id: ARBA00092121
description: 'Annotates fungal proteins in CATH FunFam 3.10.20.30:FF:000003 (Developmentally-regulated GTP-binding protein 1) with GO:1903833 (positive regulation of cellular response to amino acid starvation). Currently covers 0 proteins.'
status: COMPLETE
rule_type: ARBA
rule:
  rule_id: ARBA00092121
  condition_sets:
  - number: 1
    conditions:
    - condition_type: FUNFAM
      value: 3.10.20.30:FF:000003
      curie: CATH.FunFam:3.10.20.30:FF:000003
      label: Developmentally-regulated GTP-binding protein 1
      negated: false
    - condition_type: TAXON
      value: Fungi
      curie: NCBITaxon:4751
      label: Fungi
      negated: false
    notes: ''
  go_annotations: []
  reviewed_protein_count: 0
  unreviewed_protein_count: 0
  created_date: ''
  modified_date: ''
  entries:
  - id: 3.10.20.30:FF:000003
    type: FUNFAM
    label: Developmentally-regulated GTP-binding protein 1
    appears_in_condition_sets:
    - 1
review_summary: 'ARBA00092121 represents a problematic annotation rule that lacks biological foundation. The rule attempts to connect developmentally-regulated GTP-binding proteins in fungi with positive regulation of amino acid starvation response, but this functional relationship has no support in the literature. GTP-binding proteins involved in development typically regulate morphogenesis, cell division, and vesicle trafficking, while amino acid starvation responses in fungi are mediated by well-characterized pathways involving GCN2 kinase and GCN4 transcriptional activator. The zero protein coverage indicates the rule specification is incorrect. The recent creation date (March 2025) suggests this may be an experimental annotation that should not be deployed.'
action: DEPRECATE
action_rationale: 'This rule should be removed due to: (1) Zero protein coverage indicating incorrect specification, (2) No biological basis for connecting developmentally-regulated GTP-binding proteins to amino acid starvation response regulation, (3) No literature support for this functional relationship, (4) Recent creation date suggesting experimental/problematic status.'
suggested_modifications: []
parsimony:
  assessment: ACCEPTABLE
  notes: 'Single domain condition with taxonomic restriction is appropriately simple, though the rule targets zero proteins indicating specification problems.'
literature_support:
  assessment: NONE
  notes: 'No literature evidence supports a connection between developmentally-regulated GTP-binding proteins and positive regulation of amino acid starvation response. Established amino acid starvation pathways involve different molecular mechanisms.'
  supported_by:
  - reference_id: file:rules/arba/ARBA00092121/ARBA00092121-manual-research.md
    supporting_text: 'No literature support for developmental GTPases regulating amino acid starvation. Fungal amino acid starvation primarily involves GCN2 kinase and GCN4 transcriptional activator.'
condition_overlap:
  assessment: NONE
  notes: 'Single domain condition in rule - no overlap analysis possible. Analysis shows rule targets zero proteins.'
  supported_by: []
go_specificity:
  assessment: MISMATCHED
  notes: 'GO:1903833 (positive regulation of cellular response to amino acid starvation) is not biologically appropriate for developmentally-regulated GTP-binding proteins. The term specificity is fine but mismatched to the protein function.'
  supported_by: []
taxonomic_scope:
  assessment: APPROPRIATE
  notes: 'Fungi-specific restriction is reasonable if the functional relationship were valid, but the underlying annotation is biologically incorrect.'
  supported_by: []
confidence: 0.95
references:
- id: file:rules/arba/ARBA00092121/ARBA00092121-manual-research.md
  title: Manual biological analysis
  findings:
  - statement: 'No biological basis for connecting developmental GTPases to amino acid starvation response'
  - statement: 'Rule targets zero proteins indicating specification problems'
  - statement: 'Amino acid starvation in fungi involves GCN2/GCN4 pathway, not GTPases'
  - statement: 'Recent creation date suggests experimental/problematic status'
supported_by:
- reference_id: file:rules/arba/ARBA00092121/ARBA00092121-manual-research.md
  supporting_text: 'Major concerns about this rule: Functional mismatch - No clear mechanistic connection between developmentally-regulated GTP-binding protein and positive regulation of cellular response to amino acid starvation'