Rst_2TM_1TM_TIR system

traitmech:000400 · CLASS · PROPOSED

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.

Trait evidence (11)

DOI:10.1016/j.chom.2022.02.018
Phage resistance heatmaps of the validated defense systems show the median fold resistance of three independent replicates against a panel of eight phages

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.
https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
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}.

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.
https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
Rousset et al. suggested that the TIR-containing protein could generate a nucleotide messenger that in turn could activate the associated transmembrane proteins.

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.
https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
As far as we are aware, the molecular mechanism is unknown.

The pinned DefenseFinder wiki page leaves the Rst_2TM_1TM_TIR molecular mechanism unresolved.
https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
The Rst_2TM_1TM_TIR is composed of 3 proteins: Rst_2TM_TIR, Rst_TIR_tm and Rst_1TM_TIR.

The pinned DefenseFinder wiki page describes Rst_2TM_1TM_TIR as a three-component Rst_2TM_TIR/Rst_TIR_tm/Rst_1TM_TIR system.
https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
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)

The DefenseFinder wiki illustrates a predicted three-protein Rst_2TM_1TM_TIR locus in RefSeq assembly GCF_004006575.1 on NZ_CP034787.
https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
Rousset_2022[<a href='https://doi.org/10.1016/j.chom.2022.02.018'>Rousset et al., 2022</a>] --> Origin_0 Origin_0[Escherichia coli C <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] Expressed_0[Escherichia coli C] ----> Lambda & LF82_P8 & P2 & SIAC10 & SID07 & DC1 & AC1

The DefenseFinder experimental-validation diagram links Rousset et al. to an Escherichia coli C source locus expressed in Escherichia coli C against seven phages.
https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
subgraph Title4[Protects against] Lambda LF82_P8 P2 SIAC10 SID07 DC1 AC1

The DefenseFinder experimental-validation diagram lists lambda, LF82_P8, P2, SIAC10, SID07, DC1, and AC1 in the Rst_2TM_1TM_TIR protects-against subgraph.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
Rst_2TM_1TM_TIR | 10\.1101/2021\.01\.21\.427644 | Prophage-encoded hotspots of bacterial immune systems

The DefenseFinder article registry maps the named Rst_2TM_1TM_TIR system to the Rousset et al. preprint.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
Rst_2TM_1TM_TIR Rst_2TM_1TM_TIR 3 3 Rst_2TM_1TM_TIR__Rst_1TM_TIR, Rst_2TM_1TM_TIR__Rst_2TM_TIR, Rst_2TM_1TM_TIR__Rst_TIR_tm

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.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| 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 |

The DefenseFinder HMM inventory records the Rst_1TM_TIR, Rst_2TM_TIR, and Rst_TIR_tm profiles under Rst_2TM_1TM_TIR.

Rst_2TM_1TM_TIR loci restrict phages

Conservative system-level sketch linking the named Rst_2TM_1TM_TIR three-gene locus model to multi-phage resistance.

NONMECHANISTIC · 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.

Edge evidence

Rst_2TM_1TM_TIR locus contributes to multi-phage resistance RO:0002326
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.
- https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md 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}. 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.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv Rst_2TM_1TM_TIR Rst_2TM_1TM_TIR 3 3 Rst_2TM_1TM_TIR__Rst_1TM_TIR, Rst_2TM_1TM_TIR__Rst_2TM_TIR, Rst_2TM_1TM_TIR__Rst_TIR_tm 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.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md | 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 | The DefenseFinder HMM inventory records the Rst_1TM_TIR, Rst_2TM_TIR, and Rst_TIR_tm profiles under Rst_2TM_1TM_TIR.
multi-phage resistance confers Rst_2TM_1TM_TIR system METPO:2007700
Rst_2TM_1TM_TIR-linked multi-phage resistance realizes the Rst_2TM_1TM_TIR system trait.
- https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md Rousset_2022[<a href='https://doi.org/10.1016/j.chom.2022.02.018'>Rousset et al., 2022</a>] --> Origin_0 Origin_0[Escherichia coli C <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] Expressed_0[Escherichia coli C] ----> Lambda & LF82_P8 & P2 & SIAC10 & SID07 & DC1 & AC1 The DefenseFinder experimental-validation diagram links Rousset et al. to an Escherichia coli C source locus expressed in Escherichia coli C against seven phages.
- https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md subgraph Title4[Protects against] Lambda LF82_P8 P2 SIAC10 SID07 DC1 AC1 The DefenseFinder experimental-validation diagram lists lambda, LF82_P8, P2, SIAC10, SID07, DC1, and AC1 in the Rst_2TM_1TM_TIR protects-against subgraph.
Rst_2TM_1TM_TIR system is a phage defense system rdfs:subClassOf
Rst_2TM_1TM_TIR system possession is a phage-defense-system trait.
- DOI:10.1016/j.chom.2022.02.018 Phage resistance heatmaps of the validated defense systems show the median fold resistance of three independent replicates against a panel of eight phages 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.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md Rst_2TM_1TM_TIR | 10\.1101/2021\.01\.21\.427644 | Prophage-encoded hotspots of bacterial immune systems The DefenseFinder article registry maps the named Rst_2TM_1TM_TIR system to the Rousset et al. preprint.

Provenance

Identifier source: TraitMech local identifier
Definition source: https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md

Parent traits (1)

phage defense system traitmech:000209

Synonyms (4)

Rst_2TM_1TM_TIR RELATED_SYNONYM · https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
Rst_2TM_1TM_TIR__Rst_1TM_TIR RELATED_SYNONYM · https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
Rst_2TM_1TM_TIR__Rst_2TM_TIR RELATED_SYNONYM · https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
Rst_2TM_1TM_TIR__Rst_TIR_tm 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 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.

KNOWLEDGE GAP OPEN rst-2tm-1tm-tir-mechanism-gap · raised by codex · 2026-09-27

Attached to causal_graphs#rst_2tm_1tm_tir_locus_restricts_phages

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

https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
Rousset et al. suggested that the TIR-containing protein could generate a nucleotide messenger that in turn could activate the associated transmembrane proteins.
https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
As far as we are aware, the molecular mechanism is unknown.
https://gitlab.pasteur.fr/mdm-lab/wiki/-/raw/ee7647d8/content/3.defense-systems/rst_2tm_1tm_tir.md
The Rst_2TM_1TM_TIR is composed of 3 proteins: Rst_2TM_TIR, Rst_TIR_tm and Rst_1TM_TIR.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
Rst_2TM_1TM_TIR Rst_2TM_1TM_TIR 3 3 Rst_2TM_1TM_TIR__Rst_1TM_TIR, Rst_2TM_1TM_TIR__Rst_2TM_TIR, Rst_2TM_1TM_TIR__Rst_TIR_tm
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| 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 |

Curation history

2026-09-27T02:40:20Z · MINTED_TRAITMECH_ID · codex
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.
2026-09-27T02:40:21Z · REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP · codex
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.