ARBA00001096

View original ARBA rule on UniProt

Type: ARBA
Status: COMPLETE
Action: MODIFY
Confidence: 0.80

Description

Predicts glucose-6-phosphate 1-epimerase activity (EC 5.1.3.15) based on the presence of three hierarchical InterPro domains using restrictive AND logic

Analysis Summary

Condition-set counts describe the sets recorded in this review, which may omit the full rule.

3
Domain Pairs Analyzed
1
Recorded condition sets
3
Subset Relationships
0
Redundant Annotations

Domain Overlap Analysis Table

Interactive prediction matrix showing how row entries PREDICT column entries. Cell (i,j) shows what fraction of proteins with row domain i also have column domain j. Click cells to view intersection in UniProt. Click domain IDs to view proteins with that domain.

CS 1
Aldose 1-/Glucose-6-phosp...
IPR008183 [F]
(31) 		Galactose mutarotase-like...
IPR011013 [SF]
(397) 		Glucose-6-phosphate 1-epi...
IPR025532 [F]
(5)
CS 1 Aldose 1-/Glucose-6-phosphate 1-epimerase
IPR008183 [F] (31) 		100%
100%
J:8%
(31)
16%
J:16%
(5)
Galactose mutarotase-like domain superfamily
IPR011013 [SF] (397)
8%
J:8%
(31) 		100%
1%
J:1%
(5)
Glucose-6-phosphate 1-epimerase
IPR025532 [F] (5)
100%
J:16%
(5)
100%
J:1%
(5) 		100%

Legend: Each cell shows PREDICTS % (fraction of row entry proteins that also have column entry - row PREDICTS column), Jaccard similarity (J:%), and intersection count. CS = Condition Set(s), TGT = GO annotation target.

Review Summary

This rule suffers from overly restrictive domain logic that creates unnecessary complexity and likely false negatives. The three required domains show complete subset relationships (IPR025532 ⊆ IPR008183 ⊆ IPR011013), making the AND logic redundant. The rule effectively annotates only 5 proteins when broader coverage might be appropriate for this important metabolic enzyme. The hierarchical domain redundancy violates parsimony principles and should be simplified.

Action Rationale

The rule contains hierarchical domain redundancy that makes the AND logic unnecessarily restrictive. With IPR025532 being a complete subset of both other domains, the rule effectively reduces to requiring only IPR025532, making the other conditions redundant. This overly complex design likely creates false negatives by missing legitimate glucose-6-phosphate 1-epimerases that have broader family signatures but lack the most specific domain. Simplification would improve both parsimony and sensitivity.

Rule Definition

Condition Sets

Condition Set 1

3 condition(s)

Pairwise Overlap Analysis

Condition A Condition B Count A Count B Intersection Jaccard A in B B in A Interpretation
IPR008183 IPR011013 31 397 31 0.078 1.000 0.078 SUBSET
IPR008183 IPR025532 31 5 5 0.161 0.161 1.000 SUBSET
IPR011013 IPR025532 397 5 5 0.013 0.013 1.000 SUBSET

Assessments

REDUNDANT

The rule violates parsimony due to complete subset relationships between domains. IPR025532 is entirely contained within IPR008183, which is entirely contained within IPR011013. The AND logic creates redundancy as the rule effectively reduces to requiring only the smallest domain (IPR025532), making the other conditions unnecessary.

MODERATE

Glucose-6-phosphate 1-epimerase is a well-characterized enzyme with established biological function in carbohydrate metabolism. The enzyme catalyzes the interconversion of anomeric forms of glucose-6-phosphate, which is important for proper glucose utilization. However, the specific domain architecture requirements of this rule may not reflect the full diversity of this enzyme family across different organisms.

Supporting Evidence:

  • file:rules/arba/ARBA00001096/ARBA00001096-deep-research-manual.md: Glucose-6-phosphate 1-epimerase is an important enzyme in carbohydrate metabolism: Essential for equilibrating anomeric forms of glucose-6-phosphate, Required for proper glucose utilization in many organisms, Part of the broader galactose mutarotase-like enzyme family, Conserved across many taxa but with structural variations
COMPLETE

All three domains show complete subset relationships within the single condition set. IPR025532 has 100% containment in both IPR008183 and IPR011013, while IPR008183 has 100% containment in IPR011013. This creates a hierarchical structure where all proteins are nested subsets, making the AND logic redundant.

APPROPRIATE

The rule correctly identifies the specific catalytic activity (EC 5.1.3.15) for glucose-6-phosphate 1-epimerase. This is an appropriately specific molecular function annotation that accurately reflects the enzymatic activity. The enzyme annotation is neither too broad nor too narrow for the biological function.

APPROPRIATE

No explicit taxonomic restrictions are present in the rule, which is appropriate for glucose-6-phosphate 1-epimerase as this enzyme is conserved across diverse organisms that utilize glucose. The enzyme is part of fundamental carbohydrate metabolism and should be broadly applicable across taxa.

