TraitMech

TraitMech › GENOMICS

VcaM4I system

traitmech:000514 · CLASS · PROPOSED

A type IV modification-dependent restriction system in which an organism possesses a VcaM4I-family locus encoding an EVE-HNH restriction endonuclease that recognizes 5-methylcytosine- or 5-hydroxymethylcytosine-modified DNA.

Trait evidence (7)

  • DOI:10.1093/nar/gkaa1218
    EVE domains belong to the PUA superfamily, and are present in MDREs in combination with HNH nuclease domains.

    Mierzejewska et al. support the EVE-HNH architecture of VcaM4I-family modification-dependent restriction endonucleases.

  • DOI:10.1093/nar/gkaa1218
    Here, we present a biochemical characterization of the EVE-HNH endonuclease VcaM4I and crystal structures of the protein alone, with EVE domain bound to either 5mC modified dsDNA or to 5mC/5hmC containing ssDNA.

    Mierzejewska et al. biochemically characterized VcaM4I and solved structures of apo and modified-DNA-bound enzyme.

  • DOI:10.1093/nar/gkaa1218
    The EVE domain is moderately specific for 5mC/5hmC containing DNA according to EMSA experiments.

    Mierzejewska et al. support VcaM4I EVE-domain recognition of 5mC/5hmC-containing DNA.

  • DOI:10.1093/nar/gkaa1218
    Removal of the EVE domain and inter-domain linker, but not of the EVE domain alone converts VcaM4I into a non-specific toxic nuclease.

    Mierzejewska et al. support VcaM4I as a nuclease whose domain organization modulates toxic DNA cleavage.

  • DOI:10.1093/nar/gkaa1218
    The role of the key residues in the EVE and HNH domains of VcaM4I is confirmed by digestion and restriction assays with the enzyme variants that differ from the wild-type by changes to the base binding pocket or to the catalytic residues.

    Mierzejewska et al. support the VcaM4I EVE base-binding pocket and HNH catalytic residues by digestion and restriction assays.

  • DOI:10.1093/nar/gkt747
    The new class of modification-dependent restriction enzymes was named Type IV, as distinct from the familiar modification-blocked Types I-III.

    Loenen and Raleigh define the Type IV class as modification-dependent restriction enzymes.

  • https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
    | VcaM4I | 10\.1093/nar/gkaa1218 | Crystal structures of the EVE-HNH endonuclease VcaM4I in the presence and absence of DNA |

    The pinned DefenseFinder article registry maps the VcaM4I source key to the Mierzejewska et al. structural paper.

VcaM4I restricts modified-cytosine DNA

Conservative system-level sketch linking a VcaM4I-family locus to EVE-HNH 5mC/5hmC-dependent DNA restriction and to the Type IV restriction parent trait.

NONMECHANISTIC · The graph captures VcaM4I as a named Type IV modification-dependent restriction family while leaving natural host breadth, exact modified-DNA sequence-context specificity across EVE-HNH homologs, accession-level protein examples, and DefenseFinder RM_Type_IV HMM/rules mapping unresolved.

VcaM4I restricts modified-cytosine DNA Interactive directed graph showing evidence-backed causal relationships for VcaM4I system.

Edge evidence

  • VcaM4I-family locus enables VcaM4I EVE-HNH DNA restriction RO:0002327

    VcaM4I-family loci encode EVE-HNH endonucleases that restrict 5mC/5hmC-modified DNA.

    • DOI:10.1093/nar/gkaa1218 EVE domains belong to the PUA superfamily, and are present in MDREs in combination with HNH nuclease domains. Mierzejewska et al. support the EVE-HNH architecture of VcaM4I-family modification-dependent restriction endonucleases.
    • DOI:10.1093/nar/gkaa1218 Here, we present a biochemical characterization of the EVE-HNH endonuclease VcaM4I and crystal structures of the protein alone, with EVE domain bound to either 5mC modified dsDNA or to 5mC/5hmC containing ssDNA. Mierzejewska et al. biochemically characterized VcaM4I and solved structures of apo and modified-DNA-bound enzyme.
  • VcaM4I EVE-HNH DNA restriction mitigates VcaM4I-targeted modified-cytosine DNA METPO:2007407

    VcaM4I-family EVE-HNH restriction targets 5mC- or 5hmC-modified DNA.

    • DOI:10.1093/nar/gkaa1218 The EVE domain is moderately specific for 5mC/5hmC containing DNA according to EMSA experiments. Mierzejewska et al. support VcaM4I EVE-domain recognition of 5mC/5hmC-containing DNA.
    • DOI:10.1093/nar/gkaa1218 The role of the key residues in the EVE and HNH domains of VcaM4I is confirmed by digestion and restriction assays with the enzyme variants that differ from the wild-type by changes to the base binding pocket or to the catalytic residues. Mierzejewska et al. support the VcaM4I EVE base-binding pocket and HNH catalytic residues by digestion and restriction assays.
  • VcaM4I EVE-HNH DNA restriction confers VcaM4I system METPO:2007700

    VcaM4I-family EVE-HNH DNA restriction realizes the organism-level VcaM4I system possession trait.

  • VcaM4I system is a type IV modification-dependent restriction system rdfs:subClassOf

    VcaM4I system possession is a Type IV modification-dependent restriction system trait.

    • DOI:10.1093/nar/gkaa1218 Removal of the EVE domain and inter-domain linker, but not of the EVE domain alone converts VcaM4I into a non-specific toxic nuclease. Mierzejewska et al. support VcaM4I as a nuclease whose domain organization modulates toxic DNA cleavage.
    • DOI:10.1093/nar/gkt747 The new class of modification-dependent restriction enzymes was named Type IV, as distinct from the familiar modification-blocked Types I-III. Loenen and Raleigh define the Type IV class as modification-dependent restriction enzymes.

Provenance

Identifier source
TraitMech local identifier
Definition source
DOI:10.1093/nar/gkaa1218

Parent traits (1)

Synonyms (1)

  • VcaM4I 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 VcaM4I-family breadth, modified-cytosine sequence-context specificity across natural hosts, accession-level protein examples, and DefenseFinder RM_Type_IV HMM/rules mapping before minting narrower VcaM4I mechanism or component traits.

KNOWLEDGE GAP OPEN vcam4i-defensefinder-model-gap · raised by codex · 2026-10-01

Attached to causal_graphs#vcam4i_restricts_modified_cytosine_dna

Mierzejewska et al. support VcaM4I as an EVE-HNH modification-dependent restriction endonuclease that recognizes 5mC/5hmC DNA and validate EVE-domain modified-base binding plus HNH catalytic residues by digestion and restriction assays. The pinned DefenseFinder article registry maps VcaM4I to that paper, but the pinned HMM inventory and rules table have no exact VcaM4I rows. This first-pass record therefore does not resolve a reusable DefenseFinder profile model, exact accession-level protein examples, the breadth of VcaM4I-like systems across natural hosts, or the complete set of natural modified-cytosine sequence contexts.

Evidence

Curation history

  1. · MINTED_TRAITMECH_ID · codex

    Minted VcaM4I 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 same-scope live TraitMech, METPO, history, or prior proposal record; the replacement placeholder is reserved in proposals/metpo_traitmech_v391.

  2. · REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP · codex

    Reviewed VcaM4I system during initial curation and left canonical_examples empty because Mierzejewska et al. support the purified VcaM4I enzyme, structures, and restriction assays, but not a single stable NCBITaxon strain exemplar or accession-level protein example for the organism-level VcaM4I system trait. No paid research was used.