identifier: traitmech:000337
label: CARD-NLR system
definition: A phage defense system in which an organism possesses a CARD-NLR locus
  represented by the DefenseFinder CARD_NLR model namespace, coupling bacterial CARD-like
  detector components and NLR-like profiles to subtype-specific GasderMIN, endonuclease,
  Trypsin_Phospho, or Subtilase effector profiles that can promote cell death after
  phage recognition.
definition_source: DOI:10.1101/2023.05.28.542683
trait_category: GENOMICS
term_kind: CLASS
mapping_status: PROPOSED
parent_traits:
- traitmech:000209
synonyms:
- synonym_text: CARD_NLR
  synonym_type: RELATED_SYNONYM
  source: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
- synonym_text: CARD_NLR__CARD_Protease
  synonym_type: RELATED_SYNONYM
  source: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
- synonym_text: CARD_NLR__NLR_new
  synonym_type: RELATED_SYNONYM
  source: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
evidence:
- reference: https://europepmc.org/article/PPR/PPR668921
  snippet: Here we show that CARD-like domains are present in defense systems that
    protect bacteria against phage.
  notes: The Wein et al. abstract supports CARD-like-domain systems as bacterial phage-defense
    systems.
- reference: https://europepmc.org/article/PPR/PPR668921
  snippet: The bacterial CARD is essential for protease-mediated activation of certain
    bacterial gasdermins, which promote cell death once phage infection is recognized.
  notes: The Wein et al. abstract supports bacterial CARD-mediated protease activation
    of some bacterial gasdermins after phage recognition.
- reference: https://europepmc.org/article/PPR/PPR668921
  snippet: We further show that multiple anti-phage defense systems utilize CARD-like
    domains to activate a variety of cell death effectors.
  notes: The Wein et al. abstract states that multiple anti-phage systems use CARD-like
    domains to activate varied cell-death effectors.
- reference: https://europepmc.org/article/PPR/PPR668921
  snippet: We find that these systems are triggered by a conserved immune evasion
    protein that phages use to overcome the bacterial defense system RexAB, demonstrating
    that phage proteins inhibiting one defense system can activate another.
  notes: The Wein et al. abstract reports that these systems can be triggered by a
    phage immune-evasion protein.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
  snippet: CARD_NLR | 10\.1101/2023\.05\.28\.542683 | CARD-like domains mediate anti-phage
    defense in bacterial gasdermin systems
  notes: The DefenseFinder article registry maps the CARD_NLR model namespace to the
    Wein et al. bacterial CARD-like domain anti-phage defense preprint.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
  snippet: '| CARD_NLR__CARD_Protease                          | CARD_NLR__CARD_Protease                          |
    CARD_NLR               | Custom                  | 300    |'
  notes: The DefenseFinder HMM inventory records a CARD-like protease profile under
    the CARD_NLR model namespace.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
  snippet: '| CARD_NLR__NLR_new                                | CARD_NLR__NLR_new                                |
    CARD_NLR               | Custom                  | 100    |'
  notes: The DefenseFinder HMM inventory records an NLR profile under the CARD_NLR
    model namespace.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
  snippet: '| CARD_NLR__Trypsin_Phospho                        | CARD_NLR__Trypsin_Phospho                        |
    CARD_NLR               | Custom                  | 400    |'
