CARD-NLR system

traitmech:000337 · CLASS · PROPOSED

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.

Trait evidence (13)

https://europepmc.org/article/PPR/PPR668921
Here we show that CARD-like domains are present in defense systems that protect bacteria against phage.

The Wein et al. abstract supports CARD-like-domain systems as bacterial phage-defense systems.
https://europepmc.org/article/PPR/PPR668921
The bacterial CARD is essential for protease-mediated activation of certain bacterial gasdermins, which promote cell death once phage infection is recognized.

The Wein et al. abstract supports bacterial CARD-mediated protease activation of some bacterial gasdermins after phage recognition.
https://europepmc.org/article/PPR/PPR668921
We further show that multiple anti-phage defense systems utilize CARD-like domains to activate a variety of cell death effectors.

The Wein et al. abstract states that multiple anti-phage systems use CARD-like domains to activate varied cell-death effectors.
https://europepmc.org/article/PPR/PPR668921
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.

The Wein et al. abstract reports that these systems can be triggered by a phage immune-evasion protein.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
CARD_NLR | 10\.1101/2023\.05\.28\.542683 | CARD-like domains mediate anti-phage defense in bacterial gasdermin systems

The DefenseFinder article registry maps the CARD_NLR model namespace to the Wein et al. bacterial CARD-like domain anti-phage defense preprint.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| CARD_NLR__CARD_Protease | CARD_NLR__CARD_Protease | CARD_NLR | Custom | 300 |

The DefenseFinder HMM inventory records a CARD-like protease profile under the CARD_NLR model namespace.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| CARD_NLR__NLR_new | CARD_NLR__NLR_new | CARD_NLR | Custom | 100 |

The DefenseFinder HMM inventory records an NLR profile under the CARD_NLR model namespace.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| CARD_NLR__Trypsin_Phospho | CARD_NLR__Trypsin_Phospho | CARD_NLR | Custom | 400 |

The DefenseFinder HMM inventory records a Trypsin_Phospho-profiled effector under the CARD_NLR model namespace.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
CARD_NLR CARD_NLR_Endonuclease 1 3 CARD_NLR__Endonuclease CARD_NLR__CARD_Protease, CARD_NLR__NLR_new, CARD_NLR__Trypsin CARD_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

The DefenseFinder rules table models a CARD_NLR endonuclease subtype with CARD-like and NLR-like accessory profiles.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
CARD_NLR CARD_NLR_GasderMIN 1 3 GasderMIN__bGSDM CARD_NLR__CARD_Protease, CARD_NLR__NLR_new, CARD_NLR__Trypsin CARD_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

The DefenseFinder rules table models a CARD_NLR_GasderMIN subtype with GasderMIN__bGSDM as its mandatory effector profile.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
CARD_NLR CARD_NLR_Phospho 1 3 CARD_NLR__Trypsin_Phospho CARD_NLR__CARD_Protease, CARD_NLR__NLR_new, CARD_NLR__Trypsin CARD_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

The DefenseFinder rules table models a CARD_NLR_Phospho subtype with CARD-like and NLR-like accessory profiles.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
CARD_NLR CARD_NLR_Subtilase 1 3 CARD_NLR__Subtilase_long_new CARD_NLR__CARD_Protease, CARD_NLR__NLR_new, CARD_NLR__Trypsin CARD_NLR__Endonuclease, CARD_NLR__Endonuclease_new, CARD_NLR__Phospho, CARD_NLR__Phospho_Trypsin, CARD_NLR__Trypsin_Phospho, CARD_NLR__Trypsine_Endonuclease_new, GasderMIN__bGSDM

The DefenseFinder rules table models a CARD_NLR subtilase subtype with CARD-like and NLR-like accessory profiles.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
CARD_NLR CARD_NLR_like 2 4 CARD_NLR__Endonuclease, CARD_NLR__Phospho_Trypsin, CARD_NLR__Subtilase_long_new, CARD_NLR__Trypsin_Phospho CARD_NLR__CARD_Protease, CARD_NLR__NLR_new, CARD_NLR__Trypsin

The DefenseFinder rules table also models a CARD_NLR_like subtype that requires two of several candidate effector profiles.

CARD-NLR loci activate antiphage cell-death effectors

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.

NONMECHANISTIC · 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.

