identifier: traitmech:000398
label: Rst_3HP system
definition: A phage defense system in which an organism possesses a three-protein
  Rst_3HP locus represented by DefenseFinder as a three-profile model requiring Rst_3HP__Hp1,
  Rst_3HP__Hp2, and Rst_3HP__Hp3 and experimentally linked to P1 protection when expressed
  in Escherichia coli.
definition_source: DOI:10.1016/j.chom.2022.02.018
trait_category: GENOMICS
term_kind: CLASS
mapping_status: PROPOSED
parent_traits:
- traitmech:000209
synonyms:
- synonym_text: Rst_3HP
  synonym_type: RELATED_SYNONYM
  source: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
- synonym_text: Rst_3HP__Hp1
  synonym_type: RELATED_SYNONYM
  source: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
- synonym_text: Rst_3HP__Hp2
  synonym_type: RELATED_SYNONYM
  source: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
- synonym_text: Rst_3HP__Hp3
  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: The second system comprises three genes that have no clear predicted domain
    and protect against P1.
  notes: Rousset et al. experimentally describe the unnamed three-gene P2-hotspot
    system that DefenseFinder tracks as Rst_3HP.
- 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 P2-hotspot hits, including the three-gene
    P1-restricting system, as validated defense systems in a replicated phage-resistance
    heatmap.
- reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_3hp.md
  snippet: 'The Rst_3HP system is composed of 3 proteins: Hp1, Hp2 and, Hp3. These
    proteins do not have clear predicted domains but they confer resistance against
    the phage P1 in *Escherichia coli* E1114 :ref{doi=10.1016/j.chom.2022.02.018}.'
  notes: The pinned DefenseFinder wiki page names Rst_3HP as a three-protein system
    and links Hp1, Hp2, and Hp3 to P1 resistance in Escherichia coli E1114.
- reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_3hp.md
  snippet: As far as we are aware, the molecular mechanism is unknown.
  notes: The pinned DefenseFinder wiki page leaves the Rst_3HP molecular mechanism
    unresolved.
- reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_3hp.md
  snippet: 'The Rst_3HP is composed of 3 proteins: Hp1, Hp2 and Hp3.'
  notes: The pinned DefenseFinder wiki page describes Rst_3HP as a three-component
    Hp1/Hp2/Hp3 system.
- reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_3hp.md
  snippet: The Rst_3HP system in *Aquitalea denitrificans* (GCF_009856625.1, NZ_CP047241)
    is composed of 3 proteins Hp1 (WP_159879082.1) Hp2 (WP_159879084.1) Hp3 (WP_159879086.1)
  notes: The DefenseFinder wiki illustrates a predicted three-protein Rst_3HP locus
    in RefSeq assembly GCF_009856625.1 on NZ_CP047241.
- reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_3hp.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 P2 loci \n<a href='https://ncbi.nlm.nih.gov/protein/WP_000508501.1'>WP_000508501.1</a>,\
    \ <a href='https://ncbi.nlm.nih.gov/protein/WP_112026686.1'>WP_112026686.1</a>,\n\
    <a href='https://ncbi.nlm.nih.gov/protein/WP_000756244.1'>WP_000756244.1</a>]\
    \ --> Expressed_0[Escherichia coli]\n    Expressed_0[Escherichia coli] ----> P1"
  notes: The DefenseFinder experimental-validation diagram links Rousset et al. to
    an Escherichia coli P2-locus source expressed in Escherichia coli against P1.
- reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_3hp.md
  snippet: "subgraph Title4[Protects against]\n        P1"
  notes: The DefenseFinder experimental-validation diagram lists P1 in the Rst_3HP
    protects-against subgraph.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
  snippet: Rst_3HP | 10\.1101/2021\.01\.21\.427644 | Prophage-encoded hotspots of
    bacterial immune systems
  notes: The DefenseFinder article registry maps the named Rst_3HP system to the Rousset
    et al. preprint.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
  snippet: "Rst_3HP\tRst_3HP\t3\t3\tRst_3HP__Hp1, Rst_3HP__Hp2, Rst_3HP__Hp3\t\t\t"
  notes: The DefenseFinder rules table models Rst_3HP as a three-profile system requiring
    Rst_3HP__Hp1, Rst_3HP__Hp2, and Rst_3HP__Hp3.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
  snippet: '| Rst_3HP__Hp1                                     | Rst_3HP__Hp1                                     |
    Rst_3HP                | Custom                  | 67     |

    | Rst_3HP__Hp2                                     | Rst_3HP__Hp2                                     |
    Rst_3HP                | Custom                  | 26     |

    | Rst_3HP__Hp3                                     | Rst_3HP__Hp3                                     |
    Rst_3HP                | Custom                  | 20     |'
  notes: The DefenseFinder HMM inventory records Hp1, Hp2, and Hp3 custom profiles
    under Rst_3HP.