  notes: The DefenseFinder HMM inventory records a Trypsin_Phospho-profiled effector
    under the CARD_NLR model namespace.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
  snippet: "CARD_NLR\tCARD_NLR_Endonuclease\t1\t3\tCARD_NLR__Endonuclease\tCARD_NLR__CARD_Protease,\
    \ CARD_NLR__NLR_new, CARD_NLR__Trypsin\tCARD_NLR__Phospho, CARD_NLR__Phospho_Trypsin,\
    \ CARD_NLR__Subtilase, CARD_NLR__Subtilase_long_new, CARD_NLR__Subtilase_small_new,\
    \ CARD_NLR__Trypsin_Phospho, GasderMIN__bGSDM\t"
  notes: The DefenseFinder rules table models a CARD_NLR endonuclease subtype with
    CARD-like and NLR-like accessory profiles.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
  snippet: "CARD_NLR\tCARD_NLR_GasderMIN\t1\t3\tGasderMIN__bGSDM\tCARD_NLR__CARD_Protease,\
    \ CARD_NLR__NLR_new, CARD_NLR__Trypsin\tCARD_NLR__Endonuclease, CARD_NLR__Endonuclease_new,\
    \ CARD_NLR__Phospho, CARD_NLR__Phospho_Trypsin, CARD_NLR__Subtilase, CARD_NLR__Subtilase_long_new,\
    \ CARD_NLR__Subtilase_small_new, CARD_NLR__Trypsin_Phospho, CARD_NLR__Trypsine_Endonuclease_new\t"
  notes: The DefenseFinder rules table models a CARD_NLR_GasderMIN subtype with GasderMIN__bGSDM
    as its mandatory effector profile.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
  snippet: "CARD_NLR\tCARD_NLR_Phospho\t1\t3\tCARD_NLR__Trypsin_Phospho\tCARD_NLR__CARD_Protease,\
    \ CARD_NLR__NLR_new, CARD_NLR__Trypsin\tCARD_NLR__Endonuclease, CARD_NLR__Endonuclease_new,\
    \ CARD_NLR__Subtilase, CARD_NLR__Subtilase_long_new, CARD_NLR__Subtilase_small_new,\
    \ CARD_NLR__Trypsine_Endonuclease_new, GasderMIN__bGSDM\t"
  notes: The DefenseFinder rules table models a CARD_NLR_Phospho subtype with CARD-like
    and NLR-like accessory profiles.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
  snippet: "CARD_NLR\tCARD_NLR_Subtilase\t1\t3\tCARD_NLR__Subtilase_long_new\tCARD_NLR__CARD_Protease,\
    \ CARD_NLR__NLR_new, CARD_NLR__Trypsin\tCARD_NLR__Endonuclease, CARD_NLR__Endonuclease_new,\
    \ CARD_NLR__Phospho, CARD_NLR__Phospho_Trypsin, CARD_NLR__Trypsin_Phospho, CARD_NLR__Trypsine_Endonuclease_new,\
    \ GasderMIN__bGSDM\t"
  notes: The DefenseFinder rules table models a CARD_NLR subtilase subtype with CARD-like
    and NLR-like accessory profiles.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
  snippet: "CARD_NLR\tCARD_NLR_like\t2\t4\tCARD_NLR__Endonuclease, CARD_NLR__Phospho_Trypsin,\
    \ CARD_NLR__Subtilase_long_new, CARD_NLR__Trypsin_Phospho\tCARD_NLR__CARD_Protease,\
    \ CARD_NLR__NLR_new, CARD_NLR__Trypsin\t\t"
  notes: The DefenseFinder rules table also models a CARD_NLR_like subtype that requires
    two of several candidate effector profiles.
causal_graphs:
- graph_id: card_nlr_loci_activate_cell_death_effectors
  title: CARD-NLR loci activate antiphage cell-death effectors
  description: System-level sketch linking a CARD-NLR locus to CARD-like detector
    activation, subtype-specific cell-death effector activation, and the CARD-NLR
    system trait without asserting the molecular mechanism of any one DefenseFinder
    subtype.
  scope_status: NONMECHANISTIC
  scope_notes: The graph captures CARD-NLR as a named DefenseFinder model namespace
    supported by Wein et al. CARD-like domain anti-phage defense evidence while leaving
    subtype-specific phage triggers, the effector activation sequence, GasderMIN-associated
    subtype boundaries, and endonuclease, Trypsin_Phospho, or Subtilase outputs unresolved.
  nodes:
  - node_id: card_nlr_locus
    label: CARD-NLR locus
    node_type: GENETIC_ELEMENT
    description: A bacterial anti-phage defense locus cataloged in DefenseFinder with
      CARD_NLR profiles.
