id: P0A0D2
gene_symbol: ant
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:1280
  label: Staphylococcus aureus
description: ant encodes an aminoglycoside nucleotidyltransferase in Staphylococcus aureus. UniProt/CARD identify this entry as an aminoglycoside-modifying resistance enzyme that inactivates aminoglycoside antibiotics by adenylylation/nucleotidyl transfer. UniProt names the protein 'Spectinomycin 9-adenylyltransferase' (accession P0A0D2).
existing_annotations:
- term:
    id: GO:0016779
    label: nucleotidyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: The existing MF term is directionally correct but less informative than the family-specific AMR activity aminoglycoside nucleotidyltransferase activity.
    action: MODIFY
    reason: Replace the broad or over-specific electronic term 'nucleotidyltransferase activity' with aminoglycoside nucleotidyltransferase activity based on UniProt/CARD determinant identity and the curated ARO->GO mapping.
    proposed_replacement_terms:
    - id: GO:0034068
      label: aminoglycoside nucleotidyltransferase activity
    supported_by:
    - reference_id: file:genes/STAAU/ant/ant-uniprot.txt
      supporting_text: 'CC   -!- FUNCTION: Mediates bacterial resistance to the antibiotic spectinomycin

        CC       but not streptomycin. {ECO:0000269|PubMed:2993813}.'
- term:
    id: GO:0046677
    label: response to antibiotic
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: The gene product is an antimicrobial-resistance determinant, so the antibiotic-response annotation is retained.
    action: ACCEPT
    reason: The CARD/ARO determinant identity supports an antibiotic-resistance biological role.
    supported_by:
    - reference_id: file:genes/STAAU/ant/ant-uniprot.txt
      supporting_text: 'CC   -!- FUNCTION: Mediates bacterial resistance to the antibiotic spectinomycin

        CC       but not streptomycin. {ECO:0000269|PubMed:2993813}.'
- term:
    id: GO:0070566
    label: adenylyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: The existing MF term is directionally correct but less informative than the family-specific AMR activity aminoglycoside nucleotidyltransferase activity.
    action: MODIFY
    reason: Replace the broad or over-specific electronic term 'adenylyltransferase activity' with aminoglycoside nucleotidyltransferase activity based on UniProt/CARD determinant identity and the curated ARO->GO mapping.
    proposed_replacement_terms:
    - id: GO:0034068
      label: aminoglycoside nucleotidyltransferase activity
    supported_by:
    - reference_id: file:genes/STAAU/ant/ant-uniprot.txt
      supporting_text: 'CC   -!- FUNCTION: Mediates bacterial resistance to the antibiotic spectinomycin

        CC       but not streptomycin. {ECO:0000269|PubMed:2993813}.'
- term:
    id: GO:0009012
    label: aminoglycoside 3''-adenylyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:29871922
  qualifier: enables
  negated: true
  review:
    summary: The negated annotation is retained; this ANT(9) enzyme should not be asserted as aminoglycoside 3''-adenylyltransferase activity.
    action: ACCEPT
    reason: UniProt describes this protein as a spectinomycin 9-adenylyltransferase that mediates spectinomycin but not streptomycin resistance, and the PMID:29871922 study distinguishes ANT(9) enzymes from dual ANT(3'')(9) enzymes. Accepting this row preserves the existing NOT qualifier rather than treating the specific 3'' activity as positive evidence.
    supported_by:
    - reference_id: file:genes/STAAU/ant/ant-uniprot.txt
      supporting_text: 'CC   -!- FUNCTION: Mediates bacterial resistance to the antibiotic spectinomycin

        CC       but not streptomycin. {ECO:0000269|PubMed:2993813}.'
    - reference_id: PMID:29871922
      supporting_text: ANT(9) enzymes, which only mediate resistance to spectinomycin.
- term:
    id: GO:0046677
    label: response to antibiotic
  evidence_type: IMP
  original_reference_id: PMID:2993813
  qualifier: involved_in
  review:
    summary: The gene product is an antimicrobial-resistance determinant, so the antibiotic-response annotation is retained.
    action: ACCEPT
    reason: The CARD/ARO determinant identity supports an antibiotic-resistance biological role.
    supported_by:
    - reference_id: file:genes/STAAU/ant/ant-uniprot.txt
      supporting_text: 'CC   -!- FUNCTION: Mediates bacterial resistance to the antibiotic spectinomycin

        CC       but not streptomycin. {ECO:0000269|PubMed:2993813}.'
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: PMID:29871922
  title: Structural mechanism of AadA, a dual-specificity aminoglycoside adenylyltransferase from Salmonella enterica.
  findings: []
- id: PMID:2993813
  title: Nucleotide sequence of a spectinomycin adenyltransferase AAD(9) determinant from Staphylococcus aureus and its relationship to AAD(3") (9).
  findings: []
- id: file:genes/STAAU/ant/ant-uniprot.txt
  title: UniProt flat file for ant (P0A0D2)
  findings:
  - statement: UniProt/CARD identity and protein naming for ant.
    supporting_text: 'CC   -!- FUNCTION: Mediates bacterial resistance to the antibiotic spectinomycin

      CC       but not streptomycin. {ECO:0000269|PubMed:2993813}.'
- id: file:projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml
  title: Curated ARO to GO mapping set for AMR gene families
  findings:
  - statement: Manual ARO-to-GO mappings used to identify focused AMR annotation gains.
    supporting_text: 'mapping_set_title: ARO to GO mapping (AMR gene families and resistance mechanisms)'
- id: file:projects/ANTIMICROBIAL_RESISTANCE/data/candidate_new_annotations.tsv
  title: Annotation-gain candidates from ARO to GO mappings
  findings:
  - statement: Candidate GO annotations projected from the ARO-to-GO mapping set.
    supporting_text: Candidate GO annotations that UniProtKB entries with a CARD cross-reference would gain from the
core_functions:
- description: ant covalently modifies aminoglycoside antibiotics by nucleotidyl transfer, reducing drug activity and contributing to antibiotic resistance.
  molecular_function:
    id: GO:0034068
    label: aminoglycoside nucleotidyltransferase activity
  directly_involved_in:
  - id: GO:0046677
    label: response to antibiotic
  supported_by:
  - reference_id: file:genes/STAAU/ant/ant-uniprot.txt
    supporting_text: 'CC   -!- FUNCTION: Mediates bacterial resistance to the antibiotic spectinomycin

      CC       but not streptomycin. {ECO:0000269|PubMed:2993813}.'
suggested_questions:
- question: Is the ARO-derived aminoglycoside nucleotidyltransferase activity annotation sufficiently specific for ant, or is a narrower substrate/site-specific GO term warranted?
  experts: []
suggested_experiments:
- description: Biochemically assay purified ant against representative antibiotic substrates for the inferred AMR family and measure loss of drug activity or target modification.
  experiment_type: in vitro enzyme assay