CTPS1 is a glutamine-dependent CTP synthase that couples ATP consumption to the amination of UTP, supplying CTP for nucleotide and membrane-lipid synthesis. Its homotetrameric enzyme can assemble into regulated cytoophidia in the cytoplasm and nucleus; substrate-associated human filaments enhance catalytic activity. Increased CTP supply is particularly important for proliferation of activated lymphocytes. CTPS1 also catalyzes protein asparagine deamidation: modification of histone H1 facilitates subsequent acetylation and chromatin relaxation during DNA repair, while IRF3 deamidation limits interferon induction. These catalytic roles are regulated by cellular context and phosphorylation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000785 chromatin | IDA PMID:40240600 Histone H1 deamidation facilitates chromatin relaxation for ... | ACCEPT | Summary: The directly measured H1 reaction and damage-site recruitment establish CTPS1 activity on chromatin; the original is_active_in qualifier is retained. Reason: The directly measured H1 reaction and damage-site recruitment establish CTPS1 activity on chromatin; the original is_active_in qualifier is retained. Supporting Evidence: |
| GO:0003883 CTP synthase activity | IBA GO_REF:0000033 | ACCEPT | Summary: The inherited CTP synthase activity is directly corroborated by full-length human CTPS1 biochemistry. Reason: The inherited CTP synthase activity is directly corroborated by full-length human CTPS1 biochemistry. The pinned PAINT projection places the assertion at on-path PTN000167473. Target self evidence and the number of donors are not objections. Current donor-set differences are recorded separately and do not negate the positive experimental grounding. |
| GO:0003883 CTP synthase activity | IDA PMID:16179339 Expression of Human CTP synthetase in Saccharomyces cerevisi... | ACCEPT | Summary: The complete cached abstract explicitly reports human CTPS1 expression in the yeast ura7/ura8 double mutant, measured CTP synthase activity, and cellular CTP synthesis. Reason: The complete cached abstract explicitly reports human CTPS1 expression in the yeast ura7/ura8 double mutant, measured CTP synthase activity, and cellular CTP synthesis. Original full text remains unavailable after bounded routes; retain the positive IDA with curator deference and independent purified-human-enzyme corroboration, without claiming to have inspected the 2005 Methods. |
| GO:0003883 CTP synthase activity | IDA PMID:17189248 Phosphorylation of human CTP synthetase 1 by protein kinase ... | ACCEPT | Summary: The full 2007 original measures conversion of UTP to CTP by purified, C-terminally His-tagged human CTPS1 expressed in yeast. Reason: The full 2007 original measures conversion of UTP to CTP by purified, C-terminally His-tagged human CTPS1 expressed in yeast. Spectrophotometric activity is independently checked by HPLC. Bovine PKA phosphorylates this substrate and inhibits its CTP synthase activity; the paper does not assign kinase activity to CTPS1. Supporting Evidence: |
| GO:0003883 CTP synthase activity | IDA PMID:17463002 Phosphorylation of human CTP synthetase 1 by protein kinase ... | ACCEPT | Summary: Human CTPS1 expressed in yeast or Escherichia coli catalyzes UTP-to-CTP conversion, with phosphorylation-site-dependent regulation. Reason: The original Methods and Results measure UTP-to-CTP activity of human CTPS1 expressed in yeast or E. coli. PKC phosphorylation and S462A/T455A mutations regulate the enzyme in context; CTPS1 is the phosphorylated enzyme, not the kinase. Construct and host differences, including the poorly stable double mutant, do not invalidate the measured canonical reaction. Supporting Evidence: |
| GO:0003883 CTP synthase activity | IDA PMID:28459447 Human CTP synthase filament structure reveals the active enz... | ACCEPT | Summary: Purified C-terminally His-tagged human CTPS1 expressed in yeast directly produces CTP from UTP under defined ATP, glutamine, GTP and magnesium conditions. Reason: Purified C-terminally His-tagged human CTPS1 expressed in yeast directly produces CTP from UTP under defined ATP, glutamine, GTP and magnesium conditions. H355A retains tetramers but impairs filament formation and has lower activity; this supports assembly regulation without making polymerization an absolute prerequisite for every catalytic event. Supporting Evidence: |
