id: P05789
gene_symbol: ereB
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:562
  label: Escherichia coli
description: >-
  ereB encodes erythromycin esterase type II, a plasmid-associated macrolide
  resistance enzyme in Escherichia coli. EreB inactivates erythromycin by
  hydrolyzing the macrolactone ring, yielding a modified antibiotic that no
  longer functions efficiently at the ribosome. GOA currently captures only a
  high-level antibiotic-response process, while the local UniProt record carries
  the broader carboxylic ester hydrolase activity.
existing_annotations:
- term:
    id: GO:0046677
    label: response to antibiotic
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: Correct high-level biological-process annotation for an erythromycin-inactivation enzyme.
    action: ACCEPT
    reason: >-
      EreB directly confers erythromycin resistance by enzymatic antibiotic
      inactivation. The key missing annotation is the molecular function.
    supported_by:
    - reference_id: file:genes/ECOLX/ereB/ereB-uniprot.txt
      supporting_text: "This enzyme confers resistance to erythromycin through"
    - reference_id: PMID:3523438
      supporting_text: "confers high-level resistance to erythromycin by inactivation in Escherichia coli."
- term:
    id: GO:0052689
    label: carboxylic ester hydrolase activity
  evidence_type: RCA
  original_reference_id: file:genes/ECOLX/ereB/ereB-uniprot.txt
  qualifier: enables
  review:
    summary: NEW interim molecular-function annotation present in the UniProt flat file but absent from the fetched GOA TSV.
    action: NEW
    reason: >-
      Carboxylic ester hydrolase activity is a defensible broad parent for EreB,
      but it does not capture the macrolide/erythromycin lactone-ring substrate.
      A specific macrolide esterase term is proposed below.
    additional_reference_ids:
    - PMID:3523438
    - PMID:30177927
    - file:projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml
    supported_by:
    - reference_id: file:genes/ECOLX/ereB/ereB-uniprot.txt
      supporting_text: "DR   GO; GO:0052689; F:carboxylic ester hydrolase activity"
    - reference_id: PMID:3523438
      supporting_text: "The data obtained indicated that like ereA (Ounissi and Courvalin, 1985) ereB encodes an erythromycin esterase."
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: file:genes/ECOLX/ereB/ereB-uniprot.txt
  title: UniProt flat file for ereB (P05789)
  findings:
  - statement: UniProt describes EreB as an erythromycin esterase that hydrolyzes the lactone ring.
    supporting_text: "inactivation by hydrolyzing the lactone ring of the antibiotic."
- id: PMID:3523438
  title: Analysis of the nucleotide sequence of the ereB gene encoding the erythromycin esterase type II.
  findings:
  - statement: The primary sequence paper identifies ereB as an erythromycin esterase resistance determinant.
    supporting_text: "ereB encodes an erythromycin esterase."
- id: PMID:30177927
  title: Look and Outlook on Enzyme-Mediated Macrolide Resistance.
  findings:
  - statement: Review-level synthesis explains the macrolide esterase mechanism and family context.
    supporting_text: "The enzyme identified by Courvalin and his team hydrolyzes this ester bond"
- id: file:projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml
  title: Curated ARO to GO mapping set for AMR gene families
  findings:
  - statement: The AMR mapping records macrolide/erythromycin esterase as a GO molecular-function gap.
    supporting_text: "GO has no macrolide/erythromycin esterase MF term (Ere). GO term request candidate."
core_functions:
- description: >-
    Macrolide lactone esterase activity that hydrolyzes the erythromycin
    macrolactone ring and inactivates the antibiotic.
  molecular_function:
    id: GO:0052689
    label: carboxylic ester hydrolase activity
  directly_involved_in:
  - id: GO:0046677
    label: response to antibiotic
  supported_by:
  - reference_id: file:genes/ECOLX/ereB/ereB-uniprot.txt
    supporting_text: "inactivation by hydrolyzing the lactone ring of the antibiotic."
  - reference_id: PMID:3523438
    supporting_text: "The structure of the modified erythromycin was determined by physico-chemical techniques"
proposed_new_terms:
- proposed_name: erythromycin esterase activity
  proposed_definition: >-
    Catalysis of the hydrolysis of the macrolactone ester bond of erythromycin
    or closely related macrolide antibiotics, resulting in antibiotic inactivation.
  justification: >-
    GO has only a broad carboxylic ester hydrolase term for Ere enzymes, while
    the AMR mechanism is specific hydrolysis of macrolide antibiotic lactone
    rings. The ARO mapping records this as a GO term request candidate.
  proposed_parent:
    id: GO:0052689
    label: carboxylic ester hydrolase activity
  proposed_mappings:
  - predicate: skos:exactMatch
    target_term:
      id: ARO:3000320
      label: macrolide esterase
  supported_by:
  - reference_id: PMID:3523438
    supporting_text: "ereB encodes an erythromycin esterase."
  - reference_id: file:projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml
    supporting_text: "GO has no macrolide/erythromycin esterase MF term (Ere). GO term request candidate."
suggested_questions:
- question: Should the GO term be erythromycin-specific or generalized to macrolide lactone esterase activity?
  experts: []
suggested_experiments:
- description: >-
    Measure EreB activity and product formation across 14-, 15-, and 16-membered
    macrolides to define whether an erythromycin-specific or macrolide-class term
    is the right GO scope.
  experiment_type: in vitro enzyme assay