id: A0A314KUK7
gene_symbol: NaA622
product_type: PROTEIN
status: DRAFT
aliases:
- A622
- IFRH_2
taxon:
  id: NCBITaxon:49451
  label: Nicotiana attenuata
description: >-
  NaA622 is the primary NICAT mapping for the late nicotine-pathway A622
  oxidoreductase. The recent nicotine glucosylation preprint redefines the
  tobacco A622 ortholog as a nicotinic acid N-glucoside reductase (NaGR) in the
  four-enzyme nicotine synthase cascade, making this accession the leading
  candidate for the analogous late reductase step in Nicotiana attenuata.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: file:NICAT/NaA622/NaA622-uniprot.txt
  title: UniProt entry A0A314KUK7 for Nicotiana attenuata A622 candidate
  findings:
  - statement: UniProt identifies A0A314KUK7 as an A622-like isoflavone reductase family protein
    supporting_text: 'DE   SubName: Full=Isoflavone reductase -like a622 ;'
    reference_section_type: DATABASE_ENTRY
- id: file:NICAT/NaA622/NaA622-notes.md
  title: NaA622 literature review notes
  findings:
  - statement: A622 is the late-pathway NaGR reductase in the completed nicotine synthase cascade
    supporting_text: The full nicotine glucosylation preprint redefines A622 as NaGR, a nicotinic acid N-glucoside reductase in the four-enzyme nicotine synthase cascade, making A622 a directly supported late-pathway catalyst rather than a generic oxidoreductase placeholder.
    reference_section_type: LITERATURE_REVIEW
  - statement: A622 has direct structural and mechanistic support in the glucosylation model
    supporting_text: The same paper provides strong mechanistic support for A622 by solving A622/NaGR with nicotinic acid N-glucoside and by showing that A622 loss blocks the pathway at nicotinic acid N-glucoside.
    reference_section_type: LITERATURE_REVIEW
existing_annotations:
- term:
    id: GO:0016491
    label: oxidoreductase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      This annotation is directionally correct but much too generic for the
      current state of A622 biology.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The glucosylation preprint resolves A622 as a specific late-pathway
      reductase acting on nicotinic acid N-glucoside, so the broad parent term
      no longer captures the informative chemistry of the protein.
    supported_by:
    - reference_id: file:NICAT/NaA622/NaA622-notes.md
      supporting_text: The full nicotine glucosylation preprint redefines A622 as NaGR, a nicotinic acid N-glucoside reductase in the four-enzyme nicotine synthase cascade, making A622 a directly supported late-pathway catalyst rather than a generic oxidoreductase placeholder.
      reference_section_type: LITERATURE_REVIEW
- term:
    id: GO:0042179
    label: nicotine biosynthetic process
  evidence_type: TAS
  original_reference_id: file:NICAT/NaA622/NaA622-notes.md
  review:
    summary: >-
      A nicotine-biosynthetic-process annotation is now directly supported for
      the A622 orthologous role.
    action: NEW
    reason: >-
      The recent pathway reconstruction and knockout logic place A622/NaGR in the
      core late nicotine synthase cascade rather than as a loosely associated
      oxidoreductase.
    supported_by:
    - reference_id: file:NICAT/NaA622/NaA622-notes.md
      supporting_text: The full nicotine glucosylation preprint redefines A622 as NaGR, a nicotinic acid N-glucoside reductase in the four-enzyme nicotine synthase cascade, making A622 a directly supported late-pathway catalyst rather than a generic oxidoreductase placeholder.
      reference_section_type: LITERATURE_REVIEW
core_functions:
- molecular_function:
    id: GO:0016491
    label: oxidoreductase activity
  directly_involved_in:
  - id: GO:0042179
    label: nicotine biosynthetic process
  description: >-
    NaA622 is the primary NICAT candidate for the A622/NaGR reductase step that
    reduces nicotinic acid N-glucoside during late nicotine biosynthesis.
  supported_by:
  - reference_id: file:NICAT/NaA622/NaA622-notes.md
    supporting_text: The full nicotine glucosylation preprint redefines A622 as NaGR, a nicotinic acid N-glucoside reductase in the four-enzyme nicotine synthase cascade, making A622 a directly supported late-pathway catalyst rather than a generic oxidoreductase placeholder.
    reference_section_type: LITERATURE_REVIEW
proposed_new_terms:
- proposed_name: nicotinic acid N-glucoside reductase activity
  proposed_definition: >-
    Catalysis of the NADPH-dependent reduction of nicotinic acid N-glucoside to a
    reduced dihydropyridine glucoside intermediate in nicotine biosynthesis.
  justification: >-
    GO currently captures A622 only at the generic oxidoreductase level, whereas
    the recent pathway paper resolves a substrate-specific reductase activity for
    the A622 ortholog.
  proposed_parent:
    id: GO:0016491
    label: oxidoreductase activity
  supported_by:
  - reference_id: file:NICAT/NaA622/NaA622-notes.md
    supporting_text: The full nicotine glucosylation preprint redefines A622 as NaGR, a nicotinic acid N-glucoside reductase in the four-enzyme nicotine synthase cascade, making A622 a directly supported late-pathway catalyst rather than a generic oxidoreductase placeholder.
    reference_section_type: LITERATURE_REVIEW
suggested_questions:
- question: Does A0A314KUK7 account for most NaGR flux in Nicotiana attenuata roots, or is the alternate IFRH_0 paralog also catalytically competent in vivo?
- question: Is the attenuata A622 protein substrate-selective for nicotinic acid N-glucoside in the same way as the tobacco NaGR ortholog?
suggested_experiments:
- description: Compare recombinant A0A314KUK7 and IFRH_0 proteins in side-by-side nicotinic acid N-glucoside reduction assays with NADPH.
  experiment_type: biochemical enzyme assay
  hypothesis: A0A314KUK7 is the dominant NICAT NaGR paralog.
- description: Knock out the primary A622 mapping in roots and profile nicotinic acid N-glucoside, downstream glucosides, and nicotine accumulation after topping or herbivory induction.
  experiment_type: genetic perturbation plus metabolite profiling
  hypothesis: Loss of the primary A622 paralog will block late-pathway flux upstream of nicotine.