ura7

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: Cytoplasm localization well-supported by phylogenetic analysis (IBA). The deep research confirms Cts1 is predominantly cytosolic, existing as both diffuse pool and organized filaments. This represents accurate core localization. Reason: IBA evidence correctly identifies cytoplasmic localization. Deep research corroborates that Cts1 functions as a cytosolic enzyme for CTP synthesis. This is a core cellular component annotation. Supporting Evidence: file:SCHPO/ura7/ura7-deep-research.md Cts1 is predominantly a cytosolic enzyme, consistent with its role in nucleotide biosynthesis in the cytoplasm
GO:0042802 identical protein binding	IBA GO_REF:0000033	ACCEPT	Summary: CTP synthase forms homotetramers as the active enzyme form, which can further polymerize into filaments. This protein-protein interaction is essential for enzymatic function and represents a core molecular property. Reason: The homotetramer formation is well-established for CTP synthase enzymes across species. This self-association is required for catalytic activity and is a fundamental aspect of enzyme function. Supporting Evidence: file:SCHPO/ura7/ura7-deep-research.md Functionally, Cts1 operates as a homotetramer. Four identical Cts1 subunits assemble into a ring-shaped tetramer, which is the active form needed for catalysis
GO:0003883 CTP synthase activity	IBA GO_REF:0000033	ACCEPT	Summary: CTP synthase activity is the defining molecular function of this enzyme. IBA correctly identifies this core function based on phylogenetic conservation. Enzyme catalyzes ATP + UTP + glutamine → CTP + ADP + phosphate + glutamate. Reason: This is the primary and essential molecular function of ura7/cts1. The enzyme is well-characterized biochemically across species. This annotation accurately captures the core catalytic activity. Supporting Evidence: file:SCHPO/ura7/ura7-deep-research.md CTP synthase catalyzes the ATP-dependent amination of UTP to form CTP, using L-glutamine as the nitrogen donor... This reaction represents the final and rate-limiting step in de novo CTP biosynthesis file:SCHPO/ura7/ura7-deep-research-falcon.md CTPS catalyzes the ATP-dependent amination of UTP to CTP, using glutamine-derived ammonia delivered through an intramolecular tunnel file:SCHPO/ura7/ura7-deep-research-falcon.md is the sole essential CTPS enzyme catalyzing ATP-dependent UTP→CTP conversion, using glutamine-derived ammonia and regulated by GTP activation and CTP feedback inhibition
GO:0006241 CTP biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: CTP biosynthetic process is the primary biological function of CTP synthase. The enzyme catalyzes the final step of de novo CTP synthesis, converting UTP to CTP. Essential for cell viability as deletion is lethal. Reason: This accurately describes the core biological process mediated by ura7/cts1. The enzyme is essential for CTP production required for nucleic acid synthesis and cell proliferation. Well-supported by phylogenetic and functional evidence. Supporting Evidence: file:SCHPO/ura7/ura7-deep-research.md As the sole CTP synthase in fission yeast, Cts1 is essential for pyrimidine nucleotide biosynthesis. It enables the de novo CTP biosynthetic process (GO:0006241) by producing CTP from UTP file:SCHPO/ura7/ura7-deep-research-falcon.md fission yeast as a model with a single CTPS gene, encoded at the cts1 locus PMID:38203781 S. pombe only harbors one CTPS isoform encoded by a single locus cts1 on chromosome I
GO:0097268 cytoophidium	IBA GO_REF:0000033	ACCEPT	Summary: Cytoophidium formation is well-established for CTP synthase. IBA correctly predicts this based on conservation across species. Direct experimental evidence also exists showing temperature-sensitive cytoophidium assembly in S. pombe. Reason: Cytoophidium formation is a conserved feature of CTP synthase enzymes. Both phylogenetic inference and direct experimental evidence (PMID:31611173) confirm Cts1 forms these filamentous structures in S. pombe. Supporting Evidence: file:SCHPO/ura7/ura7-deep-research.md Cts1 exhibits a remarkable ability to assemble into filamentous subcellular structures called cytoophidia... Each fission yeast cell generally contains two Cts1 filaments: a long, thick cytoophidium in the cytoplasm and a shorter, thinner filament associated with the nucleus file:SCHPO/ura7/ura7-deep-research-falcon.md cytoophidia that are highly abundant during logarithmic growth (reported >90% of cells) and largely disappear in stationary phase PMID:38203781 cytoophidia were present in over 90% of fission yeast cells (Figure 1A,C) and subsequently disappeared during the stationary phase