| GO:0003883 CTP synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: CTP synthase is the experimentally demonstrated human reaction and agrees with RHEA:26426 and EC:6.3.4.2. Reason: CTP synthase is the experimentally demonstrated human reaction and agrees with RHEA:26426 and EC:6.3.4.2. The current-rule reconstruction finds no human match in the present ARBA00089001 rule; that source-version discrepancy must remain visible, but it does not negate the other aggregate sources or direct human chemistry. Do not rewrite the original multi-source tuple. |
| GO:0003883 CTP synthase activity | IGI PMID:16179339 Expression of Human CTP synthetase in Saccharomyces cerevisi... | ACCEPT | Summary: The 2005 abstract explicitly reports complementation of yeast lacking both URA7 and URA8 by human CTPS1. Reason: The 2005 abstract explicitly reports complementation of yeast lacking both URA7 and URA8 by human CTPS1. Preserve this curated URA7-linked IGI source separately from the other partner and from IDA; no full-text-only assay detail is asserted. Supporting Evidence: |
| GO:0003883 CTP synthase activity | IGI PMID:16179339 Expression of Human CTP synthetase in Saccharomyces cerevisi... | ACCEPT | Summary: The 2005 abstract explicitly reports complementation of yeast lacking both URA7 and URA8 by human CTPS1. Reason: The 2005 abstract explicitly reports complementation of yeast lacking both URA7 and URA8 by human CTPS1. Preserve this curated URA8-linked IGI source separately from the other partner and from IDA; no full-text-only assay detail is asserted. Supporting Evidence: |
| GO:0003883 CTP synthase activity | IMP PMID:24870241 CTP synthase 1 deficiency in humans reveals its central role... | ACCEPT | Summary: Human CTPS1 deficiency, CTPS1-specific knockdown and wild-type reconstitution link reduced CTP synthase activity to the gene. Reason: Human CTPS1 deficiency, CTPS1-specific knockdown and wild-type reconstitution link reduced CTP synthase activity to the gene. Direct nucleotide measurements and CTP/cytidine rescue are consistent with the independently purified enzyme reaction; the exon-18 disease lesion is not the official N-terminally truncated splice product. |
| GO:0003883 CTP synthase activity | TAS PMID:2113467 Molecular cloning of the human CTP synthetase gene by functi... | ACCEPT | Summary: The complete 1990 abstract reports complementation of a hamster cytidine auxotroph deficient in CTP synthase and cloning of a human 591-aa coding sequence. Reason: The complete 1990 abstract reports complementation of a hamster cytidine auxotroph deficient in CTP synthase and cloning of a human 591-aa coding sequence. Retain the TAS activity, also independently established by later purified human CTPS1 assays. Only the abstract was read here; this is not a new claim about uninspected original Methods. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: BioPlex detects CTPS2-bait/CTPS1-prey copurification in HEK293T cells. Reason: The affinity-purification context is resolved by the literal human CTPS2-bait/CTPS1-prey record from the 2017 HEK293T BioPlex experiment (record 50); the C-terminally tagged bait is not an isolated catalytic domain. The positive association with the independently characterized CTPS2 enzyme supports the enzyme-partner class. Paralog co-assembly is compatible with that limited binding claim; a purified interface, fixed heteromer or new regulatory activity is not inferred. Proposed replacements: enzyme binding |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: Three HuRI records detect the human CTPS1–CTPS2 pair in a yeast two-hybrid system. Reason: Three literal HuRI records (51, 52 and 59) reproduce the human CTPS1–CTPS2 pair in the yeast two-hybrid screening/validation system. Both protein sequences and recorded ROGIDs match the official displayed products; the yeast host is not a human-cell assay. This pair-specific two-hybrid evidence is distinct from the lysate co-assembly detected by the other sources. Enzyme binding identifies the experimentally established CTPS2 partner class; it does not assign CTPS2 catalysis or regulation to CTPS1. Proposed replacements: enzyme binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: The later BioPlex screen again detects CTPS2-bait/CTPS1-prey association. Reason: The literal 2021 BioPlex record 61 reports human CTPS2-bait/CTPS1-prey