View original ARBA rule on UniProt
Predicts GO:0045454 "cell redox homeostasis" for proteins across 9 condition sets covering diverse redox-related protein families including nitric oxide synthases, thioredoxins, glutathione reductases, peroxiredoxins, and other oxidative stress response proteins with taxonomic restrictions
Condition-set counts describe the sets recorded in this review, which may omit the full rule.
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.
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.
This rule demonstrates significant biological and curation concerns. While it correctly identifies several core redox homeostasis proteins (glutathione reductase, thioredoxins, peroxiredoxins), it suffers from: 1) Domain redundancy with identical protein sets across different FunFams, 2) Inclusion of proteins with questionable primary redox functions (KRIT1, Por1p), 3) Overly fragmented taxonomic scope suggesting annotation bias, and 4) Mechanistic incoherence mixing electron transfer enzymes, radical generators, and structural proteins. The rule would benefit from consolidation and removal of over-annotations.
The rule requires modification rather than removal because it contains legitimate redox homeostasis proteins (glutathione reductase, thioredoxins, peroxiredoxins) that warrant the GO:0045454 annotation. However, significant issues include: 1) Complete redundancy in condition set 3 (KRIT1 domains with Jaccard=1.0), 2) High overlap in condition set 1 (NOS domains with 70% overlap), 3) Questionable inclusion of KRIT1 (primarily developmental) and Por1p (primarily transport), and 4) Fragmented taxonomic scope. These issues can be addressed through consolidation and refinement while preserving the core biological validity.
These InterPro domains also map to the rule's GO term(s) via InterPro2GO but are not part of any condition set in this rule. They may represent alternative domain signatures that predict the same function.
| Condition A | Condition B | Count A | Count B | Intersection | Jaccard | A in B | B in A | Interpretation |
|---|---|---|---|---|---|---|---|---|
3.40.50.80:FF:000003
|
3.90.1230.10:FF:000001
|
26 | 20 | 19 | 0.704 | 0.731 | 0.950 | HIGH_OVERLAP |
| Condition A | Condition B | Count A | Count B | Intersection | Jaccard | A in B | B in A | Interpretation |
|---|---|---|---|---|---|---|---|---|
1.20.80.10:FF:000016
|
1.25.40.20:FF:000120
|
3 | 4 | 3 | 0.750 | 1.000 | 0.750 | SUBSET |
1.20.80.10:FF:000016
|
2.30.29.30:FF:000227
|
3 | 3 | 3 | 1.000 | 1.000 | 1.000 | REDUNDANT |
1.25.40.20:FF:000120
|
2.30.29.30:FF:000227
|
4 | 3 | 3 | 0.750 | 0.750 | 1.000 | SUBSET |
| Condition A | Condition B | Count A | Count B | Intersection | Jaccard | A in B | B in A | Interpretation |
|---|---|---|---|---|---|---|---|---|
3.30.390.30:FF:000003
|
3.50.50.60:FF:000141
|
18 | 3 | 3 | 0.167 | 0.167 | 1.000 | SUBSET |
Rule contains significant redundancy: condition set 3 has complete domain overlap (Jaccard=1.0), condition set 1 has high overlap (Jaccard=0.70), and condition set 4 shows subset relationship. With 9 condition sets, the rule is overly complex for the biological diversity it captures.
Mixed literature support - strong for core redox proteins (glutathione reductase, thioredoxins, peroxiredoxins) but weak for proteins with indirect roles (KRIT1, Por1p). The diverse mechanisms represented suggest this may be more of a functional grouping than a mechanistically coherent pathway.
Analysis reveals concerning overlap patterns: Set 3 contains completely redundant domains (Jaccard=1.0), Set 1 has high overlap (Jaccard=0.70), and Set 4 shows subset relationships. This indicates poor curation and unnecessary complexity.
GO:0045454 "cell redox homeostasis" is appropriately broad for the mechanistic diversity represented, though some proteins may warrant more specific terms (e.g., specific enzymatic activities for glutathione reductase, thioredoxin).
Highly fragmented taxonomic restrictions (Primates-only NOS, various fungal subgroups, plant subgroups) suggest annotation bias rather than genuine lineage-specific evolution. Redox homeostasis is fundamental across life domains and may warrant broader scope.