GO:0019856 pyrimidine nucleobase biosynthetic process	IBA GO_REF:0000033	MODIFY	Summary: This term is broader than CTP biosynthesis, encompassing pyrimidine nucleobase production. While CTP synthase contributes to pyrimidine metabolism, this annotation is somewhat imprecise as the enzyme works with nucleotides, not nucleobases directly. Reason: CTP synthase converts UTP to CTP (nucleotide to nucleotide conversion), not directly involved in nucleobase synthesis. The more accurate term would be GO:0006221 (pyrimidine nucleotide biosynthetic process) which correctly describes nucleotide-level metabolism. Proposed replacements: pyrimidine nucleotide biosynthetic process Supporting Evidence: file:SCHPO/ura7/ura7-deep-research.md As the enzyme governing CTP levels, Cts1 plays a role in the broader metabolism of pyrimidine nucleotides within the cell
GO:0003883 CTP synthase activity	IEA GO_REF:0000120	ACCEPT	Summary: Duplicate annotation of CTP synthase activity with IEA evidence. The IBA annotation above already correctly captures this core function with stronger evidence. IEA provides supporting computational evidence. Reason: While duplicative with the IBA annotation, this IEA annotation correctly identifies the core molecular function through automated methods. Both annotations are accurate and reinforce the primary enzyme activity. Supporting Evidence: file:SCHPO/ura7/ura7-deep-research.md CTP synthase activity (GO:0003883) – Cts1 catalyzes the reaction ATP + UTP + glutamine + H₂O → CTP + ADP + phosphate + glutamate
GO:0006221 pyrimidine nucleotide biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Accurate broad biological process annotation. CTP synthase contributes to pyrimidine nucleotide biosynthesis by producing CTP. This correctly captures the metabolic context of the enzyme function. Reason: This annotation correctly places CTP synthase in the broader context of pyrimidine nucleotide metabolism. The enzyme produces CTP, a key pyrimidine nucleotide required for RNA and DNA synthesis. Supporting Evidence: file:SCHPO/ura7/ura7-deep-research.md Pyrimidine nucleotide metabolic process (GO:0006221) – As the enzyme governing CTP levels, Cts1 plays a role in the broader metabolism of pyrimidine nucleotides within the cell
GO:0006241 CTP biosynthetic process	IEA GO_REF:0000002	ACCEPT	Summary: Duplicate annotation of CTP biosynthetic process with IEA evidence from InterPro. Correctly identifies the core biological process. Complements the IBA annotation with computational support. Reason: IEA annotation based on InterPro domain analysis correctly identifies the CTP biosynthetic function. This is accurate and represents the primary biological role of the enzyme. Supporting Evidence: file:SCHPO/ura7/ura7-deep-research.md CTP biosynthetic process (de novo CTP biosynthesis) (GO:0006241) – cts1 is involved in the pathway producing CTP from simpler precursors, constituting the last step of de novo pyrimidine ribonucleotide synthesis
GO:0000166 nucleotide binding	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: Generic nucleotide binding annotation based on keyword mapping. While technically correct (enzyme binds ATP, UTP, GTP), this is too broad and uninformative compared to specific substrate/cofactor binding annotations. Reason: While CTP synthase does bind nucleotides (ATP, UTP as substrates; GTP as allosteric regulator), this generic term provides little functional information. More specific terms like ATP binding (GO:0005524) or UTP binding would be more informative. Supporting Evidence: file:SCHPO/ura7/ura7-deep-research.md The C-terminal domain... binds the substrate UTP and co-substrate ATP... GTP acts as an allosteric activator of CTP synthase, binding to the GAT domain file:SCHPO/ura7/ura7-deep-research-falcon.md GTP as an allosteric effector required for efficient glutamine hydrolysis file:SCHPO/ura7/ura7-deep-research-falcon.md Product CTP acts as a feedback inhibitor**, competitively binding at the UTP site
GO:0005524 ATP binding	IEA GO_REF:0000043	ACCEPT	Summary: ATP binding is correct as ATP is a co-substrate in the CTP synthase reaction. However, this annotation alone provides limited functional insight compared to the full enzymatic activity annotation. Reason: ATP binding is accurate - ATP is required as co-substrate for the amination reaction. While somewhat generic, it correctly identifies a specific nucleotide binding function of the enzyme. Supporting Evidence: file:SCHPO/ura7/ura7-deep-research.md CTP synthase catalyzes the ATP-dependent amination of UTP to form CTP... The C-terminal domain constitutes the synthetase domain, which binds the substrate UTP and co-substrate ATP file:SCHPO/ura7/ura7-deep-research-falcon.md an N-terminal synthase (ammonia ligase) domain that binds ATP/UTP and performs the phosphorylation/amination chemistry, and
