id: ARBA00043370
description: 'Rule assigns GO:0140115 "export across plasma membrane" to proteins matching 12 complex condition sets covering diverse transporter families including sugar transporters, ABC transporters, MFS transporters, P-type ATPases, and antiporters across various taxonomic groups'
status: COMPLETE
rule_type: ARBA
rule:
  rule_id: ARBA00043370
  entries: []
  condition_sets: []
  go_annotations:
    - go_id: GO:0140115
      go_label: export across plasma membrane
  reviewed_protein_count: 0
  unreviewed_protein_count: 0
  created_date: '2023-10-01'
  modified_date: '2025-03-21'
review_summary: 'CRITICAL ISSUE: Rule exhibits severe over-annotation by assigning overly specific directional and locational assumptions to diverse transporter families. GO curators have flagged this rule (issue #6140) because they "don''t know (and can''t infer) the location, substrate or direction" of covered transporters. The 12 condition sets cover functionally diverse transporters that may import, export, or work bidirectionally across various cellular membranes.'
action: DEPRECATE
action_rationale: 'This rule should be deprecated due to systematic over-annotation. The assignment of "export across plasma membrane" makes unjustified assumptions about (1) subcellular localization (plasma membrane), (2) transport direction (export vs import), and (3) functional specificity across diverse transporter families. Many covered transporters (MFS, ABC, P-type ATPases) are known to function bidirectionally and localize to various cellular membranes. The rule lacks biological coherence and creates false-positive annotations.'
suggested_modifications:
- 'Replace with more general transport-related GO terms that do not assume direction or specific membrane localization'
- 'Consider separate rules for well-characterized transporter subfamilies with appropriate evidence'
parsimony:
  assessment: OVERLY_COMPLEX
  notes: 'Rule contains 12 complex condition sets with different taxonomic restrictions, indicating lack of biological coherence. The diverse structural criteria (sugar transporters, ABC transporters, MFS, P-type ATPases, antiporters) suggest this rule inappropriately aggregates functionally distinct transporter families.'
literature_support:
  assessment: CONTRADICTED
  notes: 'No direct literature evidence supports the blanket assignment of "export across plasma membrane" to such diverse transporter families. GO curators explicitly state they cannot infer location, substrate, or direction for these transporters.'
  supported_by:
  - reference_id: file:rules/arba/ARBA00043370/ARBA00043370-deep-research-manual.md
    supporting_text: 'GO curators report inability to infer location, substrate or direction of covered transporters (GitHub issue #6140)'
condition_overlap:
  assessment: SIGNIFICANT
  notes: 'The 12 condition sets show concerning diversity, mixing sugar transporters, ABC transporters, MFS transporters, P-type ATPases, and antiporters across different taxonomic groups. This heterogeneity suggests the rule lacks focused biological rationale.'
  supported_by:
  - reference_id: file:rules/arba/ARBA00043370/ARBA00043370.enriched.json
    supporting_text: 'Rule contains 12 heterogeneous condition sets covering diverse transporter families'
go_specificity:
  assessment: MISMATCHED
  notes: 'GO:0140115 "export across plasma membrane" is overly specific for the diverse transporters covered. The term assumes both membrane localization and transport direction that cannot be reliably inferred from the structural criteria used in the rule conditions.'
  supported_by:
  - reference_id: https://github.com/geneontology/go-annotation/issues/6140
    supporting_text: 'GO curators cannot infer location, substrate or direction of covered transporters'
taxonomic_scope:
  assessment: TOO_BROAD
  notes: 'Rule applies to highly diverse taxonomic groups (Bacteria, Fungi, Plants, Animals) with different condition sets for each, suggesting biological incoherence rather than evolutionarily conserved function.'
  supported_by:
  - reference_id: file:rules/arba/ARBA00043370/ARBA00043370.enriched.json
    supporting_text: 'Condition sets span Bacteria, Fungi, Viridiplantae, Embryophyta, Primates, and other diverse taxa'
confidence: 0.9
references:
- id: file:rules/arba/ARBA00043370/ARBA00043370-deep-research-manual.md
  title: Manual deep research analysis
  findings:
  - statement: 'GO curators report inability to infer location, substrate or direction for covered transporters'
  - statement: 'Rule covers diverse transporter families with known bidirectional and multi-localization properties'
  - statement: 'The 12 condition sets suggest biological incoherence rather than focused functional annotation'
- id: https://github.com/geneontology/go-annotation/issues/6140
  title: 'ARBA2GO issue: GO:0140115 | export across plasma membrane ARBA00043370'
  findings:
  - statement: 'GO curators state: "We don''t know (and can''t infer) the location, substrate or direction of these transporters"'
supported_by:
- reference_id: file:rules/arba/ARBA00043370/ARBA00043370-deep-research-manual.md
  supporting_text: 'Comprehensive analysis of rule structure and curator concerns'
- reference_id: https://github.com/geneontology/go-annotation/issues/6140
  supporting_text: 'Direct curator feedback on annotation issues'