# Curated Pfam entry review (entry-centric; see src/ai_gene_review/schema/pfam_entry_review.yaml).
# Sidecar to the machine-fetched PF14681-metadata.yaml (do not hand-edit metadata).
# Hand-curated; examples/counter-examples verified against UniProt (reviewed entries).
pfam_id: PF14681
pfam_name: UPRTase
pfam_description: Uracil-phosphoribosyltransferase-like domain; eponymously Upp, but also found in uridine kinases.
interpro:
  id: InterPro:IPR000836
  label: PRTase_dom
  type: Domain
  member_pfams:
  - id: Pfam:PF14681
    label: UPRTase
    is_subject: true
    note: uracil PRTase-like domain (contains the real Upp, but also uridine-kinase fusions)
  - id: Pfam:PF00156
    label: Pribosyltran
    note: generic phosphoribosyltransferase domain (APRT/HGPRT/amido-PRT/etc.)
  go_status: ABSENT
  mapping_viability: NOT_VIABLE
  viability_reason: >-
    InterPro:IPR000836 spans many PRT substrates via the generic Pribosyltran sibling,
    so a uracil-specific term cannot sit on the entry.
proposed_annotations:
- term:
    id: GO:0004845
    label: uracil phosphoribosyltransferase activity
  relation:
    id: RO:0002327
    label: enables
  aspect: molecular_function
  confidence: LOW
  status: REJECTED
  rationale: >-
    REJECTED on member verification. The canonical bacterial Upp (UniProt:P0A8F0,
    EC 2.4.2.9) genuinely belongs to PF14681, so the family is named for a real function.
    However, reviewed PF14681 members also include uridine/uridine-cytidine kinases
    (EC 2.7.1.48) that do not have uracil phosphoribosyltransferase activity. Because
    the family itself is functionally heterogeneous, a uracil-PRTase term would
    over-annotate even at the Pfam level, not only at the InterPro entry.
  supporting_examples:
  - accession: UniProt:P0A8F0
    protein_name: UPP_ECOLI (uracil phosphoribosyltransferase / UPRTase)
    organism: Escherichia coli K12
    ec: 2.4.2.9
    reviewed: true
    note: The eponymous, correctly-annotated member; confirms the family is named for a real enzyme.
  counter_examples:
  - accession: UniProt:Q9NWZ5
    protein_name: UCKL1_HUMAN (uridine-cytidine kinase-like 1)
    organism: Homo sapiens
    member_pfam: Pfam:PF14681
    ec: 2.7.1.48
    reviewed: true
    reason: Same family (PF14681) but a uridine-cytidine kinase, not a uracil PRTase. Proves the family is heterogeneous.
  - accession: UniProt:P27515
    protein_name: URK1_YEAST (uridine kinase / uridine monophosphokinase)
    organism: Saccharomyces cerevisiae
    member_pfam: Pfam:PF14681
    ec: 2.7.1.48
    reviewed: true
    reason: Same family, kinase activity; a uracil-PRTase term would mis-annotate it.
notes: >-
  Cautionary case: the Pfam name and the seed (Upp) suggest a clean uracil-PRTase
  mapping, but reviewed membership shows the family also captures uridine kinases.
  Refining this would need a sub-family (clan/architecture) signature, not the whole Pfam.