id: ARBA00090718
description: Rule assigns (S)-2-hydroxyglutarate dehydrogenase activity (GO:0047545) to proteins containing CATH FunFam 3.40.50.720:FF:000041 (D-3-phosphoglycerate dehydrogenase domain)
status: COMPLETE
rule_type: ARBA
rule:
  rule_id: ARBA00090718
  condition_sets:
  - number: 1
    conditions:
    - condition_type: FUNFAM
      value: 3.40.50.720:FF:000041
      curie: CATH.FunFam:3.40.50.720:FF:000041
      label: D-3-phosphoglycerate dehydrogenase
      negated: false
    notes: ''
  go_annotations: []
  reviewed_protein_count: 0
  unreviewed_protein_count: 0
  created_date: ''
  modified_date: ''
  entries:
  - id: 3.40.50.720:FF:000041
    type: FUNFAM
    label: D-3-phosphoglycerate dehydrogenase
    appears_in_condition_sets:
    - 1
    protein_count: 13
    related_entries:
    - relationship: EQUIV
      target_id: IPR030862
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 13
    - relationship: PREDICTS
      target_id: GO:0047545
      containment: 1.0
      jaccard_similarity: 0.063
      intersection_count: 13
      exclusive_count: 0
  - id: IPR030862
    type: INTERPRO
    source: ipr2go
    protein_count: 3
    asserted_predicted_go_terms:
    - GO:0047545
    related_entries:
    - relationship: EQUIV
      target_id: 3.40.50.720:FF:000041
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 3
    - relationship: PREDICTS
      target_id: GO:0047545
      containment: 1.0
      jaccard_similarity: 0.014
      intersection_count: 3
      exclusive_count: 0
review_summary: This rule contains a critical functional mismatch, assigning (S)-2-hydroxyglutarate dehydrogenase activity to proteins with D-3-phosphoglycerate dehydrogenase domains. These are biochemically distinct enzymatic activities with different substrates, products, and metabolic roles. The rule creates false positive annotations and should be removed.
action: DEPRECATE
action_rationale: Clear functional mismatch between condition (D-3-phosphoglycerate dehydrogenase) and annotation ((S)-2-hydroxyglutarate dehydrogenase). These enzymes have distinct substrates, products, cofactors, and metabolic pathways. The rule produces false positive annotations and should be deprecated to prevent misleading functional genomics analyses.
suggested_modifications: []
parsimony:
  assessment: PARSIMONIOUS
  notes: Single condition set with one FunFam condition is structurally simple and parsimonious, though functionally incorrect
literature_support:
  assessment: CONTRADICTED
  notes: Biochemical literature clearly distinguishes D-3-phosphoglycerate dehydrogenase (EC 1.1.1.95, serine biosynthesis) from (S)-2-hydroxyglutarate dehydrogenase (EC 1.1.99.2, 2-hydroxyglutarate metabolism). No evidence found for dual functionality.
  supported_by:
  - reference_id: file:rules/arba/ARBA00090718/ARBA00090718-deep-research-manual.md
    supporting_text: These are biochemically distinct enzymatic activities with different substrates (D-3-phosphoglycerate vs (S)-2-hydroxyglutarate), products, cofactors, and metabolic pathways
condition_overlap:
  assessment: NONE
  notes: Single condition set with one FunFam condition - no internal overlap possible. External analysis shows 0 overlap with related IPR030862
  supported_by:
  - reference_id: file:rules/arba/ARBA00090718/ARBA00090718-analysis.txt
    supporting_text: '3.40.50.720:FF:000041 ↔ IPR030862: Jaccard similarity: 0.000, Interpretation: DISJOINT'
go_specificity:
  assessment: MISMATCHED
  notes: GO:0047545 ((S)-2-hydroxyglutarate dehydrogenase activity) is appropriately specific but incorrectly matched to the D-3-phosphoglycerate dehydrogenase domain condition
  supported_by:
  - reference_id: file:rules/arba/ARBA00090718/ARBA00090718-deep-research-manual.md
    supporting_text: The GO term is specific and accurate for its intended enzyme, but mismatched to proteins containing D-3-phosphoglycerate dehydrogenase domains
taxonomic_scope:
  assessment: TOO_BROAD
  notes: No taxonomic restrictions applied. Rule would incorrectly annotate D-3-phosphoglycerate dehydrogenases across all taxa with wrong enzymatic activity
  supported_by:
  - reference_id: file:rules/arba/ARBA00090718/ARBA00090718-deep-research-manual.md
    supporting_text: The rule applies broadly without taxonomic restriction, creating false positive annotations across all domains of life
confidence: 0.9
references:
- id: file:rules/arba/ARBA00090718/ARBA00090718-deep-research-manual.md
  title: Deep research analysis - Manual curation
  findings:
  - statement: D-3-phosphoglycerate dehydrogenase and (S)-2-hydroxyglutarate dehydrogenase are biochemically distinct enzymes
  - statement: Different substrates, products, cofactors, and metabolic pathways
  - statement: No evidence for dual functionality in the literature
  - statement: Rule creates false positive annotations with high confidence
- id: file:rules/arba/ARBA00090718/ARBA00090718-analysis.txt
  title: Quantitative domain overlap analysis
  findings:
  - statement: Perfect containment (1.0) of FunFam proteins in GO term annotation
  - statement: Low Jaccard similarity (0.063) indicates concentrated false positives
  - statement: No overlap with related InterPro term IPR030862
supported_by:
- reference_id: file:rules/arba/ARBA00090718/ARBA00090718-deep-research-manual.md
  supporting_text: This rule presents a critical functional mismatch that suggests incorrect annotation
- reference_id: file:rules/arba/ARBA00090718/ARBA00090718-analysis.txt
  supporting_text: Analysis showed perfect containment (1.0) with low Jaccard similarity (0.063), indicating concentrated false positives