identifier: traitmech:000244 label: CapRel system definition: A phage defense system in which an organism possesses a fused CapRel toxin-antitoxin locus encoding an N-terminal toxSAS toxin domain and a C-terminal antitoxin sensor domain that together can restrict bacteriophage propagation. definition_source: DOI:10.1038/s41586-022-05444-z trait_category: GENOMICS term_kind: CLASS mapping_status: PROPOSED parent_traits: - traitmech:000209 synonyms: - synonym_text: CapRel toxin-antitoxin system synonym_type: EXACT_SYNONYM source: DOI:10.1038/s41586-022-05444-z - synonym_text: fused CapRel system synonym_type: EXACT_SYNONYM source: DOI:10.1038/s41586-022-05444-z evidence: - reference: DOI:10.1038/s41586-022-05444-z snippet: protects Escherichia coli against diverse phages notes: Zhang et al. support CapRelSJ46 as a fused CapRel toxin-antitoxin antiphage system that protects E. coli against several phages. - reference: DOI:10.1038/s41586-022-05444-z snippet: newly synthesized major capsid protein binds directly to the C-terminal domain notes: Zhang et al. support direct sensing of a phage major capsid protein by the CapRelSJ46 C-terminal antitoxin domain. - reference: DOI:10.1038/s41586-022-05444-z snippet: This open state enables CapRelSJ46 to pyrophosphorylate tRNAs and inhibit translation notes: Zhang et al. connect phage-triggered CapRel activation to tRNA pyrophosphorylation, translation blockade, and restriction of viral infection. - reference: DOI:10.1038/s41586-022-05444-z snippet: fused CapRels can provide anti-phage defence, with variable phage specificity notes: Zhang et al. support treating fused CapRel loci as a family-level phage-defense system rather than only one CapRelSJ46 instance. - reference: DOI:10.1038/s41586-024-08039-y snippet: can directly bind and sense two completely unrelated and structurally different proteins using the same sensory domain notes: Zhang et al. independently support CapRelSJ46 as a direct phage-trigger-sensing immune protein and show that a single sensory domain can recognize more than one phage trigger. - reference: DOI:10.1038/s41586-024-08039-y snippet: can fully evade CapRelSJ46 defence only when both triggers are mutated notes: Zhang et al. connect multifactorial trigger sensing to CapRel-mediated defense during Bas11 phage infection. causal_graphs: - graph_id: caprel_phage_triggered_translation_blockade title: CapRel sensors couple phage trigger binding to translation blockade description: Evidence-backed process sketch linking a fused CapRel toxin-antitoxin locus to direct phage-protein sensing, toxSAS activation, tRNA pyrophosphorylation, translation inhibition, and restricted phage propagation. scope_status: NONMECHANISTIC scope_notes: The graph captures CapRelSJ46 major-capsid-protein and Gp54 trigger evidence without claiming one universal CapRel phage trigger, allosteric route, escape route, or phage specificity across all fused CapRel homologs. nodes: - node_id: caprel_locus label: CapRel locus node_type: GENETIC_ELEMENT description: A fused CapRel toxin-antitoxin locus encoding an N-terminal toxSAS toxin domain and a C-terminal antitoxin sensor domain. - node_id: phage_trigger_binding label: phage trigger binding node_type: BIOLOGICAL_PROCESS description: Direct binding of a phage-encoded trigger protein to the CapRel antitoxin sensor domain. - node_id: caprel_toxin_activation label: CapRel toxSAS activation node_type: BIOLOGICAL_PROCESS description: Relief of autoinhibition that activates the N-terminal CapRel toxSAS toxin domain. - node_id: trna_pyrophosphorylation label: tRNA pyrophosphorylation node_type: BIOLOGICAL_PROCESS description: Pyrophosphorylation of transfer RNAs by activated CapRel toxSAS toxin activity. - node_id: translation_blockade label: translation blockade node_type: BIOLOGICAL_PROCESS description: Inhibition of cellular translation downstream of CapRel-mediated tRNA pyrophosphorylation. - node_id: restricted_phage_propagation label: restricted phage propagation node_type: BIOLOGICAL_PROCESS description: Reduced bacteriophage propagation in cells whose CapRel system has blocked translation. - node_id: caprel_system_trait label: CapRel system node_type: TRAIT grounding: traitmech:000244 description: Possession of a genome-encoded fused CapRel toxin-antitoxin 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: caprel_locus predicate: contributes to predicate_id: RO:0002326 object: