id: P00557
gene_symbol: hph
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:562
  label: Escherichia coli
description: hph encodes an aminoglycoside phosphotransferase in Escherichia coli. UniProt/CARD identify this entry as an aminoglycoside-modifying resistance enzyme that inactivates aminoglycosides by phosphorylation. UniProt names the protein 'Hygromycin-B 4-O-kinase' (accession P00557).
existing_annotations:
- term:
    id: GO:0034071
    label: aminoglycoside phosphotransferase activity
  evidence_type: RCA
  original_reference_id: file:projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml
  qualifier: enables
  review:
    summary: 'NEW candidate annotation from the curated ARO->GO mapping: aminoglycoside phosphotransferase activity.'
    action: NEW
    reason: The UniProt record cross-references a CARD/ARO AMR determinant, and the curated ARO->GO mapping projects the family-specific molecular function aminoglycoside phosphotransferase activity. This focused draft accepts the candidate as a curator lead for this AMR determinant.
    additional_reference_ids:
    - file:projects/ANTIMICROBIAL_RESISTANCE/data/candidate_new_annotations.tsv
    - file:genes/ECOLX/hph/hph-uniprot.txt
    supported_by:
    - reference_id: file:projects/ANTIMICROBIAL_RESISTANCE/data/candidate_new_annotations.tsv
      supporting_text: "P00557\tARO:3002655\tARO:3000114\tnarrower\tRO:0002327\tGO:0034071\taminoglycoside phosphotransferase activity"
    - reference_id: file:genes/ECOLX/hph/hph-uniprot.txt
      supporting_text: 'CC   -!- FUNCTION: The aminoglycoside phosphotransferases achieve inactivation

        CC       of their antibiotic substrates by phosphorylation. Only phosphorylates

        CC       hygromycin and closely related compounds such as demethyl analogs and'
- term:
    id: GO:0046677
    label: response to antibiotic
  evidence_type: RCA
  original_reference_id: file:projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml
  qualifier: involved_in
  review:
    summary: 'NEW process annotation: hph is an AMR determinant involved in antibiotic response/resistance.'
    action: NEW
    reason: CARD/ARO identity places this gene in an antimicrobial-resistance determinant family; response to antibiotic is the appropriate high-level GO biological process for the resistance role.
    additional_reference_ids:
    - file:genes/ECOLX/hph/hph-uniprot.txt
    supported_by:
    - reference_id: file:genes/ECOLX/hph/hph-uniprot.txt
      supporting_text: DR   CARD; ARO:3002655; APH(4)-Ia; ARO:0001004; antibiotic inactivation.
references:
- id: file:genes/ECOLX/hph/hph-uniprot.txt
  title: UniProt flat file for hph (P00557)
  findings:
  - statement: UniProt/CARD identity and protein naming for hph.
    supporting_text: 'CC   -!- FUNCTION: The aminoglycoside phosphotransferases achieve inactivation

      CC       of their antibiotic substrates by phosphorylation. Only phosphorylates

      CC       hygromycin and closely related compounds such as demethyl analogs and'
- 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: hph phosphorylates aminoglycoside antibiotics, reducing drug activity and contributing to antibiotic resistance.
  molecular_function:
    id: GO:0034071
    label: aminoglycoside phosphotransferase activity
  directly_involved_in:
  - id: GO:0046677
    label: response to antibiotic
  supported_by:
  - reference_id: file:genes/ECOLX/hph/hph-uniprot.txt
    supporting_text: 'CC   -!- FUNCTION: The aminoglycoside phosphotransferases achieve inactivation

      CC       of their antibiotic substrates by phosphorylation. Only phosphorylates

      CC       hygromycin and closely related compounds such as demethyl analogs and'
suggested_questions:
- question: Is the ARO-derived aminoglycoside phosphotransferase activity annotation sufficiently specific for hph, or is a narrower substrate/site-specific GO term warranted?
  experts: []
suggested_experiments:
- description: Biochemically assay purified hph against representative antibiotic substrates for the inferred AMR family and measure loss of drug activity or target modification.
  experiment_type: in vitro enzyme assay