ApeA system

traitmech:000334 · CLASS · PROPOSED

A phage defense system in which an organism possesses a single-component ApeA locus represented by the DefenseFinder Gao_Ape__ApeA profile, encoding an oligomeric HEPN-domain antiviral ribonuclease whose activation can cleave RNA substrates to restrict bacteriophage infection.

Trait evidence (11)

DOI:10.64898/2026.01.26.701840
Here, we focus on ApeA, a HEPN-domain antiviral protein that confers immunity through cleavage of host tRNAs within their anticodon loops.

Juozapaitis et al. describe ApeA as a HEPN-domain antiviral protein that cleaves host tRNAs within their anticodon loops.
DOI:10.64898/2026.01.26.701840
Both ApeA homologs confer protection at low MOI but not at high MOI, when most cells are infected

Juozapaitis et al. show that Ec1ApeA and Ec2ApeA protect at low multiplicity of infection but not high multiplicity, supporting abortive-infection behavior.
DOI:10.64898/2026.01.26.701840
activity of Ec1ApeA and Ec2ApeA proteins was abrogated by HEPN active site R521A and R502A mutations respectively

HEPN active-site mutations abrogated antiviral activity in the tested Ec1ApeA and Ec2ApeA proteins.
DOI:10.64898/2026.01.26.701840
Together, these results demonstrate that Ec1ApeA exhibits endoribonuclease activity targeting the tRNA anticodon loop, which is specifically activated during bacteriophage infection.

Ec1ApeA exhibits infection-activated endoribonuclease activity targeting the tRNA anticodon loop.
DOI:10.64898/2026.01.26.701840
In vitro ribonuclease assays showed that under our experimental conditions tRNA cleavage by wild-type Ec2ApeA was activated by dpCG

Ec2ApeA tRNA cleavage can be activated by deoxydinucleotides in vitro, supporting ligand-stimulated ApeA RNase activity for one ApeA variant.
DOI:10.64898/2026.03.20.713152
We show that two ApeA homologs, Ec1ApeA and Ps2ApeA, protect against a variety of single-stranded RNA phages.

Drobysheva et al. show that Ec1ApeA and Ps2ApeA protect against single-stranded RNA phages.
DOI:10.64898/2026.03.20.713152
results show that ApeA stops RNA phage replication by directly cleaving the phage genome.

Drobysheva et al. support direct phage-genome cleavage as an ApeA RNA-phage defense output.
DOI:10.64898/2026.03.20.713152
In the case of infection with RNA phages, we did not see evidence for induced cell death by Ec1ApeA

Drobysheva et al. distinguish Ec1ApeA RNA-phage defense from cell-death abortive infection.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
Gao_Ape | 10\.1126/science\.aba0372 | Diverse enzymatic activities mediate antiviral immunity in prokaryotes

The DefenseFinder article registry maps the named Gao_Ape system to the Gao et al. prokaryotic antiviral-immunity paper.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
Gao_Ape Gao_Ape 1 1 Gao_Ape__ApeA

The DefenseFinder rules table models Gao_Ape as a single-mandatory-profile system with the Gao_Ape__ApeA profile.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| Gao_Ape__ApeA | Gao_Ape__ApeA | Gao_Ape | Custom | 18 |

The DefenseFinder HMM inventory records ApeA under the Gao_Ape model namespace.

ApeA loci activate HEPN RNase antiphage outputs

Conservative system-level sketch linking a Gao_Ape/ApeA locus to HEPN RNase activation, host tRNA anticodon-loop cleavage during DNA-phage abortive infection, phage genomic RNA cleavage during non-abortive RNA-phage defense, and the ApeA system trait.

NONMECHANISTIC · The graph captures ApeA as a named DefenseFinder single-component system with alternate HEPN RNase outputs while leaving natural-host accession breadth, homolog- and phage-class-specific trigger differences, direct RNA-loop sensing by Ec1ApeA, the exact DNA-phage nuclease inputs to Ec2ApeA deoxydinucleotide signaling, and activity of additional homologs unresolved.

