identifier: traitmech:000327
label: Hesat system
definition: A phage defense system in which an organism possesses a Hesat locus that
  can restrict bacteriophage infection.
definition_source: DOI:10.1093/nar/gkae671
trait_category: GENOMICS
term_kind: CLASS
mapping_status: PROPOSED
parent_traits:
- traitmech:000209
synonyms:
- synonym_text: Hesat
  synonym_type: EXACT_SYNONYM
  source: DOI:10.1093/nar/gkae671
evidence:
- reference: DOI:10.1093/nar/gkae671
  snippet: Based on comparative sequence analysis (BLASTN and BLASTP) and on functional
    and structural analysis (HHpred and InterPro) the remaining seven antiphage systems
    (out of the twenty identified) did not display significant homology to any previously
    described antiphage system, thus rendering them novel antiphage systems (Table
    1). These systems were named after cheese, cattle or fermentation related deities
    (Rhea, Aristaios, Kamadhenu, Fliodhais, Audmula, Rugutis and Hesat)
  notes: Grafakou et al. named Hesat among seven not previously described lactococcal
    antiphage systems.
- reference: DOI:10.1093/nar/gkae671
  snippet: Except for Hesat, which was cloned in pPTPi with the addition of its native
    signals, all novel systems were cloned in the high-copy number vector pNZ44 (Supplementary
    Table S2). All discovered systems, except Fliodhais, are single gene antiphage
    systems.
  notes: Grafakou et al. identify Hesat as a single-gene novel antiphage system cloned
    with native signals in pPTPi.
- reference: DOI:10.1093/nar/gkae671
  snippet: For Hesat, no domain was predicted by HHpred and InterPro. Dali analysis
    reports significant hits with the colicin-D toxic domain (PDB ID 1V74; Figure
    4N, O), which specifically cleaves the anticodon loop of all four tRNA(Arg) iso-acceptors,
    thereby resulting in cell death (68). Therefore, it is proposed that Hesat upon
    phage infection is activated to block translation, which is in accordance with
    its abortive infection phenotype.
  notes: Grafakou et al. report that Hesat had no HHpred or InterPro domain prediction,
    and they propose a colicin-D-like translation-blocking activity upon phage infection.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
  snippet: Hesat | 10\.1093/nar/gkae671 | Discovery of antiphage systems in the lactococcal
    plasmidome
  notes: The DefenseFinder article registry maps the named Hesat system to the Grafakou
    et al. lactococcal antiphage-system discovery paper.
causal_graphs:
- graph_id: hesat_locus_restricts_phage
  title: Hesat loci confer bacterial phage defense
  description: Conservative system-level sketch linking possession of a Hesat locus
    to restricted bacteriophage propagation without asserting the unresolved phage
    trigger or molecular output.
  scope_status: NONMECHANISTIC
  scope_notes: The graph captures Hesat as a named single-gene lactococcal anti-phage
    system while leaving its direct phage trigger, molecular substrate, experimentally
    validated antiviral effector output, natural locus breadth, and the absence of
    pinned DefenseFinder HMM or rule rows unresolved.
  nodes:
  - node_id: hesat_locus
    label: Hesat locus
    node_type: GENETIC_ELEMENT
    description: A single-gene Hesat anti-phage defense locus described among lactococcal
      plasmid-encoded phage-resistance systems.
  - node_id: restricted_phage_propagation
    label: restricted phage propagation
    node_type: BIOLOGICAL_PROCESS
    description: Reduced propagation of bacteriophage in cells carrying the Hesat
      system.
