id: ARBA00026708 description: Rule predicting peroxisome organization (GO:0007031) based on multiple InterPro domains and CATH FunFam classifications across different taxonomic groups. The rule uses 10 condition sets targeting various peroxisomal proteins including peroxins and peroxisome division factors. status: COMPLETE rule_type: ARBA rule: rule_id: ARBA00026708 condition_sets: - number: 1 conditions: - condition_type: INTERPRO value: IPR006845 curie: InterPro:IPR006845 label: Unknown function (peroxisomal) negated: false - condition_type: INTERPRO value: IPR013083 curie: InterPro:IPR013083 label: Unknown function (peroxisomal) negated: false - condition_type: INTERPRO value: IPR017375 curie: InterPro:IPR017375 label: Unknown function (peroxisomal) negated: false notes: Multi-domain condition set without taxonomic restriction. The combination of three InterPro domains suggests a complex peroxisomal protein requiring multiple functional domains for proper peroxisome organization. - number: 2 conditions: - condition_type: INTERPRO value: IPR008733 curie: InterPro:IPR008733 label: Unknown function (plant peroxisomal) negated: false - condition_type: PANTHER value: PTHR12652 curie: PANTHER:PTHR12652 label: Peroxisomal protein (plant) negated: false - condition_type: TAXON value: '33090' curie: NCBITaxon:33090 label: Viridiplantae negated: false notes: Plant-specific peroxisomal proteins combining InterPro and PANTHER classifications. Plants have unique peroxisomal functions including glyoxylate cycle enzymes not found in animals. - number: 3 conditions: - condition_type: INTERPRO value: IPR010482 curie: InterPro:IPR010482 label: Unknown function (fungal peroxisomal) negated: false - condition_type: TAXON value: '4751' curie: NCBITaxon:4751 label: Fungi negated: false notes: Fungal-specific peroxisomal protein domain with taxonomic restriction. Fungi have specialized peroxisomal functions for fatty acid beta-oxidation. - number: 4 conditions: - condition_type: FUNFAM value: 2.130.10.10:FF:000372 curie: CATH.FunFam:2.130.10.10:FF:000372 label: Peroxisomal protein family negated: false - condition_type: TAXON value: '2759' curie: NCBITaxon:2759 label: Eukaryota negated: false notes: Eukaryotic CATH FunFam for peroxisomal organization proteins. - number: 5 conditions: - condition_type: FUNFAM value: 3.30.40.10:FF:000266 curie: CATH.FunFam:3.30.40.10:FF:000266 label: Peroxisomal protein family (metazoan) negated: false - condition_type: TAXON value: '33208' curie: NCBITaxon:33208 label: Metazoa negated: false notes: Animal-specific peroxisomal organization proteins. - number: 6 conditions: - condition_type: FUNFAM value: 1.10.510.10:FF:000397 curie: CATH.FunFam:1.10.510.10:FF:000397 label: Peroxisomal protein family (fungal) negated: false - condition_type: TAXON value: '4751' curie: NCBITaxon:4751 label: Fungi negated: false notes: Additional fungal-specific CATH FunFam for peroxisome organization. - number: 7 conditions: - condition_type: FUNFAM value: 1.25.40.10:FF:000167 curie: CATH.FunFam:1.25.40.10:FF:000167 label: Peroxisomal protein family (plant) negated: false - condition_type: TAXON value: '33090' curie: NCBITaxon:33090 label: Viridiplantae negated: false notes: Plant-specific CATH FunFam for peroxisome organization proteins. - number: 8 conditions: - condition_type: FUNFAM value: 1.25.40.10:FF:000218 curie: CATH.FunFam:1.25.40.10:FF:000218 label: Peroxisomal protein family (Dikarya) negated: false - condition_type: TAXON value: '451864' curie: NCBITaxon:451864 label: Dikarya negated: false notes: Dikarya-specific (higher fungi) peroxisomal organization proteins. - number: 9 conditions: - condition_type: FUNFAM value: 3.40.50.300:FF:000473 curie: CATH.FunFam:3.40.50.300:FF:000473 label: Peroxisomal protein family (Ascomycota) negated: false - condition_type: TAXON value: '4890' curie: NCBITaxon:4890 label: Ascomycota negated: false notes: Ascomycota-specific peroxisomal organization proteins. - number: 10 conditions: - condition_type: FUNFAM value: 1.20.120.1240:FF:000002 curie: CATH.FunFam:1.20.120.1240:FF:000002 label: Universal peroxisomal protein family negated: false notes: Universal CATH FunFam for peroxisome organization without taxonomic restriction, suggesting a highly conserved peroxisomal function. go_annotations: - go_id: GO:0007031 go_label: peroxisome organization aspect: BP reviewed_protein_count: 0 unreviewed_protein_count: 0 created_date: '2021-10-20' modified_date: '2025-09-20' entries: - id: IPR006845 