Edge evidence

Gao_Ape locus contributes to ApeA HEPN RNase activity RO:0002326
ApeA loci encode a HEPN-domain antiviral RNase, and DefenseFinder models Gao_Ape as a single-profile ApeA system.
- DOI:10.64898/2026.01.26.701840 Here, we focus on ApeA, a HEPN-domain antiviral protein that confers immunity through cleavage of host tRNAs within their anticodon loops. Juozapaitis et al. connect ApeA to HEPN-domain antiviral RNase activity.
- DOI:10.64898/2026.01.26.701840 activity of Ec1ApeA and Ec2ApeA proteins was abrogated by HEPN active site R521A and R502A mutations respectively HEPN active-site mutations eliminated activity in Ec1ApeA and Ec2ApeA.
- DOI:10.64898/2026.03.20.713152 We show that two ApeA homologs, Ec1ApeA and Ps2ApeA, protect against a variety of single-stranded RNA phages. Drobysheva et al. support HEPN-dependent Ec1ApeA and Ps2ApeA RNA-phage defense.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv Gao_Ape Gao_Ape 1 1 Gao_Ape__ApeA The DefenseFinder rules table models Gao_Ape as a single-mandatory-profile system with the Gao_Ape__ApeA profile.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md | Gao_Ape__ApeA | Gao_Ape__ApeA | Gao_Ape | Custom | 18 | The DefenseFinder HMM inventory records ApeA under the Gao_Ape model namespace.
ApeA HEPN RNase activity contributes to tRNA anticodon-loop cleavage RO:0002326
Activated ApeA HEPN RNase cleaves host tRNAs within their anticodon loops.
- DOI:10.64898/2026.01.26.701840 Together, these results demonstrate that Ec1ApeA exhibits endoribonuclease activity targeting the tRNA anticodon loop, which is specifically activated during bacteriophage infection. Ec1ApeA endoribonuclease activity targets the tRNA anticodon loop during phage infection.
- DOI:10.64898/2026.01.26.701840 In vitro ribonuclease assays showed that under our experimental conditions tRNA cleavage by wild-type Ec2ApeA was activated by dpCG Ec2ApeA tRNA-cleavage activity can be reconstituted in vitro with deoxydinucleotide ligands.
tRNA anticodon-loop cleavage contributes to abortive phage restriction RO:0002326
ApeA-mediated host tRNA cleavage arrests translation during abortive phage defense.
- DOI:10.64898/2026.01.26.701840 We further demonstrate that ApeA functions as an abortive infection system by cleaving host tRNAs within their anticodon loops to arrest translation Juozapaitis et al. link ApeA tRNA anticodon-loop cleavage to translation arrest during abortive infection.
abortive phage restriction confers ApeA system METPO:2007700
ApeA low-MOI protection and abortive infection realize the ApeA system possession trait.
- DOI:10.64898/2026.01.26.701840 Both ApeA homologs confer protection at low MOI but not at high MOI, when most cells are infected Ec1ApeA and Ec2ApeA low-MOI protection supports ApeA as an abortive infection system.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md Gao_Ape | 10\.1126/science\.aba0372 | Diverse enzymatic activities mediate antiviral immunity in prokaryotes The DefenseFinder article registry maps the named Gao_Ape system to the Gao et al. prokaryotic antiviral-immunity paper.
ApeA HEPN RNase activity contributes to phage genomic RNA cleavage RO:0002326
Ec1ApeA HEPN RNase activity cleaves infecting RNA-phage genomes.
- DOI:10.64898/2026.03.20.713152 results show that ApeA stops RNA phage replication by directly cleaving the phage genome. Drobysheva et al. show that ApeA can stop RNA-phage replication by direct phage-genome cleavage.
phage genomic RNA cleavage contributes to non-abortive RNA-phage restriction RO:0002326
ApeA-dependent cleavage of the phage genome restricts RNA-phage replication without host-cell death.
- DOI:10.64898/2026.03.20.713152 results show that ApeA stops RNA phage replication by directly cleaving the phage genome. Direct phage-genome cleavage is the main ApeA output in the assayed RNA-phage infection model.
- DOI:10.64898/2026.03.20.713152 In the case of infection with RNA phages, we did not see evidence for induced cell death by Ec1ApeA Drobysheva et al. found no evidence for Ec1ApeA-induced cell death during RNA-phage infection.
non-abortive RNA-phage restriction confers ApeA system METPO:2007700
Non-abortive RNA-phage restriction realizes one ApeA system defense output.
- DOI:10.64898/2026.03.20.713152 We show that two ApeA homologs, Ec1ApeA and Ps2ApeA, protect against a variety of single-stranded RNA phages. Drobysheva et al. show that ApeA homologs can protect against single-stranded RNA phages.
ApeA system is a phage defense system rdfs:subClassOf
ApeA system possession is a phage-defense-system trait.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md Gao_Ape | 10\.1126/science\.aba0372 | Diverse enzymatic activities mediate antiviral immunity in prokaryotes The DefenseFinder article registry maps the named Gao_Ape system to the Gao et al. prokaryotic antiviral-immunity paper.

Provenance

Identifier source: TraitMech local identifier
Definition source: DOI:10.64898/2026.01.26.701840

Parent traits (1)

phage defense system traitmech:000209

Synonyms (2)

ApeA RELATED_SYNONYM · DOI:10.64898/2026.01.26.701840
Gao_Ape RELATED_SYNONYM · https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.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 ApeA natural-host loci, homolog-specific DNA-phage versus RNA-phage triggers, phage nuclease inputs, phage genomic RNA targets, abortive versus non-abortive outputs, and subtype activity before minting narrower ApeA mechanism children.

KNOWLEDGE GAP OPEN apea-trigger-and-homolog-scope-gap · raised by codex · 2026-09-21

Attached to causal_graphs#gao_ape_hepn_rnase_restricts_phage

Juozapaitis et al. support DNA-phage ApeA abortive infection through host tRNA anticodon-loop cleavage, Drobysheva et al. support non-abortive RNA-phage defense through phage-genomic-RNA cleavage, and DefenseFinder models Gao_Ape with the Gao_Ape__ApeA profile. This first record stays at system level because the curated evidence leaves homolog- and phage-class-specific trigger logic, the full DNA-versus-RNA substrate split, activity of additional homologs, and accession-level natural-host breadth unresolved.

Curation history

2026-09-21T11:03:58Z · MINTED_TRAITMECH_ID · codex
Minted ApeA 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_v211.
2026-09-21T11:04:58Z · REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP · codex
Reviewed the ApeA canonical_examples gap and left canonical_examples empty: the current evidence supports a named single-component phage-defense system, DefenseFinder Gao_Ape/ApeA profiles, and heterologously assayed ApeA homologs, but does not yet cite a directly observed natural microbial taxon with a source-backed Gao_Ape/ApeA locus. No paid research was used.
2026-09-21T11:20:58Z · ADDRESS_PR_REVIEW · codex
Broadened the ApeA root definition, graph, evidence, and discussion after the PR 1190 adversarial review filed issue 1191, adding the March 2026 RNA-phage ApeA preprint and separating Juozapaitis host-tRNA abortive infection from Drobysheva phage-genomic-RNA non-abortive restriction.