-uniprot.txt Reaction=L-glutamine + H2O = L-glutamate + NH4(+); |
| GO:0016597 amino acid binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO amino acid binding from the ATCase/OTCase superfamily (aspartate-binding domain). True (L-aspartate is a substrate) but subsumed by ATCase activity. Reason: Substrate binding subsumed by aspartate carbamoyltransferase activity. Supporting Evidence: file:SCHPO/ura1/ura1-uniprot.txt Reaction=carbamoyl phosphate + L-aspartate = N-carbamoyl-L-aspartate + |
| GO:0016743 carboxyl- or carbamoyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO carboxyl- or carbamoyltransferase activity from the ATCase/OTCase superfamily; parent of the specific aspartate carbamoyltransferase activity. Reason: Too general; the specific activity is known. Proposed replacements: aspartate carbamoyltransferase activity Supporting Evidence: file:SCHPO/ura1/ura1-uniprot.txt Reaction=carbamoyl phosphate + L-aspartate = N-carbamoyl-L-aspartate + |
| GO:0016810 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro2GO from IPR011059 (metal-dependent hydrolase composite domain), which here matches the defective DHOase-like domain that lacks dihydroorotase activity (see NOT annotation). The term is only true coincidentally through the glutaminase sub-activity of the GATase domain, which is captured by GO:0004359. Reason: Mapping is from the catalytically defective DHOase-like domain. Supporting Evidence: file:SCHPO/ura1/ura1-uniprot.txt The DHOase domain is defective. The third step of the de novo |
| GO:0044205 'de novo' UMP biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway UPA00070 (UMP biosynthesis via de novo pathway, steps 1-2). Correct; core BP. Supporting Evidence: file:SCHPO/ura1/ura1-uniprot.txt PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway; |
| GO:0046872 metal ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO metal ion binding from the ATP-grasp domain; CPSase binds Mg2+/Mn2+ with ATP. True cofactor binding, not a core function. Reason: Cofactor binding subsumed by CPSase activity. Supporting Evidence: file:SCHPO/ura1/ura1-uniprot.txt Note=Binds 4 Mg(2+) or Mn(2+) ions per subunit. |
| GO:1901137 carbohydrate derivative biosynthetic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: ARBA carbohydrate derivative biosynthetic process; ura1 products (carbamoyl phosphate, carbamoyl aspartate) are not carbohydrate derivatives; the term is reachable only via the downstream nucleotide product. Same call as S. cerevisiae URA2. Reason: Very broad ARBA term not informative for the ura1 steps. Supporting Evidence: file:SCHPO/ura1/ura1-uniprot.txt Multifunctional protein that encodes the first 2 enzymatic |
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