# Curated Pfam entry review (entry-centric; see src/ai_gene_review/schema/pfam_entry_review.yaml).
# Sidecar to the machine-fetched PF27512-metadata.yaml (do not hand-edit metadata).
# Hand-curated; examples/counter-examples verified against UniProt (reviewed entries).
pfam_id: PF27512
pfam_name: LeuD
pfam_description: Small (LeuD) subunit of 3-isopropylmalate dehydratase (isopropylmalate isomerase).
interpro:
  id: InterPro:IPR000573
  label: AconitaseA/IPMdHydase_ssu_swvl
  type: Domain
  member_pfams:
  - id: Pfam:PF27512
    label: LeuD
    is_subject: true
    note: 3-isopropylmalate dehydratase small subunit
  - id: Pfam:PF00694
    label: Aconitase_C
    note: aconitase/IPM-isomerase swivel domain; shared by aconitase (a different enzyme)
  go_status: ABSENT
  mapping_viability: NOT_VIABLE
  viability_reason: >-
    The entry is the shared aconitase/IPM-isomerase "swivel" domain. Aconitase
    (PF00694 members, EC 4.2.1.3) is a distinct enzyme acting on citrate/isocitrate, so
    a 3-isopropylmalate dehydratase term on the entry would be wrong for aconitases.
proposed_annotations:
- term:
    id: GO:0003861
    label: 3-isopropylmalate dehydratase activity
  relation:
    id: RO:0002327
    label: enables
  aspect: molecular_function
  confidence: HIGH
  status: PROPOSED
  rationale: >-
    Every reviewed member of PF27512 is annotated as the 3-isopropylmalate dehydratase
    small subunit (LeuD, EC 4.2.1.33) across diverse bacteria; the family is tightly and
    uniformly function-specific, with no contradicting members found.
  supporting_examples:
  - accession: UniProt:P30126
    protein_name: LEUD_ECOLI (3-isopropylmalate dehydratase small subunit / IPMI)
    organism: Escherichia coli K12
    ec: 4.2.1.33
    reviewed: true
  - accession: UniProt:A0ZZS8
    protein_name: LEUD_BIFAA (3-isopropylmalate dehydratase small subunit)
    organism: Bifidobacterium adolescentis
    ec: 4.2.1.33
    reviewed: true
  counter_examples:
  - accession: UniProt:P21399
    protein_name: ACOHC_HUMAN (cytoplasmic aconitate hydratase / IRP1)
    organism: Homo sapiens
    member_pfam: Pfam:PF00694
    ec: 4.2.1.3
    reviewed: true
    reason: Aconitase (citrate/isocitrate), a different reaction; shares only the swivel domain on the entry.
- term:
    id: GO:0009098
    label: L-leucine biosynthetic process
  relation:
    id: RO:0002331
    label: involved in
  aspect: biological_process
  confidence: HIGH
  status: PROPOSED
  rationale: >-
    LeuD (with LeuC) catalyses the second step of leucine biosynthesis; the BP follows
    directly from the uniformly assigned MF above.
  supporting_examples:
  - accession: UniProt:P30126
    protein_name: LEUD_ECOLI (3-isopropylmalate dehydratase small subunit)
    organism: Escherichia coli K12
    ec: 4.2.1.33
    reviewed: true
notes: >-
  PF27512 is one of the cleanest cases: uniform reviewed membership, a single distinct
  sibling (aconitase) that supplies the counter-example for why the entry can't carry the term.