  - node_id: card_like_detector_activation
    label: CARD-like detector activation
    node_type: BIOLOGICAL_PROCESS
    description: Activation of a bacterial CARD-like detector within a CARD-NLR system.
  - node_id: cell_death_effector_activation
    label: cell-death effector activation
    node_type: BIOLOGICAL_PROCESS
    description: Activation of a gasdermin or other subtype-specific cell-death effector
      by a CARD-like anti-phage defense system.
  - node_id: phage_triggered_cell_death
    label: phage-triggered cell death
    node_type: BIOLOGICAL_PROCESS
    description: Host cell death promoted by a CARD-like bacterial anti-phage defense
      system.
  - node_id: card_nlr_system_trait
    label: CARD-NLR system
    node_type: TRAIT
    grounding: traitmech:000337
    description: Possession of a genome-encoded CARD-NLR 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: card_nlr_locus
    predicate: contributes to
    predicate_id: RO:0002326
    object: card_like_detector_activation
    description: CARD-NLR loci couple CARD-like and NLR-like DefenseFinder profiles
      to subtype-specific effector profiles.
    evidence:
    - reference: https://europepmc.org/article/PPR/PPR668921
      snippet: Here we show that CARD-like domains are present in defense systems
        that protect bacteria against phage.
      notes: Wein et al. support bacterial CARD-like domains as parts of anti-phage
        defense systems.
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
      snippet: '| CARD_NLR__CARD_Protease                          | CARD_NLR__CARD_Protease                          |
        CARD_NLR               | Custom                  | 300    |'
      notes: The DefenseFinder HMM inventory records a CARD-like protease profile
        under the CARD_NLR model namespace.
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
      snippet: '| CARD_NLR__NLR_new                                | CARD_NLR__NLR_new                                |
        CARD_NLR               | Custom                  | 100    |'
      notes: The DefenseFinder HMM inventory records an NLR profile under the CARD_NLR
        model namespace.
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
      snippet: "CARD_NLR\tCARD_NLR_Endonuclease\t1\t3\tCARD_NLR__Endonuclease\tCARD_NLR__CARD_Protease,\
        \ CARD_NLR__NLR_new, CARD_NLR__Trypsin\tCARD_NLR__Phospho, CARD_NLR__Phospho_Trypsin,\
        \ CARD_NLR__Subtilase, CARD_NLR__Subtilase_long_new, CARD_NLR__Subtilase_small_new,\
        \ CARD_NLR__Trypsin_Phospho, GasderMIN__bGSDM\t"
      notes: The DefenseFinder rules table models a CARD_NLR endonuclease subtype
        with CARD-like and NLR-like accessory profiles.
  - subject: card_like_detector_activation
    predicate: contributes to
    predicate_id: RO:0002326
    object: cell_death_effector_activation
    description: Bacterial CARD-like domains activate subtype-specific cell-death
      effectors.
    evidence:
    - reference: https://europepmc.org/article/PPR/PPR668921
      snippet: We further show that multiple anti-phage defense systems utilize CARD-like
        domains to activate a variety of cell death effectors.
      notes: Wein et al. report multiple CARD-like-domain anti-phage systems that
        activate cell-death effectors.
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
      snippet: "CARD_NLR\tCARD_NLR_GasderMIN\t1\t3\tGasderMIN__bGSDM\tCARD_NLR__CARD_Protease,\
        \ CARD_NLR__NLR_new, CARD_NLR__Trypsin\tCARD_NLR__Endonuclease, CARD_NLR__Endonuclease_new,\
        \ CARD_NLR__Phospho, CARD_NLR__Phospho_Trypsin, CARD_NLR__Subtilase, CARD_NLR__Subtilase_long_new,\
        \ CARD_NLR__Subtilase_small_new, CARD_NLR__Trypsin_Phospho, CARD_NLR__Trypsine_Endonuclease_new\t"
      notes: The DefenseFinder rules table models a CARD_NLR_GasderMIN subtype with
        GasderMIN__bGSDM as its mandatory effector profile.