References (2)

Raw YAML

View Source YAML 
id: ARBA00001096
description: 'Predicts glucose-6-phosphate 1-epimerase activity (EC 5.1.3.15) based on the presence of three hierarchical InterPro domains using restrictive AND logic'
status: COMPLETE
rule_type: ARBA
rule:
  rule_id: ARBA00001096
  condition_sets:
  - number: 1
    conditions:
    - condition_type: INTERPRO
      value: IPR008183
      curie: InterPro:IPR008183
      label: Aldose 1-/Glucose-6-phosphate 1-epimerase
      negated: false
    - condition_type: INTERPRO
      value: IPR011013
      curie: InterPro:IPR011013
      label: Galactose mutarotase-like domain superfamily
      negated: false
    - condition_type: INTERPRO
      value: IPR025532
      curie: InterPro:IPR025532
      label: Glucose-6-phosphate 1-epimerase
      negated: false
    notes: ''
    pairwise_overlap:
    - condition_a: IPR008183
      condition_b: IPR011013
      protein_database: SWISSPROT
      count_a: 31
      count_b: 397
      intersection_count: 31
      a_minus_b_count: 0
      b_minus_a_count: 366
      jaccard_similarity: 0.07808564231738035
      containment_a_in_b: 1.0
      containment_b_in_a: 0.07808564231738035
      interpretation: SUBSET
    - condition_a: IPR008183
      condition_b: IPR025532
      protein_database: SWISSPROT
      count_a: 31
      count_b: 5
      intersection_count: 5
      a_minus_b_count: 26
      b_minus_a_count: 0
      jaccard_similarity: 0.16129032258064516
      containment_a_in_b: 0.16129032258064516
      containment_b_in_a: 1.0
      interpretation: SUBSET
    - condition_a: IPR011013
      condition_b: IPR025532
      protein_database: SWISSPROT
      count_a: 397
      count_b: 5
      intersection_count: 5
      a_minus_b_count: 392
      b_minus_a_count: 0
      jaccard_similarity: 0.012594458438287154
      containment_a_in_b: 0.012594458438287154
      containment_b_in_a: 1.0
      interpretation: SUBSET
  go_annotations: []
  reviewed_protein_count: 0
  unreviewed_protein_count: 0
  created_date: ''
  modified_date: ''
  entries:
  - id: IPR008183
    type: INTERPRO
    label: Aldose 1-/Glucose-6-phosphate 1-epimerase
    appears_in_condition_sets:
    - 1
    protein_count: 31
    related_entries:
    - relationship: PREDICTS
      target_id: IPR011013
      containment: 1.0
      jaccard_similarity: 0.078
      intersection_count: 31
      exclusive_count: 0
    - relationship: PREDICTED_BY
      target_id: IPR025532
      containment: 1.0
      jaccard_similarity: 0.161
      intersection_count: 5
      exclusive_count: 0
  - id: IPR011013
    type: INTERPRO
    label: Galactose mutarotase-like domain superfamily
    appears_in_condition_sets:
    - 1
    protein_count: 397
    related_entries:
    - relationship: PREDICTED_BY
      target_id: IPR008183
      containment: 0.078
      jaccard_similarity: 0.078
      intersection_count: 31
      exclusive_count: 366
    - relationship: PREDICTED_BY
      target_id: IPR025532
      containment: 1.0
      jaccard_similarity: 0.013
      intersection_count: 5
      exclusive_count: 0
  - id: IPR025532
    type: INTERPRO
    label: Glucose-6-phosphate 1-epimerase
    appears_in_condition_sets:
    - 1
    protein_count: 5
    related_entries:
    - relationship: PREDICTS
      target_id: IPR008183
      containment: 0.161
      jaccard_similarity: 0.161
      intersection_count: 5
      exclusive_count: 26
    - relationship: PREDICTS
      target_id: IPR011013
      containment: 0.013
      jaccard_similarity: 0.013
      intersection_count: 5
      exclusive_count: 392
review_summary: 'This rule suffers from overly restrictive domain logic that creates unnecessary complexity and likely false negatives. The three required domains show complete subset relationships (IPR025532 ⊆ IPR008183 ⊆ IPR011013), making the AND logic redundant. The rule effectively annotates only 5 proteins when broader coverage might be appropriate for this important metabolic enzyme. The hierarchical domain redundancy violates parsimony principles and should be simplified.'
action: MODIFY
action_rationale: 'The rule contains hierarchical domain redundancy that makes the AND logic unnecessarily restrictive. With IPR025532 being a complete subset of both other domains, the rule effectively reduces to requiring only IPR025532, making the other conditions redundant. This overly complex design likely creates false negatives by missing legitimate glucose-6-phosphate 1-epimerases that have broader family signatures but lack the most specific domain. Simplification would improve both parsimony and sensitivity.'
suggested_modifications:
- 'Simplify to single condition using only IPR025532 (Glucose-6-phosphate 1-epimerase) as it contains the most specific annotation signal'