Core redox proteins (glutathione reductase, thioredoxins, peroxiredoxins) strongly support GO:0045454 annotation
KRIT1 and Por1p show questionable relevance - primarily developmental and transport functions respectively
Domain redundancy indicates poor curation, particularly complete overlap in condition set 3
Fragmented taxonomic scope suggests annotation bias rather than biological restriction
id: ARBA00085337
description: 'Predicts GO:0045454 "cell redox homeostasis" for proteins across 9 condition sets covering diverse redox-related protein families including nitric oxide synthases, thioredoxins, glutathione reductases, peroxiredoxins, and other oxidative stress response proteins with taxonomic restrictions'
status: COMPLETE
rule_type: ARBA
rule:
rule_id: ARBA00085337
condition_sets:
- number: 1
conditions:
- condition_type: FUNFAM
value: 3.40.50.80:FF:000003
curie: CATH.FunFam:3.40.50.80:FF:000003
label: Nitric oxide synthase
negated: false
- condition_type: FUNFAM
value: 3.90.1230.10:FF:000001
curie: CATH.FunFam:3.90.1230.10:FF:000001
label: Nitric oxide synthase, brain
negated: false
- condition_type: TAXON
value: Primates
curie: NCBITaxon:9443
label: Primates
negated: false
notes: ''
pairwise_overlap:
- condition_a: 3.40.50.80:FF:000003
condition_b: 3.90.1230.10:FF:000001
protein_database: SWISSPROT
count_a: 26
count_b: 20
intersection_count: 19
a_minus_b_count: 7
b_minus_a_count: 1
jaccard_similarity: 0.7037037037037037
containment_a_in_b: 0.7307692307692307
containment_b_in_a: 0.95
interpretation: HIGH_OVERLAP
- number: 2
conditions:
- condition_type: FUNFAM
value: 3.40.30.10:FF:000104
curie: CATH.FunFam:3.40.30.10:FF:000104
label: Thioredoxin
negated: false
- condition_type: TAXON
value: Fungi
curie: NCBITaxon:4751
label: Fungi
negated: false
notes: ''
- number: 3
conditions:
- condition_type: FUNFAM
value: 1.20.80.10:FF:000016
curie: CATH.FunFam:1.20.80.10:FF:000016
label: Krev interaction trapped protein 1
negated: false
- condition_type: FUNFAM
value: 1.25.40.20:FF:000120
curie: CATH.FunFam:1.25.40.20:FF:000120
label: krev interaction trapped protein 1 isoform X1
negated: false
- condition_type: FUNFAM
value: 2.30.29.30:FF:000227
curie: CATH.FunFam:2.30.29.30:FF:000227
label: krev interaction trapped protein 1 isoform X1
negated: false
notes: ''
pairwise_overlap:
- condition_a: 1.20.80.10:FF:000016
condition_b: 1.25.40.20:FF:000120
protein_database: SWISSPROT
count_a: 3
count_b: 4
intersection_count: 3
a_minus_b_count: 0
b_minus_a_count: 1
jaccard_similarity: 0.75
containment_a_in_b: 1.0
containment_b_in_a: 0.75
interpretation: SUBSET
- condition_a: 1.20.80.10:FF:000016
condition_b: 2.30.29.30:FF:000227
protein_database: SWISSPROT
count_a: 3
count_b: 3
intersection_count: 3
a_minus_b_count: 0
b_minus_a_count: 0
jaccard_similarity: 1.0
containment_a_in_b: 1.0
containment_b_in_a: 1.0
interpretation: REDUNDANT
- condition_a: 1.25.40.20:FF:000120
condition_b: 2.30.29.30:FF:000227
protein_database: SWISSPROT
count_a: 4
count_b: 3
intersection_count: 3
a_minus_b_count: 1
b_minus_a_count: 0
jaccard_similarity: 0.75
containment_a_in_b: 0.75
containment_b_in_a: 1.0
interpretation: SUBSET
- number: 4
conditions:
- condition_type: FUNFAM
value: 3.30.390.30:FF:000003
curie: CATH.FunFam:3.30.390.30:FF:000003
label: Glutathione reductase
negated: false
- condition_type: FUNFAM
value: 3.50.50.60:FF:000141
curie: CATH.FunFam:3.50.50.60:FF:000141
label: Glutathione reductase
negated: false
- condition_type: TAXON
value: Eukaryota
curie: NCBITaxon:2759
label: Eukaryota
negated: false
notes: ''
pairwise_overlap:
- condition_a: 3.30.390.30:FF:000003
condition_b: 3.50.50.60:FF:000141
protein_database: SWISSPROT
count_a: 18
count_b: 3
intersection_count: 3
a_minus_b_count: 15
b_minus_a_count: 0
jaccard_similarity: 0.16666666666666666
containment_a_in_b: 0.16666666666666666
containment_b_in_a: 1.0
interpretation: SUBSET
- number: 5
conditions:
- condition_type: FUNFAM
value: 2.40.160.10:FF:000016
curie: CATH.FunFam:2.40.160.10:FF:000016
label: Por1p
negated: false
- condition_type: TAXON
value: Dikarya
curie: NCBITaxon:451864
label: Dikarya
negated: false
notes: ''
- number: 6
conditions:
- condition_type: FUNFAM
value: 3.40.30.10:FF:000003
curie: CATH.FunFam:3.40.30.10:FF:000003
label: Peroxiredoxin 1
negated: false
- condition_type: TAXON
value: Saccharomycetes
curie: NCBITaxon:4891
label: Saccharomycetes
negated: false
notes: ''
- number: 7
conditions:
- condition_type: FUNFAM
value: 3.40.30.10:FF:000013
curie: CATH.FunFam:3.40.30.10:FF:000013
label: Blast:Protein SCO1 homolog, mitochondrial
negated: false
- condition_type: TAXON
value: Ascomycota
curie: NCBITaxon:4890
label: Ascomycota
negated: false
notes: ''
- number: 8
conditions:
- condition_type: FUNFAM
value: 3.40.30.10:FF:000063
curie: CATH.FunFam:3.40.30.10:FF:000063
label: 2-Cys peroxiredoxin BAS1, chloroplastic
negated: false
- condition_type: TAXON
