identifier: traitmech:000400
label: Rst_2TM_1TM_TIR system
definition: A phage defense system in which an organism possesses a three-protein
  Rst_2TM_1TM_TIR locus represented by DefenseFinder as a three-profile model requiring
  Rst_2TM_1TM_TIR__Rst_1TM_TIR, Rst_2TM_1TM_TIR__Rst_2TM_TIR, and Rst_2TM_1TM_TIR__Rst_TIR_tm
  and experimentally linked to multi-phage protection when expressed in Escherichia
  coli C.
definition_source: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
trait_category: GENOMICS
term_kind: CLASS
mapping_status: PROPOSED
parent_traits:
- traitmech:000209
synonyms:
- synonym_text: Rst_2TM_1TM_TIR
  synonym_type: RELATED_SYNONYM
  source: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
- synonym_text: Rst_2TM_1TM_TIR__Rst_1TM_TIR
  synonym_type: RELATED_SYNONYM
  source: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
- synonym_text: Rst_2TM_1TM_TIR__Rst_2TM_TIR
  synonym_type: RELATED_SYNONYM
  source: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
- synonym_text: Rst_2TM_1TM_TIR__Rst_TIR_tm
  synonym_type: RELATED_SYNONYM
  source: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
evidence:
- reference: DOI:10.1016/j.chom.2022.02.018
  snippet: Phage resistance heatmaps of the validated defense systems show the median
    fold resistance of three independent replicates against a panel of eight phages
  notes: The Figure 5 legend frames the cloned Rst_2TM_1TM_TIR hit as one of the validated
    defense systems in a replicated phage-resistance heatmap.
- reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
  snippet: The Rst_2TM_1TM_TIR system is carried by the P2-like phage AC1 and protects
    *Escherichia coli* C against lambda, LF82_P8 and P2 phages. This system is composed
    of three proteins, Rst_TIR_tm, which contains a TIR (Toll/interleukin-1 receptor)
    domain, Rst_1TM_TIR, which contains a transmembrane helix (TM) and Rst_2TM_TIR,
    that contains two TMs :ref{doi=10.1016/j.chom.2022.02.018}.
  notes: The pinned DefenseFinder wiki page names Rst_2TM_1TM_TIR as a three-protein
    system and links the AC1 locus to lambda, LF82_P8, and P2 protection in Escherichia
    coli C.
- reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
  snippet: Rousset et al. suggested that the TIR-containing protein could generate
    a nucleotide messenger that in turn could activate the associated transmembrane
    proteins.
  notes: The pinned DefenseFinder wiki page records the unresolved Rousset et al.
    hypothesis that the TIR-containing protein could produce a nucleotide messenger
    that activates the transmembrane proteins.
- reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
  snippet: As far as we are aware, the molecular mechanism is unknown.
  notes: The pinned DefenseFinder wiki page leaves the Rst_2TM_1TM_TIR molecular mechanism
    unresolved.
- reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
  snippet: 'The Rst_2TM_1TM_TIR is composed of 3 proteins: Rst_2TM_TIR, Rst_TIR_tm
    and Rst_1TM_TIR.'
  notes: The pinned DefenseFinder wiki page describes Rst_2TM_1TM_TIR as a three-component
    Rst_2TM_TIR/Rst_TIR_tm/Rst_1TM_TIR system.
- reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
  snippet: The Rst_2TM_1TM_TIR system in *Escherichia coli* (GCF_004006575.1, NZ_CP034787)
    is composed of 3 proteins Rst_TIR_tm (WP_023140578.1) Rst_1TM_TIR (WP_001534953.1)
    Rst_2TM_TIR (WP_023140577.1)
  notes: The DefenseFinder wiki illustrates a predicted three-protein Rst_2TM_1TM_TIR
    locus in RefSeq assembly GCF_004006575.1 on NZ_CP034787.
- reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
  snippet: "Rousset_2022[<a href='https://doi.org/10.1016/j.chom.2022.02.018'>Rousset\
    \ et al., 2022</a>] --> Origin_0\n    Origin_0[Escherichia coli C\n<a href='https://ncbi.nlm.nih.gov/protein/WP_001534952.1'>WP_001534952.1</a>,\
    \ <a href='https://ncbi.nlm.nih.gov/protein/WP_001534953.1'>WP_001534953.1</a>,\
    \ <a href='https://ncbi.nlm.nih.gov/protein/WP_001534955.1'>WP_001534955.1</a>]\
    \ --> Expressed_0[Escherichia coli C]\n    Expressed_0[Escherichia coli C] ---->\
    \ Lambda & LF82_P8 & P2 & SIAC10 & SID07 & DC1 & AC1"
  notes: The DefenseFinder experimental-validation diagram links Rousset et al. to
    an Escherichia coli C source locus expressed in Escherichia coli C against seven
    phages.
- reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
  snippet: "subgraph Title4[Protects against]\n        Lambda\n        LF82_P8\n \
    \       P2\n        SIAC10\n        SID07\n        DC1\n        AC1"
  notes: The DefenseFinder experimental-validation diagram lists lambda, LF82_P8,
    P2, SIAC10, SID07, DC1, and AC1 in the Rst_2TM_1TM_TIR protects-against subgraph.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
  snippet: Rst_2TM_1TM_TIR | 10\.1101/2021\.01\.21\.427644 | Prophage-encoded hotspots
    of bacterial immune systems
  notes: The DefenseFinder article registry maps the named Rst_2TM_1TM_TIR system
    to the Rousset et al. preprint.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
  snippet: "Rst_2TM_1TM_TIR\tRst_2TM_1TM_TIR\t3\t3\tRst_2TM_1TM_TIR__Rst_1TM_TIR,\
    \ Rst_2TM_1TM_TIR__Rst_2TM_TIR, Rst_2TM_1TM_TIR__Rst_TIR_tm\t\t\t"
  notes: The DefenseFinder rules table models Rst_2TM_1TM_TIR as a three-profile system
    requiring Rst_2TM_1TM_TIR__Rst_1TM_TIR, Rst_2TM_1TM_TIR__Rst_2TM_TIR, and Rst_2TM_1TM_TIR__Rst_TIR_tm.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
  snippet: '| Rst_2TM_1TM_TIR__Rst_1TM_TIR                     | Rst_2TM_1TM_TIR__Rst_1TM_TIR                     |
    Rst_2TM_1TM_TIR        | Custom                  | 20     |

    | Rst_2TM_1TM_TIR__Rst_2TM_TIR                     | Rst_2TM_1TM_TIR__Rst_2TM_TIR                     |
    Rst_2TM_1TM_TIR        | Custom                  | 20     |

    | Rst_2TM_1TM_TIR__Rst_TIR_tm                      | Rst_2TM_1TM_TIR__Rst_TIR_tm                      |
    Rst_2TM_1TM_TIR        | Custom                  | 20     |'
  notes: The DefenseFinder HMM inventory records the Rst_1TM_TIR, Rst_2TM_TIR, and
    Rst_TIR_tm profiles under Rst_2TM_1TM_TIR.
causal_graphs:
- graph_id: rst_2tm_1tm_tir_locus_restricts_phages
  title: Rst_2TM_1TM_TIR loci restrict phages
  description: Conservative system-level sketch linking the named Rst_2TM_1TM_TIR
    three-gene locus model to multi-phage resistance.
  scope_status: NONMECHANISTIC
  scope_notes: The graph captures Rst_2TM_1TM_TIR as a named DefenseFinder three-profile
    phage-defense system while leaving native host breadth, accession-level component
    grounding, the putative nucleotide messenger, and the mechanism of phage restriction
    unresolved.
  nodes:
  - node_id: rst_2tm_1tm_tir_locus
    label: Rst_2TM_1TM_TIR locus
    node_type: GENETIC_ELEMENT
    description: A three-gene Rst_TIR_tm/Rst_1TM_TIR/Rst_2TM_TIR phage-defense locus
      represented by the custom DefenseFinder Rst_2TM_1TM_TIR profiles.
  - node_id: multi_phage_resistance
    label: multi-phage resistance
    node_type: BIOLOGICAL_PROCESS
    description: Resistance against multiple phages in a host expressing an Rst_2TM_1TM_TIR
      locus.
  - node_id: rst_2tm_1tm_tir_system_trait
    label: Rst_2TM_1TM_TIR system
    node_type: TRAIT
    grounding: traitmech:000400
    description: Possession of a genome-encoded Rst_2TM_1TM_TIR 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: rst_2tm_1tm_tir_locus
    predicate: contributes to
    predicate_id: RO:0002326
    object: multi_phage_resistance
    description: The pinned DefenseFinder wiki links AC1 Rst_2TM_1TM_TIR to protection
      against multiple phages, and DefenseFinder models Rst_2TM_1TM_TIR as a three-profile
      system.
    evidence:
    - reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
      snippet: The Rst_2TM_1TM_TIR system is carried by the P2-like phage AC1 and
        protects *Escherichia coli* C against lambda, LF82_P8 and P2 phages. This
        system is composed of three proteins, Rst_TIR_tm, which contains a TIR (Toll/interleukin-1
        receptor) domain, Rst_1TM_TIR, which contains a transmembrane helix (TM) and
        Rst_2TM_TIR, that contains two TMs :ref{doi=10.1016/j.chom.2022.02.018}.
      notes: The pinned DefenseFinder wiki page names Rst_2TM_1TM_TIR as a three-protein
        system and links the AC1 locus to lambda, LF82_P8, and P2 protection in Escherichia
        coli C.