copurification in HEK293T cells. This demonstrates association in a lysate complex rather than proving a purified binary interface. The positive association with the independently characterized CTPS2 enzyme supports the enzyme-partner class. Paralog co-assembly is compatible with that limited binding claim; a purified interface, fixed heteromer or new regulatory activity is not inferred. Proposed replacements: enzyme binding |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: OpenCell detects CTPS2 with endogenously tagged CTPS1 in triplicate IP-MS. Reason: The original OpenCell interaction CSV identifies CTPS1 bait and CTPS2 prey at row 6465, with enrichment 5.75498 and reported stoichiometry estimate 0.222. The study uses endogenously fluorescent-tagged HEK293T baits and triplicate IP-MS. This target-specific source record is separate from the absent current IntAct join and does not establish fixed heteromer stoichiometry. The positive association with the independently characterized CTPS2 enzyme supports the enzyme-partner class. Paralog co-assembly is compatible with that limited binding claim; a purified interface, fixed heteromer or new regulatory activity is not inferred. Proposed replacements: enzyme binding |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: The U2OS AP-MS source network contains the measured CTPS1–CTPS2 edge. Reason: The actual U2OS AP-MS network deposited for this paper contains edge 605930 between CTPS2 (ENSG00000047230) and CTPS1 (ENSG00000171793). The original Methods use C-terminal Flag–HA baits and lysate purification. This is a measured association in the source network, not a predicted structural contact or inference from colocalization. The positive association with the independently characterized CTPS2 enzyme supports the enzyme-partner class. Paralog co-assembly is compatible with that limited binding claim; a purified interface, fixed heteromer or new regulatory activity is not inferred. Proposed replacements: enzyme binding |
| GO:0005634 nucleus | IDA PMID:24503052 CTP synthase forms cytoophidia in the cytoplasm and nucleus. | ACCEPT | Summary: The recovered original reports human CTPS1–GFP in nuclear as well as cytoplasmic cytoophidia in HeLa cells (Figure 5). Reason: The recovered original reports human CTPS1–GFP in nuclear as well as cytoplasmic cytoophidia in HeLa cells (Figure 5). This direct construct-localization evidence supports nucleus, independently reinforced by later endogenous damage-site/chromatin experiments. Mouse live-imaging constructs elsewhere in the paper are distinguished from the human Figure 5 assay. |
| GO:0005634 nucleus | IDA PMID:40240600 Histone H1 deamidation facilitates chromatin relaxation for ... | ACCEPT | Summary: The chromatin-associated H1 reaction and nuclear damage-site recruitment support nuclear activity, not merely predicted localization. Reason: The chromatin-associated H1 reaction and nuclear damage-site recruitment support nuclear activity, not merely predicted localization. Supporting Evidence: |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Official nuclear subcellular mapping is corroborated by human primary recruitment experiments; the original located_in qualifier is retained. Reason: Official nuclear subcellular mapping is corroborated by human primary recruitment experiments; the original located_in qualifier is retained. Supporting Evidence: |
| GO:0005694 chromosome | EXP PMID:40240600 Histone H1 deamidation facilitates chromatin relaxation for ... | ACCEPT | Summary: Damage-associated chromatin enrichment supports chromosome-associated location without claiming mitotic-specific occupancy. Reason: Damage-associated chromatin enrichment supports chromosome-associated location without claiming mitotic-specific occupancy. Supporting Evidence: |
| GO:0005694 chromosome | IEA GO_REF:0000044 | ACCEPT | Summary: The official chromosome mapping agrees with direct chromatin recruitment; retain broad location without an invented constitutive distribution. Reason: The official chromosome mapping agrees with direct chromatin recruitment; retain broad location without an invented constitutive distribution. Supporting Evidence: |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: The actual PTN000167476 IBD is on the human target path and the MSA reproduces the 591-aa sequence. Reason: The actual PTN000167476 IBD is on the human target path and the MSA reproduces the 591-aa sequence. Human cellular localization directly supports cytoplasmic CTPS1, including regulated filaments. The broad cytoplasm term remains correct; no donor-count or target-self-evidence objection is raised. |
