identifier: traitmech:000509 label: EcoKMcrA system definition: A type IV modification-dependent restriction system in which an organism possesses an EcoKMcrA mcrA locus encoding a methylcytosine- and hydroxymethylcytosine-dependent restriction endonuclease whose nuclease active site is required for efficient restriction of DNA modified in the correct sequence context. definition_source: DOI:10.1093/nar/gky731 trait_category: GENOMICS term_kind: CLASS mapping_status: PROPOSED parent_traits: - traitmech:000496 synonyms: - synonym_text: EcoKMcrA synonym_type: RELATED_SYNONYM source: DOI:10.1093/nar/gky731 evidence: - reference: DOI:10.1093/nar/gky731 snippet: Escherichia coli McrA (EcoKMcrA) acts as a methylcytosine and hydroxymethylcytosine dependent restriction endonuclease. notes: Czapinska et al. support EcoKMcrA as an E. coli McrA modification-dependent restriction endonuclease that targets methylcytosine- and hydroxymethylcytosine-containing DNA. - reference: DOI:10.1093/nar/gky731 snippet: We present a biochemical characterization of EcoKMcrA that includes the first demonstration of its endonuclease activity notes: Czapinska et al. experimentally demonstrated EcoKMcrA endonuclease activity in vitro. - reference: DOI:10.1093/nar/gky731 snippet: In cells, EcoKMcrA specifically restricts DNA that is modified in the correct sequence context. This activity is impaired by mutations of the nuclease active site, unless the enzyme is highly overexpressed. notes: Czapinska et al. support cellular modified-DNA restriction by EcoKMcrA and tie efficient restriction to the nuclease active site. - reference: DOI:10.1093/nar/gkt747 snippet: The new class of modification-dependent restriction enzymes was named Type IV, as distinct from the familiar modification-blocked Types I-III. notes: Loenen and Raleigh define the Type IV class as modification-dependent restriction enzymes. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md snippet: '| EcoKMcrA | 10\.1093/nar/gky731 | Activity and structure of EcoKMcrA | ' notes: The pinned DefenseFinder article registry maps the EcoKMcrA source key to the Czapinska et al. Activity and structure of EcoKMcrA paper. causal_graphs: - graph_id: ecokmcra_restricts_modified_cytosine_dna title: EcoKMcrA restricts modified-cytosine DNA description: Conservative system-level sketch linking an EcoKMcrA mcrA locus to modified-cytosine DNA restriction and to the Type IV restriction parent trait. scope_status: NONMECHANISTIC scope_notes: The graph captures EcoKMcrA as a named E. coli K-strain McrA Type IV modification-dependent restriction system while leaving EcoKMcrA-family breadth, sequence-context specificity across natural hosts, accession-level protein examples, and DefenseFinder RM_Type_IV HMM/rules mapping unresolved. nodes: - node_id: ecokmcra_locus label: EcoKMcrA mcrA locus node_type: GENETIC_ELEMENT description: A locus encoding an EcoKMcrA methylcytosine- and hydroxymethylcytosine-dependent restriction endonuclease. - node_id: modified_cytosine_dna label: modified-cytosine DNA node_type: ENVIRONMENTAL_FACTOR description: DNA containing methylcytosine or hydroxymethylcytosine in a sequence context recognized by EcoKMcrA. - node_id: ecokmcra_modified_dna_restriction label: EcoKMcrA modified-DNA restriction node_type: BIOLOGICAL_PROCESS description: Nuclease-active-site-dependent restriction of modified DNA by EcoKMcrA. - node_id: ecokmcra_system_trait label: EcoKMcrA system node_type: TRAIT grounding: traitmech:000509 description: Possession of a genome-encoded EcoKMcrA modification-dependent restriction system. - node_id: type_iv_modification_dependent_restriction label: type IV modification-dependent restriction system node_type: TRAIT grounding: traitmech:000496 description: Possession of a genome-encoded Type IV modification-dependent restriction system. edges: - subject: ecokmcra_locus predicate: enables predicate_id: RO:0002327 object: ecokmcra_modified_dna_restriction description: The EcoKMcrA mcrA locus encodes a modified-cytosine-dependent restriction endonuclease. evidence: - reference: DOI:10.1093/nar/gky731 snippet: Escherichia coli McrA (EcoKMcrA) acts as a methylcytosine and hydroxymethylcytosine dependent restriction endonuclease. notes: Czapinska et al. support EcoKMcrA as an E. coli McrA modification-dependent restriction endonuclease that targets methylcytosine- and hydroxymethylcytosine-containing DNA. - reference: DOI:10.1093/nar/gky731 snippet: We present a biochemical characterization of EcoKMcrA that includes the first demonstration of its endonuclease activity notes: Czapinska et al. experimentally demonstrated EcoKMcrA endonuclease activity in vitro. - subject: ecokmcra_modified_dna_restriction predicate: mitigates predicate_id: METPO:2007407 object: modified_cytosine_dna description: EcoKMcrA-dependent Type IV restriction targets DNA modified in the correct sequence context. evidence: - reference: DOI:10.1093/nar/gky731 snippet: Electrophoretic mobility shift assay (EMSA) and footprinting experiments suggest that the N-terminal domains can sense the presence and sequence context of modified cytosines. notes: Czapinska et al. support EcoKMcrA sensing of the presence and sequence context of modified cytosines. - reference: DOI:10.1093/nar/gky731 snippet: In cells, EcoKMcrA specifically restricts DNA that is modified in