ARBA00090718 (S)-2-hydroxyglutarate dehydrogenase activity (GO:0047545)

id: ARBA00090718
description: >-
  Assigns GO:0047545 ((S)-2-hydroxyglutarate dehydrogenase activity) to proteins that have the FAD
  dependent oxidoreductase domain (IPR006076), the FAD/NAD(P)-binding domain superfamily (IPR036188)
  and membership of PANTHER family PTHR43104 (L-2-hydroxyglutarate dehydrogenase, mitochondrial).
status: COMPLETE
rule_type: ARBA
rule:
  rule_id: ARBA00090718
  condition_sets:
  - number: 1
    conditions:
    - condition_type: INTERPRO
      value: IPR006076
      curie: InterPro:IPR006076
      label: FAD dependent oxidoreductase
      negated: false
    - condition_type: INTERPRO
      value: IPR036188
      curie: InterPro:IPR036188
      label: FAD/NAD(P)-binding domain superfamily
      negated: false
    - condition_type: PANTHER
      value: PTHR43104
      curie: PANTHER:PTHR43104
      label: L-2-HYDROXYGLUTARATE DEHYDROGENASE, MITOCHONDRIAL
      negated: false
    notes: >-
      UniProtKB release 2026_04: 17 reviewed entries match this set; 17 of them carry GO:0047545 or
      a descendant, 14 of those by a manual-evidence GO annotation. 10704 unreviewed entries match.
  go_annotations:
  - go_id: GO:0047545
    go_label: (S)-2-hydroxyglutarate dehydrogenase activity
    aspect: MF
  entries: []
  reviewed_protein_count: 0
  unreviewed_protein_count: 0
  created_date: '2025-03-21'
  modified_date: '2026-07-18'
  retrieved_date: '2026-11-09'
  source_condition_set_count: 1
review_summary: >-
  The live rule has one condition set, a three-way conjunction that selects the L-2-hydroxyglutarate
  dehydrogenase family. All 17 reviewed entries that match it carry GO:0047545, 14 of them by manual
  evidence, including experimentally characterised enzymes from human, Arabidopsis, Drosophila and
  Escherichia coli. The rule is sound.
action: ACCEPT
action_rationale: >-
  The single condition set was examined. Every reviewed match is annotated with the consequent and
  the family is the one the GO term describes. The counts are from Swiss-Prot, which is also what
  ARBA learns its rules from, so they show the condition sets are coherent rather than giving an independent
  error rate for unreviewed entries.
go_specificity:
  assessment: APPROPRIATE
  notes: >-
    GO:0047545 is the activity of the family named by PTHR43104, and is the term carried with IDA
    evidence by its characterised members (Q9H9P8, Q9LES4, P37339).
annotation_assessments:
- annotation_kind: GO_TERM
  value: GO:0047545
  label: (S)-2-hydroxyglutarate dehydrogenase activity
  assessment: CORRECT
  matched_protein_count: 17
  incorrect_protein_count: 0
  correct_examples:
  - Q9H9P8
  - Q9LES4
  - P37339
  - Q9VJ28
  notes: >-
    Q9H9P8 (human L2HGDH): GO:0047545 IDA, PMID:16005139. Q9LES4 (Arabidopsis L2HGDH): GO:0047545
    IDA, PMID:26203119. P37339 (E. coli lhgD): GO:0047545 IDA, PMID:30498244. Q9VJ28 (Drosophila L2HGDH):
    GO:0047545 IDA, PMID:37995940. Source: QuickGO annotation search, retrieved 2026-11-09.
confidence: 0.85
corrections:
- date: '2026-11-10'
  withdrawn_claim: >-
    The rule's condition is CATH FunFam 3.40.50.720:FF:000041 (D-3-phosphoglycerate dehydrogenase),
    so the rule assigns the activity to phosphoglycerate dehydrogenases.
  correction: >-
    The live rule has no FunFam condition. Its one condition set is IPR006076 AND IPR036188 AND PANTHER:PTHR43104,
    the L-2-hydroxyglutarate dehydrogenase family. The verdict was reached on a condition that is
    not in the rule as retrieved.
  error_type: STALE_RULE_VERSION
  evidence:
  - >-
    UniProt ARBA API, ARBA00090718, modified 2026-07-18, retrieved 2026-11-09: one condition set,
    InterPro IPR006076 AND InterPro IPR036188 AND PANTHER PTHR43104.
  - >-
    PANTHER:PTHR43104 name: L-2-HYDROXYGLUTARATE DEHYDROGENASE, MITOCHONDRIAL (interpro/panther/panther.obo).
- date: '2026-11-10'
  withdrawn_claim: >-
    No evidence was found that a D-3-phosphoglycerate dehydrogenase has 2-hydroxyglutarate dehydrogenase
    activity.
  correction: >-
    Escherichia coli SerA (P0A9T0), the protein the FunFam is named after, has a curated second activity
    on 2-oxoglutarate and 2-hydroxyglutarate, and carries GO:0047545 with IDA evidence. The curated
    reaction is on the (R) isomer, so whether the (S) term is the right one for SerA is an open question
    for the annotation of that protein; it does not bear on the live rule.
  error_type: REFUTED_BY_CURATED_ANNOTATION
  evidence:
  - >-
    UniProtKB P0A9T0: AltName 2-oxoglutarate reductase, EC 1.1.1.399, ECO:0000269 PubMed:8550422;
    catalytic activity (R)-2-hydroxyglutarate + NAD(+) = 2-oxoglutarate + NADH.
  - >-
    UniProtKB P0A9T0: DR GO; GO:0047545; F:(S)-2-hydroxyglutarate dehydrogenase activity; IDA:EcoCyc.
  - >-
    PMID:8550422, title: A novel alpha-ketoglutarate reductase activity of the serA-encoded 3-phosphoglycerate
    dehydrogenase of Escherichia coli K-12 and its possible implications for human 2-hydroxyglutaric
    aciduria.
- date: '2026-11-10'
  withdrawn_claim: >-
    Containment 1.0 with Jaccard similarity 0.063 between the condition and the GO term indicates
    concentrated false positives.
  correction: >-
    Containment 1.0 means every reviewed protein with the condition already carries the term, which
    is the opposite of a false positive. A low Jaccard value only says that many other proteins carry
    the term too.
  error_type: LOW_RECALL_IS_NOT_WRONG
  evidence:
  - >-
    UniProtKB release 2026_04: 13 reviewed entries carry FunFam 3.40.50.720:FF:000041; the old file's
    own table recorded 13 of 13 with GO:0047545.
- date: '2026-11-10'
  withdrawn_claim: Quantitative overlap figures were cited from a file ARBA00090718-analysis.txt.
  correction: >-
    That file is not in the rule folder, so the figures cannot be checked and are no longer cited.
  error_type: UNSUPPORTED_SOURCE
  evidence:
  - >-
    rules/arba/ARBA00090718/ contains only the review, its HTML rendering and a deep-research note.
references:
- id: PMID:16005139
  title: >-
    The gene mutated in l-2-hydroxyglutaric aciduria encodes l-2-hydroxyglutarate dehydrogenase
  findings:
  - statement: Reference for the IDA annotation of GO:0047545 on human L2HGDH (Q9H9P8).