# Curated Pfam entry review (entry-centric; see src/ai_gene_review/schema/pfam_entry_review.yaml).
# Sidecar to the machine-fetched PF16363-metadata.yaml (do not hand-edit metadata).
# Hand-curated; examples/counter-examples verified against UniProt (reviewed entries).
pfam_id: PF16363
pfam_name: GDP_Man_Dehyd
pfam_description: NDP-sugar-modifying extended-SDR domain; named for GDP-mannose 4,6-dehydratase but broader.
interpro:
  id: InterPro:IPR016040
  label: NAD(P)-bd_dom
  type: Domain
  member_pfams:
  - id: Pfam:PF16363
    label: GDP_Man_Dehyd
    is_subject: true
    note: extended-SDR domain shared across NDP-sugar dehydratases/epimerases/decarboxylases
  - id: Pfam:PF13460
    label: NAD_binding_10
    note: generic NAD(P)-binding Rossmann domain
  go_status: ABSENT
  mapping_viability: NOT_VIABLE
  viability_reason: >-
    InterPro:IPR016040 is a generic NAD(P)-binding fold, so a substrate-specific
    dehydratase term cannot sit on the entry.
proposed_annotations:
- term:
    id: GO:0008446
    label: GDP-mannose 4,6-dehydratase activity
  relation:
    id: RO:0002327
    label: enables
  aspect: molecular_function
  confidence: LOW
  status: REJECTED
  rationale: >-
    REJECTED on member verification. Although GDP-mannose 4,6-dehydratase (GMDS,
    EC 4.2.1.47) is a member, reviewed PF16363 membership also includes a UDP-glucose
    4-epimerase (GALE, EC 5.1.3.2) and a UDP-glucuronate decarboxylase (UXS1,
    EC 4.1.1.35). The family is a shared NDP-sugar-modifying extended-SDR domain, not a
    GDP-mannose-dehydratase-specific signature, so the term would over-annotate even at
    the Pfam level.
  supporting_examples:
  - accession: UniProt:O60547
    protein_name: GMDS_HUMAN (GDP-mannose 4,6 dehydratase / GMD)
    organism: Homo sapiens
    ec: 4.2.1.47
    reviewed: true
    note: The eponymous member; correctly a GDP-mannose 4,6-dehydratase.
  counter_examples:
  - accession: UniProt:Q14376
    protein_name: GALE_HUMAN (UDP-glucose 4-epimerase)
    organism: Homo sapiens
    member_pfam: Pfam:PF16363
    ec: 5.1.3.2
    reviewed: true
    reason: Same family (PF16363) but an epimerase, a different reaction; proves the family is heterogeneous.
  - accession: UniProt:Q8NBZ7
    protein_name: UXS1_HUMAN (UDP-glucuronic acid decarboxylase 1)
    organism: Homo sapiens
    member_pfam: Pfam:PF16363
    ec: 4.1.1.35
    reviewed: true
    reason: Same family but a decarboxylase; a GDP-mannose-dehydratase term would mis-annotate it.
notes: >-
  Cautionary case: the Pfam name overstates specificity. The shared extended-SDR fold
  unifies several NDP-sugar enzymes; substrate specificity is not captured by this Pfam alone.