  - node_id: hesat_system_trait
    label: Hesat system
    node_type: TRAIT
    grounding: traitmech:000327
    description: Possession of a genome-encoded Hesat 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: hesat_locus
    predicate: contributes to
    predicate_id: RO:0002326
    object: restricted_phage_propagation
    description: The lactococcal plasmidome screen discovered Hesat as a named single-gene
      antiphage system, and the DefenseFinder article registry maps the Hesat system
      to that discovery paper.
    evidence:
    - reference: DOI:10.1093/nar/gkae671
      snippet: Based on comparative sequence analysis (BLASTN and BLASTP) and on functional
        and structural analysis (HHpred and InterPro) the remaining seven antiphage
        systems (out of the twenty identified) did not display significant homology
        to any previously described antiphage system, thus rendering them novel antiphage
        systems (Table 1). These systems were named after cheese, cattle or fermentation
        related deities (Rhea, Aristaios, Kamadhenu, Fliodhais, Audmula, Rugutis and
        Hesat)
      notes: Grafakou et al. named Hesat as one of the novel lactococcal antiphage
        systems.
    - reference: DOI:10.1093/nar/gkae671
      snippet: Except for Hesat, which was cloned in pPTPi with the addition of its
        native signals, all novel systems were cloned in the high-copy number vector
        pNZ44 (Supplementary Table S2). All discovered systems, except Fliodhais,
        are single gene antiphage systems.
      notes: Grafakou et al. identify Hesat as a single-gene antiphage system.
    - reference: DOI:10.1093/nar/gkae671
      snippet: For Hesat, no domain was predicted by HHpred and InterPro. Dali analysis
        reports significant hits with the colicin-D toxic domain (PDB ID 1V74; Figure
        4N, O), which specifically cleaves the anticodon loop of all four tRNA(Arg)
        iso-acceptors, thereby resulting in cell death (68). Therefore, it is proposed
        that Hesat upon phage infection is activated to block translation, which is
        in accordance with its abortive infection phenotype.
      notes: Grafakou et al. propose that Hesat blocks translation after phage infection
        while leaving that molecular output unresolved.
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
      snippet: Hesat | 10\.1093/nar/gkae671 | Discovery of antiphage systems in the
        lactococcal plasmidome
      notes: The DefenseFinder article registry maps the named Hesat system to the
        Grafakou et al. lactococcal antiphage-system discovery paper.
  - subject: restricted_phage_propagation
    predicate: confers
    predicate_id: METPO:2007700
    object: hesat_system_trait
    description: Hesat-mediated phage restriction realizes the Hesat system trait.
    evidence:
    - reference: DOI:10.1093/nar/gkae671
      snippet: For Hesat, no domain was predicted by HHpred and InterPro. Dali analysis
        reports significant hits with the colicin-D toxic domain (PDB ID 1V74; Figure
        4N, O), which specifically cleaves the anticodon loop of all four tRNA(Arg)
        iso-acceptors, thereby resulting in cell death (68). Therefore, it is proposed
        that Hesat upon phage infection is activated to block translation, which is
        in accordance with its abortive infection phenotype.
      notes: Grafakou et al. treat Hesat as having an abortive infection phenotype
        and propose a translation-blocking mechanism upon phage infection.
  - subject: hesat_system_trait
    predicate: is a
    predicate_id: rdfs:subClassOf
    object: phage_defense_system
    description: Hesat system possession is a phage-defense-system trait.
    evidence:
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
      snippet: Hesat | 10\.1093/nar/gkae671 | Discovery of antiphage systems in the
        lactococcal plasmidome
      notes: The DefenseFinder article registry maps the named Hesat system to the
        Grafakou et al. lactococcal antiphage-system discovery paper.
discussions:
- discussion_id: hesat-mechanism-gap
  prompt: Resolve Hesat phage triggers and effector outputs before minting narrower
    Hesat mechanism children.
  kind: KNOWLEDGE_GAP
  status: OPEN
  rationale: Grafakou et al. and DefenseFinder support Hesat as a named single-gene
    anti-phage system, but the direct trigger, experimentally validated molecular
    substrate, antiviral effector output, natural locus breadth, and profile-to-component
    model are not resolved enough here to assert a narrower mechanistic child trait.
  attaches_to:
  - causal_graphs#hesat_locus_restricts_phage
  posed_by: codex
  posed_date: '2026-09-21'
curation_history:
- timestamp: '2026-09-21T04:55:54Z'
  curator: codex
  action: MINTED_TRAITMECH_ID
  changes: Minted Hesat 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_v204.
  llm_assisted: true