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
      snippet: "Rst_2TM_1TM_TIR\tRst_2TM_1TM_TIR\t3\t3\tRst_2TM_1TM_TIR__Rst_1TM_TIR,\
        \ Rst_2TM_1TM_TIR__Rst_2TM_TIR, Rst_2TM_1TM_TIR__Rst_TIR_tm\t\t\t"
      notes: The DefenseFinder rules table models Rst_2TM_1TM_TIR as a three-profile
        system requiring Rst_2TM_1TM_TIR__Rst_1TM_TIR, Rst_2TM_1TM_TIR__Rst_2TM_TIR,
        and Rst_2TM_1TM_TIR__Rst_TIR_tm.
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
      snippet: '| Rst_2TM_1TM_TIR__Rst_1TM_TIR                     | Rst_2TM_1TM_TIR__Rst_1TM_TIR                     |
        Rst_2TM_1TM_TIR        | Custom                  | 20     |

        | Rst_2TM_1TM_TIR__Rst_2TM_TIR                     | Rst_2TM_1TM_TIR__Rst_2TM_TIR                     |
        Rst_2TM_1TM_TIR        | Custom                  | 20     |

        | Rst_2TM_1TM_TIR__Rst_TIR_tm                      | Rst_2TM_1TM_TIR__Rst_TIR_tm                      |
        Rst_2TM_1TM_TIR        | Custom                  | 20     |'
      notes: The DefenseFinder HMM inventory records the Rst_1TM_TIR, Rst_2TM_TIR,
        and Rst_TIR_tm profiles under Rst_2TM_1TM_TIR.
  - subject: multi_phage_resistance
    predicate: confers
    predicate_id: METPO:2007700
    object: rst_2tm_1tm_tir_system_trait
    description: Rst_2TM_1TM_TIR-linked multi-phage resistance realizes the Rst_2TM_1TM_TIR
      system trait.
    evidence:
    - reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
      snippet: "Rousset_2022[<a href='https://doi.org/10.1016/j.chom.2022.02.018'>Rousset\
        \ et al., 2022</a>] --> Origin_0\n    Origin_0[Escherichia coli C\n<a href='https://ncbi.nlm.nih.gov/protein/WP_001534952.1'>WP_001534952.1</a>,\
        \ <a href='https://ncbi.nlm.nih.gov/protein/WP_001534953.1'>WP_001534953.1</a>,\
        \ <a href='https://ncbi.nlm.nih.gov/protein/WP_001534955.1'>WP_001534955.1</a>]\
        \ --> Expressed_0[Escherichia coli C]\n    Expressed_0[Escherichia coli C]\
        \ ----> Lambda & LF82_P8 & P2 & SIAC10 & SID07 & DC1 & AC1"
      notes: The DefenseFinder experimental-validation diagram links Rousset et al.
        to an Escherichia coli C source locus expressed in Escherichia coli C against
        seven phages.
    - reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
      snippet: "subgraph Title4[Protects against]\n        Lambda\n        LF82_P8\n\
        \        P2\n        SIAC10\n        SID07\n        DC1\n        AC1"
      notes: The DefenseFinder experimental-validation diagram lists lambda, LF82_P8,
        P2, SIAC10, SID07, DC1, and AC1 in the Rst_2TM_1TM_TIR protects-against subgraph.
  - subject: rst_2tm_1tm_tir_system_trait
    predicate: is a
    predicate_id: rdfs:subClassOf
    object: phage_defense_system
    description: Rst_2TM_1TM_TIR system possession is a phage-defense-system trait.
    evidence:
    - reference: DOI:10.1016/j.chom.2022.02.018
      snippet: Phage resistance heatmaps of the validated defense systems show the
        median fold resistance of three independent replicates against a panel of
        eight phages
      notes: The Figure 5 legend frames the cloned Rst_2TM_1TM_TIR hit as one of the
        validated defense systems in a replicated phage-resistance heatmap.