type: INTERPRO label: Unknown function (peroxisomal) appears_in_condition_sets: - 1 protein_count: 0 related_entries: [] - id: IPR013083 type: INTERPRO label: Unknown function (peroxisomal) appears_in_condition_sets: - 1 protein_count: 0 related_entries: [] - id: IPR017375 type: INTERPRO label: Unknown function (peroxisomal) appears_in_condition_sets: - 1 protein_count: 0 related_entries: [] - id: IPR008733 type: INTERPRO label: Unknown function (plant peroxisomal) appears_in_condition_sets: - 2 protein_count: 0 related_entries: [] - id: PTHR12652 type: PANTHER label: Peroxisomal protein (plant) appears_in_condition_sets: - 2 protein_count: 0 related_entries: [] - id: IPR010482 type: INTERPRO label: Unknown function (fungal peroxisomal) appears_in_condition_sets: - 3 protein_count: 0 related_entries: [] - id: 2.130.10.10:FF:000372 type: FUNFAM label: Peroxisomal protein family appears_in_condition_sets: - 4 protein_count: 0 related_entries: [] - id: 3.30.40.10:FF:000266 type: FUNFAM label: Peroxisomal protein family (metazoan) appears_in_condition_sets: - 5 protein_count: 0 related_entries: [] - id: 1.10.510.10:FF:000397 type: FUNFAM label: Peroxisomal protein family (fungal) appears_in_condition_sets: - 6 protein_count: 0 related_entries: [] - id: 1.25.40.10:FF:000167 type: FUNFAM label: Peroxisomal protein family (plant) appears_in_condition_sets: - 7 protein_count: 0 related_entries: [] - id: 1.25.40.10:FF:000218 type: FUNFAM label: Peroxisomal protein family (Dikarya) appears_in_condition_sets: - 8 protein_count: 0 related_entries: [] - id: 3.40.50.300:FF:000473 type: FUNFAM label: Peroxisomal protein family (Ascomycota) appears_in_condition_sets: - 9 protein_count: 0 related_entries: [] - id: 1.20.120.1240:FF:000002 type: FUNFAM label: Universal peroxisomal protein family appears_in_condition_sets: - 10 protein_count: 0 related_entries: [] review_summary: ARBA00026708 presents significant concerns regarding annotation accuracy and rule design. The rule uses 10 condition sets to predict GO:0007031 (peroxisome organization) but suffers from multiple issues. First, many InterPro domains lack specific functional annotation, increasing false positive risk. Second, the broad taxonomic scope may lead to over-annotation of organisms with reduced or absent peroxisomes. Third, the rule lacks negative conditions to exclude proteins from other organellar systems (mitochondria, ER) that may share similar domains. Fourth, GO:0007031 is a very broad organizational term that may capture proteins with indirect roles rather than direct peroxisome organization functions. The rule would benefit from more specific GO terms and additional constraints to reduce false positives. action: MODIFY action_rationale: While peroxisome organization is a legitimate biological process and the rule attempts to capture genuine peroxisomal proteins, the current design has significant specificity issues. Many condition sets use poorly annotated InterPro domains, and the broad GO term increases risk of over-annotation. The rule should be refined with (1) more specific GO terms for distinct aspects of peroxisome organization (e.g., GO:0016559 peroxisome fission, GO:0016558 peroxisome fusion), (2) negative conditions to exclude mitochondrial/ER proteins, (3) validation that annotated organisms actually possess peroxisomes, and (4) replacement of poorly annotated InterPro domains with more specific alternatives. suggested_modifications: - Replace broad GO:0007031 with more specific child terms based on protein function - Add negative conditions to exclude non-peroxisomal organellar proteins - Validate taxonomic scope to exclude organisms lacking peroxisomes - Replace poorly annotated InterPro domains with better characterized alternatives - Consider splitting into separate rules for different aspects of peroxisome organization - Add literature-validated positive examples to guide refinement parsimony: assessment: OVERLY_COMPLEX notes: The rule contains 10 condition sets targeting the same broad biological process. While kingdom-specific peroxisome differences exist, many condition sets likely identify the same core peroxisomal proteins through different domain classification systems. The rule would benefit from consolidation and validation of unique coverage provided by each condition set. supported_by: - reference_id: file:rules/arba/ARBA00026708/ARBA00026708-deep-research-manual.md supporting_text: The rule covers All eukaryotes (some condition sets), Viridiplantae (plants), Fungi and subgroups (Dikarya, Ascomycota), Metazoa (animals). Potential Issues include Over-broad annotation peroxisome organization mechanisms may differ significantly between kingdoms, Domain promiscuity Some domains might appear in non-peroxisomal contexts, Missing specificity Lack of negative conditions to exclude false positives literature_support: assessment: MODERATE notes: Peroxisome organization is a well-established biological process with strong literature support. However, the specific domains and proteins targeted by this rule lack detailed functional characterization in many cases. Known peroxins (PEX proteins) and peroxisome division factors are well-studied, but the InterPro domains in this rule often have unclear functional annotations. supported_by: - reference_id: file:rules/arba/ARBA00026708/ARBA00026708-deep-research-manual.md supporting_text: The major players in peroxisome biogenesis include PEX1, PEX6 AAA+ ATPases involved in peroxisome matrix protein import, PEX3, PEX16, PEX19 Membrane protein insertion machinery, PEX5, PEX7 Peroxisome targeting signal (PTS) receptors, PEX11 Peroxisome division protein, PEX13, PEX14 Docking complex components condition_overlap: assessment: SIGNIFICANT notes: Without quantitative analysis, it's likely that many condition sets identify overlapping protein sets through different classification systems (InterPro vs CATH FunFam). The taxonomic restrictions may provide some separation, but core peroxisomal proteins are often conserved across kingdoms and could be captured by multiple condition sets. supported_by: - reference_id: file:rules/arba/ARBA00026708/ARBA00026708-deep-research-manual.md supporting_text: Basic peroxisome machinery is conserved across eukaryotes, Kingdom-specific adaptations exist, particularly in plants vs animals vs fungi, Some organisms (certain parasites) have lost peroxisomes entirely go_specificity: assessment: TOO_BROAD notes: GO:0007031 (peroxisome organization) is a very broad term that encompasses multiple distinct processes including peroxisome biogenesis, fission, fusion, inheritance, and degradation. More specific child terms would be more appropriate for different classes of peroxisomal proteins (e.g., GO:0016559 for fission proteins, GO:0016560 for protein import). supported_by: - reference_id: file:rules/arba/ARBA00026708/ARBA00026708-deep-research-manual.md supporting_text: Peroxisome organization is a highly conserved process involving (1) Membrane biogenesis Formation of peroxisomal membranes, (2) Matrix protein import PTS1 and PTS2 pathway proteins, (3) Division/proliferation Peroxisome fission machinery, (4) Quality control Protein degradation and organelle maintenance taxonomic_scope: assessment: TOO_BROAD notes: The rule covers very broad taxonomic ranges including all eukaryotes for some condition sets. This risks annotating organisms that have lost peroxisomes (certain parasites, some anaerobic organisms) or have highly reduced peroxisomal systems. Taxonomic restrictions should be validated against known peroxisome distribution. supported_by: - reference_id: file:rules/arba/ARBA00026708/ARBA00026708-deep-research-manual.md supporting_text: Very broad taxonomic scope may lead to over-annotation, Different mechanisms of peroxisome organization across kingdoms, Risk of annotating organisms that lack peroxisomes confidence: 0.45 references: - id: file:rules/arba/ARBA00026708/ARBA00026708-deep-research-manual.md title: Manual deep research analysis of ARBA00026708 findings: - statement: Rule targets peroxisome organization through multiple condition sets but suffers from domain specificity issues and overly broad taxonomic scope - statement: Many InterPro domains lack detailed functional annotation, increasing risk of false positives from proteins with other primary functions - statement: Rule lacks negative conditions to exclude mitochondrial or ER proteins that might share similar domains - id: GO:0007031 title: peroxisome organization GO term definition findings: - statement: A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a peroxisome - statement: Very broad term encompassing multiple distinct processes that would benefit from more specific child term usage supported_by: - reference_id: file:rules/arba/ARBA00026708/ARBA00026708-deep-research-manual.md supporting_text: This rule annotates proteins with GO:0007031 (peroxisome organization) based on multiple condition sets targeting different taxonomic groups