- 'Alternatively, use OR logic across the domains to capture broader family members while maintaining specificity'
- 'Validate that simplified rule maintains annotation accuracy while improving coverage'
parsimony:
  assessment: REDUNDANT
  notes: 'The rule violates parsimony due to complete subset relationships between domains. IPR025532 is entirely contained within IPR008183, which is entirely contained within IPR011013. The AND logic creates redundancy as the rule effectively reduces to requiring only the smallest domain (IPR025532), making the other conditions unnecessary.'
literature_support:
  assessment: MODERATE
  notes: 'Glucose-6-phosphate 1-epimerase is a well-characterized enzyme with established biological function in carbohydrate metabolism. The enzyme catalyzes the interconversion of anomeric forms of glucose-6-phosphate, which is important for proper glucose utilization. However, the specific domain architecture requirements of this rule may not reflect the full diversity of this enzyme family across different organisms.'
  supported_by:
  - reference_id: file:rules/arba/ARBA00001096/ARBA00001096-deep-research-manual.md
    supporting_text: 'Glucose-6-phosphate 1-epimerase is an important enzyme in carbohydrate metabolism: Essential for equilibrating anomeric forms of glucose-6-phosphate, Required for proper glucose utilization in many organisms, Part of the broader galactose mutarotase-like enzyme family, Conserved across many taxa but with structural variations'
condition_overlap:
  assessment: COMPLETE
  notes: 'All three domains show complete subset relationships within the single condition set. IPR025532 has 100% containment in both IPR008183 and IPR011013, while IPR008183 has 100% containment in IPR011013. This creates a hierarchical structure where all proteins are nested subsets, making the AND logic redundant.'
  supported_by:
  - reference_id: file:rules/arba/ARBA00001096/ARBA00001096-analysis.yaml
    supporting_text: 'containment_a_in_b: 1.0, containment_b_in_a: 1.0, interpretation: SUBSET'
go_specificity:
  assessment: APPROPRIATE
  notes: 'The rule correctly identifies the specific catalytic activity (EC 5.1.3.15) for glucose-6-phosphate 1-epimerase. This is an appropriately specific molecular function annotation that accurately reflects the enzymatic activity. The enzyme annotation is neither too broad nor too narrow for the biological function.'
  supported_by:
  - reference_id: file:rules/arba/ARBA00001096/ARBA00001096.enriched.json
    supporting_text: 'alpha-D-glucose 6-phosphate = beta-D-glucose 6-phosphate, ecNumber: 5.1.3.15'
taxonomic_scope:
  assessment: APPROPRIATE
  notes: 'No explicit taxonomic restrictions are present in the rule, which is appropriate for glucose-6-phosphate 1-epimerase as this enzyme is conserved across diverse organisms that utilize glucose. The enzyme is part of fundamental carbohydrate metabolism and should be broadly applicable across taxa.'
  supported_by:
  - reference_id: file:rules/arba/ARBA00001096/ARBA00001096-deep-research-manual.md
    supporting_text: 'Conserved across many taxa but with structural variations'
confidence: 0.8
references:
- id: file:rules/arba/ARBA00001096/ARBA00001096-deep-research-manual.md
  title: Deep research analysis - Manual curation
  findings:
  - statement: 'Glucose-6-phosphate 1-epimerase catalyzes interconversion of anomeric forms of glucose-6-phosphate, essential for glucose metabolism'
  - statement: 'Rule contains hierarchical domain redundancy with complete subset relationships between IPR025532, IPR008183, and IPR011013'
  - statement: 'AND logic is overly restrictive and may cause false negatives by missing legitimate enzyme variants'
- id: file:rules/arba/ARBA00001096/ARBA00001096-analysis.yaml
  title: Domain overlap quantitative analysis
  findings:
  - statement: 'Three subset relationships identified with 100% containment patterns indicating hierarchical domain structure'
  - statement: 'Average Jaccard similarity of 0.084 suggests minimal unique coverage from multiple domains'
supported_by:
- reference_id: file:rules/arba/ARBA00001096/ARBA00001096-deep-research-manual.md
  supporting_text: 'The rule uses AND logic requiring all three domains simultaneously. Given the subset relationships: Only proteins with ALL THREE domains will be annotated, This likely reduces to just the 5 proteins in IPR025532, The broader domains add no additional coverage'
- reference_id: file:rules/arba/ARBA00001096/ARBA00001096-analysis.yaml
  supporting_text: 'Analyzed 3 domain-domain pairs and 0 domain-GO pairs across entire rule. Average Jaccard similarity: 0.084. 0 pairs with >50% overlap, 3 subset relationships.'