value: eudicotyledons
curie: NCBITaxon:71240
label: eudicotyledons
negated: false
notes: ''
- number: 9
conditions:
- condition_type: FUNFAM
value: 3.40.30.10:FF:000250
curie: CATH.FunFam:3.40.30.10:FF:000250
label: Thioredoxin F-type, chloroplastic
negated: false
- condition_type: TAXON
value: Viridiplantae
curie: NCBITaxon:33090
label: Viridiplantae
negated: false
notes: ''
go_annotations: []
reviewed_protein_count: 0
unreviewed_protein_count: 0
created_date: ''
modified_date: ''
entries:
- id: 1.20.80.10:FF:000016
type: FUNFAM
label: Krev interaction trapped protein 1
appears_in_condition_sets:
- 3
protein_count: 3
related_entries:
- relationship: EQUIV
target_id: 3.40.50.80:FF:000003
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: 3.90.1230.10:FF:000001
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: 3.40.30.10:FF:000104
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: PREDICTS
target_id: 1.25.40.20:FF:000120
containment: 1.0
jaccard_similarity: 0.75
intersection_count: 3
exclusive_count: 0
- relationship: EQUIV
target_id: 2.30.29.30:FF:000227
containment: 1.0
jaccard_similarity: 1.0
intersection_count: 3
exclusive_count: 0
- relationship: EQUIV
target_id: 3.30.390.30:FF:000003
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: 3.50.50.60:FF:000141
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: 2.40.160.10:FF:000016
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: 3.40.30.10:FF:000003
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: 3.40.30.10:FF:000013
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: 3.40.30.10:FF:000063
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: 3.40.30.10:FF:000250
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: IPR004502
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: IPR011900
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: IPR011902
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: IPR011909
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: IPR014223
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: IPR044182
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: IPR046952
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: PREDICTS
target_id: GO:0045454
containment: 1.0
jaccard_similarity: 0.004
intersection_count: 3
exclusive_count: 0
- id: 1.25.40.20:FF:000120
type: FUNFAM
label: krev interaction trapped protein 1 isoform X1
appears_in_condition_sets:
- 3
protein_count: 4
related_entries:
- relationship: EQUIV
target_id: 3.40.50.80:FF:000003
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 3.90.1230.10:FF:000001
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 3.40.30.10:FF:000104
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: PREDICTED_BY
target_id: 1.20.80.10:FF:000016
containment: 0.75
jaccard_similarity: 0.75
intersection_count: 3
exclusive_count: 1
- relationship: PREDICTED_BY
target_id: 2.30.29.30:FF:000227
containment: 1.0
jaccard_similarity: 0.75
intersection_count: 3
exclusive_count: 0
- relationship: EQUIV
target_id: 3.30.390.30:FF:000003
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 3.50.50.60:FF:000141
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 2.40.160.10:FF:000016
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 3.40.30.10:FF:000003
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 3.40.30.10:FF:000013
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 3.40.30.10:FF:000063
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 3.40.30.10:FF:000250
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: IPR004502
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: IPR011900
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: IPR011902
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: IPR011909
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: IPR014223
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: IPR044182
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: IPR046952
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: PREDICTS
target_id: GO:0045454
containment: 1.0
jaccard_similarity: 0.005
intersection_count: 4
exclusive_count: 0
- id: 2.30.29.30:FF:000227
type: FUNFAM
label: krev interaction trapped protein 1 isoform X1
appears_in_condition_sets:
- 3
protein_count: 3
related_entries:
- relationship: EQUIV
target_id: 3.40.50.80:FF:000003
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: 3.90.1230.10:FF:000001
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: 3.40.30.10:FF:000104
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: 1.20.80.10:FF:000016
containment: 1.0
jaccard_similarity: 1.0
intersection_count: 3
exclusive_count: 0
- relationship: PREDICTS
target_id: 1.25.40.20:FF:000120
containment: 0.75
jaccard_similarity: 0.75
intersection_count: 3
exclusive_count: 1
- relationship: EQUIV
target_id: 3.30.390.30:FF:000003