| GO:0005737 cytoplasm | IDA PMID:24503052 CTP synthase forms cytoophidia in the cytoplasm and nucleus. | ACCEPT | Summary: Figure 5 of the recovered original localizes human CTPS1–GFP to cytoplasmic filaments in HeLa cells. Reason: Figure 5 of the recovered original localizes human CTPS1–GFP to cytoplasmic filaments in HeLa cells. Nuclear structures are also observed, so this positive location does not imply exclusive cytoplasmic residence or equal distribution of every product. Supporting Evidence: |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: The official cytosolic location is consistent with human-cell CTPS1 distribution and the cytosolic nucleotide-synthesis reaction. Reason: The official cytosolic location is consistent with human-cell CTPS1 distribution and the cytosolic nucleotide-synthesis reaction. The 2014 HEK293 experiment reports wild-type human CTPS1 largely in the cytosol while the engineered E161K mutant forms long filaments; this is not evidence that all cytosolic CTPS1 is polymerized. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-73647 | ACCEPT | Summary: The actual Reactome catalyst chain is R-HSA-73647 → catalyst 73537 → tetramer 504052 → four occurrences of CTPS1 entity 73536 (UniProt P17812, residues 1–591), with cytosol on the enzyme and complex. Reason: The actual Reactome catalyst chain is R-HSA-73647 → catalyst 73537 → tetramer 504052 → four occurrences of CTPS1 entity 73536 (UniProt P17812, residues 1–591), with cytosol on the enzyme and complex. CTPS1 catalyzes the UTP-to-CTP reaction rather than serving as an input. |
| GO:0006139 nucleobase-containing compound metabolic process | TAS PMID:2113467 Molecular cloning of the human CTP synthetase gene by functi... | MODIFY | Summary: Human CTPS1 performs the CTP-producing step within this broader metabolic process. Reason: The positive metabolic assertion is valid but CTP biosynthetic process states the actual product more precisely. The 1990 abstract identifies the human enzyme by functional complementation of a CTP-synthase-deficient auxotroph, and later purified human enzyme directly produces CTP. This is a refinement of a positive source, not a rejection of its abstract-only access. This replaces a broader ancestor with an already represented specific process while preserving the independent source assertion; the ancestor is not rejected as biologically false. Proposed replacements: CTP biosynthetic process |
| GO:0006221 pyrimidine nucleotide biosynthetic process | IEA GO_REF:0000002 | MODIFY | Summary: The family mapping is valid; CTP biosynthesis specifies the target reaction. Reason: The InterPro-associated pyrimidine nucleotide biosynthesis assertion is biologically sound. CTPS1 specifically performs UTP-to-CTP synthesis, so CTP biosynthetic process is the more informative replacement for this target. A broad family mapping need not be false to justify a gene-specific refinement. This replaces a broader ancestor with an already represented specific process while preserving the independent source assertion; the ancestor is not rejected as biologically false. Proposed replacements: CTP biosynthetic process |
| GO:0006241 CTP biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: CTP biosynthesis is directly performed by human CTPS1 and is compatible with the on-path PTN000167473 IBD and its experimental descendants. Reason: CTP biosynthesis is directly performed by human CTPS1 and is compatible with the on-path PTN000167473 IBD and its experimental descendants. Preserve the phylogenetic assertion and its literal donor set; neither self evidence nor donor count is a reason to reject it. |
| GO:0006241 CTP biosynthetic process | IDA PMID:16179339 Expression of Human CTP synthetase in Saccharomyces cerevisi... | ACCEPT | Summary: The 2005 complete abstract reports cellular CTP synthesis by the human enzyme in the yeast double mutant. Reason: The 2005 complete abstract reports cellular CTP synthesis by the human enzyme in the yeast double mutant. This is a human gene-product assay in a heterologous host, not a direct measurement in human cells. Independent later full originals establish the same chemistry; retain the source-specific IDA with its full-text access limitation. |
