View original ARBA rule on UniProt
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.
Condition-set counts describe the sets recorded in this review, which may omit the full rule.
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.
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.
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.
Plant-specific peroxisomal proteins combining InterPro and PANTHER classifications. Plants have unique peroxisomal functions including glyoxylate cycle enzymes not found in animals.
Fungal-specific peroxisomal protein domain with taxonomic restriction. Fungi have specialized peroxisomal functions for fatty acid beta-oxidation.
Eukaryotic CATH FunFam for peroxisomal organization proteins.
Animal-specific peroxisomal organization proteins.
Additional fungal-specific CATH FunFam for peroxisome organization.
Plant-specific CATH FunFam for peroxisome organization proteins.
Dikarya-specific (higher fungi) peroxisomal organization proteins.
Ascomycota-specific peroxisomal organization proteins.
Universal CATH FunFam for peroxisome organization without taxonomic restriction, suggesting a highly conserved peroxisomal function.
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.
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.
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.
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).
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.
Rule targets peroxisome organization through multiple condition sets but suffers from domain specificity issues and overly broad taxonomic scope
Many InterPro domains lack detailed functional annotation, increasing risk of false positives from proteins with other primary functions
Rule lacks negative conditions to exclude mitochondrial or ER proteins that might share similar domains
A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a peroxisome
Very broad term encompassing multiple distinct processes that would benefit from more specific child term usage
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