identifier: traitmech:000497 label: Tha system definition: A phage defense system in which an organism possesses a Tha tail-activated HEPN anti-phage locus that can be activated by incoming-phage minor tail proteins to mediate nonspecific RNase-linked defense. definition_source: DOI:10.1038/s41564-024-01661-6 trait_category: GENOMICS term_kind: CLASS mapping_status: PROPOSED parent_traits: - traitmech:000209 synonyms: - synonym_text: Tha synonym_type: EXACT_SYNONYM source: DOI:10.1038/s41564-024-01661-6 - synonym_text: tail-activated, HEPN domain-containing anti-phage system synonym_type: EXACT_SYNONYM source: DOI:10.1038/s41564-024-01661-6 - synonym_text: Tha__Tha synonym_type: RELATED_SYNONYM source: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md evidence: - reference: DOI:10.1038/s41564-024-01661-6 snippet: multiple Staphylococcus aureus prophages encode Tha (tail-activated, HEPN (higher eukaryotes and prokaryotes nucleotide-binding) domain-containing anti-phage system) notes: Rostol et al. define Tha as a tail-activated HEPN anti-phage system encoded by multiple S. aureus prophages. - reference: DOI:10.1038/s41564-024-01661-6 snippet: We demonstrate the function of two Tha systems, Tha-1 and Tha-2, activated by distinct tail proteins notes: Rostol et al. support multiple experimentally tested Tha variants that are activated by different phage tail proteins. - reference: DOI:10.1038/s41564-024-01661-6 snippet: Tha is a non-specific RNase that is activated by conserved minor tail proteins from temperate phages notes: Rostol et al. connect the Tha anti-phage system to minor-tail-protein activation and nonspecific RNase activity. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md snippet: '| Tha | 10\.1038/s41564-024-01661-6 | Bacteriophages avoid autoimmunity from cognate immune systems as an intrinsic part of their life cycles | ' notes: The pinned DefenseFinder article registry maps the Tha source key to the primary Nat Microbiol Tha paper. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md snippet: '| Tha__Tha | | Tha | Custom | 20 |' notes: The pinned DefenseFinder HMM inventory lists one Tha__Tha custom HMM row under the Tha system namespace. canonical_examples: - taxon_id: NCBITaxon:1280 taxon_label: Staphylococcus aureus note: Rostol et al. report that multiple Staphylococcus aureus prophages encode Tha and experimentally test Tha-1 and Tha-2 antiphage defense in S. aureus RN4220. reference: DOI:10.1038/s41564-024-01661-6 causal_graphs: - graph_id: tha_tail_activated_hepn_rnase_defense title: Tha systems activate HEPN RNase defense after tail cues description: Conservative system-level sketch linking a Tha locus to incoming-phage minor-tail-protein activation, Tha HEPN RNase activity, and phage-defense-system possession. scope_status: NONMECHANISTIC scope_notes: The graph captures the Tha system at family scope without asserting that all Tha variants sense the same minor tail protein, have the same cognate Ith inhibitor, block the same phages, share the same native prophage organization, or map to a DefenseFinder rules row. nodes: - node_id: tha_locus label: Tha locus node_type: GENETIC_ELEMENT description: A phage-encoded Tha locus encoding a tail-activated HEPN anti-phage system. - node_id: minor_tail_protein_activation label: minor-tail-protein activation node_type: BIOLOGICAL_PROCESS description: Activation of Tha by incoming-phage minor tail proteins during bacteriophage infection. - node_id: tha_hepn_rnase_activity label: Tha HEPN RNase activity node_type: MOLECULAR_FUNCTION description: Nonspecific RNase activity mediated by a Tha HEPN domain after activation by a cognate minor tail protein. - node_id: tha_system_trait label: Tha system node_type: TRAIT grounding: traitmech:000497 description: Possession of a genome-encoded Tha 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: tha_locus predicate: contributes to predicate_id: RO:0002326 object: minor_tail_protein_activation description: Tha loci encode HEPN anti-phage proteins that can be activated by structural tail proteins of incoming phages. evidence: - reference: DOI:10.1038/s41564-024-01661-6 snippet: a defence system activated by structural tail proteins of incoming phages notes: Rostol et al. define Tha as a defense system activated by incoming-phage structural tail proteins. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md snippet: '| Tha | 10\.1038/s41564-024-01661-6 | Bacteriophages avoid autoimmunity from cognate immune systems as an intrinsic part of their life cycles | ' notes: The pinned DefenseFinder article registry maps the Tha source key to the primary Nat Microbiol Tha paper. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md snippet: '| Tha__Tha | | Tha | Custom | 20 |' notes: The pinned DefenseFinder HMM inventory lists one Tha__Tha custom HMM row under the Tha system namespace. - subject: minor_tail_protein_activation predicate: activates predicate_id: RO:0002213 object: tha_hepn_rnase_activity description: Incoming-phage minor tail proteins activate Tha HEPN-domain RNase activity. evidence: - reference: DOI:10.1038/s41564-024-01661-6 snippet: Tha is a non-specific RNase that is activated by conserved minor tail proteins from temperate phages notes: Rostol et al. connect conserved minor tail proteins to Tha RNase activation. - subject: tha_hepn_rnase_activity predicate: confers predicate_id: METPO:2007700 object: tha_system_trait description: Tha-mediated nonspecific RNase activity realizes the Tha system trait. evidence: - reference: DOI:10.1038/s41564-024-01661-6 snippet: confirming that Tha-1 is a non-specific RNase notes: Rostol et al. validate Tha-1 nonspecific RNase activity. - subject: tha_system_trait predicate: is a predicate_id: rdfs:subClassOf object: phage_defense_system description: Tha system possession is a phage-defense-system trait. evidence: - reference: DOI:10.1038/s41564-024-01661-6 snippet: Tha-1 is an anti-phage system that causes autoimmunity when improperly regulated notes: Rostol et al. experimentally tested the anti-phage properties of Tha-1. discussions: - discussion_id: tha-variant-profile-rule-gap prompt: Resolve Tha variant boundaries, exact minor-tail-protein triggers, Ith inhibitor relationships, native host breadth, and DefenseFinder rule/profile coverage before minting narrower Tha mechanism children. kind: KNOWLEDGE_GAP status: OPEN rationale: Rostol et al. support Tha-1 and Tha-2 as S. aureus prophage-encoded Tha systems activated by distinct incoming-phage minor tail proteins. The pinned DefenseFinder registries map the Tha source key to the same primary paper and list one Tha__Tha custom HMM row, but no exact Tha system rule row was present in the pinned rules table. The first TraitRecord therefore stays at Tha-system scope until separate review resolves variant boundaries, exact activators, Ith inhibitor relationships, native host breadth, and model coverage. evidence: - reference: DOI:10.1038/s41564-024-01661-6 snippet: Tha systems can also block reproduction of the induced tha-positive prophages notes: Rostol et al. report Tha autoimmunity and inhibition by cognate overlapping antisense Ith proteins. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md snippet: '| Tha | 10\.1038/s41564-024-01661-6 | Bacteriophages avoid autoimmunity from cognate immune systems as an intrinsic part of their life cycles | ' notes: The pinned DefenseFinder article registry maps the Tha source key to the primary Nat Microbiol Tha paper. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md snippet: '| Tha__Tha | | Tha | Custom | 20 |' notes: The pinned DefenseFinder HMM inventory lists one Tha__Tha custom HMM row under the Tha system namespace. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv notes: A structured first-pass search of the pinned DefenseFinder rules table found no exact Tha system row. attaches_to: - causal_graphs#tha_tail_activated_hepn_rnase_defense posed_by: codex posed_date: '2026-09-30' curation_history: - timestamp: '2026-09-30T17:20:02Z' curator: codex action: MINTED_TRAITMECH_ID changes: Minted Tha 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; the replacement placeholder is reserved in proposals/metpo_traitmech_v374. llm_assisted: true - timestamp: '2026-09-30T17:20:03Z' curator: codex action: REVIEW_CANONICAL_EXAMPLE_EVIDENCE changes: Reviewed Tha system canonical_examples and kept Staphylococcus aureus because Rostol et al. report that multiple S. aureus prophages encode Tha and experimentally test plasmid-carried Tha-1 and Tha-2 in S. aureus RN4220 phage-challenge assays. No paid research was used. llm_assisted: true