| GO:0006241 CTP biosynthetic process | IDA PMID:28459447 Human CTP synthase filament structure reveals the active enz... | ACCEPT | Summary: The reconstituted human CTPS1 assay directly measures CTP production from UTP. Reason: The reconstituted human CTPS1 assay directly measures CTP production from UTP. The protein performs the biosynthetic reaction; it is not merely required as a substrate or a downstream proliferation marker. Yeast expression and the in vitro filament conditions remain explicit. Supporting Evidence: |
| GO:0006241 CTP biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: The CTPS family mapping to CTP biosynthesis is directly corroborated by human enzyme assays. Reason: The CTPS family mapping to CTP biosynthesis is directly corroborated by human enzyme assays. Preserve the original IPR033828 electronic source and its qualifier; no replacement is needed at this already precise product level. |
| GO:0006241 CTP biosynthetic process | IMP PMID:24870241 CTP synthase 1 deficiency in humans reveals its central role... | ACCEPT | Summary: The original human patient and reconstitution experiments measure reduced CTP production in CTPS1-deficient lymphocytes and restoration by wild-type CTPS1. Reason: The original human patient and reconstitution experiments measure reduced CTP production in CTPS1-deficient lymphocytes and restoration by wild-type CTPS1. CTPS1 directly performs nucleotide biosynthesis, rather than merely being a marker of activated or proliferating cells. |
| GO:0009410 response to xenobiotic stimulus | TAS PMID:7981751 Clustered base substitutions in CTP synthetase conferring dr... | MARK AS OVER ANNOTATED | Summary: Hamster CTPS feedback-regulatory mutants alter drug susceptibility; this does not establish a human CTPS1 xenobiotic-response function. Reason: The original study expresses hamster CTPS feedback-regulatory mutants in CTPS-deficient CHO cells and measures resistance to ara-C, 5-FU and CPEC. Constitutive changes in nucleotide-pool regulation establish a resistance phenotype, but do not identify a CTPS1-performed response to xenobiotic exposure. The paper specifically identifies phosphorylated CPEC as a direct CTPS inhibitor; ara-C and 5-FU are not thereby established as direct CTPS inhibitors. Even the proposed effect of the mutations on CPEC binding is presented as requiring further biochemical evidence. Human sequence conservation does not substitute for a human response assay. The broad TAS process therefore exceeds the demonstrated enzyme and mutant-context evidence. Supporting Evidence: |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | UNDECIDED | Summary: The complete abstract describes YTS-cell membrane proteomics, including integral and transiently associated proteins, but the original target-level table and full Methods remain inaccessible after bounded publisher and repository searches. Reason: The complete abstract describes YTS-cell membrane proteomics, including integral and transiently associated proteins, but the original target-level table and full Methods remain inaccessible after bounded publisher and repository searches. The current membrane definition includes attached proteins, so lack of a transmembrane segment would not refute the HDA annotation. Preserve the literal source and defer its particular CTPS1 assignment rather than infer contamination or absence. Supporting Evidence: |
| GO:0019856 pyrimidine nucleobase biosynthetic process | IBA GO_REF:0000033 | MODIFY | Summary: The actual IBD is positively placed at PTN000167473 on the human path, and its SGD:S000000135 descendant has a current IMP assertion from PMID:1753946; no topology, donor-count or circularity defect is alleged. Reason: The actual IBD is positively placed at PTN000167473 on the human path, and its SGD:S000000135 descendant has a current IMP assertion from PMID:1753946; no topology, donor-count or circularity defect is alleged. The term nevertheless denotes pyrimidine nucleobase formation, whereas demonstrated human CTPS1 amination retains the ribose triphosphate and produces the nucleotide CTP. Prefer CTP biosynthetic process as a chemical-object correction while preserving the positive original source. The donor original was not read here, so this is not a verdict that its experimental annotation is wrong. The two terms are not in an ancestor/descendant relation in the typed closure. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN000167473 UNRESOLVED The literal GO:0019856 IBD is on the human CTPS1 path, with current experimental URA7 grounding (SGD:S000000135; IMP PMID:1753946). Node placement and positive biosynthesis are sound. The nucleotide-versus-nucleobase term is corrected for human CTPS1 chemistry; the unread donor original is not declared erroneous. Proposed replacements: CTP biosynthetic process |