causal_graphs:
- graph_id: rst_3hp_locus_restricts_p1
  title: Rst_3HP loci restrict P1 phage
  description: Conservative system-level sketch linking a named Rst_3HP three-gene
    locus model to P1 phage resistance.
  scope_status: NONMECHANISTIC
  scope_notes: The graph captures Rst_3HP as a named DefenseFinder three-profile phage-defense
    system while leaving native host breadth, Hp1/Hp2/Hp3 molecular activities, profile-to-gene
    mapping, the direct phage trigger, and the P1 restriction mechanism unresolved.
  nodes:
  - node_id: rst_3hp_locus
    label: Rst_3HP locus
    node_type: GENETIC_ELEMENT
    description: A three-gene Hp1/Hp2/Hp3 phage-defense locus represented by the custom
      DefenseFinder Rst_3HP profiles.
  - node_id: p1_phage_resistance
    label: P1 phage resistance
    node_type: BIOLOGICAL_PROCESS
    description: Resistance against phage P1 in a host expressing an Rst_3HP locus.
  - node_id: rst_3hp_system_trait
    label: Rst_3HP system
    node_type: TRAIT
    grounding: traitmech:000398
    description: Possession of a genome-encoded Rst_3HP 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_3hp_locus
    predicate: contributes to
    predicate_id: RO:0002326
    object: p1_phage_resistance
    description: Rousset et al. linked a cloned three-gene P2-hotspot system to P1
      protection, and DefenseFinder models Rst_3HP as a three-profile Hp1/Hp2/Hp3
      system.
    evidence:
    - reference: DOI:10.1016/j.chom.2022.02.018
      snippet: The second system comprises three genes that have no clear predicted
        domain and protect against P1.
      notes: Rousset et al. experimentally describe the unnamed three-gene P2-hotspot
        system that DefenseFinder tracks as Rst_3HP.
    - reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_3hp.md
      snippet: 'The Rst_3HP system is composed of 3 proteins: Hp1, Hp2 and, Hp3. These
        proteins do not have clear predicted domains but they confer resistance against
        the phage P1 in *Escherichia coli* E1114 :ref{doi=10.1016/j.chom.2022.02.018}.'
      notes: The pinned DefenseFinder wiki page names Rst_3HP as a three-protein system
        and links Hp1, Hp2, and Hp3 to P1 resistance in Escherichia coli E1114.
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
      snippet: "Rst_3HP\tRst_3HP\t3\t3\tRst_3HP__Hp1, Rst_3HP__Hp2, Rst_3HP__Hp3\t\
        \t\t"
      notes: The DefenseFinder rules table models Rst_3HP as a three-profile system
        requiring Rst_3HP__Hp1, Rst_3HP__Hp2, and Rst_3HP__Hp3.
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
      snippet: '| Rst_3HP__Hp1                                     | Rst_3HP__Hp1                                     |
        Rst_3HP                | Custom                  | 67     |

        | Rst_3HP__Hp2                                     | Rst_3HP__Hp2                                     |
        Rst_3HP                | Custom                  | 26     |

        | Rst_3HP__Hp3                                     | Rst_3HP__Hp3                                     |
        Rst_3HP                | Custom                  | 20     |'
      notes: The DefenseFinder HMM inventory records Hp1, Hp2, and Hp3 custom profiles
        under Rst_3HP.
  - subject: p1_phage_resistance
    predicate: confers
    predicate_id: METPO:2007700
    object: rst_3hp_system_trait
    description: Rst_3HP-linked P1 resistance realizes the Rst_3HP system trait.
    evidence:
    - reference: DOI:10.1016/j.chom.2022.02.018
      snippet: The second system comprises three genes that have no clear predicted
        domain and protect against P1.
      notes: Rousset et al. experimentally describe the unnamed three-gene P2-hotspot
        system that DefenseFinder tracks as Rst_3HP.
    - reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_3hp.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 P2 loci \n\
        <a href='https://ncbi.nlm.nih.gov/protein/WP_000508501.1'>WP_000508501.1</a>,\
        \ <a href='https://ncbi.nlm.nih.gov/protein/WP_112026686.1'>WP_112026686.1</a>,\n\
        <a href='https://ncbi.nlm.nih.gov/protein/WP_000756244.1'>WP_000756244.1</a>]\
        \ --> Expressed_0[Escherichia coli]\n    Expressed_0[Escherichia coli] ---->\
        \ P1"
      notes: The DefenseFinder experimental-validation diagram links Rousset et al.
        to an Escherichia coli P2-locus source expressed in Escherichia coli against
        P1.
    - reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_3hp.md
      snippet: "subgraph Title4[Protects against]\n        P1"
      notes: The DefenseFinder experimental-validation diagram lists P1 in the Rst_3HP
        protects-against subgraph.
  - subject: rst_3hp_system_trait
    predicate: is a
    predicate_id: rdfs:subClassOf
    object: phage_defense_system
    description: Rst_3HP 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 P2-hotspot hits, including the
        three-gene P1-restricting system, as 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_3HP | 10\.1101/2021\.01\.21\.427644 | Prophage-encoded hotspots
        of bacterial immune systems
      notes: The DefenseFinder article registry maps the named Rst_3HP system to the
        Rousset et al. preprint.
discussions:
- discussion_id: rst-3hp-host-mechanism-gap
  prompt: Resolve Rst_3HP native host breadth, Hp1/Hp2/Hp3 molecular activities, profile-to-gene
    mapping, and the mechanism of P1 restriction before minting narrower Rst_3HP mechanism
    children.
  kind: KNOWLEDGE_GAP
  status: OPEN
  rationale: Rousset et al. support a three-gene P2-hotspot system with no clear predicted
    domains that protects against P1, and DefenseFinder represents Rst_3HP as a required
    Hp1/Hp2/Hp3 three-profile model. This first system-level record leaves native
    host breadth, profile-to-gene mapping, the molecular activities of Hp1, Hp2, and
    Hp3, and the P1 restriction mechanism unresolved.
  evidence:
  - reference: DOI:10.1016/j.chom.2022.02.018
    snippet: The second system comprises three genes that have no clear predicted
      domain and protect against P1.
    notes: Rousset et al. experimentally describe the unnamed three-gene P2-hotspot
      system that DefenseFinder tracks as Rst_3HP.
  - reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_3hp.md
    snippet: As far as we are aware, the molecular mechanism is unknown.
    notes: The pinned DefenseFinder wiki page leaves the Rst_3HP molecular mechanism
      unresolved.
  - reference: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_3hp.md
    snippet: 'The Rst_3HP is composed of 3 proteins: Hp1, Hp2 and Hp3.'
    notes: The pinned DefenseFinder wiki page describes Rst_3HP as a three-component
      Hp1/Hp2/Hp3 system.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
    snippet: "Rst_3HP\tRst_3HP\t3\t3\tRst_3HP__Hp1, Rst_3HP__Hp2, Rst_3HP__Hp3\t\t\
      \t"
    notes: The DefenseFinder rules table models Rst_3HP as a three-profile system
      requiring Rst_3HP__Hp1, Rst_3HP__Hp2, and Rst_3HP__Hp3.
  attaches_to:
  - causal_graphs#rst_3hp_locus_restricts_p1
  posed_by: codex
  posed_date: '2026-09-27'
curation_history:
- timestamp: '2026-09-27T01:03:20Z'
  curator: codex
  action: MINTED_TRAITMECH_ID
  changes: Minted Rst_3HP 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_v275.
  llm_assisted: true
- timestamp: '2026-09-27T01:03:21Z'
  curator: codex
  action: REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP
  changes: Reviewed Rst_3HP during canonical-example issue 444 enforcement and left
    canonical_examples empty because the sources support a cloned P2-hotspot Hp1/Hp2/Hp3
    locus assayed in Escherichia coli and a DefenseFinder RefSeq model example, but
    not a direct native microbial isolate exemplar with experimentally verified Rst_3HP
    activity. No paid research was used.
  llm_assisted: true