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
      snippet: "CARD_NLR\tCARD_NLR_Phospho\t1\t3\tCARD_NLR__Trypsin_Phospho\tCARD_NLR__CARD_Protease,\
        \ CARD_NLR__NLR_new, CARD_NLR__Trypsin\tCARD_NLR__Endonuclease, CARD_NLR__Endonuclease_new,\
        \ CARD_NLR__Subtilase, CARD_NLR__Subtilase_long_new, CARD_NLR__Subtilase_small_new,\
        \ CARD_NLR__Trypsine_Endonuclease_new, GasderMIN__bGSDM\t"
      notes: The DefenseFinder rules table models a CARD_NLR_Phospho subtype with
        CARD-like and NLR-like accessory profiles.
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
      snippet: "CARD_NLR\tCARD_NLR_Subtilase\t1\t3\tCARD_NLR__Subtilase_long_new\t\
        CARD_NLR__CARD_Protease, CARD_NLR__NLR_new, CARD_NLR__Trypsin\tCARD_NLR__Endonuclease,\
        \ CARD_NLR__Endonuclease_new, CARD_NLR__Phospho, CARD_NLR__Phospho_Trypsin,\
        \ CARD_NLR__Trypsin_Phospho, CARD_NLR__Trypsine_Endonuclease_new, GasderMIN__bGSDM\t"
      notes: The DefenseFinder rules table models a CARD_NLR subtilase subtype with
        CARD-like and NLR-like accessory profiles.
  - subject: cell_death_effector_activation
    predicate: contributes to
    predicate_id: RO:0002326
    object: phage_triggered_cell_death
    description: Activated gasdermin and non-gasdermin CARD-NLR effectors can promote
      defense-associated cell death.
    evidence:
    - reference: https://europepmc.org/article/PPR/PPR668921
      snippet: The bacterial CARD is essential for protease-mediated activation of
        certain bacterial gasdermins, which promote cell death once phage infection
        is recognized.
      notes: Wein et al. support CARD-dependent gasdermin activation and cell death
        after phage recognition.
    - reference: https://europepmc.org/article/PPR/PPR668921
      snippet: We further show that multiple anti-phage defense systems utilize CARD-like
        domains to activate a variety of cell death effectors.
      notes: Wein et al. generalize CARD-like-domain activation to multiple cell-death
        effector classes.
  - subject: phage_triggered_cell_death
    predicate: confers
    predicate_id: METPO:2007700
    object: card_nlr_system_trait
    description: CARD-like effector-associated cell death realizes the CARD-NLR phage-defense-system
      output.
    evidence:
    - reference: https://europepmc.org/article/PPR/PPR668921
      snippet: We find that these systems are triggered by a conserved immune evasion
        protein that phages use to overcome the bacterial defense system RexAB, demonstrating
        that phage proteins inhibiting one defense system can activate another.
      notes: Wein et al. support CARD-like-domain system triggering by a bacteriophage
        immune-evasion protein.
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
      snippet: "CARD_NLR\tCARD_NLR_like\t2\t4\tCARD_NLR__Endonuclease, CARD_NLR__Phospho_Trypsin,\
        \ CARD_NLR__Subtilase_long_new, CARD_NLR__Trypsin_Phospho\tCARD_NLR__CARD_Protease,\
        \ CARD_NLR__NLR_new, CARD_NLR__Trypsin\t\t"
      notes: The DefenseFinder rules table also models a CARD_NLR_like subtype that
        requires two of several candidate effector profiles.
  - subject: card_nlr_system_trait
    predicate: is a
    predicate_id: rdfs:subClassOf
    object: phage_defense_system
    description: CARD-NLR system possession is a phage-defense system trait.
    evidence:
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
      snippet: CARD_NLR | 10\.1101/2023\.05\.28\.542683 | CARD-like domains mediate
        anti-phage defense in bacterial gasdermin systems
      notes: The DefenseFinder article registry maps the CARD_NLR model namespace
        to the Wein et al. bacterial CARD-like domain anti-phage defense preprint.
