CapRel system

traitmech:000244 · CLASS · PROPOSED

A phage defense system in which an organism possesses a fused CapRel toxin-antitoxin locus encoding an N-terminal toxSAS toxin domain and a C-terminal antitoxin sensor domain that together can restrict bacteriophage propagation.

Trait evidence (6)

  • DOI:10.1038/s41586-022-05444-z
    protects Escherichia coli against diverse phages

    Zhang et al. support CapRelSJ46 as a fused CapRel toxin-antitoxin antiphage system that protects E. coli against several phages.

  • DOI:10.1038/s41586-022-05444-z
    newly synthesized major capsid protein binds directly to the C-terminal domain

    Zhang et al. support direct sensing of a phage major capsid protein by the CapRelSJ46 C-terminal antitoxin domain.

  • DOI:10.1038/s41586-022-05444-z
    This open state enables CapRelSJ46 to pyrophosphorylate tRNAs and inhibit translation

    Zhang et al. connect phage-triggered CapRel activation to tRNA pyrophosphorylation, translation blockade, and restriction of viral infection.

  • DOI:10.1038/s41586-022-05444-z
    fused CapRels can provide anti-phage defence, with variable phage specificity

    Zhang et al. support treating fused CapRel loci as a family-level phage-defense system rather than only one CapRelSJ46 instance.

  • DOI:10.1038/s41586-024-08039-y
    can directly bind and sense two completely unrelated and structurally different proteins using the same sensory domain

    Zhang et al. independently support CapRelSJ46 as a direct phage-trigger-sensing immune protein and show that a single sensory domain can recognize more than one phage trigger.

  • DOI:10.1038/s41586-024-08039-y
    can fully evade CapRelSJ46 defence only when both triggers are mutated

    Zhang et al. connect multifactorial trigger sensing to CapRel-mediated defense during Bas11 phage infection.

CapRel sensors couple phage trigger binding to translation blockade

Evidence-backed process sketch linking a fused CapRel toxin-antitoxin locus to direct phage-protein sensing, toxSAS activation, tRNA pyrophosphorylation, translation inhibition, and restricted phage propagation.

NONMECHANISTIC · The graph captures CapRelSJ46 major-capsid-protein and Gp54 trigger evidence without claiming one universal CapRel phage trigger, allosteric route, escape route, or phage specificity across all fused CapRel homologs.

CapRel sensors couple phage trigger binding to translation blockade Interactive directed graph showing evidence-backed causal relationships for CapRel system.

Edge evidence

  • CapRel locus contributes to CapRel toxSAS activation RO:0002326

    Fused CapRel loci encode the N-terminal toxin domain and C-terminal antitoxin sensor domain that keep CapRel inhibited until phage trigger binding.

    • DOI:10.1038/s41586-022-05444-z regulates the toxic N-terminal region, serving as both antitoxin and phage infection sensor Zhang et al. support the C-terminal CapRel domain as both antitoxin and phage-infection sensor.
  • phage trigger binding activates CapRel toxSAS activation RO:0002213

    Binding of phage-encoded triggers to the C-terminal CapRel sensor relieves autoinhibition of the toxSAS domain.

    • DOI:10.1038/s41586-022-05444-z major capsid protein binds directly to the C-terminal domain Zhang et al. identify phage major capsid protein as a direct CapRelSJ46 trigger.
    • DOI:10.1038/s41586-024-08039-y directly binds and senses two completely unrelated and structurally different phage proteins using the same sensor domain Zhang et al. show that CapRelSJ46 can directly sense an alternative Gp54 trigger.
  • CapRel toxSAS activation contributes to tRNA pyrophosphorylation RO:0002326

    CapRel trigger binding activates the toxSAS domain that pyrophosphorylates tRNAs.

    • DOI:10.1038/s41586-022-05444-z This open state enables CapRelSJ46 to pyrophosphorylate tRNAs Zhang et al. connect relief of autoinhibition to CapRel toxSAS-mediated tRNA pyrophosphorylation.
  • tRNA pyrophosphorylation contributes to translation blockade RO:0002326

    tRNA pyrophosphorylation blocks cellular translation during CapRel antiviral activation.

    • DOI:10.1038/s41586-022-05444-z pyrophosphorylate tRNAs, which blocks translation Zhang et al. identify translation blockade as the immediate outcome of CapRel-mediated tRNA pyrophosphorylation.
  • translation blockade contributes to restricted phage propagation RO:0002326

    Translation blockade contributes to restriction of the infecting phage.

    • DOI:10.1038/s41586-022-05444-z blocks translation to restrict viral infection Zhang et al. connect translation blockade to restriction of viral infection.
  • restricted phage propagation confers CapRel system METPO:2007700

    CapRel-dependent restriction of phage propagation realizes the CapRel system trait.

  • CapRel system is a phage defense system rdfs:subClassOf

    CapRel system possession is a phage-defense-system trait.

    • DOI:10.1038/s41586-022-05444-z a fused anti-phage toxin-antitoxin system Zhang et al. place CapRelSJ46 in the anti-phage toxin-antitoxin-system family.

Provenance

Identifier source
TraitMech local identifier
Definition source
DOI:10.1038/s41586-022-05444-z

Synonyms (2)

  • CapRel toxin-antitoxin system EXACT_SYNONYM · DOI:10.1038/s41586-022-05444-z
  • fused CapRel system EXACT_SYNONYM · DOI:10.1038/s41586-022-05444-z

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 CapRel trigger breadth, phage escape routes, and family-specific activation before minting narrower CapRel mechanism children.

KNOWLEDGE GAP OPEN caprel-trigger-and-family-breadth-gap · raised by codex · 2026-09-18

Not yet attached to a section of this record — a curator sets attaches_to (e.g. causal_graphs#some_edge) so the gap shows beside the mechanism it concerns.

Zhang et al. support CapRelSJ46 sensing of a major capsid protein and an unrelated Gp54 trigger, but fused CapRel homologs need separate review before TraitMech asserts one universal phage trigger, CapRel escape route, tRNA target spectrum, or phage specificity across the family.

Curation history

  1. · MINTED_TRAITMECH_ID · codex

    Minted CapRel system as a DOI-backed GENOMICS TraitRecord under phage defense system after an ignored-and-hidden duplicate review found no exact live TraitMech, METPO, or prior proposal record; the replacement placeholder is reserved in proposals/metpo_traitmech_v121.

  2. · UPDATED_DEFINITION · codex

    Tightened the CapRel system definition around fused CapRel locus possession and expanded a dangling CapRel activation snippet after late Copilot feedback in issue 1001.