| GO:0032480 negative regulation of type I interferon production | IEA GO_REF:0000107 | ACCEPT | Summary: Exact mouse P70698 donor IDA PMID:39719712 supports IFN suppression through IRF3 deamidation. Reason: Exact mouse P70698 donor IDA PMID:39719712 supports IFN suppression through IRF3 deamidation. Human endogenous HEK293T/THP-1 perturbations corroborate the process; the original IEA transfer remains distinct from human cellular corroboration; no human organismal assay is claimed. Supporting Evidence: |
| GO:0032480 negative regulation of type I interferon production | ISS GO_REF:0000024 | ACCEPT | Summary: Exact mouse donor/source and direct IRF3 reaction support the ISS process assertion, with unspecified expression-construct identity and mouse organismal scope explicit. Reason: Exact mouse donor/source and direct IRF3 reaction support the ISS process assertion, with unspecified expression-construct identity and mouse organismal scope explicit. Supporting Evidence: |
| GO:0042098 T cell proliferation | IDA PMID:8530356 Importance of ribonucleotide availability to proliferating T... | KEEP AS NON CORE | Summary: The 1995 abstract reports nucleotide pools, synthesis-inhibitor responses and proliferation in primary human T lymphocytes; it does not isolate CTPS1 from CTPS2. Reason: The available 1995 abstract reports nucleotide pools, synthesis-inhibitor responses and proliferation in primary human T lymphocytes, without separating CTPS1 from CTPS2. The original experimental assignment is retained with curator deference because the full target assays were not recovered and the proliferative role of CTPS1-mediated CTP supply is independently established. PMID:24870241 provides that separate CTPS1-specific context; it does not retroactively demonstrate which paralog the earlier paper assayed. Retain this downstream cellular role as non-core, with the original IDA source and its access limit unchanged. |
| GO:0042098 T cell proliferation | IMP PMID:24870241 CTP synthase 1 deficiency in humans reveals its central role... | KEEP AS NON CORE | Summary: Human patient cells, CTPS1 knockdown, wild-type reconstitution and CTP/cytidine supplementation connect the catalytic CTP-supply step to activated T-cell division. Reason: Human patient cells, CTPS1 knockdown, wild-type reconstitution and CTP/cytidine supplementation connect the catalytic CTP-supply step to activated T-cell division. This is a well-supported cellular role beyond the compact enzymatic core, not an assignment of T-cell-receptor signaling or a necessity-only NEW process. Supporting Evidence: |
| GO:0042100 B cell proliferation | IMP PMID:24870241 CTP synthase 1 deficiency in humans reveals its central role... | KEEP AS NON CORE | Summary: The human study measures impaired B-cell proliferation after receptor stimulation in CTPS1-deficient cells and relates it to insufficient nucleotide supply. Reason: The human study measures impaired B-cell proliferation after receptor stimulation in CTPS1-deficient cells and relates it to insufficient nucleotide supply. Preserve this contextual IMP; EBV-transformed B-cell behavior and CTPS2 compensation are distinguished from a universal failure of every B-cell state. Supporting Evidence: |
| GO:0042802 identical protein binding | IBA GO_REF:0000033 | ACCEPT | Summary: Human CTPS1 structures and reconstitution establish homotetramers and repeated identical-subunit contacts in filaments. Reason: Human CTPS1 structures and reconstitution establish homotetramers and repeated identical-subunit contacts in filaments. This supports identical protein binding. It does not require a separate binding-only core alongside the catalytic unit, and a homotetramer must not be relabeled as a homodimer merely because the latter is a child term. |
