# Curated Pfam entry review (entry-centric; see src/ai_gene_review/schema/pfam_entry_review.yaml).
# Sidecar to the machine-fetched PF13561-metadata.yaml (do not hand-edit metadata).
# Hand-curated; examples/counter-examples verified against UniProt (reviewed entries).
pfam_id: PF13561
pfam_name: adh_short_C2
pfam_description: Short-chain dehydrogenase/reductase (SDR) domain; named for enoyl-ACP reductase but generic SDR.
interpro:
  id: InterPro:IPR002347
  label: SDR_fam
  type: Family
  member_pfams:
  - id: Pfam:PF13561
    label: adh_short_C2
    is_subject: true
    note: generic SDR domain (contains FabI and FabG and many other SDRs)
  - id: Pfam:PF00106
    label: adh_short
    note: generic short-chain dehydrogenase/reductase domain
  go_status: ABSENT
  mapping_viability: NOT_VIABLE
  viability_reason: >-
    InterPro:IPR002347 is the generic SDR family spanning thousands of substrates, so no
    specific activity fits the entry.
proposed_annotations:
- term:
    id: GO:0016631
    label: enoyl-[acyl-carrier-protein] reductase [NAD(P)H] activity
  relation:
    id: RO:0002327
    label: enables
  aspect: molecular_function
  confidence: LOW
  status: REJECTED
  rationale: >-
    REJECTED on member verification. Enoyl-ACP reductase FabI (UniProt:P0AEK4,
    EC 1.3.1.9) is a member, but so is 3-oxoacyl-ACP reductase FabG (UniProt:P0AEK2,
    EC 1.1.1.100) -- a different FAS-II reaction -- along with many unrelated SDRs
    (L-xylulose reductase, carbonyl reductases). PF13561 is a generic SDR domain, not an
    enoyl-ACP-reductase-specific signature, so the term would over-annotate even at the
    Pfam level. (The Pfam description "Enoyl-(Acyl carrier protein) reductase" is
    misleading relative to actual membership.)
  supporting_examples:
  - accession: UniProt:P0AEK4
    protein_name: FABI_ECOLI (enoyl-[acyl-carrier-protein] reductase [NADH] FabI)
    organism: Escherichia coli K12
    ec: 1.3.1.9
    reviewed: true
    note: A genuine enoyl-ACP reductase member -- but not representative of the whole family.
  counter_examples:
  - accession: UniProt:P0AEK2
    protein_name: FABG_ECOLI (3-oxoacyl-[acyl-carrier-protein] reductase FabG)
    organism: Escherichia coli K12
    member_pfam: Pfam:PF13561
    ec: 1.1.1.100
    reviewed: true
    reason: Same family (PF13561) but a ketoacyl-ACP reductase, a different reaction; decisive proof the family is not enoyl-ACP-reductase-specific.
  - accession: UniProt:Q7Z4W1
    protein_name: DCXR_HUMAN (L-xylulose reductase)
    organism: Homo sapiens
    member_pfam: Pfam:PF13561
    ec: 1.1.1.10
    reviewed: true
    reason: Same family, an unrelated carbonyl-sugar reductase; would be mis-annotated by an enoyl-ACP-reductase term.
notes: >-
  Cautionary case and the clearest negative: FabI and FabG -- two distinct FAS-II
  enzymes -- share PF13561, so the family encodes the SDR fold, not a specific activity.