caprel_toxin_activation description: Fused CapRel loci encode the N-terminal toxin domain and C-terminal antitoxin sensor domain that keep CapRel inhibited until phage trigger binding. evidence: - reference: DOI:10.1038/s41586-022-05444-z snippet: regulates the toxic N-terminal region, serving as both antitoxin and phage infection sensor notes: Zhang et al. support the C-terminal CapRel domain as both antitoxin and phage-infection sensor. - subject: phage_trigger_binding predicate: activates predicate_id: RO:0002213 object: caprel_toxin_activation description: Binding of phage-encoded triggers to the C-terminal CapRel sensor relieves autoinhibition of the toxSAS domain. evidence: - reference: DOI:10.1038/s41586-022-05444-z snippet: major capsid protein binds directly to the C-terminal domain notes: Zhang et al. identify phage major capsid protein as a direct CapRelSJ46 trigger. - reference: DOI:10.1038/s41586-024-08039-y snippet: directly binds and senses two completely unrelated and structurally different phage proteins using the same sensor domain notes: Zhang et al. show that CapRelSJ46 can directly sense an alternative Gp54 trigger. - subject: caprel_toxin_activation predicate: contributes to predicate_id: RO:0002326 object: trna_pyrophosphorylation description: CapRel trigger binding activates the toxSAS domain that pyrophosphorylates tRNAs. evidence: - reference: DOI:10.1038/s41586-022-05444-z snippet: This open state enables CapRelSJ46 to pyrophosphorylate tRNAs notes: Zhang et al. connect relief of autoinhibition to CapRel toxSAS-mediated tRNA pyrophosphorylation. - subject: trna_pyrophosphorylation predicate: contributes to predicate_id: RO:0002326 object: translation_blockade description: tRNA pyrophosphorylation blocks cellular translation during CapRel antiviral activation. evidence: - reference: DOI:10.1038/s41586-022-05444-z snippet: pyrophosphorylate tRNAs, which blocks translation notes: Zhang et al. identify translation blockade as the immediate outcome of CapRel-mediated tRNA pyrophosphorylation. - subject: translation_blockade predicate: contributes to predicate_id: RO:0002326 object: restricted_phage_propagation description: Translation blockade contributes to restriction of the infecting phage. evidence: - reference: DOI:10.1038/s41586-022-05444-z snippet: blocks translation to restrict viral infection notes: Zhang et al. connect translation blockade to restriction of viral infection. - subject: restricted_phage_propagation predicate: confers predicate_id: METPO:2007700 object: caprel_system_trait description: CapRel-dependent restriction of phage propagation realizes the CapRel system trait. evidence: - reference: DOI:10.1038/s41586-022-05444-z snippet: fused CapRels can provide anti-phage defence notes: Zhang et al. support fused CapRels as anti-phage defense systems. - subject: caprel_system_trait predicate: is a predicate_id: rdfs:subClassOf object: phage_defense_system description: CapRel system possession is a phage-defense-system trait. evidence: - reference: DOI:10.1038/s41586-022-05444-z snippet: a fused anti-phage toxin-antitoxin system notes: Zhang et al. place CapRelSJ46 in the anti-phage toxin-antitoxin-system family. discussions: - discussion_id: caprel-trigger-and-family-breadth-gap prompt: Resolve CapRel trigger breadth, phage escape routes, and family-specific activation before minting narrower CapRel mechanism children. kind: KNOWLEDGE_GAP status: OPEN rationale: Zhang et al. support CapRelSJ46 sensing of a major capsid protein and an unrelated Gp54 trigger, but fused CapRel homologs need separate review before TraitMech asserts one universal phage trigger, CapRel escape route, tRNA target spectrum, or phage specificity across the family. posed_by: codex posed_date: '2026-09-18' curation_history: - timestamp: '2026-09-18T15:19:24Z' curator: codex action: MINTED_TRAITMECH_ID changes: Minted CapRel system as a DOI-backed GENOMICS TraitRecord under phage defense system after an ignored-and-hidden duplicate review found no exact live TraitMech, METPO, or prior proposal record; the replacement placeholder is reserved in proposals/metpo_traitmech_v121. llm_assisted: true - timestamp: '2026-09-18T15:43:45Z' curator: codex action: UPDATED_DEFINITION changes: Tightened the CapRel system definition around fused CapRel locus possession and expanded a dangling CapRel activation snippet after late Copilot feedback in issue 1001. llm_assisted: true