| GO:0042802 identical protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | ACCEPT | Summary: The literal 2014 human two-hybrid self-pair is preserved as record 3. Reason: The literal 2014 human two-hybrid self-pair is preserved as record 3. Exact sequences/ROGIDs support the recorded displayed protein. Independent human-enzyme structures establish homotetramers and stacked-tetramer contacts, making this positive self-association coherent with the catalytic assembly. It is not automatically narrowed to homodimerization. No separate binding-only core is needed. |
| GO:0042802 identical protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | ACCEPT | Summary: The three literal HuRI human CTPS1 self-pairs are preserved as records 0–2. Reason: The three literal HuRI human CTPS1 self-pairs are preserved as records 0–2. Exact sequences/ROGIDs support the recorded displayed protein. Independent human-enzyme structures establish homotetramers and stacked-tetramer contacts, making this positive self-association coherent with the catalytic assembly. It is not automatically narrowed to homodimerization. No separate binding-only core is needed. |
| GO:0044210 'de novo' CTP biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: The existing de novo CTP biosynthesis assertion is supported: CTPS1 directly performs the UTP-to-CTP step, with substrate conversion and inhibitor/cytidine-salvage contrast in the assessed originals. Reason: The existing de novo CTP biosynthesis assertion is supported: CTPS1 directly performs the UTP-to-CTP step, with substrate conversion and inhibitor/cytidine-salvage contrast in the assessed originals. It need not perform every upstream pyrimidine-ring synthesis step to participate. Retain this existing assertion; do not add a duplicate NEW biosynthesis annotation. |
| GO:0090407 organophosphate biosynthetic process | IEA GO_REF:0000117 | MODIFY | Summary: The matched rule supports a broad biosynthetic role that can be specified as CTP synthesis. Reason: The current ARBA00029048 projection matches human branch 17. GO:0090407 has an organophosphate name and children that include the CTP pathway but an inconsistent definition mentioning deoxyribose phosphate. Preserve this ontology anomaly explicitly; it is not evidence that CTPS1 produces deoxyribose phosphate. Refine the broad positive mapping to the measured CTP biosynthetic process, whose typed ancestry includes GO:0090407. This replaces a broader ancestor with an already represented specific process while preserving the independent source assertion; the ancestor is not rejected as biologically false. Proposed replacements: CTP biosynthetic process |
| GO:0097268 cytoophidium | IBA GO_REF:0000033 | ACCEPT | Summary: The on-path PTN000167476 IBD is corroborated by purified human CTPS1 forming stacked-tetramer filaments. Reason: The on-path PTN000167476 IBD is corroborated by purified human CTPS1 forming stacked-tetramer filaments. Substrate-associated human filaments can be highly active, unlike the inhibited bacterial filament state tested in the same 2017 paper. Retain cytoophidium at this regulated assembly scope; do not imply all cellular filaments are active or that all official splice products assemble equivalently. |
| GO:0097268 cytoophidium | IDA PMID:24503052 CTP synthase forms cytoophidia in the cytoplasm and nucleus. | ACCEPT | Summary: The recovered full original and Figure 5 directly show human CTPS1–GFP cytoplasmic and nuclear cytoophidia in HeLa cells. Reason: The recovered full original and Figure 5 directly show human CTPS1–GFP cytoplasmic and nuclear cytoophidia in HeLa cells. Mouse fusion dynamics in other figures and the absence of every-product testing remain separate. Cytoophidia are a regulated structural location, not proof that every filament is constitutively active. Supporting Evidence: |
| GO:0097268 cytoophidium | IDA PMID:25223282 Ack kinase regulates CTP synthase filaments during Drosophil... | ACCEPT | Summary: Although the paper foregrounds Drosophila oogenesis, its actual Results and Methods include human MCF7 CTPS1/ACK1 colocalization and human wild-type/E161K CTPS1–GFP in HEK293 cells. Reason: Although the paper foregrounds Drosophila oogenesis, its actual Results and Methods include human MCF7 CTPS1/ACK1 colocalization and human wild-type/E161K CTPS1–GFP in HEK293 cells. These directly support human filament localization. The E161K assembly behavior and fly rescue do not establish equal activity for the official short splice product. Supporting Evidence: |