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: 3.50.50.60:FF:000141
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: 2.40.160.10:FF:000016
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: 3.40.30.10:FF:000003
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: 3.40.30.10:FF:000013
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: 3.40.30.10:FF:000063
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: 3.40.30.10:FF:000250
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: IPR004502
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: IPR011900
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: IPR011902
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: IPR011909
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: IPR014223
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: IPR044182
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: EQUIV
target_id: IPR046952
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 3
- relationship: PREDICTS
target_id: GO:0045454
containment: 1.0
jaccard_similarity: 0.004
intersection_count: 3
exclusive_count: 0
- id: 2.40.160.10:FF:000016
type: FUNFAM
label: Por1p
appears_in_condition_sets:
- 5
protein_count: 2
related_entries:
- relationship: EQUIV
target_id: 3.40.50.80:FF:000003
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 2
- relationship: EQUIV
target_id: 3.90.1230.10:FF:000001
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 2
- relationship: EQUIV
target_id: 3.40.30.10:FF:000104
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 2
- relationship: EQUIV
target_id: 1.20.80.10:FF:000016
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 2
- relationship: EQUIV
target_id: 1.25.40.20:FF:000120
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 2
- relationship: EQUIV
target_id: 2.30.29.30:FF:000227
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 2
- relationship: EQUIV
target_id: 3.30.390.30:FF:000003
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 2
- relationship: EQUIV
target_id: 3.50.50.60:FF:000141
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 2
- relationship: EQUIV
target_id: 3.40.30.10:FF:000003
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 2
- relationship: EQUIV
target_id: 3.40.30.10:FF:000013
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 2
- relationship: EQUIV
target_id: 3.40.30.10:FF:000063
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 2
- relationship: EQUIV
target_id: 3.40.30.10:FF:000250
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 2
- relationship: EQUIV
target_id: IPR004502
containment: 0.0
jaccard_similarity: 0.0
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jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: 3.40.30.10:FF:000250
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: IPR004502
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: IPR011900
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: IPR011902
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: IPR014223
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: IPR044182
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: IPR046952
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: PREDICTS
target_id: GO:0045454
containment: 1.0
jaccard_similarity: 0.009
intersection_count: 7
exclusive_count: 0
- id: IPR014223
type: INTERPRO
source: ipr2go
protein_count: 4
asserted_predicted_go_terms:
- GO:0045454
related_entries:
- relationship: EQUIV
target_id: 3.40.50.80:FF:000003
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 3.90.1230.10:FF:000001
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 3.40.30.10:FF:000104
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 1.20.80.10:FF:000016
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 1.25.40.20:FF:000120
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 2.30.29.30:FF:000227
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 3.30.390.30:FF:000003
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 3.50.50.60:FF:000141
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 2.40.160.10:FF:000016
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 3.40.30.10:FF:000003
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 3.40.30.10:FF:000013
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 3.40.30.10:FF:000063
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 3.40.30.10:FF:000250
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: IPR004502
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: IPR011900
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: IPR011902
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: IPR011909
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: IPR044182
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: IPR046952
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: PREDICTS
target_id: GO:0045454
containment: 1.0
