id: Q06DK7
gene_symbol: tetX
product_type: PROTEIN
aliases:
- tet(X)
status: DRAFT
taxon:
  id: NCBITaxon:403776
  label: Sphingobacterium sp. (strain PM2-P1-29)
description: >-
  tetX encodes an FAD-dependent tetracycline monooxygenase from Sphingobacterium
  sp. PM2-P1-29. The enzyme uses NADPH and oxygen to hydroxylate tetracycline at
  carbon 11a, initiating tetracycline breakdown and inactivation. This
  antibiotic-destruction activity explains the tetracycline resistance phenotype
  of the source organism and of heterologous hosts expressing tetX.
existing_annotations:
- term:
    id: GO:0000166
    label: nucleotide binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000104
  qualifier: enables
  review:
    summary: >-
      Broad cofactor-binding annotation. TetX binds flavin/nucleotide cofactors,
      but the informative function is FAD-dependent tetracycline monooxygenase
      activity.
    action: KEEP_AS_NON_CORE
    reason: >-
      The annotation is compatible with the FAD/NADPH-dependent enzyme record, but
      it is too general to represent the core biological activity.
    supported_by:
    - reference_id: file:genes/SPHSM/tetX/tetX-uniprot.txt
      supporting_text: "Name=FAD"
- term:
    id: GO:0004497
    label: monooxygenase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Correct core molecular function, but much broader than the TetX-specific
      tetracycline C11a monooxygenase/destructase activity.
    action: ACCEPT
    reason: >-
      UniProt and the cached TetX papers directly support a monooxygenase that
      acts on tetracycline. GO currently has only the broader monooxygenase term;
      a specific TetX/tetracycline 11a-monooxygenase term is proposed below.
    supported_by:
    - reference_id: file:genes/SPHSM/tetX/tetX-uniprot.txt
      supporting_text: "An FAD-requiring monooxygenase active on some tetracycline"
    - reference_id: PMID:19187139
      supporting_text: "tet(X) encodes for a NADP-dependent monooxygenase that requires oxygen to degrade tetracycline"
    - reference_id: PMID:26038239
      supporting_text: "TetX is a flavin-dependent monooxygenase."
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Cytoplasmic localization is consistent with a soluble bacterial antibiotic-inactivation enzyme.
    action: ACCEPT
    reason: >-
      The UniProt record carries the cytoplasm GO annotation and does not indicate
      secretion or membrane localization.
    supported_by:
    - reference_id: file:genes/SPHSM/tetX/tetX-uniprot.txt
      supporting_text: "DR   GO; GO:0005737; C:cytoplasm"
- 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 for a tetracycline-inactivation resistance enzyme.
    action: ACCEPT
    reason: >-
      The response/resistance annotation is biologically sound, but the core value
      for this review is the missing precise molecular-function term.
    supported_by:
    - reference_id: file:genes/SPHSM/tetX/tetX-uniprot.txt
      supporting_text: "DR   CARD; ARO:3000205; tet(X); ARO:0001004; antibiotic inactivation."
    - reference_id: PMID:26038239
      supporting_text: "It has been reported to inactivate all tested tetracyclines."
- term:
    id: GO:0071949
    label: FAD binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: Correct cofactor-binding annotation for a flavin-dependent monooxygenase.
    action: KEEP_AS_NON_CORE
    reason: >-
      FAD binding is mechanistically relevant but secondary to the catalytic
      antibiotic-inactivation activity.
    supported_by:
    - reference_id: file:genes/SPHSM/tetX/tetX-uniprot.txt
      supporting_text: "Name=FAD"
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000104
  title: Electronic Gene Ontology annotations created by transferring manual GO annotations between related proteins based on shared sequence features
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: file:genes/SPHSM/tetX/tetX-uniprot.txt
  title: UniProt flat file for tetX (Q06DK7)
  findings:
  - statement: UniProt describes TetX as an FAD-dependent monooxygenase that hydroxylates tetracycline at C11a.
    supporting_text: "Reaction=tetracycline + NADPH + O2 + H(+) = 11a-hydroxytetracycline"
- id: PMID:19187139
  title: Sphingobacterium sp. strain PM2-P1-29 harbours a functional tet(X) gene encoding for the degradation of tetracycline.
  findings:
  - statement: The source strain carries functional tetX and transforms tetracycline.
    supporting_text: "Sphingobacterium sp. PM2-P1-29 demonstrated the ability to transform tetracycline compared with killed controls."
- id: PMID:26038239
  title: Transformation of tetracycline by TetX and its subsequent degradation in a heterologous host.
  findings:
  - statement: TetX inactivates tetracyclines and affects tetracycline resistance in a heterologous host context.
    supporting_text: "TetX is a flavin-dependent monooxygenase. It has been reported to inactivate all tested tetracyclines."
- 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 TetX/tetracycline destructase as a GO molecular-function term gap.
    supporting_text: "GO has no Tet(X)/tetracycline-destructase (flavin-dependent tetracycline monooxygenase) MF term."
core_functions:
- description: >-
    FAD-dependent tetracycline monooxygenase activity that hydroxylates
    tetracycline at C11a, leading to antibiotic inactivation and degradation.
  molecular_function:
    id: GO:0004497
    label: monooxygenase activity
  directly_involved_in:
  - id: GO:0046677
    label: response to antibiotic
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: file:genes/SPHSM/tetX/tetX-uniprot.txt
    supporting_text: "Reaction=tetracycline + NADPH + O2 + H(+) = 11a-hydroxytetracycline"
  - reference_id: PMID:26038239
    supporting_text: "We also describe new metabolites formed after tetracycline transformation by TetX"
proposed_new_terms:
- proposed_name: tetracycline 11a-monooxygenase activity
  proposed_definition: >-
    Catalysis of the NADPH- and oxygen-dependent hydroxylation of tetracycline
    at carbon 11a, producing 11a-hydroxytetracycline and initiating tetracycline
    antibiotic inactivation.
  justification: >-
    GO has only the broad monooxygenase activity term for TetX, but TetX-family
    AMR determinants have a substrate- and position-specific antibiotic
    destruction activity supported by Rhea/EC information and experimental TetX
    literature.
  proposed_parent:
    id: GO:0004497
    label: monooxygenase activity
  proposed_mappings:
  - predicate: skos:exactMatch
    target_term:
      id: ARO:3000036
      label: tetracycline inactivation enzyme
  supported_by:
  - reference_id: file:genes/SPHSM/tetX/tetX-uniprot.txt
    supporting_text: "Reaction=tetracycline + NADPH + O2 + H(+) = 11a-hydroxytetracycline"
  - reference_id: file:projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml
    supporting_text: "GO has no Tet(X)/tetracycline-destructase (flavin-dependent tetracycline monooxygenase) MF term."
suggested_questions:
- question: Should GO add a TetX-family tetracycline 11a-monooxygenase activity term distinct from generic monooxygenase activity?
  experts: []
suggested_experiments:
- description: >-
    Assay purified TetX against tetracycline-class substrates and identify
    11a-hydroxylated products by LC-MS to delimit substrate scope for the GO term.
  experiment_type: in vitro enzyme assay