Edge evidence

CARD-NLR locus contributes to CARD-like detector activation RO:0002326
CARD-NLR loci couple CARD-like and NLR-like DefenseFinder profiles to subtype-specific effector profiles.
- https://europepmc.org/article/PPR/PPR668921 Here we show that CARD-like domains are present in defense systems that protect bacteria against phage. Wein et al. support bacterial CARD-like domains as parts of anti-phage defense systems.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md | CARD_NLR__CARD_Protease | CARD_NLR__CARD_Protease | CARD_NLR | Custom | 300 | The DefenseFinder HMM inventory records a CARD-like protease profile under the CARD_NLR model namespace.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md | CARD_NLR__NLR_new | CARD_NLR__NLR_new | CARD_NLR | Custom | 100 | The DefenseFinder HMM inventory records an NLR profile under the CARD_NLR model namespace.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv CARD_NLR CARD_NLR_Endonuclease 1 3 CARD_NLR__Endonuclease CARD_NLR__CARD_Protease, CARD_NLR__NLR_new, CARD_NLR__Trypsin CARD_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 The DefenseFinder rules table models a CARD_NLR endonuclease subtype with CARD-like and NLR-like accessory profiles.
CARD-like detector activation contributes to cell-death effector activation RO:0002326
Bacterial CARD-like domains activate subtype-specific cell-death effectors.
- https://europepmc.org/article/PPR/PPR668921 We further show that multiple anti-phage defense systems utilize CARD-like domains to activate a variety of cell death effectors. Wein et al. report multiple CARD-like-domain anti-phage systems that activate cell-death effectors.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv CARD_NLR CARD_NLR_GasderMIN 1 3 GasderMIN__bGSDM CARD_NLR__CARD_Protease, CARD_NLR__NLR_new, CARD_NLR__Trypsin CARD_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 The DefenseFinder rules table models a CARD_NLR_GasderMIN subtype with GasderMIN__bGSDM as its mandatory effector profile.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv CARD_NLR CARD_NLR_Phospho 1 3 CARD_NLR__Trypsin_Phospho CARD_NLR__CARD_Protease, CARD_NLR__NLR_new, CARD_NLR__Trypsin CARD_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 The DefenseFinder rules table models a CARD_NLR_Phospho subtype with CARD-like and NLR-like accessory profiles.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv CARD_NLR CARD_NLR_Subtilase 1 3 CARD_NLR__Subtilase_long_new CARD_NLR__CARD_Protease, CARD_NLR__NLR_new, CARD_NLR__Trypsin CARD_NLR__Endonuclease, CARD_NLR__Endonuclease_new, CARD_NLR__Phospho, CARD_NLR__Phospho_Trypsin, CARD_NLR__Trypsin_Phospho, CARD_NLR__Trypsine_Endonuclease_new, GasderMIN__bGSDM The DefenseFinder rules table models a CARD_NLR subtilase subtype with CARD-like and NLR-like accessory profiles.
cell-death effector activation contributes to phage-triggered cell death RO:0002326
Activated gasdermin and non-gasdermin CARD-NLR effectors can promote defense-associated cell death.
- https://europepmc.org/article/PPR/PPR668921 The bacterial CARD is essential for protease-mediated activation of certain bacterial gasdermins, which promote cell death once phage infection is recognized. Wein et al. support CARD-dependent gasdermin activation and cell death after phage recognition.
- https://europepmc.org/article/PPR/PPR668921 We further show that multiple anti-phage defense systems utilize CARD-like domains to activate a variety of cell death effectors. Wein et al. generalize CARD-like-domain activation to multiple cell-death effector classes.
phage-triggered cell death confers CARD-NLR system METPO:2007700
CARD-like effector-associated cell death realizes the CARD-NLR phage-defense-system output.
- https://europepmc.org/article/PPR/PPR668921 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. Wein et al. support CARD-like-domain system triggering by a bacteriophage immune-evasion protein.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv CARD_NLR CARD_NLR_like 2 4 CARD_NLR__Endonuclease, CARD_NLR__Phospho_Trypsin, CARD_NLR__Subtilase_long_new, CARD_NLR__Trypsin_Phospho CARD_NLR__CARD_Protease, CARD_NLR__NLR_new, CARD_NLR__Trypsin The DefenseFinder rules table also models a CARD_NLR_like subtype that requires two of several candidate effector profiles.
CARD-NLR system is a phage defense system rdfs:subClassOf
CARD-NLR system possession is a phage-defense system trait.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md CARD_NLR | 10\.1101/2023\.05\.28\.542683 | CARD-like domains mediate anti-phage defense in bacterial gasdermin systems The DefenseFinder article registry maps the CARD_NLR model namespace to the Wein et al. bacterial CARD-like domain anti-phage defense preprint.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv CARD_NLR CARD_NLR_Endonuclease 1 3 CARD_NLR__Endonuclease CARD_NLR__CARD_Protease, CARD_NLR__NLR_new, CARD_NLR__Trypsin CARD_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 The DefenseFinder rules table models a CARD_NLR endonuclease subtype with CARD-like and NLR-like accessory profiles.

Provenance

Identifier source: TraitMech local identifier
Definition source: DOI:10.1101/2023.05.28.542683

Parent traits (1)

phage defense system traitmech:000209

Children (5)

Synonyms (3)

CARD_NLR RELATED_SYNONYM · https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
CARD_NLR__CARD_Protease RELATED_SYNONYM · https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
CARD_NLR__NLR_new RELATED_SYNONYM · https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md

kg-microbe context

No kg-microbe node embedding matched this record in the 2026-04-25 deepwalk.

Discussions and Knowledge Gaps (1)

Open questions attached to this trait. Seeded by just knowledge-gap-scan and curated; see the corpus-wide index.

Resolve CARD-NLR subtype effectors, phage triggers, natural-host examples, and GasderMIN subtype boundaries before minting narrower CARD-NLR mechanism children.

KNOWLEDGE GAP OPEN card-nlr-subtype-mechanism-gap · raised by codex · 2026-09-21

Attached to causal_graphs#card_nlr_loci_activate_cell_death_effectors

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.

Curation history

2026-09-21T13:47:08Z · MINTED_TRAITMECH_ID · codex
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.
2026-10-02T19:23:11Z · TRACK_NARROWER_RECORD · codex
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.
2026-10-02T21:05:01Z · TRACK_NARROWER_RECORD · codex
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.
2026-10-03T00:02:51Z · TRACK_NARROWER_RECORD · codex
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.