GO:0016874 ligase activity	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: Generic ligase activity annotation. While CTP synthase is classified as a ligase (EC 6.3.4.2), this broad term is uninformative compared to the specific CTP synthase activity annotation. Reason: This overly broad annotation provides minimal functional information. The specific CTP synthase activity (GO:0003883) annotation already captures the enzyme function precisely. Generic ligase activity adds no value. Supporting Evidence: file:SCHPO/ura7/ura7-deep-research.md RecName: Full=CTP synthase; EC=6.3.4.2... AltName: Full=UTP--ammonia ligase
GO:0097268 cytoophidium	IEA GO_REF:0000117	ACCEPT	Summary: Duplicate cytoophidium annotation with IEA evidence from ARBA machine learning. Correctly identifies this cellular component. Complements the IBA and IDA evidence for this localization. Reason: Machine learning models correctly predict cytoophidium formation, which is well-established for CTP synthase. This annotation is accurate and supported by experimental evidence from other sources. Supporting Evidence: PMID:31611173 Temperature-sensitive cytoophidium assembly in Schizosaccharomyces pombe... CTPS forms filamentous structures termed cytoophidia
GO:0044210 'de novo' CTP biosynthetic process	IEA GO_REF:0000041	ACCEPT	Summary: Specific and accurate annotation for de novo CTP biosynthesis based on UniPathway mapping. This correctly identifies the enzyme role in synthesizing CTP from precursors rather than salvage pathways. Reason: This annotation accurately captures the specific metabolic pathway - de novo CTP synthesis. CTP synthase catalyzes the final step in de novo CTP production, distinguishing it from salvage pathway enzymes. Supporting Evidence: file:SCHPO/ura7/ura7-deep-research.md This reaction represents the final and rate-limiting step in de novo CTP biosynthesis... It enables the de novo CTP biosynthetic process (GO:0006241) by producing CTP from UTP
GO:0097268 cytoophidium	IDA PMID:31611173 Temperature-sensitive cytoophidium assembly in Schizosacchar...	ACCEPT	Summary: Direct experimental evidence for cytoophidium formation in S. pombe. Study demonstrates temperature-sensitive assembly of CTPS filaments, with detailed characterization of their dynamics and regulation. Reason: Strong experimental evidence directly showing Cts1 forms cytoophidia in S. pombe. Study used CTPS-YFP to visualize filaments and demonstrated their temperature sensitivity, making this a high-quality direct observation. Supporting Evidence: PMID:31611173 During the early-to-middle exponential phase (OD600 = 0.1–1.0), cytoophidia were highly abundant, being present in more than 90% of cells... We have previously identified that CTPS forms cytoophidia in S. pombe PMID:38203781 The CTPS H359A mutant fission yeast was viable but did not form cytoophidia file:SCHPO/ura7/ura7-deep-research-falcon.md Mutation of a conserved histidine (His359→Ala, H359A) abolishes cytoophidium formation without lethality
GO:0005737 cytoplasm	HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ...	ACCEPT	Summary: High-throughput direct assay showing cytoplasmic localization. Part of large-scale ORFeome study that determined localization of ~90% of S. pombe proteome using YFP tagging. Reason: Direct experimental evidence from systematic protein localization study. HDA provides strong support for cytoplasmic localization, consistent with the enzyme metabolic function. 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	ISO GO_REF:0000024	ACCEPT	Summary: Cytosol annotation based on manual transfer from orthologs. More specific than cytoplasm, correctly identifying the soluble cytoplasmic fraction where CTP synthesis occurs. Reason: ISO evidence correctly identifies cytosolic localization based on ortholog data. This is more specific than general cytoplasm and accurately describes where the enzyme functions in nucleotide metabolism. Supporting Evidence: file:SCHPO/ura7/ura7-deep-research.md Cts1 is predominantly localized in the cytosol where it carries out CTP synthesis. The majority of Cts1 enzyme resides in the cytoplasmic compartment, often visible as diffuse cytosolic signal or organized into filaments
GO:0006207 'de novo' pyrimidine nucleobase biosynthetic process	ISO GO_REF:0000024	MODIFY	Summary: This annotation refers to nucleobase biosynthesis, but CTP synthase works at the nucleotide level (UTP to CTP), not nucleobase level. The term is imprecise for this enzyme function. Reason: CTP synthase converts nucleotides (UTP→CTP), not nucleobases. The more accurate term would be de novo pyrimidine nucleotide biosynthetic process or specifically de novo CTP biosynthetic process (GO:0044210). Proposed replacements: 'de novo' CTP biosynthetic process Supporting Evidence: file:SCHPO/ura7/ura7-deep-research.md This reaction represents the final and rate-limiting step in de novo CTP biosynthesis, producing cytidine 5′-triphosphate (CTP)