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
      snippet: "CARD_NLR\tCARD_NLR_Endonuclease\t1\t3\tCARD_NLR__Endonuclease\tCARD_NLR__CARD_Protease,\
        \ CARD_NLR__NLR_new, CARD_NLR__Trypsin\tCARD_NLR__Phospho, CARD_NLR__Phospho_Trypsin,\
        \ CARD_NLR__Subtilase, CARD_NLR__Subtilase_long_new, CARD_NLR__Subtilase_small_new,\
        \ CARD_NLR__Trypsin_Phospho, GasderMIN__bGSDM\t"
      notes: The DefenseFinder rules table models a CARD_NLR endonuclease subtype
        with CARD-like and NLR-like accessory profiles.
discussions:
- discussion_id: card-nlr-subtype-mechanism-gap
  prompt: Resolve CARD-NLR subtype effectors, phage triggers, natural-host examples,
    and GasderMIN subtype boundaries before minting narrower CARD-NLR mechanism children.
  kind: KNOWLEDGE_GAP
  status: OPEN
  rationale: Wein et al. support CARD-like domains in multiple anti-phage defense
    systems that activate cell-death effectors, and DefenseFinder models CARD_NLR
    subtypes with gasdermin, endonuclease, CARD_NLR_Phospho, CARD_NLR_Subtilase, and
    CARD_NLR_like rule profiles. CARD-NLR GasderMIN, endonuclease, phospho, subtilase,
    and CARD-NLR-like TraitRecords now capture the five DefenseFinder CARD_NLR rule-row
    subtypes, but exact phage triggers, CARD-to-effector activation sequence, accession-level
    natural-host components, CARD_NLR_Subtilase_long_new HMM inventory coverage, CARD_NLR_like
    multi-effector semantics, and standalone GasderMIN versus CARD_NLR_GasderMIN mechanism
    boundaries remain unresolved.
  attaches_to:
  - causal_graphs#card_nlr_loci_activate_cell_death_effectors
  posed_by: codex
  posed_date: '2026-09-21'
curation_history:
- timestamp: '2026-09-21T13:47:08Z'
  curator: codex
  action: MINTED_TRAITMECH_ID
  changes: Minted CARD-NLR system as a DOI- and stable-URL-backed GENOMICS TraitRecord
    under the phage defense system parent 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_v214.
  llm_assisted: true
- timestamp: '2026-10-02T19:23:11Z'
  curator: codex
  action: TRACK_NARROWER_RECORD
  changes: Documented CARD-NLR subtilase as split out in the open CARD-NLR subtype
    discussion after minting traitmech:000553 for the DefenseFinder-backed CARD_NLR_Subtilase
    child; exact subtilase substrates, CARD_NLR_Subtilase_long_new HMM inventory coverage,
    CARD_NLR_GasderMIN, CARD_NLR_like, and finer activation mechanisms remain open.
  llm_assisted: true
- timestamp: '2026-10-02T21:05:01Z'
  curator: codex
  action: TRACK_NARROWER_RECORD
  changes: Documented CARD-NLR GasderMIN as split out in the open CARD-NLR subtype
    discussion after minting traitmech:000555 for the DefenseFinder-backed CARD_NLR_GasderMIN
    child; CARD_NLR_like and finer CARD-NLR activation mechanisms remain open.
  llm_assisted: true
- timestamp: '2026-10-03T00:02:51Z'
  curator: codex
  action: TRACK_NARROWER_RECORD
  changes: Documented CARD-NLR-like as split out in the open CARD-NLR subtype discussion
    after minting traitmech:000559 for the DefenseFinder-backed CARD_NLR_like child;
    exact two-of-four effector-profile semantics, CARD_NLR__Subtilase_long_new HMM
    inventory coverage, and finer CARD-NLR activation mechanisms remain open.
  llm_assisted: true