jaccard_similarity: 0.005
intersection_count: 4
exclusive_count: 0
- id: IPR044182
type: INTERPRO
source: ipr2go
protein_count: 7
asserted_predicted_go_terms:
- GO:0045454
related_entries:
- relationship: EQUIV
target_id: 3.40.50.80:FF:000003
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: 3.90.1230.10:FF:000001
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: 3.40.30.10:FF:000104
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: 1.20.80.10:FF:000016
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: 1.25.40.20:FF:000120
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: 2.30.29.30:FF:000227
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: 3.30.390.30:FF:000003
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: 3.50.50.60:FF:000141
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: 2.40.160.10:FF:000016
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: 3.40.30.10:FF:000003
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: 3.40.30.10:FF:000013
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: 3.40.30.10:FF:000063
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: 3.40.30.10:FF:000250
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: IPR004502
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: IPR011900
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: IPR011902
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: IPR011909
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: IPR014223
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: EQUIV
target_id: IPR046952
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 7
- relationship: PREDICTS
target_id: GO:0045454
containment: 1.0
jaccard_similarity: 0.009
intersection_count: 7
exclusive_count: 0
- id: IPR046952
type: INTERPRO
source: ipr2go
protein_count: 56
asserted_predicted_go_terms:
- GO:0045454
related_entries:
- relationship: EQUIV
target_id: 3.40.50.80:FF:000003
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 56
- relationship: EQUIV
target_id: 3.90.1230.10:FF:000001
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 56
- relationship: EQUIV
target_id: 3.40.30.10:FF:000104
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 56
- relationship: EQUIV
target_id: 1.20.80.10:FF:000016
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 56
- relationship: EQUIV
target_id: 1.25.40.20:FF:000120
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 56
- relationship: EQUIV
target_id: 2.30.29.30:FF:000227
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 56
- relationship: PREDICTED_BY
target_id: 3.30.390.30:FF:000003
containment: 0.321
jaccard_similarity: 0.321
intersection_count: 18
exclusive_count: 38
- relationship: PREDICTED_BY
target_id: 3.50.50.60:FF:000141
containment: 0.054
jaccard_similarity: 0.054
intersection_count: 3
exclusive_count: 53
- relationship: EQUIV
target_id: 2.40.160.10:FF:000016
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 56
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target_id: 3.40.30.10:FF:000003
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 56
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target_id: 3.40.30.10:FF:000013
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 56
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target_id: 3.40.30.10:FF:000063
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 56
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target_id: 3.40.30.10:FF:000250
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 56
- relationship: EQUIV
target_id: IPR004502
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 56
- relationship: EQUIV
target_id: IPR011900
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 56
- relationship: EQUIV
target_id: IPR011902
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 56
- relationship: EQUIV
target_id: IPR011909
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 56
- relationship: EQUIV
target_id: IPR014223
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 56
- relationship: EQUIV
target_id: IPR044182
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 56
- relationship: PREDICTS
target_id: GO:0045454
containment: 1.0
jaccard_similarity: 0.071
intersection_count: 56
exclusive_count: 0
review_summary: 'This rule demonstrates significant biological and curation concerns. While it correctly identifies several core redox homeostasis proteins (glutathione reductase, thioredoxins, peroxiredoxins), it suffers from: 1) Domain redundancy with identical protein sets across different FunFams, 2) Inclusion of proteins with questionable primary redox functions (KRIT1, Por1p), 3) Overly fragmented taxonomic scope suggesting annotation bias, and 4) Mechanistic incoherence mixing electron transfer enzymes, radical generators, and structural proteins. The rule would benefit from consolidation and removal of over-annotations.'
