identifier: traitmech:000415 label: Clover system definition: A phage defense system in which an organism possesses a Clover anti-phage system whose CloA deoxynucleoside triphosphohydrolase dynamically responds to an activating phage cue and to a CloB-produced inhibitory p3diT nucleotide signal to coordinate nucleotide-pool disruption during antiviral immunity. definition_source: DOI:10.1038/s41586-026-10135-0 trait_category: GENOMICS term_kind: CLASS mapping_status: PROPOSED parent_traits: - traitmech:000209 synonyms: - synonym_text: Clover synonym_type: EXACT_SYNONYM source: DOI:10.1038/s41586-026-10135-0 evidence: - reference: DOI:10.1038/s41586-026-10135-0 snippet: Here we identify Clover, a bacterial anti-phage defence system that overcomes this trade-off by encoding a deoxynucleoside triphosphohydrolase enzyme (CloA) that dynamically responds to both an activating phage cue and an inhibitory nucleotide immune signal produced by a partnering regulatory enzyme (CloB). notes: Yu and Kranzusch define Clover as a bacterial anti-phage defence system encoding CloA and CloB. - reference: DOI:10.1038/s41586-026-10135-0 snippet: Analysis of phage restriction by Clover in cells and reconstitution of enzymatic function in vitro demonstrate that CloA is a dGTPase that responds to viral enzymes that increase cellular levels of dTTP. notes: Yu and Kranzusch support CloA as a Clover dGTPase that responds to viral enzymes that increase cellular dTTP. - reference: DOI:10.1038/s41586-026-10135-0 snippet: To restrain CloA activation in the absence of infection, we show that CloB synthesizes a dTTP-related inhibitory nucleotide signal, p3diT notes: Yu and Kranzusch support CloB synthesis of the inhibitory p3diT nucleotide signal. - reference: DOI:10.1038/s41586-026-10135-0 snippet: Cryo-electron microscopy structures of CloA in activated and suppressed states reveal how dTTP and p3diT control distinct allosteric sites and regulate effector function. notes: Yu and Kranzusch resolve activated and suppressed CloA states controlled by dTTP and p3diT. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md snippet: '| Clover | 10\.1038/s41586-026-10135-0 | Nucleotide signals coordinate activation and inhibition of bacterial immunity |' notes: The pinned DefenseFinder article registry maps the named Clover system to the Yu and Kranzusch nucleotide-signal anti-phage-defense paper. The pinned HMM inventory and rules table do not list Clover, so this row is name-to-paper evidence rather than model-component evidence. causal_graphs: - graph_id: clover_dttp_p3dit_regulated_dgtpase title: Clover coordinates CloA activation and inhibition description: Conservative sketch linking a Clover locus to p3diT-gated CloA dGTPase activity, regulation of antiviral immunity, and Clover system possession. scope_status: NONMECHANISTIC scope_notes: The graph captures Clover at the experimentally supported CloA/CloB dGTPase-regulation level without asserting exact native host breadth, full sensitive-phage breadth, profile-to-component mappings, or a DefenseFinder detection rule absent from the pinned model files. nodes: - node_id: clover_locus label: Clover locus node_type: GENETIC_ELEMENT description: A Clover anti-phage locus encoding the CloA dGTPase and partnering CloB regulatory enzyme. - node_id: cloa_dgtpase_activation label: CloA dGTPase activation node_type: BIOLOGICAL_PROCESS description: Activation of CloA deoxynucleoside triphosphohydrolase activity in response to a phage cue linked to increased dTTP. - node_id: clob_p3dit_synthesis label: CloB p3diT synthesis node_type: BIOLOGICAL_PROCESS description: CloB synthesis of a dTTP-related p3diT inhibitory nucleotide signal that suppresses CloA activation without infection. - node_id: clover_system_trait label: Clover system node_type: TRAIT grounding: traitmech:000415 description: Possession of a genome-encoded Clover phage-defense system. - node_id: phage_defense_system label: phage defense system node_type: TRAIT grounding: traitmech:000209 description: Possession of one or more genome-encoded immune systems that inhibit bacteriophage infection. edges: - subject: clover_locus predicate: enables predicate_id: RO:0002327 object: cloa_dgtpase_activation description: A Clover locus encodes the CloA dGTPase that responds to viral enzymes increasing cellular dTTP. evidence: - reference: DOI:10.1038/s41586-026-10135-0 snippet: Here we identify Clover, a bacterial anti-phage defence system that overcomes this trade-off by encoding a deoxynucleoside triphosphohydrolase enzyme (CloA) that dynamically responds to both an activating phage cue and an inhibitory nucleotide immune signal produced by a partnering regulatory enzyme (CloB). notes: Yu and Kranzusch identify Clover as the system encoding CloA and CloB. - reference: DOI:10.1038/s41586-026-10135-0 snippet: Analysis of phage restriction by Clover in cells and reconstitution of enzymatic function in vitro demonstrate that CloA is a dGTPase that responds to viral enzymes that increase cellular levels of dTTP. notes: Yu and Kranzusch connect Clover to dTTP-responsive CloA dGTPase activity. - subject: clover_locus predicate: enables predicate_id: RO:0002327 object: clob_p3dit_synthesis description: A Clover locus encodes CloB, which synthesizes the inhibitory p3diT signal. evidence: - reference: DOI:10.1038/s41586-026-10135-0 snippet: To restrain CloA activation in the absence of infection, we show that CloB synthesizes a dTTP-related inhibitory nucleotide