| GO:0140861 DNA repair-dependent chromatin remodeling | IDA PMID:40240600 Histone H1 deamidation facilitates chromatin relaxation for ... | ACCEPT | Summary: CTPS1 catalyzes the H1 modification that enables downstream acetylation/chromatin relaxation; purified reaction, catalytic rescue and deamidation-mimic rescue establish performed work rather than nucleotide-supply necessity. Reason: CTPS1 catalyzes the H1 modification that enables downstream acetylation/chromatin relaxation; purified reaction, catalytic rescue and deamidation-mimic rescue establish performed work rather than nucleotide-supply necessity. Supporting Evidence: |
| GO:0160260 protein asparagine deamidase activity | EXP PMID:40240600 Histone H1 deamidation facilitates chromatin relaxation for ... | ACCEPT | Summary: Human H1.4 reaction directly establishes protein asparagine deamidase activity; independently studied IRF3 expands the substrate scope, so generic enzyme class is meaningful alongside the H1 child. Reason: Human H1.4 reaction directly establishes protein asparagine deamidase activity; independently studied IRF3 expands the substrate scope, so generic enzyme class is meaningful alongside the H1 child. |
| GO:0160260 protein asparagine deamidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Both exact mouse experimental donor and human H1-linked RHEA:57416 reaction support this composite IEA enzyme class. Reason: Both exact mouse experimental donor and human H1-linked RHEA:57416 reaction support this composite IEA enzyme class. Source objects remain unchanged. |
| GO:0160260 protein asparagine deamidase activity | ISS GO_REF:0000024 | ACCEPT | Summary: MGI:1858304 is mouse Ctps1/P70698 with direct PMID:39719712 deamidase evidence; human H1 reaction independently corroborates protein-asparagine chemistry. Reason: MGI:1858304 is mouse Ctps1/P70698 with direct PMID:39719712 deamidase evidence; human H1 reaction independently corroborates protein-asparagine chemistry. Keep original ISS evidence. Supporting Evidence: |
| GO:0160264 histone H1N76/N77 asparagine deamidase activity | IDA PMID:40240600 Histone H1 deamidation facilitates chromatin relaxation for ... | ACCEPT | Summary: Purified human-HeLa-cDNA-derived CTPS1 modifies H1.4 N76/N77 with inactive/no-enzyme controls and direct biochemical endpoints; substrate-specific child term is supported. Reason: Purified human-HeLa-cDNA-derived CTPS1 modifies H1.4 N76/N77 with inactive/no-enzyme controls and direct biochemical endpoints; substrate-specific child term is supported. Supporting Evidence: |
| GO:1902340 negative regulation of chromosome condensation | IDA PMID:40240600 Histone H1 deamidation facilitates chromatin relaxation for ... | ACCEPT | Summary: Catalysis initiates the H1-deamidation/EP300-acetylation sequence that reduces chromatin compaction; MNase/ATAC and mutant rescue substantiate negative condensation at DNA damage, without a mitosis-only claim. Reason: Catalysis initiates the H1-deamidation/EP300-acetylation sequence that reduces chromatin compaction; MNase/ATAC and mutant rescue substantiate negative condensation at DNA damage, without a mitosis-only claim. Supporting Evidence: |
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Download this section (compressed HTML)Q: Does the official 360-aa product retain any protein-deamidase activity or form regulated filaments despite loss of residues 1–231?
Suggested experts: CTPS structural enzymology
Q: Can the curated membrane-proteomics assignment be resolved against the CTPS1-specific peptide/table entry from PMID:19946888?
Suggested experts: Membrane proteomics
Q: Should the GO:0090407 definition be reconciled with its organophosphate label and nucleotide-biosynthesis descendants?
Suggested experts: Gene Ontology
Experiment: Compare sequence-verified full-length and official residues 232–591 products in matched purified UTP-to-CTP, H1/IRF3 deamidation and filament assays, with catalytic-dead controls and direct product measurements.
Hypothesis: The N-terminally truncated product may differ from the canonical enzyme in nucleotide synthesis, protein deamidation and assembly.
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