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
      snippet: Rst_2TM_1TM_TIR | 10\.1101/2021\.01\.21\.427644 | Prophage-encoded
        hotspots of bacterial immune systems
      notes: The DefenseFinder article registry maps the named Rst_2TM_1TM_TIR system
        to the Rousset et al. preprint.
discussions:
- discussion_id: rst-2tm-1tm-tir-mechanism-gap
  prompt: Resolve Rst_2TM_1TM_TIR native host breadth, accession-level components,
    the proposed TIR-derived nucleotide messenger, and the downstream transmembrane
    activation mechanism before minting narrower Rst_2TM_1TM_TIR mechanism children.
  kind: KNOWLEDGE_GAP
  status: OPEN
  rationale: The pinned DefenseFinder wiki supports a three-component AC1 Rst_2TM_1TM_TIR
    system that protects Escherichia coli C against multiple phages, and DefenseFinder
    represents Rst_2TM_1TM_TIR as a required three-profile model. Rousset et al. proposed
    that the TIR-containing protein could generate a nucleotide messenger to activate
    associated transmembrane proteins, but the wiki still records the molecular mechanism
    as unknown.
  evidence:
  - reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
    snippet: Rousset et al. suggested that the TIR-containing protein could generate
      a nucleotide messenger that in turn could activate the associated transmembrane
      proteins.
    notes: The pinned DefenseFinder wiki page records the unresolved Rousset et al.
      hypothesis that the TIR-containing protein could produce a nucleotide messenger
      that activates the transmembrane proteins.
  - reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
    snippet: As far as we are aware, the molecular mechanism is unknown.
    notes: The pinned DefenseFinder wiki page leaves the Rst_2TM_1TM_TIR molecular
      mechanism unresolved.
  - reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
    snippet: 'The Rst_2TM_1TM_TIR is composed of 3 proteins: Rst_2TM_TIR, Rst_TIR_tm
      and Rst_1TM_TIR.'
    notes: The pinned DefenseFinder wiki page describes Rst_2TM_1TM_TIR as a three-component
      Rst_2TM_TIR/Rst_TIR_tm/Rst_1TM_TIR system.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
    snippet: "Rst_2TM_1TM_TIR\tRst_2TM_1TM_TIR\t3\t3\tRst_2TM_1TM_TIR__Rst_1TM_TIR,\
      \ Rst_2TM_1TM_TIR__Rst_2TM_TIR, Rst_2TM_1TM_TIR__Rst_TIR_tm\t\t\t"
    notes: The DefenseFinder rules table models Rst_2TM_1TM_TIR as a three-profile
      system requiring Rst_2TM_1TM_TIR__Rst_1TM_TIR, Rst_2TM_1TM_TIR__Rst_2TM_TIR,
      and Rst_2TM_1TM_TIR__Rst_TIR_tm.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
    snippet: '| Rst_2TM_1TM_TIR__Rst_1TM_TIR                     | Rst_2TM_1TM_TIR__Rst_1TM_TIR                     |
      Rst_2TM_1TM_TIR        | Custom                  | 20     |

      | Rst_2TM_1TM_TIR__Rst_2TM_TIR                     | Rst_2TM_1TM_TIR__Rst_2TM_TIR                     |
      Rst_2TM_1TM_TIR        | Custom                  | 20     |

      | Rst_2TM_1TM_TIR__Rst_TIR_tm                      | Rst_2TM_1TM_TIR__Rst_TIR_tm                      |
      Rst_2TM_1TM_TIR        | Custom                  | 20     |'
    notes: The DefenseFinder HMM inventory records the Rst_1TM_TIR, Rst_2TM_TIR, and
      Rst_TIR_tm profiles under Rst_2TM_1TM_TIR.
  attaches_to:
  - causal_graphs#rst_2tm_1tm_tir_locus_restricts_phages
  posed_by: codex
  posed_date: '2026-09-27'
curation_history:
- timestamp: '2026-09-27T02:40:20Z'
  curator: codex
  action: MINTED_TRAITMECH_ID
  changes: Minted Rst_2TM_1TM_TIR system as a stable-URL-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_v277.
  llm_assisted: true
- timestamp: '2026-09-27T02:40:21Z'
  curator: codex
  action: REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP
  changes: Reviewed Rst_2TM_1TM_TIR during canonical-example issue 444 enforcement
    and left canonical_examples empty because the sources support a cloned P2-like-phage
    AC1 locus assayed in Escherichia coli C and a DefenseFinder RefSeq model example,
    but not a direct native microbial host exemplar with experimental Rst_2TM_1TM_TIR
    activity. No paid research was used.
  llm_assisted: true