signal, p3diT notes: Yu and Kranzusch connect CloB to p3diT synthesis. - subject: clob_p3dit_synthesis predicate: negatively regulates predicate_id: RO:0002212 object: cloa_dgtpase_activation description: The CloB-produced p3diT nucleotide signal binds CloA and suppresses CloA activation. evidence: - reference: DOI:10.1038/s41586-026-10135-0 snippet: To restrain CloA activation in the absence of infection, we show that CloB synthesizes a dTTP-related inhibitory nucleotide signal, p3diT notes: Yu and Kranzusch support p3diT-dependent suppression of CloA activation. - subject: cloa_dgtpase_activation predicate: confers predicate_id: METPO:2007700 object: clover_system_trait description: Regulated CloA effector activity realizes Clover antiviral immunity. evidence: - reference: DOI:10.1038/s41586-026-10135-0 snippet: Our results define how nucleotide signals coordinate both activation and inhibition of antiviral immunity notes: Yu and Kranzusch frame nucleotide-mediated CloA activation and inhibition as coordinated antiviral immunity. - reference: DOI:10.1038/s41586-026-10135-0 snippet: Cryo-electron microscopy structures of CloA in activated and suppressed states reveal how dTTP and p3diT control distinct allosteric sites and regulate effector function. notes: Yu and Kranzusch show that dTTP and p3diT regulate Clover effector function through distinct CloA sites. - subject: clover_system_trait predicate: is a predicate_id: rdfs:subClassOf object: phage_defense_system description: Clover system possession is a phage-defense-system trait. evidence: - reference: DOI:10.1038/s41586-026-10135-0 snippet: Here we identify Clover, a bacterial anti-phage defence system that overcomes this trade-off by encoding a deoxynucleoside triphosphohydrolase enzyme (CloA) that dynamically responds to both an activating phage cue and an inhibitory nucleotide immune signal produced by a partnering regulatory enzyme (CloB). notes: Yu and Kranzusch define Clover as a bacterial anti-phage defence system. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md snippet: '| Clover | 10\.1038/s41586-026-10135-0 | Nucleotide signals coordinate activation and inhibition of bacterial immunity |' notes: The pinned DefenseFinder article registry maps the named Clover system to the Yu and Kranzusch nucleotide-signal anti-phage-defense paper. The pinned HMM inventory and rules table do not list Clover, so this row is name-to-paper evidence rather than model-component evidence. discussions: - discussion_id: clover-defensefinder-model-gap prompt: Resolve Clover native host breadth, sensitive-phage breadth, profile-to-component coverage, and DefenseFinder HMM/rules coverage before minting narrower Clover mechanism children. kind: KNOWLEDGE_GAP status: OPEN rationale: Yu and Kranzusch support Clover as a bacterial anti-phage defence system whose CloA dGTPase is activated and suppressed by nucleotide signals, while the pinned DefenseFinder article registry names a Clover system. The pinned DefenseFinder HMM inventory and rules table have no Clover rows, and the evidence does not yet resolve native host breadth, full target-phage breadth, or profile-to-activity modeling. evidence: - reference: DOI:10.1038/s41586-026-10135-0 snippet: Cryo-electron microscopy structures of CloA in activated and suppressed states reveal how dTTP and p3diT control distinct allosteric sites and regulate effector function. notes: Yu and Kranzusch support a CloA/CloB mechanism regulated by dTTP and p3diT. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md snippet: '| Clover | 10\.1038/s41586-026-10135-0 | Nucleotide signals coordinate activation and inhibition of bacterial immunity |' notes: The pinned DefenseFinder article registry maps the named Clover system to the Yu and Kranzusch nucleotide-signal anti-phage-defense paper. The pinned HMM inventory and rules table do not list Clover, so this row is name-to-paper evidence rather than model-component evidence. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md notes: The pinned DefenseFinder HMM inventory does not list Clover, leaving profile-level components unresolved. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv notes: The pinned DefenseFinder rules table does not list Clover, leaving rule-level detection criteria unresolved. attaches_to: - causal_graphs#clover_dttp_p3dit_regulated_dgtpase posed_by: codex posed_date: '2026-09-27' curation_history: - timestamp: '2026-09-27T19:36:20Z' curator: codex action: MINTED_TRAITMECH_ID changes: Minted Clover system as a DOI-backed GENOMICS TraitRecord under phage defense system after an ignored-and-hidden duplicate review found no exact live TraitMech, METPO, history, or prior proposal record; kept the graph at CloA/CloB dGTPase-regulation level because the pinned DefenseFinder article row is not backed by pinned HMM or rules rows; the replacement placeholder is reserved in proposals/metpo_traitmech_v292. llm_assisted: true - timestamp: '2026-09-27T19:36:21Z' curator: codex action: REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP changes: Reviewed Clover system during canonical-example issue 444 enforcement and left canonical_examples empty because the sources support cloned Salmonella enterica and Escherichia coli operon expression in phage-challenge assays plus a DefenseFinder article-registry system name, but not a direct native microbial isolate exemplar with experimentally verified endogenous Clover activity. No paid research was used. llm_assisted: true