action: MODIFY
action_rationale: 'The rule requires modification rather than removal because it contains legitimate redox homeostasis proteins (glutathione reductase, thioredoxins, peroxiredoxins) that warrant the GO:0045454 annotation. However, significant issues include: 1) Complete redundancy in condition set 3 (KRIT1 domains with Jaccard=1.0), 2) High overlap in condition set 1 (NOS domains with 70% overlap), 3) Questionable inclusion of KRIT1 (primarily developmental) and Por1p (primarily transport), and 4) Fragmented taxonomic scope. These issues can be addressed through consolidation and refinement while preserving the core biological validity.'
suggested_modifications:
- 'Remove redundant domains in condition set 3: eliminate either 1.20.80.10:FF:000016 or 2.30.29.30:FF:000227 (identical protein coverage)'
- 'Consolidate condition set 1: merge overlapping NOS domains or provide justification for maintaining both'
- 'Remove KRIT1-related condition set 3: primary function is vascular development, redox role is secondary'
- 'Review Por1p inclusion in condition set 5: primarily a metabolite transporter with indirect redox involvement'
- 'Evaluate taxonomic restrictions: consider broader scope for conserved redox mechanisms'
- 'Consider more specific GO terms for mechanistically distinct proteins'
parsimony:
assessment: REDUNDANT
notes: 'Rule contains significant redundancy: condition set 3 has complete domain overlap (Jaccard=1.0), condition set 1 has high overlap (Jaccard=0.70), and condition set 4 shows subset relationship. With 9 condition sets, the rule is overly complex for the biological diversity it captures.'
literature_support:
assessment: MODERATE
notes: 'Mixed literature support - strong for core redox proteins (glutathione reductase, thioredoxins, peroxiredoxins) but weak for proteins with indirect roles (KRIT1, Por1p). The diverse mechanisms represented suggest this may be more of a functional grouping than a mechanistically coherent pathway.'
supported_by:
- reference_id: file:rules/arba/ARBA00085337/ARBA00085337-deep-research-manual.md
supporting_text: 'Strong candidates: Glutathione reductase, thioredoxins, peroxiredoxins - these are core redox homeostasis proteins. Questionable candidates: KRIT1 (developmental protein with oxidative stress sensitivity), Por1p (transporter with indirect redox involvement)'
condition_overlap:
assessment: SIGNIFICANT
notes: 'Analysis reveals concerning overlap patterns: Set 3 contains completely redundant domains (Jaccard=1.0), Set 1 has high overlap (Jaccard=0.70), and Set 4 shows subset relationships. This indicates poor curation and unnecessary complexity.'
supported_by: []
go_specificity:
assessment: APPROPRIATE
notes: 'GO:0045454 "cell redox homeostasis" is appropriately broad for the mechanistic diversity represented, though some proteins may warrant more specific terms (e.g., specific enzymatic activities for glutathione reductase, thioredoxin).'
supported_by: []
taxonomic_scope:
assessment: TOO_NARROW
notes: 'Highly fragmented taxonomic restrictions (Primates-only NOS, various fungal subgroups, plant subgroups) suggest annotation bias rather than genuine lineage-specific evolution. Redox homeostasis is fundamental across life domains and may warrant broader scope.'
supported_by: []
confidence: 0.6
references:
- id: file:rules/arba/ARBA00085337/ARBA00085337-deep-research-manual.md
title: Manual deep research analysis of ARBA00085337
findings:
- statement: 'Core redox proteins (glutathione reductase, thioredoxins, peroxiredoxins) strongly support GO:0045454 annotation'
- statement: 'KRIT1 and Por1p show questionable relevance - primarily developmental and transport functions respectively'
- statement: 'Domain redundancy indicates poor curation, particularly complete overlap in condition set 3'
- statement: 'Fragmented taxonomic scope suggests annotation bias rather than biological restriction'
supported_by:
- reference_id: file:rules/arba/ARBA00085337/ARBA00085337-analysis.yaml
supporting_text: 'Analysis reveals concerning overlap patterns with complete redundancy (Jaccard=1.0) and significant overlaps requiring consolidation'