the correct sequence context. This activity is impaired by mutations of the nuclease active site, unless the enzyme is highly overexpressed. notes: Czapinska et al. support cellular modified-DNA restriction by EcoKMcrA and tie efficient restriction to the nuclease active site. - subject: ecokmcra_modified_dna_restriction predicate: confers predicate_id: METPO:2007700 object: ecokmcra_system_trait description: EcoKMcrA-dependent Type IV restriction realizes the organism-level EcoKMcrA system possession trait. evidence: - reference: DOI:10.1093/nar/gky731 snippet: In cells, EcoKMcrA specifically restricts DNA that is modified in the correct sequence context. This activity is impaired by mutations of the nuclease active site, unless the enzyme is highly overexpressed. notes: Czapinska et al. support cellular modified-DNA restriction by EcoKMcrA and tie efficient restriction to the nuclease active site. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md snippet: '| EcoKMcrA | 10\.1093/nar/gky731 | Activity and structure of EcoKMcrA | ' notes: The pinned DefenseFinder article registry maps the EcoKMcrA source key to the Czapinska et al. Activity and structure of EcoKMcrA paper. - subject: ecokmcra_system_trait predicate: is a predicate_id: rdfs:subClassOf object: type_iv_modification_dependent_restriction description: EcoKMcrA system possession is a Type IV modification-dependent restriction system trait. evidence: - reference: DOI:10.1093/nar/gky731 snippet: Escherichia coli McrA (EcoKMcrA) acts as a methylcytosine and hydroxymethylcytosine dependent restriction endonuclease. notes: Czapinska et al. support EcoKMcrA as an E. coli McrA modification-dependent restriction endonuclease that targets methylcytosine- and hydroxymethylcytosine-containing DNA. - reference: DOI:10.1093/nar/gkt747 snippet: The new class of modification-dependent restriction enzymes was named Type IV, as distinct from the familiar modification-blocked Types I-III. notes: Loenen and Raleigh define the Type IV class as modification-dependent restriction enzymes. discussions: - discussion_id: ecokmcra-defensefinder-model-gap prompt: Resolve EcoKMcrA-family breadth, methylcytosine and hydroxymethylcytosine sequence-context specificity across natural hosts, accession-level protein examples, and DefenseFinder RM_Type_IV HMM/rules mapping before minting narrower EcoKMcrA mechanism or component traits. kind: KNOWLEDGE_GAP status: OPEN rationale: Czapinska et al. support E. coli EcoKMcrA as a methylcytosine- and hydroxymethylcytosine-dependent restriction endonuclease with cellular modified-DNA restriction activity tied to the nuclease active site, and the pinned DefenseFinder article registry maps EcoKMcrA to that paper. The pinned HMM inventory and rules table have no exact EcoKMcrA rows. This first-pass record therefore does not resolve a reusable DefenseFinder profile model, exact accession-level protein examples, the breadth of EcoKMcrA-like systems beyond E. coli K strains, or the complete set of natural methylcytosine and hydroxymethylcytosine sequence contexts. evidence: - reference: DOI:10.1093/nar/gky731 snippet: Escherichia coli McrA (EcoKMcrA) acts as a methylcytosine and hydroxymethylcytosine dependent restriction endonuclease. notes: Czapinska et al. support EcoKMcrA as an E. coli McrA modification-dependent restriction endonuclease that targets methylcytosine- and hydroxymethylcytosine-containing DNA. - reference: DOI:10.1093/nar/gky731 snippet: In cells, EcoKMcrA specifically restricts DNA that is modified in the correct sequence context. This activity is impaired by mutations of the nuclease active site, unless the enzyme is highly overexpressed. notes: Czapinska et al. support cellular modified-DNA restriction by EcoKMcrA and tie efficient restriction to the nuclease active site. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md snippet: '| EcoKMcrA | 10\.1093/nar/gky731 | Activity and structure of EcoKMcrA | ' notes: The pinned DefenseFinder article registry maps the EcoKMcrA source key to the Czapinska et al. Activity and structure of EcoKMcrA paper. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md notes: A structured first-pass search of the pinned DefenseFinder HMM inventory found no exact EcoKMcrA row. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv notes: A structured first-pass search of the pinned DefenseFinder rules table found no exact EcoKMcrA system row. attaches_to: - causal_graphs#ecokmcra_restricts_modified_cytosine_dna posed_by: codex posed_date: '2026-10-01' curation_history: - timestamp: '2026-10-01T07:10:00Z' curator: codex action: MINTED_TRAITMECH_ID changes: Minted EcoKMcrA system as a DOI- and DefenseFinder-backed GENOMICS TraitRecord under the type IV modification-dependent restriction 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_v386. llm_assisted: true - timestamp: '2026-10-01T07:10:02Z' curator: codex action: REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP changes: Reviewed EcoKMcrA system during initial curation and left canonical_examples empty because Czapinska et al. support the E. coli K-strain EcoKMcrA enzyme and the DefenseFinder EcoKMcrA source key, but not a single stable NCBITaxon strain exemplar or accession-level protein example for the organism-level EcoKMcrA system trait. No paid research was used. llm_assisted: true