id: O67972
gene_symbol: arr
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:1772
  label: Mycolicibacterium smegmatis
description: >-
  arr encodes the Mycolicibacterium smegmatis rifampin ADP-ribosyltransferase
  Arr-1. Arr ribosylates rifampin, causing antibiotic inactivation and
  contributing substantially to intrinsic low susceptibility to rifampin in this
  organism. The current GO representation is missing from the fetched GOA file
  and GO lacks a substrate-specific rifampin mono-ADP-ribosyltransferase term.
existing_annotations:
- term:
    id: GO:0016740
    label: transferase activity
  evidence_type: RCA
  original_reference_id: file:genes/MYCSM/arr/arr-uniprot.txt
  qualifier: enables
  review:
    summary: >-
      NEW interim molecular-function annotation. UniProt carries only the broad
      transferase GO line, while the specific function is rifampin
      mono-ADP-ribosyltransferase activity.
    action: NEW
    reason: >-
      The GOA TSV fetched for this accession is empty, but the UniProt flat file
      contains a transferase GO cross-reference and CARD identifies Arr-1 as an
      antibiotic-inactivation determinant. A more specific GO term should be
      requested.
    additional_reference_ids:
    - PMID:9371349
    - file:projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml
    supported_by:
    - reference_id: file:genes/MYCSM/arr/arr-uniprot.txt
      supporting_text: "DE   SubName: Full=Rifampin ADP-ribosyl transferase"
    - reference_id: PMID:9371349
      supporting_text: "Mycobacterium smegmatis inactivates rifampin by ribosylating this antibiotic."
- term:
    id: GO:0046677
    label: response to antibiotic
  evidence_type: RCA
  original_reference_id: PMID:9371349
  qualifier: involved_in
  review:
    summary: NEW high-level process annotation for Arr-mediated rifampin resistance.
    action: NEW
    reason: >-
      Arr directly inactivates rifampin and gene disruption increases rifampin
      susceptibility. The process term is high-level, but it is appropriate for
      this antibiotic-inactivation determinant.
    additional_reference_ids:
    - file:genes/MYCSM/arr/arr-uniprot.txt
    supported_by:
    - reference_id: PMID:9371349
      supporting_text: "Targeted disruption of the gene in M. smegmatis resulted in mutants with much increased susceptibility to rifampin"
    - reference_id: file:genes/MYCSM/arr/arr-uniprot.txt
      supporting_text: "DR   CARD; ARO:3002846; arr-1; ARO:0001004; antibiotic inactivation."
references:
- id: file:genes/MYCSM/arr/arr-uniprot.txt
  title: UniProt flat file for arr (O67972)
  findings:
  - statement: UniProt identifies this entry as rifampin ADP-ribosyl transferase Arr-1.
    supporting_text: "DR   CARD; ARO:3002846; arr-1; ARO:0001004; antibiotic inactivation."
- id: PMID:9371349
  title: Ribosylative inactivation of rifampin by Mycobacterium smegmatis is a principal contributor to its low susceptibility to this antibiotic.
  findings:
  - statement: Genetic disruption and biochemical assays identify Arr-mediated rifampin ribosylation as a resistance mechanism.
    supporting_text: "Targeted disruption of the gene in M. smegmatis resulted in mutants with much increased susceptibility to rifampin"
- 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 Arr as a GO molecular-function gap because the nearest ADP-ribosyltransferase terms are wrong for rifampin mono-ADP-ribosylation.
    supporting_text: "GO's nearest term GO:0003950 is NAD+ poly-ADP-ribosyltransferase"
core_functions:
- description: >-
    Rifampin mono-ADP-ribosyltransferase activity that ribosylates rifampin and
    inactivates the antibiotic.
  molecular_function:
    id: GO:0016740
    label: transferase activity
  directly_involved_in:
  - id: GO:0046677
    label: response to antibiotic
  supported_by:
  - reference_id: PMID:9371349
    supporting_text: "A 600-bp subclone responsible for ribosylating activity and resistance carried an open reading frame"
  - reference_id: file:genes/MYCSM/arr/arr-uniprot.txt
    supporting_text: "DE   SubName: Full=Rifampin ADP-ribosyl transferase"
proposed_new_terms:
- proposed_name: rifampin mono-ADP-ribosyltransferase activity
  proposed_definition: >-
    Catalysis of the transfer of ADP-ribose to rifampin, producing a
    ribosylated rifampin derivative with reduced antibiotic activity.
  justification: >-
    Existing GO ADP-ribosyltransferase terms are protein- or poly-ADP-ribose
    focused and do not fit Arr, whose substrate is rifampin. The broad
    transferase term loses the antibiotic-inactivation mechanism.
  proposed_parent:
    id: GO:0016740
    label: transferase activity
  proposed_mappings:
  - predicate: skos:exactMatch
    target_term:
      id: ARO:3000390
      label: rifampin ADP-ribosyltransferase (Arr)
  supported_by:
  - reference_id: PMID:9371349
    supporting_text: "Mycobacterium smegmatis inactivates rifampin by ribosylating this antibiotic."
  - reference_id: file:projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml
    supporting_text: "Arr is a mono-ADP-ribosyltransferase"
suggested_questions:
- question: Should the Arr GO term be named for rifampin specifically, or for the broader rifamycin class if substrate evidence supports it?
  experts: []
suggested_experiments:
- description: >-
    Purify Arr-1 and measure ADP-ribosylation of rifampin and related rifamycins
    by LC-MS to define the substrate range for a GO term.
  experiment_type: in vitro enzyme assay